IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
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IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
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Designed to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
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After a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
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Our innovative Book Series format brings you:
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Topic Focused Publications - Each topic showcases high impact subject areas
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Renowned Editorial Expertise - Series Editors, Topic Editors, and a team of international Board Members that permanently support each Book Series
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Fast Publishing - quick turnaround which is unique for book publishing
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The benefit of ISSN and ISBN for increased citation and indexing possibilities
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IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\n
IntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
We invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
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Note: Edited in October 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"8873",leadTitle:null,fullTitle:"Optical Coherence Tomography and Its Non-medical Applications",title:"Optical Coherence Tomography and Its Non-medical Applications",subtitle:null,reviewType:"peer-reviewed",abstract:"Optical coherence tomography (OCT) is a promising non-invasive non-contact 3D imaging technique that can be used to evaluate and inspect material surfaces, multilayer polymer films, fiber coils, and coatings. OCT can be used for the examination of cultural heritage objects and 3D imaging of microstructures. With subsurface 3D fingerprint imaging capability, OCT could be a valuable tool for enhancing security in biometric applications. OCT can also be used for the evaluation of fastener flushness for improving aerodynamic performance of high-speed aircraft. More and more OCT non-medical applications are emerging. In this book, we present some recent advancements in OCT technology and non-medical applications.",isbn:"978-1-78984-262-3",printIsbn:"978-1-78984-261-6",pdfIsbn:"978-1-83880-801-3",doi:"10.5772/intechopen.81767",price:119,priceEur:129,priceUsd:155,slug:"optical-coherence-tomography-and-its-non-medical-applications",numberOfPages:224,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"04048c4d925e4a7256014a26cf19c40c",bookSignature:"Michael R. Wang",publishedDate:"May 27th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8873.jpg",numberOfDownloads:7352,numberOfWosCitations:6,numberOfCrossrefCitations:10,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:17,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:33,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 1st 2018",dateEndSecondStepPublish:"February 28th 2019",dateEndThirdStepPublish:"June 7th 2019",dateEndFourthStepPublish:"March 18th 2019",dateEndFifthStepPublish:"September 8th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!0,featuredMarkup:null,editors:[{id:"6356",title:"Dr.",name:"Michael",middleName:null,surname:"Wang",slug:"michael-wang",fullName:"Michael Wang",profilePictureURL:"https://mts.intechopen.com/storage/users/6356/images/system/6356.jpg",biography:"Michael R. Wang is Professor of the Department of Electrical and Computer Engineering, University of Miami. He received his PhD degree in 1992 from the Department of Electrical Engineering, University of California, Irvine. His research is focused on integrated photonic devices, optical interconnects, holography, lithography, spectral imaging, and optical coherence tomography. He has developed optical coherence tomography systems to support various medical and industrial 3D imaging applications. Dr. Wang has been a principal investigator and/or project leader in many US government-sponsored projects. He has been an invited author and editor on lithography by IntechOpen. He has authored/coauthored more than 200 journal papers, proceedings, and conference presentations. He is a fellow of SPIE, a senior member of OSA, and a member of ARVO.",institutionString:"University of Miami",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Miami",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"228",title:"Optics and Lasers",slug:"optics-and-lasers"}],chapters:[{id:"68161",title:"Dynamic Range Enhancement in Swept-Source Optical Coherence Tomography",doi:"10.5772/intechopen.88084",slug:"dynamic-range-enhancement-in-swept-source-optical-coherence-tomography",totalDownloads:718,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The imaging penetration depth of an optical coherence tomography (OCT) system is limited by the dynamic range of the system. In a common case that signals exceed the dynamic range of a Fourier domain OCT (FDOCT) system, saturation artifacts degrade the image quality. In this chapter, we demonstrate some new cost-effective techniques to improve the dynamic range of a swept-source OCT (SSOCT) system. For example, one method is based on a dual-channel detection technique to enhance the dynamic range by reconstructing the saturated signals due to strong reflection of the sample surface. Another method utilizes a tunable high-pass filter to compensate the attenuation of light signal in deep tissue. It was demonstrated that these techniques can improve the dynamic range of an SSOCT system by more than 10 dB with a low bit-depth analog-to-digital converter.",signatures:"Jun Zhang, Xinyu Li and Shanshan Liang",downloadPdfUrl:"/chapter/pdf-download/68161",previewPdfUrl:"/chapter/pdf-preview/68161",authors:[{id:"293458",title:"Prof.",name:"Jun",surname:"Zhang",slug:"jun-zhang",fullName:"Jun Zhang"},{id:"304957",title:"Dr.",name:"Xinyu",surname:"Li",slug:"xinyu-li",fullName:"Xinyu Li"},{id:"304958",title:"Dr.",name:"Shanshan",surname:"Liang",slug:"shanshan-liang",fullName:"Shanshan Liang"}],corrections:null},{id:"72186",title:"Multi-Frame Superresolution Optical Coherence Tomography for High Lateral Resolution 3D Imaging",doi:"10.5772/intechopen.92312",slug:"multi-frame-superresolution-optical-coherence-tomography-for-high-lateral-resolution-3d-imaging",totalDownloads:770,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"We report that high lateral resolution and high image quality optical coherence tomography (OCT) imaging can be achieved by the multi-frame superresolution technique. With serial sets of slightly lateral shifted low resolution C-scans, our multi-frame superresolution processing of these special sets at each depth layer can reconstruct a higher resolution and quality lateral image. Layer by layer repeat processing yields an overall high lateral resolution and quality 3D image. In theory, the superresolution with a subsequent deconvolution processing could break the diffraction limit as well as suppress the background noise. In experiment, about three times lateral resolution improvement has been verified from 24.8 to 7.81 μm and from 7.81 to 2.19 μm with the sample arm optics of 0.015 and 0.05 numerical apertures, respectively, as well as the image quality doubling in dB unit. The improved lateral resolution for 3D imaging of microstructures has been observed. We also demonstrated that the improved lateral resolution and image quality could further help various machine vision algorithms sensitive to resolution and noise. In combination with our previous work, an ultra-wide field-of-view and high resolution OCT has been implemented for static non-medical applications. For in vivo 3D OCT imaging, high quality 3D subsurface live fingerprint images have been obtained within a short scan time, showing beautiful and clear distribution of eccrine sweat glands and internal fingerprint layer, overcoming traditional 2D fingerprint reader and benefiting important biometric security applications.",signatures:"Kai Shen, Hui Lu, Sarfaraz Baig and Michael R. Wang",downloadPdfUrl:"/chapter/pdf-download/72186",previewPdfUrl:"/chapter/pdf-preview/72186",authors:[{id:"6356",title:"Dr.",name:"Michael",surname:"Wang",slug:"michael-wang",fullName:"Michael Wang"},{id:"283389",title:"Ph.D.",name:"Kai",surname:"Shen",slug:"kai-shen",fullName:"Kai Shen"},{id:"283446",title:"Dr.",name:"Hui",surname:"Lu",slug:"hui-lu",fullName:"Hui Lu"},{id:"283447",title:"Dr.",name:"Sarfaraz",surname:"Baig",slug:"sarfaraz-baig",fullName:"Sarfaraz Baig"}],corrections:null},{id:"68213",title:"OCT in Applications That Involve the Measurement of Large Dimensions",doi:"10.5772/intechopen.88186",slug:"oct-in-applications-that-involve-the-measurement-of-large-dimensions",totalDownloads:667,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The application of optical coherence tomography (OCT) technique is not very common when measuring large dimensions is required. This type of measurements can be critical to achieve satisfactory results in the manufacturing process of precision parts. Components and structures ranging from submillimeter to several centimeters size can be found in many fields including automotive, aerospace, semiconductor, and data storage industries to name a few. In this chapter, an interferometric system based on the swept source optical coherence tomography (SS-OCT) technique, which has a wide measurement range and good axial resolution, is presented and its constituent parts are analyzed. The scheme includes a self-calibration stage based on fiber Bragg gratings (FBGs) that allows monitoring the spectral position of the light source in each scan, having the advantage of being a passive system that requires no additional electronic devices. Several applications of the system are described, including measurement of distances up to 17 cm, characterization of multilayer transparent and semitransparent structures, simultaneous determination of thickness of the wall, internal and external diameter of glass ampoules or similar containers, thickness measurements in opaque samples or where the refractive index is unknown, etc.",signatures:"Nélida A. Russo, Eneas N. Morel, Jorge R. Torga and Ricardo Duchowicz",downloadPdfUrl:"/chapter/pdf-download/68213",previewPdfUrl:"/chapter/pdf-preview/68213",authors:[{id:"297408",title:"Dr.",name:"Nelida",surname:"Russo",slug:"nelida-russo",fullName:"Nelida Russo"},{id:"297410",title:"Dr.",name:"Eneas",surname:"Morel",slug:"eneas-morel",fullName:"Eneas Morel"},{id:"297413",title:"Dr.",name:"Jorge",surname:"Torga",slug:"jorge-torga",fullName:"Jorge Torga"},{id:"297414",title:"Dr.",name:"Ricardo",surname:"Duchowicz",slug:"ricardo-duchowicz",fullName:"Ricardo Duchowicz"}],corrections:null},{id:"68072",title:"Low Cost Open-Source OCT Using Undergraduate Lab Components",doi:"10.5772/intechopen.88031",slug:"low-cost-open-source-oct-using-undergraduate-lab-components",totalDownloads:781,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Instrument cost is one of the factors limiting the adoption of optical coherence tomography (OCT) from a wider range of applications. We present a couple of OCT devices using optical components which are commonly found in undergraduate-level optics laboratories. These low-cost devices have lower signal-to-noise ratios (SNR) than top-of-the-line commercial offerings, yet can serve most of the needs of academic laboratories. A time-domain full-field (TD-FF-) OCT device has been assembled with Arduino control, which yields sub-4-μm axial and lateral resolutions. This device is useful where quick sample acquisition is not critical, but high resolution is paramount, for example with samples from material-science, or ex-vivo stabilized biological samples. Next, we discuss a spectral-domain (SD-) OCT device which delivers real-time video rate B-scans. This device is useful where real-time signal acquisition is desirable, for example with in-vivo biological samples. Cross-platform open-source software control for both these devices is also made available.",signatures:"Hari Nandakumar and Shailesh Srivastava",downloadPdfUrl:"/chapter/pdf-download/68072",previewPdfUrl:"/chapter/pdf-preview/68072",authors:[{id:"293593",title:"Mr.",name:"Hari",surname:"Nandakumar",slug:"hari-nandakumar",fullName:"Hari Nandakumar"},{id:"293601",title:"Dr.",name:"Shailesh",surname:"Srivastava",slug:"shailesh-srivastava",fullName:"Shailesh Srivastava"}],corrections:null},{id:"70478",title:"Optical Coherence Tomography for Polymer Film Evaluation",doi:"10.5772/intechopen.90445",slug:"optical-coherence-tomography-for-polymer-film-evaluation",totalDownloads:683,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Development of functional polymer films and film stacks has been under increasing demand to create new generations of novel, compact, light-weight optics. Optical coherence tomography (OCT) is capable of evaluating all the important optical properties of a film or film stack, including topology of surfaces or layer-to-layer interfaces, the refractive index and thickness, and polarization property. By engineering the scanning architecture of an OCT system, high-precision metrology of films of either flat or spherical geometry is achieved. In this chapter, the system design, metrology methodologies, and examples of OCT for film metrology are discussed to provide both the knowledge foundation and the engineering perspectives. The advanced film metrology capabilities offered by OCT play a key role in the manufacturing process maturity of newly developed films. Rapid advancement in the field of OCT is foreseen to drive the application toward in-line film metrology and facilitate the rapid growth of innovative films in the industry.",signatures:"Jianing Yao and Jannick P. Rolland",downloadPdfUrl:"/chapter/pdf-download/70478",previewPdfUrl:"/chapter/pdf-preview/70478",authors:[{id:"307465",title:"Dr.",name:"Jianing",surname:"Yao",slug:"jianing-yao",fullName:"Jianing Yao"},{id:"309133",title:"Prof.",name:"Jannick",surname:"Rolland",slug:"jannick-rolland",fullName:"Jannick Rolland"}],corrections:null},{id:"68363",title:"Fouling Monitoring in Membrane Filtration Systems",doi:"10.5772/intechopen.88464",slug:"fouling-monitoring-in-membrane-filtration-systems",totalDownloads:608,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Membrane filtration systems are employed in the water industry to produce drinking water and for advanced wastewater treatment. Fouling is considered the main problem in membrane filtration systems. Fouling occurs when the biomass deposited on the membrane surface leads to a membrane performance decline. Most of the available techniques for characterization of fouling involve the analysis of membrane samples after membrane autopsies. This approach provides information ex-situ destructively at the end of the filtration process. Optical coherence tomography (OCT) gained attention in the last years as noninvasive imaging technique, capable of acquiring scans in-situ and nondestructively. The online OCT monitoring enables visualizing and studying the biomass deposition over time under continuous operation. This approach allows to relate the impact of the fouling on the process. In the last years, the suitability of OCT as in-situ and nondestructive tool for the study of fouling in membrane filtration systems has been evaluated. The OCT has been employed to study the fouling in different membrane geometry and configuration for the treatment of seawater and wastewater. Nowadays, the OCT is employed to better understand the role of biomass structure on the filtration mechanisms.",signatures:"Luca Fortunato",downloadPdfUrl:"/chapter/pdf-download/68363",previewPdfUrl:"/chapter/pdf-preview/68363",authors:[{id:"293639",title:"Dr.",name:"Luca",surname:"Fortunato",slug:"luca-fortunato",fullName:"Luca Fortunato"}],corrections:null},{id:"69295",title:"Nondestructive Characterization of Drying Processes of Colloidal Droplets and Latex Coats Using Optical Coherence Tomography",doi:"10.5772/intechopen.89380",slug:"nondestructive-characterization-of-drying-processes-of-colloidal-droplets-and-latex-coats-using-opti",totalDownloads:624,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter, we review the applications of optical coherence tomography (OCT) on the nondestructive characterization of the drying processes of colloidal droplets and latex coatings. Employing time-lapse, high-speed imaging, OCT can be used to monitor the dynamic process of drying colloidal droplets. With the aid of high-scattering, micron-sized tracer particles, fluid flows have been captured; phase boundaries are also visible in liquid crystal droplets; and the speckle contrast analysis differentiates the dynamics of particles, showing the packing process and the coffee ring phenomenon. In a waterborne latex coat, time-lapse OCT imaging reveals spatial changes of microstructures, i.e., detachment of latex, cracks, and shear bands; with speckle contrast analysis, 1D and 2D particles’ packing process that is initiated from latex/air interface can also be monitored over time. OCT can serve as an experimental platform for fundamental studies of drying colloidal systems. In the future, OCT can also be employed as an in-line quality control tool of polymer coatings and paints for industrial applications.",signatures:"Yongyang Huang, Hao Huang, Zhiyu Jiang, Lanfang Li, Willie Lau, Mohamed El-Aasser, Hsin-Chiao Daniel Ou-Yang and Chao Zhou",downloadPdfUrl:"/chapter/pdf-download/69295",previewPdfUrl:"/chapter/pdf-preview/69295",authors:[{id:"296946",title:"Prof.",name:"Chao",surname:"Zhou",slug:"chao-zhou",fullName:"Chao Zhou"},{id:"310491",title:"Dr.",name:"Yongyang",surname:"Huang",slug:"yongyang-huang",fullName:"Yongyang Huang"},{id:"310492",title:"Dr.",name:"Hao",surname:"Huang",slug:"hao-huang",fullName:"Hao Huang"},{id:"310493",title:"Mr.",name:"Zhiyu",surname:"Jiang",slug:"zhiyu-jiang",fullName:"Zhiyu Jiang"},{id:"310494",title:"Dr.",name:"Lanfang",surname:"Li",slug:"lanfang-li",fullName:"Lanfang Li"},{id:"310495",title:"Dr.",name:"Willie",surname:"Lau",slug:"willie-lau",fullName:"Willie Lau"},{id:"310496",title:"Prof.",name:"Mohamed",surname:"El-Aasser",slug:"mohamed-el-aasser",fullName:"Mohamed El-Aasser"},{id:"310497",title:"Prof.",name:"H. Daniel",surname:"Ou-Yang",slug:"h.-daniel-ou-yang",fullName:"H. Daniel Ou-Yang"}],corrections:null},{id:"68201",title:"OCT for Examination of Cultural Heritage Objects",doi:"10.5772/intechopen.88215",slug:"oct-for-examination-of-cultural-heritage-objects",totalDownloads:691,totalCrossrefCites:5,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Optical coherence tomography (OCT) was first time reported as a tool for examination of cultural heritage objects in 2004. It is mainly used for the examination of subsurface structure of easel paintings (such as varnishes and glazes) and has also been successfully used for inspection of other types of artworks, provided that they contain layers that are permeable to the probing light. This chapter discusses the last applications of OCT in this area with an emphasis on synergy with some other noninvasive techniques such as large-scale X-ray fluorescence (XRF) scanning and reflective Fourier transform infrared (FTIR) spectroscopy. After this part, there is a detailed description of the high-resolution OCT instrument developed by the authors specifically for the study of works of art. Next, two examples are given for the structural examination of works of art: in the former, the subsurface layers of an easel painting are presented, and in the latter, the painting on reverse of the glass is examined, when the inspection must be carried out through the glass. Finally, an application for the assessment of chemical varnish removal from an easel panel painting is discussed in details.",signatures:"Piotr Targowski, Magdalena Kowalska, Marcin Sylwestrzak and Magdalena Iwanicka",downloadPdfUrl:"/chapter/pdf-download/68201",previewPdfUrl:"/chapter/pdf-preview/68201",authors:[{id:"285270",title:"Prof.",name:"Piotr",surname:"Targowski",slug:"piotr-targowski",fullName:"Piotr Targowski"},{id:"285353",title:"Dr.",name:"Magdalena",surname:"Iwanicka",slug:"magdalena-iwanicka",fullName:"Magdalena Iwanicka"},{id:"307981",title:"Dr.",name:"Magdalena",surname:"Kowalska",slug:"magdalena-kowalska",fullName:"Magdalena Kowalska"},{id:"307982",title:"Dr.",name:"Marcin",surname:"Sylwestrzak",slug:"marcin-sylwestrzak",fullName:"Marcin Sylwestrzak"}],corrections:null},{id:"68190",title:"Quantitative Mapping of Strains and Young Modulus Based on Phase-Sensitive OCT",doi:"10.5772/intechopen.88068",slug:"quantitative-mapping-of-strains-and-young-modulus-based-on-phase-sensitive-oct",totalDownloads:724,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter we consider mapping of local strains and tissue elasticity in optical coherence tomography (OCT) based on analysis of phase-sensitive OCT scans. Conventional structural OCT scans correspond to spatially resolved mapping of the backscattering intensity of the probing optical beam. Deeper analysis of such sequentially acquired multiple OCT scans can be used to extract additional information about motion of scatterers in the examined region. Such detailed analysis of OCT scans has already resulted in creation of OCT-based visualization of blood microcirculation, which has been implemented in several commercially available devices, especially for ophthalmic applications. Another functional extension of OCT emerging in recent years is the OCT-based elastography, i.e., mapping of local strains and elastic properties in the imaged region. Here, we describe the main principles of local strain mapping in phase-sensitive OCT with a special focus on the recently proposed efficient vector method of estimation of interframe phase-variation gradients. The initially performed mapping of local strains is then used for realization of quantitative compressional elastography, i.e., mapping of the Young modulus and obtaining stress-strain dependences for the studied samples. The discussed principles are illustrated by simulated and experimental examples of elastographic OCT-based visualization. The presented elastographic principles are rather general and can be used in a wide area of biomedical and technical applications.",signatures:"Vladimir Y. Zaitsev, Lev A. Matveev, Alexander A. Sovetsky and Alexander L. Matveyev",downloadPdfUrl:"/chapter/pdf-download/68190",previewPdfUrl:"/chapter/pdf-preview/68190",authors:[{id:"294983",title:"Dr.",name:"Vladimir",surname:"Zaitsev",slug:"vladimir-zaitsev",fullName:"Vladimir Zaitsev"},{id:"307118",title:"Dr.",name:"Lev",surname:"Matveev",slug:"lev-matveev",fullName:"Lev Matveev"},{id:"307119",title:"Mr.",name:"Alexander",surname:"Sovetsky",slug:"alexander-sovetsky",fullName:"Alexander Sovetsky"},{id:"307120",title:"Dr.",name:"Alexander",surname:"Matveyev",slug:"alexander-matveyev",fullName:"Alexander Matveyev"}],corrections:null},{id:"70108",title:"OCT with a Visible Broadband Light Source Applied to High-Resolution Nondestructive Inspection for Semiconductor Optical Devices",doi:"10.5772/intechopen.90117",slug:"oct-with-a-visible-broadband-light-source-applied-to-high-resolution-nondestructive-inspection-for-s",totalDownloads:512,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Optical coherence tomography with a visible broadband light source (vis-OCT) was developed for high-resolution and nondestructive measurements of semiconductor optical devices. Although a near-infrared (NIR) light source should be used for medical OCT to obtain deep penetration of biological samples, a visible broadband light source is available as a low-coherence light source for industrial products. Vis-OCT provides higher axial resolution than NIR-OCT, because the axial resolution of an OCT image is proportional to the square of the center wavelength of the light source. We developed vis-OCT with an axial resolution of less than 1 μm in air and obtained cross-sectional profiles and images of ridge-type waveguides having heights and widths of several μm. Additionally, we performed cross-sectional measurements and imaging of a stacked semiconductor thin layer. The measured values were similar to those measured by scanning electron microscopy, and the effectiveness of vis-OCT for nondestructive inspection of semiconductor optical devices was demonstrated.",signatures:"Nobuhiko Ozaki, Kazumasa Ishida, Tsuyoshi Nishi, Hirotaka Ohsato, Eiichiro Watanabe, Naoki Ikeda and Yoshimasa Sugimoto",downloadPdfUrl:"/chapter/pdf-download/70108",previewPdfUrl:"/chapter/pdf-preview/70108",authors:[{id:"173222",title:"Dr.",name:"Nobuhiko",surname:"Ozaki",slug:"nobuhiko-ozaki",fullName:"Nobuhiko Ozaki"},{id:"312411",title:"Mr.",name:"Kazumasa",surname:"Ishida",slug:"kazumasa-ishida",fullName:"Kazumasa Ishida"},{id:"312412",title:"Mr.",name:"Tsuyoshi",surname:"Nishi",slug:"tsuyoshi-nishi",fullName:"Tsuyoshi Nishi"},{id:"312414",title:"Dr.",name:"Hirotaka",surname:"Ohsato",slug:"hirotaka-ohsato",fullName:"Hirotaka Ohsato"},{id:"312415",title:"Dr.",name:"Eiichiro",surname:"Watanabe",slug:"eiichiro-watanabe",fullName:"Eiichiro Watanabe"},{id:"312417",title:"Dr.",name:"Naoki",surname:"Ikeda",slug:"naoki-ikeda",fullName:"Naoki Ikeda"},{id:"312418",title:"Dr.",name:"Yoshimasa",surname:"Sugimoto",slug:"yoshimasa-sugimoto",fullName:"Yoshimasa Sugimoto"}],corrections:null},{id:"70723",title:"Optical Coherence Tomography for Non-Contact Evaluation of Fastener Flushness",doi:"10.5772/intechopen.90753",slug:"optical-coherence-tomography-for-non-contact-evaluation-of-fastener-flushness",totalDownloads:578,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Outside of the medical field, spectral domain optical coherence tomography (SD-OCT) is sparsely used. As such, we explored the possibility and practicality of using SD-OCT as a tool to evaluate fastener flushness and countersink surface profiles. A SD-OCT device was built with a handheld galvanometer scanner that weighed only 0.5 lb. Not only it does not require scan center alignment, but it is also capable of quickly producing measurements of fastener flushness, radius, slant angle, countersink edge radius, and surface angle. With the X-Y two-line scanning method, measurements take only 90 ms. The SD-OCT device used to obtain these measurements uses a lens with 60 mm focal length and a broadband light source of 840 nm center wavelength and 45 nm spectral bandwidth. With these components, the SD-OCT device is able to provide an axial depth resolution of 8.5 μm and a lateral resolution of 19 μm. The axial depth resolution can be improved by using a wider bandwidth light source. Furthermore, the device is able to produce 3D surface profiles of fasteners and countersinks using multi-line scans.",signatures:"James H. Wang and Michael R. 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1. Introduction
Since its advent in 1925, Nuclear Cardiology has undergone multiple changes in technology including detectors, computers, changes in protocols, various approaches to stress including physiologic and pharmacologic methods, changes in the type of isotope utilized and finally concerns over the distribution of radioactive isotopes and efforts to improve the detection of heart disease while reducing radiation dosage to both patients and health care workers alike. We will divide this chapter into five Sections. First, we will review the work that led to the discovery that the technetium-99m isotopes, like thallium-201, redistribute. Secondly, we will look at currently employed Cardiac imaging using Single Photon Emission Computed Tomography (SPECT) cameras for detecting technetium-99m isotopes (principally Sestamibi). Thirdly, we will consider how these isotopes are injected, distributed and redistributed within Cardiac tissue. Fourth, we will look at how single injection stress-stress imaging can not only increase the accuracy of SPECT imaging of the heart, detecting the most critically diseased coronary vessels while reducing the amount of radioactive isotope injected into the patient, who will subsequently expose others to this radiation and finally, we will look at how rest-rest comparisons of isotope redistribution can be used to differentiate between viable and non-viable damaged myocardial tissue using SPECT cameras.
At the completion of this chapter, clinician and scientist alike, will (1) better understand the physics of SPECT imaging of the heart, (2) will better understand the kinetics of technetium-99m isotopes (which are applicable to thallium-201 and other isotopes, given differences in redistribution times), (3) be able to better detect heart disease with special emphasis placed on ischemic heart disease, while addressing issues of patient radiation safety (4) be able to differentiate viable from non-viable cardiac tissue and (5) be able to utilize SPECT cameras to extract both anatomic and physiologic information, not currently possible with single isotope injection, single camera imaging systems, including Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT). Currently, imaging with PET cameras, cannot be completed rapidly enough to allow for measurements of redistribution properties of PET isotopes, nor is it clear if any of these isotopes (ammonia, FDG, Rb-82, etc) actually have redistribution properties, while MRI and Coronary CT currently are only able to yield anatomic information and are unable to measure physiologic redistribution of isotopes. This chapter will describe the recent advances in single isotope injection, single camera imaging (FHRWW) while explaining why the practice of rest-stress imaging has failed to deliver on the promises made.
2. Discovering the redistribution properties of technetium-99m isotopes
The development of Nuclear Cardiology (discussed in detail later in this chapter) evolved through the utilization of Thallium-201 (Tl-201) by the 1970’s. The protocol at that time consisted of stressing the patient and injecting 1-3 mCi (74-111 MBq) intravenously into the patients venous system and continuing to exercise the patient for an additional minute prior to ceasing exercise (Fleming, 1991a, 1999a). The patient was then “recovered” and underwent “stress” imaging one hour after initiation of the patients exercise session. While imaging one hour after exercise is clearly not a period of time when the individual is “stressed”, the terminology persisted since this image was the first image obtained following the stress. Subsequently, these images became known as “stress” images. Over time, thallium distribution changed and consequently the appearance of the images themselves changed. This became known as “redistribution” since the distribution of Th-201 changed with time. For lack of a better term, this second image was coined a “resting” image and their comparison was used to define changes, which were thought to represent ischemia and possibly infarction. As we shall see in subsequent sections, neither Blumgart (1926) nor Gorlin (1959) considered this to be so and a better understanding of their work might have saved Nuclear Cardiology decades of misdirection. However, the actual ability to detect infarction was not through the rest image obtained in this manner; but rather, a resting (Parkey 1976, Ahmad 1979, Walsh 1977) image obtained by using Tc-99m pyrophosphate (Tc-99 PYP), which required imaging of the heart within 48-72 hours of the time of infarction to accurately detect. Efforts to replace Tc-99m PYP with newer imaging agents (Khaw 1999) not only emphasize the limitations of timing and possible overlap of bone activity; but, the importance of utilization of resting images and not stress images to determine the presence or absence of damaged (infarction, stunned, hibernating) myocardium, as emphasized by Blumgart (1926) and Gorlin (1959).
Over time, the lessons of Blumgart and Gorlin were all but forgotten and the terms “stress” and “rest” anthropomorphically took on a life and meaning of their own. Instead of viewing comparative Nuclear images obtained under same state conditions at two different points in time, which could then be compared to look for changes in distribution of isotope scintillation consistent with changes in supply (blood flow) and function (cellular, including mitochondria), the introduction of technetium-99m isotopes were introduced with directions by the manufacturers that clinicians and scientists needed to give two injections (rest stress), instead of one (stress-redistribution) used for Tl-201. In the first instance, teboroxime (Fleming 1991a) was reported as having too rapid a “washout” (another term for redistribution), which would prevent multiple imaging given the camera acquisition speed of the time, while Sestamibi would be promoted as having no washout allowing one to chose when they wanted to image the patient; a property which would be warmly welcomed by nuclear medicine departments concerned with the number of studies being ordered and nuclear departments scheduling issues. Truly, this alleged property of Sestamibi was a welcomed relief for such scheduling issues. This misinformation continued to drive the market reducing study accuracy despite multiple studies reporting that Sestamibi did in fact redistribute. By using this redistribution property, investigators have been better able to define heart failure (Hurwitz 1993, 1998, Saha 1994, Giubbini 1995, Sugiura 2006, Kumita 2002), cardiomyopathy (Matsuo 2007, Ikawa 2007, Meissner 2002) and coronary artery vasospasm (Ono 2002, 2003). Perhaps the most compelling work was published by Maublant (1988), prior to the introduction of Sestamibi into the United States. This work revealed that Sestamibi has a 28 minute washout under non-ischemic conditions while the work of Crane (1993), which was funded by the pharmaceutical company itself, demonstrated that under ischemic conditions, the washout of Sestamibi occurred more rapidly due to mitochondrial calcium overload. This information, to date, continues to appear within package inserts as shown in Table 1 and is now described as having “minimal cardiac redistribution,” encouraging physicians to use multiple doses for studies.
REST
STRESS
Heart
Liver
Heart
Liver
Time
Biological
Effective
Biological
Effective
Biological
Effective
Biological
Effective
5 min.
1.2
1.2
19.6
19.4
1.5
1.5
5.0
5.8
30 min.
1.1
1.0
12.2
11.5
1.4
1.3
4.5
4.2
1 hour
1.0
0.9
5.6
5.0
1.4
1.2
2.4
2.1
2 hours
1.0
0.8
2.2
1.7
1.2
1.0
0.9
0.7
4 hours
0.8
0.5
0.7
0.4
1.0
0.6
0.3
0.2
Table 1.
study in a dog myocardial ischemia model reported that Technetium TC99m Sestamibi undergoes myocardial distribuion (redistribution), although more slowly and less completely than thalous chloride Tl-201. A study in a dog myocardial infarction model reported that the drug showed no redistribution of any consequence. Definitive human studies to demonstrate possible redistribution have not been reported. In patients with documented myocardial infarction, imaging revealed the infarct up to four hours post dose.Cardiolite US PI 513121-0309 (3-16-2009 package insert)
After our initial work (Fleming 1991a) with these Tc-99m isotopes in 1989, we published several papers (Fleming 1995, 1998, 1999a-b, 1992a-b, 2000a-b, 2002a-b) under the misinformation that two injections of these compounds were required and like many others we failed to fully understand the work of Blumgart and Gorlin. By 1999-2000, Sestamibi was being used for the detection of breast cancer. The company involved with this work (under the trade name Miraluma) was concerned that clinicians were not ordering the study due to what was perceived as incorrect results. Studies performed show “abnormal” results without the detection of biopsy proven breast cancer. However, the tissue while not cancerous was not “normal” either and considerable confusion existed at the time. We were asked to conduct breast imaging studies and developed a method for simultaneous detection of both heart disease and breast disease. The results were published (Fleming 2002c-e, 2003a-c) and presented at several meetings as shown in Figure 2. While beyond the scope of this text, it resulted in our looking more closely at the information, which the nuclear computer was seeing (Fleming 2003d) and which we were not; viz. the actual scintigraphic counts from regions of interest (ROIs) as shown in Figure 3 for the breast and Figure 4 for the heart. This approach not only gave us a greater insight as to the cause of angina, viz. regional blood flow differences (Fleming 2003d); but, it allowed us to additionally see for the first time detectable evidence of an activated thymus gland (Fleming 2003e) with enlargement and increased isotope uptake associated with coronary artery disease/inflammation (Fleming 1999c, 2003e, 2008a) and providing further evidence of underlying coronary artery disease. This same state physiologic approach allowed us to compare images of the heart taken at 5 minutes and 60 minutes following pharmacologic stressing of the heart utilizing a single injection of the isotope Sestamibi. These rather crude early findings (Figure 4) clearly demonstrated that individuals with ischemic heart disease revealed different distribution patterns of Sestamibi within cardiac tissue at 5 and 60 minutes post stress, proving that Sestamibi in fact “redistributes” within the heart and confirmed the information reported by others as noted above and as we will see in the remainder of this chapter, it has been confirmed by others world wide as well as recent work out of both UCLA and Harvard (Sheikine 2010). We have also demonstrated (Fleming 2009) that technetium-99m tetrofosmin (trade name Myoview) similarly redistributes. Since it is imperative that comparison images be performed on the same SPECT camera to allow meaningful comparisons of the two images, we will now turn our attention to the details of when nuclear SPECT cameras provide us the information we are seeking and when they do not.
Figure 1.
Acquisition of Heart and Breast Image 5 Minutes After Stress Injection
Information obtained from the package insert of this product reports that “Definitive human studies to demonstrate possible redistribution have not been reported.” The information provided as discussed in the text and literature clearly shows this not to be the case.
Following pharmacologic stress and injection of sestamibi, images of cardiac and breast tissue were acquired using a SPECT camera 5-minutes after cessation of stress. Detection of thymic tissue, while not noted in this individual, has been published by us elsewhere (Fleming 2003e).
Here breast enhanced scintigraphy test (BEST) images from three different women are quantified using regions of interest (ROIs) and compared with results (immediately below each image) obtained by Dr. William Dooley using ductoscopy. The results of tissue specimens were confirmed pathologically as representing inflammatory tissue and cancer respectively as shown in the images. This study provided further information as to the ability to reliable “quantify” differences on Nuclear imaging using ROI and the role of scintigraphy measurement in diagnosing both heart disease and breast cancer.
Figure 2.
Analysis of regions of interest (ROIs) of breast tissue
Figure 3.
Analysis of regions of interest (ROIs) from Cardiac bullseye images
While qualitative Gestalt of images are frequently utilized for both clinical and scientific work, regions 1 (mean count of 1379.22) and 2 (mean count of 1485.42) represents an almost 8% difference in count activity which cannot be appreciated visually. The quantification of the differences in regions (ROIs) of interest (Fleming 2003d) was utilized to demonstrate that angina is not the result of narrowed arteries; but rather, the reduced ability of diseased arteries to vasodilate to the extent that non-diseased coronary arteries can dilate (viz. regional blood flow differences) under the influence of pharmacologic stress.
Figure 4.
a-c. Early comparisons of coronary artery disease showing differences in Sestamibi distribution at 5 and 60 minutes post stressing of the heart. a) 5 Minute post-stress image taken on NucLear MAC SPECT Camera; b) 60 Minute post-stress image taken on NucLear MAC SPECT Camera; c) Washout of Sestamibi as determined by NucLear MAC Spect Camera system
This early study SPECT camera image reveals an anterior image of the heart acquired 5 minutes after peak cardiac stress and Sestamibi injection, demonstrating no regional defects in isotope activity.
This qualitative study, performed in 2001 of the same patient in figure 4a, shows washout of Sestamibi compared with the 5-minute image. Here there are both distal anterior and apical reductions in isotope in addition to a dilated right ventricle. Clearly, these early 2001 studies demonstrated that Sestamibi redistributes throughout cardiac tissue with different results seen at 5 and 60 minutes post-stress. This is confirmed in the “washout” study seen in Figure 4c.
Bullseye definition of “washout” made by the same SPECT camera system using it’s computer software to compare the two sets of images shown above (4a and 4b). The results show a qualitative (blue) redistribution/washout in the distal anterior and apical regions. Clearly, these 2001 images show differences in isotope distribution between the 5 and 60-minute images. Similar findings have now been reported by others, including researchers at UCLA and Harvard Universities (Sheikine 2010).
3. The Fleming-Harrington nuclear imaging uncertainty principle. Understanding the physics of how nuclear SPECT cameras really work?
Abstract: The introduction of the Heisenberg Uncertainty principle and Nuclear Cardiology occurred simultaneously in 1925-1927. Thirty years later the Anger gamma camera would allow for a more sophisticated radioactive isotope counting to determine the presence or absence of disease. When employed with technetium-99m isotopes, ischemic heart disease can be inferred by differences in visual appearance of cardiac images. These gestalts of imaging results have been separated from the quantitative information recorded by the cameras computer. We investigated whether current camera and computer systems are sophisticated enough to quantify differences between images to be clinically relevant. Our study demonstrated that efforts to “sharpen” image appearance does so at a reduction in “accuracy”. Like Heisenberg, this work shows that one cannot know the exact location and the amount of activity simultaneously and that a decision must be made for accuracy over image sharpness if one is to truly quantify differences in isotope concentration between images.
In 1927, Werner Heisenberg (Heisenberg 1927), published his “Uncertainty principle” which in brief states that it is impossible to simultaneously know both the position and momentum of an electron or any other particle with any degree of accuracy or “certainty.” To define the location of an electron required interaction with it. This interaction would result in movement of the electron and as a result, would move the electron. The best one could achieve is knowledge of where the electron was at the time of interaction.
The first utilization of nuclear isotopes for medical imaging and evaluation of heart disease was conducted by Blumgart (1926) in February of 1925 when he injected himself with Radium C, which emits alpha and beta particles and gamma rays. As such, the Geiger counter chamber developed by Blumgart and Yens, could detect the passage of blood carrying the radium. The studies would first be published in 1926 (Blumgart 1926) and become known as “circulation time” and would dynamically define myocardial contractility by comparing changes in count activity over time.
In 1957, Hal Anger (1957) demonstrated the first gamma camera designed to detect the emission of radioactive decay emanating from the patient. In essence, a modern Geiger counter which could be held some distance from the chest to measure isotope decay while present in cardiac tissue. The decay (scintillation) is detected by the camera after being absorbed by the camera crystal (usually sodium iodide) with the subsequent release of an electron from the sodium iodide, which is subsequently detected by a photomultiplier (PMT) tube. These scintillations are tallied by the computer. These anger cameras have been used to image various regions of the body using radioactive isotopes which are known to localize to the tissues in question. For cardiac disease this has primarily included thallium-201 and technetium-99m.
The utilization of these cameras have been assumed to be able to detect changes in isotope availability by “counting” the amount of radioactivity as described and translating this information into a black and white or color format image for human viewing and interpretation of disease. However, to the best our knowledge, no such experimentation has been carried out to determine if today’s gamma cameras can in fact accurately count radioactive decay required for image comparison. This quantification is necessary to compare redistribution of isotopes and to avoid errors in interpretation. This requires more than simply the ability to produce pictures of different brightness; it requires actual ability to measure differences in isotope decay (scintillation), as did Blumgarts Geiger counter. This is the basis of devices used to determine human radiation exposure and is a requirement in diagnostic imaging. To investigate this we conducted a series of experiments with known quantities of Tc-99m and utilized two different matrixes commonly employed in clinical cardiology to determine if the cameras are able to accurately measure radioactive decay.
The acquisition of technetium-99m isotopes for diagnostic purposes results from the radioactive decay of the parent compound (Molybdenum) to the daughter compound (technetium-99m) is shown in Figure 5. The half-life for technetium-99m is 6.01 hours as shown in Figure 8. Each sample of technetium-99m contained 10.1 mCi (37.37 MBq) of radioactive compound. Each sample was sealed in a syringe preventing any leakage of material. If the cameras are able to accurately measure isotope decay, the camera should reveal a 10% reduction in count activity from the first image and the second image taken 55 minutes later.
Utilizing a Philips Forte Dual head single photon emission computed tomography (SPECT) camera with general all purpose collimators, the camera was set to (1) a 64 x 64 matrix and (2) 128 x 128 matrix settings. As shown in Figure 7a-c, the greater the matrix (pixel) settings per image, the greater the localization of isotope emission within the field of view and the sharper the image. However, for each pixel, there are surrounding septa of lost information forming the border of the pixel. The question is whether the increase in image “sharpness” comes at the expense of “accuracy” of radioactive isotope count activity, which is the basis for image comparisons.
As shown in Figure 8a, the initial radioactive count obtained over 5 minutes from a syringe of 37.37 MBq of radioactive tc-99m using a 64 by 64 pixel matrix was 1,405,721. Using the same matrix and imaging 55 minutes later, Figure 8b shows the counts collected over 5 minutes were 1,251,359. The decay curve for tc-99m means that there should have been a 10% reduction in count activity. In this instance, there was a 10.98% reduction in measured isotope activity. When efforts to improve image “sharpness” were made by changing the matrix to 128 x 128, Figure 8c shows the initial count activity measured over 5 minutes was 3,473,001. When the syringe was reimaged 55 minutes later using the 128 x 128 matrix, the counts collected over a 5 minute period, as shown in Figure 8d, were 2,966,394. While there was an increase in actual radioactive count activity compared with the 64 x 64 matrix, this came at a cost of accuracy with a 14.59% reduction in radioactive count activity. This is 4.68 times the data lost as was seen with the 64 x 64 matrix.
While the visual appearance desired by most clinicians to make diagnostic decisions is important, images can be manipulated to confirm what the diagnostician is looking for. These adjustments may lead to incorrect conclusions and visual interpretations alone may lead to incorrect conclusions. When done at social gatherings, these visual illusions as shown in Figure 9 can be entertaining. When done to determine if someone has ischemic heart disease, such illusions can be more distressing. For that reason, multiple researchers have been trying to develop algorithms, which will reduce this human error. It is impossible to reduce this human error, if Section of the error is the result of instrumentation.
These findings have demonstrated that independent of the visual image seen by the clinician, this information is dependent upon the accuracy of the computers ability to detect the radioactive decay of isotope needed to make image comparisons. Like, Heisenberg’s uncertainty principle, this uncertainty principle comes at a cost. The ability to detect the location of the emission of the gamma ray is influenced by the matrix surrounding the acquired image of the heart. This precision of location comes at the cost of lost accuracy as to the number of gamma rays being emitted. Given this spatial limitation (sharpness) versus accuracy, like Heisenberg we are left with a dilemma. Do we sacrifice accuracy for “sharpness” or should we be more concerned with the necessary accuracy required to compare images (Fleming 2009b, 2010a-b, Sheikine 2010), thereby reducing errors made in evaluation of the extent of ischemic heart disease?
Now that we have defined the limitations and accuracy of our SPECT cameras to define the presence or absence of disease, we can now turn our attention to understanding the kinetics of nuclear isotopes, with particular attention to technetium-99m compounds (viz. Sestamibi) to better understand how to best study the heart using our SPECT cameras.
As shown, PMTs are composed of glass tube with a vacuum inside. Photons leaving the patient would approach the PMT from left to right, striking the photocathode material first. This results in electrons being produced as a consequence of the photoelectric effect. The focusing electrode subsequently directs these toward the electron multiplier composed of a series of electrodes (dynodes), each with a more positive voltage than the next. The electrons are accelerated toward the first dynode, arriving with a greater energy. This results in low energy electrons being generated by the first dynode, which are in turn accelerated toward the second dynode and so on. The process is known as secondary emission and results in an amplification of the original scintillation. The electrons finally reach the anode (far right Section of PMT) where the accumulated charge results in a sharp current pulse indicating the arrival of the photon at the photocathode.
Figure 5.
Decay of Technetium-99m
The production of technetium by bombardment of a molybdenum atom with deuterons was first documented by Carol Perrier and Emilio Segre in 1937. Technetium-99m (meta stable) decays to Technetium 99 through the release of a gamma (photons) rays of 140.5 keV (98.6%) and 142.6 keV (1.4%) as shown. The final result is Technetium-99 (Tc-99) with a half-life of 210,000 years.
Figure 6.
Radioactive decay curve of Technetium-99m
The radioactive decay of technetium-99m is shown. The physical half-life for Tc-99m is 6.01 hours. Given this information, one can calculate that over the course of 55 minutes there is a 10% decay of the isotope. In clinical studies looking at sestamibi redistribution to determine ischemia (Fleming 2009b, 2010a) the initial stress imaging is made at 5 minutes with the second imaging at 60 minutes.
An effort to improve image “sharpness” (Figure 7a) is the result of increasing the number of pixels in a given field. Cameras set up with a 64 x 64 matrix (pixel) resolution, will result in a more blurred image, while a matrix of 128 x 128 (pixels) will increase image “sharpness.” As seen in Figures 7b and 7c, the cost of increasing “sharpness” occurs at the cost of more septa separating each pixel, which reduces the area available for information acquisition. Each septa itself is excluded from acquiring information on radioactive decay, exchanging information for sharpness.
Figure 7.
a-c. The greater the number of pixels, the “sharper” the image “appears”. a.) Increasing the number of pixels increases image “sharpness”. b.) Fewer pixels reduce “sharpness” while increasing scintillation detection. c.) More pixels increase image “sharpness” but at the expense of scintillation detection
Figure 8.
Verification of Technetium-99m-Sestamibi Count Imaging
A 37.37 MBq syringe of technetium-99m-sestamibi is placed under the camera and counts acquired over 5 minutes. The same syringe is reimaged 55 minutes later for an equal amount of time. When the 64 x 64 matrix was used, the original count was 1,405,721, the second image count was 1,251,359, representing 89% of the original count activity. When the resolution was increased to 128 x 128 matrix, there was an additional 50% loss in data, with a 5-minute image (different syringe sample) count of 3,473,001. The second image count 55 minutes later was 2,966,394, representing a count decrease of 14.6%, 4.6 % more than should have been shown. This reduction is due to data lost as a result of increased grid lines forming the increased number of pixels per image. Subsequently, total information is lost at the gain of localization information (FH Uncertainty principle). Since we are looking for total cell uptake of the tracer, one must use the 64 x 64 matrix as a better index of isotope activity in exchange for resolution.
Figure 9.
The importance of recognizing visual illusions
Visual illusions such as this shown here can result in incorrect diagnostic decisions when depended upon by the clinician. This particular illusion demonstrates visual problems resulting from pixel information. When these illusions are the result of instrumentality, diagnosticians cannot reliably use them to make clinical decisions and the utilization of attenuation algorithms cannot reliably reduce these errors, making it even more important that we know what our nuclear cameras are truly capable of measuring and how to most accurately use them.
4. The kinetics of radioactive isotope distribution from vein to heart to cells to redistribution
Imaging protocols are frequently employed by clinicians with an incomplete understanding of the kinetics of a given isotope. Consequently, patients receive more isotope than may be necessary and under the wrong conditions for detection of the question at hand. E.g. the utilization of stress-rest OR rest-stress imaging, frequently results in two injections of radioactive isotope, when only one is needed, resulting in comparing apples and oranges. Resting images as discussed elsewhere in this chapter are useful only for determining tissue viability and do not augment coronary artery blood flow (viz. coronary or stenosis flow reserve) as discussed in Figure 12 below and elsewhere in this chapter and as such cannot be used to determine the presence or absence of ischemia. Similarly, resting images are not helpful for comparison with stress images as discussed in Section IV of this chapter and results in failure to accurately detect ischemia along with assignment of ischemia to the wrong regions of myocardium, leading to continued frustration for those using stress-rest protocols. In this Section of the chapter, we will review the process by which nuclear isotopes are injected, delivered and redistributed throughout the myocardium allowing us to better understand how we can take advantage of these properties to increase our detection of ischemia and as we shall see in Section V, the ability to detect myocardial viability.
Figure 10.
Diagram of coronary artery prior to injection of radioactive isotope
Figure 10 represents an artery with the lumen of the artery at the top of the image. On the left side is a critically narrowed artery with a vulnerable plaque, the region immediately below that represents myocytes when ischemic as seen under the microscope. Immediately below this is the appearance of mitochondria under severe ischemic conditions. Note the reduction in myofibrils and mitochondria under severe ischemic conditions. In the middle third of the image, at the top, lies a normal appearing coronary lumen with normal appearing myocyte with normal concentration of mitochondria immediately below the myocytes image. The right Section of the image represents diseased artery initially represented by extension outward as first demonstrated by Glagov (1987) from pathology specimens with encroachment into the lumen as we proceed from left to right. Immediately below the artery is the microscopic appearance of mildly damaged myocytes with the lower Section of the image revealing a reduction in the numbers of mitochondria present in regions with mild to moderate ischemia, but, more than the region of vulnerable plaque (left side of image) where severe ischemia is present.
Figure 11 shows the longitudinal and cross-sectional effects of an artery without disease on the left and a region of artery with inflammatory coronary artery disease resulting in ischemia. Arteries free of disease can vasodilate upon command to increase coronary blood flow while arteries with inflammation are unable to dilate to the same degree. These differences can be detected and measured in the nuclear laboratory as we have shown (Fleming2008a).
Figure 12 shows the relationship between coronary (stenosis) flow reserve and percent diameter narrowing. As established by Gould (1990) in dogs and in humans by Fleming (1991b, 1994) the greater the amount of inflammatory coronary artery disease (ischemia), the less the flow reserve and the greater the reduction in an arteries ability to carry blood flow along with radioactive isotopes to a region of myocardium where the isotope can cross the capillary membrane and migrate into myocytes for uptake and detection. These differences in flow were first established by Poiseuille (1840) in the laboratory.
Figure 11.
Demonstrates the capability of coronary arteries to dilate to increase coronary blood flow, viz. stenosis (or coronary) flow reserve, to meet increased myocardial oxygen and nutrient demands with “stress”
Figure 12.
Actual coronary flow reserve in humans as influenced by anatomic narrowing of coronary arteries
Figure 13 shows the injection of sestamibi into the right antecubital region immediately following stress. The radioactive material can be measured as documented by Blumgart (1926) to determine circulation time and myocardial status.
Figure 14 shows the same artery from Figure 10, with the initial pass of radioactive isotope material through the lumen.
Figure 13.
Initial injection of technetium-99m into the right antecubital vein
Figure 14.
Cartoon depiction of radioactive isotope initially entering a coronary artery.
Figure 15.
Cartoon depiction of delivery of radioactive compound from a coronary artery into the myocardium
This figure shows the passage of radioactive isotope (sestamibi) from the lumen into the myocardial tissues 5 minutes after injection into the venous system following “stress”. Passage from lumen to tissue is dependent upon four variables. First, when there is a region of artery is inflamed, there is (a) reduced passage of material through the region from the narrowing as well as a reduction in the dilatation of the artery to carry radioactive material as described in Figure 12. Secondly, as the wall of the artery is inflamed and thickened, there is an increased impediment to the movement of sestamibi through such a region in contrast to a non-inflamed region. Thirdly, as a region becomes ischemic, the mitochondria are less able to retain the sestamibi due to calcium overload (Crane 1993, Lenzi 2003, Kodavanti 2008) and there are fewer mitochondria to retain the sestamibi. Finally, sestamibi is a lipophilic compound (Maublant 1988) which when passing through (a) a lipid laden plaque and (b) an inflamed region or region with increased mitochondrial activity (Fleming 2000c) due to the white blood cells (greater mitochondrial concentration is required of these cells if they are to be able to respond to inflammatory stimuli including diseased arteries or bacteria which may or may not play a role in a disease artery) will have a greater uptake (Fleming 2002c-e, 2003a-c) of sestamibi, reducing the amount of radioactive tracer passing through the lumen into myocardial tissue with its mitochondria.
Figure 16.
Electron microscopic images of mitochondria showing the outer and inner membranes along with cristae and matrix
Figure 17.
SPECT image of distribution of Sestamibi within myocardial tissue which can be qualitatively Gestalted or quantitatively measured as done here
Figure 16 shows three mitochondria under different sets of conditions, as shown in Figure 15. The far left mitochondria shows the reduced delivery of sestamibi in a region of vulnerable plaque where the reduced lumen size, reduced flow reserve ability, the increased lipid laden material will result in a reduction in delivery of sestamibi to the mitochondria in the region. The middle panel shows a mitochondria receiving maximum delivery of sestamibi from an artery, which is able to vasodilate and carry maximum amount of isotope with no impedance to delivery of the isotope to the mitochondria and non-ischemic mitochondria. The far right panel shows more sestamibi delivery than the region with vulnerable plaque, with reductions due to limitations in lumen size and reduced flow reserve, but, not as limited as that occurring with the region of vulnerable plaque.
Figure 17 shows an actual myocardial perfusion image obtained 5 minutes after injection of sestamibi with three regions of interest (ROIs) measured in regions of (a) a vulnerable plaque (23,600), (b) a normal region (27,110) and finally (c) a region with ischemia without critical narrowing or vulnerable plaque (26,660).
Figure 18.
Coronary artery cartoon showing redistribution of radioactive isotope (in this instance sestamibi) with time
Figure 18 shows the effect of 55 additional minutes (60 minutes post-stress) of perfusion of tissue with sestamibi. During this time, there has been additional delivery of sestamibi to each of the regions of the heart. As established by Maublant (1988), the washout for sestamibi is 28 minutes. Crane(1993) established that ischemia affects the calcium concentration within mitochondria resulting in calcium overload and decreased potentiation for sestamibi retention. Between these two factors in addition to the four reasons discussed with Figure 15, regions of critically narrowed arteries or arteries with vulnerable plaque, as shown in the left side of the figure will have an increase in radioactive (sestamibi) count (concentration) at 60 minutes compared with that seen at 5 minutes. In the middle of the figure, the region of myocardium supplied with a normally functioning artery without narrowing sees a constant uptake and washout of Sestamibi (Maublant 1988) with the expected decay in isotope of 10% as shown in Figure 19. During this time, the greater amount of radioactive material present in the normal region provides a concentration gradient for increased delivery of isotope (sestamibi) to the region with critical narrowing and/or vulnerable plaque, adding to the increased delivery in isotope in this region over time. This increased delivery of isotope is defined as washin as will be discussed below. The far right hand Section of the diagram shows the effect of decreased retention of sestamibi by ischemic mitochondria (Crane 1993) with a greater than expected (10% by technetium-99m isotope decay) reduction in isotope concentration returning from the mitochondria into regions of normal tissue with a greater capacity to retain sestamibi for a greater period of time, or return of the isotope into the vascular space where isotope is delivered for excretion (Sattari 2001) from the body.
Figure 19.
Decay curve of technetium-99m
Figure 19 shows the decay curve seen for technetium-99m compounds. Over the course of 55 minutes (the time difference between imaging at 5 minutes and 60 minutes), there is a 10% isotope decay, which will result in the “normal” reduction in isotope seen over a 55-minute period of time.
Figure 20.
Changes in mitochondrial movement (redistribution) of sestamibi over time
Figure 20 shows the uptake/release of sestamibi by mitochondria at 60 minutes post-stress. When compared with Figure 16, it is clear that mitochondria (far left) in the critically narrowed/vulnerable plaque regions are now receiving greater concentrations of sestamibi as described in Figure 18. The mitochondria in the middle image shows continual uptake and release of sestamibi given the unimpaired delivery of the isotope and normal mitochondrial calcium levels leaving an unimpeded mitochondrial uptake and release of sestamibi. The far right panel reflects the findings noted in Figure 16, where there is relatively unimpeded delivery of sestamibi to the mitochondria, with increased release due to the effect of ischemia upon mitochondrial calcium concentration and mitochondrial function.
Figure 21 shows the results of sestamibi concentration and measurement of radioactive levels of sestamibi at 60 minutes post-stress. These results show what is described above, viz. and increase in concentration in the region of the vulnerable plaque/critically narrowed coronary artery with a count of 30,470. The region with normal blood flow and normal functioning mitochondria shows a count of 25,472 while the ischemic region without a critical narrowing or vulnerable plaque shows impairment in mitochondrial function as described above with a count of 15,407 despite reasonable delivery of the radioactive isotope sestamibi. This single 60-minute image minus the actual ROI counts, appears completely normal qualitatively leading one to detect no ischemia when it is used for rest to stress comparisons, which Gorlin (1959) demonstrated could not be used as a method for detecting ischemia.
Figure 21.
Measurement of sestamibi redistribution as quantitatively measured, allowing for assessment of both physiologic and anatomic information, which cannot be determined by comparing images using a visual Gestalt
Figure 22.
Anatomic information obtained from coronary angiography which was compared with physiologic information obtained from Sestamibi redistribution
Figure 22 shows the results of coronary angiography with detection of vulnerable plaques, normal arterial regions and regions of ischemia matching the findings of wash in and washout; but, not matching the results of the single 60-minute image displayed in Figure 21 when using only a qualitative method in stark contrast to a comparison of change seen between the 5-minute and 60-minute images above.
Figure 23.
Comparing quantitative sestamibi information between stress-stress imaging
Figure 23 represents the results of what is seen when the quantitative measurement of ROIs are compared for (a) regions of critically narrowed/vulnerable plaque regions (wash in) where radioactive concentration is seen to increase between the 5 and 60-minute images, (b) when disease is not present (both flow and mitochondrial function are unimpaired) and the change is count activity can be accounted for on the basis of isotope decay (Figure 19). As we have seen, the isotope (sestamibi) is not merely taken up and retained but as demonstrated by both Maublant (1988) and then Crane (1993), the isotope undergoes uptake and release, the rate of which is determined by ischemia and mitochondrial function. Finally, (c) washout is seen as an initial near normal delivery of isotope with impaired retention independent of the delivery of the isotope owing to mitochondrial calcium overload resulting from ischemia.
Figure 24.
Single injection, single camera imaging assessment of anatomic AND physiologic information obtainable by quantitative measurement of Sestamibi redistribution
Figure 24 summarizes all of the information seen both with changes in isotope concentration (washin, normal, washout); but, more importantly compares this with findings seen on coronary angiography, enhancing decision making capabilities from this physiologic change (Fleming 2008b, 2009a) in isotope over time.
Armed with the understanding of how our Nuclear SPECT cameras work and how these isotopes redistribute over time, we can now better understand the process by which we can best use our nuclear cameras to detect ischemic heart disease. It is estimated that in the United States alone, some 10 million nuclear heart scans are performed each yearly. Of these some 80,000 to 140,000 individuals will be told following their (Heart 2011) “rest-stress” SPECT myocardial perfusion imaging (MPI) studies, that they have no ischemic heart disease whatsoever. Of these 40,000 to 70,000 will go home and die from a heart attack. Evidence indicates that these individuals have “normal” appearing 60-minute post-stress studies and are only detected by finding a decreased uptake at 5-minutes post stress, viz. “wash-in.” The “rest-stress” approach simply cannot detect these individuals. In the next Section of this chapter, we will look at the evidence proving this and scientifically establish why so many people are being misdiagnosed and what we can do about it.
5. Fleming Harrington Stress SPECT protocol reduces radioactive dosage and increases ischemia detection. The detection of ischemic heart disease is accomplished by comparing multiple images of the heart following stress. (ischemia equals stress imaging)
Background: Radioisotope manufacturers, nuclear camera manufacturers, standard guidelines for myocardial perfusion imaging, all assume rapid isotope uptake followed by an essentially static retention mechanism. Contrariwise, the historic first nuclear cardiology study found measurement of nuclear isotope blood flow kinetics to be diagnostic of heart disease. No clinical investigations appear to have followed that classic finding. We assessed the clinical diagnostic utility of time course myocardial perfusion measurements following single injections.
Methods: One hundred twenty patients suspected of having heart disease underwent Sestamibi stress images taken at 5 and at 60 minutes following completion of cardiac stress. Quantitative (FRHWW) redistribution differences between the images were assessed. FHRWW results were compared with angiographic findings.
Results: Parabolic regression of stenosis on redistribution yielded an effect size of R(CI95%) = 0.72 to 0.95, (P=3.8×10-8). Fifteen percent of individuals with “normal” appearing 60 minute SPECT images were noted to having coronary artery disease using both redistribution data and coronary angiography requiring stent placement. These individuals had “wash in” of Sestamibi (isotope uptake greater at 60 minutes than 5 minutes) and signaled patients at risk of undergoing an acute cardiac event due to vulnerable plaques or tight lesions placing significant amounts of myocardium at risk of infarction. One of the individuals who did not require cardiac catheterization based upon the FHRWW data, underwent coronary angiography based upon rest-stress results AND had a major adverse event as a result of the subsequent cardiac catheterization. There was no detectable CAD, confirming the FHRWW findings and the need for caution in individuals undergoing invasive procedures.
Conclusions: Dynamic “uptake /release” models appear to be a superior alternative to the common “uptake/retention” models of technetium-99m isotopes used in nuclear myocardial perfusion imaging. This sequential quantitative diagnostic model, reinforces the work by Blumgart, enabling more accurate diagnosis of coronary artery disease and providing for intervention in individuals requiring stents or bypass, whom would otherwise be missed on rest-stress imaging protocols while avoiding unnecessary coronary angiography among individuals with “normal” Sestamibi redistribution.
While diagnostic testing and decision making in the treatment of atherosclerotic coronary artery disease (ASCAD/CAD) tends to revolve around evidence of anatomic [cardiac catheterization (Fleming1991b), coronary computed tomography, intravascular ultrasound (Taki 2001, St Goar 1991), et cetera] disease, it has been well established that this inflammatory (Fleming 1999c, 2000c-d) process may smolder for years and that up to 85% of all myocardial infarctions occur with < 30% diameter narrowing. It is; therefore, important for us to look for new ways to uncover this smoldering inflammatory disease process when intervention may be more beneficial to the patient and potentially less costly to the patient and society at a time when health care costs are a major issue.
When teenagers learn to buy their first automobile, they learn an important lesson. Not every car that looks good runs well. This same lesson applies to the diagnosis and treatment of ASCAD. The lesson is to determine how well the car runs, or in this case, how well the heart runs. Hence the importance of physiologic testing; i.e. testing to see how well the heart runs. Prior to nuclear imaging of the heart, now called myocardial perfusion (Maddahi 2001, Kern 2006) imaging (MPI), patients ran on a treadmill (exercise stress testing/EST) under the belief that this would precipitate chest pain (angina) and perhaps electrocardiographic and hemodynamic changes which would indicate problems with coronary blood flow. Until recently, it was believed that this was purely the result of narrowing within the lumen of the artery. It has since been demonstrated that angina is the result of regional blood flow (Fleming 2000e, 2003d) differences; hence, the importance of quantifying such areas of the heart by analyzing regions of interest (ROI). These differences in regional blood flow work through mechanisms as of yet not completely understood. The ability to precipitate these differences in regional blood flow can be accomplished via the utilization of MPI and pharmacologic or exercise stress testing. A major limitation with utilizing single 60 minute images for interpreting the presence of ischemia on MPI are attenuation artifacts. Such artifacts include anterior attenuation from breast tissue, diaphragmatic attenuation from abdominal obesity, hypertrophic differences in walls of the heart, bundle branch anomalies, et cetera. These attenuation issues have not been significantly corrected with the addition of attenuation correction protocols. While nuclear tracers (isotopes) have improved over the years, many misconceptions (Beller 1990, Fleming 1991a, Sinusas 1994, Dahlberg 1994, Glover 1995, Hurwitz 1996, Husain 2007) have plagued the field limiting the accuracy of MPI with sensitivities and specificities remaining at 65-90% in most published investigations (Parameswaran 2006).
In 1926 Blumgart first proposed nuclear imaging techniques for the detection of heart disease. His method clearly proposed serial assessment of isotope count activity to determine cardiac function. Decades passed before Love (1965) discussed the potential future of Nuclear Cardiology and pointed out that rest images (Gorlin 1959) were useless in the detection of coronary artery narrowing. With the advent of technetium-99m- sestamibi, clinicians believed that the isotope was taken up by myocardial tissue within minutes of injection and remained fixed within myocytes. Crane (1993) demonstrated this was not so and demonstrated that retention of sestamibi was dependent upon ischemia and cellular viability. This opened the door to the discovery of changes in isotope count over the course of time and reinforced Blumgart’s 1926 paper. During our initial (Fleming 2003e, 2008) efforts to better understand the underlying inflammatory component of CAD via MPI, five and sixty minute imaging revealed differences in the qualitative appearances of images seen following pharmacologic stressing of individuals as predicted by Blumgart (1926), Love (1965) and Crane (1993). As noted below, others have noticed these differences as well. Furthermore, comparisons of the initial 5-minute imaging with the 60-minute imaging demonstrated different results from the simple “uptake/retention” rest-stress model. Other investigators have noted similar differences between 5 minute and 60 minute imaging of the heart (Hurwitz 1993, 1998, Saha 1994, Giubbini 1995, Pace 2005) allowing for enhanced detection of congestive heart failure (Hurwitz 1998, Kumita 2002, Sugiura 2006, Matsuo 2007), cardiomyopathies (Meissner 2002, Ikawa 2007), Prinzmetal \'s angina (Ono 2002, 2003) and underlying coronary artery disease (Meerdink 1990, Richter 1995, Shin 1995, Takeishi 1996, Takahashi 1996, Fujiwara 1998, Hurwitz 1998, Ayalew 2000, 2002, Liu 2001, Kumita 2002, Tanaka 2006, Fukushima 2007, VanBrocklin 2007) including evidence of wash-in (Meerdink 1990, Richter 1995) indicative of critical lesions not detected by conventional MPI. In the same way that thrombolysis in myocardial infarction (TIMI) flow is used to look for changes (sometimes subtle, sometimes not) in coronary blood flow in the catch lab, multiple imaging following pharmacologic or EST allows us to take a more advanced look at the physiologic function of the heart, unmasking ischemic heart disease missed by rest-stress imaging.
Given these recent investigations into improving the detection of ischemia by quantifying isotope counts on multiple (sequential) images following pharmacologic and exercise stress, we set out to determine (1) are nuclear cameras used in the “clinical” setting today able to detect differences in radioactive isotope counts over a period of time, which would allow these cameras to detect changes in flow and retention of isotope over time (2) what are the optimal imaging times for the detection of ischemia and (3) how do these changes in isotope counts compare with percent diameter stenosis as seen on coronary angiography?
5.1. Methods
5.1.1. Single Photon Emission Computed Tomography (SPECT) cameras
The Philips Forte Dual Head SPECT camera used general all (GAP) purpose collimators with the heads positioned at 90 degrees per manufacturers specifications. A 15% window was used with a 64 by 64 matrix. In the first Section of this study, we additionally looked at differences between 64 x 64 matrix and 128 x 128 matrix. Imaging occurred 5 and 60 minutes post stress with processing of images as described in the literature (Fleming 1991a, 2003e, 2008). Jet stream software was used per manufacturer’s instructions to quantitatively measure regions of interest (ROIs).
The Picker Axis Dual Head SPECT camera used a low energy general all (LEGAR-PAR) purpose collimator with parallel hole positioning. The heads were positioned at 102 degrees per manufacturer specifications. Picker camera software was used for ROI measurements.
Determining if Nuclear Cameras used in “Clinical” Practice are able to detect changes in isotope count over time.
Establishing technetium-99m decay by radioactive count measurement: Based upon the half-life of technetium-99m, a stable source representing the “uptake/retention” model (viz. a syringe filled with the isotope) has a 10% decay over 55 minutes with a retention of ~90% of the radioactive counts over a 55 minute (the difference between 5 and 60 minute images) span of time. In an effort to establish whether “clinically” used cameras are able to measure this physical decay in technetium-99m, we studied a 37.37 MBq (10.1 mCi) sample of sestamibi at baseline and again 55 minutes later. As shown in Figure 8, the resting isotope count was 1,405,721 while the second image obtained 55 minutes later was 1,251,359 representing 89% of the original count activity. Independent of the actual amount of activity which is taken up by a region of myocardium, if the “uptake/retention” model was correct, images taken 55 minutes after the original image would yield counts of 90% of that seen in the first image.
Fleming-Harrington Redistribution Wash-in (FHRWW) Washout (Fleming 2009a-b, 2010a): Using Multiple SPECT Camera Images of the Heart to Determine Changes Between 5 and 60-Minute Images.
Optimal Timing to Measure Changes in Radioactive (Sestamibi) Isotope Activity.
Measuring regions of interest (ROIs) to quantify changes in technetium-99m isotopes between 5 and 60-minute images to look for changes in isotope “uptake/retention.” We began with the knowledge acquired from the first Section of this study, that we needed to use the 64 x 64 matrix to accurately measure changes in radioactive decay. We then proceeded to analyze ROIs at 5-minutes (Figure 25) and at 60-minutes (Figure 26). FHRWW calculations (discussed below) demonstrated that the “uptake/retention” model was clearly wrong as seen by the increase in count activity in the anterior wall (23,600 at 5-minutes and 30,470 at 60 minutes) while the inferior region without ischemia demonstrated a 6% reduction in count activity.
Establishing the optimal time sequence for image acquisition to measure radioactive counts: Using this particular individual (Figures 25 and 26), during this second phase of the investigation, we additionally compared the basal anterolateral, mid anterolateral, basal anterior, mid anterior, basal inferior, mid inferior basal, inferoseptal and mid inferoseptal ROIs and compared the results with that obtained from coronary angiography. We then measured radioactivity in each of the 8 ROIs over the course of an hour, with the salient findings reported in Figure 27. These results were compared with our previous studies (Fleming 2003e, 2008) which revealed the ideal timing for detection of inflammatory changes and based upon the expected 10% decay of technetium-99m over a span of 55 minutes, the remainder of our work (FRHWW) focused on ROIs obtained at 5 and 60 minutes post stress. These results confirm that Sestamibi does NOT follow an “uptake/retention” model; but rather an “uptake/release” model consistent with Sestamibi redistribution (FHRWW).
5.2. Calculating FHRWW
By comparing 5 and 60-minute imaging, the expected decay of Tc-99m is 10%. Actual counts from individual ROIs can then be taken and actual redistribution (FHRWW) can be calculated as follows.
FHRWW (Total Heart)==ROI counts (total heart) at 5 minutes − ROI counts (total heart) at 60 minutesROI counts (total heart) at 5 minutes×100−10E1
Where 100 places the answer in percent minus the 10 % expected decay.
FHRWW for a particular myocardial ROI ==ROI counts (region) at 5 minutes −ROI counts (region) at 60 minutesROI counts (region) at 5 minutes×100−10E2
This can be re-written as:
Let the 5 minute counts =‘x’, let the 60 minute counts=‘y’, and let % washout=‘100*w’E3
Comparing washout/wash-in results with coronary angiographic assessment of percent diameter stenosis.
One hundred twenty patients (ages 25 to 82 years) with suspected coronary artery disease underwent myocardial perfusion imaging after signing informed consent per Institutional protocol following adenosine (n=30), lexiscan (n=61), dobutamine (Fleming 1995, 1999a, Calnon 1997, 1999, Matsunari 2001), n=4 or treadmill (Fleming 1991a, 1999a), n=25 stress. Following standardized protocols already published (Fleming 2009a-b, 2010a) MPI using both the rest-stress and stress-stress (FHRWW) approach were compared with coronary angiography (Fleming 1992a-b).
Statistical Analysis. Quantification of isotope counts was made using the specific nuclear computer software provided by the nuclear camera companies. These quantified counts were recorded with calculations of FHRWW as noted above. Correlation coefficients, confidence intervals and p-value (significance levels) were determined between %DS and FHRWW using product-moment correlation and least squares regression fitting the hypothesized model of y=cx2. Using the null hypothesis for n = 120 patients, we estimated odds ratios (ORs) for predicting final diagnosis from nuclear procedures. ORs were determined against coronary angiography results for both the rest/stress images and FHRWW images. Statistical analysis and graphics were developed using R-2.6.0 and GGobi software.
5.3. Results
To the best of our knowledge verification of the ability of a nuclear camera used for “clinical” purposes to measure sequential radioactive counts confirming differences in technetium-99m-sestamibi resulting from the physical decay of the isotope has not previously been reported in the literature. The first phase of this study was to confirm that cameras used clinically are able to detect differences in radioactivity accurately, assuming they employ the correct matrix to do so. To prove this, we used 37.37 MBq of technetium-99m-sestamibi with both a 64 x 64 matrix and a 128 x 128 matrix. The results of the 64 x 64 and 128 x 128 matrices are shown in Figure 8. Over a 55 minute period of time, the expected decay of technetium-99m would be 10%, leaving a residual activity of 90% of the original counts. This represents a true “uptake/retention” model since the radioactive compound is retained within the syringe. Using the 64 x 64 matrix, the radioactive counts went from 1,405,721 to 1,251,359 representing an 11% decay with a residual 89% of the original isotope activity. The 128 x 128 matrix reported 3,473,001 at baseline and a count of 2,966,394 55-minutes later for a decay of 14.6% with a residual of 85.4% of the original isotope activity. For this reason, the 64 x 64 matrix more correctly demonstrated the expected decay of the isotope based upon the physical half-life of Tc-99m and was therefore chosen as the standard for performing these studies.
The second question related to the timing of data collection. Prior studies (Fleming 2003e, 2008) demonstrated the ability to detect inflammatory markers on SPECT images at 5 minutes; but, not at later periods of time. Figure 27 displays the results of radioactivity measured using the clinical camera with a 64 x 64 matrix. As shown, the peak detectable radioactivity was measured between 5 and 10 minutes post injection for individuals with “no” coronary artery disease or coronary artery disease without “critical” lesions or “vulnerable” plaques. In individuals with “critical” lesions and/or vulnerable plaques, radioactive counts increase from 5 to 60 minutes, viz. wash-in (Fleming 2009a-b, 2010a). Combined with the results of instrumentation (Figure 10), the ability to detect ischemia based upon blood flow and cellular uptake and release of sestamibi, is best made by comparing counts at 5 minutes and 60 minutes.
The final component of our study compared results of rest-stress imaging and FHRWW with angiographic (%DS) data. There were no differences observed between individuals who were stressed either physically or pharmacologically. Outcomes were not changed by the stressor used, as the comparison between rest/stress and FHRWW determination of redistribution was independent of the type of stress. The use of regional wall motion information was used with both the rest/stress protocol and the FHRWW approach, which made it possible to look for wall motion abnormalities and ejection fraction using either approach. Since these observations are identical, regardless of which method was used to report ischemia, we do not report them here.
We analyzed the results of rest/stress image comparisons and FHRWW redistribution images and compared them with findings obtained from coronary angiography. For the rest/stress images, the OR for detecting ischemia was 4.9 with a CI (95%) of 2.3 to 10.3. For FHRWW, the OR was 56.8 with a CI (95%) of 27.5 to 117.2. When the results of these ORs were compared, the t value was greater than 6.6 (P <.0001). We obtained results of %DS for each of the epicardial arteries and their branches, and plotted these results against the redistribution results for each of the eight ROIs. This could only be done with the redistribution data, which provided quantitative results, which could be compared with the quantitative results obtained angiographically.
Comparison of the rest/stress image results with the angiographic results showed a sestamibi rest/stress imaging sensitivity of 67%. Of the false negative results (n = 22), 18% (n = 4) had critically narrowed arteries or arteries with vulnerable plaques whose 60-minute images appeared completely normal (Pace 2005, Fleming 2008). However, evaluation of the 5-minute images for redistribution (using FHRWW), revealed both qualitative and quantitative decreased uptake, demonstrating a washin effect. The 60-minute post stress images miss this washin phenomena when looked at independent of the 5-minute images, yielding incorrect results. The standard rest/stress images also yielded a specificity of 88%; of which, only one participant (0.8%) who underwent a coronary angiogram had an adverse outcome requiring cardiopulmonary resuscitation (Hurwitz 1993).
FHRWW calculation was made first by comparing the total radioactive counts of the heart at 5 minutes with the total counts of the heart measured at 60 minutes. The eight regions of interest (ROIs) were then compared using both the 5 and 60-minute image information. Analysis of eight ROIs appears to provide the optimal analysis of specific coronary artery beds (left anterior descending, circumflex and right). These regions include the basal anterior, mid anterior, basal anterolateral, mid anterolateral, basal inferior/posterior, mid inferior, basal inferoseptal and mid inferoseptal. Examples of some of these regions are shown in Figures 25, 26, 28a-c and 29a-d. These multiple examples show how, independent of different color scales and cameras used to qualitatively estimate ischemia; quantitative measurements can be made independently and without interference from hepatic and other tissue uptake. Washout (counts greater at 5 minutes than 60 minutes, excluding the expected isotope decay) and washin (noted counts greater at 60 minutes than 5 minutes) were plotted against the percent diameter stenosis (%DS) determined on coronary angiography. Washin was seen in 15% of the individuals studied and was associated with “normal” appearing 60-minute images. When the results of washout/washin were compared with %DS, a parabolic relationship was demonstrated with F = 70.4, df(1,21), (P=3.8×10-8), R(CI95%) = 0.72 to 0.95.
5.4. Discussion
The advent of nuclear cardiology by Blumgart beginning in 1925 yielded a new era of medicine with the use of radioactive materials to perform physiologic testing which requires sequential measurements as described by Blumgart to be performed correctly. Unfortunately, decades elapsed (Love 1965) before such nuclear materials were made readily available for “clinical” use. The first agent being Thallium-201 (Tl-201) was plagued with limitations including a long half-life (72 hours) resulting in the need to use relatively low doses (6.8-11.1 MBq) of the isotope. Given the limitations (Fleming 1992a, 1995) of Compton scatter, tissue attenuation and the emission of mercury x-rays from the isotope, cameras could not acquire adequate counts for imaging until 60 minutes had elapsed. Given the passage of time, much of what Blumgart discussed had been lost to history (Love 1965). With the advent of Molybdenum-99, Technetium-99m generators, the ability to perform clinical studies using technetium tagged agents (e.g. teboroxime, sestamibi, myoview, et cetera) with shorter half-lifes (6 hours) allowing greater doses (up to 1110 MBq) and less Compton scatter and tissue attenuation issues yielded what “appeared to be cleaner images”. These images were still plagued with attenuation issues and were reported to be “taken up and retained” within minutes of intravenous injections. Despite the report by DuPont (Crane 1993) and multiple other research and clinical (Everett 1977, Fleming 1992b, 2003e, Aodah 2007, Fallahi 2008) studies discussed above and below, which have clearly established that these isotopes redistribute and do not “stick”, most clinicians have continued to ignore Blumgart’s teaching of performing sequential evaluations under same state conditions and have subsequently limited their investigation of coronary artery disease to single post-stress imaging despite the teaching of nuclear imaging which notes that “a better indicator of organ function is the change in the activity in a particular organ with time.” Newer clinical observations and publications (Sheikine 2010) have since been made confirming our earlier observations from 2000-2001.
Inconsistencies in analysis of cardiac imaging have led some researchers (Fleming 2002b, Toriyama 2005, Oregon 2008) to recommend that these clinical studies be standardized quantitatively; something this study has accomplished. In medical school we were taught that there were two ways to understand the results of a test. The first is to compare it against the population (e.g. one obtains an electrocardiogram to look for evidence of ischemia or infarction), the second is to compare it with the results of that test which the patient had previously (e.g. poor R-wave progression may actually represent loss of R-waves and evidence of a prior anteroseptal injury/infarction which can be made more confidently in the presence of a change in the electrocardiogram for that patient, opposed to the confidence one has in making such a diagnosis when this is the first electrocardiogram). The same problem applies with looking at a region of the heart on a single 60 minute image post stress. Issues of tissue attenuation including (1) breast artifacts in the anterior wall, (2) diaphragmatic attenuation inferiorly, (3) differences in wall thickness (asymmetric septal hypertrophy) and (4) conduction disturbances influencing timing of systole (left bundle branch morphology) are examples of errors made when one region of myocardium is compared with another region (e.g. a single 60 minute image) instead of comparing a region with itself (5 and 60 minute images) and looking for change. Unless there is a change in breast tissue or abdominal obesity between the 5 and 60 minute image, errors resulting from soft tissue attenuation of photon activity are eliminated. The same applies for changes in wall thickness and conduction issues; unless there is a change between the 5 and 60 minute image, the region is being compared with itself and such artifacts are eliminated.
Despite an absence of research to support the ability of “clinical” nuclear cameras to accurately detect changes in radioactive counts which match the expected decay of the nuclear isotope in question clinicians have used these cameras to assess the presence or absence of disease in patients. As Archie Cochrane and history has taught us it is truly dangerous to assume that the way we have been doing something is the correct way to do it in the absence of data to confirm we are right. The first Section of this study demonstrated that the cameras we used in this study were able to accurately detect the decay of technetium-99m-sestamibi over a 10% decay. This was best appreciated using the 64 x 64 matrix. Even though manufactures support the use of 128 x 128 matrix as giving greater detail, the use of the 128 x 128 matrix reported a greater decay in the isotope than is physically possible suggesting that information is lost; perhaps as a result of “modulation transfer function” (a concept well known to photographers and imaging engineers).
During the second and third Section of our study we looked at the timing sequence, which would yield the most valuable information, not only regarding detecting changes in radioactivity with cardiac tissue, but the ability to detect markers of inflammation (Fleming 1999c, 2000c, 2003e, 2008, Kern 2006). Our previous findings clearly demonstrated the importance of looking for markers of inflammation when detectable, i.e. at 5 minutes post stress. During this study and our most recent work (Fleming 2009a-b, 2010a) we clearly demonstrated that in individuals who had ischemia with non-critical narrowing of arteries, that maximum radioactivity was present during the first 5 to 10 minutes. The inability to maintain the Sestamibi in regions of ischemia has previously been termed “washout” and represents an inability to retain the isotope within the mitochondria in the region. This clearly confirms the work of Crane (1993), who demonstrated that sestamibi redistributes AND is not retained in regions of “ischemia.” Our studies also proved this to be the case, independent of which technetium-99m isotope (Fleming 2009a) was used or which form of stressor (Fleming 2009a-b, 2010a) was used. Our current study clearly demonstrates this to be true in the “clinical” setting and disproves the “uptake/retention” theory in favor of an continual FHRWW “uptake/release” model which would explain not only the loss of isotope to an ischemic myocardial region over time; but, also accounts for “wash-in.” “Wash-in” was noted in 15% of the cases where regions of myocardium were supplied by “critically” narrowed arteries and arteries whose “vulnerable plaques” were ready to rupture. In these individuals the combination of severely disturbed flow through critically narrowed and/or unstable coronary lumen passages and relatively large regions of ischemic myocardium with impaired ability to accumulate sestamibi, results in a delay in initial isotope counts. From this perspective, uptake is a function of isotope availability (myocardial blood flow) and cellular health; retention is transient with release of the isotope back into the blood stream or redistribution to other cells, a function of cellular health and re-uptake subject to a cellular refractory period. As a result the delay in isotope delivery is not noted if stress imaging is limited to 60 minute imaging. These individuals, despite “normal” appearing 60 minute images, were at risk of experiencing an acute coronary event with loss of substantial amounts of myocardial tissue.
5.5. Conclusion
The standard “uptake/retention” model was observed only in subjects who demonstrated no evidence of coronary ischemia or infarction. In reality, such an “uptake/retention” model is simply an illusion. It is the rapid “uptake/release”, “uptake/release”, “uptake/release” in non-ischemic, non-infarcted myocardial tissue that makes it appear that the isotope is taken up and retained. In other words, if the amount being released and the amount being taken up are equal, one will not detect a change in isotope count over time, minus the slight decrease occurring from isotope decay. Such individuals would appear to have no change in isotope concentration despite continual turnover of isotope. “Uptake/release” was demonstrated via washout in individuals with coronary ischemia and a delayed “uptake/release” in individuals with washin due to critically narrowed and unstable plaqued regions supplying significant amounts of myocardium. Wash-in and washout are terms used to convey different types of CHANGE in isotope concentrations which occur over time at different rates to indicate the type of lesions present in the individual being studied. The results of these changes can be compared with changes found on cardiac catheterization as shown in Figure 30. As we continue to expand the number of individuals being studied with this method, it is clear that specific regional information can be determined from the parabolic equations used here and graphically displayed in Figure 30. The utilization of this knowledge will allow us to better determine which patients will benefit most from coronary angiography and has now been confirmed “qualitatively” by investigators at UCLA and Harvard Universities (Sheikine 2010). With the advent of nuclear cameras capable of faster image acquisition, we will undoubtedly be able to compare washout of the more rapidly redistributing technetium-99m compounds such as Teboroxime (Fleming 1990a-c, 1991a, 1992b, Goldstein 1991). Given the failure of rest-stress imaging to deliver on the promise of detecting ischemia and tissue viability due to their failure to image the heart as explained by Blumgart (1926) and Gorlin (1959), it is clear that FHRWW represents a superior method as we have already seen above and will see below.
We expect that the FHRWW protocol will replace other outdated and incorrectly proposed protocols due to its accuracy, simplicity, and reduction in amount of radioactive material used for imaging allowing for (1) a further reduction in the amount of radioactive material required for ischemic imaging, (2) faster imaging times (3) with FHRWW the ability to calculate %DS directly from nuclear imaging and (4) when coupled with previously published flow reserve equations (Figure 14), the ability to calculate stenosis (Fleming 1994) flow reserve directly from FHRWW. The Fleming Harrington Redistribution Wash-in Washout quantification of technetium-99m isotopes will allow for the first time (Fleming 2010c), the acquisition of both Anatomic and Physiologic data from a single radioisotope injection, single camera imaging system, including Positron Emission (PET) Tomography (Fleming 1999a), Magnetic Resonance Imaging, or Computed Tomography (CT).
As mentioned in the first Section of this chapter, the desire to know if the patient has undergone myocardial damage or injury (infarction, stunning or hibernation) has long been a question of interest. While, today it may appear to be much less of a concern given the increased availability to measure cardiac enzymes and look for evidence of regional wall motion abnormalities, either by echocardiography, nuclear, magnetic resonance or other imaging modalities, the detection of wall motion abnormalities and elevated cardiac enzymes does not tell us if the tissue damage is full thickness (Figure 12) and permanent, or partial thickness and recoverable. This is the true value of “resting” nuclear imaging. However, just like ischemic imaging, the detection of tissue damage, requires multiple same state condition (viz. rest-rest) imaging, which we will discuss in the next and final Section of this chapter.
Figure 25.
SPECT image acquired 5 minutes post stress with regions of interest including the total heart, anterior and inferior myocardial regions
Static image acquired at 5 minutes with regions of interest (ROI) showing total heart count of 374,930. The anterior ROI representing the basal anterior region of the perfused by the left anterior descending artery shows 23,600 counts while the inferior ROI shows 27,110 counts.
Figure 26.
SPECT image acquired 60 minutes post stress with regions of interest including the total heart, anterior and inferior myocardial regions
Reconstruction of the same myocardial regions noted in figure 1, this time taken from the dynamic image result obtained at 60 minutes post stress, showing a total heart count of 216,886. The anterior ROI shows an increase in count activity (wash-in) of 30,470 compared with the activity of 23,600 (Figure 1) obtained at 5 minutes. The inferior ROI shows a count of 25,472 compared with the count activity of 27,110 (Figure 1) obtained 5 minutes post stress.
Figure 27.
Determination of Optimal Timing of Image Acquisition
The radioactive counts acquired in eight different myocardial regions vary with time and disease. This graphic demonstrates changes between 5, 10 and 45 minutes post stress. This graph demonstrates that the “uptake/retention” model of technetium-99m-sestamibi is incorrect and that “uptake/release” of technetium-99m-sestamibi occurs throughout the first 45 minutes following stress.
Figure 28.
c. Radioactive Counts Acquired at 5 and 60 Minutes Post Stress
Anterior images reveal ROI counts at 5 and 60 minutes in the basal anterolateral (A, K), mid anterolateral (B, L), mid inferoseptal (D, N) and basal inferoseptal (C, M) respectively. The counts are shown below the images. The lateral images reveal ROI counts at 5 and 60 minutes in the basal anterior (G, O), mid anterior (H, P), mid inferior (J, R) and basal inferoposterior (I, Q) regions respectively. The total heart and lung counts are not shown or discussed in this paper; however, their ROIs are represented by square boxes of equal size in the anterior images.
Anterior images reveal ROI counts at 5 and 60 minutes in the basal anterolateral (1, 1), mid anterolateral (2, 2), mid inferoseptal (4, 4) and basal inferoseptal (3, 3) respectively. The counts are shown below the images. The lateral images reveal ROI counts at 5 and 60 minutes in the basal anterior (1, 1), mid anterior (2, 2), mid inferior (4, 4) and basal inferoposterior (3, 3) regions respectively. The total heart and lung counts are not shown or discussed in this paper; however, their ROIs are represented by square boxes of equal size in the anterior images.
Figure 29.
Radioactive Counts acquired at 5 and 60 Minutes Post Stress
Figure 30.
Parabolic Regression of Washout on Percent Diameter Stenosis
Percent diameter stenosis noted on coronary angiography was plotted against the results of washout. Stenosis = 0.011×Washout2, F = 70.4, df(1,21), (P=3.8×10-8), R(CI95%) = 0.72 to 0.95, Graphic bands show the standard error of the fit. The region of “No Ischemia” is marked in green. “Wash in” is displayed in red to the left of the “No Ischemia” region, while “Washout” is to the right of the “No Ischemia” zone.
6. FHRWW rest-rest SPECT viability imaging - cardiac viability measured using resting FHRWW redistribution of sestamibi: the scientific evidence proves “sestamibi redistributes and is not mitochondrial superglue”
Abstract: Sequential imaging of the heart began in 1926 with the emphasis by Blumgart1 on detecting changes in isotope over time. In recent years this change in isotope has been defined as “washout/wash in” and has been used to better define ischemia. Our investigations of sestamibi have demonstrated that not only can multiple post-stress images be used to more accurately define ischemia as defined below; but also, multiple resting images can be used to differentiate between viable and infracted myocardium.
The introduction of Nuclear Cardiology in 1926 by Blumgart (1926) established a protocol of sequential imaging/counts to differentiate people with heart disease from those without. In 1959 Gorlin demonstrated the importance of differentiating between resting studies, which provided information regarding tissue damage, from stress studies, which provided important information relevant to ischemia. With the introduction of technetium-99m compounds in the late 1980’s, clinicians erroneously assumed that sestamibi was taken up by cardiac tissue within minutes and retained. Crane (1993) proved that the uptake of sestamibi by myocytes was dependent upon mitochondrial calcium, which in turn was dependent upon ischemia. This was confirmed clinically by Hurwitz (1998) and many (Ono 2002, 2003, Fleming 2008b, 2009) others. Our investigations have included initial observations regarding cellular viability. We present a case report of the promise of sestamibi in distinguishing between viable and infracted myocardium.
Case Report. Mr. JW is a 56 year-old Caucasian male who presented to the Emergency Department with chest pressure. His risk factors for heart disease included tobacco use, hyperlipidemia and borderline glucose intolerance. No electrocardiographic changes (Figure 31) were noted. Over the course of the next 24-36 hours both his Troponin and CK-MB levels were noted to be elevated and he was taken to the coronary angiography suite where a 100% occluded first obtuse marginal was stented. Also noted were a 20% mid-left anterior descending (LAD) and 50% distal LAD lesion, which were not treated.
6.1. Redistribution/washout information
The patient was brought to the nuclear laboratory 3 days after undergoing coronary angiography to evaluate the extent of myocardial damage. He was given an injection of 370 MBq (10 mCi) of sestamibi and had static images (FH Washout) taken 5-minutes and 60-minutes later (Fleming 2008b, 2009). Dynamic images were subsequently taken looking for wall motion abnormalities. The patient then underwent adenosine sestamibi (1110 MBq) imaging following the same protocol as that used for the resting images. The results of the counts obtained from the resting images are shown in Figure 34. The dynamic resting study demonstrated no regional wall motion abnormality and a near absence of isotope activity in the lateral wall. The dynamic stress study showed lateral wall hypokinesis.
In previous years, technetium pyrophospate was used and later abandoned to define the presence or absence of myocardial infarction (MI) when cardiac enzymes were obtained too late to determine non-q-wave MIs. Of great interest is the ability to determine if an area which appears infracted (Figure 33) on resting studies represents potentially viable tissue, which would benefit from revascularization. Clearly, sestamibi does not simply “stick” to myocardial cells; but, as emphasized by Crane3 is dependent upon mitochondrial calcium, which is subsequently influenced by ischemia. Once cellular death has occurred, mitochondrial function ceases and mitochondrial calcium “overload” results.
In this patient the final 60 minute counts equaled that of the remaining “clearly viable” myocardium and as such is “viable” despite the appearance on the 60-minute resting dynamic study from which only infarction can be inferred. The 60-minute dynamic rest study revealed no regional wall motion abnormality while the dynamic stress study revealed “hypokinesis”, not “akinesis”. The initial 5-minute static resting counts demonstrated that either injury (viable) or infarction had occurred in the anterolateral region. It is the comparison of the two sets of resting image “counts” which allows the distinction between viable and infarcted tissue. Had the anterolateral region been infarcted, then the myocytes would not have been able to concentrate any sestamibi and both 5 and 60 minute counts would be lower than the remaining viable myocardium. These findings support the speculation by Crane in 1993, that “99m-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium” and that by comparing results at 5 and 60-minutes, we can distinguish between viable and non-viable myocardium.
Figure 31.
Electrocardiogram
The patients resting electrocardiogram showed no evidence q-wave or ST changes.
The radioactive counts for each of 8 regions of myocardium are shown. The count activity present at 5 minutes is shown in blue and is greater than that seen for the count activity at 60 minutes. By 60 minutes, most of the myocardium had the same count activity despite the appearance present in figure 3. Note that the count activity in the anterolateral region is much lower initially than the count activity present in the remaining myocardium indicating that a non-q-wave myocardial “damage” has occurred in the anterolateral region. However, the presence of sestamibi activity at 5-minutes indicates viability anterolaterally.
Figure 32.
and 60-Minute Rest Image Counts
Figure 33.
Results of the dynamic 60-minute rest image
The resting image obtained 60 minutes post injection of isotope shows a significant reduction in isotope in the anterolateral wall despite similar count activity as shown in figure 1. The electrocardiogram in table 1 shows no evidence of q-wave development or ST changes.
7. Conclusion
As this chapter has emphasized, the development of Nuclear Cardiology by Blumgart in 1926 saw a bright future allowing clinicians and scientists the opportunity to look within the body by detecting the emission of radioactive decay from tissue following its injection, distribution and redistribution. The radioactive compounds are not static and their movement (redistribution) allows us the unique opportunity to understand where there are and how they change position with time. This movement is a reflection of delivery (blood) and uptake (cellular and mitochondrial) and redistribution of the isotope over time. Just as the solutes within our cells and interstitial space are not static, so it is with the radioactive isotopes we inject. The movement of these radioactive isotopes over time allows us to understand both the Anatomy and the Physiology of the interior of our bodies. More importantly, understanding when to image and for what purpose is key to understanding what processes we are actually measuring (either qualitatively or quantitatively). In the case of ischemia, these comparisons must be made between “stress” images, while for tissue viability, these comparisons must be made under “resting” conditions. While Blumgart and Gorlin were clear as to these points, much of the energy expended in Nuclear Imaging of the Heart has failed to address these errors. As such, coronary arteriography has remained the “Gold” standard for the anatomic detection of heart disease. As our recent understanding has improved, so has our detection of disease and our ability to reduce the amount of radiation our patients receive and that which we receive secondarily. Seventy-five years after Blumgarts original work, we have peered through the uncertainty of our equipment and the limitations of our old methods. Today, we can truly detect heart disease and utilize it to improve the care provided to our patients and be confident of our diagnoses and treatment. We have replaced the “Gold” standard of coronary angiography which can only provide anatomic information of coronary (Figure 34) lumen disease (Fleming 2000f, 2001) with a “Platinum” standard providing both anatomic and physiologic information required for the better detection and treatment (Figure 35) of coronary artery disease.
Figure 34.
Coronary angiographic detection of disease
Coronary angioscopy with tissue specimens show immediately to the right of each following death of the individual. The upper panels show an individual with plaque intruding into the coronary lumen. The bottom panels represent a patient without visible lumen disease. As evidenced by the pathology specimen, the inflammatory plaque laid beneath the endothelial layer and was not detectable by visual inspection of the coronary lumen either by angioscopy or conventional cardiac catheterization and contrast injection. Nonetheless, this inflammatory plaque (Fleming 1999c-d, 2000g, 2002f, 2003d-f, 2008a, 2009b) is physiologically responsible for angina and plaque rupture leading to death. Such individuals may be easily missed by the angiogram and stress-rest approaches; but, can be unmasked by FHRWW stress-stress imaging (Fleming 2009b) as demonstrated in this chapter.
Figure 35.
Chest pain algorithm11 using FHRWW
Efforts to improve acute chest pain analysis employing FHRWW can be used to distinguish between the most critically ill individuals who will have critically narrowed arteries or arteries with vulnerable inflammatory plaques by virtue of wash-in findings defined by reduced isotope at 5 minute post pharmacologic stress imaging and normal appearing isotope concentrations at 60-minutes post-stress from those without such critical disease.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/16142.pdf",chapterXML:"https://mts.intechopen.com/source/xml/16142.xml",downloadPdfUrl:"/chapter/pdf-download/16142",previewPdfUrl:"/chapter/pdf-preview/16142",totalDownloads:2759,totalViews:420,totalCrossrefCites:0,totalDimensionsCites:8,totalAltmetricsMentions:1,introChapter:null,impactScore:5,impactScorePercentile:92,impactScoreQuartile:4,hasAltmetrics:1,dateSubmitted:"November 18th 2010",dateReviewed:"February 23rd 2011",datePrePublished:null,datePublished:"July 5th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/16142",risUrl:"/chapter/ris/16142",book:{id:"344",slug:"establishing-better-standards-of-care-in-doppler-echocardiography-computed-tomography-and-nuclear-cardiology"},signatures:"Richard M. Fleming and Gordon M. Harrington",authors:[{id:"47432",title:"Dr.",name:"Richard M.",middleName:null,surname:"Fleming",fullName:"Richard M. Fleming",slug:"richard-m.-fleming",email:"rmfmd7@hotmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/47432/images/system/47432.png",institution:null},{id:"112635",title:"Prof.",name:"Gordon M.",middleName:null,surname:"Harrington",fullName:"Gordon M. Harrington",slug:"gordon-m.-harrington",email:"gordon.harrington@uni.edu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Iowa",institutionURL:null,country:{name:"United States of America"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Discovering the redistribution properties of technetium-99m isotopes",level:"1"},{id:"sec_3",title:"3. The Fleming-Harrington nuclear imaging uncertainty principle. Understanding the physics of how nuclear SPECT cameras really work?",level:"1"},{id:"sec_4",title:"4. The kinetics of radioactive isotope distribution from vein to heart to cells to redistribution",level:"1"},{id:"sec_5",title:"5. Fleming Harrington Stress SPECT protocol reduces radioactive dosage and increases ischemia detection. The detection of ischemic heart disease is accomplished by comparing multiple images of the heart following stress. (ischemia equals stress imaging)",level:"1"},{id:"sec_5_2",title:"5.1. Methods",level:"2"},{id:"sec_5_3",title:"5.1.1. Single Photon Emission Computed Tomography (SPECT) cameras",level:"3"},{id:"sec_7_2",title:"5.2. Calculating FHRWW",level:"2"},{id:"sec_8_2",title:"5.3. Results",level:"2"},{id:"sec_9_2",title:"5.4. Discussion",level:"2"},{id:"sec_10_2",title:"5.5. Conclusion",level:"2"},{id:"sec_12",title:"6. FHRWW rest-rest SPECT viability imaging - cardiac viability measured using resting FHRWW redistribution of sestamibi: the scientific evidence proves “sestamibi redistributes and is not mitochondrial superglue”",level:"1"},{id:"sec_12_2",title:"6.1. Redistribution/washout information",level:"2"},{id:"sec_14",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'AhmadM.LoganK. W.MartinR. H.\n\t\t\t\t\t1979\n\t\t\t\t\tDoughnut pattern of technetium-99m pyrophosphate myocardial uptake in patients with acute myocardial infarction: A sign of poor long-term prognosis.\n\t\t\t\t\tAm J Cardiol\n\t\t\t\t\t44\n\t\t\t\t\t1317 .'},{id:"B2",body:'AngerH.\n\t\t\t\t\t1957 A new instrument for mapping gamma-ray emitters. 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[Epub ahead of print]'},{id:"B14",body:'Fleming RM, et al.\n\t\t\t\t\t1990a Feasibility of SPECT Perfusion Imaging with Technetium 99 -m Teboroxime: Comparison to Thallium- 201 and Quantitative Coronary Arteriography. 5th World Congress of Nuclear Medicine and Biology, European Journal of Nuclear Medicine, Montreal, Canada.\n\t\t\t'},{id:"B15",body:'Fleming RM, et al.\n\t\t\t\t\t1990b Tc-99m Teboroxime SPECT Imaging: Comparison to Thallium 201 and Quantitative Coronary Arteriography. Circulation 82(4):III-652.'},{id:"B16",body:'Fleming RM, et al.\n\t\t\t\t\t1990c Nuclear Cardiology and Imaging- Myocardial Scintigraphy II on the Feasibility of SPECT Perfusion Imaging with Technetium 99 -m Teboroxime: Comparison to Thallium-201 and Quantitative Coronary Arteriography. XIIth European Heart Journal 11:277.'},{id:"B17",body:'Fleming RM, et al.\n\t\t\t\t\t1991a A Comparison of Technetium 99-m Teboroxime Tomography to Automated Quantitative Coronary Arteriography and Thallium- 201 SPECT. J Am Coll. Cardiol. 17\n\t\t\t\t\t12971302 .'},{id:"B18",body:'Fleming RM, et al.\n\t\t\t\t\t1991b\n\t\t\t\t\tPatterns in visual interpretation of coronary arteriograms as detected by quantitative coronary arteriography. J Am Coll Cardiol 18\n\t\t\t\t\t94551 .'},{id:"B19",body:'FlemingR. M.GibbsH. R.SwaffordJ.\n\t\t\t\t\t1992a\n\t\t\t\t\tUsing Quantitative Coronary Arteriography to Redefine SPECT Sensitivity and Specificity.\n\t\t\t\t\tAm J Physiol Imag. 7\n\t\t\t\t\t5965 .'},{id:"B20",body:'Fleming RM.\n\t\t\t\t\t1992b\n\t\t\t\t\tDetecting Coronary Artery Disease Using SPECT Imaging: A Comparison of Thallium-201 and Teboroxime.\n\t\t\t\t\tAm J Physiol Imag\n\t\t\t\t\t7\n\t\t\t\t\t1\n\t\t\t\t\t2023 .'},{id:"B21",body:'Fleming RM, Harrington GM.\n\t\t\t\t\t1994\n\t\t\t\t\tQuantitative coronary arteriography and its assessment of atherosclerosis. Section II. Calculating stenosis flow reserve from percent diameter stenosis. Angiology\n\t\t\t\t\t45\n\t\t\t\t\t83540 .'},{id:"B22",body:'Fleming RM, Rose CH, Feldmann KM.\n\t\t\t\t\t1995 Comparing a High Dose Dipyridamole SPECT ImagingProtocol with Dobutamine and Exercise Stress Testing Protocols. Angiology\n\t\t\t\t\t46\n\t\t\t\t\t7\n\t\t\t\t\t547556 .'},{id:"B23",body:'Fleming RM, Feldmann KM.\n\t\t\t\t\t1998\n\t\t\t\t\tComparing a High Dose Dipyridamole SPECT Imaging Protocol with Dobutamine and Exercise Stress Testing Protocols. Section II: Using High-Dose Dipyridamole to Determine Lung-to-Heart Ratios. Intern J Angiol\n\t\t\t\t\t7\n\t\t\t\t\t325328 .'},{id:"B24",body:'Fleming RM.\n\t\t\t\t\t1999a Chapter 31. Nuclear Cardiology: Its Role in the Detection and Management of Coronary Artery Disease Textbook of Angiology. John C. Chang Editor, Springer-Verlag New York, NY. 397406 .'},{id:"B25",body:'Fleming RM, Feldmann KM.\n\t\t\t\t\t1999b\n\t\t\t\t\tComparing a High Dose Dipyridamole SPECT Imaging Protocol with Dobutamine and Exercise Stress Testing Protocols. Section III: Using Dobutamine to Determine Lung-to-Heart Ratios, Left Ventricular Dysfunction and a Potential Viability Marker. Inter J Angiol\n\t\t\t\t\t8\n\t\t\t\t\t2226 .'},{id:"B26",body:'Fleming RM.\n\t\t\t\t\t1999c Chapter 64. The Pathogenesis of Vascular Disease. Textbook of Angiology. John C. Chang Editor, Springer-Verlag New York, NY. 787798 .'},{id:"B27",body:'Fleming RM.\n\t\t\t\t\t1999d Chapter 29. Atherosclerosis: Understanding the relationship between coronary artery disease and stenosis flow reserve. Textbook of Angiology. John C. Chang Editor, Springer-Verlag, New York, NY. 381387 .'},{id:"B28",body:'Fleming RM.\n\t\t\t\t\t2000a The Clinical Importance of Risk Factor Modification: Looking at Both Myocardial Viability (MV) and Myocardial Perfusion Imaging (MPI) Intern J Angiol 9\n\t\t\t\t\t5569 .'},{id:"B29",body:'Fleming RM.\n\t\t\t\t\t2000b\n\t\t\t\t\tThe Natural Progression of Atherosclerosis in an Untreated Patient with Hyperlipidemia: Assessment via Cardiac PET. Intern J Angiol\n\t\t\t\t\t9\n\t\t\t\t\t7073 .'},{id:"B30",body:'Fleming RM.\n\t\t\t\t\t2000c\n\t\t\t\t\tThe Fleming Unified Theory of Vascular Disease: A link between atherosclerosis, inflammation and bacterially aggravated atherosclerosis (BAA). Angiol 51\n\t\t\t\t\t879 .'},{id:"B31",body:'FlemingR. M.BoydL.ForsterM.\n\t\t\t\t\t2000d Unified Theory Approach Reduces Heart Disease and Recovers Viable Myocardium. 42nd Annual World Congress- International College of Angiology, San Diego, California, USA, June 29, 2000.\n\t\t\t'},{id:"B32",body:'FlemingR. M.BoydL.ForsterM.\n\t\t\t\t\t2000e Angina is Caused by Regional Blood Flow Differences- Proof of a Physiologic (Not Anatomic) Narrowing, Joint Session of the European Society of Cardiology and the American College of Cardiology, Annual American College of Cardiology Scientific Sessions, Anaheim, California, USA, 12 March 2000, 49th (Placed on internet www.prous.com for physician training and CME credit, April 2000.)'},{id:"B33",body:'Fleming RM.\n\t\t\t\t\t2000f\n\t\t\t\t\tShortcomings of coronary angiography. Letter to the Editor. Cleve Clin J Med 67:450 EOF1 EOF .'},{id:"B34",body:'FlemingR. M.BoydL.ForsterM.\n\t\t\t\t\t2000g Reversing Heart Disease in the New Millennium- The Fleming Unified Theory, Angiology 51\n\t\t\t\t\t10\n\t\t\t\t\t617629 .'},{id:"B35",body:'Fleming RM.\n\t\t\t\t\t2001\n\t\t\t\t\tCoronary Artery Disease is More than Just Coronary Lumen Disease.\n\t\t\t\t\tAmer J Card\n\t\t\t\t\t88\n\t\t\t\t\t599600 .'},{id:"B36",body:'Fleming RM.\n\t\t\t\t\t2002a High-Dose Dipyridamole and Gated Sestamibi SPECT Imaging Provide Diagnositic Resting and Stress Ejection Fractions Useful for Predicting the Extent of Coronary Artery Disease. Angiology\n\t\t\t\t\t53\n\t\t\t\t\t4\n\t\t\t\t\t415421 .'},{id:"B37",body:'Fleming RM.\n\t\t\t\t\t2002b A Tate-en-Tate Comparison of Ejection Fraction and Regional Wall Motion Abnormalities as Measured by Echocardiography and Gated Sestamibi SPECT. Angiology 53\n\t\t\t\t\t313321 .'},{id:"B38",body:'Fleming RM.\n\t\t\t\t\t2002c Breast enhanced scintigraphy test demonstrates improvement in breast inflammation in women consuming soy protein. The Journal of Nutrition 132:575S.'},{id:"B39",body:'Fleming RM.\n\t\t\t\t\t2002d\n\t\t\t\t\tMitochondrial Uptake of Sestamibi Distinguishes Between Normal, Inflammatory Breast Changes, Pre-cancers and Infiltrating Breast Cancer.\n\t\t\t\t\tIntegrative Cancer Therapies\n\t\t\t\t\t1\n\t\t\t\t\t3\n\t\t\t\t\t229237 .'},{id:"B40",body:'Fleming RM, Dooley WC.\n\t\t\t\t\t2002e Breast Enhanced Scintigraphy Testing (B.E.S.T.) Distinguishes Between Normal, Inflammatory Breast Changes and Breast Cancer. A Prospective Analysis and Comparison with Mammography. Integrative Cancer Therapies 1\n\t\t\t\t\t3\n\t\t\t\t\t238245 .'},{id:"B41",body:'Fleming RM.\n\t\t\t\t\t2002f The Effect of High, Moderate and Low Fat Diets On Weight Loss and Cardiovascular Disease Risk Factors. Preventive Cardiology V(III):110118 . [http://www.medscape.com/viewarticle/438769]'},{id:"B42",body:'Fleming RM.\n\t\t\t\t2003a What effect, if any, does soy protein have on breast tissue? Integrative Cancer Therapies 2\n\t\t\t\t2258 .'},{id:"B43",body:'Fleming RM.\n\t\t\t\t\t2003b Are there differences in breast tissue as a result of hormone replacement therapy? Can BEST imaging distinguish these differences? Integrative Cancer Therapies 2\n\t\t\t\t\t22934 .'},{id:"B44",body:'Fleming RM.\n\t\t\t\t\t2003c Do women taking hormone replacement therapy (HRT) have a higher incidence of breast cancer than women who do not? Integrative Cancer Therapies\n\t\t\t\t\t2\n\t\t\t\t\t2357 .'},{id:"B45",body:'Fleming RM.\n\t\t\t\t\t2003d Angina and coronary Ischemia are the result of coronary regional Blood Flow Differences. J Amer Coll Angiol 2003;1\n\t\t\t\t\t12742 .'},{id:"B46",body:'Fleming RM.\n\t\t\t\t\t2003e Using C-Reactive Protein as a Marker of Bacteriallly Aggravated Atherosclerosis in Acute Coronary Syndromes. J Amer Coll Angiol\n\t\t\t\t\t1\n\t\t\t\t\t16571 .'},{id:"B47",body:'Fleming RM.\n\t\t\t\t\t2003f Stop Inflammation Now! with Tom Monte. Published by Putnam Books and Avery Books. December 2003.\n\t\t\t'},{id:"B48",body:'Fleming RM, Harrington GM.\n\t\t\t\t\t2008\n\t\t\t\t\tWhat is the Relationship between Myocardial Perfusion Imaging and Coronary Artery Disease Risk Factors and Markers of Inflammation?, Angiology\n\t\t\t\t\t59\n\t\t\t\t\t1625 .\n\t\t\t'},{id:"B49",body:'FlemingR. M.HarringtonG. M.BaqirR.\n\t\t\t\t\t2009 Heart Disease in Men. Chapter 3. Using Multiple Images Post-Stress to Enhance diagnostic Accuracy of Myocardial Perfusion Imaging: The Clinical Importance of Determining Washin and Washout Indicates a Parabolic Function between Coronary Perfusion (Blood Flow) and Cellular ("Uptake/Release") Function. Alice B. Todd and Margo H. Mosley Editors, Nova Publishers 75100 . (https://www.novapublishers.com/catalog/product_info.php?products _id=8409)'},{id:"B50",body:'Fleming RM, et al.\n\t\t\t\t\t2009b\n\t\t\t\t\tThe Evolution of Nuclear Cardiology takes Us Back to the Beginning to Develop Today’s “New Standard of Care” for Cardiac Imaging: How Quantifying Regional Radioactive Counts at 5 and 60 Minutes Post-Stress Unmasks Hidden Ischemia.\n\t\t\t\t\tMethodist DeBakey Cardiovascular Journal (MDCVJ) 5\n\t\t\t\t\t3\n\t\t\t\t\t4248 .'},{id:"B51",body:'Fleming RM, et al.\n\t\t\t\t\t2010a\n\t\t\t\t\tRenewed Application of an Old Method Improves Detection of Coronary Ischemia. A Higher Standard of Care. 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Clin Cardiol 33:E39 -E45.'},{id:"B93",body:'Shin WJ, et al.\n\t\t\t\t\t1995 Reverse redistribution on dynamic exercise and dipyridamole stress technetium-99m-MIBI myocardial SPECT. J Nucl Med\n\t\t\t\t\t36\n\t\t\t\t\t20535\n\t\t\t'},{id:"B94",body:'Sinusas AJ, et al.\n\t\t\t\t\t1994 Redistribution of 99m-Tc-sestamibi and 201-Tl in the presence of a severe coronary artery stenosis. Circulation 89\n\t\t\t\t\t233241 .\n\t\t\t'},{id:"B95",body:'St. Goar FG, et al.\n\t\t\t\t\t1991 Intravascular ultrasound imaging of angiographically normal coronary arteries: An in vivo comparison with quantitative angiography. JACC 18\n\t\t\t\t\t9528 .\n\t\t\t'},{id:"B96",body:'SugiuraT.et al.\n\t\t\t\t\t2006 Usefulness of Tc-99m methoxyisobutylisonitrile scintigraphy for evaluating congestive heart failure. J Nucl Cardiol\n\t\t\t\t\t13\n\t\t\t\t\t648 .'},{id:"B97",body:'TakeishiY.et al.\n\t\t\t\t\t1996 Reverse redistribution of technetium-99m-sestamibi following direct PTCA in acute myocardial infarction. 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Ann Nucl Med\n\t\t\t\t\t20\n\t\t\t\t\t34956 .'},{id:"B101",body:'ToriyamaT.et al.\n\t\t\t\t\t2005 99mTc-sestamibi scintigraphy in the prediction of cardiac events in patients with congestive heart failure. 7th International conference of Nuclear Cardiology-European Society of Cardiology 2005.'},{id:"B102",body:'VanBrocklin HF, et al.\n\t\t\t\t\t2007 Mitochondrial avid radioprobes. Preparation and evaluation of 7’(Z)-[125I]iodorotenone and 7’(Z)-[125I]iodorotenol. Nucl Med Biol\n\t\t\t\t\t34\n\t\t\t\t\t10916 .\n\t\t\t'},{id:"B103",body:'Walsh WF, et al.\n\t\t\t\t\t1977 Assessment of diagnostic value of technetium-99m pyrophosphate myocardial scintigraphy in 80 patients with possible acute myocardial infarction. Br Heart J\n\t\t\t\t\t39\n\t\t\t\t\t974981 .'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Richard M. Fleming",address:"",affiliation:'
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1. Introduction
Medicinal plants are very vital in their uses for medication, besides providing ecological, economic, and cultural services. The world primary means of treating diseases and fighting infections have been based on the use of medicinal plants. From ancient times, plants have been rich sources of effective and safe medicines [1]. Globally, about 64% of the total world population is reliant on traditional medicine for their healthcare needs [2]. According to the World Health Organization (WHO), nearly 3.5 billion people in developing countries including Ethiopia believe in the efficiency of plant remedies and use them regularly [3].
Ethiopia is located in the Horn of Africa between 3 and 15° northing, latitude, and 33 and 48° easting, longitude, and is also comprised of nine national regional states and two administrative states with varied agroecological zones. Since the country is characterized by a wide range of ecological, edaphic, and climatic condition, Ethiopia is also very diverse in its flora composition [4]. The flora of Ethiopia is estimated to contain close to 6500–7000 species including medicinal plants; of those, 12–19% are endemic to the country [5]. The medicinal plants have been used for various types of human and animal treatments in the country. According to [6, 7], in Ethiopia, about 80% of human population and 90% of livestock rely on traditional medicine. As also stated by many authors (e.g. [6, 7]), the medicinal plants have shown very effective medicinal values for some diseases of humans and livestock.
Even due to the trust of communities on medicinal values of traditional medicines, culturally associated traditions, and their relatively low cost, medicinal plants are highly demanded in Ethiopia [7]. Inadequate health centers and shortage of medicines and personnel in clinics might be the other reasons for driving the people of Ethiopia, in general, and the low-income community and the rural people, in particular, to the traditional health centers, whereby increasing the demand of medicinal plants.
However, these plants have got little attention regarding the documentation of scientific names, uses, ecology, and conservation in Ethiopia, in particular and world-wise, in general. Moreover, in Ethiopia, traditional medicine is faced with a problem of sustainability and continuity mainly due to the loss of taxa of medicinal plants [8, 9] besides having lack of quality control for herbal medicines. The main causes for the loss and decline of diversity of plants in Ethiopia are human-made factors [10, 11, 12]. Habitat destruction and deforestation for commercial timber and forest encroachment for urbanization, investment, agriculture, and other land uses are the major causes of the loss of many thousand hectares of forest that harbor medicinal plants yearly for the past several decades. In addition to these, the medicinal plant materials and associated traditional knowledge are being lost due to the lack of systematic conservation, research, proper utilization, and documentation [13]. The knowledge on identifying and managing the medicinal plants with their parts, use, and ecology is mostly associated with local and elder people, who transmitted their knowledge verbally. Such verbal transmissions of knowledge on medicinal plants have thus resulted in eroding and loss of knowledge and the plant materials as well. The quantity and quality of the safety and efficacy data on traditional medicine are also far from sufficient to meet the criteria needed to support its use worldwide [14]. Therefore, assessing and documenting the medicinal plants along with their useful medicinal parts, use, and ecology in Ethiopia, as well as revising the quality control for herbal materials and medicine, are very crucial for giving priority to their conservation and sustainable utilization.
2. Materials and methods
The materials for this review were published documents. However, regarding the screening of medicinal plants, some medicinal plants not yet identified or available in more than one article being revised during this revision time, and published before 2000 with their uses, were not listed and included for this review analysis so as to increase the quality of the present review, provide the current information to the readers, and restrict the revised papers. Based on this, of the total (32) revised documents, 15 articles, which are assessing the different medicinal plants with their uses and parts, were revised for documenting the medicinal plants for this review. Additionally, the habitats (ecology) of each medicinal plant were assessed from the Flora Volumes of Ethiopia and Eritrea and [15], besides the articles revised for listing the medicinal plants for this review. The data were analyzed and described quantitatively using frequency, percentage, tables, and figures via applying Microsoft Excel Spreadsheet 2010 and SPSS with version 20, as well as qualitatively using content analysis, narrating via drawing sub-contents.
3. Medicinal plants: their parts, uses, and ecology reviewed
Traditional healers in Ethiopia utilize the herbal resources available in nature for various disease treatments. As reported before, approximately 800 species of the medicinal plants grown in Ethiopia are used for treating about 300 medical conditions [16]. However, based on the present review, the number of medicinal plants and the treatments/medications identified and listed are limited as presented here under section by section.
3.1 Medicinal plants and their growth forms and parts used
3.1.1 Composition and growth forms of medicinal plants
As reported by many authors [6, 7, 12, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27], there are different types of medicinal plant species with their parts, habitats, and disease types being treated and described here in Table 1. Accordingly, as depicted in Table 1, there were 80 medicinal plant species with 63 genera, used by the local communities for various human treatments. Among other revised, the common medicinal plants used for treating and curing various diseases are Aloe species, Eucalyptus globulus, Hagenia abyssinica, Cupressus macrocarpa, Buddleja polystachya, Acmella caulirhiza, Acacia species, Citrus species, Clematis species, Coffee Arabica, Croton macrostachyus, Euphorbia species, Ficus sycomorus, and Moringa stenopetala (Table 1).
For treating wound by squeezing the leaves and creaming on the wound [22, 24]
Bridelia scleroneura Mul. Arg.
T
Open woodland Dry riverine forest
Seeds
For curing skin diseases by crushing and applying on wound parts [12, 18, 19]
Brucea anti dysenterica Fresen.
Abalo
S/T
Montane, evergreen forest margins
Leaves
For treating cancer, skin problem, leprosy, and external parasites [6, 25]
Buddleja polystachya Fresen.
Anfar
T
Degraded woodland in cultivated fields, around houses
Leaves
For treating the cattle eye diseases by chewing and spitting on the affected area [18, 22]
Calpurnia aurea (Ait.) Benth.
Digita
S
Forest margins, bushland/grassland, favored by over grazing
Leaves Roots Seeds
For preventing poisonous snake bite by boiling the leaves and drinking with honey [12, 24] For curing amebiasis by crushing and boiling with leaf of coffee for drink. The seeds can be used as a fish-poison or as a cure for dysentery [12]
Capparis tomentosa Lam
S
Riverine forest, grassland with scattered trees
Bark
For curing sore, anthrax, and evil eye using the powder of the bark with hot water [18, 20]
Carica papaya L.
papaya
T
Home gardens, small and large plantations
Seeds
Used for treating diarrhea and ascariasis by drinking the ground and boiled seeds with honey [12, 19, 27]
Carissa edulis (Forsk.)
Agam
S
Open Acacia bushland
Root
Used for shorten the labor period just before delivery of women [19, 21]
Carissa spinarum L.
Agam
S
Disturbed areas, along edges of roads, riverine vegetation
Roots
Used for preventing evil eye by inhaling the smoke of pounded roots. It is also used for treating wounds via applying the powder of the roots [12, 17, 19, 27]
Disturbed habitats by roads and paths, bushland, woodland, savannah
Root
For preventing gonorrhea and hemorrhoids as well as for toothache [12, 20, 22]
Verbascum sinaiticum Benth.
H
Disturbed sites
Root/leaves
For treating heart disease, cancer, trypanosomiasis [6, 20, 27]
Premna schimperi Engl.
Chocho
S
Degraded and secondary forests, grassy meadows and along paths in forests
Root Leaves
Used for treating mastitis Used for preventing boils [12, 18]
Solanum nigrum
Embuay
H
In cultivation and ruderal areas, on road-, hill-, river- or streamsides; in bushland areas
Leaves roots, stems
Leaf, root, and stalk are used for cancerous sores and wound treatments. Stems eaten as pot herb for virility in men and for dysmenorrhea in females, for dysentery, and sore throat [21, 24]
Solanum incanum L.
Tikur awud
H
Cultivated and riverine gallery forest, disturbed habitats
Leaves/roots
Used for curing bleeding, menstruation, amebiasis [12, 17, 18, 19, 20]
Stephania abyssinica (Dill. and A. Rich.) Walp. (Etse Eyesus, Nech- Hareg)
Yayit hareg
Cl
In thickets bordering forest margins, hillsides, cultivated fields, in clearings
Root
For treating external tumor/cancer and stomachache [6, 12, 8, 24, 25]
Stereospermum kunthianum Cham.
Arziniya
S/T
Open woodland and savanna, widespread in tropical Africa
Bark
Used for treating kidney via drinking the juice crushed from bark [12, 13, 19]
Tamarindus indica L.
Humer/Roqa
T
Grassland, woodland Combretum bushland, riparian
Fruit
Used for curing stomachache; it is also used for treating bile and intestinal worm using the fruit juice with hot water in the morning before breakfast [12, 19]
For curing stomach diseases, cough, and asthma [21, 25]
Tragia cordata Michx.
Alebilabet
H
Among open rock bushlands
Root
For treating urinary tract and external parasite [12, 18, 19]
Tribulus terrestris L.
Kurnchit
H
Open and disturbed places, often on sandy soils
Stem Fruit Seed
For curing scabrous skin diseases For congestion, headache, hepatitis, liver, vertigo, stomatitis, kidneys, liver, and vision For treating anemia, hemorrhoid coughs, fluxes, and stomatitis [21]
Urtica pilulifera L.
Sama
H
Unknown
Leaves
For curing sore joints by mixing the plant juice with oil; provide cure for rheumatism and hemorrhage [18, 21]
Vernonia amygdalina Del.
Girawa
S
Bush/woodland, forest habitats, home gardens
Leaves
For preventing headache and intestinal worm and for treating tumor/cancer in general [6, 7, 12, 18, 20, 22, 24, 26, 27]
Xanthium strumarium L.
Deha nikel
H
Wet forest margins, in riverine vegetation by streamside
Oil from the fruit kernel is applied to fresh wounds to prevent infections and also used by some people, who have their ears or lips pierced Used for treating stomachache and tonsillitis [6, 12, 19, 20]
Based on the review, all plant growth forms were not equally used as remedies, because of the difference in distribution among the growth forms. Accordingly, the life forms of medicinal plants reviewed constituted 18 trees (22.78%), 23 shrubs (29.11), 29 herbs (36.71%), 3 climbers (3.81%), 4 trees/shrubs (5.06%), and 2 herbs/shrubs (2.53%) (Figure 1). Of all life forms, herbs were, thus, the major medicinal plants used by the community for human treatment followed by shrubs and trees.
Figure 1.
Life forms/habits of medicinal plants reviewed with their percentage (%).
3.1.2 Medicinal plant parts used for preparation of traditional remedies
The review indicated that the plant parts used for medication preparation by the traditional healers are variables. Healers mostly used fresh specimens from commonly available plants [25] to prepare remedies for their patients; this might be mostly due to the effectiveness of fresh medicinal plant parts in treatment since the contents are not lost before use compared to the dried ones [12]. As also referred from many authors, the traditional healers have harvested leaves, roots, barks, seeds, fruits, stems, flowers, barks, seeds, or latex of medicinal plants (Figure 2) to prepare their traditional medicines for their patient treatments. As depicted in Figure 2, most remedies were prepared from the leaf (32.98%) and root (29.79%) parts of the medicinal plants to treat the diseases compared to the other parts of them. This finding of the review is in line with the findings of the majority of authors’ papers (e.g. [18, 25, 27]). The main reason that many traditional medicine practitioners used the leaf parts compared to others for remedial preparation is due to their accessibility and for preventing them from extinction [25]. In fact, harvesting the root parts of the medicinal plant for preparation of traditional medicines has negative consequences on the existence of the plants themselves in the future. That is why most of the medicinal plants are currently at risk, declining highly due to them using their root parts besides other human pressures.
Figure 2.
Distribution of medicinal plant parts used for disease traditional treatments by healers.
3.2 Uses of medicinal plants in treating different disease types
Using these medicinal plants revised in Table 1, the local communities could be able to treat about 69 disease types. The disease types treated by these various medicinal plants were skin disease, gonorrhea, diarrhea, wound, tapeworm, snake bites, stomachache, headache, evil eye, heartburn, cancer/tumor, and malaria (see Table 1 for the detail). Particularly, most of the patients (who come from rural areas) with their perspective disease types have been treated by traditional healers, before coming to clinics and/or hospitals located far away by many kilometers from their residential areas. The disease types most frequently treated by traditional medications (traditional healers) provided by those medicinal plants were stomachaches, wounds, cancers/tumors, skin diseases, headaches, toothaches, and coughs and diarrhea, which took the first, second, third, fourth, fifth, sixth, and seventh ranks, respectively, although the majority of disease types were frequently treated less than four times, ranging from one to three times (Table 2). This also points out that one medicinal plant species can be used for treating more than one disease types.
Disease type categories and their rank based on their frequency being treated by different medicinal plant species (as described in Table 1).
Because of this, medicinal plants are very vital in providing traditional medicines, prepared by local healers, and thereby used for treating and curing different types of diseases that affected the local communities, where they occurred. Even, following the traditional uses and effectiveness of the medicinal plants [23], the traditional healers are also popular by the local societies, providing cultural values. The study of [23] also confirmed that the traditional health practitioners are with a good knowledge of medicinal plants used to treat different diseases of their locals.
In addition to these contributions pertinent to traditional medications and cultural values, the individual medicinal plants could provide regulating, provisioning, and supporting services. For instance, they could provide regulating services via regulating soil erosion, climate change, disease, pollution, and pollination; they also provide provisioning services such as fuel wood, timber for house construction, food (fruits, honey), and fodder and shelter for wild animals [11]. Hence, almost all of the medicinal plants are multipurpose species, providing more than one benefits.
3.3 Ecology and/or habitats of medicinal plants
As referred from the revised documents for this review, the habitat preference of medicinal plants varied from place to place (Table 1). As referred in Table 1 and Figure 3 drawn from the review, the majority of medicinal plants were available along the edges of river/streams and wetlands, disturbed sites, grasslands, cultivated lands, woodlands, bushland, grasslands, and home gardens. Generally, the majority of medicinal plants were found in wild compared to those plants found in cultivated and home gardens together. Many of the authors of the reviewed articles (e.g. [12, 23, 25]) confirmed that the majority of medicinal plants were collected from natural habitats or wild by traditional practitioners compared from home gardens. Among medicinal plants found along stream/riverbanks (Figure 3), the majority of them are supposed to be medicinal plants having herbal life forms/habits (Figure 1). This could be due to their shallow roots, which cannot bring water from the deep parts of their habitats.
Figure 3.
Summary of distributions of medicinal plants along their major habitat categories in Ethiopia.
Because of the anthropogenic factors such as over harvesting, fire/deforestation, agricultural expansion, overgrazing, and urbanization [25, 28], most of the medicinal plants have also been lost. This implies that the availability and accessibility of most medicinal plants in Ethiopia are also very difficult [25]. Hence, most of the medicinal plants were restricted to areas (such as cliffs, hills/mountains, gorges, disturbed areas, riverbanks, and valleys of wild) which are not easily accessible to use/harvest them. Not only is this, but also the knowledge of traditional practitioners pertinent to identification of medicinal plants with their parts and ecology and the process of preparation of herbal medicines and medication with their quality/effectiveness are declined/lost since the knowledge is mostly transferred orally from generation to generation, not documented. Therefore, the effects of human on the natural habitat of medicinal plants are the problems for the conservation of medicinal plants and associated knowledge of traditional healers [12]. With the present ecological and socioeconomic changes, medicinal plants together with the associated ethnobotanical knowledge in Ethiopia are under serious threat and may be lost at alarming rate.
Under such circumstances, the use of plants for medicinal purposes will also decline, and consequently the once effective traditional healthcare system will also be lost [19]. Hence, documenting medicinal plants with their uses and ecology as well as the knowledge of traditional practitioners is so vital. Moreover, it is very essential to give conservation priority for those medicinal plants through protecting them where they are found, propagating them in cultivated areas and home gardens, and creating awareness to the locals. Hence, following community and research-based approach is advised to save medicinal plants from their loss and extinction.
4. Applied plant anatomy: quality control of herbal medicine
4.1 General overview
Plant materials are used throughout developed and developing countries as home remedies, as over-the-counter drug products, and as raw materials for the pharmaceutical industry, which represent a substantial proportion of the global drug market [29]. Thus, the traditional herbal medicines and their preparations have been widely used for thousands of years in many countries. Therefore, it is so essential to overview here some modern control histological techniques or tests, suitable standards, and practical experiences used for assessing the quality of medicinal materials and their products. Quality control of herbal medicine using histological techniques and pharmaceutical practices is also very vital for avoiding the risks happened on patients and the beliefs in services provided by traditional healers. According to [30], quality control is a phrase that refers to processes involved in maintaining the quality or validity of the manufactured products. However, the quality control of herbal medicine is beyond this, meaning it is the management of medicinal plants and their products during cultivation, identification process of the plant species with their parts and localities (their being free from polluted environment causing diseases), and medicine preparation including its components, medication processes, storage standards, and dosage; all should be taken into account. This means, without proper all-round quality control, there is no assurance that the contents of the herbs contained in the package are the same as what are stated outside the package [30]. Climatic factors (prevailing temperature, rainfall, humidity, altitude of the growing region, light), nutritional factors (nutrients, pH, cation exchange capacity), harvesting factors (age, season, collection time, plant organ), and post-harvesting factors (storage hygiene, drying process) are the major factors affecting the contents and composition of medicinal plant raw materials and their products [29, 30]. For these, some of the most important laboratory test methods (histological techniques), common sense, and good pharmaceutical practices are used [29]. Techniques such as thin-layer chromatography and microscopic and electrophoretic techniques are widely used to evaluate the quality of herbal drugs [14, 29, 31] and the content and quality of meats [32] as well. These techniques and good pharmaceutical practices are also used to support the development of national standards based on local market conditions, with due regard to existing national legislation and national and regional norms [29]. Therefore, improved and currently available pharmaceutical analytical methods led to improvements in harvesting schedules, cultivation techniques, storage, product purity, and activity and stability of active compounds [30].
4.2 Major quality control methods for medicinal plant materials and their products
Among others, thin-layer chromatography, macroscopic and microscopic examinations, gas chromatography and volatile components, and electrophoretic techniques [14, 29] are the most important quality control methods for medicinal plant materials and their products, described briefly here below.
4.2.1 Macroscopic and microscopic examinations
Herbal materials are categorized based on sensory, macroscopic, and microscopic characteristics, which are the first steps toward establishing the identity and the degree of purity of such materials, and should be carried out before any further tests undertaken, according to [29]. Therefore, to establish identity, purity, and quality, visual inspection (macroscopic examination) provides the simplest and quickest means. Herbal materials should be entirely free from visible signs of contamination such as insects, molds (fungi), and other animal contamination, including animal excreta; any soil, stones, sand, dust, and other foreign inorganic matter must also be removed before herbal materials are cut or ground for testing [29]. Moreover, plant parts used for medication with abnormal odor, discoloration, slime, or signs of deterioration should be detected to exclude them from being used for medication products.
Moreover, during storage, products should be kept in a clean and hygienic place for avoiding contamination occurring; special care should also be taken to avoid formation of molds, since they may produce aflatoxins [29]. For determination of foreign matter and storage conditions, macroscopic examination can properly be employed for determining the presence of foreign matter in whole or cut plant materials. For these, common sense and good pharmaceutical practices are used. Such common senses and good pharmaceutical practices can, even, be used after laboratory tests since the test procedures cannot take account of all possible impurities in deciding whether an unusual substance not detectable by the prescribed tests can be tolerated [29]. For instance, if a sample is found to be significantly different from the specifications in terms of color, consistency, odor, or taste, it is considered as not fulfilling the requirements. However, such examination may need further microscopic examination for either rejecting or accepting their requirements.
4.2.2 Thin-layer chromatography (TLC)
This technique is simple, can be employed for multiple sample analysis, and so has manyfold possibilities of detection in analyzing herbal medicines [14]. The report of [29] also confirmed that TLC is used for evaluating herbal materials and their preparations; particularly, it is valuable for the qualitative determination of small amounts of impurities.
4.2.3 Gas chromatography (GC) and volatile components
Many pharmacologically active components in herbal medicines are volatile chemical compounds; thereby, the analysis of volatile compounds by gas chromatography is very important in the analysis of herbal medicines [14]. GC is a useful analytical tool in the research field of herbal medicines via analyzing their volatile oils, which have a number of advantages: (1) the GC of the volatile oil gives a reasonable “fingerprint” which can be used to identify the plant and to detect the presence of impurities in the volatile oil, and (2) the extraction of the volatile oil is relatively straightforward and can be standardized, and the components can be readily identified using GC analysis [14].
4.2.4 Electrophoretic method
It is a good tool for producing the chemical fingerprints of the herbal medicines and has similar technical characteristics of liquid chromatography [14]. Electrophoretic method, especially capillary electrophoresis (CE), used in the analysis of herbal medicines, is a versatile and powerful separation tool with a high-separation efficiency and selectivity when analyzing mixtures of low-molecular-mass components [14].
5. Conclusions
There are various forms of medicinal plants including trees, shrubs, climbers, and herbs; of those herbal medicinal plants are dominantly used for different human and animal treatments in Ethiopia. These plants are collected mainly from riverbanks, cultivated areas, bushlands, forest, woodlands, and grasslands, among others. They are used for treatments of stomachaches, dysentery, diarrhea, asthma, cancer, evil eyes, earaches, sores of throat and gum, cough, and so on. For such treatments, these medicinal plants have specific parts used for treatment; most of them are leaves and roots. Hence, traditional medicine plays a significant role in the healthcare of the majority of the people in developing countries, including Ethiopia, and medicinal plants provide valuable contribution to this practice. However, the vegetative resources that are unique to the country, particularly used for medication, are dwindling due to continuous exploitation and pressure on the limited resources. Hence, conservation priority should be given to such medicinal plants and their habitats besides the knowledge of traditional practice of medication via designing appropriate strategies, particularly in the rural areas of the country, where there are less accessibility to clinics and hospitals with their medicines and health experts (doctors). Community- and research-based conservation mechanisms could be an appropriate approach for mitigating the problems pertinent to the loss of medicinal plants and their habitats and for documenting medicinal plants and the knowledge of traditional healers on how to prepare and provide the traditional medication to their patients. Medicinal plants should be multiplied through medicinal gardens, proper handling practices, and scientific development. Moreover, for controlling the quality of medicinal plant materials and their products, chromatography, electrophoretic, macroscopic/microscopic techniques, and pharmaceutical practices are the most important tools.
Acknowledgments
The authors would like to thank Debre Birhan University of Ethiopia for its library facilitation while writing this manuscript. We also extend our thanks to Hirut Fisiha for assisting us during editing and revising of this manuscript.
Conflict of interest
The authors declare that there is no any conflict of interest between authors and other organizations as well.
Department of Midwifery, College of Health Sciences, Debre Birhan University, Ethiopia
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Open Access background
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IntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
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IntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
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Open Science
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Open Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
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Open Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
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Open Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
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Promoting open and publicly accessible education tools
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Reproducible research data and re-analysis
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Public availability and re-usability of scientific data
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Public accessibility and transparency of scientific communication
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Transparent peer-review and publishing practices
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Using web-based tools to facilitate scientific collaboration
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Supporting exchange of knowledge and research materials between disciplines
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Supporting exchange of knowledge and research materials between scientific communities and industry.
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We aim at improving the quality and availability of scholarly communication by promoting and practicing:
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\n
IntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\n
At IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
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“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\n
Open Access Standards followed by IntechOpen
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OAI-PMH
\n\n
As a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\n
License
\n\n
Book chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\n
Peer Review Policies
\n\n
All scientific works are Peer Reviewed prior to publishing. Read more
\n\n
OA Publishing Fees
\n\n
The Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\n
Digital Archiving Policy
\n\n
IntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\n
Open Science
\n\n
Open Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\n
Open Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\n
Open Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\n
\n\t
Promoting open and publicly accessible education tools
\n\t
Transparency in experimental methodology, observation, and collection of data
\n\t
Reproducible research data and re-analysis
\n\t
Public availability and re-usability of scientific data
\n\t
Public accessibility and transparency of scientific communication
\n\t
Transparent peer-review and publishing practices
\n\t
Using web-based tools to facilitate scientific collaboration
\n\t
Supporting exchange of knowledge and research materials between disciplines
\n\t
Supporting exchange of knowledge and research materials between scientific communities and industry.
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We aim at improving the quality and availability of scholarly communication by promoting and practicing:
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Open Access
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Open Data
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Open Metrics and Impact
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Open Source
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Taguchi method is a broadly accepted method of DOE, which has proven in producing high-quality products at subsequently low cost.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Rahul Davis and Pretesh John",authors:[{id:"199438",title:"Mr.",name:"Rahul",middleName:null,surname:"Davis",slug:"rahul-davis",fullName:"Rahul Davis"}]},{id:"64216",doi:"10.5772/intechopen.81170",title:"CNN Approaches for Time Series Classification",slug:"cnn-approaches-for-time-series-classification",totalDownloads:3415,totalCrossrefCites:20,totalDimensionsCites:28,abstract:"Time series classification is an important field in time series data-mining which have covered broad applications so far. Although it has attracted great interests during last decades, it remains a challenging task and falls short of efficiency due to the nature of its data: high dimensionality, large in data size and updating continuously. With the advent of deep learning, new methods have been developed, especially Convolutional Neural Network (CNN) models. In this paper, we present a review of our time series CNN approaches including: (i) a data-level approach based on encoding time series into frequency-domain signals via the Stockwell transform, (ii) an algorithm-level approach based on an adaptive convolutional layer filter that suits the time series in hand, and (iii) another algorithm-level approach adapted to time series classification tasks with limited annotated data, which is a global, fast and light-weight framework based on a transfer learning technique with a source learning task similar or different but related to the target learning task. These approaches are implemented on identifying human activities including normal movements of typical subjects and disorder-related movements such as stereotypical motor movements of autistic subjects. Experimental results show that our approaches improve performance of time series classification.",book:{id:"8362",slug:"time-series-analysis-data-methods-and-applications",title:"Time Series Analysis",fullTitle:"Time Series Analysis - Data, Methods, and Applications"},signatures:"Lamyaa Sadouk",authors:[{id:"257943",title:"Ph.D.",name:"Lamyaa",middleName:null,surname:"Sadouk",slug:"lamyaa-sadouk",fullName:"Lamyaa Sadouk"}]},{id:"56653",doi:"10.5772/intechopen.70230",title:"Bayesian Hypothesis Testing: An Alternative to Null Hypothesis Significance Testing (NHST) in Psychology and Social Sciences",slug:"bayesian-hypothesis-testing-an-alternative-to-null-hypothesis-significance-testing-nhst-in-psycholog",totalDownloads:3428,totalCrossrefCites:14,totalDimensionsCites:19,abstract:"Since the mid-1950s, there has been a clear predominance of the Frequentist approach to hypothesis testing, both in psychology and in social sciences. Despite its popularity in the field of statistics, Bayesian inference is barely known and used in psychology. Frequentist inference, and its null hypothesis significance testing (NHST), has been hegemonic through most of the history of scientific psychology. However, the NHST has not been exempt of criticisms. Therefore, the aim of this chapter is to introduce a Bayesian approach to hypothesis testing that may represent a useful complement, or even an alternative, to the current NHST. The advantages of this Bayesian approach over Frequentist NHST will be presented, providing examples that support its use in psychology and social sciences. Conclusions are outlined.",book:{id:"5964",slug:"bayesian-inference",title:"Bayesian Inference",fullTitle:"Bayesian Inference"},signatures:"Alonso Ortega and Gorka Navarrete",authors:[{id:"203438",title:"Dr.",name:"Alonso",middleName:null,surname:"Ortega",slug:"alonso-ortega",fullName:"Alonso Ortega"},{id:"208842",title:"Dr.",name:"Gorka",middleName:null,surname:"Navarrete",slug:"gorka-navarrete",fullName:"Gorka Navarrete"}]},{id:"59936",doi:"10.5772/intechopen.75007",title:"Application of Principal Component Analysis to Image Compression",slug:"application-of-principal-component-analysis-to-image-compression",totalDownloads:1819,totalCrossrefCites:12,totalDimensionsCites:15,abstract:"In this chapter, an introduction to the basics of principal component analysis (PCA) is given, aimed at presenting PCA applications to image compression. Here, concepts of linear algebra used in PCA are introduced, and PCA theoretical foundations are explained in connection with those concepts. Next, an image is compressed by using different principal components, and concepts such as image dimension reduction and image reconstruction quality are explained. Also, using the almost periodicity of the first principal component, a quality comparative analysis of a compressed image using two and eight principal components is carried out. Finally, a novel construction of principal components by periodicity of principal components has been included, in order to reduce the computational cost for their calculation, although decreasing the accuracy.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Wilmar Hernandez and Alfredo Mendez",authors:null}],mostDownloadedChaptersLast30Days:[{id:"59209",title:"Utilization of Response Surface Methodology in Optimization of Extraction of Plant Materials",slug:"utilization-of-response-surface-methodology-in-optimization-of-extraction-of-plant-materials",totalDownloads:5470,totalCrossrefCites:64,totalDimensionsCites:97,abstract:"Experimental design plays an important role in several areas of science and industry. Experimentation is an application of treatments applied to experimental units and is then part of a scientific method based on the measurement of one or more responses. It is necessary to observe the process and the operation of the system well. For this reason, in order to obtain a final result, an experimenter must plan and design experiments and analyzes the results. One of the most commonly used experimental designs for optimization is the response surface methodology (RSM). Because it allows evaluating the effects of multiple factors and their interactions on one or more response variables it is a useful method. In this section, recent studies have been compiled which aim to extraction of plant material in high yield and quality and determine optimum conditions for this extraction process.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Alev Yüksel Aydar",authors:[{id:"218870",title:"Dr.",name:"Alev Yüksel",middleName:null,surname:"Aydar",slug:"alev-yuksel-aydar",fullName:"Alev Yüksel Aydar"}]},{id:"60864",title:"Statistical Methodology for Evaluating Business Cycles with the Conditions of Their Synchronization and Harmonization",slug:"statistical-methodology-for-evaluating-business-cycles-with-the-conditions-of-their-synchronization-",totalDownloads:1372,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The importance of the topic of business cycle research and their interaction is due to the fact that the cyclical nature of development is a universal feature of the market economy (regardless of the level of development of the country’s economy and the principles of its organization). In all cases, cyclical ups and downs depend not only on internal system cyclical processes and their factors in countries but also on the consequences of intercountry interaction. The ability to measure and predict business cycles, taking into account their mutual influence, is a prerequisite for the development of an adequate business policy of countries and their associations.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Elena Zarova",authors:null},{id:"60246",title:"Statistical Research of Investment Appeal of Russian Regions",slug:"statistical-research-of-investment-appeal-of-russian-regions",totalDownloads:1014,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"In this chapter, the methodological results directed on realization statistical research of investment appeal of Russian regions are offered. Methodological basis of research is the method of the dynamic standard, index and the coefficient analysis and the method of paired comparisons. The results of the study: (1) the method of the dynamic standard for creation of statistical model of region investment appeal is offered; (2) the normative model of region investment appeal to measure the productivity of the realization of regions investment policy in Russia is created; (3) new factors of region investment appeal are investigated and (4) statistically valid conclusions are drawn and practical recommendations are made. The results of the study are addressed to the Ministry of Economic Development of the Russian Federation in order to justify the amount of federal targeted investment programs financing in Russian regions.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Burtseva Tatiana Alexsandrovna",authors:null},{id:"56460",title:"Application of Taguchi-Based Design of Experiments for Industrial Chemical Processes",slug:"application-of-taguchi-based-design-of-experiments-for-industrial-chemical-processes",totalDownloads:3222,totalCrossrefCites:27,totalDimensionsCites:54,abstract:"Design of experiment is the method, which is used at a very large scale to study the experimentations of industrial processes. It is a statically approach where we develop the mathematical models through experimental trial runs to predict the possible output on the basis of the given input data or parameters. The aim of this chapter is to stimulate the engineering community to apply Taguchi technique to experimentation, the design of experiments, and to tackle quality problems in industrial chemical processes that they deal with. Based on years of research and applications, Dr. G. Taguchi has standardized the methods for each of these DOE application steps. Thus, DOE using Taguchi approach has become a much more attractive tool to practicing engineers and scientists. And since the last four decades, there were limitations when conventional experimental design techniques were applied to industrial experimentation. And Taguchi, also known as orthogonal array design, adds a new dimension to conventional experimental design. Taguchi method is a broadly accepted method of DOE, which has proven in producing high-quality products at subsequently low cost.",book:{id:"5856",slug:"statistical-approaches-with-emphasis-on-design-of-experiments-applied-to-chemical-processes",title:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes",fullTitle:"Statistical Approaches With Emphasis on Design of Experiments Applied to Chemical Processes"},signatures:"Rahul Davis and Pretesh John",authors:[{id:"199438",title:"Mr.",name:"Rahul",middleName:null,surname:"Davis",slug:"rahul-davis",fullName:"Rahul Davis"}]},{id:"59936",title:"Application of Principal Component Analysis to Image Compression",slug:"application-of-principal-component-analysis-to-image-compression",totalDownloads:1823,totalCrossrefCites:12,totalDimensionsCites:15,abstract:"In this chapter, an introduction to the basics of principal component analysis (PCA) is given, aimed at presenting PCA applications to image compression. Here, concepts of linear algebra used in PCA are introduced, and PCA theoretical foundations are explained in connection with those concepts. Next, an image is compressed by using different principal components, and concepts such as image dimension reduction and image reconstruction quality are explained. Also, using the almost periodicity of the first principal component, a quality comparative analysis of a compressed image using two and eight principal components is carried out. Finally, a novel construction of principal components by periodicity of principal components has been included, in order to reduce the computational cost for their calculation, although decreasing the accuracy.",book:{id:"6703",slug:"statistics-growing-data-sets-and-growing-demand-for-statistics",title:"Statistics",fullTitle:"Statistics - Growing Data Sets and Growing Demand for Statistics"},signatures:"Wilmar Hernandez and Alfredo Mendez",authors:null}],onlineFirstChaptersFilter:{topicId:"166",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. 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For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. 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He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. 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She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. 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He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. 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Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11405,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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