Characteristics of common positron emitters.
\\n\\n
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\\nIntechOpen 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.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'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.
\n\nDesigned 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.
\n\nAfter 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.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen 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\nIntechOpen 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.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: 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:"3008",leadTitle:null,fullTitle:"Practical Applications in Biomedical Engineering",title:"Practical Applications in Biomedical Engineering",subtitle:null,reviewType:"peer-reviewed",abstract:"Biomedical Engineering is an exciting and emerging interdisciplinary field that combines engineering with life sciences. The relevance of this area can be perceived in our everyday lives every time we go to hospital, receive medical treatment or even when we buy health products such as an automatic blood pressure monitor device. Over the past years we have experienced a great technological development in health care and this is due to the joint work of engineers, mathematicians, physicians, computer scientists and many other professionals.\nThis book introduces a collection of papers organized into three sections that provide state of the art examples of practical applications in Biomedical Engineering in the area of Biomedical Signal Processing and Modelling, Biomaterials and Prosthetic Devices, and Biomedical Image Processing.",isbn:null,printIsbn:"978-953-51-0924-2",pdfIsbn:"978-953-51-6287-2",doi:"10.5772/3331",price:139,priceEur:155,priceUsd:179,slug:"practical-applications-in-biomedical-engineering",numberOfPages:424,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"bd1f79b8d401570af1db3f9b7548d627",bookSignature:"Adriano O. Andrade, Adriano Alves Pereira, Eduardo L. M. Naves and Alcimar B. Soares",publishedDate:"January 9th 2013",coverURL:"https://cdn.intechopen.com/books/images_new/3008.jpg",numberOfDownloads:45448,numberOfWosCitations:53,numberOfCrossrefCitations:13,numberOfCrossrefCitationsByBook:8,numberOfDimensionsCitations:61,numberOfDimensionsCitationsByBook:8,hasAltmetrics:1,numberOfTotalCitations:127,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 29th 2011",dateEndSecondStepPublish:"December 20th 2011",dateEndThirdStepPublish:"June 15th 2012",dateEndFourthStepPublish:"August 23rd 2012",dateEndFifthStepPublish:"October 23rd 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{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,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"151483",title:"Dr.",name:"Alcimar",middleName:"Barbosa",surname:"Soares",slug:"alcimar-soares",fullName:"Alcimar Soares",profilePictureURL:"https://mts.intechopen.com/storage/users/151483/images/3666_n.jpg",biography:"Dr. Alcimar B. Soares received the B.S. degree in Electrical Engineering at the Federal University of Uberlândia, Brazil, in 1987, where he also concluded his MSc in the area of Artificial Intelligence in 1990. He received his PhD in Biomedical Engineering at the University of Edinburgh, UK, in 1997, and completed a post-doctoral research fellowship at the department of Biomedical Engineering of the Johns Hopkins University, USA, in 2014. Has was the Head of the Graduate Program of Electrical Engineering from 2002 to 2004, Head of the Faculty of Electrical Engineering from 2004 to 2008, and Dean for Research and Graduate Studies of the Federal University of Uberlândia from 2008 to 2012. He also was the Head of the Committees for the creation of the Biomedical Engineering Undergraduate and Graduate Programs of the Federal University of Uberlândia in 2005 and 2012, respectively. Dr. Soares is currently a Full Professor and Head of the Biomedical Engineering Lab at the Faculty of Electrical Engineering of the Federal University of Uberlândia, Brazil. He is the Editor-in-Chief of the Research on Biomedical Engineering journal and Associate-Editor of the Medical & Biological Engineering & Computing journal. He is also member of various scientific societies, such as the IEEE Engineering in Medicine and Biology Society, the Brazilian Society of Biomedical Engineering, the Brazilian Society of Electromyography and Kinesiology and the International Society of Electromyography and Kinesiology. His research interests include modeling and estimation of neuromotor control systems, brain machine interfaces and rehabilitation and assistive devices.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},coeditorTwo:{id:"252334",title:"Dr.",name:"Adriano",middleName:"Alves",surname:"Pereira",slug:"adriano-pereira",fullName:"Adriano Pereira",profilePictureURL:"https://mts.intechopen.com/storage/users/252334/images/system/252334.jpg",biography:null,institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:{id:"252335",title:"Dr.",name:"Eduardo",middleName:null,surname:"Naves",slug:"eduardo-naves",fullName:"Eduardo Naves",profilePictureURL:"https://mts.intechopen.com/storage/users/252335/images/system/252335.jpg",biography:"Eduardo Naves obtained his BSc degree in Electrical Engineering at the Federal University of Uberlandia, Brazil, in 1994, where he also received his MSc and PhD degrees in 2001 and 2006, both in Biomedical Engineering. From 2001 to 2006 he was Assistant Professor at the Department of Computer Science from the Federal University of Goias, Brazil. In 2006, he joined the Faculty of Electrical Engineering from the Federal University of Uberlandia (FEELT-UFU), where he served as the postdoctoral researcher of biomedical engineering from 2008 to 2009. From 2009 to 2010, at the Laboratory of Design, Optimization and Modeling of Systems (LCOMS) from the University of Lorraine, Metz, France. Currently, he is a professor of the FEELT-UFU and head of the Assistive Technology Lab (NTA-UFU), who is affiliated with the National Net of Research, Development and Innovation on Assistive Technology from the Ministry of Science, Technology, Innovation and Communications of Brazil (MCTIC). Dr. Naves has more than eighteen years of experience in biomedical engineering. His research interests include the design, evaluation and optimization of biomedical instruments applied to rehabilitation engineering and assistive technology as well as the biomechanical analysis of the human movement. You have authored, and co-authored a number of peer-reviewed publications in these areas. evaluation and optimization of biomedical instruments applied to rehabilitation engineering and assistive technology as well as the biomechanical analysis of the human movement. You have authored, and co-authored a number of peer-reviewed publications in these areas. evaluation and optimization of biomedical instruments applied to rehabilitation engineering and assistive technology as well as the biomechanical analysis of the human movement. 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The most common radionuclides for PET radiopharmaceuticals include 11C, 15O, 13N, 18F, 68Ga and 82Rb (Table 1). In addition to radiation issue, short half-lives of these positron emitters (78 sec~110 min) definitely result in unavoidable limitations on manufacturing (including production and following quality control (QC) analyses) and clinical use of PET radiopharmaceuticals. Above are all practical challenges for a conventional pharmaceutical industry. Hence, commercial large-scale manufacturing and small-scale preparation of PET radiopharmaceuticals are respectively allowed in radiopharmaceutical industries and the radiopharmacy of hospitals in most countries worldwide. Moreover, both practices in radiopharmaceutical industries and hospitals are clearly regulated by national competence authorities, such as Food and Drug Administration (FDA) of the United States (U.S.) and
Radionuclide | \nHalf-life | \nMax specific activity (Ci/μmol) | \nß+ (%) | \nMax Eß (MeV) | \nMax ß+ range (mm) | \nProduction route | \n
---|---|---|---|---|---|---|
11C | \n20 min | \n9220 | \n99 | \n0.96 | \n4.1 | \nCyclotron | \n
15O | \n123 sec | \n90,800 | \n100 | \n1.19 | \n5.1 | \nCyclotron | \n
13N | \n10 min | \n18,900 | \n100 | \n1.72 | \n7.3 | \nCyclotron | \n
18F | \n110 min | \n1710 | \n97 | \n0.635 | \n2.4 | \nCyclotron | \n
68Ga | \n68 min | \n2766 | \n88 | \n1.9 | \n8.2 | \nCyclotron/ Generator | \n
82Rb | \n78 sec | \n150,400 | \n95 | \n3.35 | \n14.1 | \nGenerator | \n
Characteristics of common positron emitters.
In the other hand, a pharmacopeia is a national compendium of drug quality standards, such as U.S. Pharmacopeia (USP) and European Pharmacopeia (EP), and is always recognized as an official compendium. Drug standards listed in pharmacopeia monographs are usually enforced to be compliance under drug-related provisions at national level in order to prevent the marketing of inconsistent drugs and to reduce possible risks in public health. Although PET radiopharmaceuticals listing in pharmacopeia monographs sometimes do not mean for marketing authorization under national approval and reimbursement decision of medical insurance [1], some countries have enabled the clinical use (i.e., use for routine patient care with/without reimbursement or with/without national approval) or clinical trials as long as their qualities are in conformity with USP or EP standards, even no good manufacturing practice (
In the other hand, specific QC procedures and specification of some PET radiopharmaceuticals have been listed in USP or EP. However, because of short half-lives of PET radiopharmaceuticals, QC tests prior to human administration within such a short period is a huge challenge. As a result, some quality exceptions are usually allowed for PET radiopharmaceuticals. Also, several efficient and quick tests have been developed for rapid QC tests of clinical PET radiopharmaceuticals.
\nThis chapter first aims to provide an overview of regulations of manufacturing and clinical use of PET radiopharmaceuticals in U.S. and Europe. Secondly, the chapter will introduce the general quality aspect for PET radiopharmaceuticals. Finally, this chapter will end with the brief introduction of PET radiopharmaceuticals listed in the monographs of latest USP (USP 40) or EP (EP 9.0) (Table 2).
\nRadionuclide | \nCompound | \nUSP | \nEP | \n
---|---|---|---|
11C | \n[11C]CO | \n✓* | \n\n |
[11C-methyl]Methionine | \n✓* | \n✓ | \n|
N-[11C-methyl]Flumazenil | \n✓* | \n✓ | \n|
[11C]N-methylspiroperidol | \n✓* | \n\n | |
[11C-methoxy]Raclopride | \n✓* | \n✓ | \n|
[1-11C]Sodium Acetate | \n✓* | \n✓ | \n|
13N | \n[13N]NH3 | \n✓ | \n✓ | \n
15O | \n[15O]CO | \n\n | ✓ | \n
[15O]H2O | \n✓* | \n✓ | \n|
18F | \n[18F]FCH | \n\n | ✓ | \n
[18F]FDG | \n✓ | \n✓ | \n|
[18F]FDOPA (prepared by electrophilic substitution) | \n✓* | \n✓ | \n|
[18F]FET | \n\n | ✓ | \n|
[18F]FLT | \n\n | ✓ | \n|
[18F]FMISO | \n\n | ✓ | \n|
[18F]NaF | \n✓ | \n✓ | \n|
68Ga | \n[68Ga]Ga-Citrate | \n\n | ✓ | \n
[68Ga]Ga-DOTA-TOC | \n\n | ✓ | \n|
82Rb | \n[82Rb]rubidium chloride | \n✓ | \n\n |
PET radiopharmaceuticals listed in USP and EP.
These monographs of 8 FDA-unapproved PET radiopharmaceuticals have been omitted from USP since May 1, 2015 (USP 38).
In U.S., the clinical use of all radiopharmaceuticals has been regulated by FDA since 1975. Briefly, the regulatory process can be divided into two types. They are: 1. IND submission for investigational and research purposes by an individual or a commercial manufacturer, and 2. submissions of Notice of Claimed Investigational Exemption (NCIE), an abbreviated new drug application (ANDA) or New Drug Application (NDA) for commercial marketing only by a commercial manufacturer. However, because of the increasing clinical need of PET radiopharmaceuticals, based on FDA Modernization Act (FDAMA) in 1997 [2], PET radiopharmaceuticals were first categorized as positron-emitting drugs. In the same time, all PET radiopharmaceutical manufacturing facilities in U.S. were programmatically to compliant with PET drug GMP-compliance guideline or with USP General Chapter <823> [3], and further registered as manufacturers. Till now, these legal manufacturers could on-site
In the other hand, USP is annually published by a nonprofit organization since 1820, U.S. Pharmacopeial Convention, and such organization also worked with FDA and specialists in academia and companies to establish monographs or general chapters. Typically, USP monographs are typically developed after FDA approval of the drug product for commercial marketing and thus a USP monograph of an FDA-approved drug has been used as one basis for a reimbursement decision. The first USP monograph for a PET drug was published in 1990 [4] and it described the quality specification and analytic methods for [18F]FDG injection. However, there had been an exception for 4 approved and 8 unapproved PET drugs listed in USP monographs till 2013. Moreover, not only these 12 monographs were provided to U.S. Pharmacopeial Convention by various academic sponsors with un-validated data and outdated analytic methods, but also these unapproved 8 PET drugs have limited commercial application without FDA-approved NDA or ANDA. Consequently, based on recommendations of the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Committee [1], U.S. Pharmacopeial Convention announced the omission of the monographs of 8 unapproved PET drugs on June 2014 and the omission initiative became official on December 1, 2014.
\nIn Europe, radiopharmaceuticals have been recognized as a special group of medicines. Thus, the preparation and clinical use of PET radiopharmaceuticals have been regulated and variously adopted by member states. Similar to USP, EP has legal status in Europe. Compared to the USA, EP is only for drug quality and is independent of licensing status or clinical utility of such drug. Regarding to PET radiopharmaceuticals, corresponding monographs are elaborated by a group that is composed of academic, commercial and regulatory specialists. From another point of view, a number of EU member states have set up a regulatory framework from the definitions of “magistral and officinal formulae” that is listed in Article 3 of Directive 2001/83 [5]. Additionally, “in-house” small-scale preparation of PET radiopharmaceuticals is allowed without the requirements of a marketing authorization based on various national laws of European countries [5]. Both a general chapter of EP entitled “Extemporaneous Preparation of Radiopharmaceuticals” [6] and the new PIC/S guidance document with Annex 3 on radiopharmaceuticals [7] are published and worked as comprehensive guidelines for such magistral approach. Furthermore, because of the special characteristics of PET radiopharmaceuticals, the clinical studies using diagnostic radiopharmaceuticals do not fall within the GMP-compliance regulations of conventional drugs from EU Regulation no 536/2014 of 16 April 2014 [8, 9]. On brief summary, no matter EP or PIC/S document, they both clearly define a clear distinction between PET radiopharmaceuticals and conventional medicine, and further provide the corresponding guidance. All would be significantly helpful and powerful in promotion and development of PET radiopharmaceuticals in Europe.
\nEven costly implementation and maintenance of quality system for a PET radiopharmaceutical manufacturing (or preparing) site [10, 11], it is still thought to be cost-effective [12]. Moreover, it will be helpful for qualified patient care, regulatory requirements, optimization of safety and efficacy for patient care and a reliable quantitative performance in both diagnostic and therapeutic nuclear medicine procedures [13]. Therefore, GMP-compliant PET manufacturing (or preparing) process including production, QC, quality assurance (QA), package and distribution has been required by competent authorities in many countries worldwide. Furthermore, during these years, the concept of “Quality by Design (QbD)” based on guidelines of International Conference on Harmonization (ICH) (ICH Q8 [14], ICH Q9 [15], and ICH Q10 [16]) has been the fundamental topic in pharmaceutical field and an appropriate quality system has been widely required to implement in many radiopharmaceutical manufacturing sites (Figure 1). Briefly, QA covers whole process and GMP specifically characterizes those production and QC activities that guarantee products are produced under the constant scrutiny of quality standards [17], although the association of QA, GMP, and QC throughout whole pharmaceutical process is slightly different in various guidelines.
\nThe inter-relationship for whole quality system in PET radiopharmaceutical manufacturing.
Particularly, QC procedure of PET radiopharmaceutical is usually critical and essential, since it is synthesized every day or is small-scale “prepared “in radiopharmacy of a hospital. A typical QC programme of a PET radiopharmaceutical is involved from radionuclide production to final product release and a series of QC tests for PET radiopharmaceuticals basically include:
Appearance, by visual assessment;
pH determination;
Radionuclidic identification, by gamma-ray spectrometry or half-life measurement;
Radionuclidic purity, by gamma-ray spectrometry;
Chemical purity, by high-pressure liquid chromatography (HPLC) or by thin-layer chromatography (TLC);
Radiochemical purity, by HPLC with a radioactivity detector or by TLC with a radioactivity scanner;
Residual solvents, by gas chromatography (GC);
Bacterial endotoxins, by a rabbit test or limulus amebocyte lysate (LAL) test;
Radioactivity, by a validated dose calibrator and.
Sterility, by incubating the sample with fluid thioglycollate medium (FTM) at 30~35°C for 14 days or with soybean casein digest (SCD) medium at 20~25°C for 14 days.
However, because of short-lives of PET radiopharmaceuticals, some lengthy tests cannot be performed prior to release for human use and are allowable to perform within a short time after the release. Furthermore, in addition to the limited time for QC of PET radiopharmaceuticals, limited personneal for
Cellular protein synthesis is a well-control process for enzymes, membrane receptors, structural proteins, and growth factors [18]. Most importantly, increased cellular protein synthesis is often characterized in malignant growth [19]. Otherwise, decreased protein synthesis is found in certain neurodegenerative disorders [20]. Thus, the ability to
Chemical structures of PET radiopharmaceuticals listed in this chapter.
The GABAA/benzodiazepine receptor complex is also known as the central benzodiazepine receptor and specifically mediates all pharmacologic properties of ethanol, zinc, picrotoxin and some drugs such as benzodiazepines (sedative, anxiolytic, anticonvulsant, myorelaxant), barbiturates (cerebral protection) and neuroactive steroids [35]. Based on a benzodiazepine antagonist, N-[11C-methyl]Flumazenil ([11C]FMZ) (Figure 2) [36] has been developed and known for its excellent kinetic properties for the image quantification [37]. Moreover, [11C]FMZ has been considered as a versatile PET tracer for assessment of several conditions, such as neuronal damage in head injury [38], epilepsy [39], stroke-induced penumbral areas of infarction [40] and Alzheimer’s disease (AD) [41].
\nDopamine (DA) plays an important role in every-day brain functions including experiencing pleasure, regulating attention, and learning to control urges. Dysfunction of DA circuits has been thought to be related to various psychiatric diseases such as Parkinson’s diseases (PD), addiction, attention-deficit hyperactivity disorder, and schizophrenia [42]. Studying
Acetate is a molecule quickly picked-up by cells to convert into acetyl-CoA by acetyl-CoA synthetase (EC 6.2.1.1 according to Enzyme Commission Number) and participates in cytoplasmic lipid synthesis, which is believed to be increased in tumors. Thus, [1-11C] Sodium Acetate ([11C]Ac) (Figure 2) [56, 57] has been proved clinical usefulness in prostate cancer (PC) [58], hepatocellular carcinoma (HCC), lung cancer, nasopharyngeal carcinoma [33], renal cell carcinoma, bladder carcinoma and brain tumors [59]. Furthermore, [11C]Ac has been used to clinically measure myocardial oxygen consumption since 2010 [60] and used in some rare conditions, such as thymoma, cerebellopontine angle schwannoma, angiomyolipoma of the kidney, encephalitis, and multiple myeloma [59].
\nCoronary flow reserve (CFR) is calculated as the ratio of hyperemic to rest absolute myocardial blood flow (MBF) and is a particularly useful parameter in the assessment of adverse cardiovascular events such as epicardial coronary stenosis, diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion [61]. Routinely used [13N]Ammonia ([13N]NH3) is not only a useful 13N-labeled PET imaging agent for assessing regional blood flow in tissues [62], but a well-validated radiotracer for clinical management of patients with coronary artery disease [62, 63, 64]. Moreover, recently [13N]NH3 has been used in PC, because the up-regulation of NH3 during
[15O]CO is one of the most common tracers used for noninvasively measuring oxygen consumption and blood volume [70, 71]. Additionally, [15O]CO is crucial for the evaluation of acute stroke patients. Moreover, measurement of myocardial oxygen consumption is a useful tool to clarify the relationship between MBF and oxygen extraction fraction (OEF), because both OEF and MBF are important indicators in describing myocardial function [72].
\nAlthough the short half-life (123 sec) of 15O results in the challenges in clinical use, [15O]H2O is still the preferred tracer because of its ease production from generator, effectiveness and safety for patient use [73]. Particularly, PET with [15O]H2O has been a standard method and most reliable approach for quantitative measurement of cerebral blood
Choline is a precursor for the biosynthesis of phospholipids which are essential components of all membranes and is phosphorylated by choline kinase (CK) to produce phosphatidylcholine. Upregulated CK is known in cancer cells, thus it further leads to increased uptake of choline in tumor cells with the excess need for phospholipid biosynthesis [77, 78]. Consequently, 18F-labeled choline analogs, [18F]fluoromethylcholine ([18F]FCH) (Figure 2) [79, 80] has been a promising tumor imaging agents for various types of tumors include brain [80], breast, thyroid, lung, liver and prostate [81]. Particularly, [18F]FCH has been shown to be better than [18F]FDG for PC and HCC detections [81].
\nSince its synthesis in 1976, 2-fluorine-[18F]fluorodeoxyglucose ([18F]FDG) [82] (Figure 2) has been the most widely used radiotracer for PET studies in neuroscience, cardiology and oncology (Table 3) [83]. After FDA approval in 1997, [18F]FDG with PET or PET/CT scanner became an established imaging tool in the clinical assessment of many neoplasms, as well as the nonmalignant diseases including dementia, myocardial ischaemia, inflammation and infection [84].
\nClassification | \nDisease | \nApplication | \n
---|---|---|
Neurology | \nAlzheimer’s Disease | \n— | \n
Epilepsy | \nPre-surgical evaluation for epileptogenic foci (85–90% accuracy). | \n|
Cardiology | \nMyocardial Viability | \nAssessment of myocardial viability prior to cardiac surgery | \n
Identify high-risk patients | \nSelect patients who will benefit from bypass | \n|
Psychiatry | \nSchizophrenia | \n— | \n
Depression | \n— | \n|
Oncology | \nTumor Evaluation | \nDifferentiate recurrent/residual tumor from necrosis. | \n
Tumor Staging | \nMalignant vs. benign. Lung nodules, primary breast and colon cancers. | \n|
Tumor Monitoring | \nResponse to therapy. | \n|
Tumor Localization | \nMetastases, abnormal sites | \n|
Infection and Inflammation | \nOrthopedic infections | \n— | \n
Summary for clinical application of [18F]FDG [83].
Dihydroxyphenylalanine (DOPA) has been known as an intermediate in the catecholamine synthesis pathway. One of the 18F-radiolabeled analogs, 3,4-dihydroxy-6-[18F]fluoro-
Na+-independent system L amino acid transporters (LATs) preferentially transports amino acids with large neutral side chains, including L-leucine, L-phenylalanine, and L-tyrosine. O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) (Figure 2) [103] belongs to the class of large neutral amino acids, which are transported via specific amino acid transporters especially of LATs [104]. Although data today still not reveal which the transporter(s) responsible for [18F]FET accumulation in cells [105], [18F]FET has been well known for its high uptake in brain tumors and its potential for grading tumors particularly gliomas [106, 107]. Summarily, [18F]FET has been well-investigated in differential diagnosis, grading, prognostication, treatment response assessment, and differentiating pseudoprogression from non-specific post-therapeutic changes [108, 109, 110]. Switzerland was the first country to approve [18F]FET PET for clinical use in brain tumor imaging since 2014 [105].
\nCellular proliferation plays an important role in cancer and has been an important imaging target of PET radiopharmaceuticals, especially with the aim targeting of DNA synthesis. Since the approach to the measurement of DNA synthesis in humans was explored in the early 1970s, based on an antiviral agent developed by Medivir, [18F]fluorothymidine ([18F]FLT, also known as [18F]Alovudine) (Figure 2) [111, 112] has been designed with intracellularly trapping of its phosphorylated metabolite within cells [113]. Up to now, [18F]FLT has been widely investigated in oncologic setting comprising tumor detection, staging, restaging, and response assessment to treatment [114, 115, 116] and [18F]FLT imaging has several clinical advantages including noninvasive procedure, three-dimensional tumor images and simultaneous detection of multiple tumor sites [117]. Also, [18F]FLT is capable to evaluate tumor heterogeneity in day-to-day practice [118].
\nHypoxia means insufficient oxygen availability of a cell occurring both in health and is acknowledged by the observation of Gray
The bone is the most common place of tumor metastases next to the lung and liver [128]. Therefore, early and accurate diagnosis of the metastatic bone diseases thus plays an important role for an establishment of adequate therapeutic strategy [129]. [18F]Sodium fluoride ([18F]NaF) was introduced in 1962 and approved by FDA in 1972 [130]. [18F]NaF is a high sensitive bone-seeking PET radiopharmaceutical and is considered as an excellent substitute for traditionally used 99mTc-labeled tracers, because its favorable characteristics of negligible protein binding, and rapid blood pool clearance. With 99mTc supply around the world is gradually become a crisis due to the shortage of 99Mo-source material [131, 132], the clinical use of [18F]NaF keeps increasing worldwide. Additionally, uptake of [18F]NaF reflects blood flow and bone remodeling [133], and [18F]NaF have been proposed for the use in detection of benign and malignant osseous abnormalities that also allows the regional characterization of lesions in metabolic bone diseases [134, 135].
\nIn addition to war and famine, bacterial infection has still been one of major worldwide causes for human morbidity and mortality for centuries [136, 137]. Because of the trapping of gallium in the extravascular compartment for inflammatory or infectious sites with the increased capillary permeability [138], and the iron-like binding characteristics in bacterial siderophores and activated lactoferrin in neutrophils [139, 140], gallium is thought to be indirectly uptaken by macrophages [141, 142] or directly uptaken by bacteria [143]. Thus, [67Ga]gallium citrate ([68Ga]Ga-Citrate) has been used for clinical imaging of infection and inflammation since 1984 [144]. The utilities of [68Ga]Ga-Citrate include the monitoring of osteomyelitis, diskitis, intra-abdominal infection, tuberculosis and interstitial nephritis, as well as the localization of infection in patients with cellulitis and abscesses [145, 146].
\nNETs arised from neuroendocrine cells and are one of slow-growing tumors with year-by-year increased incidence rate and 75% of overall 5-y survival, which is strongly dependent on stage and grade of the tumor [147]. Because NETs has been known for its unique overexpression of somatostatin receptors (SSTrs) on the tumor cells [148], SSTr-targeting PET radiopharmaceuticals provide a promising and useful approach for both diagnostic imaging and further peptide receptor radionuclide therapy (PRRT), such as 68Ga-labeled DOTA-(Tyr3)-octreotide acetate ([68Ga]Ga-DOTA-TOC) (Figure 2) [149]. Because octreotide is a subset of the amino acid in somatostatin and has been demonstrated to avidly bind to SSTr [150], [68Ga]Ga-DOTA-TOC has been recognized for its affinity toward both the type 2 somatostatin receptor (SSTr2) and the type 5 somatostatin receptor (SSTr5) [151, 152, 153, 154]. Also, [68Ga]Ga-DOTA-TOC was the first PET radiopharmaceutical to clinically localize to NETs in 2001 [155] and has been widely used in Europe and several other countries to assist the therapy planning and accurate diagnosis of NETs patients [156]. In addition, [68Ga]Ga-DOTA-TOC is valuable for neuroectodermal tumors, Hurthle cell thyroid carcinoma, prostate cancer patients with bone metastases and autoimmune thyroid disease like Graves’ disease and Hashimoto’s disease [145, 146].
\nJust like previous described [13N]NH3 and [15O]H2O, [82Rb]Rubidium chloride ([82Rb]RbCl) has been reported for directly proportional relationship between its uptake and MBF since 1954 [157]. In addition, several studies have demonstrated the good diagnostic accuracy of [82Rb]RbCl in monitoring of cardiac flow [158, 159]. Subsequently, 82Sr/82Rb generator (CardioGen-82®) of Bracco Diagnostics has been approved by FDA for clinical cardiac imaging since 1989 (NDA 19–414). Therefore, production and administration of [82Rb]RbCl can be well coordinated with the 82Sr/82Rb generator in clinic [160], although a short half-life (78 sec) of 82Rb. In brief, the clinical advantages of [82Rb]RbCl cardiac imaging include its capacity to accurately quantify MBF and a low delivered radiation exposure for a rest/stress test resulted from its very short half-life [160].
\nWith the development of imaging technology, more and more pharmaceutical industry and hospitals worldwide have paid attentions on clinical potential of PET radiopharmaceuticals. However, because of special characteristics of PET radiopharmaceuticals, current pharmaceutical regulatory is probably inapplicable and would be a hurdle for clinical use of PET radiopharmaceuticals in most countries. Thus, as these official monographs of PET radiopharmaceuticals listing in USP or EP, it is definitely worthy to work together for more pharmacopeia monographs and a PET radiopharmaceutical-specific regulatory for benefits of patient-centered care in the future.
\nThis work has been supported in part by grants from the National Taiwan University Hospital, Grants NTUH107-S3882.
\nWe declare no conflict of interest.
Even though frequently less considered, the guidewires are the most fundamental tools to track throughout the vessels, to cross stenoses or occlusions, and to be able to deliver the desired therapy to the target lesion of a given vessel. A thorough knowledge of how they are built and in what way this impacts on their specific characteristics and applications is crucial for any vascular specialist who wishes to succeed. In fact, considering the vast number of options, a correct choice and utilization of a guidewire can frequently be the difference between success and failure of a revascularization, avoiding many possible complications that can jeopardize the final result.
The selection of a guidewire with a correct length can be very relevant to adequately reach and treat the target vessel. For this decision, distance from the access to the vessel to be treated and the shaft length of the sheaths and catheters to be used (either if it is a diagnostic catheter, a balloon catheter, or a delivery device of a stent or a stent graft) needs to be considered. In fact, this apparently less relevant subject may threaten the entire procedure.
Depending on the manufacturer, guidewires can range from 80 to 450 cm. Additionally, some guidewires may allow the connection of an extension during the procedure. This is particularly the case when a coronary guidewire is used as it is designed for rapid exchange devices.
There is a trick that can help in extreme circumstances and as bailout option only. During the removal of a catheter from inside the patient, it is possible to connect an inflation syringe device to the guidewire port of the catheter, just after losing the guidewire, and inflate inside the port, which will keep the guidewire in place. It is crucial to perform this maneuver under fluoroscopy as the guidewire may move forward and the external tip can even migrate and be lost inside the patient.
Even if there are several diameters available, the most commonly used guidewires to cross stenoses and occlusions in peripheral arteries have 0.014″, 0.018″, or 0.035″ in diameter. At this point, it will be relevant to recall the relation between the different units used in endovascular devices, as so: 1 French (F) = 1/3 millimeter = 0.013 inches. It is quite obvious that the thicker the guidewire, the stiffer it is and the more support it allows, even if the core material of it is also very relevant for those properties.
They are several factors that someone should keep in mind when choosing the diameter of a guidewire:
The vessel(s) to be tracked. The smaller the vessels to be tracked, the smaller the guidewire should be. For instance, in the iliac arteries or in the aorta, the guidewires usually used are 0.035″ in diameter, as it is when a crossover at the aortic bifurcation is necessary. In tibial vessels, 0.018″ or 0.014″ guidewires are usually the preferred diameters and in the delicate foot arteries, the 0.014″ guidewires are the rule. Another issue is the distance from the access to the target vessel(s). Logically, the longer the distance, the more support will be needed and the thicker the guidewire will need to be.
The target vessel(s). As for the vessels to be tracked, the smaller the vessel, the thinner the guidewire should usually be.
The kind of lesion(s) to be treated (stenosis versus occlusion). Even if occlusions are usually more difficult to cross, some stenoses can be particularly challenging. In fact very tight heavily calcified stenoses may initially allow the passage of a thicker guidewire, but can preclude the crossing of catheters with the corresponding caliber. In these situations, a downsizing of the guidewire diameter is required. For instance, in tibial vessels of diabetic patients, particularly those with end-stage renal disease, calcified stenoses can be crossed with a 0.018″ guidewire, but frequently, the balloon catheter is not able to cross impelling the change to a 0.014″ system (Figure 1).
The devices planned to be used and their respective platform.
The support needed to deliver the intended devices.
The operator’s preference. In many instances, several guidewires with different diameters can be used. This will depend on the experience of the operator with a particular guidewire or the institutional availability. Most of the times, there is no right or wrong as long as the aim of the intervention is successfully fulfilled.
A, B—Anterior tibial artery with very calcified and tight stenoses. C—Posterior tibial artery of the same patient (diabetic and on hemodialysis). The stenoses were successfully crossed and treated with angioplasty with a 0.014″ guidewire.
There is no clearly accepted nomenclature that can reproductively relate a word or a group of words to the stiffness of a guidewire. As so, it is possible to find several guidewires with the label stiff, extra stiff, super stiff, or even ultra-stiff, without any objective information of its real stiffness. Flexural modulus is an engineering parameter related to a wire’s resistance to bending (Figure 2). This measure is rarely displayed on the guidewire packaging or within the catalog [1]. Yet, it represents an objective method to quantify the stiffness of a guidewire.
Generically, the guidewire is supported at two points that are equidistant to a third point where a vertical force is applied. The force needed to bend the guidewire to a given extent determines its stiffness.
This property is more frequently used to describe the body of the guidewire, but its use in the description of the tip of the guidewire can be very useful too. The stiffer the body of a guidewire is, the more support it will allow to deliver the intended endovascular devices to the target vessel. On the other end, a higher stiffness of the body reduces the ability of the guidewire to track the vessel tree. Concerning the tip, a higher stiffness increases the penetration capacity, but also turns the tip more aggressive to vessel wall increasing the risk of dissection or perforation.
It represents the capacity of a guidewire to navigate through the arterial tree, especially through curves of tortuous vessels. As so, floppier guidewires have a better trackability than stiffer guidewires.
It characterizes the ability of a guidewire to easily cross a lesion without buckling or kinking. Several features of the guidewire can optimize this capacity, depending on whether it is a stenosis or a chronic total occlusion.
Pushability can be defined by the percentage or amount of a given forward force applied to the proximal end of the guidewire that is transmitted to the distal end of the guidewire. Usually, the stiffer and broader the guidewire, the more pushability it gives. This characteristic is particularly relevant in crossing long and/or calcified chronic total occlusions, either in an intraluminal or subintimal way.
Torqueability represents the ability to apply a given rotational force at the proximal end of the guidewire and have that force transmitted efficiently and with the less delay possible, to achieve proper control of the distal tip. This feature is very relevant to determine the path of the guidewire and, consequently, to navigate inside the arterial tree (for instance, to go from the popliteal artery to the anterior tibial artery without a curved catheter) or to cross lesions. Torqueability is very dependent on the material used in the core and the distance from the access to the tip of the guidewire. As an example, guidewires with a stainless-steel core lose most their torqueability when used in a crossover fashion.
A basic knowledge of the engineering aspects of the guidewire technology is quite relevant to understand more thoroughly how a given guidewire is expected to behave in different conditions.
A guidewire has essentially four major components (Figures 3 and 4):
the body;
the tip;
the cover of both the body and tip;
the final coating of both the body and tip.
Basic composition of a guidewire.
A—Spring coils design. B—Guidewire with a complete polymer jacket and coating. C—Hybrid covering.
A guidewire has a core that goes all the way through the body and finishes at the tip, where it may or may not reach the end of the guidewire (Figure 5). The core can be made of nitinol (alloy of nickel and titanium), stainless steel, or another metallic alloy. Nitinol allows more flexibility, memory (ability to maintain the original shape), and resistance to bending. Stainless steel increases the stiffness of the guidewire, but is less resistant to bending, so it is easier to irreversibly kink a guidewire with a stainless-steel core than a guidewire with a nitinol core. Other alloys will provide intermediate characteristics. Some guidewires may also have hybrid cores with stainless steel in the body and nitinol in the tip. In addition to its composition, its thickness straightforwardly corresponds to its stiffness: the thicker the core, the greater the stiffness and support. Therefore, the core is decisive for the behavior of the guidewire concerning its stiffness, torqueability, pushability, and trackability.
A, B, C—Core-to-tip design. The core taper is longer and segmented in B and C. D – Shaping ribbon design.
There are essentially two main inner designs concerning the tip (Figure 5):
the core finishes at the end of the tip in a variable tapered format (core-to-tip design) [2]. In this configuration, the tip has more pushability and torque, a higher penetration capacity, and a better tactile feel (see below). On the other hand, the tip is more prone to inadvertently perforate a vessel, to prolapse to an undesired vessel during tracking the arterial tree (Figure 6A) and to be irreversibly damaged (especially if the core is made of stainless steel). The length of the core taper and its configuration in a continuous or segmented design will enhance or attenuate the enumerated characteristics (Figure 5A–C).
The core does not reach the end of the tip (shaping ribbon design) [2]. With this configuration, the end of the tip is wrapped in a small flexible metal ribbon, providing the continuity of the guidewire (Figure 5D). This design provides a less aggressive and flexible tip, less prone to prolapse (Figure 6B), easier to shape, though at the cost of a less tip torque control.
A—A guidewire with a core-to-tip design has more difficulties in tracking the arterial tree and can prolapse to an undesired vessel. B—A guidewire with a shaping ribbon design tracks the intended vessel much more easily. Arrows indicate the natural direction of each guidewire.
The outer diameter of conventional guidewires is usually the same throughout its length. However, in more dedicated devices, the tip has a progressive reduction of the diameter (tapered tip design—Figure 7), going, for instance, from 0.014″ to 0.009″ [2]. This characteristic increases the penetration capacity but turns the tip much more aggressive and prone to vessel perforation. These guidewires are almost exclusively utilized in chronic total occlusions and should be handled with extreme care.
An example of a tapered tip design.
The core of the guidewire is usually covered either by coils or by a polymer component (Figure 4). When all the core is surrounded only by spring coils (spring coils design), it enhances tactile feel (see below), but adds friction when navigating the arterial tree, reducing trackability. However, this additional friction tends to stabilize the wire distally to the target lesion, making the guidewire less prone to move backward or forward. On the other hand, a polymer jacket along all the guidewire including the tip provides a very smooth surface improving trackability at the cost of losing tactile feel. Some guidewires have a hybrid covering or polymer covering all the body but leaving the coils of the tip naked, also referred to as “sleeves” [3]. This configuration allows good trackability of the body maintaining tactile feel mostly intact.
Most of contemporary guidewires have a thin hydrophilic or hydrophobic coating applied at the final manufacturing process (Figure 4). Hydrophilic coating (e.g., polyethylene oxide or polyvinyl pyrolidone) needs water to be activated and to become slippery, but once wet, it allows an extremely low coefficient of friction [4]. As a result, it makes vessels easier to track and stenoses simpler to cross but leads to a decreased tactile feel, increasing the risk of dissection or perforation. Paradoxically, if a guidewire with hydrophilic coating gets dry, it loses lubricity and can get stuck, for instance, inside a catheter. Conversely, hydrophobic coatings (e.g., polytetrafluoroethylene or silicones) do not require water for activation [4]. As their name indicates, they repel water and create a smooth, “wax-like” surface [3]. Hydrophobic coating reduces friction but leads to a less slippery guidewire with enhanced tactile feel. Frequently, hydrophobic coatings are applied to guidewire bodies to facilitate movement inside plastic catheters [4]. Nevertheless, both coatings can coexist in a single guidewire, allowing their respective specific characteristics to be present either at the tip or throughout the body. In some configurations, even the tip can have both coatings, for instance, hydrophobic at the end for tactile feel and tip control purposes and hydrophilic intermediate segment for smooth crossing. Moreover, both hydrophilic and hydrophobic coatings may chafe or degrade with use [4]. This can account for the deterioration in wire performance at times noted during long procedures, particularly when wires are working through areas of severe tortuosity and friction or after numerous device exchanges [4]. This can even lead the guidewire to get fixed inside the catheter, forcing both devices to be removed as one piece, jeopardizing the therapy of the targeted vessel.
Even though, they are common to all guidewires used in endovascular procedures, the characteristics that will be discussed here are much more relevant in the 0.014″ and 0.018″ guidewires.
It reports to the ability of a guidewire in transmitting tactile information from its tip to the hands of the interventionist. Even though it is a relatively subjective property, the possibility of the interventionist to feel the behavior of the tip when tracking vessels or crossing lesions (e.g., the tip goes freely or finds resistance) can help avoiding complications and improving results.
There is an inverse relationship between lubricity and tactile feel (Figure 8). Moreover, specific features can enhance tactile feel such as the core-to-tip design and the spring coil design.
Components combination influencing the relationship between lubricity and tactile feel.
The tip load represents the stiffness of the tip and is defined by the force needed to deflect to bend the tip 2 mm when the wire is fixed 10 mm above its end (Figure 9). It is a quite well-defined and reproducible parameter and therefore a comparable property. But as it is expressed in grams, it can generate confusion making some to think that the guidewire has effectively added weights at the tip. The tip load of the 0.014″ and 0.018″ guidewires utilized in peripheral interventions can range from 0.5 up to 35 g or more. The higher the tip load, the more aggressive the tip is. The lower it is, the softer and atraumatic it is.
Tip load test.
The penetration capacity can be defined by the perpendicular force exerted over a defined area (i.e., pressure). It will depend on the tip load and the profile of the tip. For the same tip load, a guidewire that has a tapered tip will have a much higher penetration capacity than a more conventional nontapered tip. Additionally, adding a catheter (either a balloon catheter or a support catheter) very close to the end of the tip also adds penetration capacity as it prevents the tip to bend.
Most of the 0.035″ guidewires used in peripheral interventions come in a preshaped format from the manufacturer. The more common available shapes are straight, angled, and J-shaped. The latter is the least traumatic. As so, it can be the best guidewire to use to deliver the intended devices to a target vessel. It can also be quite useful in tracking throughout a previously placed patent stent because the tip will not get stuck in the struts of the stent, neither will go between the stent and the vessel wall. Straight tips are more adequate to cross occlusions and angled tips to track vessels and to cross stenoses.
On the other hand, the vast majority of the 0.014″ and 0.018″ guidewires available for peripheral purposes comes in a straight shape and needs to be shaped. As so, shapeability characterizes the capacity of the guidewire tip to be angulated and shaped by the interventionist and shape retention represents its ability to maintain the intended shape over time [3]. These properties depend on the tip design and materials. Accordingly, a core-to-tip design with a core made of stainless steel is particularly easy and accurate to be shaped, but almost impossible to be reshaped. Conversely, nitinol core makes the tip more difficult to be shaped because it tends to return to its original form (memory) but is more reshapeable.
The tip of the GW can be shaped using the puncture needle (for moderately angulated curves), with the non-cutting edge of the blade (for sharp angulations) or with the inserter (for both) (Videos 1 and 2, https://bit.ly/3jPF7aj).
The desired shape depends on the primary purpose the guidewire will be used (Figure 10). Moderately angled continuous curves are very useful to track throughout the artery tree or to select a target vessel (Figure 10A). Several sharp angulations may help in selecting arteries with an acute takeoff such as the anterior tibial artery (Figure 10B). A very short sharply angled curve (usually no more than 1 mm) is intended to perform forceful and well-controllable drilling (Figure 10C).
Tip shaping. A—Moderately angled continuous curve. B—Two sharp angles. C—Very short sharply angled curve.
An accurate knowledge of the discussed characteristics of each guidewire will permit the proper choice for every specific situation and also to create an adequate local laboratory portfolio. In practice, a vascular interventionist will rather need to thoroughly master a relatively small number of guidewires, instead of scarcely knowing many.
The purpose of guidewires in a peripheral procedure can be summarized as:
getting to the target vessel;
crossing the target lesion;
give support to deliver the intended devices to the target lesion in a safely way.
Most of the interventionists have one or two “workhorse” guidewires, which are the guidewires that will be chosen to initiate the procedure and get to the target vessel. Their common characteristics are: good trackability and torqueability to navigate throughout the arterial tree, correct body stiffness to deliver catheters and sheaths to the intended vessel, and a tip as atraumatic as possible. They can also be used as an initial approach to the target lesion.
One additional aspect to take into account when choosing a guidewire is the catheter that will be also used. As such, for stenoses and some occlusions in larger vessels, such as the iliac arteries, an angled diagnostic or support catheter can be preferred to guide the tip of the guidewire to the center of the vessel, avoiding a subintimal track. Meanwhile, a straight support catheter or a balloon catheter would be the primary option for most of the stenoses and for occlusions in smaller vessels such as the tibial arteries.
One of the best friends of a vascular interventionist is the torquer (Figure 11). It is the most proper manner to control the orientation of the guidewire tip. Therefore, its utilization is of utmost relevance in tracking difficult anatomies or in crossing challenging lesions (for instance, if the drilling technique is to be employed).
Example of a torquer.
After having crossed the target lesion, the guidewire should be advanced very smoothly to the distal segment of the vessel. Confirmation through contrast injection that the true lumen has been reached after crossing the lesion is a basic but essential step. If a guidewire with a very aggressive tip was used to cross the lesion, it should be replaced by a much safer guidewire with good body stiffness for support (frequently the initial workhorse guidewire is adequate for this intent), sometimes after having shaped the tip as a loop (J-shaped like). During the delivery of the intended devices to the target lesion, it is of paramount importance to avoid inadvertent retraction of the guidewire, particularly after a complex crossing step and to prevent back and forth or shaking motion of the guidewire. That is why the tip of the guidewire should be on sight at almost all times. In summary, the two goals are: to secure the access to the target vessel and lesion; to avoid any trauma to the distal intact vessels.
The opening “workhorse” guidewire can be used in an initial attempt to cross the target lesion. Nevertheless, in many circumstances, a more dedicated guidewire will be required.
To cross a stenosis, it is perceptibly fundamental to stay intraluminal. For that purpose, the guidewire does not need to have increased stiffness, pushability, or penetration capacity. The tip should probably be hydrophilic as tactile feel is less relevant in those situations, and this can also improve the crossability of the guidewire. The tip is typically shaped in soft curve (Figure 10A), to be directed to the opposite direction of the stenosis. Specifically in tibial vessels, a 0.014″ guidewire can be preferable as in the case showed in Figure 1.
A chronic total occlusion is generally defined as an occluded artery of 3 months duration or longer [5]. When the vascular interventionist faces a chronic total occlusion, the best guidewire is obviously the one that successfully crosses the lesion. Nevertheless, there are several issues to consider in an attempt to cross a chronic total occlusion:
The target artery. In fact, some arteries can be quite challenging to recanalize. For instance, an occlusion of the anterior tibial artery from its origin is, most of the times, very challenging to cross anterogradely because of the difficulty to engage the ostium. In those circumstances, adjuvant retrograde approach can be very helpful.
The length of the occlusion. Longer occlusions are more difficult to cross and involve additional struggle to keep the guidewire in an intraluminal track. Moreover, the guidewire should have a stiffer body to support the crossing of a balloon or a support catheter, and it can also frequently require segmental pre-dilatations.
The associated calcification. Depending on its length, location (entry point of the occlusion and/or in its core), and whether it is concentric or eccentric, calcification can greatly complicate the crossing of an occlusion or the reentry after a subintimal path. It also increases the risk of complications such as perforations or ateroembolization. On another hand, medial calcification can occasionally help in defining the limits of the vessel and consequently can guide the interventionist to stay intraluminal.
Visible run-off. As a rule, the end of the chronic total occlusion should be clearly defined. Nevertheless, in some instances, such as in tibial vessels with very poor collateralization, it may not be initially adequately outlined and only appears after having crossed the occlusion.
This technique is particularly indicated for engaging softer chronic total occlusions with microchannels [6]. It is frequently the first approach. For that intent, the initial “workhorse” guidewire with a soft hydrophilic tip and a body with some stiffness can be the option as reduced surface friction enhances passage through the chronic total occlusion core. The tip should initially be shaped in a single, long shallow bend (Figure 10A), and movement consists of simultaneous smooth tip rotation and gentle probing. But during the crossing, the interventionist should stay vigilant, as the guidewire has reduced tactile feel and typically advances with minimal resistance, frequently resulting in inadvertent entry to the subintimal space [7].
If the sliding technique fails after a few attempts (one should not insist on this technique as it is easy to create several subintimal tracks that will jeopardize a desirable intra-luminal crossing), then the drilling technique should be tried. In this technique, a guidewire with a core-to-tip design with an uncovered tip should be preferred to enhance tactile feel. The tip is bended in a very short extension (Figure 10C) and clockwise and counterclockwise rotations of the guidewire are performed while the tip is pushed modestly against the chronic total occlusion (Figure 12). The important issue in this technique is that one does not push the guidewire very hard. Placing the balloon or the support catheter very close to the tip increases the penetration capacity. If the tip of the guidewire does not advance any more with gentle pushing, it is by far better to exchange for a stiffer tip and body guidewire, rather than continue pushing. If one pushes the wire hard, it will easily go into the subintimal space. Yet, when a stiffer guidewire is used, it may be difficult to perceive whether the tip has been engaged in the true or in a false lumen inside the chronic total occlusion. The movement of the tip may help in distinguishing one from the other. Typically, when the guidewire is in the subadventitial space, the tip budges markedly. Tactile feel from the guidewire during pullback can also aid as true lumen usually offers higher resistance. This technique has an increased risk of perforation, especially when using stiff tips guidewires [7].
Drilling technique. Adapted from [
The penetration technique comes next if the drilling technique does not succeed or when the interventionist has a chronic total occlusion with very calcified cap. In this technique, the preferred guidewires have a very aggressive tip (core to-tip design, uncovered tapered tip, with increased tip load, and a subsequent high penetration capacity) and a relatively stiff body. The tip shape is essentially straight, and a less rotational tip motion and a more direct forward probing is used in comparison to the drilling technique (Figure 13). Again, placing the balloon or the support catheter very close to the tip increases the penetration capacity and reduces the propensity of the tip to bend. Additionally, the distal target must be clearly identified and careful monitoring of the progressive guidewire advancement should be done. The guidewires employed in this technique should not be used to deliver the intended devices to the target lesion as the tip can easily damage the distally intact vessels. It is a technique with a particularly augmented risk of complications [7].
Penetrating technique. Adapted from [
It is usually the last technique to be employed, even if it can be a first option in specific situations such as very long chronic total occlusions. For this technique, a guidewire with a stiff body and a soft short tip with hydrophilic coating is usually preferable. The short tip allows a short loop. After having created the loop, the guidewire is advanced to the end of the occlusion. To reenter into the true lumen, the loop has to be undone. Sometimes, the guidewire needed to be exchanged to a guidewire with a reduced diameter (if the initial guidewire was not a 0.014″ guidewire), with an uncovered tip (to increase the tactile feel and reduce the tendency to stay in the subintimal space that a hydrophilic tips has), a good torqueability, and an angled shaped tip (to be able to direct this one to the true lumen). Sometimes moving the balloon or the support catheter and the guidewire as one can be very useful (Video 3, https://bit.ly/3jPF7aj and Figure 14). If the loop, during the crossing, becomes too large, it means that most certainly, a perforation has occurred. In these situations, the guidewire should be retracted and an another subintimal track should be pursued.
A, B—Initial angiogram showing a long occlusion of the anterior tibial artery. C—Confirmation that the true lumen has been reached after a subintimal crossing of the occlusion (Video 3,
When the antegrade approach is not successful, a retrograde puncture may be required. Retrograde puncture of the popliteal artery is usually not a big issue. However, at below-the-knee level, since arteries are quite small and fragile and frequently the tibial or peroneal artery to be punctured is the unique artery to the foot, extreme care must be the rule. As so, after having performed the puncture with a 21G needle (either guided by ultrasound or by X-ray), a guidewire is to be engaged inside the artery. To avoid additional injury to the artery, the devices introduced in it should be kept at the strict minimum. That why usually it is most preferable to initially advance only the guidewire without any catheter or sheath (Figure 15). Therefore, the guidewire to be chosen needs to have a hydrophilic stiff body due to the lack of a sheath, the relevance of having adequate torqueability to guide the tip and to perform the snaring of the guidewire, and a potential need for an additional catheter if the guidewire does not reach the true lumen or the same subintimal track made anterogradely. A 0.018″ diameter guidewire is probably the best option as it is still a delicate guidewire, but with more support than a 0.014″ guidewire. The tip should be soft and most probably hydrophilic to track easily the punctured vessel retrogradely. As no sheath should usually be introduced, hard push on the guidewire can lead to irreversible kinging of its body, which can jeopardize the intervention.
After a retrograde puncture of the peroneal artery, a guidewire was inserted in it lumen, without any sheath or catheter.
This technique consists in creating a loop with the guidewire from the anterior tibial artery to the posterior tibial artery, or the reverse, through the foot vessels [8, 9]. The most common pathway is through dorsalis pedis artery, deep plantar artery, deep plantar arterial arch, lateral plantar artery, and posterior tibial artery. Indications for this technique are similar to the retrograde access. However, it can be performed when no distal vessels are available for puncture, being also less invasive. Moreover, this technique can improve the outflow for tibial arteries.
However, complications related to foot vessels manipulation can precipitate a serious worsening of the ischemic condition. Taking this into account, the guidewire to be chosen to this technique needs to have a soft hydrophilic tip to easily track through tortuous foots vessels without damaging them. The body should also have reduced stiffness to track across the created loop, that’s why usually a 0.014″ guidewire is preferred.
The manipulation with a guidewire of smaller vessels such as the tibial and foot arteries can precipitate vasospasm. This can be quite common in young patients or in vessels with no calcification. It is very relevant to be able to recognize it and consequently avoid the confusion with atherosclerotic stenoses and perform angioplasty on those arteries, which can lead to dissection or even rupture (Figure 16). Several drugs can be administered intra-arterially to solve the issue. Agents commonly used for this purpose are nitroglycerin, verapamil, or papaverine. The dose to be injected should consider the blood pressure of the patient. The hemodynamic status of the patient should also be closely checked after the administration. They ideally should be given selectively through a diagnostic catheter to the target vessel. The guidewire can be gently withdrawn to a more proximal segment of the vessel, but without losing the ostium and consequently the access to the vessel.
A—Initial angiogram showing an occlusion of the tibioperoneal trunk and a quite healthy posterior tibial artery. B—After having crossed the occlusion, a 0.018″ guidewire was advanced inside the posterior tibial artery causing diffuse spasm of the artery (string of beads appearance). C—Few minutes after having selectively administrated 200 μg of nitroglycerin, the posterior tibial artery is widely open again.
A perforation or an arteriovenous fistula that occurs while attempting to cross a chronic total occlusion is rarely of any clinical significance as it will almost constantly closes within few minutes when only a guidewire or a low-profile catheter has passed extraluminally [10] (Figures 17 and 18). Thus, one should be sure to be inside the vessel before inflating a balloon. Removing the devices to above the proximal cap of the chronic total occlusion and reattempting to cross the lesion from the top, may allow successful path and aid in solving the perforation or the arteriovenous fistula. When those complications do not auto-resolve, external compression guided by angiography or temporary vessel occlusion with a balloon can be attempted. Sometimes a covered stent may be needed. In very rare situations, coil embolization must be envisaged.
A—Perforation of the lateral plantar artery; extraluminal contrast is easily noticed. B—Peroneal arteriovenous fistula. Adapted from [
A—Occlusion of the popliteal artery, tibio-peroneal trunk, and proximal segment of peroneal artery. B—Perforation occurred while trying to cross the occlusion through the initial antegrade approach. C & D—Final result after a retrograde puncture of the peroneal artery and successful crossing of the occlusion.
An unintended wall dissection or perforation of an intact vessel distally after having crossed the target lesion can be quite challenging to solve and can threaten the success of the procedure or even worsen the ischemic condition of the patient. Therefore, the most relevant concerning this issue is to adopt correct guidewire choices and strategies to avoid it.
X-ray fluoroscopy is still the gold standard imaging technique for the vast majority of endovascular procedures currently performed. Therefore, most of the endovascular devices, guidewires included, are designed to optimally perform under X-ray. However, its inherent ionizing radiation leads to safety concerns not only to the healthcare professionals, but also to the patients. As a result, recent advancements have been made toward magnetic resonance guided endovascular interventions [11]. Magnetic resonance imaging is a noninvasive, radiation-free imaging technique that can provide not only morphologic but also functional information (e.g., blood flow, tissue oxygenation, diffusion, or perfusion), which can potentially influence decisions during a procedure [11]. Yet, magnetic resonance guided interventions face a major challenge due to the presence of a large magnetic field, which limits the utilization of the currently available materials, including guidewires. Despite these challenges, significant progress has been recently made in the development of biocompatible, magnetic resonance safe, and visible interventional devices [11]. The guidewires presently used in the endovascular field have a long metallic core. In a magnetic resonance environment, it can create artifacts and can also induce thermal injury. As a result, new dedicated guidewires have been designed with the metallic core replaced by polymers reinforced by glass fibers or fiber composites. Those guidewires demonstrated to have improved stiffness and kink resistance [11]. Further research and development regarding magnetic resonance compatible devices and magnetic resonance imaging techniques will probably lead to a shift in the future standards of endovascular procedures.
Guidewires are the cornerstone of any endovascular revascularization. Therefore, a correct knowledge of the engineering aspects of wire technology can be the difference between failure and success as it allows an adequate guidewire choice in any situation and for each specific crossing technique. A vascular interventionist should subsequently master a relatively small number of guidewires to be able to fully translate in practice his theoretical knowledge on guidewire design.
Video materials referenced in this chapter are available at: https://bit.ly/3jPF7aj.
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',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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\n\nThe following terminology applies to these Terms and Conditions, Privacy Statement, Disclaimer Notice, and any or all Agreements:
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Achilias"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10681",title:"Biodegradation Technology of Organic and Inorganic Pollutants",subtitle:null,isOpenForSubmission:!1,hash:"9a6e10e02788092872fd249436898e97",slug:"biodegradation-technology-of-organic-and-inorganic-pollutants",bookSignature:"Kassio Ferreira Mendes, Rodrigo Nogueira de Sousa and Kamila Cabral Mielke",coverURL:"https://cdn.intechopen.com/books/images_new/10681.jpg",editedByType:"Edited by",editors:[{id:"197720",title:"Ph.D.",name:"Kassio",middleName:null,surname:"Ferreira Mendes",slug:"kassio-ferreira-mendes",fullName:"Kassio Ferreira Mendes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10843",title:"Persistent Organic Pollutants (POPs)",subtitle:"Monitoring, Impact and Treatment",isOpenForSubmission:!1,hash:"f5b1589f0a990b6114fef2dadc735dd9",slug:"persistent-organic-pollutants-pops-monitoring-impact-and-treatment",bookSignature:"Mohamed Nageeb Rashed",coverURL:"https://cdn.intechopen.com/books/images_new/10843.jpg",editedByType:"Edited by",editors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:218,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"29369",doi:"10.5772/32373",title:"Textile Organic Dyes – Characteristics, Polluting Effects and Separation/Elimination Procedures from Industrial Effluents – A Critical Overview",slug:"textile-organic-dyes-characteristics-polluting-effects-and-separation-elimination-procedures-from-in",totalDownloads:29487,totalCrossrefCites:128,totalDimensionsCites:321,abstract:null,book:{id:"872",slug:"organic-pollutants-ten-years-after-the-stockholm-convention-environmental-and-analytical-update",title:"Organic Pollutants Ten Years After the Stockholm Convention",fullTitle:"Organic Pollutants Ten Years After the Stockholm Convention - Environmental and Analytical Update"},signatures:"Zaharia Carmen and Suteu Daniela",authors:[{id:"91196",title:"Prof.",name:"Carmen",middleName:null,surname:"Zaharia",slug:"carmen-zaharia",fullName:"Carmen Zaharia"},{id:"92084",title:"Dr.",name:"Daniela",middleName:null,surname:"Suteu",slug:"daniela-suteu",fullName:"Daniela Suteu"}]},{id:"42059",doi:"10.5772/54048",title:"Adsorption Technique for the Removal of Organic Pollutants from Water and Wastewater",slug:"adsorption-technique-for-the-removal-of-organic-pollutants-from-water-and-wastewater",totalDownloads:30043,totalCrossrefCites:51,totalDimensionsCites:221,abstract:null,book:{id:"3426",slug:"organic-pollutants-monitoring-risk-and-treatment",title:"Organic Pollutants",fullTitle:"Organic Pollutants - Monitoring, Risk and Treatment"},signatures:"Mohamed Nageeb Rashed",authors:[{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",slug:"mohamed-nageeb-rashed",fullName:"Mohamed Nageeb Rashed"}]},{id:"27305",doi:"10.5772/39363",title:"Water Stress in Plants: Causes, Effects and Responses",slug:"water-stress-in-plants-causes-effects-and-responses",totalDownloads:28496,totalCrossrefCites:72,totalDimensionsCites:172,abstract:null,book:{id:"911",slug:"water-stress",title:"Water Stress",fullTitle:"Water Stress"},signatures:"Seyed Y. S. Lisar, Rouhollah Motafakkerazad, Mosharraf M. Hossain and Ismail M. M. Rahman",authors:[{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",slug:"ismail-m.m.-rahman",fullName:"Ismail M.M. Rahman"}]},{id:"62247",doi:"10.5772/intechopen.77315",title:"Application of Biosorption for Removal of Heavy Metals from Wastewater",slug:"application-of-biosorption-for-removal-of-heavy-metals-from-wastewater",totalDownloads:7645,totalCrossrefCites:75,totalDimensionsCites:152,abstract:"Fresh water accounts for 3% of water resources on the Earth. Human and industrial activities produce and discharge wastes containing heavy metals into the water resources making them unavailable and threatening human health and the ecosystem. Conventional methods for the removal of metal ions such as chemical precipitation and membrane filtration are extremely expensive when treating large amounts of water, inefficient at low concentrations of metal (incomplete metal removal) and generate large quantities of sludge and other toxic products that require careful disposal. Biosorption and bioaccumulation are ecofriendly alternatives. These alternative methods have advantages over conventional methods. Abundant natural materials like microbial biomass, agro-wastes, and industrial byproducts have been suggested as potential biosorbents for heavy metal removal due to the presence of metal-binding functional groups. Biosorption is influenced by various process parameters such as pH, temperature, initial concentration of the metal ions, biosorbent dose, and speed of agitation. Also, the biomass can be modified by physical and chemical treatment before use. The process can be made economical by regenerating and reusing the biosorbent after removing the heavy metals. Various bioreactors can be used in biosorption for the removal of metal ions from large volumes of water or effluents. The recent developments and the future scope for biosorption as a wastewater treatment option are discussed.",book:{id:"6137",slug:"biosorption",title:"Biosorption",fullTitle:"Biosorption"},signatures:"Sri Lakshmi Ramya Krishna Kanamarlapudi, Vinay Kumar\nChintalpudi and Sudhamani Muddada",authors:[{id:"238433",title:"Associate Prof.",name:"Sudhamani",middleName:null,surname:"Muddada",slug:"sudhamani-muddada",fullName:"Sudhamani Muddada"},{id:"244937",title:"Mrs.",name:"S L Ramyakrishna",middleName:null,surname:"Kanamarlapudi",slug:"s-l-ramyakrishna-kanamarlapudi",fullName:"S L Ramyakrishna Kanamarlapudi"},{id:"244938",title:"Mr.",name:"Vinay Kumar",middleName:null,surname:"Chintalpudi",slug:"vinay-kumar-chintalpudi",fullName:"Vinay Kumar Chintalpudi"}]},{id:"53211",doi:"10.5772/66416",title:"Biofloc Technology (BFT): A Tool for Water Quality Management in Aquaculture",slug:"biofloc-technology-bft-a-tool-for-water-quality-management-in-aquaculture",totalDownloads:16966,totalCrossrefCites:65,totalDimensionsCites:148,abstract:"Biofloc technology (BFT) is considered the new “blue revolution” in aquaculture. Such technique is based on in situ microorganism production which plays three major roles: (i) maintenance of water quality, by the uptake of nitrogen compounds generating in situ microbial protein; (ii) nutrition, increasing culture feasibility by reducing feed conversion ratio (FCR) and a decrease of feed costs; and (iii) competition with pathogens. The aggregates (bioflocs) are a rich protein-lipid natural source of food available in situ 24 hours per day due to a complex interaction between organic matter, physical substrate, and large range of microorganisms. This natural productivity plays an important role recycling nutrients and maintaining the water quality. The present chapter will discuss some insights of the role of microorganisms in BFT, main water quality parameters, the importance of the correct carbon-to-nitrogen ratio in the culture media, its calculations, and different types, as well as metagenomics of microorganisms and future perspectives.",book:{id:"5355",slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Maurício Gustavo Coelho Emerenciano, Luis Rafael Martínez-\nCórdova, Marcel Martínez-Porchas and Anselmo Miranda-Baeza",authors:[{id:"146126",title:"Dr.",name:"Maurício Gustavo Coelho",middleName:null,surname:"Emerenciano",slug:"mauricio-gustavo-coelho-emerenciano",fullName:"Maurício Gustavo Coelho Emerenciano"},{id:"186970",title:"Prof.",name:"Marcel",middleName:null,surname:"Martínez-Porchas",slug:"marcel-martinez-porchas",fullName:"Marcel Martínez-Porchas"},{id:"186971",title:"Prof.",name:"Anselmo",middleName:null,surname:"Miranda-Baeza",slug:"anselmo-miranda-baeza",fullName:"Anselmo Miranda-Baeza"},{id:"195101",title:"Dr.",name:"Luis Rafael",middleName:null,surname:"Martínez-Córdoba",slug:"luis-rafael-martinez-cordoba",fullName:"Luis Rafael Martínez-Córdoba"}]}],mostDownloadedChaptersLast30Days:[{id:"69568",title:"Water Quality Parameters",slug:"water-quality-parameters",totalDownloads:10165,totalCrossrefCites:14,totalDimensionsCites:36,abstract:"Since the industrial revolution in the late eighteenth century, the world has discovered new sources of pollution nearly every day. So, air and water can potentially become polluted everywhere. Little is known about changes in pollution rates. The increase in water-related diseases provides a real assessment of the degree of pollution in the environment. This chapter summarizes water quality parameters from an ecological perspective not only for humans but also for other living things. According to its quality, water can be classified into four types. Those four water quality types are discussed through an extensive review of their important common attributes including physical, chemical, and biological parameters. These water quality parameters are reviewed in terms of definition, sources, impacts, effects, and measuring methods.",book:{id:"7718",slug:"water-quality-science-assessments-and-policy",title:"Water Quality",fullTitle:"Water Quality - Science, Assessments and Policy"},signatures:"Nayla Hassan Omer",authors:null},{id:"58138",title:"Water Pollution: Effects, Prevention, and Climatic Impact",slug:"water-pollution-effects-prevention-and-climatic-impact",totalDownloads:21554,totalCrossrefCites:18,totalDimensionsCites:38,abstract:"The stress on our water environment as a result of increased industrialization, which aids urbanization, is becoming very high thus reducing the availability of clean water. Polluted water is of great concern to the aquatic organism, plants, humans, and climate and indeed alters the ecosystem. The preservation of our water environment, which is embedded in sustainable development, must be well driven by all sectors. While effective wastewater treatment has the tendency of salvaging the water environment, integration of environmental policies into the actor firms core objectives coupled with continuous periodical enlightenment on the present and future consequences of environmental/water pollution will greatly assist in conserving the water environment.",book:{id:"6157",slug:"water-challenges-of-an-urbanizing-world",title:"Water Challenges of an Urbanizing World",fullTitle:"Water Challenges of an Urbanizing World"},signatures:"Inyinbor Adejumoke A., Adebesin Babatunde O., Oluyori Abimbola\nP., Adelani-Akande Tabitha A., Dada Adewumi O. and Oreofe Toyin\nA.",authors:[{id:"101570",title:"MSc.",name:"Babatunde Olufemi",middleName:null,surname:"Adebesin",slug:"babatunde-olufemi-adebesin",fullName:"Babatunde Olufemi Adebesin"},{id:"187738",title:"Dr.",name:"Adejumoke",middleName:"Abosede",surname:"Inyinbor",slug:"adejumoke-inyinbor",fullName:"Adejumoke Inyinbor"},{id:"188818",title:"Dr.",name:"Abimbola",middleName:null,surname:"Oluyori",slug:"abimbola-oluyori",fullName:"Abimbola Oluyori"},{id:"188819",title:"Mrs.",name:"Tabitha",middleName:null,surname:"Adelani-Akande",slug:"tabitha-adelani-akande",fullName:"Tabitha Adelani-Akande"},{id:"208501",title:"Dr.",name:"Adewumi",middleName:null,surname:"Dada",slug:"adewumi-dada",fullName:"Adewumi Dada"},{id:"208502",title:"Ms.",name:"Toyin",middleName:null,surname:"Oreofe",slug:"toyin-oreofe",fullName:"Toyin Oreofe"}]},{id:"45422",title:"Urban Waterfront Regenerations",slug:"urban-waterfront-regenerations",totalDownloads:14203,totalCrossrefCites:4,totalDimensionsCites:12,abstract:null,book:{id:"3560",slug:"advances-in-landscape-architecture",title:"Advances in Landscape Architecture",fullTitle:"Advances in Landscape Architecture"},signatures:"Umut Pekin Timur",authors:[{id:"165480",title:"Dr.",name:"Umut",middleName:null,surname:"Pekin Timur",slug:"umut-pekin-timur",fullName:"Umut Pekin Timur"}]},{id:"24941",title:"Tsunami in Makran Region and Its Effect on the Persian Gulf",slug:"tsunami-in-makran-region-and-its-effect-on-the-persian-gulf",totalDownloads:7575,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"406",slug:"tsunami-a-growing-disaster",title:"Tsunami",fullTitle:"Tsunami - A Growing Disaster"},signatures:"Mohammad Mokhtari",authors:[{id:"52451",title:"Dr.",name:"Mohammad",middleName:null,surname:"Mokhtari",slug:"mohammad-mokhtari",fullName:"Mohammad Mokhtari"}]},{id:"66307",title:"Bio-hydrogen and Methane Production from Lignocellulosic Materials",slug:"bio-hydrogen-and-methane-production-from-lignocellulosic-materials",totalDownloads:2953,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"This chapter covers the information on bio-hydrogen and methane production from lignocellulosic materials. Pretreatment methods of lignocellulosic materials and the factors affecting bio-hydrogen production, both dark- and photo-fermentation, and methane production are addressed. Last but not least, the processes for bio-hydrogen and methane production from lignocellulosic materials are discussed.",book:{id:"7608",slug:"biomass-for-bioenergy-recent-trends-and-future-challenges",title:"Biomass for Bioenergy",fullTitle:"Biomass for Bioenergy - Recent Trends and Future Challenges"},signatures:"Apilak Salakkam, Pensri Plangklang, Sureewan Sittijunda, Mallika Boonmee Kongkeitkajorn, Siriporn Lunprom and Alissara Reungsang",authors:null}],onlineFirstChaptersFilter:{topicId:"12",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82465",title:"Agroforestry: An Approach for Sustainability and Climate Mitigation",slug:"agroforestry-an-approach-for-sustainability-and-climate-mitigation",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105406",abstract:"Agroforestry Systems (AFS), or the association of trees with crops (or animals), is a strategy for land management and use that allows production within the sustainable development: (a) environmentally (production environmentally harmonic); (b) technically (integrating existing resources on the farm); (c) economically (increase in production), and (d) socially (equality of duties and opportunities, quality of life of the family group). As an intentional integration of trees or shrubs with crop and animal production, this practice makes environmental, economic, and social benefits to farmers. Given that there is a set of definitions, rather than a single definition of Agroforestry (AF) and AFS, it is justified to explore the historical evolution and the minimum coincidences of criteria to define them and apply them in the recovery of degraded areas. Knowing how to classify AFS allows us to indicate which type or group of AFS is suitable for a particular area with its characteristics. The greatest benefit that AFS can bring to degraded or sloping areas lies in their ability to combine soil conservation with productive functions. In other words, AF is arborizing agriculture and animal production to obtain more benefits including climate change adaptation and mitigation by ecosystem services.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Ricardo O. Russo"},{id:"82754",title:"Impact of Revegetation on Ecological Restoration of a Constructed Soil in a Coal Mining in Southern Brazil",slug:"impact-of-revegetation-on-ecological-restoration-of-a-constructed-soil-in-a-coal-mining-in-southern-",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.105895",abstract:"The main problems in the constructed soils are the generation of acid mine drainage promoted by the presence of coal debris in the overburden layer and the compaction of the topsoil promoted by the machine traffic when the material used in the overburden cover is more clayey. This book chapter aimed to show an overview of the impact of more than a decade of revegetation with different perennial grasses on the chemical, physical, and biological quality of constructed soil after coal mining. The study was carried out in a coal mining area, located in southern Brazil. The soil was constructed in early 2003 and the perennial grasses, Hemarthria altissima; Paspalum notatum cv. Pensacola; Cynodon dactylon cv Tifton; and Urochloa brizantha; were implanted in November/December 2003. In 11.5, 17.6 and 18 years of revegetation soil samples were collected and the chemical, physical, and biological attributes were determined. Our results show that liming is an important practice in the restoration of these strongly anthropized soils because this positively impacts the plants’ development, facilitating the roots system expansion. Biological attributes such as soil fauna and the microorganism’s population are the attributes that possibly takes longer to establish itself in these areas.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Lizete Stumpf, Maria Bertaso De Garcia Fernandez, Pablo Miguel, Luiz Fernando Spinelli Pinto, Ryan Noremberg Schubert, Luís Carlos Iuñes de Oliveira Filho, Tania Hipolito Montiel, Lucas Da Silva Barbosa, Jeferson Diego Leidemer and Thábata Barbosa Duarte"},{id:"82936",title:"Soil Degradation Processes Linked to Long-Term Forest-Type Damage",slug:"soil-degradation-processes-linked-to-long-term-forest-type-damage",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106390",abstract:"Forest degradation impairs ability of the whole landscape adaptation to environmental change. The impacts of forest degradation on landscape are caused by a self-organization decline. At the present time, the self-organization decline was largely due to nitrogen deposition and deforestation which exacerbated impacts of climate change. Nevertheless, forest degradation processes are either reversible or irreversible. Irreversible forest degradation begins with soil damage. In this paper, we present processes of forest soil degradation in relation to vulnerability of regulation adaptability on global environmental change. The regulatory forest capabilities were indicated through soil organic matter sequestration dynamics. We devided the degradation processes into quantitative and qualitative damages of physical or chemical soil properties. Quantitative soil degradation includes irreversible loss of an earth’s body after claim, erosion or desertification, while qualitative degradation consists of predominantly reversible consequences after soil disintegration, leaching, acidification, salinization and intoxication. As a result of deforestation, the forest soil vulnerability is spreading through quantitative degradation replacing hitherto predominantly qualitative changes under continuous vegetation cover. Increasing needs to natural resources using and accompanying waste pollution destroy soil self-organization through biodiversity loss, simplification in functional links among living forms and substance losses from ecosystem. We concluded that subsequent irreversible changes in ecosystem self-organization cause a change of biome potential natural vegetation and the land usability decrease.",book:{id:"11457",title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg"},signatures:"Pavel Samec, Aleš Kučera and Gabriela Tomášová"},{id:"82828",title:"Vegetation and Avifauna Distribution in the Serengeti National Park",slug:"vegetation-and-avifauna-distribution-in-the-serengeti-national-park",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106165",abstract:"In order to examine the bird species changes within different vegetation structures, the variations were compared between Commiphora-dominated vegetations with those of Vachellia tortilis and Vachellia robusta-dominated vegetations, and also compared the birds of grassland with those of Vachellia drepanolobium and Vachellia seyal-dominated vegetations. This study was conducted between February 2010 and April 2012. A total of 40 plots of 100 m × 100 m were established. Nonparametric Mann-Whitney U-test was used to examine differences in bird species between vegetations. Species richness estimates were obtained using the Species Diversity and Richness. A total of 171 bird species representing 103 genera, 12 orders, and 54 families were recorded. We found differences in bird species distribution whereby V. tortilis has higher bird species richness (102 species), abundance, and diversity when compared with Commiphora with 66 species and V. robusta with 59 species. These results suggest that variations in bird species abundance, diversity, and distribution could be attributed to differences in the structural diversity of vegetation. Therefore it is important to maintain different types of vegetation by keeping the frequency of fire to a minimum and prescribed fire should be employed and encouraged to control wildfire and so maintain a diversity of vegetation and birds community.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Ally K. Nkwabi and Pius Y. Kavana"},{id:"82808",title:"Climate Change and Anthropogenic Impacts on the Ecosystem of the Transgressive Mud Coastal Region of Bight of Benin, Nigeria",slug:"climate-change-and-anthropogenic-impacts-on-the-ecosystem-of-the-transgressive-mud-coastal-region-of",totalDownloads:8,totalDimensionsCites:0,doi:"10.5772/intechopen.105760",abstract:"The transgressive mud coastal area of Bight of Benin is a muddy coastal complex that lies east of the Barrier/lagoon coast and stretches to the Benin River in the northwestern flank of the Niger Delta Nigeria. It constitutes a fragile buffer zone between the tranquil waters of the swamps and the menacing waves of the Atlantic Ocean. Extensive breaching of this narrow coastal plain results in massive incursion of the sea into the inland swamps with serious implications for national security and the economy. Climate change impacts from the results of meteorological information of the regions shows a gradual degradation in the past 30 years. Temperature, rainfall and humidity increase annually depict climate change, resulting from uncontrolled exploitation of natural resources is rapidly pushing the region towards ecological disasters. The ecosystem is very unique being the only transgressive mud coastal area of the Gulf of Guinea. The chapter describes the geomorphology, tidal hydrology, relief/drainage, topography, climate/meteorology, vegetation, economic characteristics, anthropogenic activities and their impacts on the ecosystem.",book:{id:"11663",title:"Vegetation Dynamics, Changing Ecosystems and Human Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11663.jpg"},signatures:"Patrick O. Ayeku"},{id:"82697",title:"Analyzing the Evolution of Land-Use Changes Related to Vegetation, in the Galicia Region, Spain: From 1990 to 2018",slug:"analyzing-the-evolution-of-land-use-changes-related-to-vegetation-in-the-galicia-region-spain-from-1",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.106015",abstract:"Considering the complex dynamics, patterns, and particularities that the Galicia region present—e.g., the fragility, shown to achieve sustainable development and growth—a study that analyzes the Land-Use related to the vegetation of this region is seen as pivotal to identifying barriers and opportunities for long-term sustainable development. Using GIS (Geographic Information Systems), the present chapter enables us to identify the dynamics and patterns of the evolution of the Land-Use Changes related to vegetation in the Galicia Region from 1990 to 2018 (years 1990, 2000, 2012, and 2018 using CORINE (Coordination of Information on the Environment) data). This study permits us to reinforce that the Land-Use Changes related to vegetation in the Galicia Region have undergone multiple changes—marked by increasing and decreasing periods. Also, can be considered a surveying baseline for the comparative analysis of similar works for different Land-Use Changes related to vegetation trends in Europe or worldwide. Land-Use Changes related to vegetation studies are reliable tools to evaluate the human activities and footprint of proposed strategies and policies in a territory. 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