",isbn:"978-1-80356-303-9",printIsbn:"978-1-80356-302-2",pdfIsbn:"978-1-80356-304-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"dd28db91ac081287c5204f82e219d67e",bookSignature:"Prof. Xiaoyan Dong and Prof. Nanbert Zhong",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11722.jpg",keywords:"Asthma, Th1/Th2 Balance, Airway Inflammation, miRNA, lncRNA, Cytokines, Signaling Pathways, Steroid Resistance, Severe Asthma, Therapeutic Targets, Biomarker, Bacterial",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 15th 2022",dateEndSecondStepPublish:"April 19th 2022",dateEndThirdStepPublish:"June 18th 2022",dateEndFourthStepPublish:"September 6th 2022",dateEndFifthStepPublish:"November 5th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Dong is a medical doctor director of respiratory in the Shanghai children's hospital. 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I am also the Founder Director of Peking University Center of Medical Genetics as well as the Founder Chairman of Dept. Medical Genetics of Peking University Health Science Center. I have a broad research interest in perinatal health, including maternal-fetal medicine with a focus on prematurity, children development, mental retardation, and developmental disabilities, and birth defects with a focus on brain developmental-relevant disorders. 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Pathology, Fertility and Sterility, BMC Public Health, Clinical and Experimental Dermatology, PLoS One, Reproductive BioMedicine (Online) and Reproductive Biology. My research studies have been founded by the NIH (USA), March of Dimes Foundation (USA), Batten Disease Support and Research Association (USA), New York State Research Foundation for Mental Hygiene (USA), Chinese Ministry of Science and Technology (Oversea Chinese Outstanding Young Investigator Award, and 973 High Tech project), Chinese Ministry of Education (211, 985 Projects), Chinese Natural Science Foundation, and Shanghai Municipal Government. My current research is focusing on the genetic and genomic study of prematurity including preterm birth and stillbirth, as well as the outcome of pregnancy, with an integrated “-omics” approach. I am also exploring rational strategies for the prevention and intervention of preterm birth with a longitudinal approach. 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1. Introduction
Imaging and quantifying various characteristics of blood flow throughout the heart is essential in modern-day cardiology. Measuring blood velocities, pressure gradients, regurgitation, stasis (and much more) is one of the most important tools physicians have for diagnosing cardiovascular pathology, stratifying severity, evaluating disease progression, and determining the most effective treatment strategies. Improving the accuracy and depth of such hemodynamic measurements is an ongoing process that continues to enhance clinical success. Two-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI) and Doppler echocardiography are currently the most widely used techniques for measuring cardiovascular blood flow in-vivo [1]. However, while these modalities provide immense value in clinical practice, they have their limitations. Velocity can only be measured in one direction; in Doppler echocardiography following the direction of the ultrasound beam and in 2D PC-MRI following the encoding direction assigned by the user. This can cause errors in flow measurements, depending on whether the beam/plane is placed at the exact location of interest and/or orthogonal to the direction of flow [2, 3]. These 2D measurements often rely heavily on mathematical assumptions that are not always valid [2]. For example, 2D calculations of pressure gradients are known to underestimate pressure recovery downstream of stenosis [4]. In addition, some techniques provide limited viewpoints of the thoracic cavity, such as trans-thoracic echocardiography and trans-esophageal echocardiography [1, 5]. It is also possible to acquire the in-plane velocities (X and Y directions) over time (two velocities + time) or the three plane velocities (X, Y, and Z directions) over time (three velocities + time).
Time-resolved three-dimensional (3D) phase-contrast magnetic resonance imaging (i.e. 4D flow MRI) is a novel non-invasive, non-ionizing imaging technique that provides accurate qualitative and quantitative assessment of blood velocity in all three principle directions [6, 7]. This allows for enhanced accuracy of previously measurable parameters obtained routinely by Doppler echocardiography, such as velocity and reverse flow, as well as the calculation of new parameters, such as wall shear stress (WSS), 3D pressure gradients, and turbulent kinetic energy (TKE). These parameters can be retrospectively visualized and quantified in volumes (rather than cross sections), over the course of a cardiac cycle, and in unlimited viewpoints. Authors can refer to 2D, 3D, 4D, 5D or 7D flow depending on the acquisition scheme used to encode the velocity directions over time. Thus, it is important to understand how the velocity acquisition is defined. In this chapter, 4D flow MRI measures 3 velocity encoded directions in a stack of planes along the cardiac cycle. As such, the ongoing development of 4D flow MRI provides great promise in improving the clinical management of cardiovascular disease.
2. Data acquisition and pre-processing
2.1 Safety and preparation
There are safety measures and recommendations that should be considered for subjects undergoing 4D flow MRI [6, 8]. Patients can fill out pre-imaging safety questionnaires that consider items that can cause a hazard or interfere with the MRI examination. The safety information may become frequently updated because of continuous and rapid changes in the MRI technology. Before starting any cardiac MRI study, compatible electrocardiogram (ECG) leads should be placed on the subject’s chest properly. The accurate synchronization of data acquisition with phases of the cardiac cycle, including different stages of contraction and relaxation, is one of the essential requirements for efficacious cardiac MRI exam. This technique is called ECG-gating. A phased-array receiver coil is required to capture the electromagnetic signals needed to create an image. Thus, it is important that receiver coils are positioned appropriately to cover the regions of interest. The use of contrast agents is optional in 4D flow MRI, but they can help increase the signal-to-noise ratio, and therefore improve the image quality.
2.2 Data acquisition
In 4D flow MRI, acquisition parameters (ex: spatial resolution, temporal resolution, field of view, etc.) are optimized and programmed into the scan protocol to provide the best possible imaging accuracy. Setting major scan parameters is primarily a fine balance between adequate temporal/spatial resolution and minimized scan time. Imaging accuracy can also be affected by artifacts (i.e., distortions in the image that are not present in reality), of which velocity encoding (Venc) is an important contributor. Velocity encoding is a user-defined parameter that sets the upper and lower limits of blood velocity which can be appropriately imaged for within the scan protocol. If the patient’s blood velocities fall above the Venc limit, aliasing will corrupt the image with artifacts in those locations. However, if the Venc range is set too high, the image can be populated with noise [9]. Furthermore, artifacts can arise from movement due to cardiac motion and breathing. As shown in Figure 1, ECG-gating compensates for cardiac motion to determine when the heart is most still, at which point images are acquired [10]. Simultaneously, diaphragmatic navigator gating compensates for breathing artifacts by similarly tracking movement of the patient’s diaphragm and acquiring images at the point of least movement [11]. This allows the patient to breath freely during the scan without creating breathing-related artifacts. These approaches are applied to provide the clearest possible images of 3D global and local blood flow characteristics. Four types of images are produced after acquisition: one magnitude image (shows anatomical structures) and three phase images (shows blood velocity along the Venc directions, often x, y, and z axes).
Figure 1.
Data acquisition for 4D flow MRI. Data acquisition covering the whole heart (large orange rectangle) is acquired using electrocardiogram-gating and respiratory control (small orange rectangle). Three-dimensional velocity-encoding (right side) is used to obtain velocity-sensitive phase images which are subtracted from reference images to calculate blood flow velocities along all three spatial dimensions (X, Y, Z) and averaged magnitude visualizing anatomy over the cardiac cycle.
The most important limiting factor for adding 4D flow to a routine clinical cardiac MRI exam is long scan times associated with multidimensional imaging over the entire cardiac cycle. In 1990s, the total scan time was roughly 40–80 minutes which made difficult its routine application in clinical settings. In recent years, scan times have been further reduced due to ongoing progress in advanced imaging techniques. Nowadays, different reconstruction techniques (parallel imaging, radial and Cartesian sampling, compressed sensing, etc.), in addition to enhanced computing power, have reduced the scan time to 3–10 minutes [12, 13, 14]. The latter is facilitating is penetration as a diagnostic tool. Finally, all acquired data are saved in the Digital Imaging and Communications in Medicine standard format in the MRI system database.
2.3 Pre-processing and correction
Due to a range of errors, image quality can be damaged by various factors including noise, eddy current effects, concomitant gradient field effects (Maxell terms), velocity aliasing, and gradient field nonlinearity. Data pre-processing is applied to rectify these potential errors using several correction strategies to make 4D flow MRI a reliable source of 3D flow visualization and quantification, as illustrated in Figure 2 [15]. Three-dimensional phase-contrast magnetic resonance angiography (3D PC-MRA) can be obtained at this stage based on acquired data from 4D flow MRI by several presented strategies without the need for further MRI acquisition. A 3D PC-MRA can display complex vascular structures and geometries of interest without requiring a contrast agent. It is vastly helpful in some situations, such as patients with contrast agent contraindication. In addition, 3D PC-MRA allows the user to retrospectively isolate specific volumes of interest for analysis.
Figure 2.
Data pre-processing. Acquired 4D flow images are pre-processed applying multiple corrections (panel A). A phase-contrast angiogram (PC-MRA) is calculated to visualize the cardiac structures and can be used for individual segmentation of vessels, panel B. the generated PC-MRA and/or segmentation can be used to mask the velocity field for appropriate visualization and analysis using planes or volumetric regions of interest, panel C. In this example a 58-year-old control volunteer is presented.
However, 4D flow MRI images present difficulties for segmentation algorithms due to extensive variability in cardiovascular structure, geometric intricacy, low resolution, high background noise and motion artifacts. For that reason, manual segmentation remains a widely used method, but manual segmentation takes a long time to perform and is prone to observer variability [16]. There are some established semi-automatic segmentation methods [17, 18, 19] which are faster than manual segmentation, nevertheless they are still operator dependent. Recent machine learning and artificial intelligence strategies have shown great ability to solve 4D flow MRI segmentation problems [20]. Machine learning algorithms are powerful techniques that train a machine (i.e. computer) to perform a specific task. Convolutional neural networks (CNNs), which is one of the deep learning techniques, forms the foundation of image segmentation. U-Net is a CNN that was developed specifically for medical image segmentation [21]. Several recent studies that focused on advancing imaging segmentation techniques. Berhane et al. developed a CNN model to segment the aorta from 4D flow MRI images [22]. The performance in this study was compared with manual segmentations, and they reported good agreement across flow and diameter along the aorta. Segmentation speed was <1 second per case, while manual segmentation required at least 360 seconds. Bratt et al. suggested a network based on the U-net and residual modules [23]. They reported similar segmentation performance, < 0.6 seconds per case, however the manual segmentation required 238 seconds per case. Wu et al. developed a combinatorial network for segmenting the left ventricle (LV) [24]. They claimed that combining networks can increase the accuracy of the segmentation.
2.4 Flow visualization and quantification
Before flow visualization and quantification, general data quality control, including visual inspection and quantitative quality control, is recommended to ensure internal data is consistent and accurate. Dedicated visualization and quantification software can be used for obtaining streamlines, pathlines, volume rendering, and/or maximum intensity projection (MIP). Streamlines represent a blood particle’s instantaneous path tangential to the velocity vector at a particular point of time, such as at peak systole. Pathlines represent a blood particle’s path over time (i.e. trajectory). Volume rendering allows us to represent voxel-by-voxel values in a dynamic spatial manner, given access to the entire field of view. A MIP is a single-plane image representing the maximum values through a given direction of the volume, similar to an X-ray image. Taken together, these flow visualization techniques reveal a wealth of information about blood flow abnormalities and cardiovascular disease progression. One of the most significant advantages 4D flow MRI is the ability to retrospectively quantify cardiac flow parameters within specified regions of interest. Flow can be analyzed within a specific volume that has been isolated via segmentation, or via a 2D cross-sectional analysis plane placed within a volume of interest. These analysis planes can be flexibly placed at any anatomical location to quantify general and advanced blood flow parameters. Some of these visualization and quantification methods will be illustrated in the following section.
3. Applications in cardiology
3.1 Congenital heart disease
Eight out of every 1000 infants are born with congenital heart disease (CHD), which encompasses all structural heart defects present at birth, including the great vessels and cardiac valves [25]. Individuals with CHD may develop many cardiac complications, even after surgical correction of the abnormality, including valve insufficiency, arrhythmias, and heart failure [25]. Tetralogy of Fallot is one of the most common forms of cyanotic (“blue baby”) CHD, accounting for about 10% of all CHD [26]. Tetralogy of Fallot involves a combination of four defects including right ventricular hypertrophy, aortic override, pulmonary stenosis, and a ventricular septal defect. These patients undergo multiple repeat surgeries and procedures over their lifetime but the hemodynamic factors contributing to the optimal quality of life and outcomes are understudied and poorly understood. Congenital heart disease can benefit from 4D flow MRI via the calculation of advanced hemodynamic parameters, such as WSS, TKE, 3D pressure mapping, and energy loss [5]. For demonstration, we primarily focus on pressure mapping, but Table 1 provides an overview of 4D flow MRI hemodynamics in CHD.
Fluid pressure measured within the cardiovascular system is widely used in CHD diagnosis, such as coarctation of the aorta, pulmonary hypertension, or atrio-ventricular septal defects. The pressure difference across structural abnormalities (ex: stenosis or ventricular septal defect) or within the LV can reveal much about the severity of the disease. Pressure mapping, based on the measured 3D blood flow velocity field, can be calculated by solving the Navier–Stokes equation, which describes the time-varying flow of a viscous, incompressible Newtonian fluid [33, 34]. This method allows for the estimation of temporally and spatially distributed pressure gradients and across a large vessel segment or cardiac chamber, Figure 3. Overall, 3D pressure mapping allows us to gain a better understanding of the basic determinants of time-varying flow in healthy and diseased hearts, which has the potential to improve our methods for diagnosing, treating, and surgically correcting CHD [35, 36].
Figure 3.
Pressure mapping. Volume rendering maps of a control (left) and a patient with repaired tetralogy of Fallot (right). Several analysis planes, including location reference. Reference plane for pressure is in yellow. RPM indicates analysis plane. LVOT: Left ventricular outflow tract; STJ: Sinotubular junction; AAo: Ascending aorta.
3.2 Mitral regurgitation
Approximately 10% of the general population will develop mitral regurgitation (MR) throughout their lifetime [37]. Mitral regurgitation is defined as systolic retrograde flow from the LV into the left atrium (LA). The main causes are classified as primary (structural or degenerative abnormality of mitral valve apparatus) or secondary (a disease of the LV interferes with function and integrity of mitral valve apparatus) [38]. This disorder generally progresses insidiously, as the heart compensates for increasing regurgitant volume via LA enlargement that partially relieves LV overload. Long-standing regurgitation yields poor outcomes as it may lead to progressively more severe regurgitation, LV failure, pulmonary hypertension, atrial fibrillation (AF), stroke, and death [39]. If MR is severe, surgery is the recommended treatment to prevent heart failure [1]. Thus, early detection and assessment is crucial, especially in elderly patients who are often ineligible for surgical intervention.
Doppler echocardiography is the most widely used tool for the assessment of MR. The commonly considered parameters when classifying MR severity are jet area, width of vena contracta, effective regurgitant orifice area, regurgitant volume, and regurgitant fraction. However, the accuracy of standard approaches used to quantify these parameters can be influenced by the mechanism of regurgitation, direction of the jet, jet momentum, LV loading condition, LA size, and the patient’s blood pressure [40, 41]. It is also important to keep in mind that these standard-of-care diagnostic tools do not permit a comprehensive in-vivo assessment of 3D blood flow which is critical to the study of complex 3D hemodynamics surrounding MR. Cardiac MRI has recently been reported as a more accurate tool for quantification of MR flow characteristics and severity grading [42, 43]. Advanced measures of vortex formation, helical flow patterns, EL, pressure mapping, and WSS have shown usefulness for assessment of valve-related disease using 4D flow MRI [44]. The shape of vortex cores have been shown to closely resemble the valve shape, while the vortex’s orientation is related to the LV inflow direction [45]. In demonstrating how to extract vortex information from 4D flow MRI, Krauter et al. showed that vortex shape, vorticity and kinetic energy (KE) strongly correlate with transmitral peak velocities [46]. Helical grade was also associated with systolic anterior motion of the mitral valve. Lastly, as shown in Figure 4, MR disturbs organized flow, resulting in a reduced contribution of left pulmonary veins to the vortical flow, potentially leading to less efficient ventricular filling and stasis [47].
Figure 4.
Mitral regurgitation. The presented case has mitral thickening with evidence of cleft in the anterior mitral leaflet. Panel A shows a whole heart streamline visualization used to locate mitral regurgitation (orange box). Panel B shows the velocity volume rendering of the velocity field. The mitral regurgitant jet was highly eccentric into the atrial wall. Panel C illustrates the multiplanar reconstruction of the velocity field which allows multiple views of the regurgitant jet. Evaluation led to a mild regurgitation grading with a regurgitant fraction of 15%.
It is important to note, however, that flow-based biomarkers still require further exploration before they can be reliably applied to daily clinical practice. The construction of ‘atlases’ that depict physiologically normal blood flow patterns through the LA shows great promise in helping identify the clinical utility of certain hemodynamic parameters and personalizing diagnoses. Normally, MR treatment is primarily based on chamber dimensions and qualitative regurgitation severity grading [48], but it is well recognized that these measures may be insufficient to guide treatment strategies and require multi-modality integration. Four-dimensional flow MRI has provided the ability to construct time-averaged 3D hemodynamic maps (i.e. atlases) from healthy subjects, which can then be used as a reference when evaluating a patient’s MR severity. For example, Goffic et al. recently developed strategies for the generation of KE and helicity atlases [49]. Their preliminary data suggest that these atlases may provide insight into hemodynamic influence on LV dysfunction progression and, thus, could have implications on personalized assessment of MR. Such atlases can be created for any hemodynamic parameter of interest and will be further elaborated on in the aortic diseases section of this chapter.
3.3 Atrial fibrillation
Atrial fibrillation is an abnormally fast heart rhythm with uncoordinated atrial activation and ineffective atrial contraction [50, 51]. Multiple simultaneous electrical signals firing within the atria lead to irregular ECG patterns and atrial activity, loss of coordinated atrial contractions, and inadequate ventricular filling. It is classified according to the duration of episodes. At an early stage, an episode of AF terminates within 7 days of onset and sinus rhythm is restored (paroxysmal AF). However, as severity progresses, the AF episode may last beyond one week (persistent AF) or does not terminate (permanent AF). The most common complication of AF is thromboembolic events such as stroke [50, 51]. Reduced LA function increases the risk of blood stasis and clot formation in the LA, especially the left atrial appendage (LAA) which is a small extension of the LA. The CHA2DS2-VASc score (accounts for patient history of: Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, Stroke, Vascular disease, Age between 65 and 74 years, and Sex) is currently recommended for stroke risk stratification for AF patients, based on clinical factors such as age, gender, and disease history [50, 51, 52]. This risk score is used to recommend the use of anticoagulants and further therapy. However, the score does not contain other individual physiologic factors, so prediction power is limited.
There have been efforts to improve diagnosis and evaluation of disease and risk-assessment of AF through analysis based on 4D flow measurements (Table 2). Although some contradictory reports exist, most of the recent studies characterizing AF blood flow with relatively large cohorts agree that there is a significant decrease of LA flow velocity in both persistent and paroxysmal AF patients [54, 55, 56, 57, 59]. Most notably, the increase of CHA2DS2-VASc score has been associated with reduced mean LA velocity [55, 56], which suggests 4D flow measurement may be able to improve risk assessment. Kinetic energy, which is proportional to the mean square of velocity, was also found to be markedly lower in AF patients than in controls [59]. Left atrial flow stasis is defined by Markl et al. [54] as the relative number of time frames, for each voxel, with flow velocity less than 0.1 m/s. Flow stasis has been confirmed by several studies to be elevated in AF patients [6, 8, 9, 10]. An example of a MIP for flow stasis is displayed in Figure 5. Also, flow patterns through the pulmonary vein into the LA have been studied [57].
Velocity (mean and peak), stasis, vorticity, vortex volume
Peak velocity and vorticity are reproducible, stable, and exhibit similar interval-scan variability between cohorts
Table 2.
Summary of 4D flow studies in AF.
LA: left atrium; LAA: left atrial appendage; PAF: paroxysmal atrial fibrillation; AF: atrial fibrillation; AF-sinus: previous history of AF, but in sinus rhythm at time of imaging; AF-afib: in AF at time of imaging; KE: kinetic energy; CHA2DS2-VASc: stroke risk stratification system that accounts for patient history of congestive heart failure, hypertension, age > 75 years, diabetes mellitus, stroke, vascular disease, age between 64 and 75 years, and sex.
Figure 5.
Left atrial stasis maps. Maximum intensity projections of stasis using a sagittal-view (top) and a top-view (bottom).
In AF patients, fragmentation of LA inflow and vortex formation in the LA was characterized, see Figure 6. This study demonstrated that vortex size increased in paroxysmal AF and was associated with a greater risk score. Similar findings of decreased velocity and increased stasis have also been found in the LAA specifically [56, 59]. However, the limited spatial resolution of 4D flow MRI may not satisfy the minimum number of voxels needed to segment the LAA accurately and reliably in a certain number of cases [6]. In a recent study, reliability and reproducibility of 4D flow parameters in AF patients were reported [60]. Left atrial peak velocity and vorticity were found to be more reproducible and independent of physiological factors than mean velocity, vortex volume and stasis.
Figure 6.
Atrial vortex dynamics in atrial fibrillation.
3.4 Bicuspid aortic valve disease and Aortopathy
Bicuspid aortic valve (BAV) disease is the most common congenital valve disease, affecting 0.5–1.4% of the general population [61, 62, 63]. While an aortic valve normally contains three functional leaflets (i.e. tricuspid), a BAV contains only two. There are different sub-types of BAV: valves that developed with only two leaflets (Type 0) and valves that developed with three leaflets containing a fusion between any adjacent pair (Type 1) [64]. Type 1 phenotypes are further subdivided depending on what leaflet pair is fused. Despite being a valvular malformation, BAV disease is closely associated with aortic dilation (BAV aortopathy) that increases patients’ risk of aortic aneurysms and dissections [65]. Traditionally, aortic diameters and growth rates have been used to stratify BAV patients at risk for aortic dissection, but these measures alone have been shown to possess limited prognostic value [66]. As well, uncertainties still exist regarding the exact pathophysiology of BAV aortopathy and the most effective timing of surgical intervention [67]. Thus, it is important to study new biomarkers that may enhance our understanding of BAV disease progression. Four-dimensional flow MRI has allowed the study of several new and promising biomarkers, such as abnormal flow patterns, WSS, and energy loss.
Eccentric flow jets and helicity are two characteristics of abnormal flow patterns that have shown strong connections with aortic dilation in BAV patients. A tricuspid aortic valve typically produces a centered systolic jet and bulk flow that is parallel to the ascending aorta, while BAVs tend to produce off-centered systolic jets (eccentric flow jets) that lead to circumferential flow and vortices (helicity). Each BAV phenotype has been shown to produce its own general pattern of jet eccentricity and helicity, and the direction and orientation of these abnormal flow patterns has been associated with patterns of aortic dilation [68, 69, 70, 71]. For example, patients with right–left coronary leaflet fusion (Type 1 RL) are more likely to produce a flow jet aimed to the right-anterior wall that associates with dilation focused at the mid-ascending aorta, while right-non coronary leaflet fusion patients (Type 1 RN) tend to produce right-posterior flow jets that associate with diffuse dilation extending to the aortic root and/or arch as well, Figure 7 [69, 70, 72]. Furthermore, Bissel et al. showed that BAV patients with normal flow jets and non-helical flow patterns tended to have similar aortic diameters to healthy volunteers [73]. While more longitudinal studies are needed to confirm causation, these studies seem to collectively suggest that abnormal flow patterns are connected to aortic dilation in BAV patients.
Figure 7.
Flow patterns and wall shear stress in a control and bicuspid valve phenotype. The white dashed lines represent the location where the sample velocity profile was obtained. These flow profiles can estimate the shear stress rate, blood flow spatial deformation. Since no flow occurs through the vessel wall, the speed of the blood flow at the vessel boundary is zero. The near wall region is the boundary layer where the wall shear stress (WSS) forces occur. The WSS expresses the force per unit area exerted in the fluid direction on the local vessel tangent (τw). Yellow dashed lines illustrate the flow profile slope near the wall. On the top, a healthy control illustrates normal flow in the proximal ascending aorta. On the bottom, samples of right–left (RL) fusion and right-non coronary (RN) fusion illustrate abnormal flow.
Wall shear stress, a measure of force exerted on the vessel wall by flowing blood, has consistently shown to be elevated in the ascending aorta of BAV patients [69, 74, 75]. The abnormal flow patterns created by a BAV are likely responsible for these increased WSS forces, and WSS itself has also been associated with regions of aortic dilation (Figure 7) [68, 69, 71, 73]. Seminal studies conducted by Bollache et al. and Guzzardi et al. demonstrated a possible physiologic mechanism behind WSS-associated aortic dilation, showing that elevated WSS levels may trigger maladaptive metalloproteinase activity which leads to medial elastin fiber degeneration and overall weaker connective tissue in the aortic wall [76]. Thus, it is thought that elevated WSS, driven by abnormal flow patterns, may be a direct mediator of aortopathy in BAV patients. This ability of 4D flow MRI to visualize flow patterns and quantify WSS may provide future clinical utility in the risk-stratification of BAV patients and identifying appropriate timing for aortic surgery.
3.5 Aortic stenosis
Aortic stenosis (AS) refers to the narrowing of the aortic valve opening, which restricts blood flow from the LV to the aorta. It is the most prevalent valvular disease in developed countries, affecting 2.4% of those >75 years of age [77]. It is commonly a result of BAV disease, chronic calcification, or rheumatic fever (in developing countries). Aortic stenosis often leads to complications such as LV dysfunction, heart failure, and aortic dilation, aneurysm and dissection [78]. Surgical repair or valve replacement are the only known definitive treatments and accurate diagnosis and staging are critical for surgical decision-making [79]. The most widely used parameters in assessing valve function include transvalvular pressure gradient, peak velocity, and valve area. However, up to 40% of AS patients present with discordant findings (ex: abnormally small valve area, but normal pressure gradient) that require additional imaging, and the heterogenous nature of onset of secondary complications (ex: different dilation patterns, different rates of progression, etc.) is not well understood [80]. Four-dimensional flow MRI research continues to enhance our understanding these issues through the novel measurement of 3D peak velocity, 3D pressure gradients, and fluid energy losses.
Peak velocity and pressure gradients across the aortic valve are key components in AS severity grading [79]. However, as previously mentioned, echocardiography and 2D PC-MRI measurements often underestimate peak velocity, due to inaccurate 2D analysis plane placement, and overestimate pressure gradients, due to exclusion of downstream pressure recovery in calculations. The 3D visualization of these parameters using 4D flow MRI allows for more accurate identification of true peak velocity and a comprehensive calculation of pressure gradients that accounts for pressure recovery in the thoracic aorta. Due to this, 4D flow MRI may be a more accurate imaging modality for AS severity grading and surgical decision-making. Although, it should be noted that 3D pressure gradient calculations assume laminar flow, which may lead to inaccuracies when measuring severely stenotic flow where turbulence exists [33].
Fluid energy loss is an advanced hemodynamic parameter that provides information regarding LV workload. There are two types of mutually exclusive fluid energy loss measurements: viscous energy loss (EL; energy lost due to friction between adjacent fluid layers with different velocities) and TKE (energy lost to turbulence) [81]. Both measurements reflect LV output lost to abnormal flow patterns and, ultimately, a greater cardiac afterload. Larger fluid energy losses place greater workloads on the LV, which can lead to LV dysfunction and heart failure. Several studies have shown the presence of significantly elevated fluid energy losses in AS patients and explored the role of TKE in improved characterization of AS severity [82, 83]. Specifically, Binter et al. found TKE to be greater in AS patients compared to controls and demonstrated TKE to be influenced by aortic and valvular morphology [83]. Taken together, this body of research suggests that fluid energy loss may provide novel AS severity measurements that are complimentary to traditional evaluation techniques. Lastly, it should be noted that jet eccentricity, helicity, and WSS measurements may serve the same purpose in the study of AS as they do in the study of BAV disease. These parameters have shown close associations with aortic dilation, a common complication in AS patients [68, 69, 73, 84, 85]. Most studies exploring these associations use BAV patient cohorts, since AS is a common finding in BAV disease.
3.6 Aortic Coarctation
Aortic coarctation (CoA) refers to a congenital narrowing of the thoracic aortic lumen, most often in the arch or descending portion, and accounts for approximately 6–8% of all congenital heart defects [86]. It often accompanies other congenital malformations, such as BAV (60%), aortic arch hypoplasia (18%), ventricular septal defect (13%), and sub AS (6%) [87]. Similar to AS, CoA causes an upstream increase in pressure, which may lead to LV dysfunction, aortic aneurysm and dissection, upper body hypertension, and stroke. Current diagnostics include computed tomographic angiography to image aortic structure and echocardiography to measure peak velocities and pressure gradients across the stenotic region. Due to the limitations of echocardiography, 4D flow MRI may provide added utility in characterizing CoA via 3D measurement of peak velocity profiles and pressure gradients.
The application of 4D flow MRI in generating 3D peak velocity profiles and pressure gradients serves the same benefits as previously mentioned in other cardiovascular disease. That is, it allows the visualization of temporally and spatially resolved flow patterns so that analysis planes may be placed in the most applicable locations and pressure recovery can be accounted for when measuring pressure drop across the CoA (Figure 8). Several studies to-date have found benefit in the use of 4D flow MRI for characterizing CoA flow patterns and evaluating post-repair hemodynamics in CoA patients [88, 89, 90].
Figure 8.
Evaluation of a coarctation of the aorta. Flow is visualized at peak systole (A) and early diastole (B). (C) Peak flow velocity (PV) across coarctation. This patient (male, 53 years old) has a type 1 LR BAV with severe aortic insufficiency (regurgitant fraction 56%), mild stenosis, coarctation measuring 21 mm, and moderate dilatation of the proximal ascending aorta (46 mm). LR: Left – Right coronary leaflet fusion; BAV: Bicuspid aortic valve.
4. Conclusion
In conclusion, 4D flow MRI is a powerful technique which can be used for calculating important clinical parameters. This chapter intended to introduce and summarize the usefulness of 4D flow for assessing cardiovascular diseases. Thanks to recent technical advances, 4D flow MRI has increased its use in cardiac MRI sites worldwide and it is in a ready-to-go state-of-art stage for clinical practicality.
Acknowledgments
Authors were supported by The University of Calgary, URGC SEM #1054341 and JG start-up funding. Research unrestricted funding was also provided by The Libin Cardiovascular Institute and Siemens Healthineers. HK, SIA, and SA received scholarship support from the Biomedical Engineering graduate program. We acknowledge the support of the Natural Science and Engineering Research Council of Canada/Conseil de recherche en science naturelles et en génie du Canada, RGPIN-2020-04549 and DGECR-2020-00204.
Conflict of interest
Authors have no conflict of interest to declare in the context of this chapter.
\n',keywords:"Cardiac flow, 4D flow MRI, hemodynamic biomarkers, and flow quantification",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/77965.pdf",chapterXML:"https://mts.intechopen.com/source/xml/77965.xml",downloadPdfUrl:"/chapter/pdf-download/77965",previewPdfUrl:"/chapter/pdf-preview/77965",totalDownloads:130,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:1,impactScore:0,impactScorePercentile:45,impactScoreQuartile:2,hasAltmetrics:1,dateSubmitted:"June 19th 2021",dateReviewed:"July 9th 2021",datePrePublished:"August 9th 2021",datePublished:"March 16th 2022",dateFinished:"August 9th 2021",readingETA:"0",abstract:"Blood flow through the heart and great vessels moves in three dimensions (3D) throughout time. However, the assessment of its 3D nature has been limited in the human body. Recent advances in magnetic resonance imaging (MRI) allow for the comprehensive visualization and quantification of in-vivo flow dynamics using four-dimensional (4D) flow MRI. In addition, this technique provides the opportunity to obtain advanced hemodynamic biomarkers such as vorticity, helicity, wall shear stress (WSS), pressure gradients, viscous energy loss (EL), and turbulent kinetic energy (TKE). This chapter will introduce 4D flow MRI which is currently used for blood flow visualization and advanced quantification of cardiac hemodynamic biomarkers. We will discuss its advantages relative to other in-vivo flow imaging techniques and describe its potential clinical applications in cardiology.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/77965",risUrl:"/chapter/ris/77965",book:{id:"10876",slug:"blood-updates-on-hemodynamics-and-on-thalassemia"},signatures:"Patrick Geeraert, Hansuk Kim, Safia Ihsan Ali, Ashifa Hudani, Shirin Aliabadi, Monisha Ghosh Srabanti, Hourieh Jamalidinan and Julio Garcia",authors:[{id:"414586",title:"Assistant Prof.",name:"Julio",middleName:null,surname:"Garcia",fullName:"Julio Garcia",slug:"julio-garcia",email:"julio.garciaflores@ucalgary.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"423610",title:"BSc.",name:"Patrick",middleName:null,surname:"Geeraert",fullName:"Patrick Geeraert",slug:"patrick-geeraert",email:"pgeeraert.pg@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}},{id:"423611",title:"MSc.",name:"Hansuk",middleName:null,surname:"Kim",fullName:"Hansuk Kim",slug:"hansuk-kim",email:"hansuk.kim@ucalgary.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}},{id:"423612",title:"BSc.",name:"Safia",middleName:null,surname:"Ihsan Ali",fullName:"Safia Ihsan Ali",slug:"safia-ihsan-ali",email:"safia.ihsanali@ucalgary.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}},{id:"423613",title:"BSc.",name:"Shirin",middleName:null,surname:"Aliabadi",fullName:"Shirin Aliabadi",slug:"shirin-aliabadi",email:"shirin.aliabadi@ucalgary.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}},{id:"423614",title:"BSc.",name:"Ashifa",middleName:null,surname:"Hudani",fullName:"Ashifa Hudani",slug:"ashifa-hudani",email:"ashifa.hudani@ucalgary.ca",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}},{id:"423615",title:"Dr.",name:"Monisha",middleName:"Ghosh",surname:"Ghosh Srabanti",fullName:"Monisha Ghosh Srabanti",slug:"monisha-ghosh-srabanti",email:"gsmonisha@graduate.utm.my",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}},{id:"423616",title:"MSc.",name:"Hourieh",middleName:null,surname:"Jamalidinan",fullName:"Hourieh Jamalidinan",slug:"hourieh-jamalidinan",email:"hj.dinan2006@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"University of Calgary",institutionURL:null,country:{name:"Canada"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Data acquisition and pre-processing",level:"1"},{id:"sec_2_2",title:"2.1 Safety and preparation",level:"2"},{id:"sec_3_2",title:"2.2 Data acquisition",level:"2"},{id:"sec_4_2",title:"2.3 Pre-processing and correction",level:"2"},{id:"sec_5_2",title:"2.4 Flow visualization and quantification",level:"2"},{id:"sec_7",title:"3. Applications in cardiology",level:"1"},{id:"sec_7_2",title:"3.1 Congenital heart disease",level:"2"},{id:"sec_8_2",title:"3.2 Mitral regurgitation",level:"2"},{id:"sec_9_2",title:"3.3 Atrial fibrillation",level:"2"},{id:"sec_10_2",title:"3.4 Bicuspid aortic valve disease and Aortopathy",level:"2"},{id:"sec_11_2",title:"3.5 Aortic stenosis",level:"2"},{id:"sec_12_2",title:"3.6 Aortic Coarctation",level:"2"},{id:"sec_14",title:"4. 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Contemporary natural history of bicuspid aortic valve disease: a systematic review. Heart. 2017;103(17):1323-1330'},{id:"B66",body:'Linda AP, Thomas TT, Eric MI, others. Aortic diameter≥ 5.5 cm is not a good predictor of type a aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD). Circulation. 2007;116(10):1120-1127'},{id:"B67",body:'Borger MA, Fedak PWM, Stephens EH, Gleason TG, Girdauskas E, Ikonomidis JS, et al. The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve–related aortopathy: Full online-only version. J Thorac Cardiovasc Surg. 2018;156(2):e41–e74'},{id:"B68",body:'Rodríguez-Palomares JF, Dux-Santoy L, Guala A, Kale R, Maldonado G, Teixidó-Turà G, et al. Aortic flow patterns and wall shear stress maps by 4D-flow cardiovascular magnetic resonance in the assessment of aortic dilatation in bicuspid aortic valve disease. 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1. Introduction
Pesticides are the integral and significant part of modern agriculture. Pesticide usage is incredibly valuable for increasing food production in fulfilling the demand of over-rising population. It has been previously stated by Webster et al. [1] that without pesticide use considerable economic losses will occur. The application rate of agricultural pesticides has swiftly augmented in different developing and developed countries [2]. Therefore, pesticides help in significant increase of yield and prevent the crop losses due to pest and pathogen attack. Application in a smaller quantity gives positive results but large quantity causes negative effect on environment, human health, and other beneficial organisms such as insects responsible for pollination [3]. However, non-judicious use causes various detrimental effects on environment and damages the ecosystem including economic loss of the farmers.
In formulated forms, pesticides are effective in very small quantity. There are many conventional pesticide formulations available in the market, which are being marketed and used in Asian countries in the form of dustable powder (DP), wettable powder (WP), emulsifiable concentrate (EC), soluble liquids (SL), etc. These conventional formulations are effective but due to certain limitations such as toxicity, cost, pest resistance, environmental contamination, death of beneficial organisms (e.g., honey bee), and human health problems they attracted interests toward advanced and safer pesticide formulation techniques [4]. Interestingly, in past 1990s, Asian countries explored certain new-generation formulation, which were solvent free, long lasting, safe and caused no effect on non-target organisms [5, 6].
With the advancement of new formulation technologies in Asian countries, many new-generation formulations have been developed to maintain a special place in international markets. In Asian countries, government supports the pesticide supply for the enhanced food production but its overuse (conventional formulations) has resulted in pesticide residue problem causing non-target and ecosystem toxicity.
In order to improve the safety of the user and ecosystem from the hazardous pesticides, Institute of Pesticide Formulation Technology (IPFT), India, has been engaged in developing new-generation formulations of synthetic as well as botanical pesticides. This chapter summarizes all the formulation advancement developed by IPFT for the safe and smart delivery of pesticide and reduces the adverse effects associated with conventional formulations.
2. Basic concept of formulation
A pesticide is the main active ingredient (actual chemical that controls pest population), which may be of synthetic chemical or botanical origin. Various chemical- and botanical-based pesticides have different physical and chemical characteristics such as solubility, viscosity, and physical state. Moreover, different pesticides act differently for various types of pest populations; for instance, some are effective for crawling insects, while the others are for flying insects. If a farmer uses active ingredient in pure form, he will face assured difficulties as follows:-
Active pesticide in unformulated form cannot spread evenly.
In pure form, pesticides show phytotoxicity and toxicity toward non-targets. Pesticide in unformulated form environment-related hazards will enhance.
After formulation development, application process is easy and convenient.
To resolve all these issues, formulation scientists formulate the active ingredient into different forms. As per the Knowles, “A pesticide formulation is a mixture of active ingredient with different inert materials to improve its stability during storage, easy handling, improves safety, application, or effectiveness towards pest population” [5].
3. Conventional formulations and their limitations
In Asia and Pacific regions, the most common formulations being used are dustable powders, emulsifiable concentrates, wettable powders, granules, soluble liquids, etc., for the control of insect pest and many pathogenic diseases [7, 8]. The most common conventional formulations are discussed below:
Dust formulations:-These formulations are for contact action pesticides. These formulations are ready to use and no need for dilutions before application. They contain very low active ingredients (usually 1–10%). The inert ingredient mainly contains talc, ash, silica, bentonite, etc. (Figure 1). These are always applied as dry and can drift easily to non-targets. These formulations are mainly used for cracks and crevices.
Granules (GR): Granular pesticide formulation mesh size is higher as compared with dust. As per the British standard, mesh size is (250–1050 microns). For sufficient activity, at least 90% granules should be in the range of British standards. Due to larger size, drift velocity decreased and less wastage occurs over due to dust formulations [9]. In granular formulation, pesticide is encrusted onto or wrapped up in absorptive particles of silica, sand, clay, and shells of walnut or corn cobs pieces, etc., as carrier materials. Granular formulations are most suitable for pre-emergence herbicides and soil insecticides (Figure 2).
Wettable powder (WP):-A WP contains active ingredient (pesticide) in a finely ground form along with wetting agents or dispersing agents (Figure 3). Wettable powders are applied by sprayers after diluting in water in the form of dilute suspensions. Wettable powders are safe to use, storing, and transporting.
Soluble powders (SP): In SP formulation, active ingredient or pesticide is mixed with the inert ingredients, which enhances the solubility of pesticide after dissolution in water (Figure 4). These SP formulations are easy to produce, economical, and stable under various temperature conditions.
Emulsifiable concentrates: Emulsifiable concentrate formulations are most common and popular formulation in Asian countries. These formulations are suitable for the low melting point active ingredients, which are highly soluble in organic solvents. These formulations are developed by dissolving active ingredients in organic solvents along with emulsifying surfactants (Figure 5).
Figure 1.
Schematic illustration showing key steps involved in dust formulation and its mode of application.
Figure 2.
Schematic representation showing key steps involved in granular formulation and its application.
Figure 3.
Diagrammatical representation showing steps involved in WP formulation and its application.
Figure 4.
Schematic representation showing key steps involved in soluble powder formulation and its application.
Figure 5.
Schematic representation showing key steps involved in EC formulation and its application.
The main limitation is linked with the organic solvents that are mainly petroleum solvents being used in Asian countries. These petroleum solvents make the formulation flammable and cause dermal toxicity to the user. To rectify the problem associated with these conventional formulations, new formulations have been developed, which are improved and advance in terms of user and environment safety.
The major objectives of IPFT (India) to develop new formulation technologies are as follows:
To make the formulation techniques of different pesticide easy and convenient application.
To make pesticide formulations labor saving.
To prepare safer formulations for user and environment.
To reduce the toxicity of pesticides toward non-targets.
To minimize environmental contamination.
To enhance bio-efficacy against different types of pests.
To make the formulation economical and lower the frequency of applications.
4. Recent advancements in agrochemical formulations
Water-dispersible granules (WDG):-A WDG formulation is also termed as dry flowables (DF). These WDG formulations are non-dusty and disperse easily in water when added in spray tanks for its finer particle size in suspension. These are the safer and targeted delivery system for the various pesticides. Main uniqueness of these formulations is convenient application due to free-flowing nature and quick disintegration in water medium and applied as dilute suspensions. Size of the diluted suspended particles is very less, that is, 30–40 μm, therefore no nozzle clogging.
More advanced form of WDG is water-soluble bag-sealed WDG. In these packing bags, WDG are in partially disintegrated form, which can easily disintegrate in spray tanks (Figure 6).
Figure 6.
Schematic representation showing key steps involved WDG formulation and its application.
Basic composition of WDG contains 50 to 90% pesticide (active ingredient) along with dispersing agents and wetting agents [10]. A dispersing agent is a type of surfactant that is added to formulations to improve the separation of the particles and inhibit particle size growth, and their settling or clumping. Pang et al. [11] reported lignosulfates as effective dispersing agent in water-dispersible granular formulations due to a high degree of sulfonation, high intrinsic viscosity property, and high molecular weights. Recently, sodium salt of methacrylic acid/styrene/sodium p-styrene sulfonate copolymer (SMSS) has synthesized a novel dispersant by free radical polymerization mechanism. This new dispersant has strong resistance to hard water and showed high performance and show above 90% suspensibility in hard water [12].
IPFT has developed water-dispersible granules of liquid pesticide such as triazophos. Recently, IPFT developed neem WDG for mosquito control. Other WG formulations that have been developed by IPFT for agricultural usage are Captan 83WG, Isoproturon 75WG, Metamitron 70 WG, Mancozeb 75WG, Chlorothalonil 75WG, Endosulfan 75WG, Carbendazim 86WG, Divrinol 50WG, Thiram 80WG, Cypermethrin 40 WG, Thiamethoxam 25 WG, Deltamethrin 25 WG, and Triazophos 20 WG.
Suspension concentrate: Suspension concentrates are the stabilized dispersion of pesticides in water medium. This is the most popular formulation due to its safe and convenient use. The suspended particle size is very fine and provides good adhesion and penetration on target surface, which results in improved bio-efficacy. It has recently identified that SC formulations show less leaching of pesticides than conventional emulsifiable concentrate formulations. Similarly, another study has identified that in SC formulations, volatilization of active ingredient in environment reduced to 33.5% compared with conventional pesticide formulations [13]. Suspension concentrates have overcome the limitations associated with conventional organic solvent-based formulations (Figure 7).
Figure 7.
Schematic key steps involved suspension concentrate formulation and its application.
The main advantages of suspension concentrates are easy application, no organic solvent used, and free from any toxicity to users and environment.
Careful selection of surfactant system is necessary to prevent hetero-flocculation (agglomeration of solid particles and droplets) during storage. There are three types of instabilities identified in SC during storage due to particle size change and they are particle aggregation, Ostwald ripening, and particle sedimentation [14].
5. Recent advances in suspension concentrate formulations
Effect of polymeric surfactant on physical stability has investigated in suspension concentrate. Polymeric surfactants provide high critical micellar concentration (CMC) and reduced Gibbs-free energy ΔG [15]. In another study, silicone surfactant is used as adjuvants in the SC formulation that results in high performance of surfactant and improves the physical stability and the quality of the formulation [16].
Particle size is also an important factor for stability as well as bio-efficacy enhancement. In a study, Vineela et al. [17] have reported that in Bacillus thuringenesis SC formulations, further reduction of particle size enhanced the bio-efficacy of formulation against Spodoptera litura (Lepidoptera: Noctuidae).
Some pesticides are photosensitive and easily decomposed. In a study, an amine-modified ligno-sulfonate surfactant was synthesized to make the SC formulation anti-photolysis [18]. Similar advancements have been conducted in IPFT on botanical-based formulations to inhibit photolysis. In addition to this, IPFT has developed several other UV protectant-based SC formulations for various SC formulations.
Entomopathogenic fungus, Beauveria bassiana, has been formulated as SC against Helicoverpa armigera larvae with LC50 value of 61.22 mg l−1 after 3 days of application [19]. Several other entomo-pathogenic fungi have been formulated as SC formulation by IPFT against various insect pests of different economically important crops such as spices and oil crops of Asian region.
Along with this IPFT has developed many synthetic and botanical pesticide SC formulations for agricultural pest control which include Isoproturon 50SC, Carbendazim 50SC, Sulfur 52SC, fipronil 5SC, thiomethxam 14.1% + Lamda cyhalothrin 10.6% SC, metamitron 70 SC, Neem SC, etc.
5.1 Capsule suspension (CS)
Capsule suspension (CS) is water-based slow release formulation containing active ingredient encapsulated inside microcapsules up to 10 microns size (Figure 8). CS formulation is a stable suspension of micro-capsules containing active ingredients and these microcapsules are synthesized by interfacial polymerization mechanism. CS formulations provide regulated, slow, and delayed the release of pesticides. This formulation is safer delivery mode by giving protection from toxic ingredients and stops the pesticide rate of degradation.
Figure 8.
Schematic representation of capsulated suspension formulation procedure a. and its application b.
5.2 Advanced features of CS
CS are water-based (free from any organic solvent) homogeneous and uniform suspension formulation. Its application is safe, and provides enhanced and efficient bio-safety with reduced phytotoxicity. In order to develop CS formulation, the active ingredients should have low solubility in water and altogether hydrolytically stable. The pesticide from microcapsules gets slowly released after application. The CS formulations are slow release formulations and theses formulations prolong the availability of pesticide at target site. The CS formulation reduces environmental contamination and leaching of pesticide and degradation of active ingredient by environmental factors like sunlight.
In a recent study, it was found that carboxy, methyl cellulose (CMC) and diallyl, dimethyl, ammonium chloride (DMDAAC) as monomers are the effective encapsulating agents of avermectin pesticide. This capsulated form gave higher performance and has excellent UV protecting property [20]. Thus, IPFT has developed CS for seed dressing for targeted delivery of pesticides without any wastage in environment [21].
Cyhalothrin is the most effective and broad-spectrum pesticide used in Central Asia. It has dual mode of action contact as well as systemic. Most efficient CS formulations developed by IPFT for sustainable agricultural applications are Lambda Cyhalothrion 10CS and Lambda Cyhalothrin 4.9CS.
5.3 Microemulsion
Microemulsion (ME) is the most efficient delivery system of botanicals as well as synthetic pesticides. By definition- “ME is a system of water, oil, and an amphiphile which is a single optically isotropic and thermodynamically stable liquid solution” [22]. Droplet size of ME is in nano-range, that is, 10 nm–20 nm. Based on dispersion medium, ME can be classified into two categories: O/W ME and W/O ME. Aqueous dilution of ME is required before spray application (Figure 8). Being a new-generation formulations, the characteristic features of MEs are nano sized, thermodynamically stable system with good penetrability, quick spreading ability, low and zero interfacial tension, and extended shelf life formulation.
6. Preparation methods of ME formulation
6.1 Phase inversion method
In phase dispersion method, dispersed phase is surfactant system along with active ingredient and water is the dispersant. The whole phase of inversion occurs in controlled temperature and other conditions for active kinetics (Figure 9).
Figure 9.
Diagrammatic representation of the phase inversion method of microemulsion.
Characteristic features of ME: ME formulation can effectively mask smell of the unpleasant active ingredients and protect pesticides from hydrolysis and oxidation. It enhances the solubility of water insoluble pesticides, regulates and slowdowns pesticide release, and increases bio-efficacy.
6.2 Use of ME in agriculture
Cyhalothrin ME was developed and found as the most promising pesticide formulation in China [23]. Carbendazim is another pesticide that was formulated as ME and its bio-efficacy was evaluated in Rhizoctonia solani [24]. Chlorpyriphos pesticide ME was successfully developed and found the most potent, safe, and environment-friendly pesticide formulations in comparison with conventional pesticide formulation in recent years [25].
Along with the synthetic pesticides, botanical-based microemulsions are well known in Asian agriculture. Essential oil in microemulsion form gives superior bioactivity as compared with emulsion forms [26]. In microemulsion system, spreading capacity and dispersion improves over applied plant surface. Therefore, microemulsion system is the important vehicle for essential oil targeted delivery in a small quality without any losses [27, 28]. In addition, essential oil bio-constituents uniformly disperse after application over active targeted sites and offers improved bio-efficacy [29].
Clove (CO) and lemongrass oil (LGO) ME have investigated as efficient antifungal agents against Fusarium oxysporum f.sp. lycopersici without any phytotoxicity to main crop [30]. Previous studies in Asian region revealed that synthetic pesticide- and botanical-originated microemulsion could be an advanced, green, safe formulation against different crop pests. Therefore, microemulsion is the one of new-generation formulations for safest delivery system.
IPFT has developed different types of microemulsions of synthetic pesticides along with botanical pesticides. In addition to this, IPFT has prepared microemulsion system with inbuilt adjuvants and synergist, which will enhance the formulation efficiency and efficacy. There are different botanical-based microemulsions have been developed and formulation techniques transferred to various agrochemical industries.
6.3 Nanoemulsion formulation
Nanoemulsions are defined as nano-sized droplets dispersion in immiscible liquids (Figure 10). Different pesticides have been formulated as nano-formulation and researchers have quantitatively estimated the pesticide content by various characterization techniques [31]. This formulation exhibits the property of encapsulation and regulated release of pesticides for extended period of time as in controlled release formulations.
Figure 10.
Diagrammatic representation of nano-formulation preparation and its application.
Characteristic features of nanoemulsion formulation techniques are small droplet size with low amount of surfactant and active ingredient. Similar to ME, NE can enhance solubility of active ingredient, increase bioactivity, and improve spreadability (during application). Moreover, it can reduce volatility and hydrolysis of active ingredient.
It has been evaluated that nanoemulsion formulation showed enhanced bio-efficacy results compared with emulsifiable concentrates (EC) and microemulsions (ME). This study was conducted in third-instar larva of Plutella xylostella [32]. Indian Agriculture Research Institute (IARI), India, has developed nano-sulfur formulation against Erysiphe cichoracearum (powdery mildew of okra) [33]. In addition to this, IARI has also developed nano-hexaconazole as effective fungicide [34]. Characteristic feature of this developed formulation is biosafety aspect, and after application of nano-hexaconazole, no impact was observed on soil nitrifiers such as blue green algae and cynobacteria species. Therefore, nano-formulations maintain the sustainable soil fertility and productivity compared with conventional formulations [35].
Many botanical-based nanoemulsions have been developed in recent years. In a study, M. longifolia oil nanoemulsion developed with droplet size 14 nm–36 nm. The results of study showed that in nanoemulsion formulation, its contact toxicity and durability increase. In a similar study, sea fennel (Crithmum maritimum) essential oil is formulated as nanoemulsion along with SiO2 nanoparticles and evaluated against Spodoptera litura. In other study, Eucalyptus oil NE prepared by emulsification method and insecticidal and repellent effect was evaluated against Sitophilus oryzae, Rhizopertha dominica, and Tribolium castaneum [36]. Nanoemulsion of Piper aduncum fruit extract has also been developed against cabbage pest Crocidolomi apavonana. Therefore, it has been concluded that botanical nanoemulsion formulation represents a new alternate for integrated pest management for organic farming promotion in Asian countries [37].
In addition to this, nanoemulsion formulation also been used as edible coating to improve the storability of fruits and vegetables in postharvest conditions for enhancing shelf life and prevention of microbial growth over fruits and vegetables [38].
IPFT has also contributed in developing many nanoemulsions of synthetic as well as bioactive pesticides and different essential oils for controlling various agriculture pests and micro-organisms. Besides this, IPFT has prepared nanoemulsion with botanical synergists and adjuvants to enhance the bioactivity and stability of nanoemulsion formulations. Moreover, combination of nanoemulsions is further developed for the amplified pest control applications in intense pest attacking conditions.
7. Emulsion in water formulation or oil in water emulsion (EW)
Emulsion in water (EW) formulation is suitable for liquid or a liquid or oily active ingredient. These formulations are dispersion of active ingredient in aqueous continuous phase (Figure 11). The size of the dispersed droplets ranges generally from 0.5 to 4–5 μm. EW formulations are obtained by high-shear emulsification process. Principally, EW formulations contain pesticides dispersed in the form fine liquid droplets in water and form oil-in-water (O/W) emulsions [39].
Figure 11.
Diagrammatical representation showing key steps of emulsion in water formulation and its application.
7.1 EW in agriculture
Lambda-cyhalothrin is broad-spectrum synthetic pesticide widely being used to control diamondback moth, cabbage caterpillar, cotton bollworm, and other pests that damage main food crops such as vegetables, soybeans, peanuts, and cotton [40]. This pesticide is commonly used in Asian countries due to its moderate toxicity, high insecticidal activity, and a long-lasting effect. However, lambda cyhalothrin previously available as EC and ME formulations pollutes the environment, costly due to loads of surfactants and consume non-renewable resources in the form of petroleum solvents [41]. Therefore, there is an urgent requirement to replace these shortcomings to further take the benefit of this broad-spectrum pesticide.
EW formulations such as limonene, peppermint oil, and spearmint oil have been developed and bio-efficacy evaluation was done on Pseudococcus longispinus. In a similar study, neem EW formulation was developed with palm oil methyl ester, RBD palm olein, and soybean oil for better adhesion and persistency. This formation was evaluated against golden apple snail. EW prepared with palm oil methyl ester showed better efficacies with LC50, 45.30 mg/l under field condition and have longer persistence t1/2 = 1.85; r2 = 97.75 on paddy leaves [42]. The formulation was found to be very effective against the pest with 90% mortality [43]. In another study, bio-larvicide Lagenidium giganteum have been formulated as EW formulation. It was investigated that in EW formulation of L. giganteum mycelium shelf life and delivery improved for good and prolonged bio-efficacy. In a similar study, entomopathogenic fungi have been formulated as emulsion in water formulation and found to be very effective against various agricultural pests. The study concluded that EW formulation showed good bio-efficacy and stability of entomopathogenic fungi over unformulated form. Hence, emulsion in water is the safe and economical formulation against agricultural pest.
In addition to agricultural field pest control, EW formulation can also be used in preparation of postharvest packaging films with anti-insect property. Recently, cinnamon oil (CO) anti-insect packaging film has been developed for repelling Plodia interpunctella (Hübner) larvae [44].
IPFT has contributed to Lambda Cyhalothrin EW, Chlorpyriphos 10 EW, etc. Recently, IPFT has optimized the neem EW formulation procedure by high shear mixing. The increase in shearing intensity reduced the droplet size and resulted in higher stability.
7.2 Mixed formulations (Suspoemulsion, ZC, ZW)
The combination formulations have broad-spectrum insecticidal activities and can be applied for insect control in different Asian countries. These mixed formulations have the user and environment-friendly applications over conventional formulations.
ZW (Capsulated Suspension (CS) + Emulsion in water (EW)
This formulation is the combination of two formulations with two different pesticides in water medium. In this, one pesticide is encapsulated inside the polymeric coating and other is in emulsified droplet form (Figure 12).
Figure 12.
Diagrammatical representation of ZC formulation and its application.
IPFT has developed ZW combination formulation of capsulated suspension (CS) of Lambda cyhalothrin with concentrated emulsion in water (EW) of chlorpyriphos, and this combination was termed as ZW [7, 8]. Main advancement of this formulation is that it is the combination of two pesticides in two different formulations, one broad-spectrum pesticide, that is, in EW formulation for quick action and lambda cyhalothrin CS for controlled release and will be effective for extended period of time and give long-term pest control [45]. This combination formulation can be used for different pesticides with good compatibility index.
The ZC formulation is the stable aqueous suspension of polymeric-encapsulated microcapsules and solid-suspended fine particles of two different pesticides. Both formulations are homogeneously mixed by wet milling and gentle shear mixing (Figure 13).
Figure 13.
Diagrammatical representation of ZC formulation and its application.
Chlorantraniliprole and thiamethoxam SC, lambda cyhalothrin and chlorantraniliprole ZC, thiamethoxam and lambda cyhalothrin ZC, beta-cyfluthrin and imidacloprid SC, and flubendiamide and thiacloprid SC efficacy have been evaluated against spotted pod borer. The study was found that ZC formulations gave superior results on the management of M. vitrata and Spodoptera litura over simple SC formulations [46].
In addition to enhanced bio-efficacy, this combination formulation has been investigated for non-targeted effects. ZC (thiamethoxam and lambda cyhalothrin under trade name Alika 247 bio-efficacy) was evaluated against Pest of Tea in West Bengal, India. The study reported that Alika 247 ZC was safe for the important natural predators found in the tea ecosystem relative to conventional formulations like EC [47]. Similarly, thiamethoxam and lambda cyhalothrin ZC impact was investigated on Population of Lady Bird Beetles in maize crop ecosystem in Gujarat, India [48].
This combination formulation has fast and quick knockdown and extended control of foliar insect pest. This formulation is basically developed for soybean aphids, Japanese beetle, grasshopper, corn rootworm beetle, stinkbugs, etc.
Institute of Pesticide Formulation Technology (IPFT) has developed Lambda cyhalothrin 14 CS with Diflubenzuron 10SC. The unique specialty of this developed ZC formulation is effective against early stages and adult stages simultaneously. The combined pesticide provides improved and synergistic activity. Besides this, formulation is suitable for immediate as well as for prolonged pest control practices.
Suspoemulsion (Suspension concentrate (SC) + Emulsion in water (EW))
Suspension (SE) is the combination of two active ingredients one in suspension concentrate (SC) and concentrated aqueous emulsion (EW) (Figure 14). Suspoemulsion is the stable colloidal suspension with fine droplets with a high degree of electrostatic, steric, and hydrophobic interactions and with lesser degree of Ostwald ripening [49].
Figure 14.
Diagrammatical representation of suspoemulsion formulation and its application.
Main advancing features are different active ingredients with different solubility or melting points can be incorporated, providing broad-spectrum pest control, and tank mixing is not required. Suspoemulsions are the most convenient formulation for the farmers to apply the correct quantity of pesticides and tank mix incompatibility problems have been removed. Surfactants and thickeners were added in suspoemulsion to prevent flocculation and separation of the dispersed phases [50].
IPFT has contributed suspoemulsion of fipronil 5% SC + Soyabean oil as Adjuvant 5% EW. The main characteristic feature of this formulation is high stability and shelf life along with good bio-efficacy to agricultural pest in Asian countries.
7.3 Botanical formulations
Different bioactive phytochemicals have been identified for good bio-efficacy. These bioactive ingredients in formulated form will play a very significant role in promotion of organic farming in Asian countries in a safe and sound way. Followings botanical formulations have been formulated by IPFT.
New generation botanical-based formulations developed in IPFT, India, are as follows:
Microemulsion:Neem oil-based microemulsions were successfully developed at IPFT, Gurgaon [51]. Different essential oil microemulsions have been developed by IPFT by using various botanical synergists and adjuvants.
Nanoemulsions: Botanical origin nanoemulsions are very fine oil-in-water nano-droplet within the size of 5 nm–100 nm [52]. These nanoemulsions have both thermodynamic and kinetic stabilities [53]. IPFT has developed combined botanical nanoemulsion of eucalyptus oil with karanja and jatropha aqueous filtrates—for controlling stored grain pest Tribolium castaneum [54]. Uniqueness of this formulation is that karanja and jatropha aqueous extract was used from biodiesel waste product and with eucalyptus oil it gives combinatory activity. This formulation is the very efficient in terms of insect pest management and waste product management.
Controlled release Formulations (CRF), microencapsulation:This formulation technology regulates the release of pesticide and decrease the toxicity of pesticide [55].Highly volatile bioactive pesticides encapsulated in a thick polymeric coating by cross-linking. Therefore, these formulations are efficient for an extended period of time.
Suspension concentrates: Suspension concentrate (SC) botanical extracts have been developed by different researchers [56]. In botanical SC, botanical active ingredient is finely grinded and then dispersed in water medium with surfactants. Particle size distribution of diluted SC formulation is in the range of 2–20 μm. These formulations are eco-friendly and user friendly. Hence, botanical SC formulations are the most suitable formulation for botanicals to retain their greener characteristics.
Oil dispersions (OD): These formulations are similar to SC formulation only dispersing medium is oil in place of water as in SC. Therefore, OD formulations have good spreading and permeation compared with SC formulation. The oil dispersion formulation is the most suited formulation for hydrolytically unstable botanical pesticides. It has been reported that oil gives synergist action with botanicals and broadens the spectrum of pest management [57]. IPFT has developed oil dispersion formulations of many plant extracts against various insect pest. Recently, IPFT has developed tomato leaves extract OD formulation and found to be very efficient against mustard aphids.
Institute of Pesticide Formulation Technology (IPFT), Gurugram in India is the only institute devoted for the development of safe and environment-friendly new-generation insecticide formulation technology. There are some new formulated products of natural insecticides such as controlled release formulations, nano-formulations, or water-based formulations, which enhance the efficacy of natural pesticides against insect pest. The work carried out at IPFT greatly emphasizes on the development and promotion of environment and user-friendly pesticide formulations, also biodegradable, with the incorporation of latest technologies, and also on their commercialization.
8. Future considerations for the promotion of safe and green biopesticides
Currently, IPFT is working toward the development of safer alternatives to banned or going to be banned agrochemicals. Research is in the process of development to safer formulations with potentially low-risk user and environment-friendly novel formulation development of various broad-spectrum pesticides that are in the verge of banned have been attracting global attention. In this context, public and private sectors cooperation is necessary to facilitate the formulation development of safe and environment-friendly improved and advanced alternative. Novel formulations improve the delivery of agrochemicals and boost up the agricultural system in near future. Most important aspect along with the development is the cost of safe formulation. Maintaining low cost of novel formulations to farmers for a given product quality and availability, particularly in developing countries, is also important. Though, new formulation strategies could give out a very promising and potential option for pest control but to attain this objective, more field research is required to assess the efficacy on specific pest problems and over rising pest problems in various cropping systems. Therefore, it is a necessary requirement for strengthening the research in this safe and green formulation technology development.
Acknowledgments
Authors would like to thanks to Institute of Pesticide Formulation Technology under Ministry of Chemicals and Fertilizer, India. The authors would like to thank Dr. Saurabh Dubey for her valuable input in the preparation of this chapter.
\n',keywords:"agriculture, agrochemicals, pesticides, new-generation formulations, pest, environment protection, user-friendly, crop protection",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/79863.pdf",chapterXML:"https://mts.intechopen.com/source/xml/79863.xml",downloadPdfUrl:"/chapter/pdf-download/79863",previewPdfUrl:"/chapter/pdf-preview/79863",totalDownloads:116,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 16th 2020",dateReviewed:"October 8th 2021",datePrePublished:"December 31st 2021",datePublished:"February 2nd 2022",dateFinished:"December 31st 2021",readingETA:"0",abstract:"The agricultural sector of Asian countries supports 60% of the global population, accounting one-fifth of the world’s agricultural land. Despite the gap between demand and supply of food is gradually increasing due to the damages caused by insect and other pest attacks on the limited agricultural land, the pest attack has influenced the entire agriculture sector either directly or indirectly, causing socioeconomic losses. To combat, farmers have been using conventional agrochemicals nonjudiciously that lead to adverse effects such as pesticide resistance, environmental contamination, and non-target toxicity. In this regard, new-generation agrochemical formulation techniques are advantageous over conventional pesticides and play a vital role in sustainable agriculture by fulfilling the demand of over-rising food supply to feed the increasing population. These formulations exhibit desired bio-efficacy at lower doses and have minimum possibility to leave pesticide residues in crop products and the environment. Institute of Pesticide Formulation Technology (IPFT), Gurugram, is one of the leading institutes in Asia, which is actively engaged in developing new-generation formulations to deliver safer, efficient, and environment-friendly pesticide formulations. So far, IPFT has developed 60 pesticide formulations and transferred technologies to different agrochemical industries globally. The new-generation formulations developed by IPFT mainly include microemulsion, nanoemulsion, capsulated suspension, nano-encapsulation, an emulsion in water, mixed formulations including several botanical pesticide formulations. The new advancement in pesticide delivery systems is very supportive in combating the crisis faced by the agricultural sector. In this chapter, formulation of different new-generation pesticides and their advancement are summarized.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/79863",risUrl:"/chapter/ris/79863",signatures:"Nusrat Iqbal, Amrish Agrawal, Md. Imteyaz Alam and Jitendra Kumar",book:{id:"8135",type:"book",title:"Agricultural Development in Asia",subtitle:"Potential Use of Nano-Materials and Nano-Technology",fullTitle:"Agricultural Development in Asia - Potential Use of Nano-Materials and Nano-Technology",slug:"agricultural-development-in-asia-potential-use-of-nano-materials-and-nano-technology",publishedDate:"February 2nd 2022",bookSignature:"Md. Asaduzzaman and Mafruha Afroz",coverURL:"https://cdn.intechopen.com/books/images_new/8135.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-137-0",printIsbn:"978-1-83968-136-3",pdfIsbn:"978-1-83968-138-7",isAvailableForWebshopOrdering:!0,editors:[{id:"171564",title:"Dr.",name:"Md",middleName:null,surname:"Asaduzzaman",slug:"md-asaduzzaman",fullName:"Md Asaduzzaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"276457",title:"Dr.",name:"Imteyaz",middleName:null,surname:"Alam",fullName:"Imteyaz Alam",slug:"imteyaz-alam",email:"imteyaz84@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Polytechnic University of Milan",institutionURL:null,country:{name:"Italy"}}},{id:"317856",title:"Ms.",name:"Nusrat",middleName:null,surname:"Iqbal",fullName:"Nusrat Iqbal",slug:"nusrat-iqbal",email:"nusratsiddiqa20@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"332608",title:"Dr.",name:"Amrish",middleName:null,surname:"Agrawal",fullName:"Amrish Agrawal",slug:"amrish-agrawal",email:"amrish.ag@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"441373",title:"Dr.",name:"Jitendra",middleName:null,surname:"Kumar",fullName:"Jitendra Kumar",slug:"jitendra-kumar",email:"dummy+441373@intechopen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Basic concept of formulation",level:"1"},{id:"sec_3",title:"3. Conventional formulations and their limitations",level:"1"},{id:"sec_4",title:"4. Recent advancements in agrochemical formulations",level:"1"},{id:"sec_5",title:"5. Recent advances in suspension concentrate formulations",level:"1"},{id:"sec_5_2",title:"5.1 Capsule suspension (CS)",level:"2"},{id:"sec_6_2",title:"5.2 Advanced features of CS",level:"2"},{id:"sec_7_2",title:"5.3 Microemulsion",level:"2"},{id:"sec_9",title:"6. Preparation methods of ME formulation",level:"1"},{id:"sec_9_2",title:"6.1 Phase inversion method",level:"2"},{id:"sec_10_2",title:"6.2 Use of ME in agriculture",level:"2"},{id:"sec_11_2",title:"6.3 Nanoemulsion formulation",level:"2"},{id:"sec_13",title:"7. Emulsion in water formulation or oil in water emulsion (EW)",level:"1"},{id:"sec_13_2",title:"7.1 EW in agriculture",level:"2"},{id:"sec_14_2",title:"7.2 Mixed formulations (Suspoemulsion, ZC, ZW)",level:"2"},{id:"sec_15_2",title:"7.3 Botanical formulations",level:"2"},{id:"sec_17",title:"8. Future considerations for the promotion of safe and green biopesticides",level:"1"},{id:"sec_18",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Webster JPG, Bowles RG, Williams NT. Estimating the Economic Benefits of Alternative Pesticide Usage Scenarios: Wheat Production in the United Kingdom. Crop Production. 1999;18:83'},{id:"B2",body:'Schreinemachers P, Tipraqsa P. Agricultural pesticides and land use intensification in high, middle and low income countries. Food Policy. 2012;37:616-626'},{id:"B3",body:'Baskar K, Sudha V, Jayakumar M. Effect of Pesticides on Pollinators. MOJ Ecology & Environmental Science. 2017;2:40-52. 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International Journal of Pharmacology. 2004;280:41-25'},{id:"B54",body:'Pant M, Dubey S, Patanjali PK, Naik SN, Sharma S. Insecticidal activity of eucalyptus oil nanoemulsion with karanja and jatropha aqueous filtrates. International Biodeterioration & Biodegradation. 2014;91:119-127'},{id:"B55",body:'Ribeiro C, Vicente AA, Teixeira JA, Miranda C. Optimization of edible coating composition to retard strawberry fruit senescence. Postharvest Biology and Technology. 2007;44:63-70'},{id:"B56",body:'Luckham PF. The physical stability of suspension concentrates with particular reference to pharmaceutical and pesticide formulations. Pesticide Science. 1989;25:25-34. DOI: 10.1002/ps.2780250105'},{id:"B57",body:'Vernner R, Bauer P. Q-TEO, a formulation concept that overcomes the incompability between water and oil. Pfalzenschutz-Nachrichten Bayer. 2007;60:7-26'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Nusrat Iqbal",address:"nusratsiddiqa20@gmail.com",affiliation:'
Institute of Pesticide Formulation Technology, India
Institute of Pesticide Formulation Technology, India
'}],corrections:null},book:{id:"8135",type:"book",title:"Agricultural Development in Asia",subtitle:"Potential Use of Nano-Materials and Nano-Technology",fullTitle:"Agricultural Development in Asia - Potential Use of Nano-Materials and Nano-Technology",slug:"agricultural-development-in-asia-potential-use-of-nano-materials-and-nano-technology",publishedDate:"February 2nd 2022",bookSignature:"Md. Asaduzzaman and Mafruha Afroz",coverURL:"https://cdn.intechopen.com/books/images_new/8135.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83968-137-0",printIsbn:"978-1-83968-136-3",pdfIsbn:"978-1-83968-138-7",isAvailableForWebshopOrdering:!0,editors:[{id:"171564",title:"Dr.",name:"Md",middleName:null,surname:"Asaduzzaman",slug:"md-asaduzzaman",fullName:"Md Asaduzzaman"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"221006",title:"Ms.",name:"Jumoke",middleName:null,surname:"Aboyewa",email:"Jhurmokei@yahoo.com",fullName:"Jumoke Aboyewa",slug:"jumoke-aboyewa",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"58514",title:"Antidiabetic and Safety Properties of Ethanolic Leaf Extract of Corchorus olitorius in Alloxan-Induced Diabetic Rats",slug:"antidiabetic-and-safety-properties-of-ethanolic-leaf-extract-of-corchorus-olitorius-in-alloxan-induc",abstract:"Diabetes is a major metabolic disease of global concern. Ethanolic extract of Corchorus olitorius leaf was investigated for antidiabetic activity in alloxan-induced diabetic rats. A total of thirty-six albino rats (Rattus norvegicus) with body weight 150.50 ± 10.50 g were randomly selected into six groups (A–F). Group A animals were non-diabetic and received 0.5 mL distilled water, groups B, C, D, E and F were made diabetic by administration of alloxan monohydrate (150 mg/kg, body weight i.p). Group B was diabetic untreated, group C was diabetic and treated with glibenclamide, while groups D, E and F received the ethanolic extract of C. olitorius leaf at a dose of 200 mg/kg, 400 mg/kg and 800 mg/kg body weight respectively. Phytochemical screening showed the presence of flavonoids, tannins, saponins, phlobatannin anthraquinones, phenol and cardiac glycoside and saponin. The blood glucose of the alloxanized rats after 72 hours which ranged from 17.30–25.33 mmol/L were significantly (p < 0.05) and progressively reduced in treated groups which compared favorably with the standard drug group. The significantly (p < 0.05) elevated levels of serum and liver bilirubin (direct and total), transaminases (AST and ALT), alkaline phosphatase, urea, creatinine, total cholesterol, triglyceride, LDL-C, as well as reduced levels of total protein, globulin, albumin and HDL-C in the diabetic untreated rats were normalized upon treatment with ethanolic extract of C. olitorius leaf. These results suggest that the ethanolic extract of C. olitorius leaf possesses antihyperglycemic property with no major side effect hence it could be considered safe for the management of diabetes.",signatures:"Arise Rotimi Olusanya, Bankole S. Ifeoluwa, Aboyewa Jumoke A.\nand Bobbo Khadijat",authors:[{id:"217205",title:"Dr.",name:"Rotimi",surname:"Arise",fullName:"Rotimi Arise",slug:"rotimi-arise",email:"ariserotimi@gmail.com"},{id:"220514",title:"Dr.",name:"Ifeoluwa",surname:"Bankole",fullName:"Ifeoluwa Bankole",slug:"ifeoluwa-bankole",email:"silverbank1@gmail.com"},{id:"221006",title:"Ms.",name:"Jumoke",surname:"Aboyewa",fullName:"Jumoke Aboyewa",slug:"jumoke-aboyewa",email:"Jhurmokei@yahoo.com"},{id:"221007",title:"Ms.",name:"Khadijat",surname:"Bobbo",fullName:"Khadijat Bobbo",slug:"khadijat-bobbo",email:"khadijantii@gmail.com"}],book:{id:"6155",title:"Diabetes Food Plan",slug:"diabetes-food-plan",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"210348",title:"Mr.",name:"Asmare Yitayeh",surname:"Gelaw",slug:"asmare-yitayeh-gelaw",fullName:"Asmare Yitayeh Gelaw",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University Of Gondar",institutionURL:null,country:{name:"Ethiopia"}}},{id:"210376",title:"Dr.",name:"Muhammed",surname:"Kizilgul",slug:"muhammed-kizilgul",fullName:"Muhammed Kizilgul",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ankara University",institutionURL:null,country:{name:"Turkey"}}},{id:"210388",title:"Ph.D.",name:"Vlad",surname:"Cristina",slug:"vlad-cristina",fullName:"Vlad Cristina",position:"assistant professor",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"211906",title:"Ph.D. Student",name:"Meltem",surname:"Mermer",slug:"meltem-mermer",fullName:"Meltem Mermer",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"217205",title:"Dr.",name:"Rotimi",surname:"Arise",slug:"rotimi-arise",fullName:"Rotimi Arise",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"217216",title:"Prof.",name:"Elhadj-Ahmed",surname:"Koceir",slug:"elhadj-ahmed-koceir",fullName:"Elhadj-Ahmed Koceir",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217216/images/5926_n.jpg",biography:"Dr. EA. Koceir, Ph.D Doctor now is a professor of Nutrition and Dietetics in Human Pathologies (NDHP), head of the Bioenergetics and Intermediary Metabolism laboratory in Faculty of Biological Sciences, Department of Biology and Physiology (USTHB, Algiers, Algeria), head of NDHP education program student’s, Member of the Algerian National medical research. He obtained his PhD thesis in Joseph Fourier University (Grenoble, France) in cell physiology and metabolism speciality. And Dr. EA. Koceir is researcher in clinical nutrition at Algiers hospitals (endocrinology and cardiovascular unit). In our laboratory, studies on the mechanisms of cellular physiology about energy flux regulation in mitochondria in liver, muscle, adipose tissue and thyroid.",institutionString:null,institution:null},{id:"220514",title:"Dr.",name:"Ifeoluwa",surname:"Bankole",slug:"ifeoluwa-bankole",fullName:"Ifeoluwa Bankole",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"221007",title:"Ms.",name:"Khadijat",surname:"Bobbo",slug:"khadijat-bobbo",fullName:"Khadijat Bobbo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"221212",title:"Dr.",name:"Ines",surname:"Gouaref",slug:"ines-gouaref",fullName:"Ines Gouaref",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"223836",title:"Dr.",name:"Bekir",surname:"Ucan",slug:"bekir-ucan",fullName:"Bekir Ucan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:230,paginationItems:[{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:"Catholic University of Valencia San Vicente Mártir, Spain",institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain. She is a Full Professor at the Department of Medicine and Animal Surgery at the same University. She developed her research activity in the field of Endocrinology, Hematology, Biochemistry and Immunology of horses. She is a scientific reviewer of several international journals : American Journal of Obstetrics and Gynecology, Comparative Clinical Pathology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology. Since 2014, she has been the Head of the Clinical Analysis Laboratory of the Hospital Clínico Veterinario from the Faculty of Veterinary, CEU-Cardenal Herrera University.",institutionString:"CEU-Cardenal Herrera University",institution:{name:"CEU Cardinal Herrera University",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. 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Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. 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After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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