Download or read book Development of Magnetic Resonance Imaging Techniques for Mouse Models of Alzheimer s Disease written by James Martin O'Callaghan and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Development of Magnetic Resonance Imaging Techniques for Mouse Models of Alzheimer s Disease written by J. M. O'Callaghan and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Magnetic Resonance Imaging Techniques for Visualising the Development of Alzheimer s Disease like Neurofibrillary Tau Pathology in Animal Models written by Ioannis Lavdas and published by . This book was released on 2010 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis describes the development of magnetic resonance imaging (MRI) techniques to visualise neurofibrillary tau pathology in transgenic mice. Neurofibrillary pathology is a prominent pathological feature of Alzheimer's disease (AD) and is closely correlated to cognitive impairment and dementia. 19F and 1H MRI methods were developed with a 4.7 T preclinical system. To facilitate these experiments, RF saddle coils were designed and constructed that show good agreement with theoretical SNR calculations and produce uniform B1 fields. A copper wire surface coil, incorporating active decoupling electronics, was built to increase the sensitivity of 19F and 1H mouse brain experiments. A stripline transmission line resonator (TLR) was also developed as a surface coil receiver and because it does not need tuning and matching adjustments, it reduces experimental set up times significantly. An ultra-short echo time (UTE) pulse sequence was developed for imaging 19F compounds, designed to attach to sites of tau pathology in the brain and which were known to exhibit very short T2 relaxation times. Ex vivo, 19F MRI experiments using these compounds indicated low penetration of the blood brain barrier and a tendency for precipitation. An RF spoiled, short TE 3D gradient echo pulse sequence was optimised to produce artefact-free T1-weighted images of the mouse brain. Measurements from a preliminary study using high resolution, T1-weighted MRI showed that the ventricular areas of a control mouse were not appreciably different from those of a transgenic mouse. Software was developed to generate automated T2 brain maps from spin echo MRI data sets and was used to compare T2 relaxation times between a control and a transgenic mouse. This experiment showed that the T2 relaxation times of the tau transgenic mouse brain were prolonged when compared to those of a control mouse.

Download or read book Innovative Imaging Techniques in Preclinical Models of Neurodegenerative Diseases written by Rodolfo Gabriel Gatto and published by Frontiers Media SA. This book was released on 2022-02-10 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Multimodal Magnetic Resonance Imaging in Alzheimer s Disease Mouse Models written by Matteo Grudny and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease (AD) is primarily thought to impact cognitive and memory function in patients. However, Apathy and depression are two of the most prevalent symptoms diagnosed in those impacted by AD and mild cognitive impairment (MCI). Current evidence suggests that starting in the early preclinical stage of Alzheimer's disease, the function of vulnerable brain regions and the communication between brain areas involved in reward and memory processing become dysregulated. This project will provide new insights on the structural and network connectivity dysregulation that manifests in AD, using magnetic resonance imaging (MRI) methods to investigate the amyloidogenic 5xFAD and BXD mouse models of Alzheimer's disease.

Download or read book In Vivo Imaging in Pharmacological Research written by Nicolau Beckmann and published by Frontiers Media SA. This book was released on 2017-08-08 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery and development of a biological active molecule with therapeutic properties is an ever increasing complex task, highly unpredictable at the early stages and marked, in the end, by high rates of failure. As a consequence, the overall process leading to the production of a successful drug is very costly. The improvement of the net outcome in drug discovery and development would require, amongst other important factors, a good understanding of the molecular events that characterize the disease or pathology in order to better identify likely targets of interest, to optimize the interaction of an active agent (small molecule or macromolecule of natural or synthetic origin) with those targets, and to facilitate the study of the pharmacokinetics, pharmacodynamics and toxicity of an active agent in suitable models and in human subjects. The objective of this Research Topic is to highlight new developments and applications of imaging techniques with the objective of performing pharmacological studies in vivo, in animal models and in humans. In the domain of drug discovery, the pharmacological and biomedical questions constitute the center of attention. In this sense, it is fundamental to keep in mind the strengths and limitations of each analytical or imaging technique. At the end, the judicious application of the technique with the aim of supporting the search for answers to manifold questions arising during a long and painstaking path provides a continuous role for imaging within the complex area of drug discovery and development.

Download or read book In Vivo Cellular and Molecular Imaging written by Eric T. Ahrens and published by Gulf Professional Publishing. This book was released on 2005-11-09 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent times there has been an explosive expansion of new imaging methodologies that are capable of visualizing specific populations of cells and molecular events in vivo. Vital imaging enhances our ability to study animal models of human development and disease, such as cancers, cardiovascular disease, diabetes, and Alzheimer's. Furthermore, non-invasive imaging may ultimately be useful for monitoring new generations of clinical molecular and cellular therapeutics, such as those utilizing viral vectors and stem cells. These new capabilities have been facilitated by the development of new imaging probes or reagents that target specific cell types, are chemically responsive to physiology, or are responsive to the presence of specific molecules, such as nucleic acids or enzymes. This volume provides an introduction to some of the most exciting methods and applications of emerging non-invasive imaging technologies using magnetic resonance imaging (MRI), positron emission tomography (PET), and various biophotonic approaches. Highlighted, are recent developments in reagent design that impart unique abilities to these imaging modalities to elucidate biological processes in vivo. * Includes 9 chapters by expert researchers in the field of imaging * Introduces new methods and applications of non-invasive imaging technologies * Covers ermerging topics in imaging such as in vivo cell cancer cells, imaging of autoimmune diseases, and maganetic resonance imaging

Download or read book Magnetic Resonance Imaging Techniques for Rodent Pulmonary Imaging written by Eriko Suzanne Yoshimaru and published by . This book was released on 2013 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: Magnetic Resonance Imaging (MRI) is a safe and widely used diagnostic imaging method that allows in vivo observation of anatomy and characterization of tissues. MRI provides a method to monitor patients without invasive measures, making it suitable for both diagnostics and longitudinal monitoring of various pathologies. A notable example of this is the work carried out by the Alzheimer's Disease Neuroimaging Initiative (ADNI), which utilizes imaging, including multiple MRI techniques, to monitor disease progression in AD patients and evaluates treatment responses and prevention strategies. Similarly, MRI has been extensively used in evaluating diseases in a variety of animal models. In order to detect subtle anatomical changes over time, small differences in MR images must be accurately extracted. Furthermore, to ensure that the extracted differences are due to anatomical changes rather than equipment variance, it becomes essential to monitor and to assess the MRI system stability. In the first chapter of the dissertation, a method for monitoring pre-clinical MRI system performance is discussed. The technique developed during the study provides a fast and simple method to monitor pre-clinical MRI systems but also has applications for all areas of MRI. The second chapter describes the development of a 3D UTE MRI method for pulmonary imaging in freely breathing mice. The development of the 3D UTE sequence for pulmonary MRI has demonstrated its ability to collect images without noticeable motion artifacts and with appreciable signal from the lung parenchyma. Furthermore, images at two distinct respiratory phases were reconstructed from a single data set, providing functional information of the rodents' lungs. Finally, in the third chapter, 3D 19F UTE MRI is evaluated for imaging in vivo distributions of perfluorocarbon (PFC) nanoemulsions for measuring pulmonary inflammation. Building upon the development of pulmonary imaging, fluorinated contrast agents made from PFCs were used to target immune cells in response to pulmonary pathology. Both 3D 1H and 19F UTE MRI were used to acquire pulmonary images of mouse models documented to have pulmonary pathology. Even though the mice had confirmed elevation in alveolar macrophage counts, no visible 19F signal accumulation within the pulmonary tissue was observed with MRI.

Download or read book The Quantitative Analysis of Vascular and Morphological Abnormalities in Mouse Models of Neurodegenerative Disease written by Kristof Govaerts (Doctor in Biomedical Sciences) and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Anatomical Phenotyping of the Mouse with Magnetic Resonance Imaging written by Brian John Nieman and published by . This book was released on 2006 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: Modern biomedical research depends heavily on mouse models of human disease and development. The prominent role of mice in the laboratory highlights the need for tools that assess their biological, physiological and anatomical status. These mouse characterization tasks are very similar to those required in assessment of human disease. Consequently, biomedical research stands to benefit from recent technological developments for clinical diagnosis. Adaptation of these techniques to the mouse scale enables direct comparison of human and mouse diseases as well as alternative and improved means of mouse characterization. This thesis therefore describes advances in high throughput MR imaging and analysis techniques. Specific emphasis is placed on developments for anatomical phenotyping. The thesis introduces mouse MRI by reviewing recent progress from the literature, including the description of high throughput multiple mouse MRI (MMMRI). Next, a MMMRI acquisition protocol is presented that was designed for anatomical visualization with T2-weighting. It is shown to produce high resolution images of the brain simultaneously in four live mice. Subsequently, artifacts were observed in some MMMRI images and determined to result from a peculiar gradient hardware imperfection. The nature and elimination of these artifacts is demonstrated. The final development in the thesis is an automated analysis methodology that improves anatomical analysis efficiency. This simplification was achieved computationally by pooling data and assessing anatomical differences between groups of mice. Together, these developments enable simpler and more powerful studies of mouse biology and its relation to human diseases. Medical imaging has revolutionized diagnosis and staging of many human ailments and promises similar reforms in mouse studies. Imaging permits non-invasive and repeatable assessment for longitudinal experiments and three-dimensional visualization of anatomical features. Magnetic resonance imaging (MRI) is one well-established modality known largely for its excellent soft tissue contrast. In order to take advantage of this feature in mouse research, certain modifications to standard clinical practices are warranted. Most notably, the clinical philosophy of individualized patient treatment must be altered so that large groups of mice can be accommodated in each study. Systematic acquisition of images and efficient analysis of data are essential to making mouse MRI studies practical.

Download or read book Whole Brain Isotropic Arterial Spin Labeling Magnetic Resonance Imaging in a Transgenic Mouse Model of Alzheimer s Disease written by James S. Curtis and published by . This book was released on 2008 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Whole Brain Isotropic Arterial Spin Labeling Magnetic Resonance Imaging in a Transgenic Mouse Model of Alzheimer s Disease written by James S. Curtis and published by . This book was released on 2008 with total page 92 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Advanced Magnetic Resonance Imaging Techniques in the Diagnosis of Alzheimer s Disease Ad and Evaluation of Ad Pathogenesis in an Aging Brain written by Ka-Fung Henry Mak and published by Open Dissertation Press. This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "Advanced Magnetic Resonance Imaging Techniques in the Diagnosis of Alzheimer's Disease (AD), and Evaluation of AD Pathogenesis in an Aging Brain" by Ka-fung, Henry, Mak, 麥嘉豐, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Background: The impact of Alzheimer's disease (AD) on society's resources and manpower has been forecasted for more than a decade, and recent statistics across the globe reveal that it is forthcoming. Pioneering work since 1980s confirmed the pathological hallmarks of the disease, such as neuritic plaques, neurofibrillary tangles, amyloid-β peptides, and microtubule-associated tau proteins. There are many gaps in the full appraisal of this complex disease, which possibly begins early in life in susceptible individuals and present at different severity and speed. In current thesis, advanced magnetic resonance imaging (MRI) techniques were evaluated for their efficacy in diagnosis, and in exploring AD pathogenesis. Methods: In MRI volumetry/perfusion and diffusion studies, 20 and 18 AD subjects (different cohorts) were recruited respectively from the memory clinic of a University hospital, while 20 and 18 cognitively normal older adults (CN) were recruited respectively from elderly centers, community and university volunteers, as well as 17 young adults in the diffusion study. In MR Spectroscopy (MRS), 30 healthy volunteers of 3 different age ranges (20-39, 40-59, 60-89) were recruited. All studies were performed using a 3-tesla MRI scanner. For MRI volumetry, a standardized T1-weighted 3D volumetric Fast Field Echo sequence, and for pulsatile Arterial Spin Labeling (ASL), a Look-Locker-based echo-planar imaging sequence was employed. Single-shot echo-planar diffusion weighted imaging was used to examine white matter (WM) integrity; diffusion sensitizing gradients (b = 800 s/mm2) applied in 16 directions, and one additional image without diffusion gradient (b0 = 0 s/mm2). Single voxel MRS was performed in the limbic regions, with point resolved spectroscopy for volume selection and excitation for water suppression. Results: Voxel Based Morphometry with Diffeomorphic Anatomical Registration using Exponentiated Lie algebra and standard registration has similarly high efficacies as manual hippocampal volumetry in discriminating AD from CN. Using pulsatile ASL, we found impairment of hemodynamic parameters other than cerebral blood flow (CBF) in moderate AD, indicative of underlying vascular abnormality. Combined MR hippocampal volumetry and ASL CBF was superior to single measure in AD diagnosis. Using diffusion tensor imaging (DTI) techniques, parallel evidence of anterior WM disintegrity in normal elderly, and more extensively in the AD was found. AD showed further loss of WM integrity in the posterior brain regions, and such WM disintegrity may result from demyelination. In aging, we found increased choline and creatine, and N-acetyl-aspartate in cingulate gyri, which might suggest glial proliferation and neuronal hypertrophy respectively. Discussion: A 'one-stop-shop' study combining structural and perfusion MRI has improved efficacy in discriminating AD from CN. DTI showed possible WM retrogenesis in normal aging and AD, although ischemic effect on WM cannot be ruled out. Our MRS study highlighted metabolic changes with age, which could be compensatory to an increased energy demand coupled with a lower CBF. Neuroimaging is likely to have a great impact on early diagnosis of AD, which will benefit patient care, prognostication and future therapy. Hopefully, insights into the physiol

Download or read book Development and Validation of Structural Magnetic Resonance Imaging MRI based Biomarkers for Diagnosis and Prognosis of Prodromal Alzheimer s Disease written by Azar Zandifar and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Alzheimer's disease (AD) is a neurodegenerative disease and the most common cause of dementia. Currently in Canada, there are about 750,000 people living with dementia with more than 60,000 new cases diagnosed each year. Considering the relative failures in recent clinical trials, combined with the promising prospect of life-style changes, early prediction of the future onset of dementia in the early stages of Alzheimer's disease continuum can be highly beneficial. Advances in better identifying future progressors may both enhance population design for clinical trials and better identify the at-risk populations for life-style interventions. This thesis focuses on enhancement of dementia onset in patients with Mild Cognitive Impairment (MCI) using structural Magnetic Resonance Images (MRI) driven markers. The volume of the hippocampus is one of the best-known MRI-based biomarkers for Alzheimer's disease. Here, it is investigated using four different automatic hippocampus segmentation methods, each enhanced with bias error correction. Results show that multi-atlas-based hippocampus segmentation methods are accurate and show high conformity with manual delineation, and they can be further enhanced using a bias correction technique. The methods compared are not significantly different in their ability to capture AD related pathology. The Cohen's d group difference in hippocampal volume between patients with Alzheimer's dementia and healthy controls is high for all the methods and is of medium size between patients with MCI who convert to dementia in the near future and to those who remain stable for all the methods.Due to the wide-spread use of hippocampal volume a recent effort has been made by researchers in the field to harmonize the hippocampus segmentation protocol. The resulting new protocol, known as the EADC-ADNI harmonized protocol or the HarP, needs more validation. I validate the protocol using a large multi-center database designed for AD biomarker research. The results show that the HarP-based automatic segmentation is an accurate hippocampal segmentation which can be used in AD-related research to capture the Alzheimer's pathology. The methods described above are used in a novel model to predict the onset of dementia in an MCI population during different follow-up periods. The model combines information from MRI-driven markers from the hippocampus and entorhinal cortex with cognitive scores at baseline and tries to predict the diagnostic stage of each subject in different time intervals following the baseline visit. The model produces promising results using information from both cognitive scores and MRI markers to reach higher performance. MRI markers are more sensitive, while cognitive scores bring specificity to the prediction. Furthermore, for a follow-up period of 5 years, the model reaches an area under the receiver operating curve of 0.92 and an accuracy of 87%. Therefore, the prognostic model demonstrates promise as a candidate to be used in the clinic to identify subjects with prodromal Alzheimer's dementia at the MCI stage. Finally, I show that the AD-related atrophy pattern is even present in cognitively normal subjects and can be captured through hippocampal-based markers. I show that there is a small effect size (as measured by Cohen's d) between hippocampal volume in subjects who progress to MCI and/or dementia or subjects who maintain their normal cognition, while the effect is of medium size for the hippocampal grade. This thesis evaluates different automatic and manual hippocampus segmentation techniques and validates hippocampus volume as the most widely used AD marker. Moreover, I present a model to predict the onset of dementia in subjects MCI. I further validate hippocampal driven markers as an Alzheimer's biomarker in very early stages of the disease. Therefore, the results of this work will improve early detection of Alzheimer's leading to decrease the prevalence of the disease." --

Download or read book Characterization of Longitudinal Neuroanatomical Effects in a Mouse Model of Alzheimer s Disease Using Deformation based Morphometry written by Johathan C. Lau and published by . This book was released on 2008 with total page 69 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Advanced Magnetic Resonance Imaging Techniques in the Diagnosis of Alzheimer s Disease AD and Evaluation of AD Pathogenesis in an Aging Brain written by and published by . This book was released on 2015 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Development of Multimodal Imaging Probes for Visualizing Neuroinflammation in Alzheimer s Disease and Traumatic Brain Injury written by Erica M. Andreozzi and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Alzheimer's disease (AD) and traumatic brain injury (TBI) are two significant neurodegenerative diseases whose delayed diagnosis limits the possibility of treatment. Over 5.4 million Americans have AD, and this number is projected to increase to 115 million worldwide by 2050 as a result of people living longer. To date, absolute diagnosis of AD can only be made posthumously through confirmation of senile plaques in brain autopsy specimens; there are no clinical signs of AD apart from severe dementia and brain atrophy, which are only detectable at mid to late stages when neurological damage is already very pronounced. As with AD, TBI is also a leading neurodegenerative disease that continues to go undetected and undiagnosed, leaving ~80,500 TBI survivors with cognitive deficits that result in greater than $56.3 billion in U.S. annual costs each year. While there is evidence suggesting that such cognitive deficits can be improved through immediate rehabilitation and pharmacological intervention post TBI, the lack of diagnostic methods makes these therapies inadequate. Thus, there is great interest in developing a method for early diagnosis of AD and TBI so that necessary treatment options can be employed and chronic, irreversible brain damaged can be prevented. Having identified activated microglia (immune cells of the brain) as contributors to the post-injury neuroinflammation that follows both AD and TBI, we have developed a novel, multimodal imaging probe targeted to activated microglia as a means of non-invasively diagnosing these diseases before the onset of cognitive deficits. Focusing on the key role of microglia in AD and TBI pathology, we aim to use multimodal (PET/MRI/optical) imaging of microglia to for diagnosis and characterization of associated neurodegeneration in order to inform the design of possible drugs. We have synthesized and characterized a multimodal, biomolecular imaging probe, mal-BSA-DOTA(Gd/64Cu), that demonstrates targeting to activated microglia in vitro. The existence of the blood brain barrier (BBB), however, poses challenges for the delivery of this probe into the brain to evaluate in vivo targeting. While rat models of TBI are known to exhibit a compromised BBB, we needed to confirm this with imaging studies. Since AD animal models do no exhibit adequate BBB disruption, we investigated solid lipid nanoparticles (SLNs) as vehicles for brain delivery of our probe. Interested in positron emission tomography (PET) because of its high in vivo sensitivity and magnetic resonance imaging (MRI) because of its high in vivo resolution, we functionalized SLNs to evaluate their performance with PET and MRI. By incorporating a lipid chelator into the SLN architecture, we developed a method to radiolabel SLNs with 64Cu for noninvasive mapping of biodistribution with PET. Preliminary in vivo biodistribution of these SLNs (64Cu-SLNs) was evaluated in mice up to 48 hr post intravenous injection using PET, and these values were then compared to ex vivo biodistribution from gamma counting organs. An additional modification of the SLNs included the loading of gadolinium (1,4,7,10-tetraazacyclododecane)-1,4,7,10-tetraacetate (Gd-DOTA), a T1-weighted contrast agent, into SLNs in order to produce a new category of stable T1-weighted MRI contrast agents that can be modified for longer blood residence time, slow release of cargo, targeting, and multimodal functionality. Intracerebroventricular injection of these Gd-loaded SLNs into mice exhibited T1 contrast enhancement in vivo using T1-weighted MRI. By demonstrating the ability to functionalize SLNs for PET and MRI functionality, we believe that these nanocarriers can serve as stable, biocompatible vehicles for delivering microglial-targeted biomolecules to the brain for early diagnosis AD and TBI.