Imaging and Multiomic Biomarker Applications

Imaging and Multiomic Biomarker Applications
Author: Yongxia Zhou
Publisher: Nova Medicine & Health
Total Pages: 0
Release: 2021-01-20
Genre: Alzheimer's disease
ISBN: 9781536190793

The well-known Alzheimer's Disease Neuroimaging Initiative (ADNI) Center provides the most advanced, comprehensive, multiparametric and up-to-date biomarkers for mild cognitive impairment (MCI) and early Alzheimer's disease (AD) projects, including neuroimaging, clinical assessments, biospecimens and genetic data. Recent developments in imaging techniques, including new molecular tracers for imaging disease burden and systematic multi-modal integration, have emerged to overcome the limitations of each single modality and individual-dependent variability. The MRI-based high-resolution structural and morphological changes in the brain, such as atrophy, and the abnormal activity/connectivity patterns of the hippocampus subfields and default mode network (DMN) modulation, together with the amyloid and tau neuropathological quantification using PET molecular tracers, could be used to predict brain changes and cognitive performance declines in early AD, including transitional MCI. Finally, a generalized and integrative model with multiple biomarkers could be built to target disease progression and symptom prediction as well as to optimize patient management.Multiomics investigates metabolomic, lipidomic, genomic, transcriptomic and proteomic perspectives by presenting an accurate biochemical profile of the organism in health and disease. The Alzheimer's Disease Metabolomics Consortium (ADMC) in partnership with ADNI is creating a comprehensive biochemical database for patients in the ADNI1 cohort, consisting of eight metabolomics datasets. The vast majorities of biospecimen data provide rich biological information to the human brain at normal and dementia status. One of the purposes is to reveal the connections between disease and multiomics such as obesity, hypertension, cholesterol imbalance and inflammation risks that might lead to neurodegenerative disease. Multiomic biomarker developments in the dementia field have provided earlier clues to novel treatments that help correct metabolic dysfunction and delay disease progression. Furthermore, the assembling of multiomics-based biomarkers including metabolites and lipids, cholesterol biosynthesis, purine metabolism, lipoprotein, bile acids, and genetics as well as their relation to the pathological amyloid and tau network could improve disease diagnosis sensitivity and reveal more diverse and complementary molecular pathways to allow for the advancement of early AD diagnosis and therapeutic prevention. In this book, we report on the significant differences of multiple biomarkers from the ADNI database including neuroimaging, clinical assessments and multiomic biospecimen/genetic data in MCI and early probable AD (pAD), and elucidate the interconnections among different metrics at various domains. Classification results with high accuracies (0.95-1) for each early dementia subtype including early MCI (EMCI), late MCI (LMCI) and pAD, and better prediction of clinical symptoms is achieved with these comprehensive biomarkers. Further longitudinal changes of imaging and neuropsychological biomarkers, and inter-correlations with baseline parameters are examined for a better illustration of disease progression association. Additionally, an analysis of the post-traumatic stress disorder biomarkers is performed with high classification accuracy. With illustrative and rigorous data analyses and confirmative results, this book provides readers with a full spectrum of biomarker research for early dementia diagnosis and treatment, and helps convey the technical development and data evaluation perspectives in advanced medical imaging and various disease application fields.

Multi-scale and Multimodal Imaging Biomarkers for the Early Detection of Alzheimer's Disease

Multi-scale and Multimodal Imaging Biomarkers for the Early Detection of Alzheimer's Disease
Author: Kilian Hett
Publisher:
Total Pages: 0
Release: 2019
Genre:
ISBN:

Alzheimer's disease (AD) is the most common dementia leading to a neurodegenerative process and causing mental dysfunctions. According to the world health organization, the number of patients having AD will double in 20 years. Neuroimaging studies performed on AD patients revealed that structural brain alterations are advanced when the diagnosis is established. Indeed, the clinical symptoms of AD are preceded by brain changes. This stresses the need to develop new biomarkers to detect the first stages of the disease. The development of such biomarkers can make easier the design of clinical trials and therefore accelerate the development of new therapies. Over the past decades, the improvement of magnetic resonance imaging (MRI) has led to the development of new imaging biomarkers. Such biomarkers demonstrated their relevance for computer-aided diagnosis but have shown limited performances for AD prognosis. Recently, advanced biomarkers were proposed toimprove computer-aided prognosis. Among them, patch-based grading methods demonstrated competitive results to detect subtle modifications at the earliest stages of AD. Such methods have shown their ability to predict AD several years before the conversion to dementia. For these reasons, we have had a particular interest in patch-based grading methods. First, we studied patch-based grading methods for different anatomical scales (i.e., whole brain, hippocampus, and hippocampal subfields). We adapted patch-based grading method to different MRI modalities (i.e., anatomical MRI and diffusion-weighted MRI) and developed an adaptive fusion scheme. Then, we showed that patch comparisons are improved with the use of multi-directional derivative features. Finally, we proposed a new method based on a graph modeling that enables to combine information from inter-subjects' similarities and intra-subjects' variability. The conducted experiments demonstrate that our proposed method enable an improvement of AD detection and prediction.

Mining Brain Imaging and Genetics Data Via Structured Sparse Learning

Mining Brain Imaging and Genetics Data Via Structured Sparse Learning
Author: Jingwen Yan
Publisher:
Total Pages: 210
Release: 2015
Genre: Alzheimer's disease
ISBN:

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual loss of brain functions, usually preceded by memory impairments. It has been widely affecting aging Americans over 65 old and listed as 6th leading cause of death. More importantly, unlike other diseases, loss of brain function in AD progression usually leads to the significant decline in self-care abilities. And this will undoubtedly exert a lot of pressure on family members, friends, communities and the whole society due to the time-consuming daily care and high health care expenditures. In the past decade, while deaths attributed to the number one cause, heart disease, has decreased 16 percent, deaths attributed to AD has increased 68 percent. And all of these situations will continue to deteriorate as the population ages during the next several decades. To prevent such health care crisis, substantial efforts have been made to help cure, slow or stop the progression of the disease. The massive data generated through these efforts, like multimodal neuroimaging scans as well as next generation sequences, provides unprecedented opportunities for researchers to look into the deep side of the disease, with more confidence and precision. While plenty of efforts have been made to pull in those existing machine learning and statistical models, the correlated structure and high dimensionality of imaging and genetics data are generally ignored or avoided through targeted analysis. Therefore their performances on imaging genetics study are quite limited and still have plenty to be improved. The primary contribution of this work lies in the development of novel prior knowledge-guided regression and association models, and their applications in various neurobiological problems, such as identification of cognitive performance related imaging biomarkers and imaging genetics associations. In summary, this work has achieved the following research goals: (1) Explore the multimodal imaging biomarkers toward various cognitive functions using group-guided learning algorithms, (2) Development and application of novel network structure guided sparse regression model, (3) Development and application of novel network structure guided sparse multivariate association model, and (4) Promotion of the computation efficiency through parallelization strategies.

Risk Factors and Outcome Predicating Biomarker of Neurodegenerative Diseases

Risk Factors and Outcome Predicating Biomarker of Neurodegenerative Diseases
Author: Chaur-Jong Hu
Publisher: Frontiers Media SA
Total Pages: 83
Release: 2019-04-03
Genre:
ISBN: 2889458024

Biomarkers for risk detection and outcome prediction of neurodegenerative diseases become more and more important for the clinical practise and neuroscience research. This eBook presents novel findings in this field, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Creutzfeldt-Jakob disease and application of neuroimaging, underlying mechanism of oxidative stress. The readers can catch new information about this emerging frontier of neurology with this eBook.

Modelling Imaging Biomarkers of Alzheimer's Disease Using Animal Models

Modelling Imaging Biomarkers of Alzheimer's Disease Using Animal Models
Author: Maxime Parent
Publisher:
Total Pages:
Release: 2016
Genre:
ISBN:

"Alzheimer's disease is a progressive neurodegenerative disorder characterized by brain amyloid-beta aggregating into plaques, intraneuronal neurofibrillary tangles and neuronal losses, eventually leading to cognitive decline and dementia. The complex interplay between these pathophysiological hallmarks is still not yet fully understood, and therapeutic approaches based on the current conceptualization of Alzheimer pathology have yet to yield potent disease-modifying treatments. To further our understanding of these pathological interactions and to guide therapeutic targets, two tools can be particularly helpful: imaging biomarkers, which allow the in vivo quantification of pathophysiological build-up and neurodegeneration even in the absence of clear clinical symptoms; and animal models, which can be used to study the specific expression of certain aspects of the pathology in a controlled environment.The combination of animal models with multimodal neuroimaging techniques provide a unique platform that can be used to test predictions generated by theoretical disease models and to validate new avenues for potential biomarkers and drug discovery. Here, we performed several studies highlighting the translational power of such approaches to further research on Alzheimer's disease pathophysiology.First, with a longitudinal and multimodal study using the McGill-R-Thy1-APP transgenic rat model of amyloid-beta pathology, we showed that even in the absence of neurofibrillary tangles or widespread neuronal death, amyloid-beta can induce marked neurodegeneration as measured with several PET and MRI markers as well as memory losses. Second, using the same transgenic model, we showed a beneficial effect of hippocampal microglial activation on memory and resting-state connectivity. Finally, using an immunolesioned rat model, we validated the use of [18F]FEOBV as a sensitive PET radiotracer able to measure specific losses of cholinergic synapses, and then confirmed these findings with [18F]FEOBV autoradiography in brain tissue of patients with Alzheimer's disease." --

Clinical use of biomarkers for neurodegenerative disorders

Clinical use of biomarkers for neurodegenerative disorders
Author: Manuel Menéndez-González
Publisher: Frontiers Media SA
Total Pages: 123
Release: 2014-12-03
Genre: Biochemical markers
ISBN: 2889194000

The prevalence of neurodegenerative disorders is increasing dramatically and one of the major challenges today is the need of early and accurate diagnosis, the other is the need of more effective therapies -in turn the development of such therapies also requires early and accurate diagnosis-. The main hope for an earlier and more accurate diagnosis comes from the use of biomarkers. Much research is being done trying to solve the many interrogates related to the role of biomarkers in clinical practice, including the early diagnosis, differential diagnosis and follow-up of neurodegenerative disorders. This is a field where translational research is intense enough to make this topic interesting for basic researchers and clinicians. Indeed, the amount and quality of articles received in response to the call for contributions was very good. This eBook contains a good amount of high quality articles devoted to diverse techniques across several neurodegenerative disorders from different perspectives, including original reports, reviews, methods reports and opinion letters on biochemical biomarkers in biological fluids, neuroimaging techniques and multidimensional approaches linking clinical findings with biomarkers. The disorders covered are also diverse: Alzheimer’s disease, Frontotemporal Dementia, Dementia with Lewy Bodies, Huntington’s disease, Parkinson’s disease among others. As we can learn from articles in this Research Topic, biomarkers are allowing us to expand the knowledge on the biological and anatomical basis of neurodegenerative diseases and to implement diagnostic techniques in clinical practice and clinical trials.

Neuroimaging in Dementia

Neuroimaging in Dementia
Author: Frederik Barkhof
Publisher: Springer Science & Business Media
Total Pages: 295
Release: 2011-02-11
Genre: Medical
ISBN: 3642008186

This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with cognitive decline. It sets out the key clinical and imaging features of the various causes of dementia and directs the reader from clinical presentation to neuroimaging and on to an accurate diagnosis whenever possible. After an introductory chapter on the clinical background, the available "toolbox" of structural and functional neuroimaging techniques is reviewed in detail, including CT, MRI and advanced MR techniques, SPECT and PET, and image analysis methods. The imaging findings in normal ageing are then discussed, followed by a series of chapters that carefully present and analyze the key findings in patients with dementias. Throughout, a practical approach is adopted, geared specifically to the needs of clinicians (neurologists, radiologists, psychiatrists, geriatricians) working in the field of dementia, for whom this book will prove an invaluable resource.

Multi-modality Inference Methods for Neuroimaging with Applications to Alzheimer's Disease Research

Multi-modality Inference Methods for Neuroimaging with Applications to Alzheimer's Disease Research
Author:
Publisher:
Total Pages: 0
Release: 2012
Genre:
ISBN:

An emphasis in ongoing Alzheimer's disease (AD) research is identifying those biomarkers which best predict future cognitive decline at the various stages of disease progression. These biomarkers can then serve as early markers for diagnosis, and for selection of subjects into clinical trials. Recent results suggest that the identification of such discriminative biomarkers is possible by adapting machine learning methods for this problem: but studies have primarily used modalities in isolation so far. The sensitivity/specificity offered by these methods is unsatisfactory for more clinically relevant questions: which Mild Cognitive Impairment (MCI) patients will convert to AD? Answering such questions requires new methods that leverage all data sources (e.g., imaging modalities, CSF measures) in conjunction. This thesis focuses on how data from multiple biomarkers should be optimally aggregated to best predict future cognitive decline, and how these models can improve clinical trials for AD. Significant improvements in sensitivity and specificity for discriminating AD, MCI, and healthy controls at the level of individual subjects are possible by making use of multiple modalities (together with longitudinal data) simultaneously. Further, these methods significantly improve sample size estimates in clinical trials, and help derive customized outcomes for evaluating new treatment procedures. This dissertaion presents new algorithms for a) introducing inductive biases into existing machine learning methods which are designed to fully capture and exploit the structure of the image data; b) combining various imaging modalities into a single predictive model via constructions based on robust loss functions, and quadratic regularizers based on modality-modality interactions; c) using the above frameworks to derive sensitive custom measures of disease progressiong from medical neuroimaging data for use in clinical trials. We present extensive empirical evaluations and theoretical evidence that illustrate how tailor-made machine learning algorithms can transform neuroimaging analysis and clinical trials.