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TR&D3: Novel Imaging Agents & Physiological Modeling for Quantitative PET/MR

基本信息

批准号：
10651783
负责人：
Marc David Normandin
金额：
$ 59.64万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-30 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10651783
关键词：
3-Dimensional Administrative Supplement Affect Affinity Animal Model Animals Binding Biodistribution Biological Biological Markers Biological Process Brain Cardiac Cardiology Cells Cellular Membrane Collaborations Complement Contrast Media Custom Data Degenerative polyarthritis Dementia Demyelinations Development Disease Endocrinology Equation Extracellular Space FDA approved Family suidae First Independent Research Support and Transition Awards Functional Magnetic Resonance Imaging Funding Half-Life Heart Heart Atrium Image Image Analysis Imaging technology Immune Immune response Impairment Incubated Inflammation Inflammatory Kidney Kinetics Label Lesion Liver Macrophage Magnetic Resonance Imaging Magnetic nanoparticles Maps Measurement Measures Membrane Potentials Methodology Methods Microelectrodes Mitochondria Modality Modeling Monkeys Mononuclear Motion Multiple Sclerosis Mus Muscle Myelin Myocardium Oncology Oryctolagus cuniculus Oxidative Stress Penetration Peptides Physiological Physiological Processes Physiology Positron-Emission Tomography Potassium Channel Preparation Primates Property Prostate Protamines Protocols documentation Radiochemistry Radiolabeled Radiometry Resolution Rodent Model Scanning Sensory Receptors Services Signal Transduction Skeletal Muscle Specificity T-Lymphocyte Techniques Technology Testing Time Tissues Tracer Translations Traumatic Brain Injury Validation Ventricular Work body system cell type data acquisition design electric field extracellular ferumoxytol first-in-human functional group gray matter human subject image translation imaging agent imaging modality imaging properties immune function immune imaging improved in vivo mitochondrial membrane molecular imaging monocyte multimodality nanoparticle nanoparticle drug nitroxyl nonhuman primate novel novel imaging technology novel marker off-label use pharmacokinetic model physiologic model pre-clinical radiotracer synergism tau Proteins voltage white matter

项目摘要

ABSTRACT PET and MRI offer complementary views of physiology. The ability to measure data from both modalities concurrently has many advantages; in addition to perfect registration, it offers the possibility of studying biological mechanisms in ways that were heretofore impossible to realize in intact animals, including human subjects. PET and MRI are based upon different physical principles and generally reflect different in vivo phenomena, so the availability of multimodal hardware and data acquisition raises new opportunities and challenges for probe development, image analysis and interpretation. Our approach to PET/MR is therefore to develop methods that exploit the complementary information from PET and MRI, including the creation of new radiotracers, acquisition protocols, and analysis techniques where appropriate. In the previous funding cycle, our pharmacokinetic modeling and radiochemistry efforts resulted in the development of imaging methods and radiotracers for PET/MR enabling non-invasive measurement of neuroreceptor signaling with PET/fMRI, mitochondrial membrane potential in cardiac studies with a voltage-sensitive tracer and extracellular volume by T1 mapping, radiolabeled nitroxide radicals for imaging oxidative stress, and development of radiolabeled nanoparticles. Our recent findings and collaborations motivated methods for improved quantification of tau burden as well as mapping cellular membrane potential and demyelination as new directions. In the renewal application, we will build on progress made during the first funding cycle and advance our technologies to their next stages of development. Specifically, we propose to develop PET/MR imaging methods and radiotracers for measuring cellular membrane potential in the myocardium and mitochondrial membrane potential outside the heart, demyelination in the brain, and immune function throughout the body. Together these novel imaging technologies span diverse organ systems, physiological processes, and potential disease applications that will be pursued in detail through interactions with numerous Collaborative and Service Projects.

摘要