Molecular Imaging of Renal Transport and Metabolism using Hyperpolarized C-13 MRI

使用超极化 C-13 MRI 进行肾脏运输和代谢的分子成像

基本信息

批准号：
9249529
负责人：
Cornelius von Morze
金额：
$ 16.4万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9249529
关键词：
Accelerometer Address Anti-Inflammatory Agents Anti-inflammatory Autopsy Biological Assay Blood Tests Carbon Chronic Kidney Failure Clinical Clinical Markers Clinical Trials Contrast Media Development Development Plans Diagnosis Diet Disease Disease model Diuresis Diuretics Drug usage Electrolytes Evaluation Fasting Fatty acid glycerol esters Glucocorticoids Gluconeogenesis Goals Hepatic Histology Hormonal Ibuprofen Image Injury Insulin Insulin Resistance Interdisciplinary Study Kidney Kidney Diseases Knockout Mice Knowledge Label Laboratories Lactic acid Lead Liver Magnetic Resonance Imaging Measures Mediating Medical Mentored Research Scientist Development Award Mentors Metabolic Metabolism Methods Modeling Molecular Monitor Mus National Institute of Diabetes and Digestive and Kidney Diseases Non-Insulin-Dependent Diabetes Mellitus Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Phosphotransferases Physiological Physiological Processes Physiology Play Pre-Clinical Model Prevalence Process Pyruvate Rattus Regulation Relaxation Renal Tissue Renal function Research Research Personnel Research Training Role Signal Transduction Silicon Dioxide Sodium Chloride Specificity Techniques Technology Time Tracer Transport Process Universities Urea Urine Work base blood glucose regulation career career development clinical imaging clinical translation clinically significant cyclopropane design diabetogenic experience glomerular filtration glucose metabolism hepatic gluconeogenesis histological specimens histological stains imaging approach imaging biomarker imaging modality imaging probe imaging study improved in vivo inhibitor/antagonist molecular imaging mouse model novel pre-clinical preclinical study prevent public health relevance safety and feasibility serial imaging skills small molecule inhibitor standard measure technique development uptake urinary virtual whole body imaging

Accelerometer Address Anti-Inflammatory Agents Anti-inflammatory Autopsy Biological Assay Blood Tests Carbon Chronic Kidney Failure Clinical Clinical Markers Clinical Trials Contrast Media Development Development Plans Diagnosis Diet Disease Disease model Diuresis Diuretics Drug usage Electrolytes Evaluation Fasting Fatty acid glycerol esters Glucocorticoids Gluconeogenesis Goals Hepatic Histology Hormonal Ibuprofen Image Injury Insulin Insulin Resistance Interdisciplinary Study Kidney Kidney Diseases Knockout Mice Knowledge Label Laboratories Lactic acid Lead Liver Magnetic Resonance Imaging Measures Mediating Medical Mentored Research Scientist Development Award Mentors Metabolic Metabolism Methods Modeling Molecular Monitor Mus National Institute of Diabetes and Digestive and Kidney Diseases Non-Insulin-Dependent Diabetes Mellitus Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Phosphotransferases Physiological Physiological Processes Physiology Play Pre-Clinical Model Prevalence Process Pyruvate Rattus Regulation Relaxation Renal Tissue Renal function Research Research Personnel Research Training Role Signal Transduction Silicon Dioxide Sodium Chloride Specificity Techniques Technology Time Tracer Transport Process Universities Urea Urine Work base blood glucose regulation career career development clinical imaging clinical translation clinically significant cyclopropane design diabetogenic experience glomerular filtration glucose metabolism hepatic gluconeogenesis histological specimens histological stains imaging approach imaging biomarker imaging modality imaging probe imaging study improved in vivo inhibitor/antagonist molecular imaging mouse model novel pre-clinical preclinical study prevent public health relevance safety and feasibility serial imaging skills small molecule inhibitor standard measure technique development uptake urinary virtual whole body imaging

展开

项目摘要

DESCRIPTION (provided by applicant): Existing clinical markers for early renal disease are very limited. Better monitoring and management of renal disease is a pressing unmet medical need. The overall goal of this project is to develop the application of new hyperpolarized carbon-13 (13C) MRI technology for monitoring renal disease. In addition to the candidate's research plan, this application for a NIDDK Mentored Research Scientist Development Award (K01) also includes a mentored career development plan for Dr. Cornelius von Morze to achieve his ultimate career goals as an independent investigator. This resubmission application contains enhanced multi-disciplinary research and training plans for improved scientific and clinical impact. Dr. von Morze will investigate new contrast mechanisms based on novel hyperpolarized (HP) 13C MR molecular imaging contrast agents to probe key renal transport and metabolic processes in preclinical models. HP urea imaging, co-polarized and imaged simultaneously with a reference tracer, will be applied to probe renal urea transport with high specificity. HP urea imaging will be applied to monitor clinically significant altered states of urea transport: progressive renal damage associated with NSAID use, and novel "urearetic" drug- induced diuresis. Molecular imaging of HP lactic acid will be investigated as a novel probe of renal gluconeogenesis, a crucial contributor to glucose homeostasis in the fasting state which is dramatically and selectively dysregulated in type 2 diabetes mellitus. These imaging studies will allow highly novel characterization of renal disease in preclinical murine models. This research aims to improve monitoring and management of renal disease with the potential for clinical translation due to the noninvasiveness, safety, and feasibility of these new molecular MR imaging methods. Dr. Cornelius von Morze's graduate work focused on advanced MRI technique development and his postdoctoral research has resulted in new technical development and applications of novel HP 13C MR molecular imaging contrast agents, particularly for renal imaging. The mentored career development plan described in this proposal will expand Dr. von Morze's breadth of knowledge with theoretical and experimental experience in preclinical models, renal physiology, biological assays and histology. He will also improve his skills for hypothesis-driven research and in laboratory management. This NIDDK K01 project has been designed to enable his long-term goal of leading world-class independent university research in MR molecular imaging of renal disease for the study of both experimental disease models and ultimately patients to address currently unmet clinical needs.

描述（由申请人提供）：早期肾脏疾病的现有临床标记非常有限。更好地监测和管理肾脏疾病是一种未满足的医疗需求。该项目的总体目标是开发新的超极化碳13（13C）MRI技术来监测肾脏疾病。除了候选人的研究计划外，NIDDK指导的研究科学家发展奖（K01）的申请还包括Cornelius von Morze博士的指导职业发展计划，以实现他作为独立研究员的最终职业目标。该重新提交的申请包含增强的多学科研究和培训计划，以改善科学和临床影响。冯·莫兹（Von Morze）博士将基于新型超极化（HP）13C MR分子成像对比剂研究新的对比机制，以探测临床前模型中关键的肾脏转运和代谢过程。 HP尿素成像，与参考示踪剂同时进行了共偏并成像，将应用于具有高特异性的探针肾尿素转运。 HP尿素成像将用于监测尿素运输的临床明显改变状态：与NSAID使用相关的进行性肾脏损伤和新型的“尿素”药物诱导的利尿作用。 HP乳酸的分子成像将被研究为一种新型的肾糖异生探针，这是对禁食状态下葡萄糖稳态的关键因素，在2型糖尿病中急剧和选择性地失去失调。这些成像研究将允许在临床前鼠模型中高度新颖的肾脏疾病表征。这项研究旨在改善对肾脏疾病的监测和管理，并由于这些新分子MR成像方法的无创，安全性和可行性而进行临床翻译的潜力。 Cornelius von Morze博士的研究生工作着重于先进的MRI技术开发，他的博士后研究导致了新型HP 13C MR分子成像对比剂的新技术开发和应用，尤其是用于肾脏成像。该提案中描述的指导职业发展计划将在临床前模型，肾脏生理学，生物学测定和组织学中利用理论和实验经验扩大冯·莫兹博士的知识广度。他还将提高他的假设驱动研究和实验室管理的技能。该NIDDK K01项目旨在实现他的长期目标，即领导世界一流的独立大学研究肾脏疾病的MR分子成像研究，以研究实验性疾病模型和最终患者，以满足当前未满足的临床需求。