MRI based phosphocreatine mapping method to assess patients with peripheral arterial disease.

基于 MRI 的磷酸肌酸绘图方法评估外周动脉疾病患者。

• 批准号: 10469525
• 负责人: JIadi Xu
• 金额: $ 42万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10469525
• 关键词: Address; Aging; Anatomy; Animal Model; Ankle; Arterial Fatty Streak; Arteries; Atherosclerosis; Blood flow; Brain; Chemicals; Clinical; Creatine; Data; Development; Diabetes Mellitus; Energy Metabolism; Evaluation; Exercise; Exercise Test; Fatigue; Functional disorder; Funding; Glutamates; Glycogen; Glycosaminoglycans; Goals; Gold; Guanidinoacetate N-Methyltransferase; Heart failure; Homeostasis; Human; Image; Imaging Techniques; Ischemia; Kinetics; Knowledge; Leg; Lower Extremity; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Metabolic; Metabolic Diseases; Metabolism; Methods; Mitochondria; Mus; Muscle; Muscle Mitochondria; Musculoskeletal Diseases; Myopathy; Network-based; Obesity; Patients; Peripheral arterial disease; Phosphocreatine; Phosphorus; Play; Polynomial Models; Population; Proteins; Recovery; Reproducibility; Resolution; Rodent; Role; Routine Diagnostic Tests; Scanning; Sensitivity and Specificity; Severities; Shapes; Signal Transduction; Skeletal Muscle; Solid; Specificity; Stenosis; Stress; Techniques; Testing; Time; Tissues; Translating; Water; Work; anatomic imaging; artificial neural network; base; clinical application; clinical practice; clinically translatable; detection sensitivity; disability; exercise intolerance; experience; hemodynamics; imaging platform; indexing; inorganic phosphate; macromolecule; magnetic field; mouse model; novel; radio frequency; rapid technique; skeletal muscle metabolism; spectroscopic imaging; success; validation studies

Peripheral arterial disease (PAD) is caused by atherosclerosis, the buildup of plaque that can obstruct blood flow in the arteries to the lower extremities. The current assessment of patients with PAD targets the anatomic or hemodynamic burden of atherosclerotic plaque stenosis with measurement of ankle-brachial index (ABI), and several imaging other techniques. However, anatomic and hemodynamic indices do not always correlate with the functional limitations and disability that PAD patients experience, and prior work suggests that the PAD population would benefit from more specific functional tissue tests. We hypothesize that metabolic maps of phosphocreatine (PCr) measures, reflecting severe skeletal muscle (SM) ischemia or downstream mitochondrial changes, may fill that gap. PCr is the most abundant high- energy phosphate present in muscle. Energy metabolism and PCr play a vital role in cellular homeostasis, but there currently are no routine diagnostic tests to noninvasively quantify or map the distribution of PCr in patients with PAD. Phosphorus (31P) magnetic resonance spectroscopy (MRS) is arguably the gold standard for the noninvasive assessment of SM mitochondrial function and high-energy phosphate content. However, due to the relatively low MR detection sensitivity and the requirement for unique hardware, 31P MRS is not used in routine clinical applications. Chemical exchange saturation transfer (CEST) MRI has emerged as a novel, high-sensitivity technique that may overcome several of the limitations of 31P MRS. However, CEST MRI is still under development and one major impediment for more widespread application is limited specificity for a particular metabolite due to spectral overlap of CEST signal from other metabolites and proteins and as well as the background signal from semi-solid macromolecules and direct saturation of water Our long-term goal is to develop clinically translatable CEST methods to extract and quantity PCr concentrations in skeletal muscle that provides a sensitive MRI approach to assess SM metabolism. If successful, this new technique should provide a completely new and sensitive method for detecting PCr in calf muscle and may play a pivotal role for the evaluation of regional musle pathophysiology change in many musculoskeletal diseases. We recently developed two new CEST techniques, dubbed as polynomial and Lorentzian line-shape fitting (PLOF) method and artificial neural network based CEST quantification method (ANNCEST) that are able to detect PCr signal with high sensitivity and specificity. We will develop and optimize the PLOF and ANNCEST methods for PCr mapping through one novel animal model and in-magnet plantar flexion exercise for human leg. The optimized CEST MRI methods will be applied on PAD patients to validate that PCr dynamic curve is correlated with the severity of the PAD. Upon the successful completion of this proposal, we anticipate developing the first rapid, high-resolution skeletal muscle energetic functional exercise test.

外周动脉疾病（PAD）是由动脉粥样硬化引起的，动脉粥样硬化是斑块的积聚，可以阻塞血管中的血液流动。 下肢的动脉目前对PAD患者的评估目标是解剖或血流动力学 动脉粥样硬化斑块狭窄的负荷与踝肱指数（ABI）的测量，以及其他几种成像 技术.然而，解剖和血流动力学指标并不总是与功能限制相关， PAD患者经历的残疾，先前的工作表明，PAD人群将受益于更多 特定功能组织测试。我们假设磷酸肌酸（PCr）的代谢图，反映了严重的 骨骼肌（SM）缺血或下游线粒体变化可能会填补这一空白。PCR是最丰富的高- 肌肉中存在能量磷酸盐。能量代谢和PCr在细胞内稳态中起着至关重要的作用，但是， 目前还没有常规的诊断测试来非侵入性地量化或绘制PAD患者中PCr的分布。 磷（31 P）磁共振波谱（MRS）可以说是无创性检查的金标准。 SM线粒体功能和高能磷酸盐含量的评估。然而，由于MR相对较低， 由于检测灵敏度和对独特硬件的要求，31 P MRS不用于常规临床应用。 化学交换饱和转移（CEST）MRI已成为一种新型的高灵敏度技术， 克服了31 P MRS的几个局限性。然而，CEST MRI仍在开发中， 更广泛应用障碍是由于特定代谢物的光谱重叠 来自其他代谢物和蛋白质的CEST信号以及来自半固体大分子的背景信号 我们的长期目标是开发临床上可翻译的CEST方法来提取和 定量骨骼肌中的PCr浓度，提供了灵敏的MRI方法来评估SM代谢。如果 这项新技术的成功，将为检测小腿肌肉中的PCR提供一种全新的、灵敏的方法， 对许多肌肉骨骼疾病局部肌肉病理生理变化的评价具有重要作用。 我们最近开发了两种新的CEST技术，称为多项式和洛伦兹线形拟合 能够检测PCr的基于人工神经网络的CEST定量方法（ANNCEST）和基于人工神经网络的CEST定量方法（PLOF）。 具有高灵敏度和特异性信号。我们将开发和优化用于PCR的PLOF和ANNCEST方法 通过一种新的动物模型和人体腿部的磁跖屈运动进行映射。优化的CEST MRI方法将应用于PAD患者，以验证PCr动态曲线与PAD严重程度相关。 垫.在成功完成这项提案后，我们预计将开发出第一个快速，高分辨率的骨骼 肌肉能量功能运动试验。