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: 10677775
• 负责人: JIadi Xu
• 金额: $ 40.93万
• 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/10677775
• 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; 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; Signal Transduction; Skeletal Muscle; Solid; Specificity; Stenosis; Stress; Techniques; Testing; Time; Tissues; Translating; Vascularization; Water; Work; anatomic imaging; artificial neural network; clinical application; clinical practice; clinical translation; detection method; 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; transmission process; 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.

外围动脉疾病（PAD）是由动脉粥样硬化引起的 下肢的动脉。当前对PAD患者的评估是解剖或血液动力学的评估 动脉粥样硬化斑块狭窄的负担与脚踝 - 桥梁指数（ABI）的测量以及其他成像其他成像 技术。但是，解剖学和血液动力学指数并不总是与功能局限性和 PAD患者经历的残疾，并且先前的工作表明，PAD人群将受益更多 特定的功能组织测试。我们假设磷酸蛋白（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是最丰富的高级 肌肉中存在磷酸盐。能量代谢和PCR在细胞稳态中起着至关重要的作用，但那里 目前尚无常规诊断测试，可以非侵入性地量化或绘制PAD患者中PCR的分布。 磷（31p）磁共振光谱（MRS）可以说是无创金标准 评估SM线粒体功能和高能磷酸盐含量。但是，由于MR相对较低 检测灵敏度和对独特硬件的需求，31p MRS不用于常规临床应用中。 化学交换饱和转移（CEST）MRI已成为一种新型高敏性技术，可能 克服31p MRS的几个局限性。但是，CEST MRI仍在开发中，一个主要 由于光谱重叠的特定代谢物的障碍，更广泛应用的特异性有限 来自其他代谢物和蛋白质以及半固体大分子的背景信号的CEST信号 水的直接饱和我们的长期目标是开发可临床翻译的CEST方法来提取和 骨骼肌中的数量PCR浓度提供了一种敏感的MRI方法来评估SM代谢。如果 成功，这项新技术应提供一种全新且敏感的方法，用于检测小腿肌肉和 对于许多肌肉骨骼疾病的区域肌肉病理生理变化的评估，可能起关键作用。 我们最近开发了两种新的CEST技术，称为多项式和Lorentzian线形拟合 （plof）方法和基于人工神经网络的CEST定量方法（ANNCEST）能够检测PCR 具有高灵敏度和特异性的信号。我们将开发和优化PCR的plof和anncest方法 通过一种新型的动物模型和人腿的碎脚足屈曲练习绘制。优化的CEST MRI方法将应用于PAD患者，以验证PCR动态曲线与 软垫。该提案成功完成后，我们预计会发展第一个快速，高分辨率的骨骼 肌肉能量功能运动测试。