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

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堆积，会阻碍血管内的血液流动。 通往四肢的动脉。目前对PAD患者的评估以解剖学或血流动力学为目标 踝臂指数(ABI)和其他几种成像方法对动脉粥样硬化斑块狭窄的影响 技巧。然而，解剖学和血流动力学指标并不总是与功能限制和 PAD患者所经历的残疾，先前的研究表明，PAD人群将受益于更多 特定的功能组织测试。我们假设磷酸肌酸(PCR)指标的代谢图反映了严重的 骨骼肌(SM)缺血或下游线粒体改变，可能会填补这一空白。聚合酶链式反应是最丰富的高- 肌肉中存在的能量磷酸盐。能量代谢和聚合酶链式反应在细胞内稳态中起着至关重要的作用，但在 目前还没有常规的诊断试验来无创性地量化或绘制PAD患者的PCR分布图。 磷(31P)磁共振波谱(MRS)可以说是无创检查的黄金标准 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，31P MRS不在常规临床应用中使用。 化学交换饱和转移(CEST)磁共振成像已经成为一种新的、高灵敏度的技术，可以 克服31PMRS的几个局限性然而，CEST MRI仍在开发中，并且是主要的 更广泛应用的障碍是由于光谱重叠而对特定代谢物的特异性有限 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 和水的直接饱和我们的长期目标是开发临床上可翻译的CEST方法来提取和 骨骼肌中的定量聚合酶链式反应浓度，为评估SM代谢提供了一种灵敏的MRI方法。如果 这项新技术的成功，将提供一种全新而灵敏的方法来检测小腿肌肉和 可能在许多肌肉骨骼疾病的局部肌肉病理生理变化的评估中起着关键作用。 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 (PLOF)方法和基于人工神经网络的CEST定量方法(ANNCEST) 信号具有高灵敏度和高特异度。我们将开发和优化用于PCR的PLOF和ANCEST方法 通过一种新的动物模型和磁铁足底屈曲运动对人类腿部进行定位。优化的CEST MRI方法将应用于PAD患者，以验证PCR动态曲线与PAD的严重程度相关 垫子。在成功完成这项计划后，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。

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.