Monitoring Oxidative Capacity in Peripheral Artery Disease Patients using MR Imaging

使用 MR 成像监测外周动脉疾病患者的氧化能力

• 批准号: 10303649
• 负责人: Dushyant Kumar
• 金额: $ 8.13万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10303649
• 关键词: 3-Dimensional; Affect; American; Anatomy; Biological Markers; Blood Circulation; Blood flow; Catheters; Cellular Metabolic Process; Chemicals; Clinical; Creatine; Creatine Kinase; Development; Diagnosis; Disease; Distal Muscular Dystrophies; Duchenne muscular dystrophy; Early identification; Evaluation; Exercise; Face; Frequencies; Half-Life; Image; Individual; Intermittent Claudication; Investigation; Kinetics; Length; Limb structure; Lower Extremity; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Maps; Measurable; Measures; Methods; Minority; Mitochondria; Modification; Monitor; Muscle; Muscle Fibers; Myocardial Infarction; Names; Noise; Operative Surgical Procedures; Oxidative Phosphorylation; Pain; Participant; Patients; Perfusion; Peripheral arterial disease; Pharmaceutical Preparations; Phosphocreatine; Phosphorus; Physiological; Protocols documentation; Quality of life; Recovery; Research; Resolution; Respiration; Risk; Scanning; Schedule; Scheme; Series; Signal Transduction; Skeletal Muscle; Stents; Stroke; Supervision; Symptoms; Testing; Therapeutic Intervention; Time; Uncertainty; Validation; Variant; Water; active lifestyle; burden of illness; clinically significant; data space; evidence base; experimental study; functional status; improved; interest; mortality; muscle metabolism; novel; patient subsets; reconstruction; temporal measurement; tool

ABSTRACT An estimated 8.5 million Americans suffer from peripheral artery disease (PAD) and it not only interferes with one’s active lifestyle; but also increases the risks for heart attacks and strokes. Most PAD patients are asymptomatic, present with atypical pain, and a minority face serious consequence of a threatened limb. Once diagnosed with PAD, a range of evidence-based therapeutic and interventional options are available, which includes supervised exercise, antithrombotic medications, and restoring circulation through catheter and surgical interventions are available. These have potentials to improve the functional status of the patient and reduce the mortality. Oxidative phosphorylation (OXPHOS) capacity in skeletal muscle are known to get compromised in PAD and hence, tools (imaging or otherwise) are needed for aiding in the early identification of patients with PAD and to monitor the effect of supervised exercise and revascularization. Phosphorus (31P) magnetic resonance spectroscopy (31PMRS) has traditionally been used as a noninvasive tool to evaluate the OXPHOS capacity and the change in intracellular pH of exercised skeletal muscle. However, it suffers from low coverage, poor spatial resolution and a very high coefficient of variation (COV) (~20-30%) with respect to half-life of phosphocreatine recovery (τPCr). Our team previously developed a novel 2D MRI method, named creatine chemical exchange saturation transfer (CrCEST) imaging, as an alternative with improved spatial resolution (~1x1 mm2) and a temporal resolution (τRes) of ~30s. Recently, we further improved on this method to enable the 3D coverage while maintaining the same τRes of 30s. The estimation of creatine recovery half-time (τCr) on a voxel-wise basis is currently not feasible due to the coarse temporal resolution (30s) combined with the low effective signal to noise ratio (eSNR) (<20) of 3D-CrCEST time-series. Rather, we performed muscle-group-specific fit, where the useful information in form of a voxel-wise inherent anatomic/physiological variation were sacrificed in return for increased SNR. In another important development, we developed a spatial regularized reconstruction approach and showed the feasibility of a noise robust reconstruction, provided τCr ≳4τRes. Given that the typical τCr of healthy control is ~45-80s for our plantar flexion exercise protocol, there is a need to improve on τRes ~10-12s. In this proposal, we aim to improve on the temporal resolution: τRes of CrCEST by implementing keyhole imaging in combination with the alteration in frequency offset (FO) schemes. By aiming to improve τRes by a factor of ~2-3x, the information content present in CrCEST time series would be sufficiently increased to enable a noise robust reconstruction of τCr-map. To reduce the component of variability with physiological origins, we plan to adjust the exercise load to avoid unpredictable and drastic changes in perfusion profile. For the validation, we will compare the findings from the proposed approach against our current 3D CrCEST protocol for comparable region of interest (ROI). Finally, we will test our hypothesis that clinical significant changes in function status of PAD patients post revascularization will be reflected by measurable changes in τCr‘s.

抽象的 估计有850万美国人患有周围动脉疾病（PAD），它不仅干扰 一个人的积极生活方式；但也增加了心脏病发作和中风的风险。大多数PAD患者是 无症状，出现非典型疼痛，而少数人面临着威胁的肢体的严重后果。一次 被诊断为PAD，提供了一系列基于证据的治疗和介入的选择， 包括监督运动，抗血栓药物以及通过导管和外科手术恢复循环 干预措施可用。这些具有改善患者功能状态并减少的潜力 死亡。已知在骨骼肌中的氧化磷酸化（OXPHOS）能力在 垫子，因此，需要工具（成像或其他）来帮助早期识别PAD患者 并监视受监督的运动和血运重建的效果。磷（31p）磁共振 传统上，光谱法（31pmr）被用作评估Oxphos容量和的无创工具 运动骨骼肌细胞内pH的变化。但是，它的覆盖率低，空间差 分辨率和非常高的变化系数（COV）（〜20-30％）相对于磷酸磷酸的半衰期 恢复（τpcr）。我们的团队以前开发了一种新颖的2D MRI方法，名为Creation Chemical Exchange 饱和转移（CRCEST）成像，作为改进空间分辨率（〜1x1 mm2）和A的替代方案 临时分辨率（τRes）约为30s。最近，我们进一步改进了这种方法以实现3D覆盖范围 同时保持相同的30秒。在体素的基础上估算创造恢复半场（τcr）的估计 目前由于粗糙的临时分辨率（30s）与低有效信号相结合，目前不可行 3D-Crcest时间序列的噪声比（ESNR）（<20）。相反，我们执行了肌肉组特异性拟合 为了回报，以体素固有的解剖/生理变异形式形式的有用信息。 SNR增加。在另一个重要的发展中，我们开发了一种空间正规化的重建方法 并显示了噪声稳健重建的可行性，提供了τcr≳4τres。鉴于典型的τcr 对于我们的足底屈曲运动方案，健康的控制是〜45-80，需要改善抽率〜10-12。 在此提案中，我们旨在改善临时分辨率：通过实施钥匙孔的CRCESTτRES 成像与频率偏移（FO）方案的变化结合。通过以一个因素改善τRES 〜2-3x，CRCEST时间序列中存在的信息内容将足够增加以启用噪声 强大的τcr-map重建。为了减少物理起源的变异性成分，我们计划 调整运动负荷，以避免灌注曲线的不可预测和急剧变化。为了验证，我们 将比较拟议方法的发现与我们当前的3D CRCEST协议的发现 感兴趣的地区（ROI）。最后，我们将检验我们的假设，即临床功能状态的显着变化 血运重建后的PAD患者将通过可测量的τcr变化反映。