Monitoring Oxidative Capacity in Peripheral Artery Disease Patients using MR Imaging

摘要 据估计，有850万美国人患有外周动脉疾病(PAD)，它不仅干扰 一个人积极的生活方式；但也增加了心脏病发作和中风的风险。大多数PAD患者 无症状，伴有非典型疼痛，少数患者面临肢体威胁的严重后果。一次 诊断为PAD，有一系列循证治疗和干预选择可用，其中 包括有监督的锻炼、抗血栓药物以及通过导管和外科手术恢复循环 干预措施是可用的。这些都有可能改善患者的功能状态，减少 死亡率。骨骼肌中氧化磷酸化(OXPHOS)的能力已知受到损害 因此，需要工具(成像或其他)来辅助PAD患者的早期识别 并监测有监督的运动和血运重建的效果。磷(31P)磁共振 光谱学(31PMRS)传统上被用作评估OXPHOS容量和 运动后骨骼肌细胞内pH的变化。然而，它存在覆盖率低、空间差的问题。 相对于磷酸肌酸的半衰期，分辨率和极高的变异系数(COV)(~20-30%) 回收(τ聚合酶链式反应)。我们的团队之前开发了一种新的2D MRI方法，名为肌酸化学交换 饱和转移(CrCEST)成像，作为一种替代方案，具有更高的空间分辨率(~1x1 mm2)和 时间分辨率(τRes)为~30s。最近，我们对这种方法进行了进一步的改进，以实现3D覆盖 同时保持30秒的相同τ分辨率。体素基础上肌酸恢复半衰期(τ-Cr)的估算 由于粗的时间分辨率(30s)与低有效信号相结合，目前是不可行的 3D-CrCEST时间序列的噪声比(ESNR)(&lt；20)。相反，我们进行了特定肌肉组的匹配，其中 以体素形式的固有解剖/生理变异形式的有用信息被牺牲以换取 提高了信噪比。在另一个重要的发展中，我们发展了一种空间正则化重建方法。 并展示了噪声稳健重建的可行性，提供了τCr≳4τRes.给定典型的τCr 对于我们的足底屈曲锻炼方案，健康对照为~45-80s，需要改进τRES~10-12s。 在该方案中，我们的目标是通过实现小孔来提高CRCEST的时间分辨率：τRES 成像与频率偏移(FO)方案的改变相结合。通过将τRES提高一个因素来实现 在~2-3倍的范围内，出现在CrCEST时间序列中的信息量将充分增加，从而能够产生噪声 τ铬-MAP的稳健重建。为了减少生理来源的可变性成分，我们计划 调整运动负荷，以避免血流灌注曲线发生不可预测和剧烈的变化。对于验证，我们 我将把提出的方法的结果与我们当前的3D CrCEST协议进行比较，以进行类似的 感兴趣区域(ROI)。最后，我们将检验我们的假设，临床上显著改变的功能状态 血管重建术后的PAD患者将通过τ-Cr的可测量变化来反映。

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.