Validation of Myocardial Oxygen Extraction Fraction Measurement with MRI

心肌氧供需失衡导致一系列生理变化 导致局部缺血病理学。虽然单独评估心肌灌注可以准确 在某些病理生理条件下评估心肌耗氧量，灌注氧 消费关系在几种情况下脱轨，包括：心肌缺血和梗塞， 肥厚性和扩张性心肌病、心力衰竭、瓣膜性心脏病和脓毒性心肌病。 重要的是，这种氧供应/灌注不匹配发生在早期-在机械功能障碍之前。因此，我们认为， 独立于灌注的心肌消耗的评估对于早期诊断是重要的， 监测这些病理生理条件。心肌氧摄取分数（mOEF），与 心肌血流（氧供应）与氧消耗的生物耦合可以提供更多的 准确评估这种平衡。例如，在缺血性心肌病中， 心外膜冠状动脉狭窄程度高通常会降低。为了避免缺血引起的损伤，mOEF 可能增加以补偿心肌灌注和向肌细胞输送氧的减少。 因此，受影响的心肌区域进入所谓的“冬眠”状态，这在心肌缺血时是有效的。 短期内在这方面，准确的mOEF评估是一种独特的工具，有可能确定 再灌注后心脏功能恢复的可能性。到目前为止，非侵入性的参考方法 体内mOEF的定量是正电子发射断层扫描（PET）。我们最近发明了一种新的对比- 自由心血管磁共振（CMR）采集方法，用于量化体内mOEF， 与PET相比的优势：我们的CMR方法具有更好的空间分辨率，更短的采集时间， 患者接受电离辐射，并且可能比PET更广泛地使用。本报告的总体目标 研究的目的是利用我们在CMR成像方面的专业知识来完善和严格验证这种新的mOEF方法。在 目标1.这项技术将在一种新的深度学习方法的帮助下开发， 图像，然后使用具有和不具有诱导的冠状动脉疾病的大型动物模型进行验证。侵入性 导管测量的和无创PET-MRI测量的mOEF将用作参考。在目标2中， mOEF方法将在体内冬眠心肌患者的小队列中进行验证， 18F-FDG-PET作为参考的可用性。虽然我们将在冬眠心肌中研究这种mOEF技术， 这种成像方法可以应用于诊断和评价治疗的范围很广， 心肌病鉴于CMR能够全面评估心肌功能， 表征和可行性，CMR mOEF验证的成功完成将提供“一站式服务” 评价心肌病患者的代谢、功能和结构异常。此外，委员会认为， 不使用静脉内造影剂快速成像的优点非常适合于重复定量 mOEF测量需要指导新的治疗干预策略的效果。

Imbalance of myocardial oxygen supply and consumption precipitates a cascade of physiological changes resulting in ischemic pathology. While assessment of myocardial perfusion alone may allow accurate assessment of myocardial oxygen consumption in some pathophysiological conditions, the perfusion-oxygen consumption relationship is derailed in several conditions, including: myocardial ischemia and infarction, hypertrophic and dilated cardiomyopathies, heart failure, valvular heart disease, and septic cardiomyopathy. Importantly, this oxygen supply/perfusion mismatch occurs early – before mechanical dysfunction. Therefore, evaluation of myocardial consumption independent of perfusion is of importance for early diagnosis and monitoring of these pathophysiological conditions. Myocardial oxygen extraction fraction (mOEF), which relates the biologic coupling of myocardial blood flow (oxygen supply) to oxygen consumption, may provide a more accurate assessment of this balance. For example, in ischemic cardiomyopathy, adequate myocardial perfusion is commonly reduced by high grade epicardial coronary artery stenoses. To avoid ischemia-caused injury, mOEF is likely to be increased to compensate for decrease in myocardial perfusion and oxygen delivery to myocytes. Consequently, the affected myocardial regions drop into a so called “hibernating” state that is effective in the short term. In this respect, an accurate mOEF assessment is a unique tool, with the potential to determine the likelihood of cardiac functional recovery after reperfusion. To date, the reference method for non-invasive quantification of mOEF in vivo is Positron Emission Tomography (PET). We recently developed a novel contrast- free cardiovascular magnetic resonance (CMR) acquisition method to quantify mOEF in vivo that has several advantages over PET: our CMR method has better spatial resolution, shorter acquisition time, does not expose the patient to ionizing radiation, and could be more widely available than PET. The overall objective of this study is to leverage our expertise in CMR imaging to refine and rigorously validate this new mOEF method. In Aim 1. This technique will be developed with assistance of a novel deep learning approach for artifact-free images and then validated using large animal models with and without induced coronary artery disease. Invasive catheter-measured and non-invasive PET-MRI-measured mOEF will be used as reference. In Aim 2, the CMR mOEF method will be validated in a small cohort of patients with hibernating myocardium in vivo, with the availability of 18F-FDG-PET as reference. Although we will study this mOEF technique in hibernating myocardium, this imaging method can be applied to the diagnosis and evaluation of treatments in a wide range of cardiomyopathies. Given the capability of CMR for the comprehensive assessment of myocardial function, tissue characterization, and viability, successful completion of CMR mOEF validation will provide a ‘one-stop shop’ evaluation of metabolic, functional, and structural abnormalities in patients with cardiomyopathy. Furthermore, the advantage of fast imaging without using an intravenous contrast agent is well-suited for repeat quantitative mOEF measurements needed to guide the effects of novel therapeutic interventional strategies.