Quantitative renal oxygenation assessment with compartment specific calibration

描述（由申请方提供）：肾缺氧在几种疾病的病理生理学中起关键作用，并与急性肾损伤以及慢性肾脏疾病的发生和进展有关。非侵入性评估肾缺氧的能力可以是用于早期评估受试者的肾健康和启动靶向治疗的重要工具，所述靶向治疗可以减缓疾病进展、减少肾小球滤过率降低的并发症并改善生活质量。基于血氧水平依赖性（BOLD）对比机制的MRI序列已用于跟踪肾氧合变化。然而，最近的研究表明，这些测量是敏感的其他混杂因素，除了氧合。仍然需要可靠的、定量的和非侵入性的肾氧合测量。在本提案中，我们将研究使用R2'作为BOLD MRI参数，并通过侵入性磷光法对血液和组织氧的独立测量进行验证。此外，我们将探索分析BOLD MRI参数图的替代方法，以最大限度地减少主观性，从而允许在实验室之间比较数据。我们的总体假设是，可以直接探测肾氧合的方法，不受混杂因素的影响，沿着对参数图的客观分析，将在临床前和临床环境中提供这些测量的广泛实用性。

DESCRIPTION (provided by applicant): Renal hypoxia plays a key role in the pathophysiology of several diseases and has been implicated in acute kidney injury and in the initiation and progression of chronic kidney disease. The ability to non-invasively assess renal hypoxia can be an important tool for assessing a subject's renal health early and initiating targeted treatment that can slow disease progression, reduce complications of the decreased glomerular filtration rate and improve quality of life. MRI sequences based on the blood oxygen level-dependent (BOLD) contrast mechanism have been used for following changes in renal oxygenation. However, recent studies have shown that these measurements are sensitive to other confounding factors in addition to oxygenation. There still exists a need for a reliable, quantitative and non-invasive measure of renal oxygenation. In this proposal, we will investigate the use of R2' as a BOLD MRI parameter and validate it against independent measures of blood and tissue oxygen by invasive phosphorimetry. Furthermore, we will explore alternative methods for analyzing BOLD MRI parametric maps to minimize subjectivity and hence allow for comparing data across laboratories. Our overall hypothesis is that methods that can directly probe renal oxygenation, without influences from confounding factors, along with an objective analysis of the parametric maps, will provide for widespread utility of these measurements both in pre-clinical and clinical settings.