Quantitative magnetization transfer MRI for evaluation of renal fibrosis

肾纤维化是大多数肾脏疾病常见的损伤的最终途径和重要生物标志物。 例如，在肾血管疾病（RVD）中，进行性肾纤维化可诱导肾损伤， 高血压早期发现纤维化和适当的干预可能会减缓肾脏疾病 进展，但足够的非侵入性策略，以检测和量化肾纤维化尚未确定。 磁共振成像（MRI）是一种新的无创性方法， 评估组织大分子组成。我们已经证明MTI可以评估狭窄的肾脏 在单侧RVD的鼠和猪模型中的纤维化。然而，MT-MRI评估肾功能的临床实用性 纤维化目前是有限的，因为它本质上是半定量的。相比之下，定量MT（qMT），基于 生物物理室模型，提供了更客观的测量组织MT属性。模型 用各种MT脉冲幅度和偏移频率采集的MR信号的拟合，结合扫描， 特异性B 0/B1/T1图，产生组织参数的更完整定义，包括“结合池 分数”是组织中大分子含量的直接量度。 这一建议的基础假设是，qMT将可靠地检测肾纤维化的发展 在1.5T和3.0T下，RVD受试者中。为了验证这一假设，这是支持强初步 数据，我们将首先开发、优化和验证qMT，用于评价狭窄后猪的纤维化 肾我们将qMT衍生的肾纤维化与参考标准以及单肾 使用尖端多探测器CT（MDCT）和MRI量化的血流动力学、功能和氧合 技术.然后，我们将确定qMT预测RVD猪肾脏恢复的能力， 血运重建此外，我们将进行一项试点研究，以测试qMT量化术后纤维化的能力。 狭窄的人类肾脏，与肾功能障碍和组织损伤的创新生物标志物相比。 三个具体目标将检验假设：具体目标1：狭窄猪肾中qMT是可行的， 在1.5和3.0 T下具有可靠性和重现性。具体目标2：qMT预测肾脏恢复潜力 到PTRA。具体目标3：qMT在狭窄的人肾脏中是可行的、可重复的，并可预测恢复。 因此，拟议的研究可能会建立一个可靠的，非侵入性的，临床可行的策略， 量化肾脏纤维化，这是肾脏结局和治疗成功的关键生物标志物。

Renal fibrosis is a final pathway and important biomarker of injury common to most forms of kidney disease. For example, in renal vascular disease (RVD) progressive renal fibrosis may induce kidney injury and hypertension. Early identification of fibrosis and adequate intervention may slow down renal disease progression, but adequate noninvasive strategies to detect and quantify renal fibrosis are yet to be identified. Magnetization transfer imaging (MTI) magnetic resonance imaging (MRI) is a novel noninvasive method to evaluate the tissue macromolecular composition. We have demonstrated that MTI can assess stenotic kidney fibrosis in murine and swine models of unilateral RVD. However, the clinical utility of MT-MRI to assess renal fibrosis is currently limited, because it is inherently semi-quantitative. In contrast, quantitative MT (qMT), based on biophysical compartment models, provides more objective measurement of tissue MT properties. A model fitting of MR signal acquired with various MT pulse amplitudes and offset frequencies, combined with scan- specific B0/B1/T1 maps, give rise to a more complete definition of tissue parameters, including a “bound pool fraction”, a direct measure of the macromolecular content in tissue. The hypothesis underlying this proposal is that qMT would reliably detect development of renal fibrosis at both 1.5T and 3.0T in subjects with RVD. To test this hypothesis, which is supported by strong preliminary data, we will initially develop, optimize, and validate qMT for evaluation of fibrosis in the post-stenotic swine kidney. We will correlate qMT-derived renal fibrosis with reference standards, as well as with single-kidney hemodynamics, function, and oxygenation, quantified using cutting-edge multi-detector CT (MDCT) and MRI techniques. We will then determine the ability of qMT to predict renal recovery in pigs with RVD undergoing revascularization. Further, we will perform a pilot study to test the ability of qMT to quantify fibrosis in the post- stenotic human kidney, in comparison to innovative biomarkers of renal dysfunction and tissue damage. Three specific aims will test the hypotheses: Specific Aim 1: qMT in stenotic swine kidneys is feasible, reliable, and reproducible at 1.5 and 3.0 T. Specific Aim 2: qMT predicts renal recovery potential in response to PTRA. Specific Aim 3: qMT in stenotic human kidneys is feasible, reproducible, and predicts recovery. The proposed studies may therefore establish a reliable, noninvasive, and clinically feasible strategy to quantify kidney fibrosis, a key biomarker for renal outcomes and therapeutic success.