Quantitative magnetization transfer MRI for evaluation of renal fibrosis

肾纤维化是大多数肾脏疾病常见的最终途径和重要的损伤生物标志物。 例如，在肾血管疾病(RVD)中，进行性肾脏纤维化可能会导致肾脏损伤和 高血压。及早发现纤维化和适当的干预可能会延缓肾脏疾病的发展 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。 磁化传递成像(MTI)磁共振成像(MRI)是一种新的非侵入性方法 评估组织的大分子组成。我们已经证明MTI可以评估狭窄的肾脏。 单侧RVD小鼠和猪模型的纤维化。然而，MT-MRI评估肾脏的临床应用价值 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 在生物物理室模型上，提供了更客观的组织MT属性测量。一位模特 用不同的MT脉冲幅度和偏移频率采集的MR信号进行拟合，结合扫描频率 具体的B0/B1/T1图，产生了组织参数的更完整的定义，包括 组分“，直接测量组织中的大分子含量。 支持这一建议的假设是，QMT可以可靠地检测肾纤维化的发展。 RVD受试者均为1.5T和3.0T。为了检验这一假说，这一假说得到了强有力的初步支持 数据，我们将初步开发、优化和验证用于评估猪狭窄后纤维化的QMT 肾脏。我们将把QMT所致的肾纤维化与参考标准以及单肾相关。 血流动力学、功能和氧合，使用尖端多探测器CT(MDCT)和MRI进行量化 技巧。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，我们将进行一项试验性研究，以测试QMT量化肝纤维化的能力。 与肾功能障碍和组织损伤的创新生物标记物相比，人类肾脏狭窄。 三个特定目标将检验假设：特定目标1：在狭窄的猪肾脏进行QMT是可行的， 可靠，在1.5和3.0T下可重复性。特定目标2：QMT预测肾脏恢复潜力 致PTRA。具体目标3：在狭窄的人类肾脏中进行QMT是可行的、可重复性的，并可预测康复。 因此，建议的研究可能会建立一种可靠的、非侵入性的、临床上可行的治疗策略 量化肾脏纤维化，这是肾脏结果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.