Noninvasive assessment of renal fibrosis using magnetization transfer MRI

描述（由申请人提供）：纤维化是慢性肾脏疾病（CKD）的共同特征和预后的重要决定因素。细胞外基质沉积是一种特异性的、潜在有用的识别瘢痕肾的生物标志物。磁化转移成像（MTI）是一种基于分子磁共振成像（MRI）的强大的无创技术，能够检测到过多的胶原沉积。因此，MTI在评估单个肾脏方面可能是非常宝贵的，但其检测肾脏纤维化的潜力尚未得到充分探索。肾血管疾病（RVD）在西方老龄化人群中越来越普遍，可引起肾脏缺血和纤维化。由于永久性损伤，经皮腔内肾血管成形术（PTRA）对狭窄肾动脉的血运重建往往不能恢复肾功能和阻止CKD的进展。我们的研究表明，RVD PTRA术后肾功能恢复失败与肾内损伤程度直接相关。遗憾的是，检测肾纤维化和充分预测RVD肾脏预后的特定工具尚未确定，并且仍然迫切需要。我们描述了新的RVD实验模型，这些模型非常接近模拟人类病理生理，并允许与临床医学相关的转化研究。我们还开发和完善了独特的成像技术，非常适合探测肾脏适应性过程。这些工具现在提供了一个评估与纤维化发展和RVD预后相关的肾功能和结构的机会。该建议的工作假设是，MTI可以检测狭窄后小鼠和猪肾脏纤维化的发展，这与随后的肾脏恢复能力相关。为了验证这一假设，我们将使用先进的无创成像技术研究狭窄性肾纤维化、功能障碍和缺氧的发生和进展。此外，mti衍生的胶原沉积指数预测肾恢复的能力将在接受PTRA和支架置入的RVD猪中进行测试。具体目标1将验证MTI可以使用高场MRI检测RAS小鼠肾纤维化发展的假设。特异性目的2将验证MTI可以通过RVD猪的临床MRI检测肾纤维化的发展的假设。具体目标3将测试

DESCRIPTION (provided by applicant): Fibrosis is a common denominator and an important determinant of outcomes in chronic kidney disease (CKD). Extracellular matrix deposition is a specific and potentially useful biomarker to identify scarred kidneys. Magnetization transfer imaging (MTI) is a powerful noninvasive technique based on molecular magnetic resonance imaging (MRI), which is capable of detecting excessive collagen deposition. Therefore, MTI could be invaluable to assess individual kidneys, yet its potential to detect renal fibrosis has no been fully explored. Renal vascular disease (RVD), which is becoming increasingly common in the aging population of the Western world, may induce kidney ischemia and fibrosis. As a result of permanent injury, revascularization of the stenotic renal artery by percutaneous transluminal renal angioplasty (PTRA) often fails to restore kidney function and arrest progression of CKD. We have shown that failure to restore renal function after PTRA in RVD is directly linked with the extent of intra-renal injury. Alas, specific tools to detect renal fibrosis and adequately predct renal outcomes in RVD are yet to be identified and remain in dire need. We have characterized novel experimental models of RVD that closely mimic human pathophysiology and allow translational studies relevant to clinical medicine. We have also developed and refined unique imaging techniques ideally suited for probing renal adaptive processes. These tools now provide an opportunity to assess renal function and structure associated with development of fibrosis and outcomes in RVD. The working hypothesis underlying this proposal is that MTI can detect in the post-stenotic murine and swine kidneys development of fibrosis, which correlates with subsequent kidney recovery capacity. To test this hypothesis, we will study development and progression of stenotic kidney fibrosis, dysfunction, and hypoxia using cutting-edge noninvasive imaging. Furthermore, the ability of MTI-derived indices of collagen deposition to predict renal recovery will be tested in RVD pigs undergoing PTRA and stenting. Three specific aims will be pursued: Specific Aim 1 will test the hypothesis that MTI can detect development of kidney fibrosis in RAS mice using high-field MRI. Specific Aim 2 will test the hypothesis that MTI can detect development of renal fibrosis using a clinical MRI in RVD pigs. Specific Aim 3 will test the hypothesis that MTI would predict renal recovery potential in response to PTRA. Noninvasive assessment of extracellular matrix deposition using MTI is a promising, cutting edge technique, which will likely contribute significantly towards management of kidney disease. The proposed studies may have broad ramifications and establish this novel, clinically feasible diagnostic strategy for RVD and CKD.