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)的一个公分母和一个重要的预后决定因素。细胞外基质沉积是识别瘢痕肾脏的一种特异且潜在有用的生物标志物。磁化传递成像(MTI)是基于分子磁共振成像(MRI)的一种强大的非侵入性技术，能够检测胶原过度沉积。因此，MTI对评估单个肾脏可能是非常有价值的，但其检测肾脏纤维化的潜力尚未被充分开发。肾血管疾病(RVD)在西方老龄化人口中越来越常见，可导致肾脏缺血和纤维化。由于永久性损伤，经皮腔内肾血管成形术(PTRA)重建狭窄的肾动脉往往不能恢复肾功能，阻止CKD的进展。我们已经证明，RVD患者PTRA术后肾功能恢复的失败与肾内损伤的程度直接相关。遗憾的是，检测肾脏纤维化和充分预测RVD肾脏结局的特定工具尚未确定，仍然迫切需要。我们已经确定了新的RVD实验模型的特征，这些模型紧密模拟人类的病理生理学，并允许与临床医学相关的转化性研究。我们还开发和改进了独特的成像技术，非常适合探测肾脏适应性过程。这些工具现在提供了一个机会来评估与纤维化发展和RVD结果相关的肾功能和结构。这一建议的工作假设是，MTI可以在狭窄后的小鼠和猪肾脏中检测到纤维化的发展，这与随后的肾脏恢复能力相关。为了验证这一假设，我们将使用尖端的非侵入性成像技术研究狭窄肾纤维化、功能障碍和缺氧的发展和进展。此外，MTI衍生的胶原沉积指数预测肾脏恢复的能力将在接受PTRA和支架置入术的RVD猪身上进行测试。将追求三个具体目标：特定目标1将验证MTI可以使用高场MRI检测RAS小鼠肾脏纤维化发展的假设。特定目标2将验证MTI可以使用临床MRI检测RVD猪肾脏纤维化发展的假设。《特定目标3》将测试 假设MTI将预测PTRA反应中的肾脏恢复潜力。使用MTI对细胞外基质沉积进行无创性评估是一种很有前途的尖端技术，它可能会对肾脏疾病的治疗做出重大贡献。拟议的研究可能会有广泛的影响，并建立这一新的、临床上可行的RVD和CKD诊断策略。

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.