Noninvasive assessment of renal fibrosis using magnetization transfer MRI

使用磁化转移 MRI 无创评估肾纤维化

• 批准号: 9352889
• 负责人: Lilach O Lerman
• 金额: $ 0.57万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-24 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352889
• 关键词: Address; Affect; Angioplasty; Atherosclerosis; Biological Markers; Brain; Characteristics; Chronic Kidney Failure; Cicatrix; Clinical; Clinical Medicine; Collagen; Data; Dependence; Deposition; Deterioration; Development; Diagnostic; Distal; Evolution; Experimental Models; Extracellular Matrix; Failure; Family suidae; Fibrosis; Functional disorder; Health; Human; Hypoxia; Image; Imaging Device; Imaging Techniques; In Situ; Individual; Injury; Intestines; Ischemia; Kidney; Kidney Diseases; Link; Lung; Magnetic Resonance Imaging; Microcirculation; Modeling; Molecular; Monitor; Mus; Organ; Outcome; Pancreas; Pathogenesis; Patients; Process; Recovery; Renal Artery Stenosis; Renal Vascular Disorder; Renal function; Secondary to; Severity of illness; Structure; Techniques; Testing; Tissues; Validation; Weight; Western World; Work; aging population; base; density; detector; hemodynamics; imaging biomarker; indexing; innovation; magnetic field; microCT; nephrogenesis; non-invasive imaging; novel; renal artery; renal ischemia; response; therapeutic target; tool; translational study

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.

描述（由申请人提供）：纤维化是慢性肾脏疾病（CKD）结局的共同特征和重要决定因素。细胞外基质沉积是一种特异的和潜在有用的生物标志物，以识别瘢痕肾。磁化传递成像（MTI）是一种基于分子磁共振成像（MRI）的强大非侵入性技术，能够检测过度的胶原蛋白沉积。因此，MTI对评估个体肾脏可能是非常宝贵的，但其检测肾纤维化的潜力尚未得到充分探讨。 肾血管疾病（RVD）在西方世界的老龄化人群中变得越来越常见，可能会引起肾缺血和纤维化。由于永久性损伤，通过经皮腔内肾血管成形术（PTRA）对狭窄肾动脉进行血运重建通常无法恢复肾功能并阻止CKD的进展。我们已经证明，RVD患者PTRA后肾功能恢复失败与肾内损伤的程度直接相关。遗憾的是，检测肾纤维化和充分预测RVD肾脏结局的特定工具尚未确定，仍然迫切需要。 我们的特点是新的实验模型RVD密切模仿人类病理生理学，并允许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机会，以评估肾功能和结构与纤维化的发展和RVD的结果。该提议的工作假设是MTI可以检测狭窄后鼠和猪肾脏中纤维化的发展，其与随后的肾脏恢复能力相关。为了验证这一假设，我们将使用最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，将在接受PTRA和支架植入术的RVD猪中检测MTI衍生的胶原沉积指数预测肾脏恢复的能力。将追求三个具体目标：具体目标1将测试MTI可以使用高场MRI检测RAS小鼠中肾纤维化的发展的假设。具体目标2将检验MTI可使用临床MRI检测RVD猪肾纤维化发展的假设。第3章测试 假设MTI可以预测PTRA后肾脏恢复潜力。使用MTI无创评估细胞外基质沉积是一种有前途的尖端技术，可能会对肾脏疾病的管理做出重大贡献。拟议的研究可能具有广泛的影响，并建立了RVD和CKD的新的临床可行的诊断策略。