Noninvasive Evaluation of Renal Allograft Fibrosis by MRI

MRI 无创评估同种异体移植肾纤维化

• 批准号: 9976272
• 负责人: Lilach O Lerman
• 金额: $ 22.2万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9976272
• 关键词: Aging; Allografting; Animal Model; Atrophic; Benchmarking; Biological Markers; Biophysics; Biopsy; Blood Pressure; Chronic; Chronic Kidney Failure; Chronic rejection of renal transplant; Cicatrix; Clinical; Complex; Consequentialism; Data; Deposition; Deterioration; Development; Disease Progression; Early Diagnosis; Early identification; End stage renal failure; Evaluation; Evolution; Family suidae; Fibrosis; Frequencies; Graft Survival; Health Care Costs; Health Professional; Human; Image; Imaging Techniques; Injury; Injury to Kidney; Interobserver Variability; Intervention; Kidney; Kidney Transplantation; Light; Living Donors; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Modeling; Monitor; Morbidity - disease rate; Mus; Outcome; Pathogenesis; Pathway interactions; Patient Recruitments; Patients; Perfusion; Physiologic pulse; Property; Proteinuria; Protocols documentation; Relaxation; Renal Blood Flow; Renal Replacement Therapy; Renal function; Reproducibility; Sampling; Sampling Errors; Scanning; Signal Transduction; Spin Labels; Standardization; Techniques; Testing; Therapeutic; Tissues; Transplant Recipients; Trichrome stain; Tubular formation; Western World; aging population; base; clinical application; clinical translation; cost; graft function; hemodynamics; human subject; imaging modality; indexing; instrument; interstitial; kidney allograft; kidney biopsy; kidney fibrosis; living kidney donor; macromolecule; magnetic field; mortality; novel; post-transplant; renal ischemia; success; tool

Renal fibrosis is a final pathway and important biomarker of injury common to aging and to most forms of chronic kidney diseases (CKD). It is assessed primarily by renal biopsy, which is prohibitively invasive and is limited by inadequate sampling. However, reliable strategies to detect renal fibrosis are yet to be identified. These notions underscore the need for reliable noninvasive tools for early detection of kidney injury, to enhance development and monitoring of therapeutic strategies. CKD involves high morbidity and mortality and substantial healthcare cost, and might eventuate in end- stage renal failure requiring renal replacement therapy. However, graft survival after kidney transplantation (KT) is suboptimal, and deterioration in function and loss of allografts are often associated with interstitial fibrosis. Monitoring the extent of fibrosis noninvasively could decrease the cost and potential complications associated with repeated biopsies, and help direct and optimize management. KT recipients also undergo protocol biopsies, which can serve as a reference and allow evaluation of techniques that aim to assess renal fibrosis. 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 ischemic kidney fibrosis in murine and swine models. 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 (an index of fibrosis). The hypothesis underlying this proposal is that qMT reliably detects development of allograft fibrosis in human subjects after KT. To test this hypothesis, we will correlate the qMT-derived bound pool fraction with renal fibrosis as per biopsy in 20 patients 4 or 7 years after living donor KT. We will also compare the bound pool fraction to renal blood flow, oxygenation, and function, and will test the ability of qMT to provide consistent assessments of fibrosis at different magnetic field strengths. Two specific aims will test the hypotheses that: Specific Aim 1: qMT provides reliable and consequential assessment of fibrosis in human kidney allografts. Specific Aim 2: Renal fibrosis assessed by qMT in human kidney allografts is reproducible at 1.5 T and 3.0 T. The proposed studies may therefore establish a reliable, noninvasive, and clinically feasible strategy to quantify kidney fibrosis, a key biomarker for renal aging, disease progression, and outcomes.

肾纤维化是衰老和大多数形式的损伤的最终途径，也是重要的损伤生物标志物 慢性肾脏疾病（CKD）。它主要通过肾脏活检进行评估，该肾脏活检被禁止侵入性并且是 通过不充分的采样限制。但是，可靠检测肾纤维化的策略尚待确定。 这些笔记强调了需要可靠的无创工具来早期发现肾脏损伤的必要性， 增强治疗策略的发展和监测。 CKD涉及高发病率，死亡率和大量医疗保健成本，可能会发生 需要肾脏替代疗法的肾衰竭。但是，肾移植后的移植物生存（KT） 是次优的，功能的定义和同种异体移植的丧失通常与间质纤维化有关。 监测非侵入性的纤维化程度可能会降低相关的成本和潜在并发症 重复活检，并有助于直接和优化管理。 KT收件人也接受协议 活检，可以作为参考并允许评估旨在评估肾纤维化的技术。 磁化转移成像（MTI）磁共振成像（MRI）是一种新型的无创方法 评估组织大分子组成。我们已经证明MTI可以评估缺血性肾脏 鼠和猪模型中的纤维化。但是，MT-MRI评估肾纤维化的临床实用性目前是 有限，因为它本质上是半定量的。相反，基于生物物理的定量MT（QMT） 隔室模型提供了组织MT性能的更客观测量。 MR的模型拟合 用各种MT脉冲放大器和偏移频率获得的信号，结合扫描特异性B0/B1/T1 地图，产生对组织参数的更完整的定义，包括“绑定池分数”，直接 组织中大分子含量的度量（纤维化指数）。 该提议的基本假设是QMT可靠地检测到同种异体移植纤维化的发展 KT之后的人类受试者。为了检验这一假设，我们将将QMT衍生的汇总分数与 活体供体KT后4或7年，在20例患者中进行肾纤维化。我们还将比较绑定 泳池分数到肾脏流动，氧合和功能，并将测试QMT提供一致的能力 评估不同磁场强度下的纤维化。两个具体目标将检验以下假设： 特定目标1：QMT提供了人类肾脏外观中纤维化的可靠和结果评估。 特定目标2：通过QMT在人肾同种异体移植物中评估的肾纤维化可重现为1.5 t和3.0 t。 因此，拟议的研究可能会建立可靠，无创和临床可行的策略 量化肾脏纤维化，这是肾脏衰老，疾病进展和结果的关键生物标志物。