Noninvasive Evaluation of Renal Allograft Fibrosis by MRI

MRI 无创评估同种异体移植肾纤维化

基本信息

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
项目类别：
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

项目摘要

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常见的最终途径和重要生物标志物慢性肾脏病 (CKD) 主要通过肾活检进行评估，这种方法具有极高的侵入性，且具有一定的侵入性。然而，检测肾纤维化的可靠策略尚未确定。这些概念强调需要可靠的非侵入性工具来早期检测肾损伤，加强治疗策略的制定和监测。 CKD 涉及高发病率和死亡率以及巨额医疗费用，并可能最终导致：需要肾脏替代治疗的阶段肾衰竭然而，肾移植（KT）后移植物存活。不是最理想的，功能恶化和同种异体移植物的损失通常与间质纤维化有关。无创监测纤维化的程度可以降低成本和潜在的相关并发症重复活检，并帮助指导和优化 KT 接受者也接受治疗方案。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) 是一种新颖的非侵入性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。然而，目前 MT-MRI 评估肾纤维化的临床应用尚不明确。有限，因为它本质上是半定量的，相反，定量 MT (qMT) 基于生物物理学。隔室模型，提供组织 MT 特性的更客观测量。 MR 模型拟合。使用各种 MT 脉冲幅度和偏移频率采集的信号，并结合扫描特定的 B0/B1/T1 地图，产生了组织参数的更完整的定义，包括“结合池分数”，一个直接的组织中大分子含量的测量（纤维化指数）。该提议的假设是 qMT 能够可靠地检测同种异体移植物纤维化的发展为了检验这一假设，我们将 qMT 衍生的结合池分数与活体供体 KT 后 4 或 7 年，根据活检结果显示肾纤维化情况。血流、氧合和肾功能的池分数，并将测试 qMT 提供一致的能力在不同磁场强度下评估纤维化将检验以下假设：具体目标 1：qMT 为人肾同种异体移植物的纤维化提供可靠且相应的评估。具体目标 2：通过 qMT 评估人肾同种异体移植物中的肾纤维化在 1.5 T 和 3.0 T 下可重复。因此，拟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。