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常见的最终途径和重要生物标志物 慢性肾脏疾病（CKD）。它主要通过肾活检来评估，这是一种侵入性很强的方法， 由于取样不充分而受到限制。然而，检测肾纤维化的可靠策略尚未确定。 这些概念强调了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大量的医疗费用，并可能最终导致 需要肾脏替代治疗阶段性肾衰竭。然而，肾移植（KT）后的移植物存活率 是次优的，并且功能的恶化和同种异体移植物的损失通常与间质纤维化有关。 无创监测纤维化程度可以降低成本和相关的潜在并发症 通过反复的活检，并帮助指导和优化管理。KT接受者也接受方案 活检，可以作为参考，并允许评估旨在评估肾纤维化的技术。 磁共振成像（MRI）是一种新的无创性方法， 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 在鼠和猪模型中的纤维化。然而，MT-MRI评估肾纤维化的临床效用目前尚不明确。 有限，因为它本质上是半定量的。相比之下，基于生物物理学的定量MT（qMT） 隔室模型提供了组织MT性质的更客观的测量。MR的模型拟合 用各种MT脉冲幅度和偏移频率采集的信号，结合扫描特定的B 0/B1/T1 图，产生了组织参数的更完整的定义，包括“结合池分数”，直接 测量组织中的大分子含量（纤维化的指标）。 这一建议的基础假设是，qMT可靠地检测同种异体移植物纤维化的发展， 人类受试者接受KT后。为了检验这一假设，我们将qMT衍生的结合池分数与 活体供肾移植后4或7年，20例患者活检显示肾纤维化。我们还将比较 合并分数对肾血流量、氧合和功能的影响，并将测试qMT提供一致性的能力， 不同磁场强度下纤维化的评估。两个具体目标将检验以下假设： 具体目标1：qMT提供了可靠的和后续的评估人肾移植物中的纤维化。 特定目的2：在1.5 T和3.0 T下，通过qMT评估的人肾移植物中的肾纤维化具有重现性。 因此，拟议的研究可能会建立一个可靠的，非侵入性的，临床可行的策略， 量化肾脏纤维化，这是肾脏衰老、疾病进展和结局的关键生物标志物。