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.

肾纤维化是损伤的最终途径和重要的生物标志物，常见于衰老和大多数形式的 慢性肾病(CKD)。它主要是通过肾活检来评估的，这是令人望而却步的侵入性和 受到抽样不足的限制。然而，检测肾纤维化的可靠策略尚未确定。 这些概念强调了对可靠的非侵入性工具的需求，以早期发现肾脏损伤， 加强治疗策略的制定和监测。 慢性肾脏病的发病率和死亡率很高，医疗费用也很高，最终可能会- 需要肾脏替代治疗的肾衰竭阶段。然而，肾移植后移植物存活率(KT) 是次优的，而功能恶化和同种异体移植物的丧失往往与间质纤维化有关。 无创监测纤维化程度可以降低成本和相关的潜在并发症 通过反复活检，并帮助指导和优化管理。KT接受者也接受礼仪 活组织检查，可作为参考，并允许评估旨在评估肾脏纤维化的技术。 磁化传递成像(MTI)磁共振成像(MRI)是一种新的非侵入性方法 评估组织的大分子组成。我们已经证明MTI可以评估缺血肾脏。 小鼠和猪的纤维化模型。然而，目前MT-MRI在评估肾纤维化方面的临床应用 有限，因为它本质上是半定量的。相比之下，基于生物物理的定量MT(QMT) 隔室模型提供了更客观的测量组织MT属性的方法。磁流变液的一种模型拟合 使用各种MT脉冲幅度和偏移频率采集的信号，结合特定于扫描的B0/B1/T1 MAP，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 测量组织中的大分子含量(纤维化的一个指标)。 这一建议背后的假设是，QMT可靠地检测到同种异体移植肝纤维化的发展。 KT后的受试者。为了验证这一假设，我们将量子力学导出的结合池分数与 20例活体肾移植术后4~7年肾活检显示肾纤维化。我们还将比较边界 池分数对肾脏血流量、氧合和功能的影响，并将检测QMT的能力提供一致 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： 具体目标1：QMT为人类移植肾的纤维化提供可靠和可靠的评估。 具体目标2：在1.5T和3.0T下，QMT评估人移植肾的肾纤维化是可重复性的。 因此，建议的研究可能会建立一种可靠的、非侵入性的和临床上可行的策略 量化肾脏纤维化，这是肾脏老化、疾病进展和预后的关键生物标志物。