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肾损伤的最终途径和重要的生物标志物