Characterization of Renal Allograft Fibrosis and Prediction of Outcome Using a Quantitative MRI Approach

使用定量 MRI 方法表征同种异体肾纤维化并预测结果

• 批准号: 10279690
• 负责人: Octavia Bane
• 金额: $ 62.59万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-08 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10279690
• 关键词: Acute; Affect; Allografting; Area; Atrophic; Biological Markers; Biopsy; Blood Vessels; Caring; Cells; Chronic; Chronic Kidney Failure; Classification; Clinical; Collagen; Data; Detection; Development; Diagnosis; Diagnostic; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Disease Progression; Early Diagnosis; Edema; End stage renal failure; Endothelium; Epithelial Cells; Etiology; Failure; Fibrosis; Functional disorder; Goals; Histopathology; Immune; Immunosuppression; Infection; Infiltration; Inflammation; Injury; Injury to Kidney; Kidney; Kidney Transplantation; Lesion; Living Donors; Longitudinal Studies; Machine Learning; Magnetic Resonance Imaging; Measurement; Measures; Methods; Modeling; Modernization; Monitor; Motion; Nature; Outcome; Pathology; Pathway interactions; Patient Monitoring; Patient-Focused Outcomes; Patients; Performance; Perfusion; Phenotype; Physiological; Prevalence; Process; Proteinuria; Protocols documentation; RNA; Reference Standards; Relaxation; Reproducibility; Risk; Sampling Errors; Severities; Staging; Statistical Methods; Statistical Models; Structure; Techniques; Testing; Time; Tissue Sample; Tissues; Transplant Recipients; Treatment Efficacy; Tubular formation; United States; Validation; Water; base; clinical encounter; clinically significant; cohort; comparative; diffusion weighted; experience; feature selection; improved; insight; inter-individual variation; interstitial; kidney allograft; kidney biopsy; kidney dysfunction; macromolecule; model building; mortality; novel; novel therapeutics; outcome prediction; patient population; post-transplant; predict clinical outcome; prognostic; renal damage; secondary outcome; statistical and machine learning; treatment choice; treatment optimization; treatment planning; urinary; virtual

Project Summary Renal transplantation is the treatment of choice for patients with end stage renal disease. However, improvements in long-term allograft survival have not matched the observed improvements in the management of rejection. Progressive allograft dysfunction is frequently encountered clinically. The final common pathway of cumulative and incremental renal damage from several etiologies identified by histopathology is interstitial fibrosis/tubular atrophy (IFTA), which is associated with progression of renal dysfunction and reduced allograft survival. Histopathologic assessment and staging of IFTA requires tissue sampling, which is limited due to its invasive nature, risk of complications, inter-individual variability and sampling error. In this proposal, we will test a non-contrast advanced multiparametric MRI (mpMRI) protocol comprised of advanced relaxometry (T1 mapping and T1) and advanced diffusion weighted imaging (IVIM-DWI) as noninvasive markers of renal allograft fibrosis. This is motivated by our preliminary data demonstrating that mpMRI yields highly repeatable parameter measurements that capture allograft fibrosis. Our preliminary experience correlating mpMRI with IFTA is valuable, as confounding physiologic and pathophysiologic variables such as vascular flow, edema and other Banff phenotypes commonly co-exist. The multiparametric approach allows us to simultaneously capture and characterize these concurrent physiologic and pathophysiologic processes. As a secondary objective, we will assess the value of urinary RNA level based biomarkers, which have been previously validated for the diagnosis of IFTA. In this proposal, we aim to: 1) acquire data in patients undergoing indication and surveillance biopsy, using a non-contrast mpMRI protocol comprised of advanced diffusion weighted and relaxometry methods in order to accurately detect and stage allograft IFTA, and 2) other histopathological Banff measures of inflammation. We will build and validate diagnostic models using advanced statistical methods including machine learning in independent model-building and validation sets of renal transplant patients for detection and staging of each Banff measure, and assess the added value of urinary biomarkers of fibrosis. 3) We will evaluate the performance of mpMRI and urinary biomarkers to predict renal outcomes in a longitudinal study for the entire patient cohort up to 24 months. Our long-term objective is to validate a robust quantitative advanced mpMRI approach and develop models that accurately and non-invasively measure renal allograft fibrosis and clinical outcome, which may potentially impact the care of renal transplant patients by enabling early detection, the non-invasive longitudinal monitoring of disease, therapeutic efficacy of new drugs and for prognostication.

项目摘要 肾移植是终末期肾病患者的首选治疗方法。然而，在这方面， 长期同种异体移植物生存率的改善与观察到的管理改善并不匹配 被拒绝进行性同种异体移植物功能障碍是临床上常见的。最后的共同途径 由组织病理学确定的几种病因引起的累积性和递增性肾损伤是间质性的 纤维化/肾小管萎缩（IFTA），这与肾功能不全的进展和同种异体移植物减少有关 生存IFTA的组织学评估和分期需要组织取样，这是有限的，由于其 侵入性、并发症风险、个体间变异性和抽样误差。 在本提案中，我们将测试一种非造影高级多参数MRI（mpMRI）方案，该方案包括： 高级弛豫测量（T1标测和T1）和高级扩散加权成像（IVIM-DWI）， 肾移植纤维化的非侵入性标志物。我们的初步数据表明， mpMRI产生捕获同种异体移植物纤维化的高度可重复的参数测量。我们的初步 将mpMRI与IFTA相关联的经验是有价值的，因为混淆了生理和病理生理 诸如血管流动、水肿和其它Banff表型的变量通常共存。多参数 这种方法使我们能够同时捕捉和表征这些并发的生理和 病理生理过程。作为次要目的，我们将评估尿RNA水平的价值， 生物标志物，其先前已被验证用于IFTA的诊断。 在本提案中，我们的目标是：1）使用 非对比mpMRI方案包括先进的弥散加权和弛豫方法， 准确检测和分期同种异体移植物IFTA，和2）炎症的其他组织病理学Banff测量。我们 将使用包括机器学习在内的先进统计方法建立和验证诊断模型， 肾移植患者的独立模型构建和验证集，用于检测和分期每个 Banff测量，并评估尿纤维化生物标志物的附加值。3)我们将评估 在一项纵向研究中，mpMRI和尿液生物标志物在预测整个 患者队列长达24个月。 我们的长期目标是验证一个强大的定量先进的mpMRI方法，并开发模型 准确和非侵入性地测量肾移植物纤维化和临床结果，这可能 影响肾移植患者的护理，使早期发现，非侵入性纵向 疾病监测、新药疗效监测和新药临床试验。