Quantification of Renal Perfusion, Diffusion and Hypoxia Using Advanced MRI Methods for Assessment of Renal Transplant Dysfunction

使用先进 MRI 方法量化肾灌注、弥散和缺氧以评估肾移植功能障碍

• 批准号: 9414913
• 负责人: Octavia Bane
• 金额: $ 6.3万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9414913
• 关键词: Acute; Acute Kidney Tubular Necrosis; Algorithms; Allografting; Anatomy; Biological Availability; Biological Markers; Biopsy; Blood Vessels; Chronic; Chronic Kidney Failure; Clinical; Consumption; Contrast Media; Data; Data Quality; Diagnosis; Dialysis procedure; Differential Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dose; Drug toxicity; Etiology; Functional Magnetic Resonance Imaging; Functional disorder; Gadolinium; Hypoxia; Image; Imaging Techniques; Kidney; Kidney Diseases; Kidney Transplantation; Laboratories; Life; Location; Magnetic Resonance Imaging; Measurable; Measures; Modeling; Morphology; Motion; Nature; Oxygen; Pathology; Patients; Perfusion; Perfusion Weighted MRI; Physiological Processes; Protocols documentation; Quality Control; Quality of life; Relaxation; Renal Plasma Flow; Renal function; Renal tubule structure; Reproducibility; Sampling; Spin Labels; Symptoms; Techniques; Testing; Therapeutic; Time; Tissue Sample; Transplant Recipients; Water; base; blood oxygen level dependent; contrast enhanced; experience; imaging approach; imaging modality; improved; insight; kidney allograft; noninvasive diagnosis; treatment choice; validation studies; virtual biopsy

Following renal transplantation, about 30-40% of patients suffer at least one episode of acute graft dysfunction. Treatment is radically different depending on the cause of renal dysfunction, which may include acute tubular necrosis (ATN), acute and chronic rejection (AR/CR) and drug toxicity. The definitive diagnosis of renal transplant dysfunction is based on percutaneous biopsy, which is invasive and difficult to repeat. Magnetic resonance imaging (MRI) provides an accurate assessment of allograft anatomy, as well as of vascular or obstructive disorders. In addition, functional MRI can provide insight into renal function using dynamic contrast-enhanced MRI (DCE-MRI, using low dose gadolinium contrast agent, which estimates renal perfusion and flow), intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI, which provides information on flow and diffusion), arterial spin labeling (ASL, which quantifies renal flow without a contrast agent), and blood oxygen level dependent imaging (BOLD, which reflects oxygen bioavailability). Although functional MRI is non-invasive, it has not yet emerged as a “virtual biopsy” because of the small number of validation studies, each generally focusing on a single MRI technique. Multiparametric MRI has the unique potential to identify intrinsic causes of renal transplant dysfunction. Specific Aim 1: Develop a quality control (QC) framework to evaluate a quantitative multiparametric MRI protocol including IVIM diffusion, DCE-MRI perfusion, ASL, and BOLD in renal transplant patients. Hypothesis: a QC framework will improve data quality and reproducibility of MRI metrics measured in renal allografts. We will build a QC and image optimization algorithm for renal functional MRI, and we will test it in 16 patients with renal transplant. Specific Aim 2: Quantify MRI parameters in renal transplant patients with normal and abnormal renal function, and assess the value of MRI parameters alone and in combination for characterizing renal dysfunction using clinical parameters and/or pathology as the reference. Hypothesis: Renal graft dysfunction can be diagnosed and characterized by a combination of biomarkers measurable by functional MRI. Renal diffusion and perfusion, as measured by IVIM parameters, renal plasma flow (RPF) measured by DCE and ASL, medullar and medullar-to-cortical ratio of the transverse relaxation time R2* (as measured by BOLD techniques) will decrease, while mean transit time (MTT) of the contrast agent through the renal tubules as measured by DCE-MRI, will increase in dysfunctional allografts compared to normally functional allografts. Furthermore, dysfunctional allografts with ATN can be distinguished from those without ATN by longer mean transit time in the renal tubules, as computed by the three-compartment model from DCE-MRI data, and by a higher ratio of medullar to cortical R2*. We will test this hypothesis in 97 renal transplant recipients with functional and dysfunctional allografts, as clinically indicated by laboratory tests and biopsy.

肾移植后，大约30-40%的患者至少发生一次急性移植物。 功能障碍。根据肾功能障碍的原因，治疗方法有很大的不同，可能包括 急性肾小管坏死(ATN)、急、慢性排斥反应(AR/CR)和药物毒性。该病的明确诊断 肾移植功能障碍的基础是经皮活检，这是侵入性的，很难重复。 磁共振成像(MRI)提供了对同种异体移植物解剖的准确评估，以及 血管或梗阻性疾病。此外，功能磁共振成像可以提供对肾功能的洞察 动态增强MRI(DCE-MRI)，使用低剂量的Gd造影剂，用于评估肾脏 灌注和血流)，体素内非相干运动扩散加权成像(IVIM-DWI)，它提供 关于血流和扩散的信息)，动脉自旋标记(ASL)，它在没有造影剂的情况下量化肾血流 和血氧水平依赖成像(BOLD，反映氧气的生物利用度)。虽然 功能磁共振是非侵入性的，但由于数量较少，它还没有成为一种“虚拟活检”。 验证性研究，每项研究通常侧重于一种单一的MRI技术。多参数磁共振成像具有独特的 有可能确定肾移植功能障碍的内在原因。 具体目标1：开发质量控制(QC)框架以评估定量多参数 肾移植患者的MRI检查方案包括IVIM扩散、DCE-MRI灌注、ASL和BOLD。 假设：质量控制框架将提高在肾脏测量的MRI指标的数据质量和重复性 异体移植。我们将构建一个用于肾功能MRI的质量控制和图像优化算法，并将在16个月内进行测试 接受肾移植的患者。 特定目标2：量化正常和异常肾移植患者的MRI参数 肾功能，并评估MRI参数单独和联合用于定性的价值 以临床参数和/或病理为参考的肾功能不全。假设：肾移植 功能障碍可以通过一系列生物标志物的组合来诊断和表征 核磁共振检查。通过IVIM参数测量肾脏扩散和灌注，通过测量肾脏血浆流量 DCE和ASL、延髓和延髓与皮质的横向松弛时间比R2*(由 BOLD技术)将减少，同时造影剂通过肾小管的平均通过时间(Mtt)将减少 根据DCE-MRI的测量，与正常功能的同种异体移植物相比，功能障碍的同种异体移植物的数量会增加。 此外，有ATN的同种异体功能障碍移植物与无ATN的同种异体移植物可以通过更长的平均时间加以区分。 根据DCE-MRI数据的三室模型计算的肾小管的通过时间，以及通过 髓质与皮质R2的比值较高。我们将在97名肾移植受者中测试这一假设 临床上实验室检查和活检显示的功能性和功能障碍的同种异体移植物。