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，约 30-40% 的患者会遭受至少一次急性移植物发作 根据肾功能障碍的原因，治疗方法截然不同，其中可能包括 急性肾小管坏死（ATN）、急性和慢性排斥反应（AR/CR）和药物毒性的明确诊断。 肾移植功能障碍基于经皮活检，具有侵入性且难以重复。 磁共振成像 (MRI) 可准确评估同种异体移植物的解剖结构以及 此外，功能性 MRI 可以利用功能性 MRI 深入了解肾功能。 动态对比增强 MRI（DCE-MRI，使用低剂量钆对比剂，可估计肾 灌注和流量），体素内不相干运动扩散加权成像（IVIM-DWI，它提供 有关流量和扩散的信息）、动脉自旋标记（ASL，无需对比即可量化肾流量） 剂）和血氧水平依赖成像（BOLD，反映氧生物利用度）。 功能性磁共振成像是非侵入性的，由于其数量较少，尚未作为“虚拟活检”出现。 验证研究通常侧重于单一 MRI 技术，具有独特的特点。 确定肾移植功能障碍的内在原因的潜力。 具体目标 1：开发质量控制 (QC) 框架来评估定量多参数 MRI 方案包括肾移植患者的 IVIM 扩散、DCE-MRI 灌注、ASL 和 BOLD。 假设：QC 框架将提高肾脏测量的 MRI 指标的数据质量和可重复性 我们将构建肾功能 MRI 的 QC 和图像优化算法，并将在 16 年进行测试。 肾移植患者。 具体目标 2：量化正常和异常肾移植患者的 MRI 参数 肾功能，并评估单独和组合 MRI 参数的价值以表征 使用临床参数和/或病理学作为参考的肾功能障碍假设：肾移植。 功能障碍可以通过可通过功能测量的生物标志物组合来诊断和表征。 MRI。肾扩散和灌注，通过 IVIM 参数测量，肾血浆流量 (RPF) 通过测量 DCE 和 ASL、横向弛豫时间 R2* 的髓质和髓质与皮质比率（通过测量 BOLD 技术）会减少，而造影剂通过肾小管的平均通过时间 (MTT) 根据 DCE-MRI 测量，与正常功能的同种异体移植物相比，功能性同种异体移植物的功能会增加。 此外，具有 ATN 的功能失调同种异体移植物可以通过更长的平均时间与无 ATN 的移植物区分开来。 肾小管中的通过时间，由 DCE-MRI 数据的三室模型和 髓质与皮质 R2* 的比例较高，我们将在 97 名肾移植受者中检验这一假设。 功能性和功能失调的同种异体移植物，如实验室测试和活检临床所示。

项目成果

Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI.

基于共识的肾脏扩散加权 MRI 临床转化技术建议。

• 发表时间: 2020-02
• 作者: Ljimani, Alexandra;Caroli, Anna;Laustsen, Christoffer;Francis, Susan;Mendichovszky, Iosif Alexandru;Bane, Octavia;Nery, Fabio;Sharma, Kanishka;Pohlmann, Andreas;Dekkers, Ilona A;Vallee, Jean;Derlin, Katja;Notohamiprodjo, Mike;Lim, Ruth P
• 通讯作者: Lim, Ruth P

Multiparametric magnetic resonance imaging shows promising results to assess renal transplant dysfunction with fibrosis.

多参数磁共振成像显示出评估肾移植功能障碍伴纤维化的良好结果。

• DOI: 10.1016/j.kint.2019.09.030
• 发表时间: 2019-10-30
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Octavia Bane;S. Hectors;Sonja Gordic;P. Kennedy;M. Wagner;Am;a Weiss;a;Rafael Khaim;Z. Yi;Weijia Zhang;V. Delaney;F. Salem;C. He;M. Menon;S. Lewis;B. Taouli
• 通讯作者: B. Taouli

T1ρ mapping for assessment of renal allograft fibrosis.

T1Ï 映射用于评估同种异体肾纤维化。

• 发表时间: 2019
• 作者: Hectors, Stefanie J;Bane, Octavia;Kennedy, Paul;El Salem, Fadi;Menon, Madhav;Segall, Maxwell;Khaim, Rafael;Delaney, Veronica;Lewis, Sara;Taouli, Bachir
• 通讯作者: Taouli, Bachir

4D flow MRI for the assessment of renal transplant dysfunction: initial results.

4D 流 MRI 用于评估肾移植功能障碍：初步结果。

• 发表时间: 2021-02
• 影响因子: 5.9
• 作者: Bane, Octavia;Said, Daniela;Weiss, Amanda;Stocker, Daniel;Kennedy, Paul;Hectors, Stefanie J;Khaim, Rafael;Salem, Fadi;Delaney, Veronica;Menon, Madhav C;Markl, Michael;Lewis, Sara;Taouli, Bachir
• 通讯作者: Taouli, Bachir