Quantitative magnetization transfer MRI for evaluation of renal fibrosis

定量磁化转移 MRI 评估肾纤维化

• 批准号: 10337329
• 负责人: Lilach O Lerman
• 金额: $ 52.83万
• 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: 2020-03-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10337329
• 关键词: Acute; Angioplasty; Animal Model; Benchmarking; Biological Markers; Biophysics; Cardiovascular system; Chronic Kidney Failure; Clinical; Complex; Data; Development; Disease Progression; Distal; Early identification; End stage renal failure; Evaluation; Evolution; Family suidae; Fibrosis; Frequencies; Health Care Costs; Health Professional; Histology; Human; Hypertension; Image; Image Analysis; Imaging Techniques; Injury; Injury to Kidney; Interobserver Variability; Intervention; Kidney; Kidney Diseases; Magnetic Resonance Imaging; Maps; Measurement; Measures; Methods; Modeling; Morbidity - disease rate; Outcome; Pathogenesis; Pathway interactions; Patients; Perfusion; Physiologic pulse; Pilot Projects; Progressive Disease; Property; Protocols documentation; Recovery; Reference Standards; Relaxation; Renal Replacement Therapy; Renal Tissue; Renal Vascular Disorder; Renal function; Reproducibility; Risk Factors; Sampling Errors; Scanning; Secondary to; Signal Transduction; Standardization; Stents; Structure; Testing; Therapeutic; Tissues; Western World; aging population; base; blood pressure control; clinical application; clinical translation; detector; functional improvement; functional restoration; hemodynamics; human subject; imaging modality; innovation; instrument; kidney biopsy; kidney dysfunction; kidney fibrosis; mortality; mouse model; nephrogenesis; non-invasive imaging; novel; porcine model; renal artery; renal ischemia; response; success; tissue biomarkers

Renal fibrosis is a final pathway and important biomarker of injury common to most forms of kidney disease. For example, in renal vascular disease (RVD) progressive renal fibrosis may induce kidney injury and hypertension. Early identification of fibrosis and adequate intervention may slow down renal disease progression, but adequate noninvasive strategies to detect and quantify renal fibrosis are yet to be identified. 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 stenotic kidney fibrosis in murine and swine models of unilateral RVD. 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. The hypothesis underlying this proposal is that qMT would reliably detect development of renal fibrosis at both 1.5T and 3.0T in subjects with RVD. To test this hypothesis, which is supported by strong preliminary data, we will initially develop, optimize, and validate qMT for evaluation of fibrosis in the post-stenotic swine kidney. We will correlate qMT-derived renal fibrosis with reference standards, as well as with single-kidney hemodynamics, function, and oxygenation, quantified using cutting-edge multi-detector CT (MDCT) and MRI techniques. We will then determine the ability of qMT to predict renal recovery in pigs with RVD undergoing revascularization. Further, we will perform a pilot study to test the ability of qMT to quantify fibrosis in the post- stenotic human kidney, in comparison to innovative biomarkers of renal dysfunction and tissue damage. Three specific aims will test the hypotheses: Specific Aim 1: qMT in stenotic swine kidneys is feasible, reliable, and reproducible at 1.5 and 3.0 T. Specific Aim 2: qMT predicts renal recovery potential in response to PTRA. Specific Aim 3: qMT in stenotic human kidneys is feasible, reproducible, and predicts recovery. The proposed studies may therefore establish a reliable, noninvasive, and clinically feasible strategy to quantify kidney fibrosis, a key biomarker for renal outcomes and therapeutic success.

肾纤维化是大多数肾脏疾病常见的损伤的最终途径，也是重要的损伤生物标志物。 例如，在肾血管疾病（RVD）中，进行性肾纤维化可能诱发肾脏损伤和 高血压。纤维化和充分干预的早期鉴定可能会减慢肾脏疾病 进展，但有足够的非侵入性策略来检测和量化肾纤维化。 磁化转移成像（MTI）磁共振成像（MRI）是一种新型的无创方法 评估组织大分子组成。我们已经证明MTI可以评估狭窄的肾脏 单侧RVD的鼠和猪模型中的纤维化。但是，MT-MRI评估肾脏的临床实用性 目前纤维化是有限的，因为它本质上是半定量的。相反，基于定量MT（QMT）， 在生物物理室模型上，提供了组织MT特性的更客观测量。模型 与各种MT脉冲放大器和偏移频率获取的MR信号的拟合，并结合扫描 特定的B0/B1/T1映射，产生更完整的组织参数定义，包括“绑定池” 分数”，直接衡量组织中的大分子含量。 该提议的基础假设是QMT将可靠地检测到肾纤维化的发展 RVD受试者的1.5T和3.0T。检验该假设，该假设得到了强大的初步支持 数据，我们最初将开发，优化和验证QMT以评估静脉后游泳的纤维化 肾。我们将将QMT衍生的肾纤维化与参考标准相关联，以及单kidney 使用尖端的多探测器CT（MDCT）和MRI量化了血液动力学，功能和氧合 技术。然后，我们将确定QMT预测RVD正在进行的猪肾脏回收的能力 血运重建。此外，我们将进行一项试验研究，以测试QMT在后质量的能力 与肾功能障碍和组织损伤的创新生物标志物相比，狭窄的人肾脏。 三个具体目标将检验假设：特定目标1：狭窄猪肾脏中的QMT是可行的， 可靠，可在1.5和3.0 T.特定目的2：QMT预测肾回收潜力以响应 到Ptra。特定的目标3：狭窄人肾中的QMT是可行的，可重复的，可以预测恢复。 因此，拟议的研究可能会建立可靠，无创和临床可行的策略 量化肾纤维化，这是肾脏结局和治疗成功的关键生物标志物。