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: 10549318
• 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 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10549318
• 关键词: Acute; Angioplasty; Animal Model; Benchmarking; Binding; Biological Markers; Biophysics; Cardiovascular system; Chronic Kidney Failure; Clinical; Clinical assessments; 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; 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; Techniques; Testing; Therapeutic; Tissues; Vascularization; Western World; aging population; 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.

肾纤维化是大多数形式的肾脏疾病常见的最终途径和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损伤和 高血压。早期发现纤维化并进行适当干预可能会减缓肾脏疾病 进展，但尚未确定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) 是一种新颖的非侵入性方法 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 小鼠和猪模型中的纤维化。然而，MT-MRI 评估肾功能的临床应用 纤维化目前受到限制，因为它本质上是半定量的。相比之下，基于定量 MT (qMT) 在生物物理室模型上，提供了组织 MT 特性的更客观的测量。一个模型 对通过各种 MT 脉冲幅度和偏移频率采集的 MR 信号进行拟合，并结合扫描 特定的 B0/B1/T1 图，产生了组织参数的更完整的定义，包括“绑定池” 分数”，组织中大分子含量的直接测量。 该提议的假设是 qMT 能够可靠地检测肾纤维化的发展 患有 RVD 的受试者为 1.5T 和 3.0T。为了检验这个假设，该假设得到了强有力的初步支持 根据数据，我们将首先开发、优化和验证 qMT，以评估狭窄后猪的纤维化 肾。我们将把 qMT 衍生的肾纤维化与参考标准以及单肾相关联 使用尖端多探测器 CT (MDCT) 和 MRI 量化血流动力学、功能和氧合 技术。然后，我们将确定 qMT 预测接受 RVD 的猪肾恢复的能力 血运重建。此外，我们将进行一项试点研究，以测试 qMT 量化术后纤维化的能力。 狭窄的人类肾脏，与肾功能障碍和组织损伤的创新生物标志物进行比较。 三个具体目标将检验这些假设： 具体目标 1：在狭窄的猪肾脏中进行 qMT 是可行的， 在 1.5 和 3.0 T 下可靠且可重复。 具体目标 2：qMT 预测肾脏恢复潜力 到 PTRA。具体目标 3：qMT 在狭窄的人类肾脏中是可行的、可重复的，并且可以预测康复。 因此，拟议的研究可能会建立一种可靠的、非侵入性的、临床上可行的策略 量化肾脏纤维化，这是肾脏结果和治疗成功的关键生物标志物。

项目成果

Impact of Peripheral Microvascular Endothelial Dysfunction on White Matter Hyperintensity.

• DOI: 10.1161/jaha.121.021066
• 发表时间: 2021-10-19
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Toya T;Sara JD;Scharf EL;Ahmad A;Nardi V;Ozcan I;Lerman LO;Lerman A
• 通讯作者: Lerman A

Risk Stratification of Patients With NonObstructive Coronary Artery Disease Using Resistive Reserve Ratio.

• DOI: 10.1161/jaha.120.020464
• 发表时间: 2021-06
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Toya T;Ahmad A;Corban MT;Ӧzcan I;Sara JD;Sebaali F;Escaned J;Lerman LO;Lerman A
• 通讯作者: Lerman A