Fibrosis Beyond the Core: A New Application of MRI to Noninvasively Quantify Whole Kidney Fibrosis

超越核心的纤维化：MRI 无创量化全肾纤维化的新应用

• 批准号: 10796499
• 负责人: Stefanie W Benoit
• 金额: $ 33.73万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10796499
• 关键词: 3-Dimensional; Abdomen; Accounting; Adult; Affect; Allografting; Amides; Arteriovenous fistula; Biological Markers; Biopsy; Cardiac; Cause of Death; Child; Childhood; Chronic Kidney Failure; Clinical; Collagen; Contrast Media; Data; Development; Diabetes Mellitus; Diagnostic Procedure; Diffusion Magnetic Resonance Imaging; Disease; Disease Outcome; Disease Progression; Early Diagnosis; Early identification; Educational workshop; Elastin; End stage renal failure; Etiology; Fibrosis; Future; Gadolinium; Goals; Health Care Costs; Hemorrhage; Histologic; Human Volunteers; Hypertension; Image; Incidence; Inflammation; Injury; Injury to Kidney; Kidney; Kidney Diseases; Kidney Transplantation; Magnetic Resonance Imaging; Maps; Measures; Medical; Medicare; Methods; Monitor; Morbidity - disease rate; Motion; National Institute of Diabetes and Digestive and Kidney Diseases; Obesity; Outcome; Pathology; Pathway interactions; Patients; Persons; Pharmacologic Substance; Physiologic pulse; Population; Preparation; Prevalence; Prevention; Process; Protons; Public Health; Radial; Renal function; Reproducibility; Research; Research Priority; Risk; Sampling; Sampling Errors; Scanning; Sedation procedure; Signal Transduction; Specificity; Techniques; Testing; Therapeutic; Time; Tissues; Transplant Recipients; Transplantation; Treatment Efficacy; United States; United States National Institutes of Health; Work; antifibrotic treatment; clinical application; clinical care; contrast enhanced; contrast imaging; data exchange; efficacy evaluation; elastography; imaging detection; imaging modality; innovation; kidney biopsy; kidney fibrosis; mortality; mortality risk; noninvasive diagnosis; novel; prognostic indicator; reconstruction; respiratory; response; treatment response; treatment trial

PROJECT SUMMARY Chronic kidney disease (CKD) is one of the leading causes of morbidity and mortality in the United States, affecting approximately 15% of the adult population. One of the best prognostic indicators of CKD progression and outcomes is kidney fibrosis, for which new treatments are being developed. Noninvasive methods to detect and quantify fibrosis, as well as monitor disease progression and/or the response to these treatments, are urgently needed. Fibrosis occurs when excess collagen accumulates in the kidney. Collagen contains a large amount of amide protons. While current magnetic resonance imaging (MRI) methods are insensitive to these amide protons, a technique called amide proton transfer (APT) contrast imaging detects signals from amide protons and, therefore, is expected to be able to detect and quantify kidney fibrosis. Kidneys present a unique imaging challenge due to inherent motion and limited spatial coverage, which can be mitigated with 3D radial acquisition techniques. The long-term goal of this project is to develop a noninvasive, noncontrast MRI method to quantify kidney fibrosis. Our objectives in this proposal are to implement and test a fast 3D radial MRI imaging and reconstruction method for quantifying kidney fibrosis. Our hypothesis is that APT contrast imaging will allow the accurate quantitation of kidney fibrosis. Our rationale is that eventually APT contrast can be used clinically to detect CKD earlier, monitor disease progression, and assess treatment efficacy in patients. We will complete the following specific aims: 1) implement a novel 3D radial acquisition strategy for acquiring whole kidney APT contrast data; and 2) test the ability of APT contrast imaging compared to existing MRI methods to quantify fibrosis in pediatric kidney transplant patients with CKD. All imaging metrics will be correlated with qualitative and quantitative histological measures at matching time points. The proposed research is innovative because it will develop a rapid 3D, noncontrast and noninvasive method of quantifying fibrosis throughout the entire kidney. These results are significant because they will provide a means of detecting, quantifying, and following renal fibrosis early in the disease process, when it may be most reversible, and monitoring response to medical treatments. This work will have an immediate positive impact by providing a novel means of assessing efficacy in treatment trials as well as providing a clinical method for evaluating disease progression and therapy response.

项目概要 慢性肾脏病（CKD）是美国发病率和死亡率的主要原因之一， 影响大约15%的成年人口。 CKD 进展的最佳预后指标之一 结果是肾纤维化，目前正在开发新的治疗方法。非侵入性检测方法 并量化纤维化，以及监测疾病进展和/或对这些治疗的反应 急需。当过量的胶原蛋白在肾脏中积聚时，就会发生纤维化。胶原蛋白含有大量 酰胺质子的量。虽然当前的磁共振成像 (MRI) 方法对这些不敏感 酰胺质子，一种称为酰胺质子转移 (APT) 对比成像的技术可检测来自酰胺的信号 质子，因此有望能够检测和量化肾纤维化。肾脏具有独特的 由于固有运动和有限的空间覆盖而带来的成像挑战，可以通过 3D 径向来缓解 采集技术。该项目的长期目标是开发一种无创、非对比 MRI 方法 量化肾脏纤维化。我们在此提案中的目标是实施和测试快速 3D 径向 MRI 成像 以及量化肾纤维化的重建方法。我们的假设是 APT 对比成像将允许 肾纤维化的准确定量。我们的理由是 APT 造影剂最终可以用于临床 及早发现 CKD、监测疾病进展并评估患者的治疗效果。我们将完成 具体目标如下：1) 实施一种新颖的 3D 径向采集策略来获取全肾 APT 对比数据； 2) 测试 APT 对比成像与现有 MRI 方法相比的量化能力 患有 CKD 的儿童肾移植患者的纤维化。所有成像指标都将与定性相关 以及匹配时间点的定量组织学测量。拟议的研究具有创新性，因为它 将开发一种快速 3D、非对比和非侵入性方法来量化整个肾脏的纤维化。 这些结果意义重大，因为它们将提供一种检测、量化和跟踪肾功能的方法。 在疾病过程的早期发现纤维化，此时纤维化可能是最可逆的，并监测对医疗的反应 治疗。这项工作将通过提供一种评估疗效的新方法来产生直接的积极影响 治疗试验以及提供评估疾病进展和治疗反应的临床方法。