Renal Microvessel Imaging for Characterization of Chronic Kidney Disease

肾脏微血管成像用于表征慢性肾脏病

• 批准号: 10581889
• 负责人: Shigao Chen
• 金额: $ 39.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-16 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10581889
• 关键词: Affect; Agreement; American; Analysis of Variance; Animals; Benchmarking; Binding; Biopsy; Blood Flow Velocity; Blood flow; Chronic Kidney Failure; Clinical; Clinical Research; Contrast Media; Decision Making; Development; Diameter; Euthanasia; Family suidae; Glomerular Filtration Rate; Health Care Costs; Histology; Human; Image; Image Enhancement; Imaging technology; Kidney; Kidney Diseases; Length; Logistic Regressions; Magnetic Resonance Imaging; Measurement; Measures; Methods; Microbubbles; Modeling; Morphology; Noise; Normal Range; Outcome; Pathology; Patients; Penetration; Performance; Perfusion; Proteinuria; ROC Curve; Random Allocation; Receiver Operating Characteristics; Reference Standards; Renal Artery Stenosis; Sampling; Scanning; Signal Transduction; Speed; Staging; Technology; Testing; Thick; Toxic effect; Ultrasonography; Validation; X-Ray Computed Tomography; arteriole; contrast enhanced; contrast enhanced computed tomography; cost effective; density; elastography; experimental study; healthy volunteer; imaging modality; imaging study; imaging system; improved; indexing; kidney biopsy; kidney cortex; kidney imaging; kidney vascular structure; meter; microCT; novel; perfusion imaging; renal damage; technology validation; tool; ultra high resolution; ultrasound; vascular bed; venule

PROJECT SUMMARY Chronic kidney disease (CKD) is estimated to affect 30 million Americans and incur healthcare cost of $30.9 billion every year. There is an urgent need of a safe and noninvasive clinical tool for accurate staging of CKD, which is essential for its management. The importance of renal parenchyma perfusion and vasculature morphology for CKD characterization has been documented by many studies, but is not used clinically due to lack of translatable imaging solutions. In this project, we will use a novel super-resolution ultrasound imaging (SRUI) technology, which can resolve 50-micron renal cortex microvessels and measure their blood flow speed in human, to quantify cortex microvessel morphology and perfusion for accurate CKD characterization. Aim 1: Technical development. New acquisition and processing methods will be developed to enhance performance of SRUI through phantom and patient experiments. Novel quantitative parameters of SRUI for renal cortex will be developed, which includes vessel density, diameter, and tortuosity, as well as mean blood flow velocity, micro- Resistive Index of arterioles and venules, and perfusion index. Aim 2: Animal validations. We will study 7 normal pigs and 14 CKD pigs with renal artery stenosis (RAS) to validate SRUI measurements using independent measurements obtained through contrast enhanced CT, micro-CT, and histology. Aim 3: Clinical study. We will study 50 healthy volunteers to establish the normal range of SRUI parameters and study 116 CKD patients with clinically indicated renal biopsy to investigate the efficacy of SRUI for CKD staging, using biopsy histology as the reference standard. Statistical difference between CKD patients and healthy controls and differences across CKD stages defined by histology will be evaluated. The association of each ultrasound parameter with histology CKD score will be assessed. Univariate and multivariate logistic regression and ROC analyses (receiver operating characteristic) analyses will be performed to assess the performance of SRUI, conventional ultrasound (renal length, cortex thickness, Doppler renal resistive index, and shear wave elastography), and clinical parameters (eGFR and proteinuria) for distinguishing histology CKD stages. A subset (N=45) of patients will be scanned by two sonographers randomly selected from a pool of five sonographers. Intraclass correlation coefficients will be used to evaluate the inter-sonographer agreement. The inter-sonographer variance will be calculated to estimate the minimum detectable difference for longitudinal follow-ups. Successful completion of this project will result in a safe, noninvasive, cost-effective, and accessible ultrasound technology for accurate characterization of chronic kidney disease to guide treatment decision making.

项目摘要 据估计，慢性肾脏疾病（CKD）影响3000万美国人，并产生30.9美元的医疗费用 每年10亿。迫切需要一种安全、无创的临床工具来对CKD进行准确分期， 这对它的管理至关重要。肾实质灌注和血管的重要性 许多研究已经记录了CKD表征的形态学，但由于以下原因而未在临床上使用： 缺乏可翻译的成像解决方案。在这个项目中，我们将使用一种新的超分辨率超声成像 （SRUI）技术，该技术可以分辨50微米的肾皮质微血管，并测量其血流速度 在人类中，量化皮质微血管形态和灌注，以准确表征CKD。 目标1：技术发展。将开发新的采集和处理方法， 通过体模和患者实验评估SRUI的性能。SRUI的新定量参数 将显影肾皮质，包括血管密度、直径和迂曲度，以及平均血流量 血流速度、微动脉和微静脉阻力指数和灌注指数。 目的2：动物验证。我们将研究7只正常猪和14只患有肾动脉狭窄（RAS）的CKD猪， 使用通过对比增强CT获得的独立测量值验证SRUI测量值， 显微CT和组织学 目的3：临床研究。我们将对50名健康志愿者进行研究，以确定SRUI参数的正常范围 并对116例有肾活检指征的CKD患者进行研究，以探讨SRUI治疗CKD的疗效 分期，使用活检组织学作为参考标准。CKD患者与 将评估健康对照和由组织学定义的CKD分期之间的差异。联盟 将评估每个超声参数和组织学CKD评分。单因素和多因素logistic 将进行回归和ROC分析（受试者操作特征）分析，以评估 SRUI的性能，常规超声（肾脏长度，皮质厚度，多普勒肾阻力指数， 和剪切波弹性成像），以及用于区分组织学的临床参数（eGFR和蛋白尿 CKD分期。一个患者子集（N=45）将由从样本池中随机选择的两名超声医师进行扫描 五个超声波技师组内相关系数将用于评估超声检查医师之间的关系 协议将计算超声医师间方差，以估计最小可检测差异 进行纵向随访。 该项目的成功完成将导致一个安全，无创，成本效益高，可访问的超声 用于准确表征慢性肾脏疾病的技术，以指导治疗决策。