Noninvasive evaluation of the intrarenal microvasculature in ADPKD

ADPKD 肾内微血管的无创评估

基本信息

批准号：
10456178
负责人：
Maria V Irazabal
金额：
$ 22.97万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456178
关键词：
Adult Automation Autosomal Dominant Polycystic Kidney Bilateral Caliber Classification Contrast Media Coupled Cystic kidney Data Development Disease Disease Progression Early Diagnosis Enrollment Evaluation Exposure to Healthcare Systems Human Image Image Enhancement Imaging Techniques Imaging technology In Vitro Injury to Kidney Interobserver Variability Intraobserver Variability Kidney Kidney Diseases Kidney Failure Knowledge Magnetic Resonance Imaging Methods Microbubbles Microcirculation Microscopic Microscopy Microvascular Dysfunction Modality Monitor Motion Nature Noise Organ Patients Penetration Perfusion Physiological Play Pre-Clinical Model Radiation Renal function Reproducibility Reproducibility of Results Resolution Risk Rodent Role Severity of illness Signal Transduction Techniques Testing Therapeutic Time Tissues Translating Ultrasonography Vascular remodeling clinically relevant contrast enhanced cost density disorder control healthy volunteer human imaging imaging biomarker imaging modality imaging study improved in vivo kidney imaging microCT nephrotoxicity patient variability preclinical study preservation renal damage sex success therapeutic target time use tool ultrasound volunteer

项目摘要

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a devastating systemic disorder and a leading cause of renal failure. It is characterized by continuous development and enlargement of bilateral renal cysts, but many pathophysiological mechanisms contributing to renal damage and failure remain poorly understood. In ADPKD, vascular remodeling has been proposed to play an important role in its progression. However, knowledge on the precise contribution to renal injury and function decline, and optimal therapeutic strategies have been hampered by the lack of tools enabling the quantitative and noninvasive assessment of the intrarenal microvasculature. Clearly, a noninvasive and direct method to assess the intrarenal microvasculature is needed. Imaging studies, such as microCT, MRI, and contrast-enhanced ultrasound, have attempted to provide noninvasive assessment of the intrarenal microvasculature in pre-clinical models. However, each of these modalities have important limitations when translating into humans, including low spatial resolution. Super-resolution ultrasound (SRU) imaging was introduced to overcome the limitation of inherent spatial resolution of ultrasound. With the use of non-nephrotoxic contrast microbubbles to break the diffraction limit of ultrasound, and the introduction of ultrasound localization microscopy which utilizes ultrafast frame rate imaging to reconstruct a super-resolved composite image, SRU has provided a paradigm-shifting tool for structural and functional evaluation of tissue microvasculature. However, in vivo human imaging, and in particular kidney imaging, poses significant challenges related to organ depth and motion. To overcome these limitations, our team implemented advanced filtering and microbubble localization and tracking techniques, which extract only microbubble signals and reliably pinpoint the center of each microbubble. The combination of SRU with these automation and post processing tools results in unprecedented microscopic-level imaging resolution at clinically relevant penetration depths, while rendering ultrasound more quantitative and less user- dependent. The working hypothesis underlying this proposal is that SRU imaging coupled with advanced filtering and microbubble localization-tracking post processing techniques would reliably and reproducibly assess the intrarenal microvasculature in patients with ADPKD from early stages of the disease. We will pursue three specific aims: Aim 1: Will introduce and evaluate SRU imaging coupled with advanced post processing techniques to assess the intrarenal microvasculature in patients with early ADPKD and controls. Aim 2: Will determine the inter-sonographer and inter-intra-observer reproducibility of microvascular parameters. Aim 3: Will determine the range of day-to-day variability of microvascular parameters in controls, and of patient-to-patient variability in ADPKD. Successful studies will introduce a powerful tool to elucidate the role of intrarenal microvascular damage in the progression of ADPKD, the microvasculature as therapeutic target, and microvascular parameters as imaging biomarkers to assess disease severity and progression.

常染色体显性多囊肾病 (ADPKD) 是一种毁灭性的系统性疾病，也是一种主要的肾功能衰竭的原因。其特点是双侧肾囊肿不断发展、增大，但导致肾损伤和衰竭的许多病理生理机制仍知之甚少。在 ADPKD 中，血管重塑被认为在其进展中发挥重要作用。然而，关于肾损伤和功能衰退的确切原因以及最佳治疗策略的知识由于缺乏能够进行定量和非侵入性评估的工具而受到阻碍肾内微血管。显然，这是一种评估肾内微血管系统的无创且直接的方法是需要的。影像学研究，例如 microCT、MRI 和对比增强超声，试图在临床前模型中提供肾内微血管系统的无创评估。然而，每个这些模式在转化为人类时具有重要的局限性，包括空间分辨率低。超分辨率超声（SRU）成像的出现是为了克服固有空间的限制超声波的分辨率。使用非肾毒性对比微泡突破衍射极限超声波，以及利用超快帧速率的超声波定位显微镜的引入 SRU 为重建超分辨率合成图像提供了一种范式转换工具组织微血管的结构和功能评估。然而，体内人体成像，以及特别是肾脏成像，对器官深度和运动提出了重大挑战。为了克服这些限制，我们的团队实施了先进的过滤和微泡定位和跟踪技术，它仅提取微泡信号并可靠地精确定位每个微泡的中心。组合 SRU 与这些自动化和后处理工具的结合产生了前所未有的显微级成像临床相关穿透深度的分辨率，同时使超声更加定量且更少的用户干扰依赖。该提案的工作假设是 SRU 成像与先进的相结合过滤和微泡定位跟踪后处理技术将可靠且可重复地从疾病早期阶段评估 ADPKD 患者的肾内微血管。我们将追求三个具体目标：目标 1：将介绍和评估 SRU 成像以及先进的后期技术用于评估早期 ADPKD 患者和对照患者肾内微血管的处理技术。目标 2：确定微血管超声检查者之间和观察者之间的可重复性参数。目标 3：确定对照中微血管参数的日常变异范围，以及 ADPKD 患者之间的变异性。成功的研究将引入一个强大的工具来阐明肾内微血管损伤在 ADPKD 进展中的作用，微血管作为治疗目标和微血管参数作为成像生物标志物来评估疾病的严重程度和进展。