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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：
10282783
负责人：
Maria V Irazabal
金额：
$ 18.92万
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 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10282783
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 Structure 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 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）是一种毁灭性的全身性疾病，也是一种主要的遗传性疾病