Noninvasive evaluation of the intrarenal microvasculature in ADPKD

ADPKD 肾内微血管的无创评估

• 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
• 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

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.

常染色体显性遗传性多囊肾病（ADPKD）是一种毁灭性的系统性疾病， 肾衰竭的原因其特征是双侧肾囊肿持续发展和增大， 但许多导致肾损伤和衰竭的病理生理机制仍然知之甚少。 在ADPKD中，血管重塑已被认为在其进展中起重要作用。然而，在这方面， 了解肾损伤和功能下降的确切原因，以及最佳治疗策略 由于缺乏能够定量和非侵入性评估的工具， 肾内微血管显然，一种无创和直接的方法来评估肾内微血管， 是必要的。影像学研究，如microCT、MRI和超声造影，试图 在临床前模型中提供肾内微血管的非侵入性评估。但每 这些模式在转化为人类时具有重要的局限性，包括低空间分辨率。 超分辨率超声（SRU）成像是为了克服固有的空间局限性而引入的 超声波的分辨率使用非肾毒性造影剂微泡突破了 超声波，并引入超声波定位显微镜，利用超快帧速率 成像重建一个超分辨率的复合图像，SRU提供了一个范式转换工具， 组织微血管结构和功能评价。然而，在体内人体成像，并在 特别是肾脏成像，提出了与器官深度和运动相关的重大挑战。克服这些 局限性，我们的团队实施了先进的过滤和微泡定位和跟踪技术， 其仅提取微泡信号并可靠地精确定位每个微泡的中心。相结合 SRU与这些自动化和后处理工具的结果在前所未有的显微镜水平成像 分辨率在临床相关的穿透深度，同时使超声更定量和更少的用户- 依赖。这项建议的工作假设是，SRU成像加上先进的 过滤和微泡定位跟踪后处理技术将可靠地和可再现地 从疾病的早期阶段评估ADPKD患者的肾内微血管。我们将 追求三个具体目标：目标1：将引入和评价SRU成像与高级后处理 处理技术，以评估早期ADPKD患者和对照组的肾内微血管。 目的2：将确定微血管超声检查者之间和观察者之间的重现性 参数目的3：确定对照组中微血管参数的每日变异性范围， 以及ADPKD患者间的变异性。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，微血管作为治疗药物 靶向和微血管参数作为成像生物标志物来评估疾病严重程度和进展。