Project Details
Description
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.
Status | Finished |
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Effective start/end date | 8/1/21 → 6/30/23 |
Funding
- National Institute of Diabetes and Digestive and Kidney Diseases: $189,245.00
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