Quantitative Micro-Computed Tomography Imaging of Vascular Dysfunction in Progressive Kidney Diseases

Area of Science:

• Nephrology
• Medical Imaging
• Vascular Biology

Background:

• Progressive kidney diseases involve endothelial injury and capillary rarefaction.
• Current methods lack quantitative, noninvasive tools for monitoring renal vessel function.
• Understanding vascular changes is crucial for diagnosing and treating kidney fibrosis.

Purpose of the Study:

• To utilize micro-computed tomography (µCT) for imaging vascular alterations in progressive kidney disease models.
• To quantitatively assess vessel functionality and structure noninvasively.
• To establish a platform for evaluating potential vascular therapeutics in renal disease.

Main Methods:

• Employed contrast-enhanced in vivo µCT for longitudinal monitoring of renal blood volume.
• Utilized high-resolution ex vivo µCT after Microfil perfusion for detailed vascular network analysis.
• Investigated three distinct murine models: ischemia-reperfusion (I/R), unilateral ureteral obstruction (UUO), and Alport mice.

Main Results:

• In vivo µCT demonstrated a progressive decline in renal relative blood volume across all models, preceding fibrosis.
• Ex vivo µCT revealed significant alterations in preglomerular arteries, including reduced diameter and branching, and increased tortuosity.
• Quantified vascular changes in models of I/R injury, UUO, and Alport nephropathy.

Conclusions:

• µCT provides a robust platform for noninvasive, quantitative assessment of vascular changes in progressive kidney diseases.
• Identified previously unrecognized macro-to-microvascular alterations associated with renal fibrosis.
• The developed µCT methodology can aid in evaluating the efficacy of vascular-targeted therapies for kidney disease.