Differential synchrotron X-ray imaging markers based on the renal microvasculature for tubulointerstitial lesions and glomerulopathy

Abstract

High resolution synchrotron microtomography capable of revealing microvessels in three dimensional (3D) establishes distinct imaging markers of mouse kidney disease strongly associated to renal tubulointerstitial (TI) lesions and glomerulopathy. Two complementary mouse models of chronic kidney disease (CKD), unilateral ureteral obstruction (UUO) and focal segmental glomerulosclerosis (FSGS), were used and five candidates of unique 3D imaging markers were identified. Our characterization to differentially reflect the altered microvasculature of renal TI lesions and/or glomerulopathy demonstrated these image features can be used to differentiate the disease status and the possible cause therefore qualified as image markers. These 3D imaging markers were further correlated with the histopathology and renal microvessel-based molecular study using antibodies against vascular endothelial cells (CD31), the connective tissue growth factor or the vascular endothelial growth factor. We also found that these 3D imaging markers individually characterize the development of renal TI lesions or glomerulopathy, quantitative and integrated use of all of them provide more information for differentiating the two renal conditions. Our findings thus establish a practical strategy to characterize the CKD-associated renal injuries by the microangiography-based 3D imaging and highlight the impact of dysfunctional microvasculature as a whole on the pathogenesis of the renal lesions.

Effects of shenkang injection on renal angiogenesis in mice with unilateral ureteral obstruction

“…Micro-CT is highly reproducible and is believed to be a reliable approach in preclinical and basic kidney researches, especially useful in vasculature-related kidney pathologies such as renal fibrosis (Hlushchuk et al, 2018). In this study, it was obviously observed that unilateral ureteral obstruction mice had dramatic loss of microvessels in fibrotic kidneys compared with the sham mice by micro-CT, showing reduction in numbers of blood vessels and vessel branching, and decrease in vessel tortuosity in the left kidneys, which were in line with Ehling et al, 2016 andLin et al, 2017. And shenkang injection alleviated loss of micro-vessels, showing obvious increases in numbers of blood vessels, vessel branching, and vessel tortuosity.…”

Micro-CT imaging and structural analysis of glomeruli in a model of Adriamycin-induced nephropathy

“…8). The sensitivity of this metric is particularly relevant to the model of focal segmental glomerulosclerosis (Adriamycin nephropathy), where podocyte injury is highly varied across glomeruli (35,36).…”

NeuroRetriever: Automatic Neuron Segmentation for Connectome Assembly

“…We expect that NR can be applied to process fluorescence images taken by super-resolution microscopy and expansion microscopy with resolution beyond the optical limit (Small and Stahlheber, 2014;Sigal et al, 2015). Also, the concept of an HDR thresholding mask is likely applicable for identifying other tree-like structures, such as tracheoles and blood vessels (Lin et al, 2017), or other types of non-fluorescent images, such as X-ray images (Ng et al, 2016). With automated NR for high-throughput single-neuron segmentation, connectome mapping for large brains with billions of neurons is now conceivable.…”