Image analysis techniques to map pyramids, pyramid structure, glomerular distribution, and pathology in the intact human kidney from 3-D MRI

Abstract

Kidney pathologies are often highly heterogenous. To comprehensively understand kidney structure and pathology, it is critical to develop tool to map tissue microstructure in the context of the whole, intact organ. Magnetic resonance imaging (MRI) can provide a unique, three-dimensional (3D) view of the kidney and allows for measurement of multiple pathologic features. Here, we develop a platform to systematically render and map gross and microstructural features of the human kidney based on 3D MRI. These features include pyramid number and morphology, and associated medulla and cortex. in a subset of these kidneys, we also map individual glomeruli and glomerular volumes using cationic ferritin enhance-MRI to report intra-renal heterogeneity in glomerular density and size. Finally, we render and measure regions of nephron loss due to pathology and individual glomerular volumes in each pyramidal unit. This work provides new tools to comprehensively evaluate the kidney across scales, with potential applications in anatomical and physiological research, transplant allograft evaluation, biomarker development, biopsy guidance, and therapeutic monitoring. These image rendering and analysis tools could eventually impact the field of transplantation medicine to improve longevity matching of donor allografts and recipients and reduce discard rates through the direct assessment of donor kidneys.

Visualization of Renal Glomeruli in Human Native Kidneys With Sensing Ultrasound Localization Microscopy

“…Other noninvasive exploration techniques, which are still in the preclinical research stage, could present interest in comparing their results with the sULM results. For example, Charlton et al 45 developed a platform to map microstructural features of the human kidney based on 3-dimensional MRI; in a subset of kidneys, they also mapped individual glomeruli and glomerular volumes using cationic ferritin-enhanced MRI. On another scale, Dunn et al 46 demonstrated that intravital and multiphoton fluorescence microscopy systems can collect optical sections from kidneys at subcellular resolution, supporting high-resolution characterizations of the glomeruli in anesthetized and surgically prepared living animals.…”

The Number and Size of Individual Kidney Medullary Pyramids is Associated with Clinical Characteristics, Kidney Biopsy Findings, and CKD Outcomes among Kidney Donors

“…The average number of pyramids found in our study was 22, lower than average compared with the results found in the study by Charlton et al ( n =35, including secondary pyramids). 10 The discrepancies are likely because of differences in methodology that allows the detection of secondary pyramids. The CT voxel size in our study ranged from 0.14 to 2.38 mm 3 , whereas the ex vivo study by Charlton et al used magnetic resonance (MR) imaging with a higher spatial resolution (voxel size ranging from 0.00047 to 0.0016 mm 3 ).…”

“…Both our study and a prior study consistently showed pyramid number to decrease with age. 10 As it would seem biologically implausible for an entire kidney lobe to disappear with healthy aging, it is more likely that pyramids merge with age because of the loss of detectable cortical columns. The association of larger pyramids with older age supports this hypothesis.…”

“…9 However, studies have also reported the presence of subtle renal columns within pyramids; these subdivisions are sometimes described as fused secondary pyramids or subpyramids that share the same papillary tip. [10][11][12] Thus, the number of pyramids in a human kidney may be less than the original number of renal lobes because of these fusions. An ex vivo study in ten kidneys found that medullary pyramid counts decreased with age and that larger cortex volume was associated with fewer and larger pyramids, but not with the total count of subpyramids.…”

“…An ex vivo study in ten kidneys found that medullary pyramid counts decreased with age and that larger cortex volume was associated with fewer and larger pyramids, but not with the total count of subpyramids. 10 Little is known about the clinical and prognostic importance of individual medullary pyramids. A method for in vivo assessment of individual medullary pyramids is first needed.…”