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

Kidney pathologies are often highly heterogeneous. To comprehensively understand kidney structure and pathology, it is critical to develop tools to map tissue microstructure in the context of the whole, intact organ. Magnetic resonance imaging (MRI) can provide a unique, three-dimensional view of the kidney and allows for measurements of multiple pathological features. Here, we developed a platform to systematically render and map gross and microstructural features of the human kidney based on threedimensional MRI. These features include pyramid number and morphology as well as the associated medulla and cortex. In a subset of these kidneys, we also mapped individual glomeruli and glomerular volumes using cationic ferritin-enhanced MRI to report intrarenal heterogeneity in glomerular density and size. Finally, we rendered and measured 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 anatomic 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. NEW & NOTEWORTHY We report the application of cutting-edge image analysis approaches to characterize the pyramidal geometry, glomerular microstructure, and heterogeneity of the whole human kidney imaged using MRI. This work establishes a framework to improve the detection of microstructural pathology to potentially facilitate disease monitoring or transplant evaluation in the individual kidney.