title: MRI-based glomerular morphology and pathology in whole human kidneys.
abstract: Nephron number (N(glom)) and size (V(glom)) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess N(glom) and V(glom) in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure N(glom) and V(glom) in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an ~6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.
authors.affiliation: Department of Radiology, Washington University School of Medicine, Saint Louis, Missouri;
authors.forename: Scott C
authors.initials: SC
authors.lastname: Beeman
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia;
authors.forename: Luise A
authors.initials: LA
authors.lastname: Cullen-McEwen
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia;
authors.forename: Victor G
authors.initials: VG
authors.lastname: Puelles
authors.affiliation: School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, Tempe, Arizona;
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, Tempe, Arizona;
authors.forename: Teresa
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Physics, College of Natural Sciences, University of Hawaii at Manoa, Honolulu, Hawaii;
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Baldelomar
authors.affiliation: Department of Anatomical Pathology, Monash Medical Centre, Clayton, Victoria, Australia;
authors.forename: John
authors.initials: J
authors.lastname: Dowling
authors.affiliation: Department of Pediatrics, Division of Nephrology, University of Virginia Medical Center, Charlottesville, Virginia;
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Charlton
authors.affiliation: Department of Pediatrics, Division of Nephrology, University of Virginia Medical Center, Charlottesville, Virginia;
authors.forename: Michael S
authors.initials: MS
authors.lastname: Forbes
authors.affiliation: Monash Biomedical Imaging, Monash University, Melbourne, Australia; and.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ng
authors.affiliation: Monash Biomedical Imaging, Monash University, Melbourne, Australia; and.
authors.forename: Qi-zhu
authors.initials: QZ
authors.lastname: Wu
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia;
authors.forename: James A
authors.initials: JA
authors.lastname: Armitage
authors.affiliation: Monash Biomedical Imaging, Monash University, Melbourne, Australia; and.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
authors.affiliation: Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia;
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
authors.affiliation: Department of Biology, College of Natural Sciences, University of Hawaii at Manoa, Honolulu, Hawaii kevinben@hawaii.edu.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Bennett
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged
keywords: cationized ferritin; chronic kidney disease; magnetic resonance imaging