MRI-based glomerular morphology and pathology in whole human kidneys

Scott Charles Beeman, Luise A Cullen-McEwen, Victor G Puelles Rodriguez, Min Zhang, Teresa Wu, Edwin Baldelomar, John P Dowling, Jennifer R Charlton, Michael Shepard Forbes, Amanda Ching Lih Ng, Qi-Zhu Wu, James A Armitage, Gary F Egan, John F Bertram, Kevin M Bennett

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Nephron number (Nglom) and size (Vglom) 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 Nglom and Vglom in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure Nglom and Vglom in functioning 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 functioning human kidneys. A fourth naive 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 3D 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 spectral analyses and may be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.
Original languageEnglish
Pages (from-to)F1381 - F1390
Number of pages10
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number11
DOIs
Publication statusPublished - 2014

Cite this

Beeman, Scott Charles ; Cullen-McEwen, Luise A ; Puelles Rodriguez, Victor G ; Zhang, Min ; Wu, Teresa ; Baldelomar, Edwin ; Dowling, John P ; Charlton, Jennifer R ; Forbes, Michael Shepard ; Ng, Amanda Ching Lih ; Wu, Qi-Zhu ; Armitage, James A ; Egan, Gary F ; Bertram, John F ; Bennett, Kevin M. / MRI-based glomerular morphology and pathology in whole human kidneys. In: American Journal of Physiology - Renal Physiology. 2014 ; Vol. 306, No. 11. pp. F1381 - F1390.
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title = "MRI-based glomerular morphology and pathology in whole human kidneys",
abstract = "Nephron number (Nglom) and size (Vglom) 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 Nglom and Vglom in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure Nglom and Vglom in functioning 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 functioning human kidneys. A fourth naive 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 3D 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 spectral analyses and may be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.",
author = "Beeman, {Scott Charles} and Cullen-McEwen, {Luise A} and {Puelles Rodriguez}, {Victor G} and Min Zhang and Teresa Wu and Edwin Baldelomar and Dowling, {John P} and Charlton, {Jennifer R} and Forbes, {Michael Shepard} and Ng, {Amanda Ching Lih} and Qi-Zhu Wu and Armitage, {James A} and Egan, {Gary F} and Bertram, {John F} and Bennett, {Kevin M}",
year = "2014",
doi = "10.1152/ajprenal.00092.2014",
language = "English",
volume = "306",
pages = "F1381 -- F1390",
journal = "American Journal of Physiology - Renal Physiology",
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publisher = "American Physiological Society",
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Beeman, SC, Cullen-McEwen, LA, Puelles Rodriguez, VG, Zhang, M, Wu, T, Baldelomar, E, Dowling, JP, Charlton, JR, Forbes, MS, Ng, ACL, Wu, Q-Z, Armitage, JA, Egan, GF, Bertram, JF & Bennett, KM 2014, 'MRI-based glomerular morphology and pathology in whole human kidneys', American Journal of Physiology - Renal Physiology, vol. 306, no. 11, pp. F1381 - F1390. https://doi.org/10.1152/ajprenal.00092.2014

MRI-based glomerular morphology and pathology in whole human kidneys. / Beeman, Scott Charles; Cullen-McEwen, Luise A; Puelles Rodriguez, Victor G; Zhang, Min; Wu, Teresa; Baldelomar, Edwin; Dowling, John P; Charlton, Jennifer R; Forbes, Michael Shepard; Ng, Amanda Ching Lih; Wu, Qi-Zhu; Armitage, James A; Egan, Gary F; Bertram, John F; Bennett, Kevin M.

In: American Journal of Physiology - Renal Physiology, Vol. 306, No. 11, 2014, p. F1381 - F1390.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - MRI-based glomerular morphology and pathology in whole human kidneys

AU - Beeman, Scott Charles

AU - Cullen-McEwen, Luise A

AU - Puelles Rodriguez, Victor G

AU - Zhang, Min

AU - Wu, Teresa

AU - Baldelomar, Edwin

AU - Dowling, John P

AU - Charlton, Jennifer R

AU - Forbes, Michael Shepard

AU - Ng, Amanda Ching Lih

AU - Wu, Qi-Zhu

AU - Armitage, James A

AU - Egan, Gary F

AU - Bertram, John F

AU - Bennett, Kevin M

PY - 2014

Y1 - 2014

N2 - Nephron number (Nglom) and size (Vglom) 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 Nglom and Vglom in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure Nglom and Vglom in functioning 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 functioning human kidneys. A fourth naive 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 3D 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 spectral analyses and may be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.

AB - Nephron number (Nglom) and size (Vglom) 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 Nglom and Vglom in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure Nglom and Vglom in functioning 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 functioning human kidneys. A fourth naive 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 3D 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 spectral analyses and may be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.

UR - http://www.ncbi.nlm.nih.gov/pubmed/24647716

U2 - 10.1152/ajprenal.00092.2014

DO - 10.1152/ajprenal.00092.2014

M3 - Article

VL - 306

SP - F1381 - F1390

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1522-1466

IS - 11

ER -