The broad, long-term goal of this work is to measure kidney nephron and glomerular volume endowment in humans, in vivo. Each nephron contains a glomerulus, which functions as a high-pressure filter of blood macromolecules. Deficits in nephrons and glomeruli have been correlated with renal diseases such as diabetes, obesity, and hypertension. There is currently no noninvasive technique to count the total number of functioning renal glomeruli and nephrons in vivo. Such a technique would enable studies of kidney and systemic disease in humans, and would open a new area of animal studies of the susceptibility to renal disease. We propose that contrast-enhanced MRI, using MRI-detectable nanoparticles targeted to the glomerular basement membrane, can be used to accurately count the total number of glomeruli and measure glomerular volume in the whole, intact kidney. This proposal is focused on establishing this technique in mice. We further propose to assess the accuracy of the technique in the presence of systemic deficits in nephron endowment in mice. Once completed, the proposed work will open the possibility of real-time, in vivo glomerular counts and volume in studies of renal and systemic diseases in animals and humans.

Public Health Relevance

The purpose of this project is to develop a molecular MRI technique to count the number of kidney glomeruli and volume ex vivo and in vivo. This work will lay the foundation for the use of MRI-detectable nanoparticle probes to study single nephron structure and function in animal models and humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21DK091722-03
Application #
8895619
Study Section
Pathobiology of Kidney Disease Study Section (PBKD)
Program Officer
Ketchum, Christian J
Project Start
2013-08-03
Project End
2015-07-31
Budget Start
2013-08-03
Budget End
2015-07-31
Support Year
Fiscal Year
2013
Total Cost
$178,014
Indirect Cost
$49,094
Name
University of Hawaii
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Zhang, Min; Wu, Teresa; Beeman, Scott C et al. (2016) Efficient Small Blob Detection Based on Local Convexity, Intensity and Shape Information. IEEE Trans Med Imaging 35:1127-37
Charlton, Jennifer R; Pearl, Valeria M; Denotti, Anna R et al. (2016) Biocompatibility of ferritin-based nanoparticles as targeted MRI contrast agents. Nanomedicine 12:1735-45
Bennett, Kevin M; Beeman, Scott C; Baldelomar, Edwin J et al. (2016) Use of Cationized Ferritin Nanoparticles to Measure Renal Glomerular Microstructure with MRI. Methods Mol Biol 1397:67-79
Baldelomar, Edwin J; Charlton, Jennifer R; Beeman, Scott C et al. (2016) Phenotyping by magnetic resonance imaging nondestructively measures glomerular number and volume distribution in mice with and without nephron reduction. Kidney Int 89:498-505
Zhang, Min; Wu, Teresa; Bennett, Kevin M (2015) Small blob identification in medical images using regional features from optimum scale. IEEE Trans Biomed Eng 62:1051-62
Beeman, Scott C; Cullen-McEwen, Luise A; Puelles, Victor G et al. (2014) MRI-based glomerular morphology and pathology in whole human kidneys. Am J Physiol Renal Physiol 306:F1381-90
Clavijo Jordan, M Veronica; Beeman, Scott C; Baldelomar, Edwin J et al. (2014) Disruptive chemical doping in a ferritin-based iron oxide nanoparticle to decrease r2 and enhance detection with T1-weighted MRI. Contrast Media Mol Imaging 9:323-32
Bertram, John F; Cullen-McEwen, Luise A; Egan, Gary F et al. (2014) Why and how we determine nephron number. Pediatr Nephrol 29:575-80
Charlton, Jennifer R; Beeman, Scott C; Bennett, Kevin M (2013) MRI-detectable nanoparticles: the potential role in the diagnosis of and therapy for chronic kidney disease. Adv Chronic Kidney Dis 20:479-87
Bennett, K M; Bertram, John F; Beeman, Scott C et al. (2013) The emerging role of MRI in quantitative renal glomerular morphology. Am J Physiol Renal Physiol 304:F1252-7

Showing the most recent 10 out of 11 publications