Manganese-Enhanced Magnetic Resonance Imaging Detects Declining Pancreatic β-Cell Mass in a Cyclophosphamide-Accelerated Mouse Model of Type 1 Diabetes
- Patrick F. Antkowiak1,
- Brian K. Stevens2,
- Craig S. Nunemaker3,
- Marcia McDuffie2,3 and
- Frederick H. Epstein1,4⇓
- 1Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia
- 2Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia
- 3Department of Medicine, University of Virginia, Charlottesville, Virginia
- 4Department of Radiology, University of Virginia, Charlottesville, Virginia
- Corresponding author: Frederick H. Epstein,
Currently, there is no ideal noninvasive method to quantify the progressive loss of pancreatic β-cell mass (BCM) that occurs in type 1 diabetes. Magnetic resonance imaging has detected gross differences in BCM between healthy and diabetic mice using the contrast agent manganese, which labels functional β-cells and increases the water proton relaxation rate (R1), but its ability to measure gradations in BCM during disease progression is unknown. Our objective was to test the hypothesis that measurements of the manganese-enhanced pancreatic R1 could detect decreasing BCM in a mouse model of type 1 diabetes. We used cyclophosphamide-accelerated BDC2.5 T-cell receptor transgenic nonobese diabetic mice, which experience development of type 1 diabetes during a 7-day time period after cyclophosphamide injection, whereas transgene-negative mice do not. We measured the manganese-enhanced pancreatic R1 before cyclophosphamide injection (day 0) and on days 3, 4, 5, and 7 afterward. Pancreatic R1 remained constant in transgene-negative mice and decreased stepwise day-to-day in transgene-positive mice, mirroring their loss of BCM, confirmed by pancreatic insulin measurements and histology. Changes in R1 in transgene-positive mice occurred before elevations in blood glucose, a clinical indicator of diabetes, suggesting potential for early noninvasive detection of changes in functional BCM.
- Received February 9, 2012.
- Accepted July 7, 2012.
- © 2013 by the American Diabetes Association.
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