Evaluation of renal hypoxia in diabetic mice by BOLD MRI.
OBJECTIVE
Renal hypoxia has been proposed to be a pathophysiologic feature of diabetic kidney disease but it has been difficult to demonstrate in vivo, particularly in mouse models of diabetes. The objective of this work was to examine the sensitivity of blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to assess renal oxygenation in vivo in a mouse model of diabetic kidney disease, the db/db mice.


METHODS
Kidney BOLD MRI studies were performed on a 3.0 T scanner using multiple gradient echo sequence with a custom-designed surface coil to acquire T2*-weighted images. Studies were performed in 10-week-old db/db mice (n = 7) and db/m controls (n = 6).


RESULTS
R2* is a measure of the tissue deoxyhemoglobin concentration and higher values of R2* are associated with hypoxia. The db/db mice had higher medullary (43.1 ± 5.1 s⁻¹ vs. 32.3 ± 3.7⁻¹ s, P = 0.001) and cortical R2* (31.7 ± 3.1 s⁻¹ vs. 27.1 ± 4.1 s⁻¹, P = 0.04) values. Using pimonidazole staining as a marker of kidney hypoxia, in kidney sections from 10-week-old db/db mice neither cortex nor medulla had significant differences as compared with 10-week-old db/m mice (cortex: db/db 2.14 ± 0.05 vs. db/m 2.02 ± 0.28, medulla: db/db 2.81 ± 0.08 vs. db/m 2.6 ± 0.08). The db/db mice demonstrated further increased cortical and medullary hypoxia when scanned again at 15 weeks of age.


CONCLUSIONS
The report shows that renal BOLD MRI is a sensitive method for the in vivo evaluation of renal hypoxia in a mouse model of diabetic kidney disease where progressive renal hypoxia can be documented over time. BOLD MRI may be useful to monitor therapeutic interventions that may improve tissue hypoxia in the diabetic kidney.
Prasad
Pottumarthi
P
Radiology Department, Center for Advanced Imaging, Northshore University Healthsystem, Evanston, IL, USA. pprasad@northshore.org
Li
Lu-Ping
LP
Halter
Sarah
S
Cabray
Joann
J
Ye
Minghao
M
Batlle
Daniel
D
D000367:Age Factors; D000818:Animals; D003928:Diabetic Nephropathies / Q000097:blood*; D000860:Hypoxia / Q000097:blood*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009593:Nitroimidazoles; D010100:Oxygen / Q000097:blood*; D013194:Staining and Labeling
D009593:Nitroimidazoles; C033815:pimonidazole; D010100:Oxygen