SynopsisOxygenation status plays a major role in renal physiology and pathophysiology and hence has attracted considerable attention in recent years. While much of the early work and a significant amount of present work is based on invasive methods or ex vivo analysis and hence restricted to animal models, BOLD (blood oxygen level dependent) MRI has been shown to extend these findings to humans. BOLD MRI is most useful in monitoring effects of physiological or pharmacological maneuvers. Several teams around the world have demonstrated reproducible data and have illustrated several useful applications. Studies supporting the use of renal BOLD MRI in characterizing disease with prognostic value have also been reported. Here, an overview of the current state-of-the art of renal BOLD MRI is provided. KeywordsBOLD; kidney; MRI; oxygenation; blood flow; renal failure IntroductionRenal oxygenation status is receiving greater attention from both the scieintific and clinical communities [1][2][3]. In most organs, regional oxygen tension (pO 2 ) closely follows the level of regional blood flow, since oxygen consumption is relatively constant. But this is not true in the kidney, where active tubular reabsorption demands more oxygen consumption whenever filtration and blood flow rise together [4]. Over a wide range of normal blood flows the renal arterio-venous oxygen gradient is remarkably constant. For the purposes of function and oxygen supply, the mammalian kidney can be considered to be made of two separate organs, cortex and medulla [4]. The flow of blood to the renal cortex normally supplies oxygen far in excess of its metabolic needs. By contrast, blood flow to the renal medulla is parsimonious. In addition, oxygen diffuses from the arterial to venous vasa recta, and the process of generating an osmotic gradient by active reabsorption of sodium requires large amount of oxygen. All these combined, result in a poorly oxygenated medulla. A non-invasive method to evaluate this heterogeneous distribution of oxygen availability within the kidney is highly desirable. Blood oxygenation level dependent (BOLD) MRI has been shown to be useful in evaluating intra-renal oxygenation status both in animal models and in humans. In this article, we provide Corresponding author for proof and reprints: Pottumarthi V. Prasad, Radiology Department / Center for Advanced Imaging, Walgreen Building, Suite G507, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201, Tel: (847) 570-1349, E-mail: pprasad@enh.org. Coauthor(s) address(es): Luping Li and Sarah Halter, Radiology Department / Center for Advanced Imaging, Walgreen Building, Suite G507, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201, Tel: (847) 570-1948, E-mail: lli2@enh.org Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is ...
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. Research Design and 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 s−1, 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.
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