Human renovascular disease: estimating fractional tissue hypoxia to analyze blood oxygen level-dependent MR

Abstract

Purpose: To test the hypothesis that fractional kidney hypoxia, measured by using blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging, correlates with renal blood flow (RBF), tissue perfusion, and glomerular filtration rate (GFR) in patients with atherosclerotic renal artery stenosis (RAS) better than regionally selected region of interest-based methods.

Materials and methods: The study was approved by the institutional review board according to a HIPAA-compliant protocol, with written informed consent. BOLD MR imaging was performed in 40 patients with atherosclerotic RAS (age range, 51-83 years; 22 men, 18 women) and 32 patients with essential hypertension (EH) (age range, 26-85 years; 19 men, 13 women) during sodium intake and renin-angiotensin blockade. Fractional kidney hypoxia (percentage of entire axial image section with R2* above 30 sec(-1)) and conventional regional estimates of cortical and medullary R2* levels were measured. Stenotic and nonstenotic contralateral kidneys were compared for volume, tissue perfusion, and blood flow measured with multidetector computed tomography. Statistical analysis was performed (paired and nonpaired t tests, linear regression analysis).

Results: Stenotic RBF was reduced compared with RBF of contralateral kidneys (225.2 mL/min vs 348 mL/min, P = .0003). Medullary perfusion in atherosclerotic RAS patients was lower than in EH patients (1.07 mL/min per milliliter of tissue vs 1.3 mL/min per milliliter of tissue, P = .009). While observer-selected cortical R2* (18.9 sec(-1) [stenosis] vs 18.5 sec(-1) [EH], P = .07) did not differ, fractional kidney hypoxia was higher in stenotic kidneys compared with kidneys with EH (17.4% vs 9.6%, P < .0001) and contralateral kidneys (7.2%, P < .0001). Fractional hypoxia correlated inversely with blood flow (r = -0.34), perfusion (r = -0.3), and GFR (r = -0.32).

Conclusion: Fractional tissue hypoxia rather than cortical or medullary R2* values used to assess renal BOLD MR imaging demonstrated a direct relationship to chronically reduced blood flow and GFR.

Figures

Figure 1a:

Methods for ROI selection on axial images. (a) T2-weighted image shows observer-selected ROIs (1–7) for multiple zones in cortex (ROIs 2, 4, and 6) and medulla (ROIs 3, 5, and 7) conventionally applied for BOLD MR data measurement. (b) Image depicts determination of fractional tissue hypoxia by outlining of the entire axial kidney section located within parenchyma. An additional ROI was placed to outline “wide segment” cortical area excluding the renal collecting system, incidental cysts, and the hilar vessels. ROIs = 1 and 2 (also on c). (c) R2* parametric map for the selected axial section, reflecting widely variable R2* levels and deoxyhemoglobin at different sites within the kidney, particularly in medullary zones.

Figure 1b:

Methods for ROI selection on axial images. (a) T2-weighted image shows observer-selected ROIs (1–7) for multiple zones in cortex (ROIs 2, 4, and 6) and medulla (ROIs 3, 5, and 7) conventionally applied for BOLD MR data measurement. (b) Image depicts determination of fractional tissue hypoxia by outlining of the entire axial kidney section located within parenchyma. An additional ROI was placed to outline “wide segment” cortical area excluding the renal collecting system, incidental cysts, and the hilar vessels. ROIs = 1 and 2 (also on c). (c) R2* parametric map for the selected axial section, reflecting widely variable R2* levels and deoxyhemoglobin at different sites within the kidney, particularly in medullary zones.

Figure 1c:

Methods for ROI selection on axial images. (a) T2-weighted image shows observer-selected ROIs (1–7) for multiple zones in cortex (ROIs 2, 4, and 6) and medulla (ROIs 3, 5, and 7) conventionally applied for BOLD MR data measurement. (b) Image depicts determination of fractional tissue hypoxia by outlining of the entire axial kidney section located within parenchyma. An additional ROI was placed to outline “wide segment” cortical area excluding the renal collecting system, incidental cysts, and the hilar vessels. ROIs = 1 and 2 (also on c). (c) R2* parametric map for the selected axial section, reflecting widely variable R2* levels and deoxyhemoglobin at different sites within the kidney, particularly in medullary zones.

Figure 2:

Graph shows fractional tissue hypoxia (R2* > 30 sec−1) in EH, RAS beyond the stenosis (RAS [SK]) and RAS in contralateral kidneys (RAS [CK]); before (solid bars) and after (open bars) administration of furosemide. Basal fractional hypoxia was higher in stenotic kidneys than in contralateral kidneys and kidneys with EH (P < .0001 and P < .001, respectively). Note that fractional hypoxia decreased after furosemide administration in all groups (* = P < .0001).

Figure 3a:

(a) Graph shows relationship between fractional kidney hypoxia (basal) of all kidneys and RBF (r = −0.34). (b) Graph shows relationship between fractional kidney hypoxia (basal) of all kidneys and single-kidney GFR (in milliliters per minute per kidney) (r = −0.32).

Figure 3b:

(a) Graph shows relationship between fractional kidney hypoxia (basal) of all kidneys and RBF (r = −0.34). (b) Graph shows relationship between fractional kidney hypoxia (basal) of all kidneys and single-kidney GFR (in milliliters per minute per kidney) (r = −0.32).

Figure 4a:

R2* parametric maps in 61-year-old man with EH (a) and 74-year-old man with atherosclerotic RAS (b) obtained by using the same color scale for R2*. Cortical R2* (ROIs 2, 4, and 6) and medullary R2* (ROIs 3, 5, and 7) obtained by using the observer-selected ROIs were similar in both kidneys (mean for EH cortex was 22 sec−1 vs 22.4 sec−1 for atherosclerotic RAS and mean for medulla was 32 sec−1 vs 32.6 sec−1, respectively); however, the fractional hypoxia in atherosclerotic RAS was far greater than that in EH (28.5% vs 11.3%). ROIs = 1–7.

Figure 4b:

R2* parametric maps in 61-year-old man with EH (a) and 74-year-old man with atherosclerotic RAS (b) obtained by using the same color scale for R2*. Cortical R2* (ROIs 2, 4, and 6) and medullary R2* (ROIs 3, 5, and 7) obtained by using the observer-selected ROIs were similar in both kidneys (mean for EH cortex was 22 sec−1 vs 22.4 sec−1 for atherosclerotic RAS and mean for medulla was 32 sec−1 vs 32.6 sec−1, respectively); however, the fractional hypoxia in atherosclerotic RAS was far greater than that in EH (28.5% vs 11.3%). ROIs = 1–7.