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 21) 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 21 [stenosis] vs 18.5 sec 21 [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 = 20.34), perfusion (r = 20.3), and GFR (r = 20.32). 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.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

Renal Relevant Radiology

“…The severity of the artifact increases at higher magnetic fields, and warrants careful selection of regions of interest. Notably, analytical methods utilizing histogram-based tools that recognize the variability of the BOLD signal intensity within the regions of interest may be capable of detecting differences (40) and introduce new markers beyond the traditional mean of R 2 * value, such as their distribution (41,42).…”

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia

“…Two ROIs were traced: one that selected the renal cortex (large segment) for estimation of cortical R2*, and the second, which included the entire kidney slice, including both cortex and medulla while excluding the renal collecting system and any incidental renal cysts to determine the fractional tissue hypoxia of the entire slice, as previously described [5].…”

“…that reflect local levels of deoxyhemoglobin within the kidney [5,[22][23][24]. We have previously shown that R2* levels are higher in stenotic kidneys compared with contralateral kidneys in ARAS and kidneys of hypertensive patients [5].…”

“…Although the kidney is abundantly perfused due to its filtration function and can tolerate moderate reductions in blood flow, severe ARAS elicits complex biological responses that eventually lead to chronic kidney injury [1][2][3]. High-grade ARAS leads to cortical and medullary hypoxia [4][5][6] and activates inflammatory pathways and tissue fibrosis in both experimental and human studies [7]. Advanced ARAS is associated with reduced glomerular filtration rate (GFR) and elevated renal vein levels of neutrophil gelatinase associated lipocalin (NGAL), tumor necrosis factor α (TNF-α) and other injury biomarkers from the poststenotic kidney [6,8,9].…”

Renal Vein Levels of MicroRNA-26a Are Lower in the Poststenotic Kidney

“…39 miR-26a level was evaluated using RT-PCR in renal vein and inferior vena cava samples in patients with RVD or EH and peripheral venous samples from healthy volunteers. Total RNAwas isolated from 400-ml plasma samples by the mirVana PARIS Total RNA Isolation Kit (Life Technologies, Carlsbad, CA).…”