Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients

Abstract

Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38-0.45) compared to controls (interquartile range = 0.29-0.38), similar to participants with SCA (interquartile range = 0.37-0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.

Diminished cerebral oxygen extraction and metabolic rate in sickle cell disease using T2 relaxation under spin tagging MRI

“…This work uses validated empirical techniques and the blood of subjects with sickle cell disease to derive an HbS T 2b model that confers improved Y v predictions in SCD when to compared with existing T 2b models. These Y v predictions and the resulting physiological conclusions are contradictory to recently published MR oximetry results in SCD (9,18,19). Given the documented limitations of the extrapolating the bovine T 2b models outside its calibrated range (13), this work calls into question recent MR oximetry conclusions (9,18,19) and demonstrates that SCD patients exhibit decreased OEF proportional to their level of anemia.…”

Validation of T2‐based oxygen extraction fraction measurement with 15O positron emission tomography

“…The MRI scans performed on each subject are shown in Figure 1A. Each subject first underwent an anatomical T 1 -weighted Magnetization-Prepared-RApid-Gradient-Echo (MPRAGE) scan, with the following parameters: sagittal imaging plane, field of view (FOV) = 256 (readout, foothead) × 224 (phase-encoding, anterior-posterior) × 176 (slice, left-right) mm 3 ; voxel size = 1.0 × 1.0 × 1.0 mm 3 ; repetition time (TR) = 2.1 seconds; echo time (TE) = 4.2 ms; echo-spacing = 9.4 ms; TI = 1.1 seconds; and scan duration = 4.3 minutes.…”

“…All PET images were reconstructed via Filter Back Projection with a 3 mm full-width-at-half-maximum, resulting in a matrix size of 128 × 128 × 63 and a voxel size of 2 × 2 × 2.4 mm 3 .…”

“…Cerebral oxygen extraction fraction (OEF) is a potential biomarker in a variety of diseases, such as Alzheimer's disease, 1,2 cerebrovascular diseases, [3][4][5][6][7][8] multiple sclerosis, 9 and sickle cell anemia. 3,[10][11][12] The current gold-standard for image-based OEF quantification inside the human brain is positron emission tomography (PET) with three different 15 O-labeled radiotracers, 13 including 15 O-labeled carbon monoxide (C 15 O) to estimate cerebral blood volume (CBV), 15 O-labeled water (H 2 15 O) to measure cerebral blood flow (CBF), and 15 O-labeled oxygen ( 15 O 2 ) to measure oxygen utilization. OEF is computed from the three in combination.…”

“…[17][18][19][22][23][24][25][26][27][28] Many of these MRI-based methods have found clinical utility in various diseases. [1][2][3]6,9,29,30 However, few studies have validated MRI-based OEF estimations with gold standard 15 O-PET, 31 which would be important to ensure the accuracy of these methods and facilitate their broader clinical applications. T 2 -relaxation-under-spin-tagging (TRUST) is a widely used MRI technique to measure whole-brain OEF based on the relationship between blood T 2 and oxygenation.…”