Oxygen Extraction Fraction Maps Research Articles

Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease.

To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2) in children with SCD. Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2. An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps. Fifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO2 in this region, which encompassed the CBF nadir, was low relative to all white matter (p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort. Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.

Dynamic measurement of oxygen extraction fraction using a multiecho asymmetric spin echo (MASE) pulse sequence.

PurposeThe oxygen extraction fraction (OEF), an important parameter for assessing brain oxygen metabolism, is a key marker of brain health. Dynamic measurement of the OEF is currently limited by the long acquisition time. In this study, a noninvasive method for rapidly and effectively assessing dynamic changes in the OEF during brain stimulation is proposed.MethodsA novel pulse sequence using the multi‐echo asymmetric spin echo with an echo‐planar imaging acquisition scheme was developed to improve the temporal resolution of functional OEF measurements. A theoretical formulation that describes the multi‐echo asymmetric spin echo signal dephasing phenomena in the presence of deoxygenated hemoglobin was established. A functional motor experiment was performed using human subjects, in which both OEF maps using the multi‐echo asymmetric spin echo sequence and blood oxygenation level–dependent maps using a ‐weighted gradient‐echo echo‐planar imaging sequence were generated and compared.ResultsThe activation maps for both OEF and blood oxygenation level–dependent maps revealed significant changes in the motor cortex. Our results, which were consistent with the previous reports, showed that the average relative changes in the OEF and blood oxygenation level–dependent signal were −22% and 2.0%, respectively.ConclusionObtaining dynamic OEF measurements during functional experiments with the proposed multi‐echo asymmetric spin echo method is feasible. Magn Reson Med 80:1118–1124, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy

Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy. Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping-oxygen extraction fraction images. Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping-oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5-249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping-oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively. Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy.

Functional oxygen extraction fraction (OEF) imaging with turbo gradient spin echo QUIXOTIC (Turbo QUIXOTIC).

QUantitative Imaging of eXtraction of Oxygen and TIssue Consumption (QUIXOTIC) is a recent technique that measures voxel-wise oxygen extraction fraction (OEF) but suffers from long scan times, limiting its application. We implemented multiecho QUIXOTIC dubbed turbo QUIXOTIC (tQUIXOTIC) that reduces scan time eightfold and then applied it in functional MRI. tQUIXOTIC utilizes a novel turbo gradient spin echo readout enabling measurement of venular blood transverse relaxation rate in a single tag-control acquisition. Using tQUIXOTIC, we estimated cortical gray matter (GM) OEF, created voxel-by-voxel GM OEF maps, and quantified changes in visual cortex OEF during a blocked design flashing checkerboard visual stimulus. Contamination from cerebrospinal fluid partial volume averaging was estimated and corrected. The average cortical GM OEF was estimated as 0.38 ± 0.06 (n = 8) using a 3.4-min acquisition. The average OEF in the visual cortex was estimated as 0.43 ± 0.04 at baseline and 0.35 ± 0.05 during activation, with an average %ΔOEF of -20%. These values are consistent with those of past studies. tQUIXOTIC successfully estimated cortical GM OEF in clinical scan times and detected changes in OEF during blocked design visual stimulation. tQUIXOTIC will be useful to monitor regional OEF clinically and in blocked design or event-related functional MRI experiments. Magn Reson Med 79:2713-2723, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

The oxygen extraction fraction (OEF) in systemic lupus erythematosus (SLE): MRI study using quantitative susceptibility mapping (QSM)

Background: Oxygen extraction fraction (OEF) can provide information about the relative deficiencies in cerebral blood supply with the tissue’s demand and the increased risk of stroke. Although, in systemic lupus erythematosus (SLE), the cerebral hypoperfusion has been related to its disease activity, there was no previous studies regarding the OEF as a risk of stroke. Recently, MRI-based OEF maps were generated from quantitative susceptibility mapping (QSM) images using extraction of venous susceptibility induced by deoxygenated hemoglobin, and the OEF using QSM (QSM-OEF) could achieve good correlation with OEF using PET.

Noninvasive Assessment of Oxygen Extraction Fraction in Chronic Ischemia Using Quantitative Susceptibility Mapping at 7 Tesla

The oxygen extraction fraction (OEF) is an effective metric to evaluate metabolic reserve in chronic ischemia. However, OEF is considered to be accurately measured only when using positron emission tomography (PET). Thus, we investigated whether OEF maps generated by magnetic resonance quantitative susceptibility mapping (QSM) at 7 Tesla enabled detection of OEF changes when compared with those obtained with PET. Forty-one patients with chronic stenosis/occlusion of the unilateral internal carotid artery or middle cerebral artery were examined using 7 Tesla-MRI and PET scanners. QSM images were obtained from 3-dimensional T2*-weighted images, using a multiple dipole-inversion algorithm. OEF maps were generated based on susceptibility differences between venous structures and brain tissues on QSM images. OEF ratios of the ipsilateral middle cerebral artery territory against the contralateral side were calculated on the QSM-OEF and PET-OEF images, using an anatomic template. The OEF ratio in the middle cerebral artery territory showed significant correlations between QSM-OEF and PET-OEF maps (r=0.69; P<0.001), especially in patients with a substantial increase in the PET-OEF ratio of 1.09 (r=0.79; P=0.004), although showing significant systematic biases for the agreements. An increased QSM-OEF ratio of >1.09, as determined by receiver operating characteristic analysis, showed a sensitivity and specificity of 0.82 and 0.86, respectively, for the substantial increase in the PET-OEF ratio. Absolute QSM-OEF values were significantly correlated with PET-OEF values in the patients with increased PET-OEF. OEF ratios on QSM-OEF images at 7 Tesla showed a good correlation with those on PET-OEF images in patients with unilateral steno-occlusive internal carotid artery/middle cerebral artery lesions, suggesting that noninvasive OEF measurement by MRI can be a substitute for PET.

Oxygen extraction fraction mapping at 3 Tesla using an artificial neural network: A feasibility study.

The oxygen extraction fraction (OEF) is an important biomarker for tissue-viability. MRI enables noninvasive estimation of the OEF based on the blood-oxygenation-level-dependent (BOLD) effect. Quantitative OEF-mapping is commonly applied using least-squares regression (LSR) to an analytical tissue model. However, the LSR method has not yet become clinically established due to the necessity for long acquisition times. Artificial neural networks (ANNs) recently have received increasing interest for robust curve-fitting and might pose an alternative to the conventional LSR method for reduced acquisition times. This study presents in vivo OEF mapping results using the conventional LSR and the proposed ANN method. In vivo data of five healthy volunteers and one patient with a primary brain tumor were acquired at 3T using a gradient-echo sampled spin-echo (GESSE) sequence. The ANN was trained with simulated BOLD data. In healthy subjects, the mean OEF was 36 ± 2% (LSR) and 40 ± 1% (ANN). The OEF variance within subjects was reduced from 8% to 6% using the ANN method. In the patient, both methods revealed a distinct OEF hotspot in the tumor area, whereas ANN showed less apparent artifacts in surrounding tissue. In clinical scan times, the ANN analysis enables OEF mapping with reduced variance, which could facilitate its integration into clinical protocols. Magn Reson Med 79:890-899, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Determination of oxygen extraction fraction using magnetic resonance imaging in canine models with internal carotid artery occlusion.

Perfusion of the penumbra tissue below the flow threshold for functional disturbance but above that for the maintenance of morphological integrity is the target for therapy in acute ischaemic stroke. The measurement of the oxygen extraction fraction (OEF) may provide a direct assessment of tissue viability, so that irreversible tissue damage and penumbra can be reliably identified. By using an asymmetric spin echo single-shot echo planar imaging (ASE-SSEPI) sequence, the quantitative OEF was obtained in the ischaemic brain tissues of canine models with internal carotid artery occlusion. TTC staining, which delineated the regions of infarct and penumbra, was used for defining the corresponding regions on OEF maps. The threshold of the OEF to discriminate the infarct cores and penumbral tissues was then determined according to the OEF values at different times. With repeated-measures ANOVA, the OEF of the infarcted regions was found to be time dependent. An OEF greater than 0.48 best predicted cortical infarction at 1.5 hr, with an area under the receiving operating characteristic curve of 0.968, a sensitivity of 97.5%, and a specificity of 92.5%. Our results may be helpful in the evaluation of tissue viability during stroke events.

Cerebral metabolic rate of oxygen (CMRO2) mapping with hyperventilation challenge using quantitative susceptibility mapping (QSM)

Our objective was to demonstrate the feasibility of using hyperventilation as an efficient vasoconstrictive challenge and prior knowledge as denoising constraints for cerebral metabolic rate of oxygen (CMRO2 ) mapping based upon quantitative susceptibility mapping (QSM). Three-dimensional (3D) multi-echo gradient echo and arterial spin labeling imaging were performed to calculate QSM and perfusion maps before and after a hyperventilation challenge in 11 healthy subjects. For comparison, this was repeated using a caffeine challenge. Whole-brain CMRO2 and oxygen extraction fraction (OEF) maps were computed using constrained optimization. Hyperventilation scans were repeated to measure reproducibility. Regional agreement of CMRO2 and OEF maps was analyzed within the cortical gray matter (CGM) using t-test and Bland-Altman plots. Hyperventilation challenge eliminates the 30-min waiting time needed for caffeine to exert its vasoconstrictive effects. Mean CMRO2 (in µmol/100g/min) obtained in CGM using the caffeine and repeated hyperventilation scans were 149 ± 16, 153 ± 19, and 150 ± 20, respectively. This corresponded to an OEF of 33.6 ± 3.4%, 32.3 ± 3.2%, and 34.1 ± 3.8% at baseline state and 39.8 ± 4.8%, 43.6 ± 6.2%, and 42.8 ± 6.8% at challenged state, respectively. Hyperventilation scans produced a good agreement of CMRO2 and OEF values. Hyperventilation is a feasible, reproducible, and efficient vasoconstrictive challenge for QSM-based quantitative CMRO2 mapping. Magn Reson Med 77:1762-1773, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Abstract WMP97: Regional Cerebral Oxygen Extraction is Elevated in Tissue at High Risk of Stroke in Pediatric Sickle Cell Disease

Introduction: Children with sickle cell disease (SCD) are at high risk of stroke. Hemispheric oxygen extraction fraction (OEF) is a predictor of stroke in adults with carotid occlusion, but OEF has not been evaluated as a predictor of stroke in children with SCD. Hypothesis: OEF is elevated in SCD children compared to controls within a region at high risk of stroke as defined by an infarct heat-map created from a separate retrospective SCD cohort. Methods: A prospective MRI study enrolled 37 children aged 5-21: 17 with SCD and no stroke, 12 with SCD and silent infarcts (median infarct volume=0.3ml), and 8 sibling controls. None were on transfusions or had overt stroke history. Voxel-wise OEF was measured using an asymmetric spin echo sequence. In a separate retrospective cohort of 67 SCD children with overt and silent stroke, infarct regions on FLAIR were manually outlined and coregistered to an average T1 map to create an infarct heat-map (Fig A) which was used to define a “high risk” ROI (defined by &gt;3% infarct density). This ROI was aligned to individual OEF maps from the prospective cohort (Fig B, average OEF map). OEF within the “high risk” ROI was compared between SCD children and controls; and between SCD children with and without infarction using Mann Whitney U tests. Results: The infarct heat-map from the retrospective cohort (Fig A) and the average OEF map from the prospective SCD cohort (Fig B) demonstrate striking co-localization of infarct density and elevated OEF. Within the “high risk” ROI, OEF was higher in SCD children compared to controls (39% [36, 46] vs. 23% [22, 27], p&lt;0.0001 (Fig C). OEF within this “high risk” ROI did not differ between SCD children with and without infarcts (40% [38, 47] vs. 38% [35, 46], p=0.6). Conclusion: OEF in SCD children is elevated in the internal borderzone, a region with high stroke risk in SCD. Regional OEF may be a marker of cerebral metabolic stress that could be exploited to stratify stroke risk in this vulnerable population.

Oxygen extraction fraction measurement using quantitative susceptibility mapping: Comparison with positron emission tomography

The purposes of this study are to establish oxygen extraction fraction (OEF) measurements using quantitative susceptibility mapping (QSM) of magnetic resonance imaging (MRI), and to compare QSM–OEF data with the gold standard 15O positron emission tomography (PET). Twenty-six patients with chronic unilateral internal carotid artery or middle cerebral artery stenosis or occlusion, and 15 normal subjects were included. MRI scans were conducted using a 3.0 Tesla scanner with a three-dimensional spoiled gradient recalled sequence. QSM images were created using the morphology-enabled dipole inversion method, and OEF maps were generated from QSM images using extraction of venous susceptibility induced by deoxygenated hemoglobin. Significant correlation of relative OEF ratio to contra-lateral hemisphere between QSM–OEF and PET–OEF was observed (r = 0.62, p < 0.001). The local (intra-section) correlation was also significant (r = 0.52, p < 0.001) in patients with increased PET–OEF. The sensitivity and specificity of OEF increase in QSM was 0.63 (5/8) and 0.89 (16/18), respectively, in comparison with PET. In conclusion, good correlation was achieved between QSM–OEF and PET–OEF in the identification of elevated OEF in affected hemispheres of patients with unilateral chronic steno-occlusive disease.

Non-invasive multiparametric qBOLD approach for robust mapping of the oxygen extraction fraction

IntroductionThe quantitative blood oxygenation level-dependent (qBOLD) method has not become clinically established yet because long acquisition times are necessary to achieve an acceptable certainty of the parameter estimates. In this work, a non-invasive multiparametric (nimp) qBOLD approach based on a simple analytical model is proposed to facilitate robust oxygen extraction fraction (OEF) mapping within clinically acceptable acquisition times by using separate measurements. MethodsThe protocol consisted of a gradient-echo sampled spin-echo sequence (GESSE), a T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) sequence, and a T2*-weighted multi-slice multi-echo gradient echo (MMGE) sequence. The GESSE acquisition time was less than 5 minutes and the extra measurement time for CPMG / MMGE was below 2 minutes each. The proposed nimp-qBOLD approach was validated in healthy subjects (N = 5) and one patient. ResultsThe proposed nimp-qBOLD approach facilitated more robust OEF mapping with significantly reduced inter- and intra-subject variability compared to the standard qBOLD method. Thereby, an average OEF in all subjects of 27±2% in white matter (WM) and 29±2% in gray matter (GM) using the nimp-qBOLD method was more stable compared to 41±10% (WM) and 46±10% (GM) with standard qBOLD. Moreover, the spatial variance in the image slice (i.e. standard deviation divided by mean) was on average reduced from 35% to 25%. In addition, the preliminary results of the patient are encouraging. ConclusionThe proposed nimp-qBOLD technique provides a promising tool for robust OEF mapping within clinically acceptable acquisition times and could therefore provide an important contribution for analyzing tumors or monitoring the success of radio and chemo therapies.

MR evaluation of cerebral oxygen metabolism and blood flow in stroke-like episodes of MELAS

Metabolic information is essential in the investigation of the pathophysiology of stroke-like episodes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Here, we used magnetic resonance imaging to evaluate the dynamic metabolic changes before and after a stroke-like episode in two patients with MELAS caused by the mitochondrial DNA mutation A3243G. We performed functional magnetic resonance imaging, including arterial spin labeling and oxygen extraction fraction imaging, and generated cerebral blood flow and oxygen extraction fraction maps. We recruited eight healthy volunteers to define the normal range of the oxygen extraction fraction. We detected a heterogeneous reduction in the oxygen extraction fraction in the brain in the interictal period as well as at the onset of a stroke-like attack. However, the oxygen extraction fraction in the stroke-like lesions normalized in the acute stage. The stroke-like lesions showed consistent hyperperfusion in the acute phase but hypoperfusion in the chronic phase. We have demonstrated the utility of using new magnetic resonance imaging techniques in the evaluation of the pathophysiology of stroke-like lesions. The increased utilization of oxygen in an acute lesion is a novel finding in our study, which might play a role in the oxidative stress.

Decreased Chronic-Stage Cortical 11 C-Flumazenil Binding After Focal Ischemia-Reperfusion in Baboons

Although the penumbra can be saved by early reperfusion, in the rat it is consistently affected by selective neuronal loss. Mapping selective neuronal loss in the living primate would be desirable. Five young adult baboons underwent (15)O positron emission tomography for cerebral blood flow, cerebral oxygen consumption, and oxygen extraction fraction mapping at baseline and serially during and after 20-hour temporary middle cerebral artery occlusion. At approximately day 30, (11)C-flumazenil (FMZ), a potential positron emission tomography marker of selective neuronal loss, and structural magnetic resonance-based infarct mapping were obtained, and the brain was perfused-fixed. Reduced FMZ binding in noninfarcted cortical middle cerebral artery areas was searched voxel-wise, and specific binding was assessed using compartmental modeling of FMZ time-activity curves. Visual inspection revealed reduced late FMZ uptake in the affected cortical territory, extending well beyond the infarct. Accordingly, the incidence of selected voxels was greater than chance, documenting mildly but significantly reduced FMZ uptake and specific binding. Serial (15)O positron emission tomography revealed moderately severe acute ischemia followed by reperfusion. Histopathology documented only mild neuronal changes in or near the affected areas. We document moderate but definite late FMZ binding decrements in noninfarcted cortical areas in the baboon, consistent with previous rat and human studies. These were acutely characterized by moderate ischemia followed by reperfusion, consistent with neuronal damage from ischemic or reperfusion injury in the salvaged at-risk tissue. Only mild histopathological changes subtended these FMZ alterations suggesting subtle processes such as isolated dendrite or synapse loss. Whether these changes impact on clinical outcome deserves studying because they may be targeted by specific neuroprotection.