Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults

Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO2 or O2 does not affect CMRO2. We evaluated the null hypothesis that two common hypercapnic stimuli, ‘CO2 in air’ and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO2 were calculated for room-air, ‘CO2 in air’ and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for ‘CO2 in air’ and carbogen, respectively). CMRO2 decreased for ‘CO2 in air’ (−13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO2 during carbogen did not significantly change. Our findings indicate that ‘CO2 in air’ is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.

Reduced magnetic resonance angiography signal intensity in the middle cerebral artery ipsilateral to severe carotid stenosis may be a practical index of high oxygen extraction fraction

Objectives Angiographic “slow flow” in the middle cerebral artery (MCA), caused by carotid stenosis, may be associated with high oxygen extraction fraction (OEF). If the MCA slow flow is associated with a reduced relative signal intensity (rSI) of the MCA on MR angiography, the reduced rSI may be associated with a high OEF. We investigated whether the MCA slow flow ipsilateral to carotid stenosis was associated with a high OEF and aimed to create a practical index to estimate the high OEF. Methods We included patients who underwent digital subtraction angiography (DSA) and MRA between 2015 and 2019 to evaluate carotid stenosis. MCA slow flow by image count using DSA, MCA rSI, minimal luminal diameter (MLD) of the carotid artery, carotid artery stenosis rate (CASr), and whole-brain OEF (wb-OEF) was evaluated. When MCA slow flow was associated with a high wb-OEF, the determinants of MCA slow flow were identified, and their association with high wb-OEF was evaluated. Results One hundred and twenty-seven patients met our inclusion criteria. Angiographic MCA slow flow was associated with high wb-OEF. We identified MCA rSI and MLD as determinants of angiographic MCA slow flow. The upper limits of MCA rSI and MLD for angiographic MCA slow flow were 0.89 and 1.06 mm, respectively. The wb-OEF was higher in patients with an MCA rSI ≤ 0.89 and ipsilateral MLD ≤ 1.06 mm than patients without this combination. Conclusions The combination of reduced MCA rSI and ipsilateral narrow MLD is a straightforward index of high wb-OEF. Key Points • The whole-brain OEF in patients with angiographic slow flow in the MCA ipsilateral to high-grade carotid stenosis was higher than in patients without it. • Independent determinants of MCA slow flow were MCA relative signal intensity (rSI) on MRA or minimal luminal diameter (MLD) of the carotid stenosis. • The wb-OEF was higher in patients with an MCA rSI ≤ 0.89 and ipsilateral MLD ≤ 1.06 mm than patients without this combination.

Application of Cluster Analysis of Time Evolution for Magnetic Resonance Imaging -Derived Oxygen Extraction Fraction Mapping: A Promising Strategy for the Genetic Profile Prediction and Grading of Glioma

Background: The intratumoral heterogeneity of oxygen metabolism and angiogenesis are core hallmarks of glioma, unveiling that genetic aberrations associated with magnetic resonance imaging (MRI) phenotypes may aid in the diagnosis and treatment of glioma.Objective: To explore the predictability of MRI-based oxygen extraction fraction (OEF) mapping using cluster analysis of time evolution (CAT) for genetic profiling and glioma grading.Methods: Ninety-one patients with histopathologically confirmed glioma were examined with CAT for quantitative susceptibility mapping and quantitative blood oxygen level–dependent magnitude-based OEF mapping and dynamic contrast-enhanced (DCE) MRI. Imaging biomarkers, including oxygen metabolism (OEF) and angiogenesis [volume transfer constant, cerebral blood volume (CBV), and cerebral blood flow], were investigated to predict IDH mutation, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, receptor tyrosine kinase (RTK) subgroup, and differentiation of glioblastoma (GBM) vs. lower-grade glioma (LGG). The corresponding DNA sequencing was also obtained. Results were compared with DCE-MRI using receiver operating characteristic (ROC) analysis.Results: IDH1-mutated LGGs exhibited significantly lower OEF and hypoperfusion than IDH wild-type tumors (all p &lt; 0.01). OEF and perfusion metrics showed a tendency toward higher values in MGMT unmethylated GBM, but only OEF retained significance (p = 0.01). Relative prevalence of RTK alterations was associated with increased OEF (p = 0.003) and perfusion values (p &lt; 0.05). ROC analysis suggested OEF achieved best performance for IDH mutation detection [area under the curve (AUC) = 0.828]. None of the investigated parameters enabled prediction of MGMT status except OEF with a moderate AUC of 0.784. Predictive value for RTK subgroup was acceptable by using OEF (AUC = 0.764) and CBV (AUC = 0.754). OEF and perfusion metrics demonstrated excellent performance in glioma grading. Moreover, mutational landscape revealed hypoxia or angiogenesis-relevant gene signatures were associated with specific imaging phenotypes.Conclusion: CAT for MRI-based OEF mapping is a promising technology for oxygen measurement and along with perfusion MRI can predict genetic profiles and tumor grade in a non-invasive and clinically relevant manner.Clinical Impact: Physiological imaging provides an in vivo portrait of genetic alterations in glioma and offers a potential strategy for non-invasively selecting patients for individualized therapies.

Brain oxygen extraction fraction mapping in patients with multiple sclerosis

We aimed to demonstrate the feasibility of whole brain oxygen extraction fraction (OEF) mapping for measuring lesion specific and regional OEF abnormalities in multiple sclerosis (MS) patients. In 22 MS patients and 11 healthy controls (HC), OEF and neural tissue susceptibility ([Formula: see text]) maps were computed from MRI multi-echo gradient echo data. In MS patients, 80 chronic active lesions with hyperintense rim on quantitative susceptibility mapping were identified, and the mean OEF and [Formula: see text] within the rim and core were compared using linear mixed-effect model analysis. The rim showed higher OEF and [Formula: see text] than the core: relative to their adjacent normal appearing white matter, OEF contrast = −6.6 ± 7.0% vs. −9.8 ± 7.8% (p < 0.001) and [Formula: see text] contrast = 33.9 ± 20.3 ppb vs. 25.7 ± 20.5 ppb (p = 0.017). Between MS and HC, OEF and [Formula: see text]were compared using a linear regression model in subject-based regions of interest. In the whole brain, compared to HC, MS had lower OEF, 30.4 ± 3.3% vs. 21.4 ± 4.4% (p < 0.001), and higher [Formula: see text], −23.7 ± 7.0 ppb vs. −11.3 ± 7.7 ppb (p = 0.018). Our feasibility study suggests that OEF may serve as a useful quantitative marker of tissue oxygen utilization in MS.

A case report: An increased oxygen extraction fraction in remote ischemic lesions after revascularization for moyamoya disease with a progression of posterior cerebral artery stenosis

The cerebral metabolism, such as the oxygen extraction fraction (OEF), in remote ischemic lesions following revascularization for moyamoya disease (MMD) has not yet been fully elucidated. We herein report a patient with an increased OEF in a remote ischemic lesion after revascularization in a case of adult-onset MMD. A 21-year-old woman suffered from a left parietal lobe infarction due to MMD. At 2 months after onset, left superficial temporal artery (STA)–middle cerebral artery (MCA) bypass and encephalo-myo-synangiosis (EMS) were performed. The postoperative course was uneventful. 15O-positron emission tomography (PET) performed at 2 months after the first operation revealed an increased OEF in the contralateral (right) frontal lobe that was suspected of being possible remote ischemia. The patient underwent right STA-MCA bypass and EMS. 15O-PET at 14 days after the second operation revealed an increased OEF in the contralateral (left) occipital lobe that was suspected of potentially being remote ischemia caused by a watershed shift. Two years after the second surgery, left occipital artery (OA)–posterior cerebral artery (PCA) anastomosis and EMS were performed due to transient right hemianopsia. Neither rebleeding nor ischemic complications occurred 2 years after the third surgery. We need to be alert for the possible progression of PCA stenosis in MMD after revascularization. It might induce remote ischemia after revascularization. OA–PCA bypass is therefore considered to be an effective treatment option in such cases.