Measurement Of Oxygen Extraction Fraction Research Articles

Comparison of cerebral oxygen extraction fraction using ASE and TRUST methods in patients with sickle cell disease and healthy controls.

Abnormal oxygen extraction fraction (OEF), a putative biomarker of cerebral metabolic stress, may indicate compromised oxygen delivery and ischemic vulnerability in patients with sickle cell disease (SCD). Elevated OEF was observed at the tissue level across the brain using an asymmetric spin echo (ASE) MR method, while variable global OEFs were found from the superior sagittal sinus (SSS) using a T2-relaxation-under-spin-tagging (TRUST) MRI method with different calibration models. In this study, we aimed to compare the average ASE-OEF in the SSS drainage territory and TRUST-OEF in the SSS from the same SCD patients and healthy controls. 74 participants (SCD: N = 49; controls: N = 25) underwent brain MRI. TRUST-OEF was quantified using the Lu-bovine, Bush-HbA and Li-Bush-HbS models. ASE-OEF and TRUST-OEF were significantly associated in healthy controls after controlling for hematocrit using the Lu-bovine or the Bush-HbA model. However, no association was found between ASE-OEF and TRUST-OEF in patients with SCD using either the Bush-HbA or the Li-Bush-HbS model. Plausible explanations include a discordance between spatially volume-averaged oxygenation brain tissue and flow-weighted volume-averaged oxygenation in SSS or sub-optimal calibration in SCD. Further work is needed to refine and validate non-invasive MR OEF measurements in SCD.

Cerebral oxygen metabolism from MRI susceptibility

This article provides an overview of MRI methods exploiting magnetic susceptibility properties of blood to assess cerebral oxygen metabolism, including the tissue oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2). The first section is devoted to describing blood magnetic susceptibility and its effect on the MRI signal. Blood circulating in the vasculature can have diamagnetic (oxyhemoglobin) or paramagnetic properties (deoxyhemoglobin). The overall balance between oxygenated and deoxygenated hemoglobin determines the induced magnetic field which, in turn, modulates the transverse relaxation decay of the MRI signal via additional phase accumulation. The following sections of this review then illustrate the principles underpinning susceptibility-based techniques for quantifying OEF and CMRO2. Here, it is detailed whether these techniques provide global (OxFlow) or local (Quantitative Susceptibility Mapping - QSM, calibrated BOLD - cBOLD, quantitative BOLD - qBOLD, QSM+qBOLD) measurements of OEF or CMRO2, and what signal components (magnitude or phase) and tissue pools they consider (intravascular or extravascular). Validations studies and potential limitations of each method are also described. The latter include (but are not limited to) challenges in the experimental setup, the accuracy of signal modeling, and assumptions on the measured signal. The last section outlines the clinical uses of these techniques in healthy aging and neurodegenerative diseases and contextualizes these reports relative to results from gold-standard PET.

Review of the Research Progress of Human Brain Oxygen Extraction Fraction by Magnetic Resonance Imaging.

In recent years, the incidence of cerebrovascular diseases (CVD) is increasing, which seriously endangers human health. The study on hemodynamics of cerebrovascular disease can help us to understand, prevent, and treat the disease. As one of the important parameters of human cerebral hemodynamics and tissue metabolism, OEF (oxygen extraction fraction) is of great value in central nervous system diseases. The use of BOLD (blood oxygen level dependent) effect offers the possibility to study cerebral hemodynamic and metabolic characteristics by MRI (magnetic resonance imaging) measurements. Therefore, this paper reviews the hemodynamic parameters of brain tissue, discusses the principles and methods of quantitative BOLD-based MRI measurements of OEF, and discusses the advantages and disadvantages of each method.

Cerebral oxygen extraction fraction MRI: Techniquesand applications.

The human brain constitutes 2% of the body's total mass but uses 20% of the oxygen. The rate of the brain's oxygen utilization can be derived from a knowledge of cerebral blood flow and the oxygen extraction fraction (OEF). Therefore, OEF is a key physiological parameter of the brain's function and metabolism. OEF has been suggested to be a useful biomarker in a number of brain diseases. With recent advances in MRI techniques, several MRI-based methods have been developed to measure OEF in the human brain. These MRI OEF techniques are based on the T2 of blood, the blood signal phase, the magnetic susceptibility of blood-containing voxels, the effect of deoxyhemoglobin on signal behavior in extravascular tissue, and the calibration of the BOLD signal using gas inhalation. Compared to 15 O PET, which is considered the "gold standard" for OEF measurement, MRI-based techniques are non-invasive, radiation-free, and are more widely available. This article provides a review of these emerging MRI-based OEF techniques. We first briefly introduce the role of OEF in brain oxygen homeostasis. We then review the methodological aspects of different categories of MRI OEF techniques, including their signal mechanisms, acquisition methods, and data analyses. The strengths and limitations of the techniques are discussed. Finally, we review key applications of these techniques in physiological and pathological conditions.

Cerebral oxygen metabolic stress is increased in children with sickle cell anemia compared to anemic controls.

Patients with sickle cell anemia (SCA) experience cerebral metabolic stress with an increase in oxygen extraction fraction (OEF) to compensate for reduced oxygen carrying capacity due to anemia. It remains unclear if anemia alone drives this metabolic stress. Using MRI, we collected voxel-wise OEF measurements to test our hypothesis that OEF would be elevated in anemic controls without SCA (AC) compared to healthy controls (HC), but OEF would be even higher in SCA compared to AC. Brain MRIs (N=159) were obtained in 120 participants (34 HC, 27 AC, 59 SCA). While hemoglobin was lower in AC versus HC (p < 0.001), hemoglobin was not different between AC and SCA cohorts (p=0.459). Whole brain OEF was higher in AC compared to HC (p < 0.001), but lower compared to SCA (p=0.001). Whole brain OEF remained significantly higher in SCA compared to HC (p=0.001) while there was no longer a difference between AC versus HC (p=0.935) in a multivariate model controlling for age and hemoglobin. OEF peaked within the border zone regions of the brain in both SCA and AC cohorts, but the volume of white matter with regionally elevated OEF in AC was smaller (1.8%) than SCA (58.0%). While infarcts colocalized within regions of elevated OEF, more SCA participants had infarcts than AC (p < 0.001). We conclude that children with SCA experience elevated OEF compared to AC and HC after controlling for the impact of anemia, suggesting that there are other pathophysiologic factors besides anemia contributing to cerebral metabolic stress in children with SCA.

Variability of Retinal Oxygen Metrics in Healthy and Diabetic Subjects.

PurposePrevious studies have reported alterations in total retinal blood flow (TRBF), oxygen delivery (DO2), oxygen metabolism (MO2), and oxygen extraction fraction (OEF) due to retinal diseases. The purposes of the current study were to determine variabilities and establish normal confidence intervals (CIs) for these metrics.MethodsA total of 22 healthy and 14 diabetic subjects participated in the study. Retinal vascular oxygen saturation (SO2) and TRBF were measured by oximetry and Doppler optical coherence tomography, respectively. DO2, MO2, and OEF were calculated from SO2 and TRBF measurements. Means, standard deviations (SDs), and CIs of metrics were determined in healthy subjects. Intra-visit variability was determined by the mean SDs of repeated measurements. Inter-visit variability was determined by the difference of measurements between two visits.ResultsTRBF was 44 ± 15 µL/min (95% CI, 37–51) in healthy subjects. Intra-visit variabilities of TRBF were 5 µL/min and 6 µL/min in healthy and diabetic subjects, respectively. Inter-visit variability of TRBF was 3 µL/min in diabetic subjects. DO2, MO2, and OEF were 8.3 ± 2.9 µLO2/min (95% CI, 7.0–9.6), 3.2 ± 0.9 µLO2/min (95% CI, 2.8–3.6), and 0.40 ± 0.08 (95% CI, 0.36–0.43), respectively, in healthy subjects. Inter-visit variabilities of DO2, MO2, and OEF were 0.6 µLO2/min, 0.1 µLO2/min, and 0.03, respectively, in diabetic subjects.ConclusionsThe findings established variabilities and normal baselines for TRBF, DO2, MO2, and OEF measurements in a small cohort of subjects.Translational RelevanceThe variability and normal baselines of retinal oxygen metrics may be useful for diagnosing and monitoring patients with retinal diseases.

The Spatiotemporal Evolution of MRI-Derived Oxygen Extraction Fraction and Perfusion in Ischemic Stroke.

PurposeThis study aimed to assess the spatiotemporal evolution of oxygen extraction fraction (OEF) in ischemic stroke with a newly developed cluster analysis of time evolution (CAT) for a combined quantitative susceptibility mapping and quantitative blood oxygen level-dependent model (QSM + qBOLD, QQ).MethodOne hundred and fifteen patients in different ischemic stroke phases were retrospectively collected for measurement of OEF of the infarcted area defined on diffusion-weighted imaging (DWI). Clinical severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Of the 115 patients, 11 underwent two longitudinal MRI scans, namely, three-dimensional (3D) multi-echo gradient recalled echo (mGRE) and 3D pseudo-continuous arterial spin labeling (pCASL), to evaluate the reversal region (RR) of the initial diffusion lesion (IDL) that did not overlap with the final infarct (FI). The temporal evolution of OEF and the cerebral blood flow (CBF) in the IDL, the RR, and the FI were assessed.ResultsCompared to the contralateral mirror area, the OEF of the infarcted region was decreased regardless of stroke phases (p < 0.05) and showed a declining tendency from the acute to the chronic phase (p = 0.022). Five of the 11 patients with longitudinal scans showed reversal of the IDL. Relative oxygen extraction fraction (rOEF, compared to the contralateral mirror area) of the RR increased from the first to the second MRI (p = 0.044). CBF was about 1.5-fold higher in the IDL than in the contralateral mirror area in the first MRI. Two patients showed penumbra according to the enlarged FI volume. The rOEF of the penumbra fluctuated around 1.0 at earlier scan times and then decreased, while the CBF decreased continuously.ConclusionThe spatiotemporal evolution of OEF and perfusion in ischemic lesions is heterogeneous, and the CAT-based QQ method is feasible to capture cerebral oxygen metabolic information.

A non-invasive reference-based method for imaging the cerebral metabolic rate of oxygen by PET/MR: theory and error analysis

Positron emission tomography (PET) remains the gold standard for quantitative imaging of the cerebral metabolic rate of oxygen (CMRO2); however, it is an invasive and complex procedure that requires accounting for recirculating [15O]H2O (RW) and the cerebral blood volume (CBV). This study presents a non-invasive reference-based technique for imaging CMRO2 that was developed for PET/magnetic resonance imaging (MRI) with the goal of simplifying the PET procedure while maintaining its ability to quantify metabolism. The approach is to use whole-brain (WB) measurements of oxygen extraction fraction (OEF) and cerebral blood flow (CBF) to calibrate [15O]O2-PET data, thereby avoiding the need for invasive arterial sampling. Here we present the theoretical framework, along with error analyses, sensitivity to PET noise and inaccuracies in input parameters, and initial assessment on PET data acquired from healthy participants. Simulations showed that neglecting RW and CBV corrections caused errors in CMRO2 of less than ±10% for changes in regional OEF of ±25%. These predictions were supported by applying the reference-based approach to PET data, which resulted in remarkably similar CMRO2 images to those generated by analyzing the same data using a modeling approach that incorporated the arterial input functions and corrected for CBV contributions. Significant correlations were observed between regional CMRO2 values from the two techniques (slope = 1.00 ± 0.04, R 2 > 0.98) with no significant differences found for integration times of 3 and 5 min. In summary, results demonstrate the feasibility of producing quantitative CMRO2 images by PET/MRI without the need for invasive blood sampling.

Bulk volume susceptibility difference between deoxyhemoglobin and oxyhemoglobin for HbA and HbS: A comparative study.

Sickle cell anemia is a blood disorder that alters the morphology and the oxygen affinity of the red blood cells. Cerebral oxygen extraction fraction measurements using quantitative BOLD contrast have been used for assessing inadequate oxygen delivery and the subsequent risk of ischemic stroke in sickle cell anemia. The BOLD signal in MRI studies relies on , the bulk volume susceptibility difference between fully oxygenated and fully deoxygenated blood. Several studies have measured for normal hemoglobin A (HbA). However, it is not known whether the value is different for sickle hemoglobin. In this study, was measured for both HbA and sickle hemoglobin. Six sickle cell anemia patients and 6 controls were recruited. Various blood oxygenation levels were achieved through in vivo manipulations to keep the blood close to its natural state. To account for the differences in oxygen affinity, Hill's equations were used to translate partial pressure of oxygen to oxygen saturation for HbA, sickle hemoglobin, and fetal hemoglobin (HbF) separately. The pH and PCO2 corrections were performed. Temperature and magnetic field drift were controlled for. A multivariate generalized linear mixed model with random participant effect was used. Assuming that is similar for HbA and HbF and that is 5/4 of for HbA, it was found that the values for HbA and sickle hemoglobin were not statistically significantly different from each other. The same value can be used for both types of hemoglobin in quantitative BOLD analysis.

Abstract 153: Non-invasive Measurement of Cerebral Tissue Oxygen Extraction Fraction is Correlated with Microdialysis Brain Injury Biomarkers During Extracorporeal Cardiopulmonary Resuscitation

Introduction: Extracorporeal membrane oxygenation (ECMO) assisted CPR (ECPR) can improve outcomes after prolonged or unsuccessful resuscitative efforts, but neurological injury remains common in survivors. The lack of routine neuromonitoring during ECPR and ECMO prohibits brain-targeted management to help improve neurological outcomes. In this study, we examine the association of non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) measurements of cerebral tissue oxygen extraction fraction (OEF), an indicator of metabolic stress, with invasively collected brain injury biomarkers to explore the utility of this monitoring modality during ECPR. Hypothesis: FD-DOS measurement of cerebral OEF is positively correlated with biomarkers of brain injury (lactate-pyruvate ratio, LPR; glycerol). Methods: Cerebral OEF was continuously monitored by FD-DOS in nine pediatric swine (8-11 kg) who underwent 30-60 minutes of manual CPR, were cannulated for ECMO, and remained on ECMO for 22-24 hours. Cerebral pyruvate, lactate, glycerol and glucose content were measured from cerebral microdialysate samples collected hourly. The correlation between OEF and microdialysis parameters were assessed using a linear mixed-effects model incorporating subject-specific random slope and intercept effects. Significance was determined at p&lt;0.05. Results: Microdialysis parameters from 192 samples were compared against non-invasive OEF values. OEF was significantly correlated with LPR (p=0.001), and relative change in glycerol (p=0.005) and glucose (p=0.020) concentrations from baseline. Conclusions: Non-invasive FD-DOS neuromonitoring of OEF demonstrated significant correlations with invasive brain injury biomarkers; increasing OEF was associated with elevated LPR and glycerol, and diminished glucose. FD-DOS detection of critical neurometabolic stress at the bedside may facilitate brain-targeted ECMO management after cardiac arrest.

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

To evaluate the accuracy of T2 -based whole-brain oxygen extraction fraction (OEF) estimation by comparing it with gold standard 15 O-PET measurements. Sixteen healthy adult subjects underwent MRI and 15 O-PET OEF measurements on the same day. On MRI, whole-brain OEF was quantified by T2 -relaxation-under-spin-tagging (TRUST) MRI, based on subject-specific hematocrit. The TRUST OEF was compared to the whole-brain averaged OEF produced by 15 O-PET. Agreement between TRUST and 15 O-PET whole-brain OEF measurements was examined in terms of intraclass correlation coefficient (ICC) and in absolute OEF values. In a subset of 10 subjects, test-retest reproducibility of whole-brain OEF was also evaluated and compared between the two modalities. Across the 16 subjects, the mean whole-brain OEF of TRUST and 15 O-PET were 36.44±4.07% and 36.45±3.65%, respectively, showing no difference between the two modalities (P=.99). TRUST whole-brain OEF strongly correlated with that of 15 O-PET (N=16, ICC=0.90, P=4×10-7 ). The coefficient-of-variation of TRUST and 15 O-PET whole-brain OEF measurements were 1.79±0.67% and 2.06±1.55%, respectively, showing no difference between the two modalities (N=10, P=.64). Further analyses on the effect of hematocrit revealed that correlation between PET OEF and TRUST OEF with assumed hematocrit remained significant (ICC=0.8, P<2×10-5 ). Whole-brain OEF measured by TRUST was in excellent agreement with gold standard 15 O-PET, with highly comparable accuracy and reproducibility. These findings suggest that TRUST MRI can provide accurate quantification of whole-brain OEF noninvasively.

Oxygen extraction fraction mapping with multi-parametric quantitative BOLD MRI: Reduced transverse relaxation bias using 3D-GraSE imaging

Magnetic resonance imaging (MRI)-based quantification of the blood-oxygenation-level-dependent (BOLD) effect allows oxygen extraction fraction (OEF) mapping. The multi-parametric quantitative BOLD (mq-BOLD) technique facilitates relative OEF (rOEF) measurements with whole brain coverage in clinically applicable scan times. Mq-BOLD requires three separate scans of cerebral blood volume and transverse relaxation rates measured by gradient-echo (1/T2∗) and spin-echo (1/T2). Although the current method is of clinical merit in patients with stroke, glioma and internal carotid artery stenosis (ICAS), there are relaxation measurement artefacts that impede the sensitivity of mq-BOLD and artificially elevate reported rOEF values.We posited that T2-related biases caused by slice refocusing imperfections during rapid 2D-GraSE (Gradient and Spin Echo) imaging can be reduced by applying 3D-GraSE imaging sequences, because the latter requires no slice selective pulses. The removal of T2-related biases would decrease overestimated rOEF values measured by mq-BOLD. We characterized effects of T2-related bias in mq-BOLD by comparing the initially employed 2D-GraSE and two proposed 3D-GraSE sequences to multiple single spin-echo reference measurements, both in vitro and in vivo. A phantom and 25 participants, including young and elderly healthy controls as well as ICAS-patients, were scanned. We additionally proposed a procedure to reliably identify and exclude artefact affected voxels. In the phantom, 3D-GraSE derived T2 values had 57% lower deviation from the reference. For in vivo scans, the formerly overestimated rOEF was reduced by −27% (p ​< ​0.001). We obtained rOEF ​= ​0.51, which is much closer to literature values from positron emission tomography (PET) measurements. Furthermore, increased sensitivity to a focal rOEF elevation in an ICAS-patient was demonstrated.In summary, the application of 3D-GraSE improves the mq-BOLD-based rOEF quantification while maintaining clinically feasible scan times. Thus, mq-BOLD with non-slice selective T2 imaging is highly promising to improve clinical diagnostics of cerebrovascular diseases such as ICAS.

Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia

AbstractChronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P < .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.

Volume-localized measurement of oxygen extraction fraction in the brain using MRI.

PurposeT2‐relaxation‐under‐spin‐tagging (TRUST) is an MR technique for the non‐invasive assessment of whole‐brain cerebral oxygen extraction fraction (OEF), through measurement of the venous blood T2 relaxation time in the sagittal sinus. A key limitation of TRUST, however, is the lack of spatial specificity of the measurement. We sought to develop a modified TRUST sequence, selective localized TRUST (SL‐TRUST), having sensitivity to venous blood T2 within a targeted brain region, and therefore achieving spatially localized measurements of cerebral tissue OEF, while still retaining acquisition in the sagittal sinus.MethodsA method for selective localization of TRUST sequence was developed, and the reproducibility of the technique was evaluated in healthy participants. Regional measurements were achieved for a single hemisphere and for a 3D‐localized 70 × 70 × 80 mm3 tissue region using SL‐TRUST and compared to a global TRUST measure. An additional measure of venous blood T1 in the sagittal sinus was used to estimate subject‐specific hematocrit. Six subjects were scanned over 4 sessions, including intra‐session repeat measurements.ResultsThe average T2 in the sagittal sinus was found to be 60.8 ± 8.9, 62.7 ± 7.9, 64.6 ± 8.4, and 66.3 ± 10.3 ms (mean ± SD) for conventional TRUST, global SL‐TRUST, hemispheric SL‐TRUST, and 3D‐localized SL‐TRUST, respectively. Intra‐, inter‐session, and inter‐subject coefficients of variation for OEF using SL‐TRUST were found to be comparable and in some cases superior to those obtained using TRUST.ConclusionOEF comparison of 2 contralateral regions was achievable in under 5 min suggesting SL‐TRUST offers potential for quantifying regional OEF differences in both healthy and clinical populations.

Characterization of MRI techniques to assess neonatal brain oxygenation and blood flow.

There is increasing interest in applying physiological MRI in neonates, based on the premise that physiological parameters may provide an early biomarker of neonatal brain health and injury. Two commonly used techniques are oxygen extraction fraction (OEF) measurement using T2 -relaxation-under-spin-tagging (TRUST) MRI and cerebral blood flow measurement using phase-contrast (PC) quantitative flow MRI, which collectively provide an assessment of the brain's oxygen consumption. However, prior research has only demonstrated proof of principle of these methods in neonates, without characterization or benchmarking of the techniques. This is because available time is limited in neonatal subjects, especially when scans are performed as add-ons to clinical scans (typically less than 5min). The work presented aims to examine the TRUST and PC MRI sequences systematically in normal neonates, through research-dedicated scan sessions. A series of characterization and optimization studies were conducted in a total of 26 radiographically normal neonates on 3T systems. Our results show that TRUST MRI at the superior sagittal sinus (SSS) provides an OEF measurement equivalent to that at the internal jugular vein (r=0.80, n=10), yet with shorter scan time. Lower resolution provided better precision in the TRUST measurement (p=0.001, n=9). Therefore, the preferred OEF measurement is to apply TRUST MRI at the SSS using a spatial resolution of 2.5mm. For PC MRI, our results showed that non-gated PC MRI yielded blood flow measurements comparable to those from the more time-consuming gated approach in neonates (r=0.89, n=7). It was also found that blood flow could be overestimated by 18% when imaging resolution is larger than 0.3mm (n=7). Therefore, non-gated PC MRI with a spatial resolution of 0.3mm is recommended for neonatal applications. In conclusion, this study verifies consistency of neonatal brain oxygenation and flow measurements across acquisition schemes and points to optimal strategies in parameter selection when using these sequences.

Elevated brain oxygen extraction fraction in preterm newborns with anemia measured using noninvasive MRI.

To test the hypothesis that cerebral oxygen extraction fraction (OEF) is elevated and inversely related to hematocrit level in anemic former very-low-birth-weight infants near term. Prospective study of non-sedated preterm infants (post-menstrual age = 36 ± 2 weeks) over a range of hematocrits (0.23-0.49). Anatomical (T1-W, T2-W, and diffusion-weighted), cerebral blood flow (CBF), and OEF 3-T MRI were utilized. Statistical analysis included Spearman's rank-order correlation testing between study variables and intraclass correlation coefficients (ICC) calculated between consecutively acquired OEF scans. Consecutive OEF measurements showed moderate-to-good agreement (ICC = 0.71; 95% CI = 0.40-0.87). OEF increased with worsening anemia (ρ = -0.58; p = 0.005), and OEF and basal ganglia CBF were positively correlated (ρ = 0.49; p = 0.023). Noninvasive OEF MRI has moderate-to-good repeatability in non-sedated former preterm infants nearing term-equivalent age. Strong correlation of elevated OEF with anemia suggests hemodynamic compensation for anemia and could establish OEF as a useful biomarker of transfusion threshold for preterm infants.

Measurement of oxygen extraction fraction by blood sampling to estimate severe cerebral hemodynamic failure and anticipate cerebral hyperperfusion syndrome following carotid artery stenting

BackgroundCerebral hyperperfusion syndrome (CHS) is likely to occur after carotid revascularization in patients with stage 2 hemodynamic failure (st2HF), in whom the oxygen extraction fraction (OEF) increases.ObjectiveThe purpose of our...

Assessing the repeatability of absolute CMRO2, OEF and haemodynamic measurements from calibrated fMRI

As energy metabolism in the brain is largely oxidative, the measurement of cerebral metabolic rate of oxygen consumption (CMRO2) is a desirable biomarker for quantifying brain activity and tissue viability. Currently, PET techniques based on oxygen isotopes are the gold standard for obtaining whole brain CMRO2 maps. Among MRI techniques that have been developed as an alternative are dual calibrated fMRI (dcFMRI) methods, which exploit simultaneous measurements of BOLD and ASL signals during a hypercapnic-hyperoxic experiment to modulate brain blood flow and oxygenation.In this study we quantified the repeatability of a dcFMRI approach developed in our lab, evaluating its limits and informing its application in studies aimed at characterising the metabolic state of human brain tissue over time. Our analysis focussed on the estimates of oxygen extraction fraction (OEF), cerebral blood flow (CBF), CBF-related cerebrovascular reactivity (CVR) and CMRO2 based on a forward model that describes analytically the acquired dual echo GRE signal.Indices of within- and between-session repeatability are calculated from two different datasets both at a bulk grey matter and at a voxel-wise resolution and finally compared with similar indices obtained from previous MRI and PET measurements. Within- and between-session values of intra-subject coefficient of variation (CVintra) calculated from bulk grey matter estimates 6.7 ± 6.6% (mean ± std.) and 10.5 ± 9.7% for OEF, 6.9 ± 6% and 5.5 ± 4.7% for CBF, 12 ± 9.7% and 12.3 ± 10% for CMRO2. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) maps showed the spatial distribution of the repeatability metrics, informing on the feasibility limits of the method.In conclusion, results show an overall consistency of the estimated physiological parameters with literature reports and a satisfactory level of repeatability considering the higher spatial sensitivity compared to other MRI methods, with varied performance depending on the specific parameter under analysis, on the spatial resolution considered and on the study design.

Abstract TP211: Gray and White Matter Hemodynamics and Metabolism Measured Using Magnetic Resonance Imaging

Background: Reliable methods used to measure cerebral hemodynamics, metabolism and autoregulation are time-consuming and invasive. Objectives: We sought to measure cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ), in the whole brain, gray and white matter and detect physiological changes in humans under normal and ≈10% reductions in mean arterial pressure (MAP). Methods: CBF was measured using pseudo continuous arterial spin labeling (pCASL). OEF was measured using a MRI asymmetric spin echo-planar imaging (EPI). The arterial content of oxygen (CaO 2 ) was computed. CMRO 2 was calculated using the equation CMRO 2 =CaO 2 xCBFxOEF. Cerebral autoregulation was determined by measuring changes in CBF, OEF and CMRO 2 in response to ≈10% reductions in MAP in stroke-free controls induced by IV Nicardipine infusion. Autoregulation was measured in the whole brain, gray matter and white matter. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Results: A total of 30 subjects were consented (Mean age 31, 93% male, 40% white, 43% black and 17% others). At baseline, CBF was measured in the whole brain (52.5±9.5 ml/100g/min), gray matter (72.0±13.0 ml/100g/min) and white matter (30.2±8.4 ml/100g/min). OEF was measured in the whole brain (0.32±0.02), gray matter (0.33±0.02) and white matter (0.30±0.01). CMRO 2 was measured in the whole brain (3.2±0.8 ml/100g/min), gray matter (4.6±1.1 ml/100g/min) and white matter (1.8±0.5 ml/100g/min). A target of 10% MAP lowering was successfully achieved in 18 subjects, resulting in a change of mean CBF in the whole brain (52 vs. 50, p=0.1), gray matter (72 vs. 69, p=0.2) and white matter (30 vs. 28, p=0.08). This translated to a AI of 0.3 ± 0.9 in the whole brain, 0.2±1.0 in the gray matter and 0.5±1.7 in the white matter. These CBF changes corroborated with no significant changes in OEF and CMRO 2 . Conclusions: MR measurement of CBF, OEF and CMRO 2 , in the whole brain, gray and white matter was comparable to measures obtained by invasive methods. Differences in these measures, as well as AI in the gray and white matter, may help understand cerebrovascular diseases that affect white matter such as lacunar strokes.

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.