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Elevated brain oxygen extraction fraction measured by MRI susceptibility relates to perfusion status in acute ischemic stroke.

ABSTRACT: Recent clinical trials of new revascularization therapies in acute ischemic stroke have highlighted the importance of physiological imaging to identify optimal treatments for patients. Oxygen extraction fraction (OEF) is a hallmark of at-risk tissue in stroke, and can be quantified from the susceptibility effect of deoxyhemoglobin molecules in venous blood on MRI phase scans. We measured OEF within cerebral veins using advanced quantitative susceptibility mapping (QSM) MRI reconstructions in 20 acute stroke patients. Absolute OEF was elevated in the affected (29.3 ± 3.4%) versus the contralateral hemisphere (25.5 ± 3.1%) of patients with large diffusion-perfusion lesion mismatch (P = 0.032). In these patients, OEF negatively correlated with relative CBF measured by dynamic susceptibility contrast MRI (P = 0.004), suggesting compensation for reduced flow. Patients with perfusion-diffusion match or no hypo-perfusion showed less OEF difference between hemispheres. Nine patients received longitudinal assessment and showed OEF ratio (affected to contralateral) of 1.2 ± 0.1 at baseline that normalized (decreased) to 1.0 ± 0.1 at follow-up three days later (P = 0.03). Our feasibility study demonstrates that QSM MRI can non-invasively quantify OEF in stroke patients, relates to perfusion status, and is sensitive to OEF changes over time. Clinical trial registration: Longitudinal MRI examinations of patients with brain ischemia and blood brain barrier permeability; clinicaltrials.org : NCT02077582.

SUBMITTER: Fan AP

PROVIDER: S-EPMC7026852 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:MRI-based oxygen extraction fraction imaging has a great potential benefit in the selection of clinical strategies for ischemic stroke patients. This study aimed to evaluate the performance of a challenge-free oxygen extraction fraction (OEF) mapping in a cohort of acute and subacute ischemic stroke patients. Consecutive ischemic stroke patients (a total of 30 with 5 in the acute stage, 19 in the early subacute stage, and 6 in the late subacute stage) were recruited. All subjects underwent MRI including multi-echo gradient echo (mGRE), diffusion weighted imaging (DWI), and 3D-arterial spin labeling (ASL). OEF maps were generated from mGRE phase + magnitude data, which were processed using quantitative susceptibility mapping (QSM) + quantitative blood oxygen level-dependent (qBOLD) imaging with cluster analysis of time evolution. Cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were reconstructed from 3D-ASL and DWI, respectively. Further, cerebral metabolic rate of oxygen (CMRO2) was calculated as the product of CBF and OEF. OEF, CMRO2, CBF, and ADC values in the ischemic cores (absolute values) and their contrasts to the contralateral regions (relative values) were evaluated. One-way analysis of variance (ANOVA) was used to compare OEF, CMRO2, CBF, and ADC values and their relative values among different stroke stages. The OEF value of infarct core showed a trend of decrease from acute, to early subacute, and to late subacute stages of ischemic stroke. Significant differences among the three stroke stages were only observed in the absolute OEF (F = 6.046, p = 0.005) and relative OEF (F = 5.699, p = 0.009) values of the ischemic core, but not in other measurements (absolute and relative CMRO2, CBF, ADC values, all values of p > 0.05). In conclusion, the challenge-free QSM + qBOLD-generated OEF mapping can be performed on stroke patients. It can provide more information on tissue viability that was not available with CBF and ADC and, thus, may help to better manage ischemic stroke patients.

Project description: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.

Project description:We analysed the importance of systemic and peripheral arteriovenous O2 difference ( a-v¯O2 difference and a-vf O2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake ( V˙O2max ). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion versus perfusion limitations vary with V˙O2max . Articles (n = 17) publishing individual data (n = 154) on V˙O2max , maximal cardiac output ( Q˙max ; indicator-dilution or the Fick method), a-v¯O2 difference (catheters or the Fick equation) and systemic O2 extraction fraction were identified. For the peripheral responses, group-mean data (articles: n = 27; subjects: n = 234) on leg blood flow (LBF; thermodilution), a-vf O2 difference and O2 extraction fraction (arterial and femoral venous catheters) were obtained. Q˙max and two-LBF increased linearly by 4.9-6.0 L · min-1 per 1 L · min-1 increase in V˙O2max (R2 = .73 and R2 = .67, respectively; both P < .001). The a-v¯O2 difference increased from 118-168 mL · L-1 from a V˙O2max of 2-4.5 L · min-1 followed by a reduction (second-order polynomial: R2 = .27). After accounting for a hypoxemia-induced decrease in arterial O2 content with increasing V˙O2max (R2 = .17; P < .001), systemic O2 extraction fraction increased up to ~90% ( V˙O2max : 4.5 L · min-1 ) with no further change (exponential decay model: R2 = .42). Likewise, leg O2 extraction fraction increased with V˙O2max to approach a maximal value of ~90-95% (R2 = .83). Muscle O2 diffusing capacity and the equilibration index Y increased linearly with V˙O2max (R2 = .77 and R2 = .31, respectively; both P < .01), reflecting decreasing O2 diffusional limitations and accentuating O2 delivery limitations. In conclusion, although O2 delivery is the main limiting factor to V˙O2max , enhanced O2 extraction fraction (≥90%) contributes to the remarkably high V˙O2max in endurance-trained individuals.

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Elevated brain oxygen extraction fraction measured by MRI susceptibility relates to perfusion status in acute ischemic stroke.

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