•Provide an overview of the magnetic susceptibility properties of blood and their contribution to the MRI signal.•Describe the principles of existing MRI oximetry methods exploiting ...susceptibility-induced signal modulations.•Review recent advances in susceptibility-based MRI techniques for quantifying cerebral oxygen metabolism.•Summarize application studies using susceptibility-based MRI oximetry on human brain aging and neurodegenerative diseases.
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.
Purpose
To map the cerebral metabolic rate of oxygen (CMRO2) by estimating the oxygen extraction fraction (OEF) from gradient echo imaging (GRE) using phase and magnitude of the GRE data.
Theory and ...Methods
3D multi‐echo gradient echo imaging and perfusion imaging with arterial spin labeling were performed in 11 healthy subjects. CMRO2 and OEF maps were reconstructed by joint quantitative susceptibility mapping (QSM) to process GRE phases and quantitative blood oxygen level‐dependent (qBOLD) modeling to process GRE magnitudes. Comparisons with QSM and qBOLD alone were performed using ROI analysis, paired t‐tests, and Bland‐Altman plot.
Results
The average CMRO2 value in cortical gray matter across subjects were 140.4 ± 14.9, 134.1 ± 12.5, and 184.6 ± 17.9 μmol/100 g/min, with corresponding OEFs of 30.9 ± 3.4%, 30.0 ± 1.8%, and 40.9 ± 2.4% for methods based on QSM, qBOLD, and QSM+qBOLD, respectively. QSM+qBOLD provided the highest CMRO2 contrast between gray and white matter, more uniform OEF than QSM, and less noisy OEF than qBOLD.
Conclusion
Quantitative CMRO2 mapping that fits the entire complex GRE data is feasible by combining QSM analysis of phase and qBOLD analysis of magnitude.
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 (CMRO
) was calculated as the product of CBF and OEF. OEF, CMRO
, 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, CMRO
, 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 (
= 6.046,
= 0.005) and relative OEF (
= 5.699,
= 0.009) values of the ischemic core, but not in other measurements (absolute and relative CMRO
, CBF, ADC values, all values of
> 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.
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, O
6
-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
< 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
< 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.
This 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).
One 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.
Compared to the contralateral mirror area, the OEF of the infarcted region was decreased regardless of stroke phases (
< 0.05) and showed a declining tendency from the acute to the chronic phase (
= 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 (
= 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.
The 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.
Abstract Contrast-enhancing magnetic resonance mechanism, employing either positive or negative signal changes, has contrast-specific signal characteristics. Although highly sensitive, negative ...contrast typically decreases the resolution and spatial specificity of MRI, whereas positive contrast lacks a high contrast-to-noise ratio but offers high spatial accuracy. To overcome these individual limitations, dual-contrast acquisitions were performed using iron oxide nanoparticles and a pair of MRI acquisitions. Specifically, vascular signals in MR angiography were positively enhanced using ultrashort echo (UTE) acquisition, which provided highly resolved vessel structures with increased vessel/tissue contrast. In addition, fast low angle shot (FLASH) acquisition yielded strong negative vessel contrast, resulting in the higher number of discernible vessel branches than those obtained from the UTE method. Taken together, the high sensitivity of the negative contrast delineated ambiguous vessel regions, whereas the positive contrast effectively eliminated the false negative contrast areas (e.g., airways and bones), demonstrating the benefits of the dual-contrast method. From the Clinical Editor In this study, the MRI properties of iron oxide nanoparticles were studied in an animal model. These contrast agents are typically considered negative contrast materials, leading to signal loss on T2* weighted images, but they also have known T1 effects as well, which is lower than that of standard positive contrast agents (like gadolinium or manganese) but is still detectable. This dual property was utilized in this study, demonstrating high sensitivity of the negative contrast in delineating ambiguous vessel regions, whereas the positive contrast eliminated false negative contrast areas (areas giving rise to susceptibility effects).
Objective: The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral ...oxygen metabolism in preeclampsia. Materials and Methods: Forty-nine women with preeclampsia (mean age 32.4 years; range, 18-44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23-40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20-42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. Results: Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361-0.812). Conclusion: Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.
Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an essential biomarker used to directly assess tissue viability and function in neurologic disorders. In ...ischemic stroke, for example, increased OEF can indicate the presence of penumbra-tissue with low perfusion yet intact cellular integrity-making it a primary therapeutic target. However, practical OEF mapping methods are not currently available in clinical settings, owing to the impractical data acquisitions in positron emission tomography (PET) and the limitations of existing MRI techniques. Recently, a novel MRI-based OEF mapping technique, termed QQ, was proposed. It shows high potential for clinical use by utilizing a routine sequence and removing the need for impractical multiple gas inhalations. However, QQ relies on the assumptions of Gaussian noise in susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low signal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic Gaussian noise in mGRE complex signals. We implemented mcQQ using a deep learning framework (mcQQ-NET) and compared it with the existing QQ-NET in simulations, ischemic stroke patients, and healthy subjects, using identical training and testing datasets and schemes. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the subacute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaffected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR, such as SNR ≤ 15 (dB). Therefore, mcQQ-NET improves OEF accuracy by more accurately reflecting realistic Gaussian noise in complex mGRE signals. Its enhanced sensitivity to OEF abnormalities, based on more realistic biophysics modeling, suggests that mcQQ-NET has potential for investigating tissue variability in neurologic disorders.
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