Oxygen Extraction Fraction Research Articles

The retinal oxygen metabolism and hemodynamics as a substitute for biochemical tests to predict nonproliferative diabetic retinopathy.

Predicting the occurrence of nonproliferative diabetic retinopathy (NPDR) using biochemical parameters is invasive, which limits large-scale clinical application. Noninvasive retinal oxygen metabolism and hemodynamics of 215 eyes from 73 age-matched healthy subjects, 90 diabetic patients without DR, 40 NPDR, and 12 DR with postpanretinal photocoagulation were measured with a custom-built multimodal retinal imaging device. Diabetic patients underwent biochemical examinations. Two logistic regression models were developed to predict NPDR using retinal and biochemical metrics, respectively. The predictive model 1 using retinal metrics incorporated male gender, insulin treatment condition, diastolic duration, resistance index, and oxygen extraction fraction presented a similar predictive power with model 2 using biochemical metrics incorporated diabetic duration, diastolic blood pressure, and glycated hemoglobin A1c (area under curve: 0.73 vs. 0.70; sensitivity: 76% vs. 68%; specificity: 64% vs. 62%). These results suggest that retinal oxygen metabolic and hemodynamic biomarkers may replace biochemical parameters to predict the occurrence of NPDR .

The changes of oxygen extraction fraction in different types of lesions in relapsing-remitting multiple sclerosis: A cross-sectional and longitudinal study.

To explore the oxygen metabolism level of different types of lesions in relapsing-remitting multiple sclerosis (RRMS) patients by oxygen extraction fraction (OEF) both cross-sectionally and longitudinally. Forty-six RRMS patients and forty-one healthy controls (HC) went MRI examination. The quantitative susceptibility mapping (QSM) and OEF map were reconstructed from a 3D multi-echo gradient echo sequence. MS lesions in white matter were classified as contrast-enhancing lesions (CELs) on post-gadolinium T1-weighted sequence, paramagnetic rim lesions (PRLs), hyperintense lesions and non-hyperintense lesions on QSM, respectively. The susceptibility and OEF of different types of lesions were compared. The susceptibility and OEF values were measured and compared among different types of lesions. Among these RRMS patients, seventeen had follow-up MRI and 232 lesions, and baseline to follow-up longitudinal changes in susceptibility and OEF were measured. PRLs had higher susceptibility and lower OEF than CELs, hyperintense lesions, and non-hyperintense lesions. The hyperintense lesions had higher susceptibility and lower OEF than non-hyperintense lesions. In longitudinal changes, PRLs had susceptibility increased (P < 0.001) and OEF decreased (P < 0.001). The hyperintense lesions showed significant decreases in susceptibility (P = 0.020), and non-hyperintense lesions showed significant increases in OEF during follow-up (P = 0.005). Notably, hyperintense lesions may convert to PRLs or non-hyperintense lesions as time progresses, accompanied by changes of OEF and susceptibility in the lesions. This study revealed tissue damage and oxygen metabolism level in different types of MS lesions. The OEF may contribute to further understanding the evolution of MS lesions.

Evaluation of renal tubular function by multiparametric functional MRI in early diabetes

PurposeTo evaluate the tubular function in an alloxan-induced type 1 diabetes mellitus (DM) rabbit model measured by renal oxygenation (R2*), oxygen extraction fraction (OEF), and renal blood flow (RBF) using blood oxygenation level dependent, asymmetric spin echo, and arterial spin labeling MRI.MethodsTwenty-six rabbits were randomized into the 3-day DM group (n = 13) and the 7-day DM group (n = 13). We performed pairs of multiparametric MRIs (before and after furosemide injection) at baseline and 3/7 days post-DM, and scored pathological kidney injury. We performed statistical analyses using non-parametric, chi-square, and Spearman correlation tests.ResultsAt baseline, medullary R2* significantly decreased by 24.97% and 16.74% in the outer and inner stripes of the outer medulla (OS and IS, p = 0.006 and 0.003, respectively) after furosemide administration. While the corresponding OEF decreased by 15.91% for OS and 16.67% for IS (both p = 0.003), and no significant change in medullary RBF was observed (p > 0.05). In the 3-day DM group, the decrease of medullary R2* and OEF post-furosemide became unremarkable, suggesting tubular dysfunction. We noticed similar changes in the 7-day DM group. Correlation analysis showed pathological tubular injury score significantly correlated with medullary ∆R2* (post-furosemide – pre-furosemide difference, r = 0.82 for OS and 0.82 for IS) and ∆OEF (r = 0.82 for OS and 0.82 for IS) (p < 0.001, respectively).Conclusion: The combination of medullary OEF and R2* in response to furosemide could detect renal tubular dysfunction in early DM.

Differential changes in blood flow and oxygen utilization in active muscles between voluntary exercise and electrical muscle stimulation in young adults.

The physiological effects on blood flow and oxygen utilization in active muscles during and after involuntary contraction triggered by electrical muscle stimulation (EMS) remain unclear, particularly compared with those elicited by voluntary (VOL) contractions. Therefore, we used diffuse correlation and near-infrared spectroscopy (DCS-NIRS) to compare changes in local muscle blood flow and oxygen consumption during and after these two types of muscle contractions in humans. Overall, 24 healthy young adults participated in the study, and data were successfully obtained from 17 of them. Intermittent (2-s contraction, 2-s relaxation) isometric ankle dorsiflexion with a target tension of 20% of maximal VOL contraction was performed by EMS or VOL for 2 min, followed by a 6-min recovery period. DCS-NIRS probes were placed on the tibialis anterior muscle, and relative changes in local tissue blood flow index (rBFI), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rMRO2) were continuously derived. EMS induced more significant increases in rOEF and rMRO2 than VOL exercise but a comparable increase in rBFI. After EMS, rBFI and rMRO2 decreased more slowly than after VOL and remained significantly higher until the end of the recovery period. We concluded that EMS augments oxygen consumption in contracting muscles by enhancing oxygen extraction while increasing oxygen delivery at a rate similar to the VOL exercise. Under the conditions examined in this study, EMS demonstrated a more pronounced and/or prolonged enhancement in local muscle perfusion and aerobic metabolism compared with VOL exercise in healthy participants.

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.

Towards tumour hypoxia imaging: Incorporating relative oxygen extraction fraction mapping of prostate with multi-parametric quantitative MRI on a 1.5T MR-linac.

Hypoxia plays a central role in tumour radioresistance. Reliable tumour hypoxia imaging would allow the monitoring of tumour response and a more personalized adaptation of radiotherapy planning. Here, we showed a proof of concept of the feasibility and repeatability of relative oxygen extraction fraction (rOEF) mapping of prostate using multi-parametric quantitative MRI (qMRI) achieved for the first time on a 1.5T MR-linac. T2, T2* relaxation times maps, and intra-voxel incoherent motion (IVIM) parametric maps mapping were computed on a 29 years old healthy volunteer. R2' and rOEF maps werecalculated based on a multi-parametric model. Long-term repeatability and repeatability coefficient (RC) were determined for each parameter according to QIBA recommendations. Mean values for the entire healthy prostate were 0.99 ± 0.14 × 10-3 mm/s2, 81 ± 2.1 × 10-3 mm/s2, 21.6 ± 3.6%, 92.7 ± 19.7 ms and 62.4 ± 17.3 ms for Dslow, Dfast, f, T2 and T2*, respectively. R2' and rOEF in the prostate were 6.1 ± 3.4 s-1 and 18.2 ± 10.1% respectively. The RC of rOEF was 4.43%. Long-term repeatability of quantitative parameters based on a test-retest ranged from 2 to 18%. qMRI parameters are measurable and repeatable on 1.5T MR LINAC. From T2, T2* and IVIM parameters maps, we were able to obtain a rOEF mapping of the prostate.These results are the first step to a non-invasive imaging of tumour hypoxia during radiotherapy leading to a biological image-guided adaptive radiotherapy.

Assessment of sepsis-associated encephalopathy by quantitative magnetic resonance spectroscopy in a rat model of cecal ligation and puncture

Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive technique to quantify neurometabolic compounds in the living brain. We used 1H-MRS to evaluate the brain metabolites in a rat model of Sepsis-associated encephalopathy (SAE) established by cecal ligation and puncture (CLP). 36 male Sprague-Dawley rats were randomly divided into sham and CLP groups. Each group was further divided into three subgroups: subgroup O, subgroup M, and subgroup N. Neurological function assessments were performed on the animals in the subgroup O and subgroup N at 24 h, 48 h, and 72 h. The animals in the subgroup M were examined by magnetic resonance imaging (MRI) at 12 h after CLP. Compared with the sham group, the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the hippocampus was significantly lower in the CLP group. The respective ratios of lactate (Lac), myo-inositol (mIns), glutamate and glutamine (Glx), lipid (Lip), and choline (Cho) to Cr in the CLP group were clearly higher than those in the sham group. Cytochrome c, intimately related to oxidative stress, was elevated in the CLP group. Neurofilament light (NfL) chain and glial fibrillary acidic protein (GFAP) scores in the CLP group were significantly higher than those in the sham group, while zonula occludens-1 (ZO-1) was downregulated. Compared with the sham group, the CLP group displayed higher values of oxygen extraction fraction (OEF), central venous–arterial partial pressure of carbon dioxide (P (cv-a) CO2), and central venous lactate (VLac). In contrast, jugular venous oxygen saturation (SjvO2) declined. In the present study, 1H-MRS could be used to quantitatively assess brain injury in terms of microcirculation disorder, oxidative stress, blood–brain barrier disruption, and glial cell activation through changes in metabolites within brain tissue.

The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease

AbstractVoxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin–labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI–measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments.

Clinical, qualitative imaging biomarkers, and tumor oxygenation imaging biomarkers for differentiation of midline-located IDH wild-type glioblastomas and H3 K27-altered diffuse midline gliomas in adults

PurposeTo compare the clinical, qualitative and quantitative imaging phenotypes, including tumor oxygenation characteristics of midline-located IDH-wildtype glioblastomas (GBMs) and H3 K27-altered diffuse midline gliomas (DMGs) in adults. MethodsPreoperative MRI data of 55 adult patients with midline-located IDH-wildtype GBM or H3 K27-altered DMG (32 IDH-wildtype GBM and 23 H3 K27-altered DMG patients) were included. Qualitative imaging assessment was performed. Quantitative imaging assessment including the tumor volume, normalized cerebral blood volume, capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), relative cerebral metabolic rate of oxygen values, and mean ADC value were performed from the tumor mask via automatic segmentation. Univariable and multivariable logistic analyses were performed. ResultsOn multivariable analysis, age (odds ratio [OR] = 0.92, P = 0.015), thalamus or medulla location (OR = 10.48, P = 0.013), presence of necrosis (OR = 0.15, P = 0.038), and OEF (OR = 0.01, P = 0.042) were independent predictors to differentiate H3 K27-altered DMG from midline-located IDH-wildtype GBM. The area under the curve, accuracy, sensitivity, and specificity of the multivariable model were 0.88 (95 % confidence interval: 0.77–0.95), 81.8 %, 82.6 %, and 81.3 %, respectively. ConclusionsAlong with younger age, tumor location, less frequent necrosis, and lower OEF may be useful imaging biomarkers to differentiate H3 K27-altered DMG from midline-located IDH-wildtype GBM. Tumor oxygenation imaging biomarkers may reflect the less hypoxic nature of H3 K27-altered DMG than IDH-wildtype GBM and may contribute to differentiation.

Oxygen extraction fraction (OEF) values and applications in neurological diseases.

One of the goals of this systematic review is to provide a meta-analysis-derived mean OEF of healthy volunteers. Another aim of this study is to indicate the OEF ranges of various neurological pathologies. Potential clinical applications of OEF metrics are presented. Peer-reviewed studies reporting OEF metrics derived from computed tomography (CT)/positron emission tomography (PET) and/or magnetic resonance imaging (MRI) were considered. Databases utilized included MEDLINE, PubMed, EMBASE, Web of Science, and Google Scholar. The Newcastle-Ottawa scoring system was used for evaluating studies. R Studio was utilized for the meta-analysis calculations when appropriate. The GRADE framework was utilized to assess additional findings. Of 2267 potential studies, 165 met the inclusion criteria. The healthy volunteer meta-analysis included 339 subjects and found a mean OEF value of 38.87 (37.38, 40.36), with a prediction interval of 32.40-45.34. There were no statistical differences in OEF values derived from PET versus MRI. We provided a GRADE A certainty rating for the use of OEF metrics to predict stroke occurrence in patients with symptomatic carotid or cerebral vessel disease. We provided a GRADE B certainty rating for monitoring treatment response in Moyamoya disease. Use of OEF metrics in diagnosing and/or monitoring other conditions had a GRADE C certainty rating or less. OEF might have a role in diagnosing and monitoring patients with symptomatic carotid or cerebral vessel disease and Moyamoya disease. While we found insufficient evidence to support measuring OEF metrics in other patient populations, in many cases, further studies are warranted.

Abstract TMP12: Large Vessel Vasculopathy is Associated With Oxygen Metabolic Stress in Children and Young Adults With Sickle Cell Disease

Background: Large-vessel vasculopathy (LVV), such as moyamoya syndrome, increases stroke risk with sickle cell disease (SCD). We hypothesized that tissue-based cerebral blood flow (CBF) and oxygen extraction fraction (OEF), as indicators of hemodynamic and metabolic stress, would differ in hemispheres with vs. without LVV. Methods: Patients underwent serial brain MRI and time-of-flight MRA to quantify voxel-wise CBF, OEF, and infarcts. LVV was defined as 75-99% stenosis of a major anterior circulation artery. Hemispheres with large vessel occlusion or revascularization surgery were excluded. Infarcted voxels were removed. Mean hemispheric (hemi-) CBF, OEF of the anterior circulation were extracted based on a vascular territory template. Hemi- OEF was normalized to whole brain OEF (nOEF). Hemi- cerebral metabolic rate of oxygen utilization (CMRO 2 ) was calculated from arterial oxygen content, hemi- CBF, and hemi- OEF. Mann-Whitney U was used to compare hemispheres with vs. without LVV. Effects of age, hemoglobin, and repeated MRIs were adjusted for in linear mixed model. Results: Of 158 patients, 221 MRI and MRAs were performed. At baseline, LVV occurred in 5% of hemispheres. Median infarct volume was larger in hemispheres with vs. without LVV (6.5 vs. 0.04 mL, p &lt;0.001). In baseline univariate analysis, hemispheres with LVV had lower CBF (25.8 vs 31.3 mL/100g/min, p =0.04), non-significantly higher nOEF (0.99 vs. 0.96, p =0.067), and lower CMRO 2 (8.1 vs. 12.4 mL/100g/min, p =0.002) vs. without LVV. In mixed model, with all MRIs included, LVV was independently associated with nOEF (β = 0.03, p =0.04) and showed a trend for association with CBF (β = -5.4, p =0.09) and CMRO 2 (β = -35.2, p =0.08). Discussion: In SCD, hemispheric OEF was increased as a compensatory response to flow-limiting stenosis, yet may be inadequate to prevent infarction as CMRO 2 decreased. Hemispheric OEF, as an indicator of increased stroke risk, may guide medical management and surgical intervention.

Abstract WMP63: Oxygen Metabolic Stress Attributes Intrinsic Vulnerability to Watershed Regions in Healthy Individuals

Introduction: Physiological imaging studies in patients with severe steno-occlusive carotid disease (SSCD) reveal hemodynamic compromise as a mechanism underlying watershed infarcts (WI). However, it is unclear if the watershed region (WR) is intrinsically vulnerable in healthy individuals. We measured cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in healthy individuals to determine if the WR was under metabolic stress, and therefore an intrinsically vulnerable region. Methods: To define a common WR, we created an “average WI density map” using MRIs from patients with diffusion restriction ipsilateral to SSCD from a single academic center (7/10 to 8/20). WI density maps were created using 5%, 10% and 15% incidence thresholds. Maps were overlaid onto coregistered CBF and OEF maps generated from pseudo-continuous arterial spin labeling (pCASL) and asymmetric spin echo sequences, respectively, performed on healthy controls aged &lt;55 with no vascular risk factors. OEF was normalized to whole brain values. White matter OEF and CBF was compared within vs. outside the WR using the Kruskal Wallis test. Results: 47 MRIs (mean age 62 years, 55 % females) were used to create average WI density maps using 3 thresholds (Fig A). Average CBF and OEF maps were created from 29 healthy volunteers (mean age 39 years, 59 % females). WI maps were superimposed on the CBF and OEF maps from healthy controls. OEF was higher (p&lt;0.001), and CBF lower (p&lt;0.001) within compared to outside the watershed regions, regardless of incidence threshold used (10% threshold shown in Fig. B-C). Conclusion: Increased OEF and decreased CBF suggest oxygen metabolic stress in the WR, suggesting that the deep white matter may be intrinsically vulnerable even in healthy individuals. Indeed, several brain pathologies (WI, white matter hyperintensities of presumed vascular origin, and multiple sclerosis lesions) are known to fall within this region.

Abstract TMP10: Children With Sickle Cell Anemia Have Impaired Cerebrovascular Reactivity

Introduction: Sickle Cell Anemia (SCA) causes lower hemoglobin, leading to increased cerebral blood flow (CBF) to maintain cerebral oxygen metabolism (CMRO 2 ). Although CBF rises in childhood to meet higher CMRO 2 demands, further compensatory increases in CBF in children with SCA may tap into a limited hemodynamic reserve, increasing risk for infarct. Cerebrovascular reactivity (CVR) reflects hemodynamic reserve by measuring the vasculature’s response to vasoactive stimuli, particularly in the gray matter (GM). We hypothesized that children with SCA have lower GM CVR, regardless of CMRO 2 . Methods: We used magnetic resonance imaging of children with and without SCA to collect pseudocontinuous arterial spin labeling (pCASL) for CBF, asymmetric spin echo for oxygen extraction fraction (OEF) and blood oxygen level dependent (BOLD) data correlated with hypercapnic challenges for CVR. Lab draws confirmed Hemoglobin (Hb) values. CMRO 2 was calculated as CBF x OEF x Arterial Oxygen Content (1.36 x Hb x SpO 2 ). Continuous variable differences between groups were analyzed using the Mann-Whitney U test, and categorical variables using the Fisher’s exact test. Linear regression assessed the relationship between CVR and Hb. Reported significant relationships survived multiple comparisons correction. Results: A total of 35 participants, ages 8–22 years had quality CVR data [9 SCA subjects (5 male) and 26 controls (9 male)]. Of these, 8 SCA and 20 controls had adequate quality metabolic data. The groups are matched by age (p=0.56) and sex (p=0.43). Children with SCA had higher GM CBF (62.0 v 49.3 mL/100g/min; p=0.03), but similar GM CMRO 2 (1.81 v 1.42 mL/100g/min; p=0.07) than controls. GM CVR was significantly lower in SCA than controls (0.17 v 0.27 %/mmHg; p=0.0003). Lower CVR was associated with lower Hb (Figure) after adjusting for age and sex (p &lt;0.0001). Conclusion: Lower GM CVR in children with SCA indicates a lower hemodynamic reserve, likely related to the degree of anemia.

Abstract TMP69: Impaired Cognitive Function and Cerebral Hemodynamics Associated With APOE4 in Asymptomatic Carotid Artery Stenosis/Occlusion

Introduction: Cerebral hypoperfusion even in asymptomatic CASO may cause cognitive impairment. We reported APOE4 induces neurovascular dysfunction and cognitive impairment in a mouse model of CASO. However, it has not been clinically investigated in patients with asymptomatic CASO. Methods: A cross-sectional observational study was conducted between January 2017 and March 2022. In a primary analysis, 91 patients with asymptomatic moderate or severe CASO who underwent cognitive tests, including the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog), and 15 O-gas positron-emission tomography (PET) were included to examine associations of cognitive impairment and cerebral hemodynamic disruption with APOE4 . To investigate hemodynamic disruption, a sensitivity analysis in 70 additional patients who underwent only 15 O-gas PET was performed. Results: Among the 91 patients with asymptomatic moderate or severe CASO, 20 (22.0%) were APOE4 carriers. In a multivariable linear regression analysis, APOE4 was an independent risk factor for a worse ADAS-Cog delayed word recall score, indicating short-term memory impairment (β = 0.21, 95% confidence interval (CI) 0.026–2.30, p = 0.045). The 15 O-gas PET showed that APOE4 was an independent risk factor for lower cerebral blood flow (CBF) in the anterior circulation territory (β = –0.31, 95%CI –0.091 to –0.015, p = 0.007), without changes in cerebral metabolic rate of oxygen (CMRO 2 ) or oxygen extraction fraction. Of 161 patients in the sensitivity analysis, 31 (19.3%) carried APOE4 , which was an independent predictor of lower CBF (β = –0.23, 95%CI –0.072 to –0.014, p = 0.004) in the anterior circulation territory. Conclusions: APOE4 may confer an increased risk of memory impairment accompanied by cerebral hemodynamic disruption in asymptomatic CASO. The present study indicated that identifying APOE4 in such patients may be useful in early detection of disease severity.

Validation of a new 3D quantitative BOLD based cerebral oxygen extraction mapping.

Quantitative BOLD (qBOLD) MRI allows evaluation of oxidative metabolism of the brain based purely on an endogenous contrast mechanism. The method quantifies deoxygenated blood volume (DBV) and hemoglobin oxygen saturation level of venous blood (Yv), yielding oxygen extraction fraction (OEF), and along with a separate measurement of cerebral blood flow, cerebral metabolic rate of oxygen (CMRO2) maps. Here, we evaluated our recently reported 3D qBOLD method that rectifies a number of deficiencies in prior qBOLD approaches in terms of repeat reproducibility and sensitivity to hypercapnia on the metabolic parameters, and in comparison to dual-gas calibrated BOLD (cBOLD) MRI for determining resting-state oxygen metabolism. Results suggested no significant difference between test-retest qBOLD scans in either DBV and OEF. Exposure to hypercapnia yielded group averages of 38 and 28% for OEF and 151 and 146 µmol/min/100 g for CMRO2 in gray matter at baseline and hypercapnia, respectively. The decrease of OEF during hypercapnia was significant (p ≪ 0.01), whereas CMRO2 did not change significantly (p = 0.25). Finally, baseline OEF (37 vs. 39%) and CMRO2 (153 vs. 145 µmol/min/100 g) in gray matter using qBOLD and dual-gas cBOLD were found to be in good agreement with literature values, and were not significantly different from each other (p > 0.1).

Multi-Echo Complex Quantitative Susceptibility Mapping and Quantitative Blood Oxygen Level-Dependent Magnitude (mcQSM + qBOLD or mcQQ) for Oxygen Extraction Fraction (OEF) Mapping.

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.

P047 Deconditioning in quiescent Crohn’s Disease patients with heightened fatigue perception

Abstract Background Heightened fatigue perception and premature exercise fatigue are common in inflammatory bowel disease (IBD). Physical deconditioning is greater in patients with increased fatigue perception relative to patients with a lower perception of fatigue, implicating deconditioning as an aetiological factor. This study used physiology and multiparametric Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) during exercise to comprehensively phenotype quiescent IBD fatigue. Methods Participant body mass and regional body composition was assessed by DEXA, and tknee extensor strength and fatiguability using isokinetic dynamometry (Cybex, USA). A supine CPET was performed using an MR-compatible Ergometer (Cardiostepper, Ergospect) to standardize relative exercise intensity for in-bore 1H MRI measures. 1H MRI data were collected on a Philips 3T Ingenia wide bore scanner using a Philips Head/Neck coil and in-built posterior coil. Across rest, steady-state exercise (50% VO2 peak) and recovery, Phase Contrast-MRI was used to compute cardiac output and cerebral blood flow (CBF), and T2 Relaxation under spin tagging (TRUST-MRI) to measure brain oxygen extraction fraction (OEF). 31P MRS data was collected on a 3T Philips Achieva using a 14cm 31P coil over the medial gastrocnemius. Ischaemic plantar flexion exercise was performed at 50% maximum voluntary contraction (MVC) using an MR-compatible ergometer (Trispect, Ergospect) during non-localized pulse-acquire 31P-MRS. 31P spectra were analysed using the AMARES function in jMRUI Beta 6.0. In vivo muscle mitochondrial flux during post-exercise PCr recovery (VPCr = kPCr * ΔPCr) where ΔPCr is PCrendrecovery –PCrendex) was quantified after reinstating limb blood flow and fitting PCr recovery to a mono-exponential function in GraphPad prism (PCr(t) = PCrinitial+(PCrend – PCrinitial)(1-exp(-k.t) where t is time from start of non-ischaemic recovery). Results 16 quiescent CD patients and 12 age and BMI matched HV’s completed the study. General fatigue score was greater in CD relative to HV (P = 0.001, Table 1). Body composition, isometric strength, fatigue development were not different between groups (Table 1). CBF response to steady-state exercise was less in CD (P = 0.003) alongside the maintenance of cardiac output and brain OEF in HV (Figure 1). VPCr following ischemic plantar flexion exercise was less in CD than HV (P = 0.02, Figure 1) (Figure 1). Conclusion Greater fatigue perception in CD was accompanied by lower CBF on exercise and blunted post-exercise PCr resynthesis, but no differences in body composition, strength and fatiguability relative to HV. These finding point to greater deconditioning in CD, corroborated by their lower daily step count relative to HV.

Brain Frontal-Lobe Misery Perfusion in COVID-19 ICU Survivors: An MRI Pilot Study.

Post-acute COVID-19 syndrome (PCS) is highly prevalent. Critically ill patients requiring intensive care unit (ICU) admission are at a higher risk of developing PCS. The mechanisms underlying PCS are still under investigation and may involve microvascular damage in the brain. Cerebral misery perfusion, characterized by reduced cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF) in affected brain areas, has been demonstrated in cerebrovascular diseases such as carotid occlusion and stroke. This pilot study aimed to examine whether COVID-19 ICU survivors exhibited regional misery perfusion, indicating cerebral microvascular damage. In total, 7 COVID-19 ICU survivors (4 female, 20-77 years old) and 19 age- and sex-matched healthy controls (12 female, 22-77 years old) were studied. The average interval between ICU admission and the MRI scan was 118.6 ± 30.3 days. The regional OEF was measured using a recently developed technique, accelerated T2-relaxation-under-phase-contrast MRI, while the regional CBF was assessed using pseudo-continuous arterial spin labeling. COVID-19 ICU survivors exhibited elevated OEF (β = 5.21 ± 2.48%, p = 0.047) and reduced relative CBF (β = -0.083 ± 0.025, p = 0.003) in the frontal lobe compared to healthy controls. In conclusion, misery perfusion was observed in the frontal lobe of COVID-19 ICU survivors, suggesting microvascular damage in this critical brain area for high-level cognitive functions that are known to manifest deficits in PCS. Physiological biomarkers such as OEF and CBF may provide new tools to improve the understanding and treatment of PCS.

Tracking the Recovery of a Mild Traumatic Brain Injury Patient utilizing a 60 s Combined Functional Near-Infrared Spectroscopy and Psychomotor Testing Approach A Case Study

Identifying and tracking the recovery of patients with mild traumatic brain injuries (mTBI) has remained elusive due to the lack of non-invasive, objective neuroimaging techniques. The purpose of this case study was to provide a proof of concept for performing a combined functional near-infrared spectroscopy (fNIRS) and 60-s psychomotor vigilance testing (60-s PVT) that can identify and track the recovery of a patient with a mTBI. The patient was a 19-year-old female acrobatics and tumbling athlete who was kicked in the left temple by a teammate. Video footage of the injury was utilized to determine the region of impact and weekly fNIRS and 60-s PVT assessments were performed throughout the 10 weeks of recovery. The patient was cleared for activity based upon symptoms at week 7; however, the patient reported increased symptomology during weeks 7 and 8 following exercise. Our fNIRS neuroimaging technique was able to detect the systemic physiological responses associated with mitochondrial dysregulation and oxygen extraction fraction at weeks 1 to 8. Based on our findings, the patient remained injured at week 8, and that the physical activity performed at weeks 7 and 8 may have regressed recovery and induced additional dysfunction resulting in increased recovery time. In conclusion, we were able to identify and track the recovery of our patient with a mTBI using our non-invasive combined fNIRS and 60-s PVT approach. Results provided real time physiological responses associated with the injury throughout the recovery process.

CMR 2-66 - Artificial Intelligence-based Quantification of Myocardial Oxygen Extraction Fraction and Blood Volume in Health with CMR: Reproducibility and Distribution

CMR 2-66 - Artificial Intelligence-based Quantification of Myocardial Oxygen Extraction Fraction and Blood Volume in Health with CMR: Reproducibility and Distribution