Depression of whole-brain oxygen extraction fraction is associated with poor outcome in pediatric traumatic brain injury.
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ABSTRACT:
SUBMITTER: Ragan DK
PROVIDER: S-EPMC3593145 | biostudies-other | 2012 Feb
REPOSITORIES: biostudies-other
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Project description:PURPOSE:T2 -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. METHODS:A 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. RESULTS:The 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. CONCLUSION:OEF 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.
| S-EPMC6772021 | biostudies-literature
Project description:Characterizing the effect of limited oxygen availability on brain metabolism during brain activation is an essential step towards a better understanding of brain homeostasis and has obvious clinical implications. However, how the cerebral oxygen extraction fraction (OEF) depends on oxygen availability during brain activation remains unclear, which is mostly attributable to the scarcity and safety of measurement techniques. Recently, a magnetic resonance imaging (MRI) method that enables noninvasive and dynamic measurement of the OEF has been developed and confirmed to be applicable to functional MRI studies. Using this novel method, the present study investigated the motor-evoked OEF response in both normoxia (21% O2) and hypoxia (12% O2). Our results showed that OEF activation decreased in the brain areas involved in motor task execution. Decreases in the motor-evoked OEF response were greater under hypoxia (-21.7% ± 5.5%) than under normoxia (-11.8% ± 3.7%) and showed a substantial decrease as a function of arterial oxygen saturation. These findings suggest a different relationship between oxygen delivery and consumption during hypoxia compared to normoxia. This methodology may provide a new perspective on the effects of mild hypoxia on brain function.
| S-EPMC8393298 | biostudies-literature
Project description:Sickle cell disease (SCD) is caused by a single amino acid mutation in hemoglobin, causing chronic anemia and neurovascular complications. However, the effects of chronic anemia on oxygen extraction fraction (OEF), especially in deep brain structures, are less well understood. Conflicting OEF values have been reported in SCD patients, but have largely attributed to different measurement techniques, faulty calibration, and different locations of measurement. Thus, in this study, we investigated the reliability and agreement of two susceptibility-based methods, quantitative susceptibility mapping (QSM) and complex image summation around a spherical or a cylindrical object (CISSCO), for OEF measurements in internal cerebral vein (ICV), reflecting oxygen saturation in deep brain structures. Both methods revealed that SCD patients and non-sickle anemia patients (ACTL) have increased OEF in ICV (42.6% ± 5.6% and 30.5% ± 3.6% in SCD by CISSCO and QSM respectively, 37.0% ± 4.1% and 28.5% ± 2.3% in ACTL) compared with controls (33.0% ± 2.3% and 26.8% ± 1.8%). OEF in ICV varied reciprocally with hematocrit (r 2 = 0.92, 0.53) and oxygen content (r 2 = 0.86, 0.53) respectively. However, an opposite relationship was observed for OEF measurements in sagittal sinus (SS) with the widely used T2-based oximetry, T2-Relaxation-Under-Spin-Tagging (TRUST), in the same cohorts (31.2% ± 6.6% in SCD, 33.3% ± 5.9% in ACTL and 36.8% ± 5.6% in CTL). Importantly, we demonstrated that hemoglobin F and other fast moving hemoglobins decreased OEF by TRUST and explained group differences in sagittal sinus OEF between anemic and control subjects. These data demonstrate that anemia causes deep brain hypoxia in anemia subjects with concomitant preservation of cortical oxygenation, as well as the key interaction of the hemoglobin dissociation curve and cortical oxygen extraction.
| S-EPMC9248375 | biostudies-literature
Project description:Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P = .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA (P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.
| S-EPMC5833262 | biostudies-literature
Project description:ObjectiveFor children hospitalized with acute traumatic brain injury (TBI), to use postdischarge insurance claims to identify: (1) healthcare utilization patterns representative of functional outcome phenotypes and (2) patient and hospitalization characteristics that predict outcome phenotype.SettingTwo pediatric trauma centers and a state-level insurance claim aggregator.PatientsA total of 289 children, who survived a hospitalization after TBI between 2009 and 2014, were in the hospital trauma registry, and had postdischarge insurance eligibility.DesignRetrospective cohort study.Main measuresUnsupervised machine learning to identify phenotypes based on postdischarge insurance claims. Regression analyses to identify predictors of phenotype.ResultsMedian age 5 years (interquartile range 2-12), 29% (84/289) female. TBI severity: 30% severe, 14% moderate, and 60% mild. We identified 4 functional outcome phenotypes. Phenotypes 3 and 4 were the highest utilizers of resources. Morbidity burden was highest during the first 4 postdischarge months and subsequently decreased in all domains except respiratory. Severity and mechanism of injury, intracranial pressure monitor placement, seizures, and hospital and intensive care unit lengths of stay were phenotype predictors.ConclusionsUnsupervised machine learning identified postdischarge phenotypes at high risk for morbidities. Most phenotype predictors are available early in the hospitalization and can be used for prognostic enrichment of clinical trials targeting mitigation or treatment of domain-specific morbidities.
| S-EPMC8249306 | biostudies-literature
Project description:This study aims to (1) investigate the neuropathology of mild to severe pediatric TBI and (2) elucidate the predictive value of conventional and innovative neuroimaging for functional outcome. Children aged 8-14 years with trauma control (TC) injury (n = 27) were compared to children with mild TBI and risk factors for complicated TBI (mildRF+, n = 20) or moderate/severe TBI (n = 17) at 2.8 years post-injury. Neuroimaging measures included: acute computed tomography (CT), volumetric analysis on post-acute conventional T1-weighted magnetic resonance imaging (MRI) and post-acute diffusion tensor imaging (DTI, analyzed using tract-based spatial statistics and voxel-wise regression). Functional outcome was measured using Common Data Elements for neurocognitive and behavioral functioning. The results show that intracranial pathology on acute CT-scans was more prevalent after moderate/severe TBI (65%) than after mildRF+ TBI (35%; p = .035), while both groups had decreased white matter volume on conventional MRI (ps ≤ .029, ds ≥ -0.74). The moderate/severe TBI group further showed decreased fractional anisotropy (FA) in a widespread cluster affecting all white matter tracts, in which regional associations with neurocognitive functioning were observed (FSIQ, Digit Span and RAVLT Encoding) that consistently involved the corpus callosum. FA had superior predictive value for functional outcome (i.e. intelligence, attention and working memory, encoding in verbal memory and internalizing problems) relative to acute CT-scanning (i.e. internalizing problems) and conventional MRI (no predictive value). We conclude that children with mildRF+ TBI and moderate/severe TBI are at risk of persistent white matter abnormality. Furthermore, DTI has superior predictive value for neurocognitive out-come relative to conventional neuroimaging.
| S-EPMC5814510 | biostudies-literature
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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Project description: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.
| S-EPMC7026852 | biostudies-literature
Project description:Ficolin-mediated activation of the lectin pathway of complement contributes to the complement-independent inflammatory processes of traumatic brain injury. Lower serum ficolin-3 levels have been demonstrated to be highly associated with unfavorable outcome after ischemic stroke. This prospective observatory study was designed to investigate the relationships between serum ficolin-3 levels and injury severity and clinical outcomes after severe traumatic brain injury.Serum ficolin-3 levels of 128 patients and 128 healthy controls were measured by sandwich immunoassays. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. Study endpoints included mortality at 1 week and 6 months and unfavorable outcome at 6 months after head trauma. Injury severity was assessed by Glasgow Coma Scale score. Multivariate logistic models were structured to evaluate the relationships between serum ficolin-3 levels and study endpoints and injury severity.Compared with the healthy controls, serum ficolin-3 levels on admission were statistically decreased in patients with severe traumatic brain injury. Serum ficolin-3 levels were independently correlated with Glasgow Coma Scale scores. Ficolin-3 was also identified as an independent prognostic predictor for 1-week mortality, 6-month mortality, and 6-month unfavorable outcome. Under receiver operating characteristics curves, ficolin-3 has similar prognostic predictive values for all study endpoints compared with Glasgow Coma Scale scores.It was proposed that lower serum ficolin-3 levels, correlated with injury severity, had the potential to be the useful, complementary tool to predict short- or long-term clinical outcomes after severe traumatic brain injury.
| S-EPMC4666053 | biostudies-literature
Project description:Cerebral oxygen extraction fraction is an important physiological index of the brain's oxygen consumption and supply and has been suggested to be a potential biomarker for a number of diseases such as stroke, Alzheimer's disease, multiple sclerosis, sickle cell disease, and metabolic disorders. However, in order for oxygen extraction fraction to be a sensitive biomarker for personalized disease diagnosis, inter-subject variations in normal subjects must be minimized or accounted for, which will otherwise obscure its interpretation. Therefore, it is essential to investigate the physiological underpinnings of normal differences in oxygen extraction fraction. This work used two studies, one discovery study and one verification study, to examine the extent to which an individual's end-tidal CO2 can explain variations in oxygen extraction fraction. It was found that, across normal subjects, oxygen extraction fraction is inversely correlated with end-tidal CO2. Approximately 50% of the inter-subject variations in oxygen extraction fraction can be attributed to end-tidal CO2 differences. In addition, oxygen extraction fraction was found to be positively associated with age and systolic blood pressure. By accounting for end-tidal CO2, age, and systolic blood pressure of the subjects, normal variations in oxygen extraction fraction can be reduced by 73%, which is expected to substantially enhance the utility of oxygen extraction fraction as a disease biomarker.
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