Cerebral Fractional Oxygen Extraction Research Articles

Does Cerebral Oxygenation Change during Peripherally Inserted Central Catheterization in Preterm Infants?

This study aimed to evaluate the effect of peripherally inserted central venous catheterization on cerebral oxygenation by near-infrared spectroscopy in very low birth weight preterm infants. Forty-one preterm infants (gestational age ≤32 weeks and birth weight ≤1,500 g) requiring peripherally inserted central venous catheter were included. Hemodynamic data and cerebral regional oxygen saturation values measured by near-infrared spectroscopy were prospectively collected before (T0) and every 5 minutes for 30 minutes following catheterization. When compared with baseline (T0) values, those values having relative maximum changes in the first 15 minutes and between 15 and 30 minutes were defined as T15 max and T30 max, respectively. Any change of more than a 10% decrease in baseline cerebral rSO2 was considered clinically significant. Additionally, any changes exceeding 20% in heart rate and mean arterial blood pressure values were considered significant. Following catheterization, the time interval to reach the baseline for cerebral regional oxygen saturation was noted. Cerebral regional oxygen saturation values at T15 max and T30 max were found to have decreased significantly in 46 and 22% of patients, respectively. A statistically significant difference was observed between these two time periods (p = 0.002); no significant differences in heart rate, mean arterial blood pressure, or cerebral fractional oxygen extraction values at T15 max and T30 max were observed. All patients reached their baseline cerebral regional oxygen saturation in a median of 25 (15-60) minutes. In very low birth weight preterm infants, monitoring cerebral regional oxygen saturation by near-infrared spectroscopy before and after peripherally inserted central venous catheterization may be useful in clinical practice. The assessment of factors affecting cerebral oxygenation and, in the case of low cerebral oxygenation, implementation of corrective actions before peripherally inserted central catheterization may offer a neuroprotective strategy. · Monitoring cerebral rSO2 by NIRS during PICC line procedure might be useful in preterm infants.. · In this study, a significant decrease in cerebral rSO2 level following catheterization was observed.. · Implementation of corrective actions before PICC line procedure may offer a neuroprotective strategy..

Cerebral oxygen extraction fraction declines with ventricular enlargement in patients with normal pressure hydrocephalus

ObjectiveNormal pressure hydrocephalus (NPH) is a neurodegenerative disease that is potentially reversible by shunt surgery in approximately 60% of patients. Imaging may provide a means to investigate brain tissue viability and oxygen metabolism in NPH patients. MethodsOxygen extraction fraction (OEF) mapping was generated from 3D multi-echo gradient echo MRI (mGRE) data using QQ-CCTV algorithm and cerebral blood flow (CBF) using 3D arterial spin labeling (ASL) MRI data, thereby calculating the cerebral metabolic rate of oxygen (CMRO2 = CBF × OEF × [H]a) in 16 NPH patients. Regression analyses using cortical gray matter and deep gray matter regions were conducted with age, gender, CSF stroke volume and normalized ventricular volume as independent variables. ResultsOEF showed significant negative correlations with normalized brain ventricular volumes in the whole brain (p = 0.004, q = 0.01), cortical gray matter (p = 0.004, q = 0.01), caudate (p = 0.02, q = 0.04), and pallidum (p = 0.03, q = 0.04), but no significant correlation with CSF stroke volume (q > 0.05). There was no significant finding with CBF or CMRO2. ConclusionIn NPH patients, low OEF in several regions was significantly correlated with large ventricular volumes, indicating decreased tissue oxygen metabolism with increased NPH severity. OEF mapping may provide a functional understanding of neurodegeneration in NPH and may improve monitoring of disease course and treatment outcomes.

Impaired oxygen extraction and adaptation of intracellular energy metabolism in cerebral small vessel disease.

We aimed to investigate whether combined phosphorous (31P) magnetic resonance spectroscopic imaging (MRSI) and quantitative mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pHi) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD). 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional31P MRSI and oxygenation-sensitive quantitative mapping (1/ =1/T2* - 1/T2) at 3 Tesla (T). PHiwas measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative values were averaged across the entire white matter (WM).Furthermore, values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls. Quantitative values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51±16.94vs. 138.19±12.66ms and 147.45±18.14vs. 137.99±12.19ms, p<0.05).WM values correlated significantly with the WMH load (ρ=0.441, p=0.006). Increased was significantly associated with more alkaline pHi(ρ=0.299, p<0.05). Both and pHi were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p=0.001 and ρ=0.452, p=0.016). This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state.

Red cell exchange transfusions increase cerebral capillary transit times and may alter oxygen extraction in sickle cell disease.

Persons with sickle cell disease (SCD) suffer from chronic hemolytic anemia, reduced blood oxygen content, and lifelong risk of silent and overt stroke. Major conventional stroke risk factors are absent in most individuals with SCD, yet nearly 50% have evidence of brain infarcts by the age of 30 years, indicating alternative etiologies for ischemia. We investigated whether radiological evidence of accelerated blood water transit through capillaries, visible on arterial spin labeling (ASL) magnetic resonance imaging, reduces following transfusion-induced increases in hemoglobin and relates to oxygen extraction fraction (OEF). Neurological evaluation along with anatomical and hemodynamic imaging with cerebral blood flow (CBF)-weighted pseudocontinuous ASL and OEF imaging with T2 -relaxation-under-spin-tagging were applied in sequence before and after blood transfusion therapy (n = 32) and in a comparator cohort of nontransfused SCD participants on hydroxyurea therapy scanned at two time points to assess stability without interim intervention (n = 13). OEF was calculated separately using models derived from human hemoglobin-F, hemoglobin-A, and hemoglobin-S. Gray matter CBF and dural sinus signal, indicative of rapid blood transit, were evaluated at each time point and compared with OEF using paired statistical tests (significance: two-sided p < 0.05). No significant change in sinus signal was observed in nontransfused participants (p = 0.650), but a reduction was observed in transfused participants (p = 0.034), consistent with slower red cell transit following transfusion. The dural sinus signal intensity was inversely associated with OEF pretransfusion (p = 0.011), but not posttransfusion. Study findings suggest that transfusion-induced increases in total hemoglobin may lengthen blood transit times through cerebral capillaries and alter cerebral OEF in SCD.

MRI assessment of cerebral oxygen extraction fraction in the medial temporal lobe

The medial temporal lobe (MTL) is a key area implicated in many brain diseases, such as Alzheimer's disease. As a functional biomarker, the oxygen extraction fraction (OEF) of MTL may be more sensitive than structural atrophy of MTL, especially at the early stages of diseases. However, there is a lack of non-invasive techniques to measure MTL-OEF in humans. The goal of this work is to develop an MRI technique to assess MTL-OEF in a clinically practical time without using contrast agents. The proposed method measures venous oxygenation (Yv) in the basal veins of Rosenthal (BVs), which are the major draining veins of the MTL. MTL-OEF can then be estimated as the arterio-venous difference in oxygenation. We developed an MRI sequence, dubbed arterial-suppressed accelerated T2-relaxation-under-phase-contrast (AS-aTRUPC), to quantify the blood T2 of the BVs, which was then converted to Yv through a well-established calibration model. MTL-OEF was calculated as (Ya−Yv)/Ya × 100%, where Ya was the arterial oxygenation. The feasibility of AS-aTRUPC to quantify MTL-OEF was evaluated in 16 healthy adults. The sensitivity of AS-aTRUPC in detecting OEF changes was assessed by a caffeine ingestion (200 mg) challenge. For comparison, T2-relaxation-under-spin-tagging (TRUST) MRI, which is a widely used global OEF technique, was also acquired. The dependence of MTL-OEF on age was examined by including another seven healthy elderly subjects. The results showed that in healthy adults, MTL-OEF of the left and right hemispheres were correlated (P=0.005). MTL-OEF was measured to be 23.9±3.6% (mean±standard deviation) and was significantly lower (P<0.0001) than the OEF of 33.3±2.9% measured in superior sagittal sinus (SSS). After caffeine ingestion, there was an absolute percentage increase of 9.1±4.0% in MTL-OEF. Additionally, OEF in SSS measured with AS-aTRUPC showed a strong correlation with TRUST OEF (intra-class correlation coefficient=0.94 with 95% confidence interval [0.91, 0.96]), with no significant bias (P=0.12). MTL-OEF was found to increase with age (MTL-OEF=20.997+0.100 × age; P=0.02). In conclusion, AS-aTRUPC MRI provides non-invasive assessments of MTL-OEF and may facilitate future clinical applications of MTL-OEF as a disease biomarker.

Measurement of Cerebral Oxygen Extraction Fraction Using Quantitative BOLD Approach: A Review.

Quantification of brain oxygenation and metabolism, both of which are indicators of the level of brain activity, plays a vital role in understanding the cerebral perfusion and the pathophysiology of brain disorders. Magnetic resonance imaging (MRI), a widely used clinical imaging technique, which is very sensitive to magnetic susceptibility, has the possibility of substituting positron emission tomography (PET) in measuring oxygen metabolism. This review mainly focuses on the quantitative blood oxygenation level-dependent (qBOLD) method for the evaluation of oxygen extraction fraction (OEF) in the brain. Here, we review the theoretic basis of qBOLD, as well as existing acquisition and quantification methods. Some published clinical studies are also presented, and the pros and cons of qBOLD method are discussed as well.

Hypoxic breathing produces more intense hypoxemia in elderly women than in elderly men.

Background: Brief hypoxic exposures are increasingly applied as interventions for aging-related conditions. To optimize the therapeutic impact of hypoxia, knowledge of the sex-related differences in physiological responses to hypoxia is essential. This study compared hypoxia-induced hypoxemic responses in elderly men and women. Methods: Seven elderly men (70.3 ± 6.0years old) and nine women (69.4 ± 5.5years old) breathed 10% O2 for 5min while arterial (SaO2; transcutaneous photoplethysmography) and cerebral tissue O2 saturation (ScO2; near-infrared spectroscopy), ventilatory frequency, tidal volume, minute-ventilation, and partial pressures of end-tidal O2 (PETO2) and CO2 (mass spectrometry) were continuously monitored. Cerebral tissue oxygen extraction fraction (OEF) equaled (SaO2-ScO2)/SaO2. Results: During 5min hypoxia SaO2 fell from 97.0 ± 0.8% to 80.6 ± 4.6% in the men and from 96.3 ± 1.4% to 72.6 ± 4.0% in the women. The slope ΔSaO2/min was steeper in the women than the men (-4.71 ± 0.96 vs. -3.24 ± 0.76%/min; p = 0.005). Although SaO2 fell twice as sharply per unit decrease in PETO2 in the women than the men (-1.13 ± 0.11 vs. -0.54 ± 0.06%/mmHg; p = 0.003), minute-ventilation per unit hypoxemia increased less appreciably in the women (-0.092 ± 0.014 vs. -0.160 ± 0.021L/min/%; p = 0.023). OEF fell with hypoxia duration in the women, but remained stable in the men. Conclusion: During 5min hypoxic breathing, elderly women experience more intense hypoxemia and reduced chemoreflex sensitivity vs. their male counterparts, which may lower OEF stability in women despite augmented O2 dissociation from hemoglobin during hypoxia. These sex-related differences merit attention when implementing brief hypoxic exposures for therapeutic purposes.

Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease

AbstractChildren with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD. Three children had prior overt strokes, 5 children had prior silent strokes, and 1 child had abnormal transcranial Doppler ultrasound velocities. CBF and OEF of HSCT recipients were compared with non-SCD control participants and with SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT, and 3 participants received 8 out of 8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 mL/100 g/min) and OEF (36.8%) were elevated compared with non-SCD control participants, declining significantly 1 to 2 years after HSCT (CBF, 72.7 mL/100 g per minute; P = .004; OEF, 27.0%; P = .002), with post-HSCT CBF and OEF similar to non-SCD control participants. Furthermore, HSCT recipients demonstrated greater reduction in CBF (−19.4 mL/100 g/min) and OEF (−8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF, −0.9 mL/100 g/min; P = .024; OEF, −3.3%; P = .001). Curative HSCT normalizes whole-brain hemodynamics in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection after HSCT in this high-risk patient population.

Silent Infarcts, White Matter Integrity, and Oxygen Metabolic Stress in Young Adults With and Without Sickle Cell Trait.

Individuals with sickle cell anemia have heightened risk of stroke and cognitive dysfunction. Given its high prevalence globally, whether sickle cell trait (SCT) is a risk factor for neurological injury has been of interest; however, data have been limited. We hypothesized that young, healthy adults with SCT would show normal cerebrovascular structure and hemodynamic function. As a case-control study, young adults with (N=25, cases) and without SCT (N=24, controls) underwent brain magnetic resonance imaging to quantify brain volume, microstructural integrity (fractional anisotropy), silent cerebral infarcts (SCI), intracranial stenosis, and aneurysms. Pseudocontinuous arterial spin labeling and asymmetric spin echo sequences measured cerebral blood flow and oxygen extraction fraction, respectively, from which cerebral metabolic oxygen demand was calculated. Imaging metrics were compared between SCT cases and controls. SCI volume was correlated with baseline characteristics. Compared with controls, adults with SCT demonstrated similar normalized brain volumes (SCT 0.80 versus control 0.81, P=0.41), white matter fractional anisotropy (SCT 0.41 versus control 0.43, P=0.37), cerebral blood flow (SCT 62.04 versus control, 61.16 mL/min/100 g, P=0.67), oxygen extraction fraction (SCT 0.27 versus control 0.27, P=0.31), and cerebral metabolic oxygen demand (SCT 2.71 versus control 2.70 mL/min/100 g, P=0.96). One per cohort had an intracranial aneurysm. None had intracranial stenosis. The SCT cases and controls showed similar prevalence and volume of SCIs; however, in the subset of participants with SCIs, the SCT cases had greater SCI volume versus controls (0.29 versus 0.07 mL, P=0.008). Of baseline characteristics, creatinine was mildly elevated in the SCT cohort (0.9 versus 0.8 mg/dL, P=0.053) and correlated with SCI volume (ρ=0.49, P=0.032). In the SCT cohort, SCI distribution was similar to that of young adults with sickle cell anemia. Adults with SCT showed normal cerebrovascular structure and hemodynamic function. These findings suggest that healthy individuals with SCT are unlikely to be at increased risk for early or accelerated ischemic brain injury.

Brain oxygen extraction and neural tissue susceptibility are associated with cognitive impairment in older individuals.

We investigated the effects of aging, white matter hyperintensities (WMH), and cognitive impairment on brain iron levels and cerebral oxygen metabolism, known to be altered in Alzheimer's disease (AD), using quantitative susceptibility mapping and MR-based cerebral oxygen extraction fraction (OEF). In 100 individuals over the age of 50 (68/32 cognitively impaired/intact), OEF and neural tissue susceptibility (χn ) were computed retrospectively from MRI multi-echo gradient echo data, obtained on a 3 Tesla MRI scanner. The effects of age and WMH on OEF and χn were assessed within groups, and OEF and χn were assessed between groups, using multivariate regression analyses. Cognitively impaired subjects were found to have 19% higher OEF and 34% higher χn than cognitively intact subjects in the cortical gray matter and several frontal, temporal, and parietal regions (p<.05). Increased WMH burden was significantly associated with decreased OEF in the cognitively impaired, but not in the cognitively intact. Older age had a stronger association with decreased OEF in the cognitively intact group. Both older age and increased WMH burden were significantly associated with increased χn in temporoparietal regions in the cognitively impaired. Higher brain OEF and χn in cognitively impaired older individuals may reflect altered oxygen metabolism and iron in areas with underlying AD pathology. Both age and WMH have associations with OEF and χn but are modified by the presence of cognitive impairment.

Correlation Between Cerebral Tissue Oxygen Saturation and Oxygen Extraction Fraction During Anesthesia: Monitoring Cerebral Metabolic Demand-supply Balance During Vasopressor Administration.

The speculation that cerebral tissue oxygen saturation (SctO 2 ) measured using tissue near-infrared spectroscopy reflects the balance between cerebral metabolic rate of oxygen and cerebral oxygen delivery has not been validated. Our objective was to correlate SctO 2 with cerebral oxygen extraction fraction (OEF) measured using positron emission tomography; OEF is the ratio between cerebral metabolic rate of oxygen and cerebral oxygen delivery and reflects the balance between these 2 variables. This cohort study was based on data collected in a previously published trial assessing phenylephrine versus ephedrine treatment in anesthetized patients undergoing brain tumor surgery. The variables of interest were measured twice over the healthy hemisphere before surgery: the first measurement performed after anesthesia induction and the second measurement performed after induction of a ∼20% increase in blood pressure using either phenylephrine or ephedrine. Data from 24 patients were analyzed. The overall vasopressor-induced relative changes in SctO 2 (ΔSctO 2 ) and OEF (ΔOEF) were 3.16% [interquartile range, -0.73% to 6.04%] and -12.5% [interquartile range, -24.0% to -6.19%], respectively. ΔSctO 2 negatively correlated with ΔOEF after phenylephrine treatment (Spearman rank correlation coefficient [ rs ]=-0.76; P =0.007), ephedrine treatment ( rs =-0.76; P =0.006), and any treatment ( rs =-0.79; P <0.001). ΔSctO 2 significantly associated with ΔOEF based on multivariable analysis with ΔOEF, relative changes in mean arterial pressure, arterial blood oxygen tension, and the bispectral index as covariates ( P =0.036). The negative correlation between changes in SctO 2 and OEF suggests that SctO 2 may reflect the cerebral metabolic demand-supply balance during vasopressor treatment. The generalizability of our findings in other clinical scenarios remains to be determined.

Normalization of Cerebral Hemodynamics after Hematopoietic Stem Cell Transplant in Children with Sickle Cell Anemia

▪BackgroundChildren with Sickle Cell Anemia (SCA) are at high risk for overt or silent strokes, and this risk may be mitigated by hematopoietic stem cell transplant (HSCT). Our research group has shown that when cerebral oxygen delivery is compromised due to anemia in SCA, the cerebral blood flow (CBF) and brain oxygen extraction fraction (OEF) increase to maintain brain tissue oxygen delivery. We used novel magnetic resonance imaging (MRI) sequences to measure OEF and CBF in children with SCA treated with HSCT, testing the hypothesis that after HSCT, OEF and CBF will be similar to control values.MethodsChildren with SCA were enrolled in a pilot prospective, observational study of MRI-measured OEF and CBF. Brain MRI exams were performed without sedation on a 3T Siemens scanner. The MRI protocol included fluid-attenuated inverse recovery (FLAIR) sequences in two planes to evaluate for strokes, asymmetric spin echo to measure tissue-level OEF, and pseudo-continuous arterial spin labeling perfusion-weighted imaging to measure CBF. HSCT recipients underwent paired brain MRI 1-2 months before and >1 year after HSCT. Controls, non-anemic siblings of SCA patients, had a single brain MRI. Pre- and post-HSCT CBF and OEF were compared within subjects and between the HSCT and control cohorts using non-parametric tests. Bivariate correlations between OEF or CBF and hemoglobin (Hb) or Hb S concentrations were tested with Spearman's rho. The level of significance was specified as p < 0.05 after adjustment by the Benjamini-Hochberg procedure.ResultsFour children (two male, median age 10 years, range 8-21 years) underwent HSCT: one had prior overt stroke, one had silent strokes, and two had no neuroimaging abnormalities. All received a reduced intensity preparative regimen of alemtuzumab, melphalan, and fludarabine. One subject received marrow from an HLA-matched unrelated donor without Hb S trait; two received marrow from HLA-identical siblings. One child who had rejected a HSCT from an HLA-identical sibling underwent re-conditioning with antithymocyte globulin and cyclophosphamide and received CD-34-selected peripheral stem cells from the same donor. All sibling donors had Hb S trait. Brain MRIs of 20 non-anemic sibling controls of median age 11 years (range 6-17 years) were included for comparison.Median OEF and CBF were significantly elevated pre-HSCT compared to controls (OEF median 0.355 vs 0.288, p = 0.012; CBF median 99.8 vs 65.1 ml/100 g/min, p = 0.018; Figure). Median post-HSCT OEF and CBF were lower than pre-HSCT values (OEF median 0.270 vs 0.355, CBF median 65.1 vs 99.8 ml/100 g/min, p = 0.13 for both), but these analyses had low power to detect significant differences due to the small sample size. Post-HSCT, recipients' OEF and CBF were similar to controls (OEF median 0.270 vs 0.288, p=0.18; CBF median CBF 65.1 vs 75.8 ml/100 g/min, p = 0.42). None of the HSCT recipients had new overt or silent strokes on FLAIR imaging or developed severe acute or chronic GVHD after HSCT.Pre-HSCT, recipients were anemic compared to controls (median Hb 9.8 vs 12.8 g/dl, p = 0.018). Pre-HSCT Hb S concentrations were lower than expected for SCA due to recent red blood cell transfusions (median 50.6%, range 39.7-77.6%). At the post-HSCT imaging timepoint, recipients' anemia had resolved (median Hb 12.4 g/dl, range 11.3-15.7 g/dl), and Hb S concentrations were consistent with their donors' levels. When all pre- and post-HSCT measurements were compared, OEF had a strong negative correlation with Hb (Spearman's rho = -0.905, p = 0.002) and a strong positive correlation with Hb S concentration (Spearman's rho = 0.970, p < 0.001). CBF had a weaker negative correlation with Hb (Spearman's rho = -0.714, p = 0.047) and positive correlation with Hb S concentration (Spearman's rho = 0.731, p = 0.040).ConclusionIn this cohort, children with SCA had normalization of OEF and CBF after successful HSCT. OEF elevation was strongly correlated with Hb S concentration and inversely correlated with Hb concentration in these HSCT recipients. Our data suggest that when curative HSCT corrects hemolytic anemia, OEF and CBF normalize. This physiologic change may provide protection against strokes following HSCT for SCA. [Display omitted] DisclosuresHulbert:Pfizer: Other: Spouse employment at Pfizer. Fields:Proclara Biosciences: Equity Ownership.

Cerebral Metabolic Stress Is Lower in Patients with Sickle Cell Anemia on Hydroxyurea Therapy

Hydroxyurea (HU) is the only medication available with neuroprotective potential in sickle cell anemia (SCA), yet the physiological mechanisms of this effect remain unclear. We utilized MRI to measure cerebral blood flow (CBF) and oxygen extraction fraction (OEF) to test our hypothesis that HU therapy relieves ongoing cerebral metabolic stress by decreasing OEF in patients with SCA. Brain MRI measured CBF (pseudo-continuous arterial spin labeling), OEF (asymmetric spin echo sequence that measures voxel-wise tissue deoxyhemoglobin) and vasculopathy (magnetic resonance angiography) in prospectively enrolled participants with SCA. FMRIB9s Linear Image Registration Tool individually co-registered CBF and OEF maps to corresponding T1 images, and FMRIB9s Automated Segmentation Tool segmented gray and white matter (GM and WM). For analysis, participants were cohorted by SCA therapy they were receiving at the time of the MRI. Group comparisons between SCA without HU, SCA with HU, and SCA pre-transfusion (pre-tx; MRI up to 24 hours before chronic tx therapy) were made with Kruskal-Wallis or chi-squared test, followed by pairwise comparisons with Mann-Whitney U test. Bivariate correlations were described with Spearman9s rho. Significance was specified as p-value Seventy-nine participants with SCA (70 HbSS, 9 HbSβ 0 thalassemia) underwent MRI. There was no significant difference in age (p = 0.965) or sex (p = 0.471) among treatment cohorts. Hemoglobin (Hb) was significantly different between cohorts (p = 0.001). While the SCA without HU cohort had a significantly lower Hb than both SCA with HU (p = 0.010) and SCA pre-tx (p There was no difference in GM (p = 0.680) or WM (p = 0.736) CBF among the 3 cohorts, even after controlling for age with multiple regression. However, there was a significant difference in GM OEF among cohorts (p To investigate potential mechanisms of metabolic stress reduction, we evaluated the relationship between OEF, total Hb, % Hb A, % Hb F and % Hb S. OEF and Hb were strongly correlated in both GM and WM (GM: spearman9s rho = -0.857, p 2 = 0.737, p = 0.003), and for WM OEF (total Hb: β = -0.041, p 2 = 0.719, p We report the first investigation into the effects of HU on cerebral oxygen metabolism in SCA. Our data suggest that HU mitigates ongoing cerebral metabolic stress by improving cerebral oxygen delivery, allowing reduction in OEF without altering CBF; however, the degree of OEF correction is not as strong as chronic tx therapy. Longitudinal evaluation of these cohorts is needed to determine if the improvement in OEF by HU is sufficient for prevention of stroke and cognitive dysfunction in patients with SCA. Disclosures Fields: Proclara Biosciences: Equity Ownership. Hulbert: Pfizer: Other: Spouse employment at Pfizer.

Monitoring of near-infrared spectrum values during packed red blood cell transfusion in pediatric intensive care unit.

Packed red blood cell (PRBC) transfusion is one of the most common treatment options in pediatric intensive care unit (PICU) which targets a better cerebral oxygenation. This study aimed to show the cerebral near-infrared spectroscopy (cNIRS) changes during PRBC transfusions in PICU. In this prospective observational study, changes in regional cerebral tissue oxygen saturation (rSO2) in pediatric patients, who required PRBC transfusion were monitored. All the cNIRS and related values were classified as baseline values. The same values were measured and calculated at the end of transfusion and named as 4th-hour values. Further measurements and calculations were made three hours later and named as 7th-hour values. Changes in cNIRS, cerebral tissue fractional oxygen extraction (CTFOE), cNIRS variability index (cNIRS-VI) were compared using Friedman test. A total of 53 PRBC transfusions were monitored. Baseline haemoglobin increased from 6.3 (5.9, 6.7) gr/dL to 8.6 (8.4, 9) gr/dL at the 7th-hour. cNIRS values improved during transfusion (P=0.012), with a concomitant decrease in cNIRS-VI and CTFOE values (P<0.001 and P=0.017 consecutively) CONCLUSION: Our study revealed that there is an increase in cNIRS and related values after transfusion compared to baseline values in critically ill children admitted to a PICU. Age of PRBC did not have an effect on delta-cNIRS or post-transfusion hemoglobin values. There is a moderate correlation between the baseline cNIRS values and delta-cNIRS value after the transfusion.

An interictal measurement of cerebral oxygen extraction fraction in MRI-negative refractory epilepsy using quantitative susceptibility mapping.

Oxygen extraction fraction (OEF) can be a factor to identify brain tissue's disability in epileptic patients. This study aimed to assess the OEF's level measurement in refractory epileptic patients (REPs) using a quantitative susceptibility mapping (QSM) method and to determine whether the OEF parameters change. QSM-OEF maps of 26 REPs and 16 healthy subjects were acquired using 3T MRI with a 64-channel coil. Eighteen regions-of-interest (ROIs) were chosen around the cortex in one appropriate slice of the brain and the mean QSM-OEF for each ROI was obtained. The correlations of QSM-OEF among different clinical characteristics of the disease, as well as between the patients and normal subjects, were also investigated. QSM-OEF was shown to be significantly higher in REPs (44.9±5.8) than that in HS (41.9±6.2) (p<0.05). Mean QSM-OEF was statistically lower in the ipsilateral side (44.5±6.6) compared to the contralateral side (46.4±6.8) (P<0.01). QSM-OEF was illustrated to have a strong positive correlation with the attack duration (r=0.6), and a moderate negative correlation with the attack frequency (r=-0.3). Using an optimized support vector machine algorithm, we could predict the disease in subjects having abnormal OEF values in the brain-selected-ROIs with sensitivity, specificity, AUC, and the precision of 0.96, 1, 0.98, and 1, respectively. The results of this study revealed that QSM-OEF of the REPs' brain is higher than that of HS, which indicates that QSM-OEF is associated with disease activity.

Cerebral Hemodynamics and Executive Function in Sickle Cell Anemia.

Individuals with sickle cell anemia experience cognitive deficits, even in the absence of cerebral infarcts or strokes. This study tested the hypothesis that elevated cerebral blood flow and oxygen extraction fraction are associated with lower executive function in individuals with sickle cell anemia. Three-Tesla brain magnetic resonance imaging was performed, including anatomic, gray matter cerebral blood flow, and global oxygen extraction fraction imaging. Executive function was measured using the working memory index from an age-appropriate Wechsler battery and tasks from the National Institutes of Health Toolbox Cognition Battery. Bivariate and multivariate models were examined (significance: P<0.05). Fifty-four participants (age range=6-31 years) with sickle cell anemia were enrolled. Hematocrit was positively related to fluid cognition, cerebral blood flow was inversely related to working memory and inhibitory control, and oxygen extraction fraction was inversely related to processing speed. Associations remained significant in multivariate analyses controlling for age, income, and infarcts. Elevated cerebral blood flow and oxygen extraction fraction, markers of hemodynamic impairment, are associated with deficits in executive function in individuals with sickle cell anemia.

Effects of mild hypoxia on oxygen extraction fraction responses to brain stimulation

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.

Integrated PET/MRI scanner with oxygen-15 labeled gases for quantification of cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen.

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) by PET with oxygen-15 labeled gases is useful for diagnosis and treatment planning in cases of chronic occlusive cerebrovascular disease. In the present study, CBF, CBV, OEF and CMRO2 were measured using the integrated design of PET/MRI scanner system. This is a first attempt to measure cerebral perfusion and oxygen metabolism using PET/MRI with oxygen-15 labeled gases. PET/MRI measurements with the steady-state method of oxygen-15 labeled gases, carbon monoxide (C15O), oxygen (15O2), and carbon dioxide (C15O2) were performed on nine healthy men. Two kinds of attenuation correction for PET were performed using MRI with Dixon sequence (DIXON) and Dixon sequence with model-based bone segmentation (DIXONbone). A real-time motion correction of PET images was also performed using simultaneously measured MR images to detect head motion. Mean and SD values of CBF, CBV, OEF, and CMRO2 in the cerebral cortices with attenuation correction by DIXON were 31 ± 4mL/100mL/min, 2.7 ± 0.2mL/mL, 0.40 ± 0.07, and 2.5 ± 0.3mL/100mL/min without real-time motion correction, and 33 ± 4mL/100mL/min, 2.7 ± 0.2mL/mL, 0.40 ± 0.07, and 2.6 ± 0.3mL/100mL/min with real-time motion correction, respectively. Values with of CBF, CBV, OEF, and CMRO2 with attenuation correction by DIXONbone were 35 ± 5mL/100mL/min, 2.8 ± 0.2mL/mL, 0.40 ± 0.07, and 2.8 ± 0.3mL/100mL/min without real-time motion correction, and 38 ± 5mL/100mL/min, 2.8 ± 0.2mL/mL, 0.40 ± 0.07, and 3.0 ± 0.4mL/100mL/min with real-time motion correction, respectively. Using PET/MRI with oxygen-15 labeled gases, CBF, CBV, OEF, and CMRO2 could be measured. Values of CBF, CBV, and CMRO2 measured with attenuation correction by DIXON were significantly lower than those measured with correction by DIXONbone. One of the reasons for this is that attenuation correction of DIXON does not take into consideration of the photon absorption by bone. OEF values, corresponding to ratios of CMRO2 to CBF, were not affected by attenuation correction methods. Values of CBF and CMRO2 with a real-time motion correction were significantly higher than those without correction. Using PET/MRI with adequate corrections, similar values of CBF, CBV, OEF, and CMRO2 as PET alone scanner system reported previously were obtained. The UMIN clinical trial number: UMIN000033382.

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.

Cerebral oxygen extraction fraction (OEF): Comparison of challenge-free gradient echo QSM+qBOLD (QQ) with 15O PET in healthy adults

We aimed to validate oxygen extraction fraction (OEF) estimations by quantitative susceptibility mapping plus quantitative blood oxygen-level dependence (QSM+qBOLD, or QQ) using 15O-PET. In ten healthy adult brains, PET and MRI were acquired simultaneously on a PET/MR scanner. PET was acquired using C[15O], O[15O], and H2[15O]. Image-derived arterial input functions and standard models of oxygen metabolism provided quantification of PET. MRI included T1-weighted imaging, time-of-flight angiography, and multi-echo gradient-echo imaging that was processed for QQ. Region of interest (ROI) analyses compared PET OEF and QQ OEF. In ROI analyses, the averaged OEF differences between PET and QQ were generally small and statistically insignificant. For whole brains, the average and standard deviation of OEF was 32.8 ± 6.7% for PET; OEF was 34.2 ± 2.6% for QQ. Bland-Altman plots quantified agreement between PET OEF and QQ OEF. The interval between the 95% limits of agreement was 16.9 ± 4.0% for whole brains. Our validation study suggests that respiratory challenge-free QQ-OEF mapping may be useful for non-invasive clinical assessment of regional OEF impairment.