Abstract TMP93: Elevated Oxygen Extraction Fraction Measured With Noninvasive MRI may be Discriminatory for Stroke Risk in Adults With Sickle Cell Anemia

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Lori C Jordan ◽  
Melissa Gindville ◽  
Allison Scott ◽  
Megan K Strother ◽  
Adetola Kassim ◽  
...  
Keyword(s):  
Linear Regression ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Risk ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Extraction Fraction ◽  
Clinical Impairment ◽  
Mean Differences ◽  
Oxygen Carrying Capacity

Introduction: No screening procedures exist for evaluating stroke risk in adults with sickle cell anemia (SCA). Reduced oxygen carrying capacity is present in SCA, which may initially be compensated for by an increase in cerebral blood flow (CBF) and then by increased oxygen extraction fraction (OEF). Hypothesis: OEF and CBF can be measured noninvasively and reproducibly with MRI using clinically-available equipment in adults with SCA; elevated OEF provides added discriminatory capacity for clinical impairment relative to vasculopathy extent and CBF alone. Methods: Structural, CBF-weighted, and MRA imaging, together with a noninvasive OEF-weighted T 2 -relaxation-under-spin-tagging (TRUST)-MRI method was applied in SCA adults (n=26) and race and age-matched controls (n=11). A Kruskal-Wallis test was applied to evaluate mean differences between SCA and control parameters. Linear regression assessed how elevated OEF correlated with increasing clinical impairment defined by presence of infarct, vasculopathy, or use of regular blood transfusions for SCA. Results: OEF had high reproducibility within the same scan session, n=37 (ICC = 0.989). Whole-brain OEF and CBF were increased in SCA adults (OEF=0.46±0.08; CBF=52.4±8.3 ml/100g/min) versus controls (OEF=0.35±0.06; CBF=43.6±5.1 ml/100g/min). Hematocrit and OEF were inversely correlated (R 2 =0.72; p<0.01). Linear regression revealed a stronger relationship of OEF than CBF with clinical impairment. In SCA adults without impairment (n=12) CBF and OEF have an inverse relationship (R 2 =0.41; p=0.01, Fig. 1A) but with clinical impairment (infarct, vasculopathy or severe pain requiring regular transfusions, n=14) CBF and OEF become uncoupled (R 2 =0.08; p=0.16; Fig. 1B) as CBF may not be able to increase further and may plateau or decline. Conclusion: TRUST-MRI OEF is a rapid, reproducible measure. OEF shows promise as screening tool for hemodynamic impairment and stroke risk in adults with SCA.

scholarly journals Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients

2016 ◽  
Vol 38 (9) ◽  
pp. 1618-1630 ◽  
Author(s):  
Jennifer M Watchmaker ◽  
Meher R Juttukonda ◽  
Larry T Davis ◽  
Allison O Scott ◽  
Carlos C Faraco ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Structural Mri ◽  
Interquartile Range ◽  
Cerebrovascular Reactivity ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Vascular Reserve ◽  
Extraction Fraction ◽  
Oxygen Carrying Capacity

Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38–0.45) compared to controls (interquartile range = 0.29–0.38), similar to participants with SCA (interquartile range = 0.37–0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.

scholarly journals Cerebral Hemodynamics and Executive Function in Sickle Cell Anemia

Stroke ◽  
2021 ◽  
Author(s):  
Kemar V. Prussien ◽  
Bruce E. Compas ◽  
Rachel E. Siciliano ◽  
Abagail E. Ciriegio ◽  
Chelsea A. Lee ◽  
...  
Keyword(s):  
Working Memory ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Executive Function ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Brain Magnetic Resonance Imaging ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Extraction Fraction

Background and Purpose: 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. Methods: 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). Results: 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. Conclusions: 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.

Elevated Cerebral Blood Oxygen Extraction in Non-Transfused Sickle Cell Disease Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1387-1387
Author(s):  
Adam M Bush ◽  
Matthew Borzage ◽  
Soyoung Choi ◽  
Thomas Coates ◽  
John C Wood
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Cell Disease ◽  
T2 Relaxation ◽  
Hemoglobin S ◽  
Cerebral Metabolic Rate ◽  
Extraction Fraction

Abstract Introduction Chronic Transfusion Therapy (CTT) has been successful in decreasing stroke frequency in patients with sickle cell disease (SCD). Despite this, indication for CTT is largely based on empirical evidence and the mechanisms by which CTT protects the brain remain unclear. CTT improves oxygen carrying capacity and lowers hemoglobin S%, but the corresponding impact on cerebral blood flow(CBF), cerebral metabolic rate (CMRO2), and oxygen extraction fraction (OEF) is unknown. Understanding the impact of these competing influences in non-transfused (NT) and chronically transfused (CT) SCD patients will inform stroke prevention. Thus, we measured CBF, CMRO2, and OEF, in NT and CT patients with SCD using magnetic resonance imaging (MRI). Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Fourteen (6 NT, 8 CT) patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. Complete blood count and hemoglobin electrophoresis were performed. Arterial oxygen saturation (SaO2) was measured via peripheral pulse oximetery. CaO2 was calculated as the product of hemoglobin, SaO2 and the oxygen density of hemoglobin (1.36 ml/g). Phase contrast imaging of the carotid and vertebral arteries was used to measure global CBF. T2 Relaxation Under Spin Tagging (TRUST) was used to measured T2 relaxation of blood within the sagittal sinus. T2 relaxation was converted to SvO2 via previously validated calibration curves. OEF represented the difference of SaO2 andSvO2 divided bySaO2. CMRO2 was calculated as the product of CBF and OEF. High resolution, 3D, T1 weighted images were used for brain volume calculation using BrainSuiteñ software. Results Table 1 summarizes the results. Hemoglobin and oxygen content were well matched between transfused and non transfused SCD patients. Cerebral metabolic rate was also nearly identical in the two groups. However, CT patients exhibited 25% higher CBF than NT SCD patients, allowing them to have a normal oxygen extraction fraction ~30%. In contrast, OEF in NT SCD patients was abnormally high (37.8%), suggesting a decreased extraction reserve. Total oxygenation index (TOI) by NIRS also trended lower in NT SCD patients, consistent with the greater oxygen extraction and lower cerebral venous saturations observed. Abstract 1387. TableCTL (reference)NTCTp value (NT vs CT)Hemoglobin (g/dl)13.5 ± 1.229.7 ± 1.259.7 ± 1.05nsCaO2 (umol O2/ml)9.85 ± .996.84 ± 1.176.95 ±.71nsCMRO2 (umol O2/100g/min)193.1 ± 44.9239.7 ± 35.3238.6 ± 38.3nsCBF (ml/100g/min)70.0 ± 12.8101.5 ± 16.6127.1 ± 23.5< 0.05OEF (%)30.0 ± 7.137.8. ± 3.0629.7 ± 7.53< 0.05NIRS TOI56.0 ± 4.0948.5 ± 4.2153.5 ± 8.760.076SvO2 (%)65.6 ± 6.856.2 ± 5.267.1 ± 6.7< 0.05 Discussion: Chronically transfused SCD patients achieve normal brain oxygenation metrics (SvO2, OEF, and NIRS) but require very high CBF to achieve this balance (lowering flow reserve). In contrast, NT SCD patients have smaller increases in CBF but require greater oxygen extraction to meet cerebrovascular demands (lowering extraction reserve). Hemoglobin S mediate changes in oxygen dissociation, blood viscosity, red cell deformability and microvascular damage potentially mediate these differences but their interplay is complicated and requires further study. Disclosures Coates: novartis: Consultancy, Honoraria, Speakers Bureau; shire: Consultancy, Honoraria; apo pharma: Consultancy, Honoraria; acceleron: Consultancy, Honoraria.

scholarly journals Hemodynamics and oxygen extraction in chronic large artery steno-occlusive disease: Clinical applications for predicting stroke risk

2017 ◽  
Vol 38 (9) ◽  
pp. 1584-1597 ◽  
Author(s):  
Colin P Derdeyn
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Carotid Artery ◽  
Stroke Risk ◽  
Arterial Stenosis ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Large Artery ◽  
Extraction Fraction ◽  
Hemodynamic Assessment

Depending on the adequacy of collateral sources of blood flow, arterial stenosis or occlusion may lead to reduced perfusion pressure and ultimately reduced blood flow in the distal territory supplied by that vessel. There are two well-defined compensatory mechanisms to reduced pressure or flow – autoregulatory vasodilation and increased oxygen extraction fraction. Other changes, such as metabolic downregulation, are likely. The positive identification of autoregulatory vasodilation and increased oxygen extraction fraction in humans is an established risk factor for future ischemic stroke in some disease states such as atherosclerotic carotid stenosis and occlusion. The mechanisms by which ischemic stroke may occur are not clear, and may include an increased vulnerability to embolic events. The use of hemodynamic assessment to identify patients with occlusive vasculopathy at an increased risk for stroke is very appealing for several different patient populations, such as those with symptomatic intracranial atherosclerotic disease, moyamoya phenomenon, complete internal carotid artery occlusion, and asymptomatic cervical carotid artery stenosis. While there is very good data for stroke risk prediction in some of these groups, no intervention based on these tools has been proven effective yet. In this manuscript, we will review these topics above and identify areas for future research.

scholarly journals Cerebellum as the Normal Reference for the Detection of Increased Cerebral Oxygen Extraction

2010 ◽  
Vol 30 (10) ◽  
pp. 1767-1776 ◽  
Author(s):  
Thomas T Jiang ◽  
Tom O Videen ◽  
Robert L Grubb ◽  
William J Powers ◽  
Colin P Derdeyn
Keyword(s):  
Stroke Risk ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Reference Region ◽  
Positron Emission Tomographic ◽  
Extraction Fraction ◽  
Kaplan Meier ◽  
Positron Emission ◽  
Hemodynamic Impairment ◽  
A Prospective Study

Hemispheric ratios of oxygen extraction fraction (OEF), a proven methodology for the detection of severe hemodynamic impairment and stroke risk, are not sensitive for detecting bilateral hemispheric increases in OEF. The aim of this study was to investigate the use of cerebellum as the reference normal. We analyzed positron emission tomographic (PET) measurements of count-based OEF and clinical data from 57 patients with unilateral atherosclerotic carotid occlusion and 13 controls enrolled in a prospective study of stroke risk. The ipsilateral, contralateral, and total cerebellum were each evaluated as possible reference regions, and the ratios of the middle cerebral artery (MCA) hemispheric OEF counts against those in each reference region were determined. A statistically significant correlation ( P<0.0001) was observed with all three MCA-to-cerebellar ratios when compared with the gold standard of ipsilateral-to-contralateral MCA hemispheric ratio. Kaplan–Meier analyses showed all MCA-to-cerebellar ratios to be predictive of stroke. By using the total cerebellum method, 7 strokes were found to have occurred in 20 patients with increased OEF ( P=0.0007), compared with 7 strokes out of 16 patients with elevated OEF using the ipsilateral or contralateral cerebellum methods ( P<0.0001). These methods may be useful for categorizing the hemodynamic status of patients with bilateral cerebral occlusive diseases, including atherosclerosis and moyamoya, to determine the association with the risk of subsequent stroke.

Abstract WMP97: Regional Cerebral Oxygen Extraction is Elevated in Tissue at High Risk of Stroke in Pediatric Sickle Cell Disease

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Andria L Ford ◽  
Kristin P Guilliams ◽  
Melanie Fields ◽  
Dustin K Ragan ◽  
Cihat Eldeniz ◽  
...  
Keyword(s):  
High Risk ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Retrospective Cohort ◽  
Stroke Risk ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Cell Disease ◽  
Heat Map ◽  
Spin Echo Sequence

Introduction: Children with sickle cell disease (SCD) are at high risk of stroke. Hemispheric oxygen extraction fraction (OEF) is a predictor of stroke in adults with carotid occlusion, but OEF has not been evaluated as a predictor of stroke in children with SCD. Hypothesis: OEF is elevated in SCD children compared to controls within a region at high risk of stroke as defined by an infarct heat-map created from a separate retrospective SCD cohort. Methods: A prospective MRI study enrolled 37 children aged 5-21: 17 with SCD and no stroke, 12 with SCD and silent infarcts (median infarct volume=0.3ml), and 8 sibling controls. None were on transfusions or had overt stroke history. Voxel-wise OEF was measured using an asymmetric spin echo sequence. In a separate retrospective cohort of 67 SCD children with overt and silent stroke, infarct regions on FLAIR were manually outlined and coregistered to an average T1 map to create an infarct heat-map (Fig A) which was used to define a “high risk” ROI (defined by >3% infarct density). This ROI was aligned to individual OEF maps from the prospective cohort (Fig B, average OEF map). OEF within the “high risk” ROI was compared between SCD children and controls; and between SCD children with and without infarction using Mann Whitney U tests. Results: The infarct heat-map from the retrospective cohort (Fig A) and the average OEF map from the prospective SCD cohort (Fig B) demonstrate striking co-localization of infarct density and elevated OEF. Within the “high risk” ROI, OEF was higher in SCD children compared to controls (39% [36, 46] vs. 23% [22, 27], p<0.0001 (Fig C). OEF within this “high risk” ROI did not differ between SCD children with and without infarcts (40% [38, 47] vs. 38% [35, 46], p=0.6). Conclusion: OEF in SCD children is elevated in the internal borderzone, a region with high stroke risk in SCD. Regional OEF may be a marker of cerebral metabolic stress that could be exploited to stratify stroke risk in this vulnerable population.

scholarly journals Reduced oxygen extraction efficiency in sickle cell anemia patients with evidence of cerebral capillary shunting

2020 ◽  
pp. 0271678X2091312
Author(s):  
Meher R Juttukonda ◽  
Manus J Donahue ◽  
Spencer L Waddle ◽  
Larry T Davis ◽  
Chelsea A Lee ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Quantitative Measure ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Arterial Blood ◽  
Endogenous Contrast ◽  
Hyperintense Signal ◽  
Cerebral Capillary ◽  
Magnetic Resonance Imaging Mri

Arterial spin labeling (ASL) magnetic resonance imaging (MRI) utilizes arterial blood water as an endogenous contrast agent to provide a quantitative measure of cerebral blood flow (CBF). Recently, hyperintense signal within dural venous sinuses in ASL images of sickle cell anemia (SCA) patients has been shown to be consistent with elevated flow velocities and may indicate capillary shunting and reduced oxygen extraction. Here, we performed oxygen extraction fraction (OEF) and CBF measurements in adults (cumulative n = 114) with ( n = 69) and without ( n = 45) SCA to test the hypothesis that hyperintense venous ASL signal is associated with reduced OEF. Higher categorical scores of shunting on ASL MRI were associated with lower OEF in participants with silent cerebral infarcts or white matter hyperintensities ( p = 0.003), but not in those without lesions ( p = 0.551). These findings indicate that venous hyperintense signal in ASL images in SCA patients may represent a marker of capillary-level disturbances in oxygen exchange efficiency and small vessel pathology.

scholarly journals Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia

Brain ◽  
2016 ◽  
Vol 139 (3) ◽  
pp. 738-750 ◽  
Author(s):  
Lori C. Jordan ◽  
Melissa C. Gindville ◽  
Allison O. Scott ◽  
Meher R. Juttukonda ◽  
Megan K. Strother ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anaemia ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Non Invasive ◽  
Extraction Fraction

Abstract 109: Non-invasive Detection of Capillary Arteriovenous Shunting in Patients With Sickle Cell Anemia

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Meher R Juttukonda ◽  
Manus J Donahue ◽  
Melissa C Gindville ◽  
Sumit Pruthi ◽  
Adetola A Kassim ◽  
...  
Keyword(s):  
Flow Velocity ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Severe Disease ◽  
Oxygen Extraction Fraction ◽  
Arteriovenous Shunting ◽  
Sagittal Sinus ◽  
Arterial Blood ◽  
Clinical Impairment ◽  
Contrast Angiography

Introduction: High blood velocity can cause rapid erythrocyte transit through capillaries, reducing efficiency of oxygen delivery to tissue (capillary arteriovenous shunting). Arterial spin labeling (ASL) is an MRI technique that utilizes magnetic labeling of arterial blood water for CBF quantitation. Labeled water that traverses capillaries without exchanging with tissue leads to hyperintense venous signal indicative of arteriovenous shunting. We hypothesized that venous hyperintensity is present in sickle cell anemia (SCA) adults, correlates with flow velocity, and corresponds with clinical impairment and oxygen extraction fraction (OEF). Methods: ASL for shunting determination, TRUST for OEF measurement, phase contrast angiography for velocity assessment, and FLAIR / MRA for infarct / vasculopathy evaluation were performed at 3T in adults with SCA (n=36) and age- and race-matched controls (n=11). Three reviewers assessed for hyperintensity in the superior sagittal sinus on ASL images (Fig) and assigned scores of 0 (none), 1 (mild, focal), 2 (significant, focal), or 3 (significant, diffuse). Shunting scores were compared with the presence of clinical impairment (prior infarcts, stenosis>50%, or severe disease requiring transfusions) and OEF. Results: Interobserver agreement was excellent (Fleiss’ κ=0.91). Consensus shunting score in SCA adults (1.2±1.1) was higher (p<0.01) than controls (0.1±0.3), Median age 27.6 y, 57% F. Elevated shunting scores were observed in SCA adults with (1.23±1.07) vs. without (1.07±1.16) clinical impairment. A trend (p=0.068) for elevated OEF was observed in those with shunting scores ≥2 (0.44±0.07) vs. those with shunting scores ≤1 (0.40±0.07). Cervical flow velocity was elevated in subjects with shunting scores ≥2 (30.2±4.8 cm/s) vs. ≤1 (25.3±4.8 cm/s). Conclusion: Venous hyperintensity in ASL images may indicate capillary arteriovenous shunting and may reflect higher clinical impairment and elevated OEF.

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