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 Preliminary evidence for cerebral capillary shunting in adults with sickle cell anemia

2017 ◽  
Vol 39 (6) ◽  
pp. 1099-1110 ◽  
Author(s):  
Meher R Juttukonda ◽  
Manus J Donahue ◽  
Larry T Davis ◽  
Melissa C Gindville ◽  
Chelsea A Lee ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Preliminary Evidence ◽  
Oxygen Extraction Fraction ◽  
3.0 T ◽  
Cerebral Capillary ◽  
Prospective Trials ◽  
Dural Venous Sinus ◽  
Venous Signal ◽  
Flow Velocities

Elevated flow velocities in adults with sickle cell anemia (SCA) may cause rapid erythrocyte transit through capillaries. This phenomenon could present as dural venous sinus hyperintensity on arterial spin labeling (ASL)-MRI and could be indicative of capillary shunting. Here, the prevalence of ASL venous hyperintensities and association with relevant physiology in adults with SCA was investigated. SCA ( n = 46) and age-matched control ( n = 16) volunteers were recruited for 3.0 T MRI. Pseudo-continuous ASL-MRI was acquired for cerebral blood flow (CBF) calculation and venous hyperintensity determination; venous signal intensity and a categorical venous score (three raters; 0 = no hyperintensity, 1 = focal hyperintensity, and 2 = diffuse hyperintensity) were recorded. Flow velocity in cervical internal carotid artery segments was determined from phase contrast data (venc = 40 cm/s) and whole-brain oxygen extraction fraction (OEF) was determined from T2-relaxation-under-spin-tagging MRI. Cerebral metabolic rate of oxygen was calculated as the product of OEF, CBF, and blood oxygen content. ASL venous hyperintensities were significantly ( p < 0.001) more prevalent in SCA (65%) relative to control (6%) participants and were associated with elevated flow velocities ( p = 0.03). CBF ( p < 0.001), but not OEF, increased with increasing hyperintensity score. Prospective trials that evaluate this construct as a possible marker of impaired oxygen delivery and stroke risk may be warranted.

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.

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.

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 Arterial blood pressure in adult Nigerians with sickle cell anemia

2010 ◽  
Vol 56 (3) ◽  
pp. 326-331 ◽  
Author(s):  
N.I. Oguanobi ◽  
B.J.C. Onwubere ◽  
O.G. Ibegbulam ◽  
S.O. Ike ◽  
B.C. Anisiuba ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Arterial Blood

Abstract W P115: Utilization of Blood Sampling Global Oxygen Extraction Fraction and SPECT to Anticipate Cerebral Hyperperfusion Syndrome Following Elective Carotid Artery Stenting

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Takahisa Mori ◽  
Tomonori Iwata ◽  
Yuhei Tanno ◽  
Shigen Kasakura ◽  
Yoshinori Aoyagi ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Carotid Artery Stenting ◽  
Blood Sampling ◽  
Oxygen Extraction Fraction ◽  
Oxygen Extraction ◽  
Cerebral Hyperperfusion Syndrome ◽  
Hyperperfusion Syndrome ◽  
Cerebral Hyperperfusion ◽  
Arterial Blood ◽  
Extraction Fraction

Background: It is required to anticipate cerebral hyperperfusion syndrome (CHS) following carotid artery stenting (CAS). Purpose: The purpose of our retrospective study was to investigate whether or not blood sampling oxygen extraction fraction (OEF) and post-CAS CBF increase in SPECT had relation to CHS following CAS. Methods: Included in our analysis were patients (1) who underwent elective CAS in our institution between October 2010 and May 2014, and (2) who underwent blood sampling for OEF calculation before and immediately after CAS, and (3) who underwent SPECT before and just after CAS. OEF was calculated from cerebral arteriovenous oxygen difference. Arterial blood was sampled from the common carotid artery and venous blood from the dominant-sided superior jugular bulb. CHS was defined as pulsatile headaches, restlessness, convulsion, and/or new neurological symptoms not due to cerebral ischemia within seven days following CAS. CBF was measured before and just after CAS. CBF increase in the CAS side was defined as follows; (post-CAS CBF ratio - pre-CAS CBF ratio) of more than 10%, where CBF ratio was defined as CAS-sided fronto-parietal CBF divided by ipsilateral cerebellar CBF (%). Evaluated were baseline features in patients, pre-CAS OEF, post-CAS OEF, CBF ratio, CBF increase and CHS. Results: During the study period, 134 patients matched our criteria for analysis. Pre-CAS OEF was 0.41+-0.06, post-CAS OEF was 0.42+-0.08, pre-CAS CBF ratio: 88.7+-15.4%, CBF increase: 1.86+-12.3%. Nine patients presented CHS. Among them, pre-CAS OEF, CBF ratio and CBF increase were significant. ROC curves showed that pre-CAS OEF of 0.46 (p<0.001, OR: 9.3), CBF ratio of 92%(p<0.05, OR: 6.5), CBF increase of 8.8% (p<0.005, OR: 6.6) were cut-off values. Among 10 patients with pre-CAS OEF of more than 0.46 and CBF increase of more than 8.8%, 4 patients presented CHS (p<0.0001, OR;15.9). Conclusion: Elevation of pre-CAS OEF and increase of post-CAS CBF were strongly related to CHS.

scholarly journals Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia

Blood ◽  
2019 ◽  
Vol 133 (22) ◽  
pp. 2436-2444 ◽  
Author(s):  
Melanie E. Fields ◽  
Kristin P. Guilliams ◽  
Dustin Ragan ◽  
Michael M. Binkley ◽  
Amy Mirro ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Metabolic Stress ◽  
Brain Magnetic Resonance Imaging ◽  
Border Zone ◽  
Oxygen Extraction Fraction ◽  
Transfusion Therapy ◽  
Whole Brain ◽  
Disease Modifying Therapy ◽  
Disease Modifying

Abstract Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P &lt; .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.

Hemoglobinuria Is a Risk Factor For Kidney Disease Progression In Sickle Cell Anemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 996-996
Author(s):  
Santosh L. Saraf ◽  
Xu Zhang ◽  
Tamir Kanias ◽  
James P. Lash ◽  
Robert E. Molokie ◽  
...  
Keyword(s):  
Steady State ◽  
Kidney Disease ◽  
Kidney Function ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Red Blood Cell Transfusion ◽  
Free Hemoglobin ◽  
Arterial Blood

Abstract Chronic kidney disease (CKD) is a frequent complication of sickle cell anemia (SCA) and is a predictor of early mortality. To determine the predictors of deteriorating kidney function in SCA, we followed 164 patients treated at the University of Illinois at Chicago for a median of 32 months (range 3-88 months). Steady-state estimated glomerular filtration (eGFR), albuminuria, and hemoglobinuria assessments were obtained at baseline and during the follow-up period. Steady-state was defined as greater than four weeks from a vaso-occlusive pain episode or a red blood cell transfusion. Hemoglobinuria was defined as positive for blood on dipstick and < 2 red blood cells on microscopy. Fifty-six (34%) of the patients had hemoglobinuria at baseline. We confirmed in a subset of 43 patients that dipstick positive hemoglobinuria (n=17) was associated with higher urine cell-free hemoglobin concentrations determined by ELISA than dipstick negative urine (n=26) (23.1 vs. 11.5 ng/mL, p<0.0001) (Figure 1). Age and mean arterial blood pressures were similar in patients with hemoglobinuria at baseline compared to those without but markers of hemolysis were higher (LDH, indirect bilirubin, AST, and reticulocyte percentage; p<0.0001). Sixty-one percent (95%CI: 48-73%) of patients with hemoglobinuria at baseline had hemoglobinuria at most recent follow up compared to 9% (95%CI: 5-18%) of patients without hemoglobinuria at baseline (p<0.0001). The proportion of patients with CKD progression defined by a 50% reduction in eGFR calculated by the CKD-EPI formula or requirement for hemodialysis or kidney transplant was higher in patients with baseline hemoglobinuria (13%, 7/56) versus without hemoglobinuria (1%, 1/108) (HR 14, 95%CI: 2-113; logrank p=0.001) (Figure 2). Progression of albuminuria category from normoalbuminuria (albuminuria < 30mg/g creatinine) to either microalbuminuria (albuminuria = 30-300 mg/g creatinine) or macroalbuminuria (albuminuria > 300mg/g creatinine) or microalbuminuria to macroalbuminuria was also higher in patients with baseline hemoglobinuria (42%, 11/26) versus without hemoglobinuria (13%, 9/67) (HR 3.1, 95%CI: 1.3-7.7; logrank p=0.004) (Figure 3). In conclusion, hemoglobinuria determined by urinalysis at steady-state is a valid assessment of increased urine cell-free hemoglobin concentration and is fairly consistent on repeat testing at steady-state visits. The presence of hemoglobinuria is significantly associated with a greater risk for progression of CKD and albuminuria. Our findings are consistent with the possibility that cell-free hemoglobin contributes to the progression of kidney disease in SCA. Further research including measures to decrease cell-free hemoglobin exposure to preserve kidney function are warranted.Figure 1Figure 1. Figure 2Figure 2. Figure 3Figure 3. Disclosures: No relevant conflicts of interest to declare.

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.

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