scholarly journals Diminished cerebral oxygen extraction and metabolic rate in sickle cell disease using T2 relaxation under spin tagging MRI

2017 ◽  
Vol 80 (1) ◽  
pp. 294-303 ◽  
Author(s):  
Adam M. Bush ◽  
Thomas D. Coates ◽  
John C. Wood
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Oxygen Extraction ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
T2 Relaxation ◽  
Spin Tagging ◽  
Tagging Mri

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.

Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias

2021 ◽  
Author(s):  
Chau Vu ◽  
Adam Bush ◽  
Soyoung Choi ◽  
Matthew Borzage ◽  
Xin Miao ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Cerebral Oxygen ◽  
Cell Disease

Cerebral Oxygen Saturation in Sickle Cell Patients Treated with Hydroxyurea:.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1677-1677
Author(s):  
Masoud Nahavandi ◽  
Fatemeh Tavakkoli ◽  
Melville Q. Wyche ◽  
Syed P. Hasan ◽  
Oswaldo Castro
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Sickle Cell ◽  
Cerebral Oxygenation ◽  
Cerebral Oximetry ◽  
Cerebral Oxygen Saturation ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
Non Invasive

Abstract Recently we reported the use of a non-invasive near-infrared optical spectroscopy technique to measure cerebral oxygenation (cerebral oximetry, rSO2%) in agroup of 27 adult patients with sickle cell disease (Eur J Clin Invest, 34:143,2004). The sickle cell patients’ rSO2 values were significantly lower (mean 47.7%) than those in normal subjects (mean 61.3%) even though none of the patients had clinical evidence of stroke or cerebral ischemia. We included patients with all Hb phenotypes, and regardless of hydroxyurea (HU) treatment. Transfusions improved cerebral oxygen saturation but the post-transfusion values still did not reach normal levels. Our findings were corroborated independently by Raj et al. who studied 25 children with sickle cell disease (J Pediat Hematol Oncol 26:279,2004). In order to determine if long-term HU treatment affects rSO2, we analyzed cerebral oximetry results in a subset of 31 patients with sickle cell anemia (Hb SS). Eleven of them were on long-term (more than 6 months) HU treatment at stable doses (1000–1500 mg/day). The table shows that the mean rSO2, Hb, Hct, and MCV in HU-treated patients were significantly higher than those in sickle cell anemia (SCA) patients not on HU. The rSO2 in HU-treated patients was 12.5% higher than in SS patients not on this drug. By comparison, we previously reported a 24% increment in rSO2 following transfusions. A group of 8 patients who were on long-term HU treatment were given also single 1000 mg oral doses of HU and their rSO2 was measured for 12 hours without noticeable change in cerebral oxygenation. Nor did rSO2 change after oxygen inhalation (3L/min). The cause of the low rSO2 in sickle cell patients is unknown and still under investigation. It is probably not related exclusively to the anemia, since, as previously reported, anemic subjects without sickle cell disease appear to have normal rSO2. These preliminary results indicate that chronic HU treatment is associated with higher rSO2 values in SCA. If validated in a larger number of patients, our findings suggest that cerebral oximetry could be a useful, non-invasive method for assessing a new in vivo effect of HU and red cell transfusion in sickle cell disease: increased blood oxygen saturation in the cerebral vasculature. HYDROXYUREA AND CEREBRAL OXYGEN SATURATION IN PATIENTS WITH SICKLE CELL DISEASE NO HYDROXYUREA (N=20) HYDROXYUREA (N=11) P value* rSO2 = cerebral oxygen saturation. *= t-test. Plus/minus figures represent SD Mean rSO2 (%) 41 ± 6.6 46 ± 7.6 0.025 Mean Hb (g/dl) 8.4 ± 1.4 9.68 ± 1.2 0.029 Mean Hct (%) 24± 3.4 28± 4.4 0.027 Mean MCV (fl) 89± 8 102± 7 0.028

Elevated Cerebral Metabolic Oxygen Consumption in Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2706-2706 ◽  
Author(s):  
Adam M Bush ◽  
Matthew Borzage ◽  
Soyoung Choi ◽  
Thomas Coates ◽  
John C Wood
Keyword(s):  
Oxygen Consumption ◽  
White Matter ◽  
Sickle Cell Disease ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Grey Matter ◽  
Brain Volume ◽  
Resting Energy Expenditure ◽  
Cell Disease ◽  
T2 Relaxation

Abstract Introduction Stroke occurs when cerebral blood flow (CBF) is inadequate to the metabolic needs of the brain. In sickle cell disease (SCD) stroke is common, however accurate quantification of basal cerebral oxygen consumption (CMRO2) has not been performed. Early PET studies suggested CMRO2 was decreased in SCD patients, but these studies lacked data regarding brain volume and gray-white matter fractions; lower CMRO2 may simply have reflected brain loss from prior stroke. In contrast, NIRS and global resting energy expenditure studies have demonstrated elevated peripheral metabolic rate in SCD patients at baseline, with further increases during painful crisis. In those studies, oxygen consumption was correlated with markers of inflammation, particularly white blood cell count, consistent with metabolic consequences of neutrophil activation. Characterizing CMRO2 in SCD provides insight into better prevention and management of stroke in the SCD population. Accordingly, we measured CBF and cerebral venous saturation (SvO2) via a recently developed magnetic resonance imaging (MRI) technique: T2 Relaxation Under Spin Tagging (TRUST). Using the Fick Principle, this allowed for quantification of oxygen extraction fraction (OEF) and the first quantitative measurements of CMRO2in SCD patients. Methods All patients were recruited with informed consent or assent and this study was approved by the CHLA IRB. Exclusion criteria included pregnancy, previous stroke, acute chest or pain crisis hospitalization within one month. Fifteen patients with SCD and 12 healthy ethnicity matched controls (CTL) were studied. Arterial oxygen saturation (SaO2) was measured via peripheral pulse oximetery. TRUST was used to measured T2 relaxation of blood within the sagittal sinus; T2 relaxation was converted to SvO2 using established calibration curves. OEF represented the difference of SaO2 andSvO2 .Phase Contrast (PC) of the carotid and vertebral arteries was used to measure global CBF. CMRO2 was calculated as the product of CBF and OEF. High resolution, 3D, T1 weighted images were used for grey-white segmentation and brain volume calculations using BrainSuiteñ software. Relative grey matter CMRO2 and white matterCMRO2 were estimated by assuming that (gm) CMRO2 was three-fold higher than (wm) CRMRO2. Complete blood count, cell free hemoglobin, LDH, and hemoglobin electrophoresis were measured at the study visit. Results Table 1 summarizes the results. To compensate for their chronic anemia, SCD patients had 67% greater CBF than control subjects, producing a normal SvO2 and OEF. Oxygen delivery also trended higher than for controls leading to higher total CMRO2 in the SCD patients. CMRO2 increases remained significant even after correction for differences in grey and white matter volumes. We found no correlation between WBC and CMRO2when tested by population. Discussion Our study demonstrates elevated cerebral metabolism in SCD, mirroring increases in global resting energy expenditure and peripheral metabolic rate described by other groups. The etiology of the increased CMRO2 is unknown but could reflect neuroinflammation or energy demands from chronic injury/repair. Regardless, our observation at least partially explains the increase of CBF beyond predicted by anemia alone. By excluding patients with overt stroke and by correcting for differences in brain volume and composition, our results are the first CMRO2 measurements in SCD that are unconfounded by brain volume loss. Given the age differences between our study and control populations, we cannot exclude developmental differences in CMRO2 among patients and controls. However, in general, CMRO2 increases with age, which would tend to lessen rather than increase the CMRO2 differences seen in our study. Table 1 Controls SCD p Age (years) 37.2 + 2.8 20.3 + 2.6 <0.05 Sex 9 F, 3 M 9 F, 6 M ns Hemoglobin (g/dl) 13.5 + 1.2 9.6 + 1.1 <0.05 WBC (103/uL) 6.1 + 2.2 11.0 + 4.2 <0.05 Sa O2 (%) 95.7 + 1.5 94.1 + 4.1 ns Sv O2 (%) 65.6 + 6.7 63.6 + 8.4 ns OEF 30.0 + 7.1 32.3 + 7.4 ns CBF (ml/100g/min) 70.0 + 4.6 116.8 + 19.1 <0.05 Cerebral O2 delivery (umol O2/100g/min) 193.0 + 44.9 239.0 + 35.7 ns Grey Matter Mass (ml) 499.6 + 72.0 528.4 + 58.1 ns White Matter Mass (ml) 444.6 + 58.2 422.9 + 59.5 ns CMRO2 (umol O2/100g/min) 193.1 + 44.9 239.0 + 35.7 <0.05 (gm)CMRO2 250.7 + 58.7 292.7 + 39.7 <0.05 (wm) CMRO2 175.5 + 41.1 204.9 + 27.8 <0.05 Disclosures Coates: Novartis: Honoraria, Speakers Bureau; Apo Pharma: Consultancy, Honoraria; Acceleron: Consultancy, Honoraria; SHire: Consultancy, Honoraria.

scholarly journals PF742 CEREBRAL OXYGEN METABOLISM MEASUREMENTS WITH MRI IN ADULTS WITH SICKLE CELL DISEASE

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 324-325
Author(s):  
L. Vaclavu ◽  
E. Petersen ◽  
H. Mutsaerts ◽  
J. Petr ◽  
C. Majoie ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Oxygen Metabolism ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
Cerebral Oxygen Metabolism

scholarly journals Assessment of Cerebral Blood Flow and Oxygen Extraction in Pediatric Sickle Cell Disease with Non-Invasive Diffuse Optical Spectroscopies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Seung Yup Lee ◽  
Eashani Sathilingam ◽  
Kyle R. Cowdrick ◽  
Rowan O. Brothers ◽  
Wilbur A. Lam ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Cost ◽  
Oxygen Extraction ◽  
Signal Quality ◽  
Cell Disease ◽  
Non Invasive

Introduction: Cerebral infarcts and associated cognitive impairments are a devastating consequence of sickle cell disease (SCD). While the underlying mechanisms are poorly understood, infarctions are thought to arise from anemia-induced microvascular perfusion abnormalities and subsequent reduced cerebrovascular reserve that is insufficient to meet tissue metabolic demands. Thus, quantification of abnormalities in microvascular cerebral blood flow (CBF) and oxygen extraction (OEF) may be useful in identifying infarct risk and monitoring therapeutic efficacy. Unfortunately, current modalities that quantify microvascular hemodynamics (e.g., PET, MRI) are prohibitively expensive, have limited availability, and require anesthesia in children &lt;6y, making them inappropriate as routine monitoring tools. Transcranial Doppler ultrasound (TCD) is currently the standard screening tool for overt stroke risk in pediatric SCD, but it only measures blood flow velocity in the large arteries, which is a poor surrogate for microvascular perfusion in sickle cell disease. Diffuse optical spectroscopies (specifically near-infrared frequency-domain spectroscopy, FDNIRS, and diffuse correlation spectroscopy, DCS) offer a low-cost, non-invasive alternative for bedside monitoring of tissue-level OEF and CBF. We previously demonstrated that FDNIRS/DCS are sensitive to elevations in resting-state OEF and CBF in children with sickle cell disease compared to healthy controls (Lee, Neurophotonics 2019), consistent with previous studies using MRI and PET. In this feasibility study, we demonstrate these optical techniques are sensitive to altered cerebral hemodynamics in sickle patients who are 1) undergoing chronic transfusion, and 2) experiencing vaso-occlusive pain episodes (VOE). Methods: To date, we have recruited 6 pediatric patients with sickle cell disease undergoing chronic transfusion (5 females and 1 male, 6 - 14 y, mean ± std hemoglobin change pre- to post-transfusion = 1 ± 0.8 g/dL) and 4 patients admitted to the Emergency department for VOE (2 females and 2 males, 8 - 18 y, mean±std hemoglobin on admission = 8.9 ± 1.6 g/dL). For the transfusion cohort, FDNIRS/DCS measurements were made immediately prior to the start of transfusion and again immediately upon completion. For the VOE cohort, FDNIRS/DCS measurements were made upon hospital admission. For all FDNIRS/DCS assessments, a custom sensor was manually held over right and left forehead to assess oxygen extraction fraction (OEF, %) and an index of microvascular cerebral blood flow (CBFi, cm2/s) (Lee, Neurophotonics 2019). Hemispheric results were averaged to yield a mean of each measured parameter. Total measurement time was less than 15 minutes. Results: In the cohort undergoing chronic transfusion, one patient data was excluded due to poor DCS signal quality. Of the remaining 5 patients, OEF and CBFi decreased after transfusion by a median of -6.4% and -30.0%, respectively (Fig 1A, B). The FDNIRS-measured OEF decrease is comparable to previous results with MRI (Guilliams, Blood 2017) that quantified both cortical OEF and CBF response to transfusion in a similarly aged cohort. However, the DCS-measured CBFi decrease is more prominent than previously reported (30% vs. 9%). The enhanced sensitivity of DCS to CBF in sickle cell disease was reported in our recent study and is likely attributed to the confounding influences of hematocrit on the DCS-measured CBFi (Sathialingam, Biomed Opt Exp 2020). In the cohort measured during VOE, one patient data was excluded due to poor FDNIRS data quality. Of the remaining 3 subjects, OEF was elevated compared to healthy controls and was on the upper range of values measured in a cohort of otherwise subjects with sickle cell disease who were without clinical complications and were measured as part of a separate study (Fig. 1C). Conclusion: These data demonstrate how FDNIRS/DCS may be used as a simple, low-cost tool for bedside assessment of cerebral hemodynamics in non-sedated sickle children that could be used to track brain health over time, particularly during periods thought to be prone to hemodynamic instability like transfusion or VOEs. Although ~20% of data was discarded in this dataset due to improper sensor positioning leading to poor signal quality, we have recently implemented real-time quality control feedback to ensure our data passes quality criteria. Disclosures Lam: Sanguina, Inc: Current equity holder in private company.

scholarly journals Cerebral oxygen metabolism in adults with sickle cell disease

2020 ◽  
Author(s):  
Lena Václavů ◽  
Jan Petr ◽  
Esben Thade Petersen ◽  
Henri J.M.M. Mutsaerts ◽  
Charles B.L. Majoie ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Oxygen Metabolism ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
Cerebral Oxygen Metabolism

Resting metabolic rate in homozygous sickle cell disease

1993 ◽  
Vol 57 (1) ◽  
pp. 32-34 ◽  
Author(s):  
A Singhal ◽  
P Davies ◽  
A Sahota ◽  
P W Thomas ◽  
G R Serjeant
Keyword(s):  
Sickle Cell Disease ◽  
Metabolic Rate ◽  
Sickle Cell ◽  
Resting Metabolic Rate ◽  
Cell Disease ◽  
Homozygous Sickle Cell Disease
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