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

Abstract

Anemia is the most common blood disorder in the world. In patients with chronic anemia, such as sickle cell disease or major thalassemia, cerebral blood flow increases to compensate for decreased oxygen content. However, the effects of chronic anemia on oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) are less well understood. In this study, we examined 47 sickle-cell anemia subjects (age 21.7 ± 7.1, female 45%), 27 non-sickle anemic subjects (age 25.0 ± 10.4, female 52%) and 44 healthy controls (age 26.4 ± 10.6, female 71%) using MRI metrics of brain oxygenation and flow. Phase contrast MRI was used to measure resting cerebral blood flow, while T 2 -relaxation-under-spin-tagging (TRUST) MRI with disease appropriate calibrations were used to measure OEF and CMRO 2 . We observed that patients with sickle cell disease and other chronic anemias have decreased OEF and CMRO 2 (respectively 27.4 ± 4.1% and 3.39 ± 0.71 ml O 2 /100 g/ min in sickle cell disease, 30.8 ± 5.2% and 3.53 ± 0.64 ml O 2 /100 g/min in other anemias) compared to controls (36.7 ± 6.0% and 4.00 ± 0.65 ml O 2 /100 g/min). Impaired CMRO 2 was proportional to the degree of anemia severity. We further demonstrate striking concordance of the present work with pooled historical data from patients having broad etiologies for their anemia. The reduced cerebral oxygen extraction and metabolism are consistent with emerging data demonstrating increased non-nutritive flow, or physiological shunting, in sickle cell disease patients.Ms. Vu and Dr. Bush contributed equally and are designated as co-first authors.

Magnetic resonance imaging metrics of oxygen extraction fraction: Contradictions or insight into pathophysiological mechanisms?

“…The observations of increased OEF by Fields et 2 This study also found that OEF in anemic controls differed from healthy controls and SCA had even larger OEF differences, however, the differences were in the opposite direction with SCA having the lowest OEF. This discrepancy could lead readers to dismiss both methods, not knowing which is correct, but once the details of each measurement technique are considered a reconciliation between these opposite observations is possible.…”

Brain Oxygen Extraction and Metabolism in Pediatric Patients With Sickle Cell Disease: Comparison of Four Calibration Models

“…T 2 -based MR oximetry such as TRUST MRI has been exploited widely due to its non-invasive property, less model assumption, short scan time and high reproducibility (Lu and Ge, 2008;Lu et al, 2012;Xu et al, 2012;Jiang et al, 2018Jiang et al, , 2021. However, inconsistent results have been reported on whether OEF and CMRO 2 are increased, decreased or unaffected in sickle cell disease (Jordan et al, 2016;Bush et al, 2018bBush et al, , 2021Juttukonda et al, 2019Juttukonda et al, , 2020Li et al, 2020;Václavů et al, 2020;Prussien et al, 2021;Vu et al, 2021) The original bovine model was derived from bovine blood, which is thought to have similar magnetic properties as normal human blood (Lu et al, 2012). However, it was also speculated that the bovine model was calibrated in a relatively small hematocrit range (35-55%), which is much higher than the hematocrit level in SCD (Lu et al, 2012;Bush et al, 2018b).…”

“…One is T 2 -based oximetry, based on the principle that oxygen content in the blood can alter the blood T 2 due to its magnetic property (Wright et al, 1991;Silvennoinen et al, 2003;Zhao et al, 2007;Lu and Ge, 2008;Lu et al, 2012). Several studies have been conducted in SCD patients to investigate the role of OEF and CMRO 2 using the T 2 -based method (Jordan et al, 2016;Bush et al, 2018bBush et al, , 2021Morris et al, 2018;Vaclavu et al, 2018;Juttukonda et al, 2019Juttukonda et al, , 2020Li et al, 2020;Václavů et al, 2020;Prussien et al, 2021;Vu et al, 2021); however, the results of these studies are variable, largely due to the calibration models used to convert venous blood T 2 to venous oxygenation (Y v ). Using a bovine blood model, Jordan et al (2016) reported increased OEF and CMRO 2 in SCD; however, it has been speculated that the bovine model may not be suitable for sickled blood, due to a much lower hematocrit range and different size, shape, and permeability of the sickled blood cell (Clark and Rossi, 1990;Gibson and Ellory, 2002).…”

Cerebral oxygen extraction fractionMRI: Techniques and applications

“…A number of studies have investigated OEF changes in SCD but reported inconsistent results. Several groups have measured global OEF in SCD using T 2 -based techniques, 5,54,81,235,[252][253][254][255][256][257] but the OEF results varied when different calibration models were used to convert blood T 2 to Y v (see Section 3.1.2). 258 Studies using the bovine calibration model 43 showed that OEF was higher in SCD patients than controls, 235,252 and OEF was reduced after blood transfusion.…”