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

Abstract

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.

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 possibility of the reduced OEF and CMRO 2 is that the high flow velocity drives down the oxygen extraction ability, which leads to the diminished oxygen metabolism. The mismatch between increased CBF and decreased OEF could be due to decreased capillary transit time (Juttukonda et al, 2020) or excessive CBF (Bush et al, 2018b) in arteriovenous shunting. On the other hand, overt stroke and SCI are often reported in SCD patients (Miller et al, 2001;Prengler et al, 2002).…”

“…One potential physiological biomarker in SCD is the oxygen extraction fraction (OEF). Due to the lack of oxygen carrying capacity of the sickled blood cell, the OEF may increase as a compensation; however, when the CBF and flow velocity increase, the OEF may also decrease due to insufficient diffusion time (Juttukonda et al, 2020) or excessive blood flow (Bush et al, 2018b) in arteriovenous shunting. Meanwhile, cerebral metabolic rate of oxygen (CMRO 2 ), which represents the oxidative metabolism of the brain, may also be altered.…”

“…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).…”

Evidence of transfusion‐induced reductions in cerebral capillary shunting in sickle cell disease

“…However, this cut-off has been arbitrarily defined. Renal and hepatic adverse events (AEs) and increases in serum creatinine (SCr) and alanine aminotransferase (ALT) have been reported in patients with transfusion hemosiderosis treated with DFX, 4,5 with most of the AEs occurring with high doses of the drug, independently of SF levels. 6,7 In our center, we tailor ICT according to transfusion iron intake, SF, and T2* magnetic resonance imaging (MRI).…”