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

Abstract

Sickle cell disease (SCD) is an inherited hemoglobinopathy with an increased risk of neurological complications. Due to anemia and other factors related to the underlying hemoglobinopathy, cerebral blood flow (CBF) increases as compensation; however, the nature of alterations in oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in SCD remains controversial, largely attributed to the different calibration models. In addition, limited studies have been done to investigate oxygen metabolism in pediatric patients. Thus, this study used a non-invasive T2-based MR oximetry, T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, to measure oxygen homeostasis in pediatric patients with SCD using four different calibration models and examined its relationship to hematological measures. It was found that, compared with controls, SCD patients showed an increased CBF, unchanged total oxygen delivery and increased venous blood T2. The results of OEF and CMRO2 were dependent on the calibration models used. When using sickle-specific, hemoglobin S (HbS) level-dependent calibration, there was a decreased OEF and CMRO2, while the bovine model showed an opposite result. OEF and CMRO2 were also associated with hemoglobin and HbS level; the direction of the relationship was again dependent on the model. Future studies with in vivo calibration are needed to provide more accurate information on the T2-Yv relationship.

A Comparison of MRI Quantitative Susceptibility Mapping and TRUST-Based Measures of Brain Venous Oxygen Saturation in Sickle Cell Anaemia

“…The results of the group-wise comparisons of Y v in patients with SCA versus healthy controls largely agree with the results of previous studies investigating the effect of SCA on Y v, and a recent comparison of the models in a pediatric population ( Lin et al, 2022 ) . An overview of these previous studies investigating Y v in SCA is shown in Table 1 , with results visualized in Figure 6 .…”

“…These models are described in detail in the Supplementary materials . Using TRUST, Y v can appear either increased or decreased in SCA relative to healthy controls depending on the calibration model used ( Lin et al, 2022 ). An overview of published studies applying TRUST in SCA subjects is shown in Table 1 .…”

Vessel‐specific quantification of cerebral venous oxygenation with velocity‐encoding preparation and rapid acquisition

“…First, six Venc values were tested (3,5,8,10,15, and 20 cm/s) with a fixed RT = 1000 ms and FA = 60 • . Similarly, three RTs (1000, 1200, and 1500 ms) were examined with a fixed Venc = 3 cm/s and FA = 60 • .…”

“…Extensive literature demonstrated the importance of cerebral oxygen extraction and metabolism in different physiological and pathological conditions, such as neural development, 1,2 normal aging, 3,4 cognitive impairment, [5][6][7][8] small vessel disease, 9 and sickle cell disease. [10][11][12][13][14] Over the last decade, an active research topic in the MRI field is to develop new techniques for noninvasive Y v measurement. [15][16][17][18][19][20][21][22][23][24][25] One important line is based on the strong dependence of blood T 2 on oxygenation.…”

Cerebral oxygen extraction fractionMRI: Techniques and applications

“…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. 253 In contrast, studies using the SCD-specific models 5,81 have reported either a reduced OEF in SCD patients, 5,[254][255][256] or no significant difference in OEF between SCD patients and controls.…”