Cerebral perfusion characteristics show differences in younger versus older children with sickle cell anaemia: Results from a multiple‐inflow‐time arterial spin labelling study

Abstract

Sickle cell anaemia (SCA) is associated with chronic anaemia and oxygen desaturation, which elevate cerebral blood flow (CBF) and increase the risk of neurocognitive complications. Arterial spin labelling (ASL) provides a methodology for measuring CBF non-invasively; however, ASL techniques using only a single inflow time are not sufficient to fully characterize abnormal haemodynamic behaviour in SCA. This study investigated haemodynamic parameters from a multi-inflow-time ASL acquisition in younger (8-12 years) and older (13-18 years) children with SCA with and without silent cerebral infarction (SCI+/-) (n = 20 and 19 respectively, 6 and 4 SCI+ respectively) and healthy controls (n = 9 and 7 respectively). Compared with controls, CBF was elevated globally in both groups of patients. In the younger SCA patients, blood oxygen content was negatively correlated with CBF in the middle and posterior cerebral artery territories and significantly positively correlated with bolus arrival time (BAT) in the anterior and middle cerebral artery territories. In older children, SCA patients had significantly shorter BAT than healthy controls and there was a significant negative correlation between CBF and oxygen content only in the territory of the posterior cerebral artery, with a trend for a correlation in the anterior cerebral artery but no relationship for the middle cerebral artery territory. In the younger group, SCI+ patients had significantly higher CBF in the posterior cerebral artery territory (SCI+ mean = 92.78 ml/100 g/min; SCI- mean = 72.71 ml/100 g/min; F = 4.28, p = 0.04), but this no longer reached significance when two children with abnormal transcranial Doppler and one with haemoglobin SC disease were excluded, and there were no significant differences between patients with and without SCI in the older children. With age, there appears to be increasing disparity between patients and controls in terms of the relationship between CBF and oxygen content in the anterior circulation, potentially predicting the risk of acute and chronic compromise of brain tissue.

Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia

“…23,24,45 Although the T1 tissue value used is likely too high for the gray and white matter ROIs, this will not have affected the fitted BAT values, and would only have had a small effect on the fitted CBF values. Whilst the absolute fitted values in these regions should therefore be interpreted with caution, and were higher than those based on the singleTI sequence and prior multiTI ASL work in gray matter, 31,32 the key comparisons were in the same direction and overall agreement. Importantly, the strength of correlations between CBF values and other parameters will not have been impacted.…”

“…blood) arrival times (BAT) across the whole brain 31 and in anterior, middle, and posterior cerebral artery territories, consistent with macrocirculatory hyperperfusion leading to faster transit times. 32 However, these studies only examined hemodynamic parameters in gray matter. Further, no ASL study (cross-sectional or longitudinal) has attempted to quantify CBF or BAT from venous signal, or assess associations with cognition in an SCA population.…”

“…Therefore, this study used singleTI and multiTI ASL to estimate CBF and BAT in gray matter, white matter, and high-signal sagittal sinus regions in patients with SCA and controls. Based on the prior singleTI 6,7,25,26 and multiTI ASL 32 studies discussed above, it was hypothesised that across all regions, CBF would be increased irrespective of sequence, and BAT reduced in patients with SCA. Associations with arterial oxygen content (CaO 2 ), disease-modifying treatments, SCI, and cognitive performance were also explored.…”

Impairment of Cerebrovascular Hemodynamics in Patients With Severe and Milder Forms of Sickle Cell Disease

“…This could be especially valuable in patients with SCD, as SCD is known to affect both large and small blood vessels. In SCD, ATT was found to be reduced compared to healthy controls (Juttukonda et al, 2017;Kawadler et al, 2018) under resting conditions. However, no studies to date have reported ATT changes in response to a cerebral vasodilatory challenge.…”

MRI detection of brain abnormality in sickle cell disease

“…To combat these challenges, some authors have advocated for correction for labeling efficiency, along with the employment of two-compartment models, but further work on the validity of ASL kinetic models in SCD patients is required. Acquisitions with multiple inflow times [ 137 , 138 ] do not require prior assumptions about the necessary delay for the fully labeled bolus of blood to arrive and allow for further characterization of hemodynamic behavior within a voxel, though there have been relatively few studies in this population [ 137 ]. Overall, whilst further validation and optimization work would be beneficial, ASL-based estimation of CBF is widely used as a biomarker of hemodynamic stress in both observational studies and treatment trials in SCD patients, with several studies demonstrating sensitivity to change.…”