In this study we assessed blood-oxygen level-dependent (BOLD)-MRI derived hemodynamic lag in pediatric patients with Sickle Cell Disease (SCD), and explored how this relates to measures of cerebrovascular reactivity (CVR) and cerebral blood flow (CBF).  

Pediatric patients with SCD face increased risk of ischaemic injury, often accompanied by increased compensatory CBF and reduced CVR. BOLD MRI-derived hemodynamic responses can be altered in conditions such as stroke, translating to temporal delays, but this has not yet been investigated in SCD. Further, the precise source of this temporal lag has not been elucidated. 

MRI brain data obtained on a 3T-Siemens MRI system from 72 SCD patients (age range 6-18;M:F=1:1.2) and 36 healthy controls (age range 7-17;M:F=1:0.7) were used for analysis. T1-weighted structural images and functional images in response to hypercapnic challenge were derived. Lag maps were calculated from BOLD data by voxel-wise cross-correlation with a reference signal averaged across grey matter. CBF and BOLD-derived CVR maps were correlated with lag using voxel-wise Pearson’s correlation. Voxel-wise between-group lag differences were assessed using a mixed-effect ANOVA. Regional lag was correlated to haematological parameters (hematocrit, absolute reticulocyte count) using Pearson’s correlation. 

Similar lag spatial distribution was observed between groups. Patients however, presented clusters of significantly increased lag within the lateral occipital cortex, frontal pole, cingulate gyrus and precuneous. Compared to controls, patients showed significant BOLD signal lead within the pre and postcentral gyri.  

Voxel-wise cross-correlation of lag with CVR and CBF was negligible (mean abs. r<0.1), with no variation across groups (one-way ANOVA P>0.8) suggesting independence of the measures. There was no significant association of hemodynamic lag with haematological parameters previously shown to correlate with CVR, reinforcing their independence. 

Hemodynamic impairment is present in SCD patients, with regional differences in lag compared to controls. Lag is poorly explained by variations in CVR or CBF alone.