Background

Blood-brain barrier (BBB) disruption may lead to endothelium dysfunction and inflammation in sickle cell disease (SCD). However, abnormalities of BBB in SCD, especially in pediatric patients for whom contrast agent administration less than optimal, have not been fully characterized.

Purpose

To examine BBB permeability to water in a group of pediatric SCD participants using a non-invasive MRI technique. We hypothesized that SCD participants will have increased BBB permeability.

Study Type

Prospective cross-sectional.

Population

26 pediatric participants (10±1 years, 15F/11M) were enrolled, including 21 SCD participants and 5 sickle cell trait (SCT) participants, who were siblings of SCD patients.

Field Strength/Sequence

3T. Water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) with echo-planer imaging, phase-contrast and T1-weighted magnetization-prepared-rapid-acquisition-of-gradient-echo (MPRAGE).

Assessment

Water extraction fraction (E), BBB permeability-surface area product (PS), cerebral blood flow (CBF), hematological measures (hemoglobin, hematocrit, hemoglobin S), neuropsychological scores (including domains of intellectual ability, attention and executive function, academic achievement and adaptive function, and a composite score). ROIs were drawn by Z.L. (6 years of experience).

Statistical Tests

Wilcoxon rank sum test and chi-square test for group comparison of demographics. Multiple linear regression analysis of PS with diagnostic category (SCD or SCT), hematological measures and neuropsychological scores. A two-tailed p value of 0.05 or less was considered statistically significant.

Results

Compared with SCT participants, SCD participants had a significantly higher BBB permeability to water (SCD: 207.0±33.3mL/100g/min, SCT: 171.2±27.2mL/100g/min,). SCD participants with typically more severe phenotypes also had a significantly leakier BBB than those with typically milder phenotypes (severe: 217.3±31.7mL/100g/min, mild: 193.3±31.8mL/100g/min,). Furthermore, more severe BBB disruption was associated with worse hematological symptoms, including lower hemoglobin concentrations (β=−8.84, 95% CI [−14.69, −3.00]), lower hematocrits (β=−2.96, 95% CI [−4.84, −1.08]), and higher hemoglobin S fraction (β=0.77, 95% CI [0.014, 1.53]).

Data Conclusion

These findings support a potential role for BBB dysfunction in SCD pathogenesis of ischemic injury.