Abstract A062: Assessment of predictive factors for infarct development in sickle cell disease

Introduction: Sickle cell disease (SCD) carries a high risk of cerebrovascular disease with an incidence of overt stroke or silent cerebral infarct (SCI) of 50% by age 30. Other than elevated transcranial doppler ultrasound in children, no standard exists for triaging patients for more aggressive therapeutic options for stroke prevention. We utilized noninvasive neuroimaging approaches to understand the mechanisms of cerebral oxygen metabolism and neurovascular dysfunction in SCD and to determine if imaging biomarkers predict future infarct development. Methods: Patients with SCD, ages 6-45 years, underwent two 3T magnetic resonance imaging (MRI) protocols approximately one year apart to assess for infarct development (defined as ≥3mm on FLAIR MRI). Cerebral blood flow (CBF) and quantitative dural venous shunting (SSS) were assessed with arterial spin labeling MRI, and oxygen extraction fraction (OEF) was assessed using T2-relaxation-under-spin-tagging MRI. Baseline measures were compared between participants who developed new or worsening infarcts (SCD+) and those who did not (SCD-) using a non-parametric Mann-Whitney test. Results: Individuals with SCD without new or worsening infarct (SCD-, n=50, 45% male, Table 1) and those who developed new or worsening infarct (SCD+, n=15, 53% male, Table 1) were evaluated twice over a follow-up time frame of approximately one year (391±173 days). OEF and CBF at baseline in the SCD- group were 41.2%±7.8% and 75.8±18.9 ml/100g/min, respectively. Values were not significantly different than those in the SCD+ group (OEF = 42.4%±6.1, p-value = 0.45, Fig. 1A; CBF = 84.8±18.5 ml/100g/min, p-value=0.11, Fig. 1B). Shunting effects, evaluated as apparent CBF at the level of the superior sagittal sinus (SSS) were significantly higher in the SCD+ group (100.0±29.4 ml/100g/min) than the SCD- group (64.3±32.3 ml/100g/min, p-value<0.001, Fig. 1C, 1D). Conclusions: Measures of the dural venous shunting effect through the SSS indicate increased risk for new or progressive infarcts, possibly related to poor offloading of oxygen in the brain parenchyma. Evaluation for other stroke risk factors and consideration for more aggressive disease-modifying therapies is recommended. Further work is needed to elucidate the role of these shunting effects and the relationship to infarct development in SCD.