Silent infarcts in sickle cell anemia occur in the borderzone region and are associated with low cerebral blood flow

Andria L. Ford, Dustin K. Ragan, Slim Fellah, Michael M. Binkley, Melanie E. Fields, Kristin P. Guilliams, Hongyu An, Lori C. Jordan, Robert C. McKinstry, Jin-Moo Lee and Michael R. DeBaun

Key points

  • The SCI density map revealed key SCI locations in the deep white matter of the frontal and parietal lobes.

  • Peak SCI density occurs in the region of nadir cerebral blood flow.


Silent cerebral infarcts (SCI) are associated with cognitive impairment in sickle cell anemia (SCA). SCI risk factors include low hemoglobin and elevated systolic blood pressure; however, mechanisms underlying their development are unclear. Using the largest, prospective study evaluating SCIs in pediatric SCA, we identified brain regions with increased SCI density. We tested the hypothesis that infarct density is greatest within regions where cerebral blood flow is lowest, further restricting cerebral oxygen delivery in the setting of chronic anemia. Neuroradiology and neurology committees reached a consensus of SCIs in 286 children in the Silent Infarct Transfusion (SIT) Trial. Each infarct was outlined and co-registered to a brain atlas to create an infarct density map. To evaluate cerebral blood flow as a function of infarct density, pseudocontinuous arterial spin labeling was performed in an independent pediatric SCA cohort. Blood flow maps were aligned to the SIT Trial infarct density map. Mean blood flow within low, moderate, and high infarct density regions from SIT Trial were compared. Logistic regression evaluated clinical and imaging predictors of overt stroke at three-year follow-up. The SIT Trial infarct density map revealed increased SCI density in the deep white matter of the frontal and parietal lobes. A relatively small region, measuring 5.6% of brain volume, encompassed SCIs from 90% of children. Cerebral blood flow was lowest in the region of highest infarct density (P<0.001). Baseline infarct volume and reticulocyte count predicted overt stroke. In pediatric SCA, SCIs are symmetrically located in the deep white matter where minimum cerebral blood flow occurs.

  • Submitted April 9, 2018.
  • Accepted July 17, 2018.