Toward Automated Detection of Silent Cerebral Infarcts in Children and Young Adults With Sickle Cell Anemia.

Background: Silent cerebral infarcts (SCI) in sickle cell anemia (SCA) are associated with future strokes and cognitive impairment, warranting early diagnosis and treatment. Detection of SCI, however, is limited by their small size, especially when neuroradiologists are unavailable. We hypothesized that deep learning may permit automated SCI detection in children and young adults with SCA as a tool to identify the presence and extent of SCI in clinical and research settings.
Methods: We utilized UNet-a deep learning model-for fully automated SCI segmentation. We trained and optimized UNet using brain magnetic resonance imaging from the SIT trial (Silent Infarct Transfusion). Neuroradiologists provided the ground truth for SCI diagnosis, while a vascular neurologist manually delineated SCI on fluid-attenuated inversion recovery and provided the ground truth for SCI segmentation. UNet was optimized for the highest spatial overlap between automatic and manual delineation (dice similarity coefficient). The optimized UNet was externally validated using an independent single-center prospective cohort of SCA participants. Model performance was evaluated through sensitivity and accuracy (%correct cases) for SCI diagnosis, dice similarity coefficient, intraclass correlation coefficient (metric of volumetric agreement), and Spearman correlation.
Results: The SIT trial (n=926; 31% with SCI; median age, 8.9 years) and external validation (n=80; 50% with SCI; age, 11.5 years) cohorts had small median lesion volumes of 0.40 and 0.25 mL, respectively. Compared with the neuroradiology diagnosis, UNet predicted SCI presence with 100% sensitivity and 74% accuracy. In magnetic resonance imaging with SCI, UNet reached a moderate spatial agreement (dice similarity coefficient, 0.48) and high volumetric agreement (intraclass correlation coefficient, 0.76; ρ=0.72; P <0.001) between automatic and manual segmentations.
Conclusions: UNet, trained using a large pediatric SCA magnetic resonance imaging data set, sensitively detected small SCI in children and young adults with SCA. While additional training is needed, UNet may be integrated into the clinical workflow as a screening tool, aiding in SCI diagnosis.
Competing Interests: Disclosures Dr Fields reports salary support in Global Blood Therapeutics, Inc, Monteore Medical Center, and Proclara Biosciences and from Washington University in St. Louis. H. An reports compensation from Pfizer, Inc, for consultant services and grants from the National Institutes of Health. Dr Binkley reports consultant services from CNS Consultants LLC and OpenCell Technologies. Dr Lee reports consultant services from Biogen. Dr McKinstry reports consultant services from NOUS Imaging, Inc, Philips, and Siemens. Dr Jordan reports compensation for expert witness and salary support from the National Institutes of Health and Vanderbilt University. Dr DeBaun reports consultant services from Forma Therapeutics, Global Blood Therapeutics, Graphite Bio, Novartis, and salary support Vanderbilt University. The other authors report no conflicts.