Brain tissue volumes were calculated in adults and children with sickle cell disease (SCD) across the lifespan for different segmentation algorithms and clinical indicators of disease. Tissue volume reductions in persons with SCD without prior stroke were detected when using FreeSurfer, but not other software, highlighting algorithm bias. Arterial oxygen content was directly related to tissue volumes when using FreeSurfer and SIENAX. Brain tissue volume was not associated with silent cerebral infarcts (SCIs). Findings highlight the subtlety of tissue volume changes in SCD, provide age-specific reference-standards, and motivate an integrated approach of anatomical and functional assessments for informing SCD care.
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