Breath-hold Blood-Oxygen Level Dependent MRI: a tool for the assessment of cerebrovascular reserve in children with Moyamoya Cover Title: Breath-hold Cerebrovascular Reactivity in Moyamoya

Background and Purpose: There is a critical need for a reliable and clinically-feasible imaging technique that can enable prognostication and selection for revascularization surgery in children with Moyamoya. Blood-oxygen level dependent MRI assessments of cerebrovascular reactivity, using voluntary breath-hold hypercapnic challenge is one such simple technique. However, its repeatability and reliability in children with Moyamoya is unknown. The current study sought to address this limitation. Methods: Children with Moyamoya underwent dual breath-hold hypercapnic challenge bloodoxygen level dependent MRI cerebrovascular reactivity studies, in the same MRI session. Within-day, within-subject repeatability of cerebrovascular reactivity estimates, derived from blood-oxygen level dependent signal, was computed. Estimates were associated with demographics, and intellectual function. Inter-rater reliability of a qualitative and clinicallyapplicable scoring scheme was assessed. Results: Twenty children (11 males; 12.1±3.3 years) with 30 MRI sessions (60 MRI scans) were included. Repeatability was "good" based on intra-class correlation (0.70±0.19). Agreement of qualitative scores was “substantial” (K=0.711) and intra-rater reliability of scores was “almost perfect” (K=0.83 and 1). Younger participants exhibited lower repeatability (p=0.027). Repeatability was not associated with cognitive function (p>0.05). However, abnormal cerebrovascular reactivity was associated with slower processing speed (p=0.015). Conclusion: Breath-hold hypercapnic challenge blood-oxygen level dependent MRI is a repeatable technique for the assessment of cerebrovascular reactivity in children with Moyamoya and is reliably interpretable for use in clinical practice. Standardization of such protocols will