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Background and Purpose: Quantitative arterial tortuosity (QAT) has been reported as an imaging biomarker of arteriopathy in pediatric arterial ischemic stroke (AIS) due to dissection and transient cerebral arteriopathy. We sought to determine if QAT abnormalities are present in cryptogenic pediatric AIS patients.Methods: Children with non-cardiogenic non-traumatic AIS and normal case controls who underwent MRA of the head and/or neck were identified by retrospective electronic medical record review. Patients with pre-existing clinical risk factors for AIS were excluded. The remaining cases were classified according to stroke subtype. The study population consisted of cryptogenic stroke cases. Patients with AIS due to spontaneous dissection were compared as positive case controls. Patients considered to have Bow Hunter’s Physiology (BHP), and normal case controls were also compared. QAT indices of 5 cervicocerebral arterial segments were measured in all patients using automated image processing software, and differences between groups were analyzed.Results: In normal children, QAT of the cervicocerebral arteries showed significant age-related variability, but no sex-related differences. In pediatric patients with cryptogenic stroke, QAT indices of the cervicocerebral arteries were significantly different relative to normal case controls (p<0.05), and similar to those measured in positive case controls with spontaneous dissection. The cervicocerebral QAT indices of pediatric AIS patients with BHP were not significantly different than those measured in normal controls.Conclusions: QAT is a specific and independent biomarker of arteriopathy in otherwise cryptogenic pediatric AIS, even when conventional clinical or imaging biomarkers of arteriopathy are absent. QAT shows promise as an independent diagnostic criterion for arteriopathy in children with AIS.