Introduction: Silent cerebral infarction (SCI) is common in children with sickle cell disease and is linked to cognitive decline, poor academic performance, and overt stroke (DeBaun, 2014). Currently, the only clinical approach to identify patients at risk of SCI involves MRI screening for school-age children (DeBaun, 2020). However, this method is costly, not easily accessible, and often requires sedation, making implementation difficult. Moreover, prophylactic therapies, such as chronic blood transfusion, have shown minimal success in preventing SCI progression. Arterial stiffening is tightly linked with the development of stroke and SCIs in heart disease and elderly populations (Mattace-Raso, 2006). However, prior work in sickle cell disease on central arterial stiffening is inconclusive and arterial stiffness of the cerebrovascular is largely unknown, especially in children (Pikilidou, 2015). Therefore, the goal of this work was to determine the feasibility of compact, point of care ultrasound in the assessment of arterial stiffening of the carotid arteries and establish normative values in children with sickle cell disease. Methods: All studies were performed with IRB approval and with informed consent. The study population included 16 pediatric patients (14.75 ± 4.54 years, 11 Male, hemoglobin 9.72± 1.78 g/dL) recruited from the Blood and Cancer Center at Dell Children's Hospital in Austin, TX. All participants had their vitals taken and their right common carotid artery imaged in supine position following at least 10 minutes rest. Imaging was performed by an experienced imaging professional (AB, 10 years experience) using a Butterfly IQ + ultrasound probe (Burlington, MA) and an Apple smartphone (Cupertino, CA) in the B-mode vascular setting. Three to ten second recordings of the carotid artery were recorded at a rate of approximately 20 frames per second. In house MATLAB scripts were developed for semiautomated cross sectional area segmentation across the cardiac cycle to calculate vessel lumen area (Figure 1). Strain was calculated using the ratio of change in systolic and diastolic area over diastolic area, and distensibility (1/stiffness) was calculated as strain/ln[SBP/DBP] (Godia, 2007). Univariate and stepwise multiple analysis was performed to determine the correlates of arterial distensibility. Results: We measured an average distensibility of 0.23 ± 0.10 (a.u) across patients. A statistically significant inverse relationship between systolic pressure and distensibility (p=0.039, R 2=0.53) was measured. Upon multivariate analysis, systolic blood pressure was the only predictor of carotid distensibility. All other factors (sex, age, height, weight, hemoglobin concentration, and diastolic blood pressure) showed a statistically insignificant relationship (p>0.05). Further Applications: Our study shows it is possible to rapidly and inexpensively measure a metric of cerebral arterial stiffness in children with sickle cell disease and that arterial stiffness is linked with systolic blood pressure. Silent cerebral infarcts in children are known to be linked with systolic blood pressure, male gender and increase with age during adolescence (DeBaun, 2012). Whether arterial stiffening predicts the prevalence and progression of SCI and the role of point of care ultrasound is an ongoing area of research.