The role of cerebral venous outflow in brain circulation has been largely underestimated, since abnormal venous outflow patterns may cause severe cerebrovascular disease, such as cerebral venous thrombosis, chronic cerebrospinal venous insufficiency. Very few studies have explored the relationship between cerebral venous outflow and cerebral arterial inflow.^1,2 Additionally, the relationship between cerebral arterial inflow and cardiac outflow has not been adequately examined. The purpose of this study was to characterize the discrepancy between cerebral arterial inflow and venous outflow as well as the relationship between cerebral arterial inflow and cardiac outflow in children and adult volunteers using 4D flow and 2D phase-contrast MRI (PC-MRI). Following IRB approval, written informed consent was obtained from 24 healthy adult and 7 children volunteers with no history of cardio- and/or cerebro-vascular disease (see Table 1 for subjects’ characteristics). All subjects were scanned on a clinical 3 Tesla MRI scanner (Siemens, Erlangen, Germany). First, ECG-gated 4D flow MRI with three-directional velocity encoding and volumetric coverage of the major cerebral arteries (Figure 1A) was performed to measure cerebral arterial inflow (Figure 1B). Two additional 2D PC-MRI scans with optimized through-plane velocity encoding were performed at the left and right transverse sinuses (Figure 1C). A third 2D PC-MRI scan was performed at the level of the proximal ascending (AAo) and descending (DAo) aorta to measure cardiac outflow (Figure 1D). A detailed description of the pulse sequence parameters is listed in Table 2. 4D flow MRI data were preprocessed using an in-house software in Matlab (The MathWorks, Natick, MA) as described by Bock et al.³ The preprocessed data were then further analyzed for flow quantification (Figure 1B right, EnSight, CEI, Apex, NC). 2D PC-MRI data were analyzed using a specialized flow analysis tool (Argus, Siemens, Germany). Cerebral arterial inflow was calculated as cumulative flow in both the bilateral internal carotid arteries (ICAs) and the basilar artery (BA) while cerebral venous outflow was computed by summing the flow in the bilateral transverse sinuses. Cerebral venous outflow, arterial inflow and their ratio as well as the ratio of cerebral arterial inflow to AAo flow were compared between adults and children using two-tailed t-tests where P < 0.05 was considered statistically significant. Relationships between flow parameters and age were assessed by Spearman’s rank correlation analysis.Comparisons of the flow parameters between children and adults as well as the relationships between flow parameters and age are summarized in Table 1. For the whole cohort, cerebral arterial inflow was linearly correlated with cerebral venous outflow (r = 0.81, P < 0.001). Cerebral arterial inflow (20.21±4.58 ml/s versus 11.78±2.03 ml/s, P < 0.001) and cerebral venous outflow (12.80±3.82 ml/s versus 9.03±2.31 ml/s, P = 0.003) were both significantly higher in children compared to adult volunteers. By comparison, the ratio of cerebral venous outflow to arterial inflow was significantly lower in children than in adults (0.63±0.11 versus 0.76±0.14, P = 0.025). Although cerebral arterial inflow (r = -0.71, P < 0.001) was negatively correlated with age in adults, cerebral venous outflow (r = -0.29, P = 0.171) as well as the outflow/inflow ratio (r = 0.16, P = 0.446) were not significantly associated with age during adulthood. The ratio of cerebral arterial inflow to AAo flow was significantly higher in children compared to adults (0.45±0.08 versus 0.15±0.02, P < 0.001), but this ratio was not significantly associated with age in children (r = -0.36, P = 0.432) and adults (r = -0.35, P = 0.095).Our findings demonstrate significant discrepancies between cerebral arterial inflow and venous outflow in children and adult volunteers, indicating that the transverse sinuses only account for a portion of cerebral venous outflow. Other venous pathways, such as the epidural, vertebral and deep cervical veins, may be responsible for draining the remaining venous outflow. Larger discrepancies of cerebral venous outflow and arterial inflow in children compared to adults suggest variable pathways of cerebral circulation. A relatively stable cerebral outflow-inflow ratio during adulthood may indicate a uniform venous draining pattern across age. The ratio of cerebral arterial inflow to AAo flow was consistent with previous reported values,⁴ and the ratio was significantly higher in children suggesting a higher proportion of blood supply to the brain and thus increased cerebral oxygen consumption in children compared to adults. The results presented here provide new insight into the understanding of normal discrepancies between cerebral outflow and inflow as well as the relationship between cerebral inflow and cardiac outflow, which may help elucidating the pathophysiology of certain cerebrovascular disorders involving abnormal cerebral hemodynamics.