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Introduction: There is recent evidence that diastolic flow reversal in the descending thoracic aorta (DAo) is prevalent in patients with atherosclerosis, enabling a mechanism for cerebral embolism. Specifically, aortic stiffness (assessed by pulse wave velocity, PWV) is a precursor of plaque formation and reverse aortic flow. The aim of this study was to 1) employ aortic 4D flow MRI for quantification of both PWV and regional flow reversal and 2) evaluate relationships between PWV, reverse flow and age in a cohort of cryptogenic stroke patients with plaques in the DAo and age-matched controls.Methods: Non-contrast free-breathing 4D flow MRI (spatial resolution = 3-3.5 x 2.2-2.6 x 2.6-3 mm3, temporal resolution=19.6 ms, venc = 150 cm/s, 1.5T Area, Siemens Germany) was performed in n=10 (age=66±7 [53-80]) patients with cryptogenic stroke and n=12 (age=68±7 [56-78]) controls. Methods were developed for the automatic quantification of global aortic PWV (by cross-correlation) and regional (voxel-wise) reverse flow based on a 3D centerline (Figure 1a-c). Reverse flow during one cardiac cycle was averaged among voxels in user-defined ROIs in the ascending aorta (AAo), aortic arch (AArch) and DAo.Results: Elevated PWV was associated with increased age in all subjects (patients: R2=0.52, p=0.02; controls: R2=0.58, p=0.004) and increased reverse flow in patients (AAo: R2=0.60, p=0.009; AArch: R2=0.73, p=0.002; DAo: R2=0.44, p=0.04) but not controls (AAo: R2=0.04, p=0.52; AArch: R2=0.25, p=0.10; DAo: R2=0.06, p=0.42) (Figure 1d).Conclusions: Evaluation by 4D flow MRI shows aortic stiffness, as measured by PWV, increases with age and is associated with pronounced reverse aortic flow in cryptogenic stroke patients with DAo plaque compared to controls, providing further evidence retrograde embolism may be a mechanism of stroke in otherwise cryptogenic stroke patients.