RATIONALE AND OBJECTIVES The ability to perform cerebral perfusion imaging (CPI) in the angiography suite has provided a new tool for diagnosis and treatment of neurovascular patients but requires comparable contrast perfusion to each cerebral hemisphere. In the angiography suite, contrast injection may be performed via an intra-arterial or intravenous (IV) route. The purpose of this study was to investigate whether a difference exists between contrast injection in the aortic arch (AA) and a peripheral vein (IV), particularly in the setting of stroke. MATERIALS AND METHODS Using three canines, both AA and IV injection protocols compatible with CPI were performed prospectively at three time points after creation of a stroke. The common carotid arteries in the resulting image data sets were segmented and the means and distributions of corresponding pixel intensities analyzed with Student's t-test. Using similar techniques, the internal carotid arteries of three patients (one female, two males, ages 69, 29, and 20) undergoing AA contrast injection with cone beam computed tomography (CBCT) cerebral imaging were analyzed and compared retrospectively with those of three random patients (one female, two males, ages 19, 57, and 35) undergoing standard head CT scans using IV contrast administration. All acquisitions followed institutionally approved protocols and informed consent. RESULTS No statistical significance (P < .05) was found when mean values for the right and left carotid artery pixel intensities were compared in the canine model or the clinical studies in which patients underwent imaging after AA or IV contrast administration. CONCLUSIONS No statistically significant difference exists between right and left carotid artery filling density using either AA or IV contrast injection methods, making both suitable for CPI in the angiography suite.