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Background During diagnostic cerebral angiography, catheter navigation requires manual contrast ‘puff’ injections delivered via tableside hand syringes, while subsequent 2D and 3D diagnostic runs use automated power injectors. This manual step introduces contrast waste from syringe dead space, air embolism risk during syringe handling, and prevents fully hands-free procedural workflows. Using power injectors to deliver navigation puffs has not been previously described. We present the first clinical experience with a closed-system approach using foot pedal-controlled puff injections via the Nemoto Press Duo Elite, a dual-port system enabling real-time digital contrast dilution, with implications for single-operator ergonomics and future remote robotic angiography.Methods This retrospective comparative cohort study compared 19 consecutive patients undergoing diagnostic cerebral angiography with foot pedal-controlled puff injections (June to July 2023) to 19 demographically matched historical controls using traditional manual hand injections (May 2021). All procedures were performed by a single operator. Both groups used 90% contrast concentration. The foot pedal delivered pre-programmed puff injections (2 mL at 1 mL/sec) for vessel navigation, while vessel-specific parameters were pre-programmed for diagnostic runs. Fluoroscopy time, radiation dose, contrast utilization, procedure time per vessel, and safety outcomes were compared.Results Groups were demographically matched (mean age 52.1±14.2 vs 50.2±12.9 years; 73.7% female in both groups). Transradial access was used in 89.5% and 94.7% of cases, respectively. Clinical indications differed between groups, with pulsatile tinnitus more common in the foot pedal group (36.8% vs 5.3%) and SAH workup more common in controls (47.4% vs 5.3%, p=0.035). All 38 procedures achieved diagnostic adequacy with no procedural complications, device malfunctions, or air bubble introductions in either group. Operator adaptation to the foot pedal technique occurred rapidly, within one to two cases.The foot pedal group demonstrated significantly shorter procedure time per vessel (11.5±4.4 vs 18.9±10.5 min/vessel, p=0.010), a 39% improvement in procedural efficiency. No significant differences were observed in fluoroscopy time (10.8±4.5 vs 13.7±7.6 min, p=0.171), radiation dose (1071.7±403.5 vs 1157.6±839.1 mGy·cm, p=0.690), or actual contrast delivered (88.7±30.9 vs 88.2±42.5 mL, p=0.966). A trend toward improved contrast efficiency per vessel was observed (23.4±9.4 vs 27.4±10.4 mL/vessel, p=0.226). Notably, the foot pedal group underwent significantly more 3D rotational runs per case (1.3±1.0 vs 0.6±0.7, p=0.030) yet maintained comparable safety and contrast metrics, strengthening the non-inferiority findings.The closed-system protocol achieved 100% adherence to the intended 90% contrast dilution ratio. The mean of 8.3±2.8 puff injections per case correlated directly with the 4.2±1.4 vessels selected. The only manual injection required was a single 5 mL access site injection at procedure initiation; all subsequent contrast delivery was exclusively through the foot pedal-controlled injector.Conclusion Foot pedal-controlled closed-system contrast delivery demonstrates non-inferiority to manual injection for diagnostic cerebral angiography, with a significant 39% reduction in procedure time per vessel (p=0.010). By extending power injector technology to navigation puffs, this approach eliminates all manual tableside contrast injection, enables precise digital contrast accounting with real-time concentration adjustment, and reduces air embolism risk. This technique establishes proof-of-concept for remote injection control as a foundational component of future robotic endovascular applications.Disclosures M. Rashad: None. O. Gandhi: None. S. Almasri: None. S. Dumasia: None. N. Yu: None. W. Ahmed: None. J. Kim: None. G. Lanzino: None. L. Bagley: None. O. Choudhri: 2; C; Nemoto Kyorindo Co., Ltd.