Reducing gadolinium-based contrast agents to lower costs, the environmental impact of gadolinium-containing wastewater, and patient exposure is still an unresolved issue. Published methods have never been compared. The purpose of this study was to compare the performance of 2 reimplemented state-of-the-art deep learning methods (settings A and B) and a proposed method for contrast signal extraction (setting C) to synthesize artificial T1-weighted full-dose images from corresponding noncontrast and low-dose images. In this prospective study, 213 participants received magnetic resonance imaging of the brain between August and October 2021 including low-dose (0.02 mmol/kg) and full-dose images (0.1 mmol/kg). Fifty participants were randomly set aside as test set before training (mean age ± SD, 52.6 ± 15.3 years; 30 men). Artificial and true full-dose images were compared using a reader-based study. Two readers noted all false-positive lesions and scored the overall interchangeability in regard to the clinical conclusion. Using a 5-point Likert scale (0 being the worst), they scored the contrast enhancement of each lesion and its conformity to the respective reference in the true image. The average counts of false-positives per participant were 0.33 ± 0.93, 0.07 ± 0.33, and 0.05 ± 0.22 for settings A-C, respectively. Setting C showed a significantly higher proportion of scans scored as fully or mostly interchangeable (70/100) than settings A (40/100, P < 0.001) and B (57/100, P < 0.001), and generated the smallest mean enhancement reduction of scored lesions (-0.50 ± 0.55) compared with the true images (setting A: -1.10 ± 0.98; setting B: -0.91 ± 0.67, both P < 0.001). The average scores of conformity of the lesion were 1.75 ± 1.07, 2.19 ± 1.04, and 2.48 ± 0.91 for settings A-C, respectively, with significant differences among all settings (all P < 0.001). The proposed method for contrast signal extraction showed significant improvements in synthesizing postcontrast images. A relevant proportion of images showing inadequate interchangeability with the reference remains at this dosage.