AbstractPurposeTo develop a method for rapid sub‐millimeter T₁, T₂, , and QSM mapping in a single scan using multi‐contrast learned acquisition and reconstruction optimization (mcLARO).MethodsA pulse sequence was developed by interleaving inversion recovery and T₂ magnetization preparations and single‐echo and multi‐echo gradient echo acquisitions, which sensitized k‐space data to T₁, T₂, , and magnetic susceptibility. The proposed mcLARO optimized both the multi‐contrast k‐space under‐sampling pattern and image reconstruction based on image feature fusion using a deep learning framework. The proposed mcLARO method with under‐sampling was validated in a retrospective ablation study and compared with other deep learning reconstruction methods, including MoDL and Wave‐MoDL, using fully sampled data as reference. Various under‐sampling ratios in mcLARO were investigated. mcLARO was also evaluated in a prospective study using separately acquired conventionally sampled quantitative maps as reference standard.ResultsThe retrospective ablation study showed improved image sharpness of mcLARO compared to the baseline network without the multi‐contrast sampling pattern optimization or image feature fusion module. The under‐sampling ratio experiment showed that higher under‐sampling ratios resulted in blurrier images and lower precision of quantitative values. The prospective study showed that small or negligible bias and narrow 95% limits of agreement on regional T₁, T₂, , and QSM values by mcLARO (5:39 mins) compared to reference scans (40:03 mins in total). mcLARO outperformed MoDL and Wave‐MoDL in terms of image sharpness, noise suppression, and artifact removal.ConclusionmcLARO enabled fast sub‐millimeter T₁, T₂, , and QSM mapping in a single scan.