AbstractPurposeThis study aims to develop a high‐efficiency and high‐resolution 3D imaging approach for simultaneous mapping of multiple key tissue parameters for routine brain imaging, including T₁, T₂, proton density (PD), ADC, and fractional anisotropy (FA). The proposed method is intended for pushing routine clinical brain imaging from weighted imaging to quantitative imaging and can also be particularly useful for diffusion‐relaxometry studies, which typically suffer from lengthy acquisition time.MethodsTo address challenges associated with diffusion weighting, such as shot‐to‐shot phase variation and low SNR, we integrated several innovative data acquisition and reconstruction techniques. Specifically, we used M1‐compensated diffusion gradients, cardiac gating, and navigators to mitigate phase variations caused by cardiac motion. We also introduced a data‐driven pre‐pulse gradient to cancel out eddy currents induced by diffusion gradients. Additionally, to enhance image quality within a limited acquisition time, we proposed a data‐sharing joint reconstruction approach coupled with a corresponding sequence design.ResultsThe phantom and in vivo studies indicated that the T₁ and T₂ values measured by the proposed method are consistent with a conventional MR fingerprinting sequence and the diffusion results (including diffusivity, ADC, and FA) are consistent with the spin‐echo EPI DWI sequence.ConclusionThe proposed method can achieve whole‐brain T₁, T₂, diffusivity, ADC, and FA maps at 1‐mm isotropic resolution within 10 min, providing a powerful tool for investigating the microstructural properties of brain tissue, with potential applications in clinical and research settings.