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Purpose  This study aims to develop a high‐resolution whole‐brain multi‐parametric quantitative MRI approach for simultaneous mapping of myelin‐water fraction (MWF), T 1 , T 2 , and proton‐density (PD), all within a clinically feasible scan time.    Methods  We developed 3D visualization of short transverse relaxation time component (ViSTa)‐MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high‐fidelity whole‐brain MWF and T 1 /T 2 /PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory‐efficient reconstruction, the ViSTa‐MRF sequence leverages an optimized 3D tiny‐golden‐angle‐shuffling spiral‐projection acquisition and joint spatial–temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa‐MRF approach, high‐fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors.    Results  The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi‐parametric mapping with high SNR and good quality. The in vivo results of 1 mm‐ and 0.66 mm‐isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5‐min whole‐brain 1 mm‐iso assessment of MWF and T 1 /T 2 /PD mappings for infant brain development and for post‐mortem brain samples.    Conclusions  In this work, we have developed a 3D ViSTa‐MRF technique that enables the acquisition of whole‐brain MWF, quantitative T 1 , T 2 , and PD maps at 1 and 0.66 mm isotropic resolution in 5 and 15 min, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

High‐resolution myelin‐water fraction and quantitative relaxation mapping using 3D ViSTa‐MR fingerprinting