Current three-dimensional (3D) MR Spin TomogrAphy in Time-Domain (MR-STAT) protocols use transient-state, gradient-spoiled gradient-echo sequences that are prone to cerebrospinal fluid (CSF) pulsation artifacts when applied to the brain. This study aims to develop a 3D MR-STAT protocol for whole-brain relaxometry that overcomes the challenges posed by CSF-induced ghosting artifacts. We optimized the flip-angle train within the Cartesian 3D MR-STAT framework to achieve two objectives: (1) minimization of the noise level in the reconstructed quantitative maps, and (2) reduction of the CSF-to-white-matter signal ratio to suppress CSF-associated pulsation artifacts. The optimized new sequence was tested on a gel/water phantom for accuracy evaluation of the quantitative maps, and on healthy volunteers to explore the effectiveness of the CSF artifact suppression and robustness of the new protocol. An optimized sequence with high parameter-encoding capability and low CSF signal response was proposed and validated in the gel/water phantom experiment. From in vivo experiments with 5 volunteers, the proposed CSF-suppressed sequence produced quantitative maps with no CSF artifacts and showed overall greatly improved image quality compared with the baseline sequence. Statistical analysis indicated low intersubject and interscan variability for quantitative parameters in gray matter and white matter (1.6%-2.4% for T1 and 2.0%-4.6% for T2), demonstrating the robustness of the new sequence. We present a new 3D MR-STAT sequence with CSF suppression that effectively eliminates CSF pulsation artifacts. The new sequence ensures consistently high-quality, 1-mm3 whole-brain relaxometry within a rapid 5.5-min scan time.
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