  Purpose: Current 3D Magnetic Resonance 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 at developing a 3D MR-STAT protocol for
whole-brain relaxometry that overcomes the challenges posed by CSF-induced
ghosting artifacts. Method: 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 signal and the associated
pulsation artifacts. The optimized new sequence was tested on a
gel/water-phantom to evaluate the accuracy of the quantitative maps, and on
healthy volunteers to explore the effectiveness of the CSF artifact suppression
and robustness of the new protocol. Results: A new optimized sequence with both
high parameter encoding capability and low CSF intensity was proposed and
initially validated in the gel/water-phantom experiment. From in-vivo
experiments with five volunteers, the proposed CSF-suppressed sequence shows no
CSF ghosting artifacts and overall greatly improved image quality for all
quantitative maps compared to the baseline sequence. Statistical analysis
indicated low inter-subject and inter-scan 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. Conclusion: We presented
a new 3D MR-STAT sequence with CSF suppression that effectively eliminates CSF
pulsation artifacts. The new sequence ensures consistently high-quality, 1mm^3
whole-brain relaxometry within a rapid 5.5-minute scan time.
