A comprehensive protocol for quantitative magnetic resonance imaging of the brain at 3 Tesla

Abstract

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous applications in the brain and body. The development of rapid, accurate, and reproducible qMRI techniques offers access to new multiparametric data, which can provide a comprehensive view of tissue pathology. This work introduces a multiparametric qMRI protocol along with full postprocessing pipelines, optimized for brain imaging at 3 Tesla and using state-of-the-art qMRI tools. The total scan time is under 50 minutes and includes eight pulse-sequences, which produce range of quantitative maps including T1, T2, and T2* relaxation times, magnetic susceptibility, water and macromolecular tissue fractions, mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR), and inhomogeneous MTR. Practical tips and limitations of using the protocol are also provided and discussed. Application of the protocol is presented on a cohort of 28 healthy volunteers and 12 brain regions-of-interest (ROIs). Quantitative values agreed with previously reported values. Statistical analysis revealed low variability of qMRI parameters across subjects, which, compared to intra-ROI variability, was x4.1 ± 0.9 times higher on average. Significant and positive linear relationship was found between right and left hemispheres' values for all parameters and ROIs with Pearson correlation coefficients of r>0.89 (P<0.001), and mean slope of 0.95 ± 0.04. Finally, scan-rescan stability demonstrated high reproducibility of the measured parameters across ROIs and volunteers, with close-to-zero mean difference and without correlation between the mean and difference values (across map types, mean P value was 0.48 ± 0.27). The entire quantitative data and postprocessing scripts described in the manuscript are publicly available under dedicated GitHub and Figshare repositories. The quantitative maps produced by the presented protocol can promote longitudinal and multi-center studies, and improve the biological interpretability of qMRI by integrating multiple metrics that can reveal information, which is not apparent when examined using only a single contrast mechanism.

Fig 1

FreeSurfer segmented ROIs, overlaid on axial (left) and coronal (right) T₁-weighted MP2RAGE images.

Fig 2. Sample contrast-weighted images for a single volunteer (F, 31 y/o).

(a, b) Anatomical scans using FLAIR and MP2RAGE scans. Relaxation weighted images include (c) T₂-weighted multi-echo SE (MESE); (d, e) T₂* weighted multi-echo Spoiled-GRE (TE = 14.2 ms) magnitude and phase images; (f) T₁-weighted inversion recovery SE-EPI; and (g) T₁-weighted single-echo spoiled-GRE (flip angle = 12°). (h, i) Diffusion-weighted images acquired using two phase-encoding directions: anterior-to-posterior and posterior-to-anterior. Inhomogeneous MT (ihMT) images: (j) Unsaturated M₀, (k) single positive saturation S⁺, (l) Dual saturation S^+-, (m) single negative saturation S^-, and (n) Dual saturation S^-+.

Fig 3. Example of quantitative maps from a single volunteer (F, 31 y/o).

Data were reformatted to show a 2D axial slice at the level of the lateral ventricles (i.e., similar slice across maps). Relaxation maps include (a) T₁, (b) T₂ and (c) T₂*. Fractional tissue volumes: (d) water (WF) and (e) macromolecules (MTVF). (f) Quantitative susceptibility map (QSM). Diffusion tensor images: (g) Mean diffusivity (MD) and (h) Fractional anisotropy (FA). Magnetization transfer (MT) related maps: (i) MT ratio (MTR) and (j) inhomogeneous MT ratio (ihMTR). Brain masks are based on FreeSurfer segmentations.

Fig 4

Correlation between quantitative values from the left vs. right hemispheres: (a) T₁, (b) T₂, (c) T₂*, (d) WF, (e) MTVF, (f) QSM, (g) MD, (h) FA, (i) MTR, and (j) ihMTR. For each parametric map, the mean values of left versus right hemispheres (total of 28 volunteers) were calculated in 11 representative ROIs (see legend) based on FreeSurfer segmentation. ROIs include cerebral WM, caudate nucleus, putamen, pallidum, thalamus, ventral diencephalon, nucleus accumbens, amygdala, hippocampus, insular cortex, and all-cortex. A linear regression equation is given for each parameter, alongside the Pearson’s correlation coefficient (r). Overall, r > 0.89 represents strong positive relationship between the two hemispheres. P-values for all correlations were < 0.001.

Fig 5. Bland-Altman analysis of scan-rescan stability across qMRI map types.

(a) T₁, (b) T₂ (c) T₂*, (d) WF, (e) MTVF, (f) QSM, (g) MD, (h) FA, (i) MTR, and (j) ihMTR. For each parametric map, the mean and difference between the two scan sessions were calculated in 12 representative ROIs (see legend): cerebral WM, caudate nucleus, putamen, pallidum, corpus callosum, thalamus, ventral diencephalon, nucleus accumbens, amygdala, hippocampus, insular cortex, and all-cortex.