The work describes a multi-parametric quantitative MRI (qMRI) protocol optimized for brain imaging and consisting of a series of well-established qMRI techniques and their corresponding postprocessing software packages. The manuscript describes all pulse sequences, scan settings, post-processing pipelines, as well as practical tips and limitations. The set of parameters includes T1, T2, and T2* relaxation times, water fraction (WF), macromolecular tissue volume fraction (MTVF), magnetization transfer ratio (MTR), inhomogeneous MTR (ihMTR), quantitative susceptibility maps (QSM), mean diffusivity (MD) and fractional anisotropy (FA). The protocol data can be further utilized to generate additional quantitative maps using application-specific postprocessing techniques. Application of the qMRI protocol for brain imaging is presented for a cohort of 28 healthy volunteers, where quantitative values were mapped across 12 brain regions-of-interest (ROIs) and across two scan sessions in order to estimate reproducibility.

The improved sensitivity and reproducibility of such qMRI protocol can be utilized for many applications. Employing quantitative MRI parameters as clinical biomarkers would greatly benefit standardization in the field – either for healthy populations or for investigating pathologies.

Quantitative MRI (qMRI) has been shown to be clinically useful for numerous pathologies 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 pathologies.

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Example of quantitative maps from a single volunteer (F, 31 y/o). Data were reformatted to exhibit 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 mask are based on FreeSurfer segmentations.

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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 a broad variety of quantitative maps including T1, T2, and T2* relaxation times, quantitative susceptibility, water and macromolecular tissue fractions, molecular diffusion maps of mean diffusivity and fractional anisotropy, magnetization transfer ratio (MTR) and inhomogeneous MTR. The protocol also offers the flexibility to produce additional maps using further postprocessing techniques. 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 for which quantitative values were estimated across 12 brain regions-of-interest (ROIs).

Statistical analysis revealed low variability of qMRI parameters across subjects compared to intra-ROI variability which was x3.7 times higher on average. Strong positive linear relationship was found between right and left hemispheres for all parameters and ROIs. Finally, scan-rescan stability demonstrated high reproducibility of the measured parameters across ROIs and volunteers.

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The quantitative maps produced by the presented protocol can promote longitudinal 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.

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Processing pipelines are available online and can be download from the following links (request for download/use require either academic license, or, a license for non-academic or commercial use):

mrQ software package: https://github.com/mezera/mrQ

EMC platform: https://beneliezer-lab.com/software-downloads-page/

ihMT pipeline: https://github.com/lsoustelle/ihmt_proc

Susceptibility calculation: https://xip.uclb.com/product/mri_qsm_tkd

Diffusion pipeline: https://github.com/GalBenZvi/dmriprep

The ihMT sequence is available upon request (guillaume.duhamel@univ-amu.fr) and requires a copyright license agreement with Aix-Marseille University. All other sequences are available in conventional clinical scanners.

 

A GitHub respiratory with processing scripts and data underlying the findings, is openly accessed for users : https://github.com/Dvirrad/Multiparametric_qMRI_data. This includes:

1. All types of quantitative and registered segmentation maps, provided in .mat format. Includes the data of all volunteers from 1st (N=28) and 2nd (N=23, denoted with '_S2') scan sessions.

2. Example raw dataset of a single volunteer, provided in .dcm format. Includes all raw images acquired using the qMRI protocol.

3. Matlab scripts to apply FreeSurfer based segmentation and registration. This requires to download and install the FreeSurfer tool from: https://surfer.nmr.mgh.harvard.edu/fswiki/DownloadAndInstall

4. Matlab scripts for extracting quantitative values per brain region of interest (ROI), based on the segmented maps.

5. Matlab scripts to produce the paper's figures and tables, based on the statistics per brain region.