A new rapid and high-resolution multi-slice inhomogeneous Magnetization Transfer protocol to evaluate diffuse and regional cervical cord myelination at 3T
Henitsoa Rasoanandrianina1,2,3, Guillaume Duhamel1,2, Aurélien Massire1,2,3, Olivier Girard1,2, Maxime Guye1,2, Jean Pelletier1,2,4, Bertrand Audoin1,2,4, and Virginie Callot1,2,3

1Aix-Marseille Univ, CNRS, CRMBM, Marseille, France, 2APHM, Hôpital Universitaire Timone, CEMEREM, Marseille, France, 3iLab-Spine International Associated Laboratory, Montreal, Marseille, France, 4Department of Neurology, CHU Timone, AP-HM, Marseille, France


The inhomogeneous Magnetization Transfer (ihMT) technique has recently been proposed as a new method to probe the cervical spinal cord (CSC) myelin-content. Studies reported so far were limited to single-slice acquisition, hence precluding investigation of the whole CSC within a short acquisition time. To overcome this limitation, a 2D multi-slice single-shot Spin-Echo-Echo-Planar Imaging (SE-EPI) read-out approach was implemented at 3T along with strategies to correct for inherent susceptibility-induced image-distortions and post-saturation relaxation effect for each slice. Validated on phantom and applied to healthy subjects and a patient with multiple sclerosis, this preliminary study shows the promising value of SE-EPI ihMT in the clinical context.


Neuroimaging is a key factor in the accurate diagnosis, prognosis and disease monitoring of various SC pathologies, especially the demyelinating Multiple Sclerosis (MS)(1). Research efforts have particularly led to a large panel of advanced techniques allowing to perform in vivo myelin MR imaging (MWF, MT/qMT, g-ratio)(2–6). In-line with these developments, the inhomogeneous Magnetization Transfer (ihMT) technique has recently been proposed as a presumably more-specific myelin-marker (7–9), with preliminary results in both the brain (10, 11) and the cervical spinal cord (CSC) (9, 12–14) demonstrating a good myelin-sensitivity. However, cross-sectional ihMT studies reported so far in the CSC were limited to single-slice acquisitions based on HASTE (half-Fourier acquired single-shot turbo spin-echo) read-out, hence preventing investigation of the whole CSC within a short acquisition time. In this study, we present a multi-slice 2D single-shot Spin-Echo Echo-Planar Imaging (SE-EPI) ihMT protocol, devoid of susceptibility-induced image-distortions and T1 relaxation effects, covering from C1 to C7 levels, compatible with a clinical scan-time (10 minutes). Combined with dedicated SC templates (AMU40(15), WM_tracts(16)), this protocol allowed for sub-millimetric regional and diffuse MT/ihMTratios quantification across the CSC.


Experiments were performed on a 3T Siemens Verio scanner using standard coils. Main parameters for the SE-EPI ihMT sequence are reported in Fig1. In addition to forward/reverse phase-encoding direction acquisition of unsaturated (M0) datasets for EPI-induced distortion correction, ascending/descending ihMT-prepared slice read-outs were acquired to mitigate the post-saturation relaxation effect occurring in each slice. B1+-field and MP2RAGE T1-mapping acquisitions (17, 18) were additionally performed for further T1 relaxation effect correction. Total scanning time for the 3 sequences was about 18 minutes. A 2D multi-gradient-echo sequence was also acquired for WM/GM segmentation. Data post-processing pipeline including denoising, distortion and motion correction, relaxation compensation and co-registration within a normalized space is also presented in Fig1. Validation of the technique was first performed on a lipid-based phantom (hair-conditioner). Then, 2 groups of 5 healthy subjects (G1: age 28.8±4.3yo; G2: age 60.2±2.9), as well as a relapsing-remitting MS patient (22yo, EDSS:1, disease duration: 2 years) were scanned. Two healthy subjects were scanned at two additional time points to evaluate reproducibility.


In silico and in vivo experiments led to reproducibility in the ihMT/MT measurements of 97%/99% and 87%/93% respectively. Fig2 and Fig3 show average ihMTratio and MTratio maps, respectively, from C1 to C6 for the two age-groups (the C7 level was not included in the present study due to non-systematic image quality (B1+ drop out, altered shim or fat contamination)). Preliminary inter-group comparisons in the different regions of interest (anterior gray matter (GM), whole white matter (WM), motor and sensory tracts) are also reported. These preliminary results showed a significant decrease of ihMTratio with age in lower levels, in both motor and sensory tracts, in line with previous study using HASTE read-out (13), whilst no significant change of MTratio was found. Fig4 illustrates MT/ihMT C1-to-C6 maps from the MS patient showing important decrease of ihMTratio in both normal-appearing and lesioned regions, as compared to young healthy subjects (average decrease of 27%), whilst moderate changes were found in MTratios (15% decrease in lesions as compared to healthy subjects values), suggesting a higher or earlier myelin-sensitivity of the ihMTratio as compared to MTratio.

Discussion / Conclusion

Accurate quantification of ihMT within the spinal cord currently requires ECG-synchronization (9), which is not yet fully compatible with 3D imaging. As an alternative to cover the whole cervical spinal cord, a multi-slice 2D imaging/processing strategy has thus been developed, allowing to collect reliable ihMT data from C1 to C6, within a scan-time compatible with clinical studies. Current methodology is under improvement to correct for B1+ inhomogeneity (16% drop-out in average at C7 level). Since fat saturation or outer volume suppression are currently not compatible with the ihMT preparation, a reduced FOV acquisition would also help minimizing fat artefact and aliasing from the neck. Despite these technical challenges, these preliminary applications on both healthy and pathological subjects already showed promising results in myelination/demyelination quantification in spinal cord tissue. This technique, which should of course be compared with other myelin imaging techniques, could be of great interest as a myelin biomarker especially in longitudinal studies and for early prognosis.


This study was supported by the French CNRS (Centre National de la Recherche Scientifique) and the French MESR (Ministère de l'Enseignement Supérieur et de la Recherche).

The authors are grateful for the time and efforts invested in this study by the patients, healthy volunteers, caregivers and clinicians of La Timone Hospital. They would also like to thank Guilherme Ribeiro for MATLAB code optimization, Veronique Gimenez, Lauriane Pini, Elisabeth Soulier and Sylviane Confort- Gouny for study logistics, volunteer recruitment and help with data acquisition.


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Fig1: Acquisition/Post-processing pipeline for the proposed 2D multi-slice Spin-Echo Echo-Planar Imaging Inhomogeneous Magnetization Transfer protocol used to quantify cervical spinal cord indices of myelination. Post-processing is performed slice by slice, here only C1 is illustrated.

Fig2: Inter-group ihMTratio analysis in healthy subjects (G1 vs. G2). Average maps from young (G1, top row images) and elderly subjects (G2, bottom row images) showing ihMTratio decrease with age, particularly in lower levels (C4-C6) confirmed by statistical results (box plots, blue: G1, red: G2). Percentage variation of ihMTratio in elderly group relative to that of young group are also reported in red. Metrics were compared using Wilcoxon’s rank test, significant decrease is indicated with underlined percentage and * (p-value <0.05).

Fig3: Inter-group MTratio analysis in healthy subjects. Average maps from young (G1, top row images) and elderly subjects (G2, bottom row images) are quite similar, confirmed by statistical results (box plots, blue: G1, red: G2) from Wilcoxon’s rank test and percentage of variation of elderly group MTratio relative to that of young group. No significant difference was found.

Fig4: MT/ihMTratio maps in one MS patient (age: 22yo; EDSS:1; disease duration: 2y) showing important decrease of both MTratio and ihMTratio in normal-appearing tissue and lesions (lesions are surrounded in red, based on T2*-w signal abnormalities). Preliminary analysis showed: 1) In the lesion, average ihMTratio/MTratio (all levels considered) of 7.6%/33% and 6.7%/34% within the motor and sensory tracts, respectively. 2) In non-lesioned sensory and motor tracts, ihMTratio was 9.49%/39% and 8.8%/38%, respectively. For comparison, mean ihMTratio/MTratio for healthy young subjects were 9.65%/39% and 9.99%/40%, respectively.

Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)