Sensitivity of the Inhomogeneous Magnetization Transfer Imaging Technique to Spinal Cord Damage in Multiple Sclerosis

Abstract

BACKGROUND AND PURPOSE: The inhomogeneous magnetization transfer technique has demonstrated high specificity for myelin, and has shown sensitivity to multiple sclerosis-related impairment in brain tissue. Our aim was to investigate its sensitivity to spinal cord impairment in MS relative to more established MR imaging techniques (volumetry, magnetization transfer, DTI). MATERIALS AND METHODS: Anatomic images covering the cervical spinal cord from the C1 to C6 levels and DTI, magnetization transfer/inhomogeneous magnetization transfer images at the C2/C5 levels were acquired in 19 patients with MS and 19 paired healthy controls. Anatomic images were segmented in spinal cord GM and WM, both manually and using the AMU 40 atlases. MS lesions were manually delineated. MR metrics were analyzed within normal-appearing and lesion regions in anterolateral and posterolateral WM and compared using Wilcoxon rank tests and z scores. Correlations between MR metrics and clinical scores in patients with MS were evaluated using the Spearman rank correlation. RESULTS: AMU 40-based C1-to-C6 GM/WM automatic segmentations in patients with MS were evaluated relative to manual delineation. Mean Dice coefficients were 0.75/0.89, respectively. All MR metrics (WM/GM cross-sectional areas, normal-appearing and lesion diffusivities, and magnetization transfer/inhomogeneous magnetization transfer ratios) were observed altered in patients compared with controls (P , .05). Additionally, the absolute inhomogeneous magnetization transfer ratio z scores were significantly higher than those of the other MR metrics (P , .0001), suggesting a higher inhomogeneous magnetization transfer sensitivity toward spinal cord impairment in MS. Significant correlations with the Expanded Disability Status Scale (r ¼-0.73/P ¼ .02, r ¼-0.81/P ¼ .004) and the total Medical Research Council scale (r ¼ 0.80/P ¼ .009, r ¼-0.74/P ¼ .02) were observed for inhomogeneous magnetization transfer and magnetization transfer ratio z scores, respectively, in normal-appearing WM regions, while weaker and nonsignificant correlations were obtained for DTI metrics. CONCLUSIONS: With inhomogeneous magnetization transfer being highly sensitive to spinal cord damage in MS compared with conventional magnetization transfer and DTI, it could generate great clinical interest for longitudinal follow-up and potential remyelinating clinical trials. In line with other advanced myelin techniques with which it could be compared, it opens perspectives for multicentric investigations. ABBREVIATIONS: AMU ¼ Aix-Marseille University; CSA ¼ cross-sectional areas; EDSS ¼ Expanded Disability Status Scale; FA ¼ fractional anisotropy; HC ¼ healthy controls; ihMT ¼ inhomogeneous magnetization transfer; ihMTR ¼ inhomogeneous magnetization transfer ratio; l // ¼ axial diffusivity; l \ ¼ radial diffusivity; MRC ¼ Medical Research Council; MT ¼ magnetization transfer; MTR ¼ magnetization transfer ratio; NA ¼ normal-appearing; SC ¼ spinal cord; TWT ¼ Timed 25-Foot Walk Test; SCT ¼ Spinal Cord Toolbox M S is a ...

Advanced spinal cord MRI in multiple sclerosis: Current techniques and future directions

“… Zhang et al (2019) reviewed preclinical and validation studies of ihMT and showed good intra- and inter-scanner reproducibility in vivo in human cerebral WM tract; further development and validation are underway ( Cohen-Adad, 2018 ). Lastly, Rasoanandrianina et al (2020) showed that ihMTR was significantly different in the SC of pwMS compared to controls, and that ihMTR showed higher sensitivity to those changes than DTI or MTR metrics. This first study applying ihMTR to the MS SC is promising, and future studies should test the reproducibility of these findings.…”

Spinal cord and brain tissue impairments as long-term effects of rugby practice? An exploratory study based on T1 and ihMTsat measures

“…Several variants of the ihMT technique have been proposed in the past, including single slice 2D ihMT-HASTE (Half-Fourier Acquisition Single-shot Turbo spin Echo) for brain ( Girard et al, 2015 ) and SC ( Girard et al, 2017 , Taso et al, 2016 , Rasoanandrianina et al, 2020 ); 3D ihMT-GRE for brain ( Mchinda et al, 2018 ) and multi-slice ihMT SE- EPI for SC ( Rasoanandrianina et al, 2017 , Rangwala et al, 2013 ). In this study, a 3D ihMT-RAGE sequence initially proposed for brain ( Varma et al, 2020 ), and recently adapted to cervical spinal cord imaging ( Troalen et al, 2018 , Forodighasemabadi et al, 2020:p.1175.…”

“…The ihMT method, on the other hand, is more specific to myelin in central nervous system (CNS) tissues ( Varma et al, 2015 , Girard et al, 2015 , Varma et al, 2015 , Duhamel et al, 2019 ). It has been used in several clinical and preclinical studies on brain ( Varma et al, 2015 , Varma et al, 2015 , Prevost et al, 2017 , Mchinda et al, 2018 , Van Obberghen et al, 2018 , Munsch et al, October 2020 , Geeraert et al, May 2017 , Ercan et al, 2018 ) and recently adapted to SC imaging to study demyelinating pathologies such as MS and normal aging ( Girard et al, 2017 , Taso et al, 2016 , Rasoanandrianina et al, 2020 , Rasoanandrianina et al, 2017 ).…”

MRI and laboratory monitoring of disease-modifying therapy efficacy and risks

“…Though there is significant interlesional heterogeneity between patients, attempts have been made to develop a ‘personalized lesion profile’ that could potentially be used as a biomarker of treatment efficacy [25]. The future development of neuro-protective or pro-reparative therapies will heighten the imperative to include such biomarkers in routine MRI monitoring of patients with MS. More hyperintensities-specific imaging techniques such as tract-specific diffusion imaging [26], myelin water imaging [27], inhomogenous magnetization transfer imaging [28] and T1/T2 relaxometry [29] may also play a role, but are beyond the scope of this review.…”