Quantitative spinal cord (SC) magnetic resonance imaging (MRI) is fraught with challenges, among which is the lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for the three main 3T MRI vendors: GE, Philips and Siemens. The protocol provides valuable metrics for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area (CSA) computation, multi-echo gradient echo for gray matter CSA, as well as magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. The spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects, as detailed in the companion paper [REF-DATA]. The spine generic protocol is open-access and its latest version can be found at: https://spinalcordmri.org/protocols. The protocol will serve as a valuable starting point for researchers and clinicians implementing new SC imaging initiatives. Note to the reviewer/editor/publisher: the companion paper is referred to as [REF-DATA]6/52 121 122dealing with cervical myelopathy and MS populations. Applications of the MethodThe proposed protocol is not geared towards a specific disease and it is suitable for imaging WM pathology (demyelination and Wallerian degeneration via axon/myelin-sensitive 122 https://mssociety.ca/about-ms-research/about-our-research-program/research-we-fund/canadian-prospect ive-cohort-study-to-understand-progression-in-ms-canproco 121 https://www.wingsforlife.com/us/research/imaging-spinal-cord-injury-and-assessing-its-predictive-value-th e-inspired-study-2675/ 9/52

Background and purpose Non‐myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract‐specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM. Methods High‐resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract‐specific diffusion metrics and corresponding electrophysiological measures and compression severity. Relationship between the degree of DCM disability, assessed by the modified Japanese Orthopaedic Association scale, and tract‐specific microstructural changes in DCM patients was also explored. Results The study identified diffusion‐derived abnormalities in the gray matter, dorsal and lateral tracts congruent with trans‐synaptic degeneration and demyelination in chronic degenerative spinal cord compression with more profound alterations in DCM than NMDC. Diffusion metrics were affected in the C3‐6 area as well as above the compression level at C3 with more profound rostral deficits in DCM than NMDC. Alterations in lateral motor and dorsal sensory tracts correlated with motor and sensory evoked potentials, respectively, whereas electromyography outcomes corresponded with gray matter microstructure. DCM disability corresponded with microstructure alteration in lateral columns. Conclusions Outcomes imply the necessity of high‐resolution tract‐specific diffusion MRI for monitoring degenerative spinal pathology in longitudinal studies.

Diffusion magnetic resonance imaging (dMRI) proved promising in patients with non-myelopathic degenerative cervical cord compression (NMDCCC), i.e., without clinically manifested myelopathy. Aim of the study is to present a fast multi-shell HARDI-ZOOMit dMRI protocol and validate its usability to detect microstructural myelopathy in NMDCCC patients. In 7 young healthy volunteers, 13 age-comparable healthy controls, 18 patients with mild NMDCCC and 15 patients with severe NMDCCC, the protocol provided higher signal-to-noise ratio, enhanced visualization of white/gray matter structures in microstructural maps, improved dMRI metric reproducibility, preserved sensitivity (SE = 87.88%) and increased specificity (SP = 92.31%) of control-patient group differences when compared to DTI-RESOLVE protocol (SE = 87.88%, SP = 76.92%). Of the 56 tested microstructural parameters, HARDI-ZOOMit yielded significant patient-control differences in 19 parameters, whereas in DTI-RESOLVE data, differences were observed in 10 parameters, with mostly lower robustness. Novel marker the white-gray matter diffusivity gradient demonstrated the highest separation. HARDI-ZOOMit protocol detected larger number of crossing fibers (5–15% of voxels) with physiologically plausible orientations than DTI-RESOLVE protocol (0–8% of voxels). Crossings were detected in areas of dorsal horns and anterior white commissure. HARDI-ZOOMit protocol proved to be a sensitive and practical tool for clinical quantitative spinal cord imaging.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/. The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.

Degenerative cervical myelopathy (DCM) is a severe consequence of degenerative cervical spinal cord (CSC) compression. The non-myelopathic stage of compression (NMDC) is highly prevalent and often progresses to disabling DCM. This study aims to disclose markers of progressive neurochemical alterations in NMDC and DCM by utilizing an approach based on state-of-the-art proton magnetic resonance spectroscopy ( 1 H-MRS).Proton-MRS data were prospectively acquired from 73 participants with CSC compression and 47 healthy controls (HC). MRS voxel was centered at C2 level. Compression-affected participants were clinically categorized as NMDC and DCM, radiologically as mild (MC) or severe (SC) compression. CSC volumes and neurochemical concentrations were compared between cohorts (HC vs. NMDC vs. DCM and HC vs. MC vs. SC) with general linear models adjusted for age and height (p FWE <0.05) and correlated to stenosis severity, electrophysiology, and myelopathy symptoms (p <0.05). While ratio of total creatine (tCr) to total N-acetylaspartate (tNAA) increased in NMDC (+11%) and in DCM (+26%) and SC (+21%), Myo-inositol/tNAA, glutamate+glutamine/tNAA and volumes changed only in DCM (+20%, +73%, and -14%) and SC (+12%, +46%, and -8%, respectively) relative to HC. Both tCr/tNAA and myo-inositol/tNAA correlated with compression severity and volume (-0.376

Aims.The relationship between freezing of gait (FOG) and regional brain atrophy has been intensively investigated, but it is still not clearly understood. The study objective was to test whether grey matter (GM) atrophy contributes to FOG in Parkinson´s disease (PD) using a surface-based algorithm. Methods. We investigated 21 patients with PD, 11 with FOG and 10 without FOG. Both groups were assessed using a FOG questionnaire and Hoehn and Yahr staging. High resolution T1-weighted brain images were acquired for each subject using a 1.5T MRI scanner. A surface-based method implemented in FreeSurfer was used to quantify the GM atrophy. A vertex-wise and region of interest (ROI) comparison of spatially normalized subject data using a general linear model and the Wilcoxon rank sum test were to assess significant group differences. Results. Higher global levels of cortical atrophy were detected in freezers, although this was not statistically significant. The vertex-wise analysis revealed significant local reduction in grey matter thickness in the left supplementary motor area, m iddle/anterior cingulate cortex, temporal pole and right frontal operculum in freezers at P<0.001, uncorrected. The ROI analysis of average thickness confirmed the regional atrophy in bilateral anterior and posterior cingulate cortices. No significant relative regional cortical atrophy was observed in non-freezers. Conclusion. FOG was associated with regional cortical atrophy, especially in mesial frontal and cingulate cortices. Our findings provide additional evidence that the development of FOG in patients with PD is associated with local structural cortical changes.

same b-vector), this artifact is not visible (mountSinai03, right panel). Such an artifact could be problematic for image registration with regularization along the S-I axis, or for performing diffusion tractography. (e) b = 0 image from a DWI scan (perform02) acquired with poor shimming and resulting signal dropout. (f) Another example of poor shimming resulting in sub-efficient fat saturation, with the fat being aliased on top of the SC. Here we show the mean DWI scan of a participant from the single subject database (perform). (g) Effect of pulsatile movement on a non-cardiac gated acquisition (single subject, juntendoAchieva). Diffusion-weighted scans (sagittal view) acquired at three b-vecs fairly orthogonal to the SC (i.e., diffusion-specific signal attenuation should be minimum in the SC), showing abrupt signal drop at a few slices (red arrows), likely due to cardiac-related pulsatile effects.

Background: Degenerative cervical spinal cord compression is becoming increasingly prevalent, yet the MRI criteria that define compression are vague, and vary between studies. This contribution addresses the detection of compression by means of the Spinal Cord Toolbox and assesses the variability of the morphometric parameters extracted with it.Methods: Prospective cross-sectional study. Two types of MRI examination, 3 and 1.5 T, were performed on 66 healthy controls and 118 participants with cervical spinal cord compression. Morphometric parameters from 3T MRI obtained by Spinal Cord Toolbox (cross-sectional area, solidity, compressive ratio, torsion) were combined in multivariate logistic regression models with the outcome (binary dependent variable) being the presence of compression determined by two radiologists. Inter-trial (between 3 and 1.5 T) and inter-rater (three expert raters and SCT) variability of morphometric parameters were assessed in a subset of 35 controls and 30 participants with compression.Results: The logistic model combining compressive ratio, cross-sectional area, solidity, torsion and one binary indicator, whether or not the compression was set at level C6/7, demonstrated outstanding compression detection (area under curve =0.947). The single best cut-off for predicted probability calculated