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

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White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human wholebrain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process.

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.

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.

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.

Electroencephalography (EEG) oscillations reflect the superposition of different cortical sources with potentially different frequencies. Various blind source separation (BSS) approaches have been developed and implemented in order to decompose these oscillations, and a subset of approaches have been developed for decomposition of multi-subject data. Group independent component analysis (Group ICA) is one such approach, revealing spatiospectral maps at the group level with distinct frequency and spatial characteristics. The reproducibility of these distinct maps across subjects and paradigms is relatively unexplored domain, and the topic of the present study. To address this, we conducted separate group ICA decompositions of EEG spatiospectral patterns on data collected during three different paradigms or tasks (resting-state, semantic decision task and visual oddball task). K-means clustering analysis of back-reconstructed individual subject maps demonstrates that fourteen different independent spatiospectral maps are present across the different paradigms/tasks, i.e. they are generally stable.

Sustained pressure stimulation of the body surface has been used in several physiotherapeutic techniques, such as reflex locomotion therapy. Clinical observations of global motor responses and subsequent motor behavioral changes after stimulation in certain sites suggest modulation of central sensorimotor control, however, the neuroanatomical correlates remain undescribed. We hypothesized that different body sites would specifically influence the sensorimotor system during the stimulation. We tested the hypothesis using functional magnetic resonance imaging (fMRI) in thirty healthy volunteers (mean age 24.2) scanned twice during intermittent manual pressure stimulation, once at the right lateral heel according to reflex locomotion therapy, and once at the right lateral ankle (control site). A flexible modeling approach with finite impulse response basis functions was employed since non-canonical hemodynamic response was expected. Subsequently, a clustering algorithm was used to separate areas with differential timecourses. Stimulation at both sites induced responses throughout the sensorimotor system that could be mostly separated into two anti-correlated subsystems with transient positive or negative signal change and rapid adaptation, although in heel stimulation, insulo-opercular cortices and pons showed sustained activation. In direct voxel-wise comparison, heel stimulation was associated with significantly higher activation levels in the contralateral primary motor cortex and decreased activation in the posterior parietal cortex. Thus, we demonstrate that the manual pressure stimulation affects multiple brain structures involved in motor control and the choice of stimulation site impacts the shape and amplitude of the blood oxygenation level-dependent response. We further discuss the relationship between the affected structures and behavioral changes after reflex locomotion therapy.