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

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.

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.