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

Objectives: The aim of this study was to evaluate the linearity, bias, intrascanner repeatability, and interscanner reproducibility of quantitative values derived from a multidynamic multiecho (MDME) sequence for rapid simultaneous relaxometry. Materials and Methods: The NIST/ISMRM (National Institute of Standards and Technology/International Society for Magnetic Resonance in Medicine) phantom, containing spheres with standardized T1 and T2 relaxation times and proton density (PD), and 10 healthy volunteers, were scanned 10 times on different days and 2 times during the same session, using the MDME sequence, on three 3 T scanners from different vendors. For healthy volunteers, brain volumetry and myelin estimation were performed based on the measured T1, T2, and PD. The measured phantom values were compared with reference values; volunteer values were compared with their averages across 3 scanners. Results: The linearity of both phantom and volunteer measurements in T1, T2, and PD values was very strong (R 2 = 0.973-1.000, 0.979-1.000, and 0.982-0.999, respectively) The highest intrascanner coefficients of variation (CVs) for T1, T2, and PD were 2.07%, 7.60%, and 12.86% for phantom data, and 1.33%, 0.89%, and 0.77% for volunteer data, respectively. The highest interscanner CVs of T1, T2, and PD were 10.86%, 15.27%, and 9.95% for phantom data, and 3.15%, 5.76%, and 3.21% for volunteer data, respectively. Variation of T1 and T2 tended to be larger at higher values outside the range of those typically observed in brain tissue.The highest intrascanner and interscanner CVs for brain tissue volumetry were 2.50% and 5.74%, respectively, for cerebrospinal fluid. Conclusions: Quantitative values derived from the MDME sequence are overall robust for brain relaxometry and volumetry on 3 T scanners from different vendors. Caution is warranted when applying MDME sequence on anatomies with relaxometry values outside the range of those typically observed in brain tissue.

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The symptoms of idiopathic normal pressure hydrocephalus (iNPH) can be improved by shunt surgery, but prediction of treatment outcome is not established. We investigated changes of the corticospinal tract (CST) in iNPH before and after shunt surgery by using diffusion microstructural imaging, which infers more specific tissue properties than conventional diffusion tensor imaging. Two biophysical models were used: neurite orientation dispersion and density imaging (NODDI) and white matter tract integrity (WMTI). In both methods, the orientational coherence within the CSTs was higher in patients than in controls, and some normalization occurred after the surgery in patients, indicating axon stretching and recovery. The estimated axon density was lower in patients than in controls but remained unchanged after the surgery, suggesting its potential as a marker for irreversible neuronal damage. In a Monte-Carlo simulation that represented model axons as undulating cylinders, both NODDI and WMTI separated the effects of axon density and undulation. Thus, diffusion MRI may distinguish between reversible and irreversible microstructural changes in iNPH. Our findings constitute a step towards a quantitative image biomarker that reflects pathological process and treatment outcomes of iNPH.

The functional characteristics of the left inferior longitudinal fasciculus (ILF) remain unclear. The present study describes a case of a right-handed 74-year-old woman with a brain tumor who showed marked deterioration in object naming ability after invasion of the tumor into the medial region of the left posterior (middle and inferior) temporal lobe just beside the atrium of the lateral ventricle. Diffusion tensor imaging showed possible interruption of the left ILF after invasion of tumor at this site. By contrast, the left superior longitudinal fasciculus (SLF) remained intact after invasion of tumor, and the inferior fronto-occipital fasciculus (IFOF) was already disrupted prior to tumor invasion. These observations indicate that intact ILF function may be required for object naming ability.

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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.

Mapping of MR fiber g-ratio, which is the ratio of the diameter of the axon to the diameter of the neuronal fiber, is introduced in this article. We investigated the MR fiber g-ratio, the axon volume fraction (AVF) and the myelin volume fraction (MVF) to evaluate microstructural changes in the spinal cord in patients with cervical spondylotic myelopathy (CSM) in vivo, using atlas-based analysis. We used diffusion MRI data acquired with a new simultaneous multi-slice accelerated readout-segmented echo planar imaging sequence for diffusion analysis for AVF calculation and magnetization transfer saturation imaging for MVF calculation. The AVFs of fasciculus gracilis in the affected side spinal cord, fasciculus cuneatus and lateral corticospinal tracts (LSCT) in the affected and unaffected side spinal cord were significantly lower (P = 0.019, 0.001, 0019, 0.000, and 0.002, respectively) than those of normal controls. No difference was found in the MVFs. The fiber g-ratio of LSCT was significantly lower (P = 0.040) in the affected side spinal cords than in the normal controls. The pathological microstructural changes in the spinal cord in patients with CSM, presumably partial axonal degenerations with preserved myelin. This technique has the potential to be a clinical biomarker in patients with CSM in vivo.