We recently reported our findings of resting state functional connectivity in the human spinal cord: in a cohort of healthy volunteers we observed robust functional connectivity between left and right ventral (motor) horns and between left and right dorsal (sensory) horns (Barry et al., 2014). Building upon these results, we now quantify the within-subject reproducibility of bilateral motor and sensory networks (intraclass correlation coefficient = 0.54–0.56) and explore the impact of including frequencies up to 0.13 Hz. Our results suggest that frequencies above 0.08 Hz may enhance the detectability of these resting state networks, which would be beneficial for practical studies of spinal cord functional connectivity.

An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication.

Patients with multiple sclerosis present with focal lesions throughout the spinal cord. There is a clinical need for non-invasive measurements of spinal cord activity and functional organization in multiple sclerosis, given the cord's critical role in the disease. Recent reports of spontaneous blood oxygenation level-dependent fluctuations in the spinal cord using functional MRI suggest that, like the brain, cord activity at rest is organized into distinct, synchronized functional networks among grey matter regions, likely related to motor and sensory systems. Previous studies looking at stimulus-evoked activity in the spinal cord of patients with multiple sclerosis have demonstrated increased levels of activation as well as a more bilateral distribution of activity compared to controls. Functional connectivity studies of brain networks in multiple sclerosis have revealed widespread alterations, which may take on a dynamic trajectory over the course of the disease, with compensatory increases in connectivity followed by decreases associated with structural damage. We build upon this literature by examining functional connectivity in the spinal cord of patients with multiple sclerosis. Using ultra-high field 7 T imaging along with processing strategies for robust spinal cord functional MRI and lesion identification, the present study assessed functional connectivity within cervical cord grey matter of patients with relapsing-remitting multiple sclerosis (n = 22) compared to a large sample of healthy controls (n = 56). Patient anatomical images were rated for lesions by three independent raters, with consensus ratings revealing 19 of 22 patients presented with lesions somewhere in the imaged volume. Linear mixed models were used to assess effects of lesion location on functional connectivity. Analysis in control subjects demonstrated a robust pattern of connectivity among ventral grey matter regions as well as a distinct network among dorsal regions. A gender effect was also observed in controls whereby females demonstrated higher ventral network connectivity. Wilcoxon rank-sum tests detected no differences in average connectivity or power of low frequency fluctuations in patients compared to controls. The presence of lesions was, however, associated with local alterations in connectivity with differential effects depending on columnar location. The patient results suggest that spinal cord functional networks are generally intact in relapsing-remitting multiple sclerosis but that lesions are associated with focal abnormalities in intrinsic connectivity. These findings are discussed in light of the current literature on spinal cord functional MRI and the potential neurological underpinnings.

Objective To examine: (1) differences in patient-reported outcomes, neuropsychological tests, and thalamic functional connectivity (FC) between patients with mild traumatic brain injury (mTBI) and healthy controls; (2) the longitudinal association between changes in these measures. Design Prospective observational case-control study. Setting Academic medical center. Participants Thirteen patients with mTBI (mean age = 39.3 years, 4 female) and 11 healthy, age and sex-matched control subjects (mean age = 37.6, 4 female) were enrolled. Interventions Not applicable. Main Outcome Measure(s) Resting-state FC (3T MRI scanner) was examined between the thalamus and the Default Mode Network (THAL-DMN), Dorsal Attention Network (THAL-DAN), and Frontoparietal Control Network (THAL-FPC). Patient-reported outcomes included pain (Brief Pain Inventory), depressive symptoms (Patient Health Questionnaire-9), post-traumatic stress disorder (PTSD Checklist), and post-concussive (Rivermead Post-Concussion Questionnaire) symptoms. Neuropsychological tests included the D-KEFS Tower test, Trails B, and Hotel task. Assessments occurred at 6 weeks and 4 months after hospitalization for patients with mTBI and at a single visit for controls. Results Student’s t-tests found increased pain and depressive, PTSD, and post-concussive symptoms, decreased performance on Trails B, increased THAL-DMN FC, and decreased THAL-DAN and THAL-FPC FC in patients with mTBI compared to healthy controls. Spearman correlation coefficient indicated that increased THAL-DAN FC from baseline to 4 months was associated with decreased pain and post-concussive symptoms (corrected p < 0.05). Conclusions Findings suggest that alterations in thalamic FC occur after mTBI and improvements in pain and post-concussive symptoms are correlated with normalization of thalamic FC over time.

Resting state functional magnetic resonance imaging (fMRI) has been used to study human brain function for over two decades, but only recently has this technique been successfully translated to the human spinal cord. The spinal cord is structurally and functionally unique, so resting state fMRI methods developed and optimized for the brain may not be appropriate when applied to the cord. This report therefore investigates the relative impact of different acquisition and processing choices (including run length, echo time, and bandpass filter width) on the detectability of resting state spinal cord networks at 3T. Our results suggest that frequencies beyond 0.08 Hz should be included in resting state analyses, a run length of ~8–12 mins is appropriate for reliable detection of the ventral (motor) network, and longer echo times – yet still shorter than values typically used for fMRI in the brain – may increase the detectability of the dorsal (sensory) network. Further studies are required to more fully understand and interpret the nature of resting state spinal cord networks in health and in disease, and the protocols described in this report are designed to assist such studies.