Functional connectivity in the dorsal network of the cervical spinal cord is correlated with diffusion tensor imaging indices in relapsing-remitting multiple sclerosis

Combes, Anna J.E.; O’Grady, Kristin P.; Rogers, Baxter P.; Schilling, Kurt G.; Lawless, Richard D.; Visagie, Mereze; Houston, Delaney; Prock, Logan; Malone, Shekinah; Satish, Sanjana; Witt, Atlee; McKnight, Colin D.; Bagnato, Francesca; Gore, John C.; Smith, Seth A.

doi:10.1016/j.nicl.2022.103127

Cited by 7 publications

(16 citation statements)

References 42 publications

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“…cervical myelopathy; Nouri et al, 2015) and that spinal cord resting-state fMRI is now being applied in such contexts – e.g. spinal cord injury (Chen et al, 2015; Sengupta et al, 2021) or multiple sclerosis (Conrad et al, 2018; Combes et al, 2022) – it will be of utmost importance to improve the reliability of segment-wise connectivity via optimization of data acquisition and analysis approaches, since only with a reliable estimate of connectivity can longitudinal studies that monitor disease progression or treatment effects be carried out successfully.…”

Section: Discussionmentioning

confidence: 99%

“…This approach could obviously be extended towards the spinal cord as well (e.g. in the context of recovery after spinal cord injury) and first steps have already been taken in this direction by assessing changes in spinal cord resting-state connectivity in sensory and motor disorders with diffuse or localized spinal pathology (Chen et al, 2015; Combes et al, 2022; Conrad et al, 2018; Martucci et al, 2019). However, before the clinical utility of resting-state metrics can be established, a necessary first step is to assess their reliability as well as the factors that influence it.…”

Section: Introductionmentioning

confidence: 99%

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Reliability of resting-state functional connectivity in the human spinal cord: assessing the impact of distinct noise sources

Kaptan¹,

Horn²,

Vannesjo

et al. 2022

Preprint

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The investigation of spontaneous fluctuations of the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord, where it has also generated initial interest from a clinical perspective. A number of resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated robust functional connectivity between the time-series of BOLD fluctuations in bilateral dorsal horns and between those in bilateral ventral horns, in line with the functional neuroanatomy of the spinal cord. A necessary step prior to extension to clinical studies is assessing the reliability of such resting-state signals, which we aimed to do here in a group of 45 healthy young adults at the clinically prevalent field-strength of 3T. When investigating connectivity in the entire cervical spinal cord, we observed fair to good reliability for dorsal-dorsal and ventral-ventral connectivity, whereas reliability was poor for within- and between-hemicord dorsal-ventral connectivity. Considering how prone spinal cord fMRI is to noise, we extensively investigated the impact of distinct noise sources and made two crucial observations: removal of physiological noise led to a reduction in functional connectivity strength and reliability - due to the removal of stable and participant-specific noise patterns - whereas removal of thermal noise considerably increased the detectability of functional connectivity without a clear influence on reliability. Finally, we also assessed connectivity within spinal cord segments and observed that while the pattern of connectivity was similar to that of whole cervical cord, reliability at the level of single segments was consistently poor. Taken together, our results demonstrate the presence of reliable resting-state functional connectivity in the human spinal cord even after thoroughly accounting for physiological and thermal noise, but at the same time urge caution if focal changes in connectivity (e.g. due to segmental lesions) are to be studied, especially in a longitudinal manner.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reliability of resting-state functional connectivity in the human spinal cord: assessing the impact of distinct noise sources

Kaptan¹,

Horn²,

Vannesjo

et al. 2022

Preprint

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“…WM lesions were found to have complex effects, causing both increases and decreases in connectivity metrics on different within-segment same-level functional networks depending on their location in different tracts and whether up- or down-stream of the GM networks of interest ( Conrad et al, 2018 ). Another study at 3T observed a link between increased resting-state connectivity in the CSC sensory network in pwRRMS and greater tissue damage as measured by DTI, suggesting that functional compensatory mechanisms may exist in the cord similarly to those observed in the brain in the early disease stages ( Combes et al, 2022 ).…”

Section: Advanced Imaging Methodsmentioning

confidence: 98%

Advanced spinal cord MRI in multiple sclerosis: Current techniques and future directions

Combes

Clarke

O’Grady

et al. 2022

NeuroImage: Clinical

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“…At 7T and higher, T2‐weighted spin‐echo (SE) sequences with a longer TE 29,78 are more used as the T2*‐weighted GRE sequences become more prone to artifacts and signal dropout 29,78 due to increased field inhomogeneities in 7T scanners 6 . Other MRI sequences that have been used for spinal cord fMRI include GRE or SE Echo Planar Imaging (GE‐EPI/SE‐EPI), 18,19,21,22,30,32,34,39,40,43,48,52,53,55–57,61,67–72,79–89 TSE or Fast Spin Echo, 2,14,25,31,33,39,47,90–101 three‐dimensional (3D) Multi‐shot GRE, 20,35,75,77,102 and Half‐Fourier Single‐Shot Turbo Spin Echo 13,36–38,41,42,44–46,49–51,58–60,62–66,73,103–108 . The use of different sequences for spinal cord fMRI is also partially due to the debate on which sequence is best for a specific contrast that depends on many not fully evaluated factors (see an example in the next section).…”

Section: Fmri Methodologies For Studying the Spinal Cordmentioning

confidence: 99%

The current state of spinal cord functional magnetic resonance imaging and its application in clinical research

Haynes,

Muhammad,

Khan

et al. 2023

Journal of Neuroimaging

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Since its development, spinal cord functional magnetic resonance imaging (fMRI) has utilized various methodologies and stimulation protocols to develop a deeper understanding of a healthy human spinal cord that lays a foundation for its use in clinical research and practice. In this review, we conducted a comprehensive literature search on spinal cord fMRI studies and summarized the recent advancements and resulting scientific achievements of spinal cord fMRI in the following three aspects: the current state of spinal cord fMRI methodologies and stimulation protocols, knowledge about the healthy spinal cord's functions obtained via spinal cord fMRI, and fMRI's exemplary usage in spinal cord diseases and injuries. We conclude with a discussion that, while technical challenges exist, novel fMRI technologies for and new knowledge about the healthy human spinal cord have been established. Empowered by these developments, investigations of pathological and injury states within the spinal cord have become the next important direction of spinal cord fMRI. Recent clinical investigations into spinal cord pathologies, for example, fibromyalgia, multiple sclerosis, spinal cord injury, and cervical spondylotic myelopathy, have already provided deep insights into spinal cord impairments and the time course of impairment‐caused changes. We expect that future spinal cord fMRI advancement and research development will further enhance our understanding of various spinal cord diseases and provide the foundation for evaluating existing and developing new treatment plans.

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Functional connectivity in the dorsal network of the cervical spinal cord is correlated with diffusion tensor imaging indices in relapsing-remitting multiple sclerosis

Cited by 7 publications

References 42 publications

Reliability of resting-state functional connectivity in the human spinal cord: assessing the impact of distinct noise sources

Reliability of resting-state functional connectivity in the human spinal cord: assessing the impact of distinct noise sources

Advanced spinal cord MRI in multiple sclerosis: Current techniques and future directions

The current state of spinal cord functional magnetic resonance imaging and its application in clinical research

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