This proposal aims to develop and evaluate novel magnetic resonance imaging methods to non-invasively detect and characterize functional networks in the human cervical spinal cord. These methods may be used clinically to establish the extent of injuries to the spinal cord and to monitor the progression of functional recovery afterwards, and may also facilitate earlier detection of several central nervous system pathologies. We propose to develop and evaluate functional magnetic resonance imaging (fMRI) to detect and quantify low-frequency fluctuations in baseline BOLD (blood oxygenation level dependent) signals as indicators of resting state functional connectivity in the human spinal cord. To date, over 2900 studies have used similar fMRI approaches to study functional connectivity in the brain, and have provided compelling evidence that low- frequency BOLD signal fluctuations are inherent in normal, healthy brains and represent an important level of organization of cortical function. However, to date no corresponding studies have conclusively demonstrated similar low-frequency correlations within spinal gray matter. The precise functioning of the spinal cord in both normal and pathological populations remains poorly understood even though studies of functional connectivity and plasticity in the spinal cord using methods other than MRI have been topics of intense research for the past two decades. The scarcity of fMRI studies mainly reflects the technical difficulties of performing fMRI in the spina cord, the failure to develop appropriate methods and coils, and the need for higher spatial resolution and greater sensitivity for imaging the spinal cord compared to the brain. We propose to address these technical challenges and limitations by using an ultra-high field (7 Tesla) MR scanner, novel fMRI image acquisition and data correction protocols, and a dedicated 16-channel radiofrequency coil array optimized for spinal imaging. The higher signal-to-noise ratio (SNR) and greater BOLD contrast from 7T fMRI has already shown significant advantages over lower field studies of the brain for detecting activation and measuring connectivity at high spatia resolution. The higher SNR permits the use of smaller voxels, and parallel coil arrays allow novel faster image acquisitions. Thus, ultra-high field MRI is uniquely poised to provide insights into spinal anatomy and functional connectivity that are not possible in practice at lower fields. We hypothesize that the proposed technical advances will be used to detect and characterize functional connectivity in the cervical spinal cord and changes that occur with injury, recovery and repair, and that these measures will complement information from other functional measures including task-based fMRI studies.

Public Health Relevance

This project will use magnetic resonance imaging to develop and evaluate methods for detecting and characterizing functional networks in the human cervical spinal cord non-invasively. These methods may be used clinically to establish the extent of injuries to the spinal cord and to monitor the progression of functional recovery afterwards. These techniques may also facilitate earlier detection of several central nervous system pathologies such as multiple sclerosis.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Medical Imaging Study Section (MEDI)
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Chen, Daofen
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Vanderbilt University Medical Center
Schools of Medicine
United States
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Barry, Robert L; Vannesjo, S Johanna; By, Samantha et al. (2018) Spinal cord MRI at 7T. Neuroimage 168:437-451
Barry, Robert L; Conrad, Benjamin N; Smith, Seth A et al. (2018) A practical protocol for measurements of spinal cord functional connectivity. Sci Rep 8:16512
Barry, Robert L; Rogers, Baxter P; Conrad, Benjamin N et al. (2016) Reproducibility of resting state spinal cord networks in healthy volunteers at 7 Tesla. Neuroimage 133:31-40
Dula, Adrienne N; Pawate, Siddharama; Dortch, Richard D et al. (2016) Magnetic resonance imaging of the cervical spinal cord in multiple sclerosis at 7T. Mult Scler 22:320-8
Wang, Zheng; Chen, Li Min; Négyessy, László et al. (2013) The relationship of anatomical and functional connectivity to resting-state connectivity in primate somatosensory cortex. Neuron 78:1116-26