A team of investigators at the MGH Martinos Center for Biomedical Imaging and Vanderbilt University Medical Center has reported a new approach to measuring spinal cord function that could help in more accurately understanding the degree of spinal cord damage in relapsing-remitting multiple sclerosis patients. They describe the approach in a paper published online this month in the journal Brain.
Echoing years of research into brain activity, the new approach takes advantage of signaling patterns in the spinal cord to characterize the impact of MS lesions, said Robert Barry, an assistant professor of radiology at Harvard Medical School and a Martinos Center investigator. Barry helped launch the present study while a faculty member at Vanderbilt, in Nashville, Tenn., and worked closely with lead author Benjamin Conrad, a graduate student in Neuroscience at Vanderbilt University, and faculty members John Gore and Seth Smith of the Vanderbilt University Institute of Imaging Science.
“Over two decades of research on human brain function have revealed that the normal, healthy brain exhibits coherent signaling patterns that are quite reproducible across time and across people,” Barry said. “The technical term in this field is called ‘resting state networks,’ and these networks have been used as biological markers of what is expected in a healthy human brain. A few years ago, our group showed that these resting state networks also exist in the normal, healthy human spinal cord. We hypothesized that a central nervous system disease, such as multiple sclerosis, would impact signaling patterns in the spinal cord in a similar manner, but this had not yet been demonstrated.”
To determine whether MS would in fact alter the signaling patterns, the researchers evaluated functional connectivity in the cervical cord gray matter using magnetic resonance imaging (MRI) in a cohort of 22 relapsing-remitting MS patients and compared the results with those from a sample of 56 healthy controls. The scans were performed at the ultra-high magnetic field strength of 7 Tesla. Because higher field strengths confer greater signal-to-noise ratios as well as other advantages, imaging at 7 Tesla allows visualization of small anatomical structures with considerably more detail than is available with conventional hospital scanners, and detection of resting-state networks with greater sensitivity.
While ultra-high-field MRI has been used for state-of-the-art brain imaging for roughly the past decade and a half, it had never been used to study the spinal cord in the ways the researchers envisioned when they began the research in late 2011 – work that was spearheaded by Barry and Smith, an associate professor of radiology at Vanderbilt and senior author of the present study. As a result, they found they needed to address a number of technical challenges in “completely novel ways,” while their progress had to be validated at every step by peer review to ensure that the research had a strong scientific foundation. Because such high levels of innovation were required, the methodologies deployed in the Brainpaper unfolded over six years of careful investigation.
This investment in time and energy paid off. The Brain study – the first to evaluate functional connectivity in the spinal cord of a diseased population – not only underscored the potential for detecting spinal cord networks, noninvasively and without employing any tasks or stimulation during imaging, it revealed notable differences in connectivity within the cohort of MS patients between areas of the cord with visible lesions.
These findings could have important implications for the management of relapsing-remitting MS. “The results from the study could provide the medical community with complementary information to characterize the impact of multiple sclerosis lesions,” Barry said. “For example, these measures may help clinicians more accurately predict the degree of recovery in relapsing-remitting patients or, in time, could be used to evaluate the efficacy of pharmacological interventions. The findings may also translate to studies of other devastating central nervous system diseases that are known to involve the spinal cord.”
Further research will help to realize the potential of the new approach for measuring spinal cord function. Teams at MGH and Vanderbilt are already looking to build upon the present study, to explore further the significance of differing MRI signal patterns in the spinal cord. Now that they have demonstrated the fundamental existence of resting-state networks and observed noninvasively the ways in which the networks can be altered by disease, they are preparing to explore how they may change through the progression of central nervous system disease.
In the photo above: The Martinos Center’s Rob Barry