In the 2023 Donald Paty Lecture, speaker Darin Okuda presented novel MRI methods that might help determine whether MS lesions have potential for future remyelination.
Much of multiple sclerosis (MS) disease severity and progression is monitored using MRI. Unfortunately, this imaging method is imperfect and often dependent on the skill of the interpreter. On the final day of the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, the Donald Paty Lecture speaker Darin Okuda, MD, challenged the audience to rethink what they see on MRI images. Okuda, a professor of neurology and the director of the Neuroinnovation Program at the University of Texas Southwestern Medical Center in Dallas, uses 3-dimensional (3D) MRI techniques to better interpret what MRI can reveal about the MS disease process.
Current MRI techniques employed in MS are often beset by false positives because of the high sensitivity of white matter hyperintensities, Okuda told the audience. Behind the scenes, however, there are even more limitations to 2-dimensional (2D) MRI in MS. Limited perspectives offered by conventional 2D anatomical planes fail to provide key information about the MS lesion, including the severity of the underlying tissue injury, the lesion age, and the nature of the surrounding tissue. Some of this can be gleaned from 3D imaging, Okuda suggested, and could help to take the management of MS beyond its current anti-inflammatory approach to the next level: remyelination.
Remyelination has long been a much-desired, but elusive, goal in MS management. Advanced imaging techniques can be valuable to evaluate an MS lesion’s future potential for remyelination, Okuda suggested. His lab uses a signal called blood oxygen level dependent (BOLD) to compare oxygenation at the MS lesion site with that of the surrounding tissue. Better oxygenation means that the surrounding tissue can support healing.
In a study analyzing 109 brain lesions from 23 people with MS, Okuda and colleagues utilized 3T T2-FLAIR and functional MRI (fMRI) imaging techniques to compile a detailed profile of the lesions, including BOLD, cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2). 3D contouring techniques were used to analyze the shape and texture of the lesions. Metabolically active lesions—those with more white matter integrity—had higher BOLD slopes, CBF, and CMRO2. Interestingly, the 3D modeling showed that these metabolically active lesions had more symmetrical shapes and more complex surface textures, compared to inactive lesions with less intact white matter integrity. Identifying lesions with potential for healing may prove to be a key component of precision medicine in MS, Okuda stressed.
Okuda’s presentation went on to describe other applications of 3D imaging. For example, assessing how the lesion is positioned in relation to the cortex can help to distinguish MS lesions from those of small vessel disease (SVD), he said. Another interesting study used 3D imaging to distinguish neurodegeneration rates in MS lesions among people with Black or African ancestry (B/AA) and those of European ancestry (EA).
Generally, people with B/AA have been shown to have a more aggressive course of MS. Okuda’s research team conducted a 2-year prospective, single-center study among 209 patients with nonprogressive MS. About one-half of subjects had B/AA ethnicity and half had E/A ethnicity. The study’s objective was to evaluate the rate of change in volume and surface at the brainstem and upper cervical spinal cord. Some differences were observed among the 2 populations in neurodegeneration rates in these areas, Okuda reported. Among B/AA individuals, significantly increased rates of surface texture change and increased rates of curvature change were observed in specific areas of the upper cervical spinal cord.
More work needs to be done in this line of research, Okuda said, but identifying vulnerable regions within the brainstem and upper cervical cord may allow for more personalized approaches to disease surveillance and management in populations of MS patients.