The Martinos Center’s Constantina A. Treaba
The development of lesions in the brain’s cortical gray matter is a strong predictor of neurological disability for people with multiple sclerosis (MS), according to a study reported today in the journal Radiology. The findings suggest a role for ultrahigh-field MRI in monitoring the progression of MS, says Constantina A. Treaba, a researcher at the MGH Martinos Center for Biomedical Imaging and first author of the study.
MS, the most common cause of chronic neurological disability in young adults in the West, was once thought to be a disease of the brain’s white matter. Recent research has shown, though, that cortical lesions – that is, lesions found in the gray matter of the outer layer of the brain – could develop even earlier than white matter lesions in the course of the disease.
The involvement of cortical lesions raises several questions, says Treaba, who works with Caterina Mainero in the Multiple Sclerosis Imaging Lab at the Martinos Center. What causes cortical gray matter damage in MS? How quickly do cortical lesions accumulate in MS, especially relative to lesions in the white matter? And what are the contributions of each of these to neurological disability in MS?
Cortical lesions are difficult to see with 3T MRI scanners, commonly used tools in neuroscience research. So, in order to address these questions, Treaba and colleagues turned to the ultrahigh-field, 7T scanner in the Center, which has more than twice the magnetic field strength and thus offers greater sensitivity than 3T systems. Using the 7T, they followed 20 relapsing-remitting and 13 secondary-progressive MS patients as well as 10 age-matched healthy controls. Relapsing-remitting is a type of MS in which symptoms can either improve or worsen, while secondary progressive is a more advanced disease characterized by more significant disability.
The findings of the study, reported in the Radiology paper, were striking. Twenty-five of the MS patients, or 80 percent, developed new cortical lesions. The number of new lesions in the gray matter of the brain was more than twice the number that developed in the white matter. Based on the higher rate of accumulation, Treaba says, cortical lesions are the strongest predictor of disability progression in MS. Notably, in this study the 7T scanner detected the lesions more frequently than did lower-field scanners in previous studies, underscoring a possible role for ultrahigh-field MRI in following the progression of MS.
“Our results could influence the way we monitor the patients with MS by including cortical lesion assessment as a required step in the evaluation of disease progression and treatment outcomes,” Treaba says.
With respect to the causes of gray matter damage in MS, the study demonstrated that grooves on the brain’s surface called sulci are both the first and the predominant regions involved in cortical lesion development. This finding, says Treaba, suggested a possible link between gray matter pathology and a neuroinflammatory process mediated by cerebrospinal fluid, the flow of which may be restricted in the sulci. They hope to explore this possible mechanism further, while also looking into which patient cohorts tend to accumulate more lesions than others.
Other authors of the Radiology paper include the Martinos Center’s Tobias Granberg, Elena Herranz, Russell Ouellette, Céline Louapre and Caterina Mainero.