Using Advanced Imaging Techniques to Better Understand MS Progression

Advanced imaging techniques are becoming necessary to further understanding of the progression of multiple sclerosis (MS), according to presenters at the 2014 Joint ACTRIMS-ECTRIMS Meeting in Boston, Massachusetts, from September 10-13.

Wolfgang Brück, MD, professor of neuropathology at Georg August University in Göttingen, Germany, kicked off the discussion by highlighting the recent insights into the pathology of MS, asserting that the disease causes both focal damage and diffuse damage. The former is a sharp-edged area of inflammatory demylineation with neuroaxonal damage, while the latter is abnormal tissue observed outside the perimeter of known lesions.

Focal lesions in the white matter are the pathological hallmark of MS. Not only are focal lesions appearing in the gray matter histopathologically distinct, but they are also difficult to detect by conventional MRI, Brück said.

“The knowledge that the gray matter is also involved in the disease pathology has, for a long time, been neglected since in conventional pathological stains as well as in conventional MRI markers you are underestimating the extensive involvement of gray matter in MS,” he said.

While conventional MRI techniques are pivotal in the diagnosis of MS and for monitoring disease progression, advanced techniques may provide new information on focal and diffuse tissue damage, according to Jens-Thomas Würfel, MD, from the University Medical Center in Göttingen.

“Using these conventional sequences … we have some drawbacks,” he said. “We are very poor in detecting brain matter lesions … also we hardly detect diffuse changes in these techniques.”

For instance, it can be difficult to know whether demylineation or remylineation is occurring through conventional MRIs.

He stressed 7 different techniques that offer the ability to acquire datasets with increased sensitivity and specificity, including double inversion recovery, magnetization transfer imaging, ultra-high-field MRI, and magnetic resonance elastography, which is in its infancy.

Würfel highlighted ultra-high-field MRI, which he has extensive experience in and which allows practitioners to detect new things. Not only does the technique show more lesions in the white matter, gray matter, and the cortex, it allows researchers to observe that MS lesions are characterized by a central vein and it develops vascularly.

“Nearly every MS lesion has a central vein that we can depict,” he said. “It’s so characteristic that nowadays we use this information to differentiate MS from other diseases … where we don’t see that.”

The newer magnetic resonance elastography looks at and quantifies biomechanical properties. Würfel recalls being surprised at how sensitive the technique was as it is also sensitive to gender and aging.

Maria Pia Sormani, PhD, from the Department of Health Sciences in Genova, Italy, explained using imaging to detect aspects of the disease that may not manifest clinically.

“Not all the relapses are associated with lesions,” she said by example. “There are many lesions that do not produce any relapse.”

While MRI provides additional information on MS because it is moderately correlated with long-term disease progression, advanced techniques are more strongly correlated with clinical disease progression, she added.