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Imaging MS: Emerging approaches for precision diagnosis and staging of MS

By Debra L. Beck

credit: Living Art Enterprises, LLC/Science Source

A number of emerging MRI measures with which to diagnose and stage multiple sclerosis (MS) are in development and nearly ready for expanded clinical use, according to a recent review article in the Multiple Sclerosis Journal.


Adding Grey Completes the Picture

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The review summarizes the evidence supporting five emerging techniques: the central vein sign (CVS), leptomeningeal inflammation/enhancement in MS, conventional and quantitative spinal cord imaging, susceptibility-weighted imaging of paramagnetic rims, and ultrahigh-field MRI.

credit: Medical Body Scans/Science Source

The central vein sign

Susceptibility-based MRI sequences enable the visualization of central veins within white-matter lesions (WMLs) that are not easily seen on T2-based sequences. The observed hypointensity is related to deoxyhemoglobin within WMLs which is often related to the presence of a central vein.

Leptomeningeal inflammation in MS

Leptomeningeal inflammation is frequently observed in both early and late stages of MS, but difficult to visualize with conventional postcontrast T1-weighted MRI sequences. Recently, postcontrast fluid attenuation inversion recovery sequences have demonstrated significantly increased sensitivity to leptomeningeal enhancement in several neurologic disease states.

Spinal cord imaging

The spinal cord is highly relevant to clinical disability and commonly involved across the spectrum of MS disease subtypes, but particularly in progressive MS. In clinical practice, lesion-based measures in the spinal cord on MRI are frequently used in the diagnosis of MS as they can demonstrate “dissemination in space.” Improved MRI sequences, including T1-based sequences (magnetization-prepared rapid gradient echo and phase-sensitive inversion recovery) in the cervical spinal cord, improve lesion conspicuity, which can facilitate an earlier diagnosis of MS.

Paramagnetic rims in MS

Chronic lesions with active, “smoldering” inflammation and slow expansion are known to be an important substrate of neurologic disease progression in MS. These chronic, active lesions are seen across the spectrum of MS, but observed particularly in progressive MS. Susceptibility-weighted imaging sequences on high-field MRI platforms (7T) are sensitive to iron content in tissue, and persistent “paramagnetic rims” around lesions has been histopathologically validated to represent chronic inflammatory infiltration related to macrophages and microglia, as well as ongoing demyelination.

Ultrahigh-field MRI

Ultrahigh-field MRI platforms, including 7T MRI platforms, allow for increased spatial resolution in comparison to lower-field platforms, enabling improved visualization of anatomic detail of brain and spinal cord tissue in various neurologic disorders. In MS, high-field MRI has been utilized in a variety of applications, with the most common being in the identification and characterization of cortical lesions, which have been much more difficult to visualize on lower-field platforms.

Ultrahigh-field MRI

Ultrahigh-field MRI platforms, including 7T MRI platforms, allow for increased spatial resolution in comparison to lower-field platforms, enabling improved visualization of anatomic detail of brain and spinal cord tissue in various neurologic disorders. In MS, high-field MRI has been utilized in a variety of applications, with the most common being in the identification and characterization of cortical lesions, which have been much more difficult to visualize on lower-field platforms.

 Nearly ready for clinical use

“Many of the techniques we discuss – and there are many more that we couldn’t include because of space – are of high interest for different reason, but amongst them I would say that the one that is very likely to be used clinically in the upcoming years is the central vein sign,” lead author Jiwon Oh, MD, PhD, a neurologist at the University of Toronto, said in an interview.

The CVS has been proposed as a highly sensitive and specific biomarker that can be used to differentiate MS from other conditions that have similar brain features.

 

Dr. Jiwon Oh

credit: Scott Camazine/Science Source

Central veins within WMLs, when visualized using the appropriate sequences (T2*-weighted or flare sequence), are suggestive of inflammation and demyelination, both pathological hallmarks of MS-related lesions. 

Importantly, several researchers have shown that the presence of a large proportion of WML demonstrating CVS has utility in distinguishing MS from other white-matter disorders.

“A 40% threshold – where greater than 40% of white-matter lesions showing the central vein signal – has been suggested as the most useful threshold to differentiate MS from other white matter disorders,” said Dr. Oh. 

Other simplified criteria have been proposed, “but if most of your lesions show a central vein, the likelihood of you having MS is extremely high,” she added. 

Dr. Oh expects that, within a few years, the sequences needed to visualize the CVS will become widely available and may be part of future recommendations and guidelines. 

The paper, cowritten with Nancy L. Sicotte, MD, chair of neurology at Cedars-Sinai Medical Center in Los Angeles, also appeared in a special ACTRIMS (Americas Committee for Treatment and Research in Multiple Sclerosis) 2019 issue focused on precision medicine approaches for MS

Improving on what is currently available

The new imaging measures promise to address some of the limitations of current techniques. Conventional MRI is a mainstay in the diagnosis and management of MS in daily practice but is beset by a number of limitations and is considered limited in its ability to appropriately diagnose the disease and predict future disability.

Commenting on the review, David Li, MD, from the University of British Columbia, Vancouver, said that “these measures are all promising in that if they work out the way that they are intended to, they will be of tremendous benefit in helping clinicians either predict or know which patients are likely to progress.”

Dr. Li, who is the emeritus director of the UBC MS/MRI Research Group, said he agrees that the CVS is probably the MRI measure closest to prime time.

In an interview, Dr. Li suggested that one challenge will be figuring out how to blend these more informative imaging findings with clinical findings.

“Progression is currently defined from a clinical perspective in terms of how patients progress, but if you look at things that happen on the MRI, things are continually progressing, yet we don’t necessarily say that what is there on the scan that is progressing is necessarily the same thing as progression as defined in the clinical world,” he said.

Another challenge – one that is ongoing – is standardization of MR imaging across different sites.

“We need to get scans to be as similar from one center to another center such that, if a patient has a scan done 2 years ago, it can be directly compared with a scan done today,” said Dr. Li.

Dr. Oh agrees. “There are guidelines that have been published that state what the bare minimum should be in terms of sequence parameters and they are a good resource that people can use to ensure that their MS protocol adheres to the minimum guidelines.” Dr. Oh and Dr. Li both contributed to the recent CMSC MRI protocol for MS.

Dr. David Li