There is no commonly-available way for clinical neurologists to use an “everyday” MRI to provide their multiple sclerosis (MS) patients with meaningful news about their disease progression, including brain tissue changes associated with physical and cognitive impairment. The reason? Conventional MRI methods in the vast majority of clinical settings are inadequate in creating scans that can be used to measure two of the most reliable known “markers” of MS progression. Only time-consuming, pre-standardized, research-quality MRIs consistently performed on the exact same MRI machines and coils have been demonstrated to produce images with sufficient detail, accuracy, and consistency to assess the volume of brain lesions and the degree of brain atrophy.

In August of this year, though, researchers from the University of Buffalo’s Buffalo Neuroimaging Analysis Center (BNAC) published their NeuroSTREAM MSBase study. The study demonstrated that neurologists using a new, open-source software—NeuroSTREAM, recently co-developed by BNAC scientists—along with the widely-available T2-FLAIR MRI protocol, a standard developed in the early 1990s for routine imaging, can perform and read scans that confidently assess reliable and clinically meaningful proxies of the two critical markers—salient central brain lesion volume (SCLV) and lateral ventricle volume (LVV)—in regular clinical routine settings and even in the face of complete scanner changes.

Looking Back to See Forward

Led by Center Director Robert Zivadinov, MD, PhD, and Neuroinformatics Director Dr. Michael Dwyer, the BNAC team and its international collaborators examined scans gathered in nine different locations of 3,228 MS patients from five countries. Examinations were retrospective, meaning the researchers looked back on 10 years of scans taken of patients who were followed for three to five years. The scans are gathered in the MSBase Registry, the largest organized repository of “real-world” MS patient data. Since 2016, BNAC has been a contributing collaborator to the free Registry, which began in 2004 and has accumulated over 52,000 patient records from 33 participating countries.

In 96 percent of the 3,000+ scans examined for the study, the team was able successfully to calculate SLCV and LVV despite the majority of patients changing scanners. The data demonstrated, for the first time, that scans from T2-FLAIR MRI methods—used to examine almost 100 percent of MS patients worldwide—can be trusted to provide accurate measurements in typical follow-up clinic examinations.

The researchers adjusted their analysis for demographic, clinical, MRI, and time-of-follow-up differences between the MS patients with and without disease progression. Across the dataset and all adjustments, LVV remained significantly related to disease progression while SCLV also remained both associated with disease progression and predictive of subsequent change in disability status.

NeuroSTREAM MSBase Algorithm Unlocks Value in Disparate Scans

Unfortunately, assessing brain atrophy using routine clinical imaging is challenging due to technical factors related to how scans are obtained and variable measurement methods. These can vary widely over time and across clinical settings, affected by inconsistent quality of MRI protocols and the mix of equipment and methodology. In fact, this study showed that, over a patient follow-up period of 3.5 years, 57 percent of cases involved changes in scanner model, software, and protocol. This confirmed earlier research that indicated that frequent changes in scanner field strength, model, software, and protocol are inevitable in real-world clinical routine follow-up of MS patients.

Accordingly, a major strength of this study was its large sample size, with data collected at nine centers including patients from five countries, using 16 different scanner types and three different scanner manufacturers.

To overcome the issues arising in routine clinical imaging, BNAC researchers used the new NeuroSTREAM technique, confirming its value as a surrogate for brain atrophy measurement in conventional T2-FLAIR scans. Despite broad variety of MRI scanner types and magnetic field strengths across the nine centers, and the fact that more than half of patients’ examinations included scanner-related changes during follow-up, these substantial scanner model, software, and protocol changes did not significantly affect the reliability of LVV and SCLV in distinguishing disease progression.

Opening Doors to More Treatment-Related Insights

The NeuroSTREAM MSBase study further supports the premise that LVV and SCLV measurement in T2-FLAIR MRIs are a meaningful and reliable measure of MS disease progression in real-word groups examined using nonstandard scanning protocols.

The approach demonstrated in this study may be most useful where only clinical T2-FLAIR is available or where scanner changes are prevalent, providing substantially more quantitative information about brain pathology and disability than is currently standard practice in MS. However, care must be taken in its use for individual patients, as protocol stability and quality factors almost certainly have a much larger impact on individual analyses compared to those at the group-level, as was done with this study.

While the methods validated in this study do not replace MRI measures obtained on research-quality MRI sequences, they facilitate broader use of easy-to-access legacy datasets for understanding predictors of MS disability, especially in real-world, treatment-related studies. They also may increase research opportunities in clinical centers that do not routinely obtain research-quality MRIs. Moreover, routine clinical scans from a far broader pool, including wider demographics and longer follow-up time, now can provide quantitative metrics that could drive new research on MS progression.

By demonstrating that LVV-based atrophy and SCLV-based lesion assessments are feasible on T2-FLAIR scans from multiple centers and are associated with MS disease progression over the mid-term, BNAC’s NeuroSTREAM MSBase study opens doors to more high-value, real-world science that can accelerate treatment or a cure.

The BNAC-led NeuroSTREAM-MSBase study was supported by collaboration with the Sydney Neuroimaging Analysis Centre, MSBase, and clinicians around the world.

Read the full paper here in Neuroimage: Clinical.
 

Building on BNAC Research

This work  builds on other studies performed by the University of Buffalo’s 21-year-old Buffalo Neuroimaging Analysis Center, led by Center Director Robert Zivadinov, M.D., Ph.D.

A list of published papers along with contact information can be found elsewhere on BNAC.net.

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