Characteristic Phase-Rim Lesions in MS Identified by Deep 3D-T1-TFE Hypointense Voxels

Overview

This study identifies a distinctive deep hypointensity on 3D T1-TFE MRI sequences corresponding to phase-rim lesions (PRLs) in multiple sclerosis (MS). These hypointense voxels serve as potential imaging biomarkers for chronic smoldering inflammation and progressive disease stages in MS.

Background

Multiple sclerosis is a chronic neurodegenerative and inflammatory demyelinating disease with heterogeneous clinical courses ranging from benign to rapidly progressive forms. Recent advances in disease-modifying therapies have improved treatment options, especially for relapsing–remitting MS and secondary progressive MS. Imaging markers such as phase-rim lesions (PRLs) and slowly expanding lesions (SELs) have been proposed to identify progressive disease and correlate with worse prognosis. However, PRLs are subtle and challenging to detect on standard MRI protocols, often requiring susceptibility-weighted imaging (SWI) which is not routinely used.

Data Highlights

The study included 20 MS patients (10 secondary progressive MS and 10 relapsing–remitting MS) matched by age, sex, and disease duration. MRI was performed on a Philips Ingenia 3 T scanner using 3DT1TFE, 3D FLAIR, and SWI sequences. PRLs were manually segmented on SWI images and compared to non-phase-rim white matter lesions. Image preprocessing involved intensity normalization and co-registration to T1-weighted reference space. The characteristic deep hypointensity of PRLs on 3DT1TFE sequences was quantitatively analyzed to assess lesion classification potential.

Key Findings

• Phase-rim lesions (PRLs) correspond to lesions with deep hypointense voxels on 3D T1-TFE MRI sequences.
• These hypointense voxels are distinct from non-phase-rim white matter lesions and correlate with chronic smoldering inflammation.
• PRLs are associated with worse clinical prognosis and are more prevalent in secondary progressive MS.
• Standard MRI protocols often miss PRLs due to their subtle appearance; SWI and advanced 3D T1 sequences improve detection.
• Intensity normalization and image co-registration enhance the identification and classification of PRLs on routine clinical MRI.

Clinical Implications

Incorporating 3D T1-TFE sequences and susceptibility-weighted imaging into routine MRI protocols may improve early detection of phase-rim lesions, facilitating timely identification of progressive MS. Recognizing these lesions as markers of chronic inflammation can guide treatment decisions and monitoring strategies, particularly for patients transitioning to secondary progressive MS.

Conclusion

Deep hypointense voxels on 3D T1-TFE MRI sequences represent a characteristic imaging signature of phase-rim lesions in multiple sclerosis. Their identification may serve as a valuable surrogate marker for chronic smoldering inflammation and progressive disease, enhancing clinical assessment and management.

References

1. Filippi et al. 2018 -- Multiple sclerosis
2. Ontaneda et al. 2021 -- Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function
3. Absinta et al. 2019 -- Chronic active multiple sclerosis lesions characterized by iron rim
4. Dal-Bianco et al. 2017 -- Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging
5. Sati et al. 2018 -- Imaging of chronic active multiple sclerosis lesions