Deeply 3D-T1-TFE hypointense voxels are characteristic of phase-rim lesions in multiple sclerosis
Pablo Naval-Baudin1,2,3,4, Albert Pons-Escoda5,6,7,8, Àngels Camins5,6,7
1Neuroradiology Section, Department of Radiology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Carrer de Feixa Llarga SN, 08907, Barcelona, Spain. pablo.naval.idi@gencat.cat.
Objectives:
The development of new drugs for the treatment of progressive multiple sclerosis (MS) highlights the need for new prognostic biomarkers. Phase-rim lesions (PRLs) have been proposed as markers of progressive disease but are difficult to identify and quantify. Previous studies have identified T1-hypointensity in PRLs. The aim of this study was to compare the intensity profiles of PRLs and non-PRL white-matter lesions (nPR-WMLs) on three-dimensional T1-weighted turbo field echo (3DT1TFE) MRI. We then evaluated the performance of a derived metric as a surrogate for PRLs as potential markers for risk of disease progression.
Methods:
This study enrolled a cohort of relapsing-remitting (n = 10) and secondary progressive MS (n = 10) patients for whom 3 T MRI was available. PRLs and nPR-WMLs were segmented, and voxel-wise normalized T1-intensity histograms were analyzed. The lesions were divided equally into training and test datasets, and the fifth-percentile (p5)-normalized T1-intensity of each lesion was compared between groups and used for classification prediction.
Results:
Voxel-wise histogram analysis showed a unimodal histogram for nPR-WMLs and a bimodal histogram for PRLs with a large peak in the hypointense limit. Lesion-wise analysis included 1075 nPR-WMLs and 39 PRLs. The p5 intensity of PRLs was significantly lower than that of nPR-WMLs. The T1 intensity-based PRL classifier had a sensitivity of 0.526 and specificity of 0.959.
Conclusions:
Profound hypointensity on 3DT1TFE MRI is characteristic of PRLs and rare in other white-matter lesions. Given the widespread availability of T1-weighted imaging, this feature might serve as a surrogate biomarker for smoldering inflammation.
Clinical Relevance Statement:
Quantitative analysis of 3DT1TFE may detect deeply hypointense voxels in multiple sclerosis lesions, which are highly specific to PRLs. This could serve as a specific indicator of smoldering inflammation in MS, aiding in early detection of disease progression.
Key Points:
• Phase-rim lesions (PRLs) in multiple sclerosis present a characteristic T1-hypointensity on 3DT1TFE MRI. • Intensity-normalized 3DT1TFE can be used to systematically identify and quantify these deeply hypointense foci. • Deep T1-hypointensity may act as an easily detectable, surrogate marker for PRLs.
Insights
Phase-rim lesions (PRLs) in multiple sclerosis show distinct T1-hypointensity on 3D T1-weighted MRI. This deep hypointensity can serve as a surrogate biomarker for smoldering inflammation and disease progression.
Area of Science:
- Neuroimaging
- Radiology
- Neurology
Background:
- Developing prognostic biomarkers for progressive multiple sclerosis (MS) is crucial for new drug development.
- Phase-rim lesions (PRLs) are potential markers of MS progression but are challenging to identify and quantify.
- Previous research indicated T1-hypointensity within PRLs.
Purpose of the Study:
- To compare the intensity profiles of PRLs and non-PRL white-matter lesions (nPR-WMLs) using 3D T1-weighted turbo field echo (3DT1TFE) MRI.
- To evaluate a derived metric from T1-intensity as a surrogate for PRLs in predicting MS disease progression.
Main Methods:
- Enrollment of relapsing-remitting and secondary progressive MS patients (n=20) with 3T MRI data.
- Segmentation of PRLs and nPR-WMLs, followed by voxel-wise normalized T1-intensity histogram analysis.
- Classification prediction using the fifth-percentile (p5)-normalized T1-intensity, with lesions divided into training and test datasets.
Main Results:
- nPR-WMLs exhibited unimodal histograms, while PRLs showed bimodal histograms with a peak in the hypointense range.
- Analysis of 1075 nPR-WMLs and 39 PRLs revealed significantly lower p5 intensity in PRLs compared to nPR-WMLs.
- A T1 intensity-based PRL classifier achieved a sensitivity of 0.526 and specificity of 0.959.
Conclusions:
- Profound T1-hypointensity on 3DT1TFE MRI is a characteristic feature of PRLs, distinguishing them from other white-matter lesions.
- Quantitative analysis of 3DT1TFE MRI can detect deeply hypointense voxels specific to PRLs.
- This deep T1-hypointensity may function as an accessible surrogate biomarker for smoldering inflammation in MS, aiding in early detection of disease progression.
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