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Published on: June 14, 2018
TSPO-PET Reveals Higher Inflammation in White Matter Disrupted by Paramagnetic Rim Lesions in Multiple Sclerosis
Ceren Tozlu1, Keith Jamison1, Yeona Kang2
1Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
Objective:
To explore whether the inflammatory activity is higher in white matter (WM) tracts disrupted by paramagnetic rim lesions (PRLs) and if inflammation in PRL-disrupted WM tracts is associated with disability in people with multiple sclerosis (MS).
Methods:
Forty-four MS patients and 16 healthy controls were included. 18 kDa-translocator protein positron emission tomography (TSPO-PET) with the 11C-PK11195 radioligand was used to measure the neuroinflammatory activity. The Network Modification Tool was used to identify WM tracts disrupted by PRLs and non-PRLs that were delineated on MRI. The Expanded Disability Status Scale was used to measure disability.
Results:
MS patients had higher inflammatory activity in whole brain WM compared to healthy controls (p=0.001). Compared to patients without PRLs, patients with PRLs exhibited higher levels of inflammatory activity in the WM tracts disrupted by any type of lesions (p=0.02) or PRLs (p=0.004). In patients with at least one PRL, inflammatory activity was higher in WM tracts highly disrupted by PRLs compared to WM tracts highly disrupted by non-PRLs (p=0.009). Elevated inflammatory activity in highly disrupted WM tracts was associated with increased disability in patients with PRL (p=0.03), but not in patients without PRL (p=0.2).
Interpretation:
This study suggests that patients with PRLs may exhibit more diffuse WM inflammation in addition to higher inflammation along WM tracts disrupted by PRLs compared to non-PRLs, which could contribute to larger lesion volumes and faster disability progression. Imaging PRLs may serve to identify patients with both focal and diffuse inflammation, guiding therapeutic interventions aimed at reducing inflammation and preventing progressive disability in MS.
Insights
Multiple sclerosis patients with paramagnetic rim lesions (PRLs) show higher white matter inflammation, which correlates with increased disability. This suggests PRLs indicate widespread inflammation and potential for faster disease progression.
Area of Science:
- Neuroimmunology
- Neuroimaging
- Clinical Neurology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
- Paramagnetic rim lesions (PRLs) represent a specific type of lesion in MS associated with active inflammation.
- Understanding the inflammatory activity within white matter (WM) tracts, particularly those affected by PRLs, is crucial for assessing disease severity and progression.
Purpose of the Study:
- To investigate whether white matter (WM) tracts disrupted by paramagnetic rim lesions (PRLs) exhibit higher inflammatory activity in multiple sclerosis (MS) patients.
- To determine if inflammation in PRL-disrupted WM tracts is associated with clinical disability in MS.
Main Methods:
- Utilized 18 kDa-translocator protein positron emission tomography (TSPO-PET) with 11C-PK11195 to quantify neuroinflammation.
- Employed the Network Modification Tool to identify WM tracts affected by PRLs and non-PRLs on MRI.
- Assessed clinical disability using the Expanded Disability Status Scale (EDSS).
Main Results:
- MS patients demonstrated significantly higher whole-brain WM inflammatory activity compared to healthy controls.
- Patients with PRLs showed elevated inflammatory activity in WM tracts affected by any lesions or specifically by PRLs compared to those without PRLs.
- Inflammatory activity was higher in WM tracts with PRLs versus non-PRLs, and this elevated inflammation correlated with increased disability in patients with PRLs.
Conclusions:
- PRLs in MS may be associated with more diffuse WM inflammation beyond focal lesions, potentially contributing to greater lesion burden and accelerated disability.
- TSPO-PET imaging of PRLs can identify patients with both focal and diffuse inflammation, aiding in targeted anti-inflammatory therapies to prevent disability progression.
