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Published on: March 1, 2017
Glial Activity Load on PET Reveals Persistent "Smoldering" Inflammation in MS Despite Disease-Modifying Treatment: 18
Tarun Singhal, Steven Cicero1, Eero Rissanen1
1From the Department of Neurology, PET Imaging Program in Neurologic Diseases.
Purpose Of The Report:
18 F-PBR06-PET targeting 18-kDa translocator protein can detect abnormal microglial activation (MA) in multiple sclerosis (MS). The objectives of this study are to develop individualized mapping of MA using 18 F-PBR06, to determine the effect of disease-modifying treatment (DMT) efficacy on reducing MA, and to determine its clinical, radiological, and serological correlates in MS patients.
Patients And Methods:
Thirty 18 F-PBR06-PET scans were performed in 22 MS patients (mean age, 46 ± 13 years; 16 females) and 8 healthy controls (HCs). Logarithmically transformed "glial activity load on PET" scores (calculated as the sum of voxel-by-voxel z -scores ≥4), "lnGALP," were compared between MS and HC and between MS subjects on high-efficacy DMTs (H-DMT, n = 13) and those on no or lower-efficacy treatment, and correlated with clinical measures, serum biomarkers, and cortical thickness.
Results:
Cortical gray matter (CoGM) and white matter (WM) lnGALP scores were higher in MS versus HC (+33% and +48%, P < 0.001). In H-DMT group, CoGM and WM lnGALP scores were significantly lower than lower-efficacy treatment ( P < 0.01) but remained abnormally higher than in HC group ( P = 0.006). Within H-DMT patients, CoGM lnGALP scores correlated positively with physical disability, fatigue and serum glial fibrillary acid protein levels ( r = 0.65-0.79, all P 's < 0.05), and inversely with cortical thickness ( r = -0.66, P < 0.05).
Conclusions:
High-efficacy DMTs decrease, but do not normalize, CoGM and WM MA in MS patients. Such "residual" MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration. Individualized mapping of translocator protein PET using 18 F-PBR06 is clinically feasible and can potentially serve as an imaging biomarker for evaluating "smoldering" inflammation in MS patients.
Insights
High-efficacy treatments reduce microglial activation in multiple sclerosis (MS) but do not normalize it. Residual inflammation in the brain is linked to disability and degeneration, highlighting the need for advanced imaging biomarkers.
Area of Science:
- Neuroimaging
- Immunology
- Neurology
Background:
- 18-kDa translocator protein (TSPO) PET imaging with 18F-PBR06 detects microglial activation (MA) in multiple sclerosis (MS).
- Understanding the impact of disease-modifying treatments (DMTs) on MA and its correlates is crucial for MS management.
Purpose of the Study:
- To develop individualized mapping of MA using 18F-PBR06 PET.
- To assess the efficacy of high-efficacy DMTs in reducing MA.
- To identify clinical, radiological, and serological correlates of residual MA.
Main Methods:
- 30 18F-PBR06-PET scans in 22 MS patients and 8 healthy controls (HCs).
- Calculation of logarithmically transformed glial activity load on PET (lnGALP) scores.
- Comparison of lnGALP between MS patients and HCs, and between DMT groups; correlation with clinical, biomarker, and imaging data.
Main Results:
- MS patients exhibited higher cortical gray matter (CoGM) and white matter (WM) lnGALP scores than HCs.
- High-efficacy DMTs significantly reduced lnGALP but did not normalize it compared to HCs.
- In H-DMT patients, CoGM lnGALP correlated with disability, fatigue, serum GFAP, and inversely with cortical thickness.
Conclusions:
- High-efficacy DMTs decrease but do not eliminate MA in MS patients.
- Residual MA in CoGM is associated with clinical disability, serum biomarkers, and cortical degeneration.
- 18F-PBR06 PET offers a feasible imaging biomarker for evaluating "smoldering" inflammation in MS.
