Abstract Details

Title Phenotyping Of Multiple Sclerosis Lesions According To Innate Immune Cell Activation Using TSPO-PET

Topic Multiple Sclerosis

Presentation(s) S26 - MS Imaging (1:24 PM-1:36 PM)

Poster/Presentation
Number 003

Background Chronic active lesions are promotors of neurodegeneration and disease progression in multiple sclerosis. They harbor a dense rim of activated innate immune cells at the lesion edge, which promote lesion growth and thereby induce damage.

Objective To develop a PET-based automated method for phenotyping of chronic multiple sclerosis lesions based on innate immune cell activation and to evaluate the prevalence of these lesions in the clinical subtypes of multiple sclerosis, and their association with disability.

Design/Methods

In total 1510 white matter T1-hypointense lesions were identified from the 67 relapsing-remitting (RRMS) and 24 secondary progressive (SPMS) patients. Innate immune cell activation at the lesion rim was measured using TSPO-PET-imaging and ¹¹C-PK11195-radioligand. A lesion was classified as rim-active if the distribution volume ratio of ¹¹C-PK11195-binding was low in the plaque core and considerably higher at the rim. If no significant ligand-binding was observed, the lesion was classified as inactive. Plaques that had considerable ligand-binding both in core and at rim were classified as overall-active. MRI and Expanded Disability Status Scale (EDSS) were performed simultaneously with PET-imaging.

Results In the SPMS cohort, an average of 19% (median, IQR 11-26) of T1 lesions were rim-active in each individual patient, compared to 10% (IQR 0-20) among RRMS patients (P=0.009). SPMS patients had a median of 3 (range 0-18) rim-active lesions, vs. 1 (range 0-11) among RRMS (P=0.029). Among the patients with rim-active lesions (n=63) the average number of active voxels at the rim was higher among SPMS versus RRMS (median 158 vs.74; P=0.022). The number of active voxels at the rim correlated significantly with EDSS (R=0.43,P<0.001), and the volume of the rim-active lesions similarly correlated with EDSS (P<0.001).

Conclusions Patients with higher disability displayed a higher proportion of rim-active lesions. The methodology offers a new tool for individual assessment of smoldering lesion burden.

Authors/Disclosures
Marjo Nylund (Turku University Hospital) PRESENTER	Ms. Nylund has received research support from The Finnish MS Foundation. Ms. Nylund has received research support from Maire Taponen Foundation. Ms. Nylund has received research support from The Finnish Cultural Foundation.
Marcus Sucksdorff, MD (University of Turku)	Dr. Sucksdorff has nothing to disclose.
	No disclosure on file
Eero Polvinen	Mr. Polvinen has nothing to disclose.
	No disclosure on file
Laura Airas, MD, PhD (Turku University Hospital)	The institution of Dr. Airas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. The institution of Dr. Airas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.