Faculdade de Medicina, Universidade de São Paulo

Author Of 1 Presentation

Imaging Poster Presentation

P0531 - 11C-PIB PET showed a distinct cerebrospinal fluid pattern in patients with progressive multiple sclerosis (ID 1913)

Abstract

Background

Neurodegeneration attributed to axonal injury following myelin damage is present from the earliest stages of multiple sclerosis (MS), however, biomarkers to predict MS-related disability, particularly in progressive disease, are still lacking. Positron emission tomography (PET) using myelin-specific tracers has the potential to address more specific underlying in vivo pathology and broaden the understanding of heterogeneity between relapsing-remitting (RRMS) and progressive MS (PMS).

Objectives

To explore possible group differences in PET imaging with carbon-11-labeled Pittsburgh compound B (11C-PIB) among MS phenotypes and compare to healthy controls (HC).

Methods

11C-PIB PET images (40-60 min post-injection) and magnetic resonance imaging (MRI) were acquired in a hybrid PET/MRI system from 30 subjects with RRMS (21/9 women/men; mean age: 35.7, ± 7.6 years), 18 with PMS (primary, n = 11 and secondary, n = 7; 11/7 women/men; mean age: 49.9, ± 8.6 years) and 20 matched-controls (15/5 women/men; mean age: 41.4, ± 12 years ). 11C-PIB PET images were co-registered using PMODTM 4.0 to an individual 3D T1-weighted image after lesion filling (lesion segmentation tool from SPMTM 8). Voxel-based analysis with proportional scaling was performed with statistical parametric mapping (SPMTM 12), using analysis of variance model (ANOVA) among groups and t-tests between two groups. The differences were considered significant when p ≤ 0.05 corrected for multiple comparisons with family-wise error (FWE) and reported when a cluster size minimum of 200 voxels.

Results

Among MS phenotypes, there was a statistically significant difference regarding disability (p <0.001). In the RRMS group, the median EDSS was 2.5 (range, 1.0 - 6.0), while PMS had median EDSS 6.5 (range 3.5 - 7.5). ANOVA showed 11C-PIB uptake differences among groups (pFWE = 0.022) disclosing decreased 11C-PIB uptake in patients with MS relative to controls, being the lateral ventricles the only cluster region superior to 200 voxels. Decreased tracer uptake was observed in the lateral ventricles of RRMS compared to HC, but was not statistically significant (2447 voxels, z-score 4.01, pFWE = 0.219) and in the PMS group compared to HC, which was statistically significant (8245 voxels, z-score = 5.01 and pFWE = 0.004). Additional work will be performed using a supervised reference region to better understand the kinetics of the 11C-PIB PET in the ventricular system and its relationship with brain volume loss.

Conclusions

11C-PIB PET imaging showed a distinct pattern of CSF in the lateral ventricles among patients with MS and healthy controls in a voxel-based assessment, significantly in the PMS group. Similar findings were previously reported in patients with RRMS, supporting the potential role of CSF profile to distinguish phenotypes and patients at risk of disease activity or progression.

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