Brigham & Women's Hospital
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology

Author Of 1 Presentation

Pathogenesis – Role of Glia Late Breaking Abstracts

LB1224 - Thalamic and whole brain atrophy are linked with white matter microglial activation: A [F-18]PBR06-PET study in multiple sclerosis  (ID 2099)

Speakers
Presentation Number
LB1224
Presentation Topic
Pathogenesis – Role of Glia

Abstract

Background

Thalamic and whole brain atrophy have been extensively studied as biomarkers of neurodegeneration in multiple sclerosis but their mechanism is not clear. [F-18]PBR06-Positron Emission Tomography (PET) is a novel molecular imaging technique to assess microglial activation.

Objectives

To determine the relationship of thalamic and whole brain atrophy with white matter (WM) microglial activation in multiple sclerosis.

Methods

22 individuals (13 MS, including 8 relapsing-remitting and 5 secondary progressive, and 9 healthy control (HC)) subjects underwent 3T MRI and [F-18]PBR06-PET. Individualized z-score maps of WM microglial activation were generated by voxel-by-voxel comparison between each subject's PET SUVR images and a control dataset. Glial activity load on PET in WM (“GALP-WM”) was calculated as the sum of voxel-by-voxel z-scores ≥4 in the WM subjects and its logarithmic transformation (“ln-GALP”) was also obtained. "Z-max" score was calculated as the highest z-score in the WM matter averaged over surrounding 5 voxels. SIENAX and FSL-FIRST pipelines determined normalized brain parenchymal volume (BPV) and thalamic volumes (Th-V) respectively. A p-value <0.05 was considered statistically significant.

Results

Th-V and BPV were lower in MS vs. HC (19.7±2.2 vs. 22.4±1.6 ml, 1376.6±81.3 vs. 1475.1±70.9 ml, both p<0.01). GALP-WM, Z-max and ln-GALP were higher in MS vs. HC (18757.9±13646 vs. 7580.5±12216, 13.2±2.9 vs. 8.3±4.1, and 9.5±0.92 vs. 7.4±1.9, all p<0.05). Th-V and BPV were inversely correlated with WM microglial activation, represented by GALP-WM, Z-max and ln-GALP (r=-0.62, -0.66 and -0.62, all p<0.01 for Th-V and r=-0.68, -0.643 and -0.678, all p<0.01 for BPV) that remained significant after adjustment for age (all p<0.05).

Conclusions

Thalamic and whole brain atrophy are linked with white matter microglial activation in MS, representing a link between neuroinflammation and neurodegeneration across central nervous system compartments. Further investigation of the “GALP” method as a novel, individualized approach for evaluating glial activity in MS is warranted. Prospective longitudinal studies to determine the impact of therapeutically targeting microglial activation on neurodegeneration in MS patients are urgently needed.

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