Evidence for inflammation in normal-appearing brain regions in patients with growing sporadic vestibular schwannoma: A PET study

Author:

Alfaifi Bandar1,Hinz Rainer1ORCID,Jackson Alan1,Wadeson Andrea23,Pathmanaban Omar N234,Hammerbeck-Ward Charlotte2,Rutherford Scott A23,King Andrew T235,Lewis Daniel236ORCID,Coope David J236

Affiliation:

1. Division of Informatics, Imaging and Data Sciences, School of Health Sciences, University of Manchester , Manchester , UK

2. Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre , Manchester , UK

3. Geoffrey Jefferson Brain Research Centre, University of Manchester , Manchester , UK

4. Division of Cell Matrix Biology & Regenerative Medicine, School of Biological Sciences, University of Manchester , Manchester , UK

5. Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester , Manchester , UK

6. Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester , Manchester , UK

Abstract

Abstract Background Nonauditory symptoms can be a prominent feature in patients with sporadic vestibular schwannoma (VS), but the cause of these symptoms is unknown. Inflammation is hypothesized to play a key role in the growth and symptomatic presentation of sporadic VS, and in this study, we investigated through translocator protein (TSPO) positron emission tomography (PET) whether inflammation occurred within the “normal appearing” brain of such patients and its association with tumor growth. Methods Dynamic PET datasets from 15 patients with sporadic VS (8 static and 7 growing) who had been previously imaged using the TSPO tracer [11C](R)-PK11195 were included. Parametric images of [11C](R)-PK11195 binding potential (BPND) and the distribution volume ratio (DVR) were derived and compared across VS growth groups within both contralateral and ipsilateral gray (GM) and white matter (WM) regions. Voxel-wise cluster analysis was additionally performed to identify anatomical regions of increased [11C](R)-PK11195 binding. Results Compared with static tumors, growing VS demonstrated significantly higher cortical (GM, 1.070 vs. 1.031, P = .03) and whole brain (GM & WM, 1.045 vs. 1.006, P = .03) [11C](R)-PK11195 DVR values. The voxel-wise analysis supported the region-based analysis and revealed clusters of high TSPO binding within the precentral, postcentral, and prefrontal cortex in patients with growing VS. Conclusions We present the first in vivo evidence of increased TSPO expression and inflammation within the brains of patients with growing sporadic VS. These results provide a potential mechanistic insight into the development of nonauditory symptoms in these patients and highlight the need for further studies interrogating the role of neuroinflammation in driving VS symptomatology.

Funder

EPSRC Cancer Imaging Centre

Publisher

Oxford University Press (OUP)

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