Alfaifi Bandar, Hinz Rainer, Jackson Alan, Wadeson Andrea, Pathmanaban Omar N, Hammerbeck-Ward Charlotte, Rutherford Scott A, King Andrew T, Lewis Daniel, Coope David J
Division of Informatics, Imaging and Data Sciences, School of Health Sciences, University of Manchester, Manchester, UK.
Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
Neurooncol Adv. 2024 Jun 8;6(1):vdae094. doi: 10.1093/noajnl/vdae094. eCollection 2024 Jan-Dec.
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.
Dynamic PET datasets from 15 patients with sporadic VS (8 static and 7 growing) who had been previously imaged using the TSPO tracer C-PK11195 were included. Parametric images of C-PK11195 binding potential (BP) 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 C-PK11195 binding.
Compared with static tumors, growing VS demonstrated significantly higher cortical (GM, 1.070 vs. 1.031, = .03) and whole brain (GM & WM, 1.045 vs. 1.006, = .03) C-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.
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.
非听觉症状可能是散发性前庭神经鞘瘤(VS)患者的一个突出特征,但这些症状的病因尚不清楚。炎症被认为在散发性VS的生长和症状表现中起关键作用,在本研究中,我们通过转位蛋白(TSPO)正电子发射断层扫描(PET)研究此类患者“看似正常”的脑内是否发生炎症及其与肿瘤生长的关系。
纳入15例散发性VS患者(8例肿瘤静止,7例肿瘤生长)的动态PET数据集,这些患者此前已使用TSPO示踪剂C-PK11195进行成像。得出C-PK11195结合潜能(BP)和分布容积比(DVR)的参数图像,并在对侧和同侧灰质(GM)和白质(WM)区域的VS生长组之间进行比较。另外进行了体素级聚类分析,以确定C-PK11195结合增加的解剖区域。
与静止性肿瘤相比,生长性VS的皮质(GM,1.070对1.031, = .03)和全脑(GM和WM,1.045对1.006, = .03)C-PK11195 DVR值显著更高。体素级分析支持基于区域的分析,并揭示了生长性VS患者中央前回、中央后回和前额叶皮质内存在高TSPO结合的簇。
我们首次提供了体内证据,证明生长性散发性VS患者脑内TSPO表达增加和存在炎症。这些结果为深入了解这些患者非听觉症状的发生机制提供了潜在线索,并强调需要进一步研究探讨神经炎症在VS症状形成中的作用。