NIMG-44. ELEVATED TRANSLOCATOR PROTEIN 18KDA BINDING IN LOW MEAN DIFFUSIVITY CLUSTERS IS A FEATURE OF THE TRANSFORMING GLIOMA AND IDH MUTANT GLIOMA MICROENVIRONMENT

Abstract

Abstract Around 95% of low-grade gliomas undergo anaplastic de-differentiation into high-grade gliomas, a process only partially understood from in vivo clinical imaging. 11 patients with suspected transforming gliomas underwent a combined magnetic resonance imaging (MRI) and positron emission tomography (PET) protocol, incorporating post-contrast T1-weighted/FLAIR acquisition for tumour delineation and diffusion tensor imaging. The PET radiotracer [11C]-(R)-PK11195 assessed translocator protein 18kDa (TSPO) distribution, whose upregulation is associated with inflammation/glioma progression. [11C]-(R)-PK11195 binding potential (BPND) maps were generated using the simplified reference tissue model, with the grey-matter cerebellar time-activity curve serving as the reference tissue input function. KMeans clustering of mean diffusivity (MD) intensity values defined spatially distinct “habitats” of high/low MD voxels within the glioma microenvironment. BPND values within high/low MD clustering habitats were evaluated, across glioma grades and isocitrate dehydrogenase (IDH) mutational status. Across all grade 2 and 3 gliomas (n= 6), mean TSPO BPND values in low MD habitats (0.0383 ±0.102) were significantly greater than high MD habitats (-0.045 ±0.142) (p= 0.003). In grade 4 gliomas (n= 5), no significant difference was observed in mean BPND values between low (0.514 ±0.176) and high (0.465 ±0.296) MD habitats (p= 0.543). IDH mutant gliomas (n= 7) exhibited significantly higher mean BPND in low MD habitats (0.116 ±0.225), relative to high habitats (0.052 ±0.287) (p= 0.021). IDH wildtype gliomas (n= 4) showed no significant differences between BPND values in low (0.498 ±0.199) and high MD habitats (0.424 ±0.325) (p= 0.467). Our novel findings demonstrate spatial heterogeneity in TSPO expression within 2/3/IDH mutant gliomas, a characteristic absent from grade 4/IDH wildtype varieties. Regions of restricted diffusion with high TSPO signal in grade 2/3/IDH mutant tumours indicate the heterogenous distribution of active TSPO-expressing immune/neoplastic cell populations, contrasting the homogenous distribution in grade 4/IDH wildtype gliomas, highlighting differences between their inflammatory profile and pathological features.