653. Effects of 10Hz transcranial focused ultrasound stimulation at the posterior cingulate cortex on cerebral glucose metabolism – a pilot fPET study

Abstract

Abstract Background Transcranial focused ultrasound stimulation (TUS) is emerging as a promising method for non-invasive and safe modulation of neuronal activity throughout the human brain [1]. Although several centers worldwide have started to investigate TUS in patient collectives, dosing of sonication parameters remains challenging. This is because conventional imaging approaches are limited in objectively measuring stimulation effects. This gap underscores the need for an innovative outcome measure to enhance the basic comprehension, as well as for planning and monitoring of interventions. To address this need, this project aims to assess the effects of TUS on the cerebral glucose metabolism, assessed with functional positron emission tomography (fPET). As target for the proof of principle, we chose to stimulate the posterior cingulate cortex (PCC), a metabolically relevant hub of the default mode network [2]. Aims & Objectives This work aims to assess whether the 10Hz TUS protocol stimulating the PCC is reflected in the cerebral glucose metabolism. Method Initially, 10 healthy participants were included in this single-blinded, pseudo-randomized, sham-controlled interventional pilot study. While 3 participants dropped out due to technical and organizational reasons, 7 successfully completed all study procedures (3 females, mean age: 26.14 ± 3.64 years). Participants underwent an online stimulation of the PCC (neuronavigated MNI coordinate x=-5, y=-35, z=35) during the fPET scan. Subjects were scanned on a long axial field of view Biograph Vision Quadra PET/CT. An ultra-low dose CT was acquired for PET attenuation correction. The 45min PET scan was initiated simultaneously with application of [18F]FDG (bolus+constant infusion, 5.47 MBq/kg). After 10min of baseline measurement, subjects were exposed to pseudorandomized stimuli (60x30s=30min comprising three distinct pseudorandomized stimuli each followed by 30” resting baseline). The stimuli were bone-conducted auditory stimuli (1) a 440Hz pure tone and (2) a sham stimulus that mimicked the audible effects of the verum, and (3) focused ultrasound. TUS was applied with a free-field Isppa of 30W/cm2, acoustic simulations estimated a mean in situ Isppa: 4.29 ± 0.46W/cm2, adhering to ITRUSST safety standards [3]. Percent signal change (PSC) in glucose metabolism, a simplified fPET outcome parameter [4], was calculated using the fPET toolbox [5]. Regressors were defined for each of the three stimulus conditions. PSC for the ultrasound condition were extracted on a whole-brain level as well as at the PCC (sphere 5 mm radius at the target coordinate) and evaluated with a one-sample t-test. Results The region-wise analysis revealed a significant effect of TUS as compared to baseline at the target, mean PSC= 8.96±8.31 (p = 0.029). The whole-brain analysis did not reveal significant differences between the three stimuli. Discussion & Conclusions The results suggest that 10Hz focused ultrasound stimulation of the PCC results in ~9% increase of glucose metabolism at the targeted area. However, as the whole-brain analysis did not show significant changes, these data remain to be replicated in well-powered larger studies. Importantly, since this is the first study to examine fPET and TUS simultaneously, it should be noted that establishing routine procedures and overcoming technical challenges was part of this pilot project.