P09.02.A A WINDOW TO THE BRAIN: MONITORING THE HUMAN BRAIN USING FUNCTIONAL ULTRASOUND (FUS)-IMAGING IN FREELY MOVING SUBJECTS WITH AN ACOUSTICALLY FAVORABLE SKULL IMPLANT

Abstract BACKGROUND To this day, the mainstay of human neuroimaging remains (functional) Magnetic Resonance Imaging (fMRI), where subjects are asked to lie completely still and silent in a noisy scanner. Many key questions in clinical care and neuroscience remain poorly studied because of fMRI’s inability to facilitate natural behavior such as locomotion or even verbal speech. What is more, due to the cost and size of an (f)MRI-machine, monitoring of morphological (i.e. tumor regrowth) or functional changes in the human brain, pre- and post-tumor resection, is often spread out over intervals of many months, leaving patients in suspense about possible tumor regrowth.With the advent of ultrafast ultrasound imaging, a new high-resolution, depth-resolved and mobile neuro-imaging technique called functional Ultrasound (fUS) has emerged. In the last decade, fUS has been applied successfully in awake neurosurgical contexts to map out hemodynamics-based functional brain activity as well as tumor tissue at a mesoscopic scale. However, given the significant aberration of ultrasound signal through human skull bone, fUS is not available outside of OR as of yet. As a first step outside of the OR, we aimed to apply fUS in freely moving subjects with a skull bone defect covered by PEEK, an acoustically favorable material. MATERIAL AND METHODS Two subjects with PEEK-implants were repeatedly imaged over a period of >1 year. One of the subjects received a PEEK-implant after infection of the autologous bone, post-resection of an astrocytoma. Each subject received a custom-fitted 3D-printed helmet based on their MRI to fixate the probe and to attach the geometry needed for optical tracking. Using an optical tracking camera, the position of the Power Doppler Image (PDI) relative to CT/(f)MRI-volumes of the subject could be determined in real-time. Images were acquired using an experimental research system (Vantage-256, Verasonics) interfaced with a 9L-D linear array (GE, 5.3 MHz). All scans were acquired with a PRF of 800 Hz. The PDIs and angle compounded beamformed frames were stored for offline processing, consisting of 3D-vascular reconstructions and functional mapping. Functional tasks focused on the sensorimotor area of the lip. For measurements outside of the lab, the acquisition system was transformed into a mobile cart, which could be pushed by the subject itself. RESULTS Trans-PEEK imaging resulted in PDIs with highly detailed vasculature of healthy brain tissue and the resection cavity, up to several centimeters in-depth, reproduced reliably over a period of >12 months. In sedentary, standing and walking conditions, we were able to produce consistent functional maps of the human brain. CONCLUSION Our current work demonstrates how fUS has the potential to become a powerful window to the brain, both in terms of vascular monitoring of tumor regrowth, as well as functional brain mapping, outside of the operating room.