Transcranial Pulse Stimulation with Ultrasound in Alzheimer’s disease – A new navigated focal brain therapy

Abstract

Ultrasound-based brain stimulation techniques offer an exciting potential to modulate the human brain in a highly focal and precisely targeted manner. However, for clinical applications the current techniques have to be further developed. We introduce a new ultrasound stimulation technique, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) and describe a first navigable clinical TPS system. Feasibility, safety and preliminary (uncontrolled) efficacy data in Alzheimers disease (AD) are provided. Simulation data, in vitro measurements with rat and human skulls/brains and clinical data in 35 AD patients were acquired in a multicentric setting (including CERAD scores and functional MRI). Preclinical results show large safety margins and patient results show high treatment tolerability. Neuropsychological scores improved significantly when tested immediately as well as 1 and 3 months after stimulation and fMRI data displayed significant connectivity increases within the memory network. The results encourage broad neuroscientific application and translation of the new method to clinical therapy and randomized sham-controlled studies.