Transcranial focused ultrasound stimulation for treatment-refractory depression

Abstract

Introduction: The transcranial focused ultrasound (tFUS) has been studied over the past decade as a potential tool for neuromodulation in humans. Although studies have been promising so far, the translation into clinical practice is still challenging. Objectives: The primary objective of this study is to develop a reproducible, clinically reliable methodology for low-intensity transcranial focused ultrasound in patients with treatment-resistant depression (TRD). To address the challenges to implement a treatment protocol, a systematic review, as well as optimization of the neuronavigation and targeting were developed. These steps were needed to finally develop a neurostimulation protocol and a pilot study. Methods: Each step of the process is composed by its own methods. The materials evolved during the course of the thesis to fit into the hardware and software available in the Centro de Tecnologia Molecular at the Federal University of Minas Gerais. Results: A systematic review was performed and described the evolution of tFUS research in humans along the years. No study in humans to treat depression was found. Neuronavigation was considered a major concern, especially for deep brain targets. Therefore, an opensource neuronavigation method was optimized to fit user-friendliness and to be adopted in a future clinical trial. To improve targeting procedures, a computational model of the International 10-20 System was studied to correctly place the transducer in real-time neuronavigation. Finally, a clinical trial protocol was stablished using the software and hardware available, leading to a pilot study with the first patient enrolled in the study. Conclusions: The tFUS is a promising neuromodulation method. This thesis provides improvements in neuromodulation procedures and proposes a clinical trial to assess the safety and efficacy of repeated sessions for TRD. However, there is still a need of replication of these methods by different centers, as well as the assessment of safety and efficacy.