Advanced Ultrasound Imaging Techniques for Monitoring and Controlling Microrobots in Tissues

Medical microrobots (MMRs) are intelligent machines with different levels of autonomy and size in the micrometer scale, which hold the potential to radically transform several therapeutic tasks in hard-to-reach body districts. The procedures that MMRs could perform in a non-invasive fashion include targeted cargo delivery, bio-sensing and diagnosis, assisted fertilization, micro-surgery, and thrombolysis. In all the envisioned applications, therapy success is highly dependent on the ability to identify, monitor and control MMRs during operation inside the body. At present, there is no available medical imaging technique that simultaneously provides real-time feedback on MMRs with sufficient contrast, spatial resolution, and penetration depth in biological tissues. This thesis partly addresses this unmet need by introducing advanced Ultrasound-based imaging techniques that leverage the specific MMRs motions for improved imaging in the human body environments. A particular focus was given to the applicability of the proposed feedback strategy to different types of MMRs, for visualization, tracking, and image-guided visual-servoing in simulated in vivo conditions. The developed techniques were demonstrated to outperform traditional ultrasound imaging such as B-mode and Doppler, enabling MMRs position tracking with precision (error below 1 body-lenght) and robustness to environmental disturbances (e.g., echogenic tissues, physiological flows and tissue motions). Overall, the results reported in this thesis represent a fundamental advancement in the attempt to effectively bring microrobotics technologies to the clinical practice. The reminder of this thesis is organized as follows: The first chapter is intended to provide a comprehensive literature review on the most promising imaging solutions for monitoring MMRs operation inside the body. The physical principles behind every reported imaging technique are investigated, in the attempt to highlight their respective advantages and disadvantages in specific clinical applications, and to identify the most promising technologies for MMRs tracking in vivo. The second chapter describes the proposed ultrasound-based imaging solutions, developed to overcome some of the current limitations of traditional techniques, and presents the methodologies implemented for experimental validation in simulated body environments. The third chapter reports and discusses the experimental results obtained with the proposed techniques, with direct comparison to traditional B-mode and Doppler imaging. Different clinically relevant case studies were targeted, by considering several types of MMRs, different environmental conditions, and closed-loop control scenarios. In the fourth chapter, the conclusions of this work are drawn and the perspectives stemming from the reported results are envisioned and discussed.