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Biomedical Engineering pres.

Methods and Systems for Rapid, Noninvasive Ablation of a Large Tissue-Target Using Histotripsy

Final Oral Examination - Jonathan Lundt

Biomedical Engineering Biomedical Engineering
Biomedical Engineering
Percutaneous local ablation techniques including radiofrequency and microwave ablation are increasingly supplanting surgical resection as the standard of care for solid-tumor intervention due to lower risk of complications, lower costs, and shorter associated hospital stays. However, these techniques present several risks associated with device insertion and traditionally struggle to treat tumors greater than 3 cm in diameter. Thermally-based high intensity focused ultrasound (HIFU) and stereotactic body radiation (SBRT) are noninvasive but have been shown to cause significant collateral damage to adjacent healthy tissues and may require an excessively long treatment time. Thus, there is an unmet need for a noninvasive ablation technique capable of treating large tumors rapidly and safely.

Histotripsy is a completely extracorporeal, non-thermal ultrasound ablation technique which uses high-amplitude, short-duration, focused acoustic pulses at low duty cycle to homogenize target-tissue into an acellular slurry by means of finely-controlled acoustic cavitation. Previous studies have demonstrated that histotripsy is capable of noninvasive tissue-ablation in vivo for a broad spectrum of applications. This dissertation investigated methods and systems toward the clinical translation of histotripsy for the treatment of large-volume tissue-targets. Hepatocellular carcinoma (HCC) was selected as a test-case to frame development efforts.

In the first part of this dissertation, strategies for accelerating treatment based on electronic focal steering of a phased array histotripsy transducer were investigated. Research was centered around the management and manipulation of residual cavitation nuclei, hundreds of which are dispersed throughout the focus following collapse of the cavitation bubble cloud produced by each histotripsy pulse and perturb subsequent de novo cavitation at the intended focus. A novel method in which low-gain regions of the therapy beam were utilized to drive the coalescence of residual nuclei via the secondary Bjerknes force was developed and validated. Results demonstrated 99.9% complete ablation of a 27-mL volume (equivalent to a sphere 3.7 cm in diameter) within 30 s.

In the second part of this dissertation, compensation methods for respiratory motion of abdominal organs during histotripsy treatment were investigated. Like HIFU, SBRT, and several imaging modalities, histotripsy is sensitive to the periodic respiratory motion of abdominal organs, which oscillate with up to 4 cm peak-to-trough amplitude and at up to 3 cm/s during normal respiration. Without compensation for respiratory motion there is an elevated risk of under-treating target-tissue, damaging adjacent healthy tissues and prolonging treatment. This part of the dissertation reviews existing methods for respiratory motion compensation, explores the feasibility of integrating these methods with histotripsy therapy, and presents a novel cavitation-based motion tracking technique. Using this technique, residual cavitation nuclei were coalesced into a small bubble-system and used as an in situ fiducial marker which was tracked throughout a predefined trajectory by a histotripsy therapy system capable of receiving acoustic backscatter signals. Results demonstrated the feasibility of receiving acoustic signals from this fiducial cavitation bubble cloud throughout a 16-cm trajectory with a mean error of 0.7 ± 0.3 mm.

In the final part of the dissertation, novel design and fabrication techniques were developed for a real-time-ultrasound-imaging guided, highly steerable phased array histotripsy transducer for liver ablation featuring arbitrarily shaped, densely, packed, and easily replaceable elements. High-powered transducers are the key enabling technology for histotripsy. Our lab has demonstrated the use of rapid prototyping methods for the fabrication of histotripsy arrays but these techniques have been limited to producing arrays with low packing density (~60%). The transducer design methods presented herein implemented a series of algorithms which analyzed human CT data to define the geometry of the array’s aperture, divided the aperture into discrete, nesting elements, and simulated the electronic focal steering range of this aperture as a function of the number of elements into which it was divided. Novel fabrication methods facilitated a very small gap (0.5 mm) between active piezoelectric material which resulted in a packing density >90%. The design of the array is presented, and the fabrication process and performance of individual elements are described. Simulation shows that this array is capable of electronically steering over a range sufficient to treat tissue-targets up to 3.6 cm in diameter in porcine or human subjects.

Chair: Zhen Xu
Biomedical Engineering Biomedical Engineering
Biomedical Engineering
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