Acoustic aberration effects have been extensively studied over the years for high intensity focused ultrasound (HIFU) due to the significant therapeutic disruption they can cause in thermal ablation procedures, often rendering the treatment ineffective without the implementation of aberration correction mechanisms. Histotripsy therapy uses highly energetic cavitation bubble clouds to mechanically fractionate tissue. The cavitation bubble cloud initiation is dependent on a pressure threshold mechanism, which allows this process to be controlled by the pressure amplitude available at the focus. The work presented herein explores the therapeutic effects of acoustic aberration in the scope of histotripsy therapy and investigates the feasibility of conducting non-invasive histotripsy procedures without using correction mechanisms in distinct therapeutic contexts likely to introduce high degrees of acoustic aberration. The first context investigated is transcostal therapy. It is demonstrated that histotripsy therapy is able to generate precise lesions through rib obstacles without aberration correction despite the presence of large grating lobes in the focal profile. An in vivo study follows, in which comparable porcine liver lesions are created through windows with full and no ribcage obstruction, inducing no visible damage on overlying tissues. The second context investigates transabdominal fetal therapy. It is shown that histotripsy therapy can achieve precise fetal tissue ablation in sheep models through the intact maternal abdomen without aberration correction. A long-term study on the impact of the therapy in the course of pregnancy is conducted, indicating the potential safety of this technique for non-invasive fetal applications. The third, and perhaps the most challenging therapeutic context involves transcranial therapy. A large aperture array transducer is specifically designed, and a novel sonication mechanism using extremely short pulses with large negative pressures is introduced. It is shown that precise cavitation lesions can be successfully generated transcranially by careful modulation of the focal pressure amplitude. Overall results show that the pressure threshold mechanism governing the initiation of histotripsy bubble clouds lends the therapy a considerable degree of immunity against acoustic aberration effects, a feature, which in combination with the low thermal impact of the therapy would be highly beneficial for a variety of non-invasive therapeutic applications.
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Acoustic Aberration in Non-Invasive Histotripsy Therapy.