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Targeted vascular occlusion is desirable for clinical therapies such as in the treatment of esophageal and gastric varices and varicose veins. The feasibility of ultrasound-mediated endothelial damage for vascular occlusion was studied. A segment of a rabbit auricular vein was treated in vivo with low duty-cycle, high peak rarefaction pressure (9 MPa) high-intensity focused ultrasound (HIFU) pulses in the presence of intravenously administered circulating microbubbles, followed by fibrinogen injection, which resulted in the formation of an acute occlusive intravascular thrombus. Further investigation and refinements of treatment protocols are necessary for producing durable vascular occlusion.

Background: High-intensity focused ultrasound (HIFU) has been in clinical use for a variety of solid tumors and cancers. Accurate and reliable calibration is in a great need for clinical applications. An extracorporeal clinical HIFU system applied for the investigational device exemption (IDE) to the Food and Drug Administration (FDA) so that evaluation of its characteristics, performance, and safety was required.Methods: The acoustic pressure and power output was characterized by a fiber optic probe and a radiation force balance, respectively, with the electrical power up to 2000 W. An in situ acoustic energy was established as the clinical protocol at the electrical power up to 500 W. Temperature elevation inside the tissue sample was measured by a thermocouple array. Generated lesion volume at different in situ acoustic energies and pathological examination of the lesions was evaluated ex vivo.Results: Acoustic pressure mapping showed the insignificant presence of side/grating lobes and pre-or post-focal peaks (≤−12 dB). Although distorted acoustic pressure waveform was found in the free field, the nonlinearity was reduced significantly after the beam propagating through tissue samples (i.e., the second harmonic of −11.8 dB at 500 W). Temperature elevation was <10°C at a distance of 10 mm away from a 20-mm target, which suggests the well-controlled HIFU energy deposition and no damage to the surrounding tissue. An acoustic energy in the range of 750-1250 J resulted in discrete lesions with an interval space of 5 mm between the treatment spots. Histology confirmed that the lesions represented a region of permanently damaged cells by heat fixation, without causing cell lysis by either cavitation or boiling.Conclusions: Our characterization and ex vivo evaluation protocol met the IDE requirement. The in-situ acoustic energy model will be used in clinical trials to deliver almost consistent energy to the various targets.

Esophageal and gastric varices are associated with significant morbidity and mortality for cirrhotic patients. The current modalities available for treating bleeding esophageal and gastric varices, namely endoscopic band ligation and sclerotherapy, require frequent sessions to obtain effective thrombosis and are associated with significant adverse effects. A more effective therapy that results in long-term vascular occlusion has the potential to improve patient outcomes. In this study, we investigated a new potential method for inducing long-term vascular occlusion by targeting segments of a rabbit’s auricular vein in vivo with low duty cycle, high peak rarefaction pressure (9 MPa) pulsed high-intensity focused ultrasound in the presence of intravenously administered ultrasound microbubbles followed by local injection of fibrinogen and a pro-inflammatory agent (ethanol, cyanoacrylate or morrhuate sodium). The novel method introduced in this study resulted in acute and long-term complete vascular occlusions when injecting a pro-inflammatory agent with fibrinogen. Future investigation and translational studies are needed to assess its clinical applicability.

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