Acoustic droplet vaporization for enhancement of thermal ablation by high intensity focused ultrasound

Abstract

Rationale and objectives: Acoustic droplet vaporization (ADV) shows promise for spatial control and acceleration of thermal lesion production. The investigators hypothesized that microbubbles generated by ADV could enhance high-intensity focused ultrasound (HIFU) thermal ablation by controlling and increasing local energy absorption.

Materials and methods: Thermal lesions were produced in tissue-mimicking phantoms using focused ultrasound (1.44 MHz) with a focal intensity of 4000 W · cm(-2) in degassed water at 37°C. The average lesion volume was measured by visible change in optical opacity and by T2-weighted magnetic resonance imaging. In addition, in vivo HIFU lesions were generated in a canine liver before and after an intravenous injection of droplets with a similar acoustic setup.

Results: Thermal lesions were sevenfold larger in phantoms containing droplets (3 × 10(5) droplets/mL) compared to phantoms without droplets. The mean lesion volume with a 2-second HIFU exposure in droplet-containing phantoms was comparable to that made by a 5-second exposure in phantoms without droplets. In the in vivo study, the average lesion volumes without and with droplets were 0.017 ± 0.006 cm(3) (n = 4; 5-second exposure) and 0.265 ± 0.005 cm(3) (n = 3; 5-second exposure), respectively, a factor of 15 difference. The shape of ADV bubbles imaged with B-mode ultrasound was very similar to the actual lesion shape as measured optically and by magnetic resonance imaging.

Conclusion: ADV bubbles may facilitate clinical HIFU ablation by reducing treatment time or requisite in situ total acoustic power and provide ultrasonic imaging feedback of the thermal therapy.

Figure 1

Size distribution of the perfluoropentane droplets.

Figure 2

Experimental setup of HIFU. The spherical section transducer is comprised of a center “imaging” element (A) surrounded by the annular “therapy” element (B). In this study, only the “therapy” element was used to generate thermal lesions. A cylindrical phantom (30 mm in diameter and 30 mm in length) is facing the transducer, and a HIFU lesion is generated at the depth of 15 mm in the phantom. A needle-type thermocouple enters the phantom from the side with the tip 2 mm away from the transducer focus.

Figure 3

The lateral beam profile at the focus of the therapy transducer (a) and the waveform acquired by the hydrophone (b).

Figure 4

Visible, macroscopic image (a) of cross-sections of HIFU lesions generated by 5 s of ultrasound exposure. In the macroscopic image, an impressive increase in lesion size is observed with droplets in concentrations of 0, 10⁴, and 10⁵ droplets/mL (from left to right). The MRI image (b) of the lesion with a droplet concentration of 10⁵ droplets/mL is in good agreement with the macroscopic finding (phantom on the right). The denatured and cross-linked proteins in the lesion provide a significant decrease the water proton mobility and thereby a decrease in water proton T₂.

Figure 5

Visible lesion volumes versus HIFU exposure duration. Each point corresponds to the average of the visible volume measured on 5 to 8 specimens at fixed experimental conditions.

Figure 6

Visible, macroscopic images (a and b) and B-mode images (c and d) of the same HIFU lesion. The top two images are in the lateral-elevational plane and the bottom two are in the axial-elevational plane. The therapy transducer and the imager were faced up towards the B-mode image (d).

Figure 7

Images displayed by thresholding the MRI data. 3D image of the layout of the HIFU lesions in the liver (a) and a corresponding projection image (b) indicating the diameters of these lesions (bar = 10 mm). The lesions at the bottom of the image, generated after ADV, were partial lesions formed at the thin edge of the liver. Therefore, they were excluded from the volume estimation.

Figure 8

Comparison of macroscopic, T₂-weighted MR and ultrasound images (left to right) of 5 s lesions without (top) and with (bottom) ADV. The shape and size of the lesion in these images are comparable indicating ultrasonic imaging of the bubbles may provide a guide for the HIFU treatment (bar = 5 mm).