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Acoustic Droplet Vaporization for Enhancement of Thermal Ablation by High Intensity Focused Ultrasound

Posted Aug 31, 2011 Updated Apr 10, 2023
By Man Zhang MD PhD , Mario L. Fabiilli PhD , Kevin J. Haworth PhD , Frederic Padilla PhD , Scott D. Swanson PhD , Oliver D. Kripfgans PhD , Paul L. Carson PhD , Jeffrey Brian Fowlkes PhD
14 min read

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.

Each year, >500,000 new cases of liver cancer are diagnosed worldwide, and the incidence is continuously increasing in the United States . Although surgical resection and liver transplantation are curative , only 20% to 30% of patients are suitable for surgery, because of contraindications and a limited number of donors . Overall, the 5-year survival rates of liver cancer are <10% . For these reasons, minimally invasive thermal therapies, including radiofrequency ablation and high-intensity focused ultrasound (HIFU) have been developed and are currently being used or evaluated for the treatment of liver masses. HIFU therapy is a noninvasive technique wherein focused ultrasound beams are emitted from a high-powered transducer to thermally ablate a tissue volume inside the body. HIFU systems commonly operate in a frequency range of 1 to 5 MHz, generating high focal intensities up to 30 kW · cm −2 . Such intensities can increase the tissue temperature beyond 60°C within the focal volume in seconds, resulting in irreversible protein denaturation, cell destruction, and associated coagulative necrosis . Two principal mechanisms, direct absorption of the transmitted pressure wave and acoustic cavitation, may cause tissue heating synergistically . The initial applications of HIFU on biologic tissues were proposed by Lynn et al . Later, Burov suggested using HIFU to treat malignant tumors. The bioeffects and specific properties of focused ultrasound on tissues have been investigated in further studies , and the physical principles associated with HIFU are becoming better understood .

HIFU treatment has distinct advantages over other focal ablative therapies. It is noninvasive and nonionizing. The focused energy is sufficient to induce thermal coagulation in a small volume within seconds, so the blood perfusion effects are minimized . However, a major difficulty has been creating homogenous, reproducible, and uniformly shaped lesions and producing these in such a manner as to treat large volumes at a rate that does not damage overlying tissues but achieves full treatment in a clinically manageable time period.

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Materials and methods

Perfluoropentane Droplet Preparation

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Figure 1, Size distribution of the perfluoropentane droplets.

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Tissue-mimicking Phantom Study

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Figure 2, Experimental setup of in vitro high-intensity focused ultrasound (HIFU). The spherical section transducer is composed 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 ( top ) and the waveform acquired by the hydrophone ( bottom ).

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In Vivo HIFU in Canine Liver

Animal preparation

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HIFU lesion generation

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Lesion Size Estimation Using Ultrasound, Visible Macroscopic Imaging, and Magnetic Resonance Imaging (MRI)

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Figure 4, Visible, macroscopic image (a) of cross-sections of high-intensity focused ultrasound lesions generated by 5 seconds of ultrasound exposure. In the macroscopic image, an impressive increase in lesion size is observed with droplets in concentrations of 0, 10 4 , and 10 5 droplets/mL ( from left to right ). The magnetic resonance image (b) of the lesion with a droplet concentration of 10 5 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.

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Statistical Analysis of Thermal Lesion Volume

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Results

In Vitro Phantom Study

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Table 1

Comparison of Lesion Volume Measured by MRI and Visible Macroscopic Imaging with 4 Seconds of HIFU Exposure

Droplet Concentration (droplets/mL) MRI Volume (cm 3 ) Optical Volume (cm 3 ) 0 (n = 8) 0.05 ± 0.01 0.04 ± 0.01 10 4 (n = 5) 0.10 ± 0.01 0.12 ± 0.02 10 5 (n = 8) 0.29 ± 0.05 0.30 ± 0.05 10 6 (n = 8) No lesion No lesion

At the concentration of 10 6 droplets/mL, copious acoustic droplet vaporization bubbles were observed, but no lesions were detected by either visible, macroscopic imaging or MRI, possibly because of the backscatter from the high-density acoustic droplet vaporization bubbles advancing the droplet vaporization proximally to shadow the focus.

HIFU, high-intensity focused ultrasound; MRI, magnetic resonance imaging.

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Figure 5, Visible lesion volumes versus high-intensity focused ultrasound (HIFU) exposure duration. Each point corresponds to the average of the visible volume measured on five to eight specimens at fixed experimental conditions.

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Figure 6, Visible, macroscopic images (a,b) and B-mode images (c,d) of the same high-intensity focused ultrasound 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 toward the B-mode image (d) .

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In Vivo Liver Study

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Figure 7, Images displayed by thresholding the magnetic resonance imaging data. Three-dimensional image of the layout of the high-intensity focused ultrasound 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 acoustic droplet vaporization, were partial lesions formed at the thin edge of the liver. Therefore, they were excluded from the volume estimation.

Figure 8, Comparison of macroscopic (a) , T2-weighted magnetic resonance (b,c) , and ultrasound images (d,e) of 5-second lesions without ( top ) and with ( bottom ) acoustic droplet vaporization. The shape and size of the lesion in these images are comparable indicating that ultrasonic imaging of the bubbles may provide a guide for the high-intensity focused ultrasound treatment (bar = 5 mm).

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Discussion

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Conclusions

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Acknowledgments

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Academic Radiology, Volume 18, Issue 9
Journals General Radiology
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