Technical note
Thermal effects of focused ultrasound energy on bone tissue

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Abstract

The effects of focused ultrasound (US) at therapeutic acoustic power levels were studied in vivo on the bone-muscle interface in rabbit thighs. The purpose of this study was to provide direction in establishing safety guidelines for treating tissue masses using focused US on or near bone. A positioning device was used to manipulate a focused US transducer (1.5 MHz) in a magnetic resonance imaging (MRI) scanner. This system was used to sonicate the femurs of 10 rabbits at acoustic power levels of 26, 39, 52 and 65 W for 10 s. The rabbits were euthanized either 4 h or 28 days after the sonications and the bone samples were harvested for histology examinations. In the femurs studied, acoustic power levels from 39 to 65 W resulted in soft tissue damage characterized grossly by coagulated tissue and bone damage depicted by yellow discoloration. Histologic examination of lesions from sonications from 39 to 65 W demonstrated that osteocyte damage and necrosis, characterized by pyknotic cells and empty lacunae, occurred within the ablation area extending through the bone. The follow-up MR images demonstrated an increase in the amount of damage in the femurs at 28 days posttreatment in comparison to images taken immediately after treatment. Focused US directed at the femur caused immediate significant thermal damage to bone in the form of osteocyte necrosis extending through the (approximately) 1 cm bone in this study. The results suggest that, when focused US energy is directed at or near bone-muscle interfaces, precautions should be taken to avoid thermal damage to the bone that can compromise its strength for extended periods. (E-mail: [email protected])

Introduction

Many studies have experimented with focused ultrasound (US) as a noninvasive method for treating soft tissue masses and for hyperthermic heating of tissue volumes ter Haar et al 1980, Ebbini and Cain 1991, Goss et al 1996, McGough et al 1996, Fujii et al 1999, Hurwitz et al 2001. In many cases, the mass of tissue that is treated is on or near bone Lin et al 2000, Lu et al 2000. For example, a high-intensity focused US device for the treatment of benign prostatic hyperplasia (BPH) has been used in clinical studies (Sanghvi et al. 1999). This clinical device has been successfully used for thermal ablation of diseased prostate tissue, although care must be taken during treatment due to the proximity of the prostate to the bony pelvis. Studies have shown that high temperatures are reached at the soft tissue/bone interface during exposure to US Lehmann et al 1967, Lehmann et al 1978, Hynynen and DeYoung 1988. This temperature elevation has caused pain during long US hyperthermia treatments, limiting the amount of power and, thus, temperatures in the tumor and in the bone. During US surgery, the patients are frequently sedated or anesthetized; this allows tumors next to the bone to be treated, but may expose the bone surface to high acoustic powers and temperatures. Therefore, the effects of the high-temperature elevations on the bone should be studied before such treatments are performed. It is generally assumed that thermal damage to the bone would be superficial due to the sharp temperature gradient Lehmann et al 1967, Lehmann et al 1978, Hynynen and DeYoung 1988. However, there are no studies demonstrating the extent of bone damage caused by a focused US surgery device. Given the increasing interest in using US for noninvasive treatment, the purpose of this study was to investigate thermal damage caused by focused US energy on bone tissue.

Section snippets

Equipment

The US field was generated by a single focused PZT, air-backed US transducer with diameter, radius of curvature and resonant frequency of 100 mm, 80 mm (F number = 0.8) and 1.5 MHz, respectively. The radiofrequency (RF) signal feeding the transducers was generated by a frequency generator (Wavetek Inc., San Diego, CA, Model 271) and amplified by an RF amplifier (ENI Inc., Rochester, NY, Model 2100L). The electrical impedance of the transducer was matched to the output impedance of the amplifier

Results

A typical pretreatment, axial T1-weighted scan of a rabbit and transducer shows the location of the transducer with respect to the femur-muscle interface (Fig. 2a). The depth of the heating from the transducer can be seen from a phase difference image (Fig. 2b) showing the focused US beam (dark area indicated by an arrow) in rabbit muscle at the femur during a 52-W acoustic power sonication. Damage (arrow) to the tissue and bone can be seen immediately posttreatment in the T1-weighted contrast

Discussion

At 23 W acoustic power, no significant bone damage was observed. This indicates a maximum safety level that would be acceptable during surgery at the bone surface. For both the acute and survival experiments of focused US near bone, the results indicate muscle and bone damage at sonication sites at power levels used in focused US surgery. Protein coagulation and consequent soft tissue damage in the form of necrosis resulted from the temperature elevation. Based on previous research, the

Acknowledgements

This research was funded by NIH grant CA46627. The authors acknowledge GE Medical Systems for providing the positioning system and the temperature-sensitive pulse sequences.

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