High Intensity Focused Ultrasound

As an ultrasound wave propagates though biologic tissues, or any medium that is not ideally viscoelastic, it is progressively absorbed and the energy is converted to heat. If the ultrasound beam is brought to a tight focus at a selected depth within the body, the high energy density produced in this region results in temperatures exceeding the threshold level of protein denaturation. As a consequence coagulative necrosis occurs.

The energy drops sharply outside the focal zone so that overlying and surrounding tissues remain unchanged. This creates an extremely sharp border between ablated and undamaged tissues. The size and location of the ablated region depend on the shape of the piezoceramic element and its respective focusing system, the ultrasound frequency and duration of insonication, the absorption coefficient of the incident tissues, and the site intensity achieved (12,38,39). In a defined biologic environment, the size of the thermal lesion can be controlled by the power and duration of the ultrasound pulse (40). With higher in situ intensities (>3500 W/cm3), cavitation phenomena with bubble implosion and mechanical tissue disruption are added, which are more difficult to control (41,42).

The antineoplastic effect of high-intensity focused ultrasound has been clearly demonstrated in vivo in a number of experimental settings.

Kishi and coworkers (43) reported on a significant reduction of implanted glioma tumors following high-intensity focused ultrasound-treatment using 1000 W/cm2 for two seconds at a frequency of 0.944 MHz. Fry and Johnson (44) implanted hamster medulloblastoma cells in rats, which were subsequently treated by high-intensity focused ultrasound (900 W/cm2, 1 MHz, seven seconds). The tumor cure rate was 29% in rats treated with high-intensity focused ultrasound and 40% in rats given a combination of high-intensity focused ultrasound and chemotherapy. Moore et al. (45) studied the effect of high-intensity focused ultrasound on the Morris 3924-A hepatoma implanted in rats. The tumor volumes in treated animals were subs-tantially smaller than those in the untreated control group. However, although the entire tumor was included in the target zone, no tumor was completely destroyed. Chapelon and associates (46) reported on the effect of high-intensity focused ultrasound on the Dunning R3327 prostatic adenocarcinoma implanted in Copenhagen rats. In Study 2 of this series, 25 rats with AT2 subline implants were treated with an acoustic intensity of 820 W/cm2. Complete tumor necrosis was achieved with this acoustic intensity in 24 cases (96%), and 16 lesions (64%) appeared to be cured, whereas all rats in the control group died of progressive tumor growth within 60 days of tumor implantation.

These data demonstrate that high-intensity focused ultrasound applied extracorpo-really is capable of inducing precise, well-controlled contact- and irradiation-free in-depth tissue destruction. However, it needs to be emphasized that none of these experimental studies were 100% successful.

In all series, some local recurrences were seen or viable cells were identified within the target zone. The reason for this phenomenon is not fully understood; most likely, the efficacy of each high-intensity focused ultrasound shot might vary, and the penetration of the ultrasound beam into tissue could be reduced in certain circumstances, such as by tissue (micro)cavitation.

The potential use of high-intensity focused ultrasound for oncologic indications raises the important issue of whether such treatment hinders or accelerates the formation of distant metastases. In various studies, no evidence of increased rate of metastases has been reported (Table 1) (46-50). Chapelon and associates (46) determined the impact of high-intensity focused ultrasound on the development of metastases of

As an ultrasound wave propagates though biologic tissues, or any medium that is not ideally viscoelastic, it is progressively absorbed and the energy is converted to heat. If the ultrasound beam is brought to a tight focus at a selected depth within the body, the high energy density produced in this region results in temperatures exceeding the threshold level of protein denaturation. As a consequence coagulative necrosis occurs.

The antineoplastic effect of high-intensity focused ultrasound has been clearly demonstrated in vivo in a number of experimental settings.

These data demonstrate that high-intensity focused ultrasound applied extracorporeally is capable of inducing precise, well-controlled contact- and irradiation-free in-depth tissue destruction. However, it needs to be emphasized that none of these experimental studies were 100% successful.

TABLE 1 ■ Rate of Metastases After in Vivo High-Intensity Focused Ultrasound of Experimental Tumors

Authors

Model

Rate of metastasis controls (%)

HIFU (%)

Goss and Fry (47)

Joshida sarcoma

43

26

Yang et al. (48)

Hepatoma 3924° in rats

21

4

Chapelon et al. (46)

Dunning R3327, prostate Ca, rats

28

16

Kaketa et al. (49)

Horie sarcoma rats

44

24

Oosterhof et al. (50)

T-6 Dunning R3327 prostate Ca, rats

25

23

Abbreviation: HIFU, high-intensity focused ultrasound.

Gelet et al. pioneered the use of transrectal high-intensity focused ultrasound for the treatment of localized prostate cancer.

experimental prostate cancer. In the control population 28% of the animals developed distant metastases, whereas in the high-intensity focused ultrasound-treated animals this percentage dropped to 16%. Similar findings were reported by Oosterhof and colleagues (50) using a T-6 Dunning R3327 rat prostate cancer subline, which was implanted in the hind limb of Fisher-Copenhagen rats. Metastases were seen in 23% of the high-intensity focused ultrasound-treated animals compared with 25% of the sham-treated animals. From these data, it can be concluded that high-intensity focused ultrasound applied to cancer tissues does not accelerate the development of distant metastases; indeed, numerous studies suggest that high-intensity focused ultrasound treatment reduces the rate of metastases (Table 1). As a result, high-intensity focused ultrasound has received considerable experimental and clinical attention.

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