Hemorrhage control in arteries using high-intensity focused ultrasound: a survival study.

High-intensity focused ultrasound (HIFU) has been shown to provide an effective method for hemorrhage control of blood vessels in acute animal studies. The objective of the current study was to investigate the long-term effects of HIFU-induced hemostasis in punctured arteries. The femoral arteries ( approximately 2mm in diameter) of 25 adult anesthetized rabbits were surgically exposed, and either punctured and treated with HIFU (n=15), served as control (no puncture and no HIFU application: n=7), or were punctured and left untreated (n=3). Treated animals were allowed to recover, and examined and/or sacrificed on days 0, 1, 3, 7, 14, 28, and 60 after treatment to obtain ultrasound images and samples of blood and tissue. Hemostasis (arrest of bleeding) was achieved in all 15 of the HIFU-treated arteries. Eleven of the arteries were patent after HIFU treatment, and four arteries were occluded, as determined by Doppler ultrasound. The median HIFU application time to achieve hemostasis was 20s (range 7-55 s) for the patent arteries and 110 s (range 50-134 s) for the occluded arteries. In untreated animals, bleeding had not stopped after 120 s. One of the occluded arteries had reopened by day 14. No immediate or delayed re-bleeding was observed after HIFU treatment. Maximal blood flow velocities were similar in HIFU-treated patent vessels and control vessels. No significant difference in hematocrits was found between HIFU-treated and control groups at different time points after the procedure. Light microscopy observations of the HIFU-treated arteries showed disorganization of adventitia, and coagulation and thinning of the tunica media. The general organization of the adventitia and tunica media recovered to normal appearance within 28 days, with some thinning of the tunica media observed up to day 60. Neointimal hyperplasia was observed on days 14 and 28. The results show that HIFU can produce effective and long-term (up to 60 days) hemostasis of punctured femoral arteries while preserving normal blood flow and vessel wall structure in the majority of vessels.

Treatment of uterine fibroid tumors in an in situ rat model using high-intensity focused ultrasound.

OBJECTIVE: To determine the efficacy and safety of high-intensity focused ultrasound (HIFU) for the treatment of uterine fibroid tumors in an in situ animal model. DESIGN: High-intensity focused ultrasound was applied intraoperatively to uterine fibroid tumors in rats. SETTING: Department of Bioengineering, and Applied Physics Laboratory, University of Washington, Seattle, Washington. ANIMAL(S): Thirty-five tumors in 27 Eker rats that had spontaneous in situ uterine fibroids were randomly assigned into two groups receiving HIFU (n = 29) or sham (n = 6) treatments. INTERVENTION(S): Animals were anesthetized, and tumors were exposed surgically. The HIFU was applied at 3.5 MHz in 10-second bursts to produce coagulative necrosis lesions (3 mm by 10 mm), spaced 5 mm apart. Sham treatments consisted of exposing the tumors, and handling them similarly to those in the HIFU treatment group, but HIFU was not applied. MAIN OUTCOME MEASURE(S): Tumor volume was measured every week transabdominally using B-mode ultrasound imaging. Gross examination and histological analysis were performed after euthanasia. RESULT(S): More than half of the tumors in the HIFU treatment group showed significant tumor volume reduction. The average tumor volume in the sham treatment group increased 40-fold. Gross and histological analysis showed coagulative necrosis of tumor cells in the HIFU treatment group. CONCLUSION(S): The HIFU may provide an effective and safe method of treating uterine fibroid tumors.

Attenuation of porcine tissues in vivo after high-intensity ultrasound treatment.

The attenuation of ultrasound (US) waves in biologic tissues is an important determinant of energy absorption and wave propagation; thus, important in optimization of high-intensity focused US (HIFU) therapy. We measured attenuation of selected porcine tissues (liver, spleen and abdominal wall) in vivo in the frequency range of 1 to 5 MHz, using the pulse-transmission method, before and after HIFU treatment. In all tissues, an increase in attenuation was observed with increasing frequency. The attenuation coefficient was higher in HIFU-treated tissues than in the untreated tissues. The lowest attenuation was measured in the liver, both in normal and HIFU-treated cases. Mechanisms that may be responsible for the observed attenuation coefficient increase in HIFU-treated tissues include thermally induced change in the tissue macromolecular structure and presence of gas/vapor bubbles due to cavitation and/or boiling.

Treatment of uterine leiomyosarcoma in a xenograft nude mouse model using high-intensity focused ultrasound: a potential treatment modality for recurrent pelvic disease.

OBJECTIVE: The objective was to test the efficacy of high-intensity focused ultrasound (HIFU) for treatment of uterine leiomyosarcoma in a Xenograft nude mouse model. METHODS: A total of 65 athymic nude mice were inoculated subcutaneously with 5 to 7 x 10(6) ELT-5B cells, a uterine leiomyosarcoma cell line derived from the Eker rat. Thirty animals showed tumor growth. The tumor volume was measured transcutaneously once a week. Animals were randomly assigned to three groups: HIFU treatment (n = 17), sham treatment (n = 7), and control (n = 6). A HIFU device, operating at a frequency of 2.0 MHz and an intensity of 2000 W/cm(2), was used for treatment. RESULTS: Within 3 weeks of a single HIFU treatment, 100% reduction in tumor volume was observed in all animals, except one. A second HIFU treatment was applied to that animal, resulting in 100% reduction in tumor volume. The tumors in the sham-treated animals continued to grow at a similar rate to that of the control group to approximately 500% of the tumor volume at the time of treatment. All animals were monitored for a maximum of 3 months. No metastasis was observed in the HIFU-treated animals. Histological examination confirmed a complete tumor disappearance after HIFU treatment. CONCLUSION: We have shown that HIFU can effectively treat uterine leiomyosarcoma tumors inoculated in Xenograft nude mice, demonstrating HIFU's potential use for treatment of recurrent uterine leiomyosarcoma.

Liver hemostasis with high-intensity ultrasound: repair and healing.

OBJECTIVE: Previous studies have shown that high-intensity focused ultrasound can effectively control bleeding from injuries of liver, spleen, and blood vessels. This study investigated long-term hemostasis and tissue repair after high-intensity focused ultrasound treatment in liver. METHODS: A total of 21 rabbits were randomly assigned to 2 groups: high-intensity focused ultrasound treatment (n = 14) and sham treatment (n = 7). All animals had sterile laparotomy and liver exposure. The high-intensity focused ultrasound-treated animals received liver incisions, 20 to 25 mm long and 4 to 6 mm deep, followed immediately by high-intensity focused ultrasound application until complete hemostasis was achieved. After recovery, sonographic images, blood samples, and histologic samples were collected immediately and on days 1, 3, 7, 14, 28, and 60 after treatment. RESULTS: All 14 liver injuries were hemostatic after an average +/- SD of 78 +/- 44 seconds of high-intensity focused ultrasound application, with no rebleeding at any time point after the treatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between the high-intensity focused ultrasound and sham groups. Alanine aminotransferase and aspartate aminotransferase levels increased immediately after surgery by as much as 285% up to day 3 and returned to normal values by day 7. Hematocrit and white blood cell counts showed no statistically significant difference from normal values at all time points. Histologic examination up to 60 days after treatment revealed scarring and liver tissue regeneration at the treatment site. CONCLUSIONS: High-intensity focused ultrasound appears to provide long-lasting hemostasis of acute liver injury. Healing and repair mechanisms after high-intensity focused ultrasound application appear to be intact.

Spleen hemostasis using high-intensity ultrasound: survival and healing.

BACKGROUND: Previous studies have shown that high-intensity focused ultrasound (HIFU) can effectively control bleeding of incised livers and spleens and punctured vessels. This current study investigated the long-term safety of HIFU in splenic hemostasis. METHODS: A total of 21 rabbits were randomly assigned to two groups: HIFU treatment (n = 14), and sham treatment (n = 7). All animals underwent sterile laparotomy and splenic exposure. The HIFU-treated animals received splenic incisions, 8 to 10 mm long and 4 to 5 mm deep, and immediate 9.6-MHz HIFU until hemostasis was achieved. After recovery, ultrasound images, blood samples, and histologic samples were collected on days 0, 1, 3, 7, 14, 28, and 60. RESULTS: All 14 splenic injuries were hemostatic after an average of 96 seconds of HIFU application. There was evidence of rebleeding in one animal between days 3 and 7 posttreatment. Subsequent blood analysis showed no significant difference in serial hematologic or coagulation measures between HIFU and sham groups. Histologic examination up to 60 days posttreatment revealed scarring and spleen tissue regeneration at the treatment site. CONCLUSION: HIFU provides an effective and safe method of achieving hemostasis after acute splenic injury.