Ultrasound phased arrays for prostate treatment.

The effect of array geometry on the steering performance of ultrasound phased arrays is examined theoretically, in order to maximize array performance under the given anatomical constraints. This paper evaluates the performance of arrays with spherical and cylindrical geometry, determined by using computer simulations of the pressure fields produced at various extremes of steering. The spherical segment arrays were truncated for insertion into the rectum, and contained either annular or linear elements. The cylindrical arrays were either flat or had a variable curvature applied along their length. Fields were computed by dividing the array elements into many point sources. The effectiveness of an array configuration when steered to a particular focal location was assessed by defining a parameter, G, as the ratio of the intensity at the desired focus to the maximum intensity of any unwanted lobes. The performance of truncated spherical arrays with annular elements was evaluated for focal steering along the array axis (in depth, in the z direction). When steered 15 mm toward the source, these truncated spherical annular arrays exhibited excellent performance, with G>5.7 for arrays containing more than 10 elements. Similarly, the spherical arrays with linear elements performed well when steered along the array axis to the same degree, with G>7 (for element widths up to 3 lambda), though many more array elements were required. However, when these arrays were steered 15 mm laterally, along the length of the prostate (the y direction), the value for G fell below 1 for element widths greater than about 1.6 lambda. It was found that the cylindrical arrays performed much better for y-direction steering (G>4, for 60 mm arrays with an element width of 1.75 lambda), but their performance was poorer when steered in the z direction (G approximately 4 for an element width of 1.5 lambda). In order to find a compromise between these extremes, a curved cylindrical array was examined, which was a cylindrical array with additional curvature along its length. These curved cylindrical arrays yielded performance between that of spherical linear arrays and cylindrical arrays, with better steering along the y direction than the spherical arrays and better z-direction steering than the cylindrical arrays.

Interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements.

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies.

Noninvasive surgery of prostate tissue by high intensity focused ultrasound: an updated report.

OBJECTIVE: To establish clinical efficacy and safety of High Intensity Focused Ultrasound (HIFU) for the treatment of benign prostatic hyperplasia (BPH) in a multiple site clinical study. METHODS: Seven clinical sites were set up for the studies, five in the USA, one in Canada and one in Japan respectively. Sixty two patients were enrolled in these three studies. Transrectal ultrasound probes made to produce sufficient acoustic power required for focused ultrasound surgery of the prostate as well as to perform imaging of the prostate, were employed in the study. The probes ware made of 2.5, 3.0, 3.5, 4.0 and 4.5 cm focal length transducers to treat varying prostate sizes and shapes and operated at 4 MHz frequency for both imaging and treatment. The employed ultrasound device produced both transverse and longitudinal images of the prostate on the same display. The images were used for selection of tissue volume, treatment planning and monitoring of tissue during the HIFU treatment cycle. The patients in the USA and Canada were followed for two years and those in Japan were followed for one year on a regular interval. The results were evaluated for changes in the peak flow rate (Qmax in ml/s), quality of life (QOL) and International Prostate Symptom Score (IPSS). RESULTS: The average pre / post treatment results at 180 days were significantly different for Qmax, QOL and IPSS 8.5/14.2 (ml/s), 4.7/2.1 and 22/10 respectively. CONCLUSION: Under this protocol, HIFU was found safe and efficacious for the treatment of BPH. The HIFU treatment produced statistically significant results for the parameters measured with least complications. Additionally, the HIFU treatment was found to be durable.

Dependence of ultrasonic attenuation and absorption in dog soft tissues on temperature and thermal dose.

The effect of temperature and thermal dose (equivalent minutes at 43 degrees C) on ultrasonic attenuation in fresh dog muscle, liver, and kidney in vitro, was studied over a temperature range from room temperature to 70 degrees C. The effect of temperature on ultrasonic absorption in muscle was also studied. The attenuation experiments were performed at 4.32 MHz, and the absorption experiments at 4 MHz. Attenuation and absorption increased at temperatures higher than 50 degrees C, and eventually reached a maximum at 65 degrees C. The rate of change of tissue attenuation as a function of temperature was between 0.239 and 0.291 Np m-1 MHz-1 degree C-1 over the temperature range 50-65 degrees C. A change in attenuation and absorption was observed at thermal doses of 100-1000 min, where a doubling of these loss coefficients was observed over that measured at 37 degrees C, presumably the result of changes in tissue composition. The maximum attenuation or absorption was reached at thermal dosages on the order of 10(7) min. It was found that the rate at which the thermal dose was applied (i.e., thermal dose per min) plays a very important role in the total attenuation absorption. Lower thermal dose rates resulted in larger attenuation coefficients. Estimation of temperature-dependent absorption using a bioheat equation based thermal model predicted the experimental temperature within 2 degrees C.

Noninvasive temperature estimation in tissue via ultrasound echo-shifts. Part II. In vitro study.

Time shifts in echo signals returning from a heated volume of tissue correlate well with the temperature changes. In this study the relationship between these time shifts (or delays) and the tissue temperature was investigated in excised muscle tissue (turkey breast) as a possible dosimetric method. Heat was induced by the repeated activation of a sharply focused high-intensity ultrasound beam. Pulse echoes were sent and received with a confocal diagnostic transducer during the brief periods when the high-intensity ultrasonic beam was inactive. The change in transit time between echoes collected at different temperatures was estimated using cross-correlation techniques. With spatial-peak temporal-peak intensities (ISPTP) of less than 950W/cm2, the delay versus temperature relationship was fit to a linear equation with highly reproducible coefficients. The results confirmed that for spatial-peak temperature increases of approximately 10 degrees C, temperature-dependent changes in velocity were the single most important factor determining the observed delay, and a linear approximation could produce accurate temperature estimations. Nonlinear phenomena that occurred during the high-intensity irradiation had no significant effect on the measured delay. At ISPTP of 1115-2698 W/cm2, the delay-temperature relationship showed a similar monotonically decreasing pattern, but as the temperature peaked its slope gradually increased. This may reflect the curvilinear nature of the velocity-temperature relationship, but it may also be related to irreversible tissue modifications and to the use of the spatial-peak temperature to experimentally characterize the temperature changes. Overall, the results were consistent with theoretical predictions and encourage further experimental work to validate other aspects of the technique.

Noninvasive ultrasonic subtotal ablation of the prostate in dogs.

OBJECTIVE: To determine whether high-intensity focused ultrasound (HIFU) can be used for subtotal ablation of the prostate gland in dogs without causing damage to surrounding tissues. DESIGN: Experimental trial. ANIMALS: Adult hounds > or = 5 years old and weighing between 20 and 30 kg. PROCEDURE: Prostatic ablation was performed in all dogs, using a transrectal HIFU probe. Acute effects of HIFU treatment were evaluated in 4 dogs. These dogs were euthanatized and necropsied 4 hours after the procedure. Chronic effects were evaluated in the other 3 dogs. Serial CBC, serum biochemical analyses, urinalyses, and transrectal ultrasonography were performed. Dogs were euthanatized and necropsied 3 months (1 dog) or 1 year (2 dogs) after HIFU treatment. RESULTS: Histologic examination of the prostate glands from the 4 dogs euthanatized 4 hours after treatment revealed that 80 to 90% of the gland had undergone hemorrhagic, liquefactive necrosis. Only slight discoloration of the prostatic capsule was detected, and there were not any gross or histologic lesions of the rectal mucosa or urinary bladder. All 3 dogs followed up after HIFU treatment developed cystic cavities within the prostate. Clinicopathologic testing did not indicate any long-term adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: This method was effective in causing subtotal ablation of prostatic tissue in dogs. Further study of morbidity is required before the technique can be used clinically.

Ultrasound and microbubbles: their generation, detection and potential utilization in tissue and organ therapy--experimental.

Ultrasound-induced cavitation in tissue and organs has been well recognized and documented. Generally, this phenomenon has been seen as something to be avoided except in cases such as lithotripsy, where its production is considered an essential part of the treatment process or as a desirable contrast media in some areas of visualization enhancement. This article covers three areas in which the phenomenon has been observed, and shows how the effect can or may be therapeutically beneficial. Studies in the pig show that implanted human gallstones and the gallbladder itself can be eliminated in a nonsurgical procedure using ultrasound-induced cavitation in the gallbladder. In the dog brain, relatively stable cavitation-induced microbubbles have been transported through the vascular system to regions outside a focal seeding site. These bubbles produce ablation of tissue volumes at a remote site when irradiated with appropriate ultrasound. The cavitation phenomenon has been observed in the dog and human prostate. In the human prostate, microbubbles transported from ultrasound-induced focal seeding sites can be readily visualized with ultrasound and may be potentially useful under controlled conditions in tissue debulking for the treatment of benign prostatic hyperplasia (BPH). A similar microbubble transport has not been seen in the dog prostate under similar ultrasound treatment parameters. The ability to detect cavitation-induced microbubbles, follow their transportation through the vascular system and excite them at the appropriate time and place provides interesting possibilities for therapy. Of course, the entire microbubble process can be avoided by working below the cavitation threshold, thereby using only the absorption of ultrasound in tissue to produce focal thermal lesions. The term microbubble is used here in the context of those bubbles which can be transported in the vascular system down to vessels diameters below the 100-microns range. This is the vessel size in the vascular field into which microbubbles are transported and can be both visualized as well as disrupted with ultrasound.

High intensity focused ultrasound for the treatment of benign prostatic hyperplasia: early United States clinical experience.

High intensity focused ultrasound via a transrectal approach was used to treat 15 patients with symptomatic benign prostatic hyperplasia. The first 10 of these 15 patients underwent continuous temperature monitoring of the periprostatic region throughout the treatment. Patients undergoing transperineal thermocouple placement for the purpose of thermometry were treated while under general or spinal anesthesia, whereas 4 of the 5 remaining patients were successfully treated using intravenous sedation alone. Of the 10 patients 9 did not demonstrate a significant temperature elevation. One patient with a small prostatic anteroposterior diameter had a transient elevation of 17C. No patient experienced a complication related to periprostatic heating. Followup was available at 90 days in all patients. At 90 days the symptom scores decreased from a pretreatment value (American Urological Association questions 1 to 7) of 31.2 (range 22 to 38) to 15.8 (range 8 to 31). Peak flow rate increased by a mean of 4.7 ml per second from 9.3 ml per second before treatment to 14.0 ml per second at 90 days. The most frequent complication was that of transient urinary retention in 11 of 15 patients (73.3%) and hematospermia in 7 (46.7%). No adverse reactions persisted at 90 days. This study represents an initial attempt using high intensity focused ultrasound to treat symptomatic benign prostatic hyperplasia. Overall, the safety and effectiveness of high intensity focused ultrasound demonstrated in this pilot study are encouraging.

High-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) is a technology that permits the use of ultrasound waves used for imaging and then focuses them as one would use a magnifying glass to focus sunlight. The ultrasound energy is absorbed by tissue and converted to heat and can be used to ablate tissue. This article summarizes the technology, mechanism of action, technique, and early clinical results of HIFU, then concludes with some potential future applications of this technology.

High-intensity focused ultrasound in the treatment of prostatic tissue.

OBJECTIVE: Beginning in 1987, high-intensity focused ultrasound was investigated in the canine model to determine the feasibility of destroying prostate tissue. After demonstrating the ability to ablate prostate tissue reliably in a canine model, a 15-patient pilot clinical study was undertaken at Indiana University in the fall of 1992. This pilot study was undertaken to assess the safety in the human clinical situation, as well as to give some early efficacy results. METHODS: The early canine feasibility studies were conducted via a suprapubic extracorporeal approach using two separate transducers, one for imaging and the other for therapy. Subsequent to this, a transrectal probe, which had the dual capability of both imaging and therapy, was developed and used to treat canine prostates in a formal, "good laboratory practice" study to determine the safety of this technology prior to beginning treatment of human benign prostatic hypertrophy. RESULTS: The formal canine studies demonstrated that prostatic tissue could be reliably ablated in the therapy zone. The dosimetry and duty cycle required to ablate canine prostatic tissue effectively was also determined in this study. The study also demonstrated that the prostatic tissue could be ablated without injury to the intervening rectal tissue or periprostatic tissue. The human pilot study has also demonstrated safety of high-intensity focused ultrasound, as well as early efficacy. CONCLUSIONS: These early clinical results are encouraging, but assessment of efficacy will require a randomized study comparing high-intensity focused ultrasound to sham and to transurethral prostatectomy. This multicenter trial is currently planned.

Liver cancer ablation with extracorporeal high-intensity focused ultrasound.

Recent animal studies have demonstrated the capacity of high-intensity focused ultrasound (HIFU) to extracorporeally ablate selective tissue targets in the liver without requiring surgical exposure of the liver or insertion of instruments into the liver. The potential value of HIFU as a noninvasive local treatment for human hepatic cancers has attracted considerable interest. This report reviews the current status of HIFU research and sets forth questions for future study.

High-intensity focused ultrasound in the treatment of prostatic disease.

Beginning in 1987, high-intensity focused ultrasound was investigated experimentally in a canine model to determine whether or not prostate tissue could be destroyed with good aiming and control. Subsequently a transrectal probe was developed and used to treat canine prostates in a formal study to determine whether or not this technology could be used to treat human benign prostatic hypertrophy. Next, after FDA approval, 15 patients were treated at Indiana University in the fall of 1992. Both canine and human studies have shown that high-intensity focused ultrasound administered via a transrectal probe is capable of creating prostate lesions without injury to intervening and surrounding tissue.

Production of prostatic lesions in canines using transrectally administered high-intensity focused ultrasound.

High-intensity focused ultrasound is a method of destroying tissue at a point distant from the transducer without injuring intervening tissue. A transrectal probe was developed and used to treat 26 canines in order to determine the feasibility of using this therapy in humans. Lesions of coagulative necrosis which evolved into cystic cavities were produced. Surrounding tissue was preserved without evidence of injury.

Extracorporeal liver ablation using sonography-guided high-intensity focused ultrasound.

RATIONALE AND OBJECTIVES: High-intensity focused ultrasound (HIFU) is the only radiation beam that can remotely destroy deep-seated tissue targets without causing damage to the intervening tissues. This study evaluates the ability of sonography-guided HIFU to extracorporeally induce liver ablation in a rabbit model. METHODS: Under sonographic guidance, the HIFU beam was transcutaneously focused at the target tissue in the liver through a subcostal approach. A computer controlled the HIFU exposure and transducer movement to destroy a preselected tissue volume. Simultaneous sonography monitored the tissue response. Ten insonated rabbits were killed from days 0 to 10, and the liver and intervening tissues were examined histologically. RESULTS: A sharply demarcated sonolesion of coagulation necrosis was produced in the liver in 9 of 10 animals. No damage was found in the intervening tissues (n = 6) when adequate acoustic coupling and proper beam path was applied. CONCLUSION: Sonography-guided HIFU might be a potential new modality for extracorporeal inducement of liver cancer ablation without resorting to laparatomy.

A reproducible rat liver cancer model for experimental therapy: introducing a technique of intrahepatic tumor implantation.

To investigate therapeutic strategies for hepatoma, it is necessary to have a reproducible animal model with a tumor growth pattern allowing accurate assessment of results. Many techniques of intrahepatic tumor implantation (IHTI) have been devised for intrahepatic tumor models. Most of them, however, have the disadvantage of high rates of artificial tumor dissemination during tumor implantation, which interferes with the evaluation of therapy. To overcome this problem, we have developed a technique of IHTI in which a piece of Gelfoam is placed into a small incision in the liver for the purpose of both hemostasis and formation of a tension-free pocket to accept the tumor implant. In 583 ACI rats receiving IHTI with Morris hepatoma 3924A, the tumor take rate was 100%. Resembling the natural course of human hepatoma, the implanted tumor grows locally early in the course of disease and eventually invades the surrounding organs causing ascites and also metastasizes to the lung. Liver microangiography demonstrated that the tumor received blood supply mainly from the hepatic artery. This IHTI technique was also compared to two other methods of IHTI: insertion of fragments without using Gelfoam and implantation with a tumor cell suspension. A significantly lower rate of early lung metastases was achieved with our technique (0%) in comparison with other two techniques (41 and 80%). We conclude that this rat liver cancer model is reproducible and allows efficient evaluation of treatment modalities for liver cancer without interference from tumor at undesirable sites.

Effects of high-intensity focused ultrasound in the treatment of experimental neuroblastoma.

This report evaluates the effect of high-intensity focused ultrasound (HIFU) on subcutaneous murine neuroblastoma C1300. HIFU treatment was administered with a focused 4-MHz quartz transducer with a peak intensity of 550 W/cm2. In experiment 1, 60 animals with tumor were divided into four groups. Group I (n = 15) were controls; group II (n = 15) received adriamycin, 5 mg/kg intraperitoneally; group III (n = 15) received HIFU; and group IV (n = 15) received both adriamycin and HIFU. All the animals in groups I and II died of tumor by 35 days. Fifty-three percent (8/15) of mice in group III and 80% (12/15) in group IV were cured with no evidence of tumor (NET) at 200 days. Log-rank statistics showed significant prolongation of survival in the groups III and IV as compared with groups I or II (P less than .05). In experiment 2, 45 animals with tumor were divided into three groups. Group I (n = 15) were controls; group II (n = 15) received HIFU; and group III (n = 15) received repeated HIFU. The results showed 47% (7/15) of mice in group II and 67% (10/15) in group III were NET at 200 days. Significant survival prolongation was achieved in groups II and III in comparison with group I (P less than .05). In experiment 3, 90 mice received either tumor (n = 60) or saline (n = 30) inoculation in the left flank. On day 5, 45 mice with tumor were treated with HIFU (group I), while the other 15 mice with tumor (group II) had a sham procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Syndrome of inappropriate antidiuretic hormone following tuberculous epididymo-orchitis in renal transplant recipient: case report.

A rare case of the inappropriate antidiuretic hormone syndrome after tuberculous epididymoorchitis in a renal transplant recipient is described. Orchiectomy was performed because of a cold abscess, following which clinical improvement was noted.

High-intensity focused ultrasound in the treatment of experimental liver cancer.

High-intensity focused ultrasound (HIFU) was used to treat Morris rat hepatoma 3924A implanted in the liver. Treatment was administered with a lens-focused 4-MHz transducer that created a focused beam of 550 W/cm2 at peak intensity. One hundred twelve rats with liver tumors were divided into two groups of 56 each. Group 1 received HIFU therapy while group 2 (the control group) did not. All rats were killed immediately or 1, 3, 7, 14, 21, or 28 days after treatment. Eight rats in each group were killed at each interval for pathologic and biochemical studies. Significant inhibition of the tumor growth was seen in the HIFU-treated group, with tumor growth inhibition rates of 65.4% to 93.1% from the third to the 28th day after treatment. Ultrasound-treated tumors showed direct thermal cytotoxic necrosis and fibrosis. An additional 56 ACl rats with liver tumors were divided into four groups of 14 each. Group 1 received doxorubicin hydrochloride intraperitoneally and HIFU therapy; group 2, HIFU therapy; group 3, doxorubicin hydrochloride; and group 4 (the control group), neither HIFU nor doxorubicin hydrochloride. Significantly improved survival rates were noted in HIFU-treated animals (groups 1 and 2) compared with those of groups 3 and 4. These data suggest that HIFU may be a useful method for local treatment of hepatic tumors.