The feasibility of MRI-guided whole prostate ablation with a linear aperiodic intracavitary ultrasound phased array.

Over the past decade, numerous minimally invasive thermal procedures have been investigated to treat benign prostate hyperplasia and prostate cancer. Of these methods, ultrasound has shown considerable promise due to its ability to produce more precise and deeper thermal foci. In this study, a linear, transrectal ultrasound phased array capable of ablating large tissue volumes was fabricated and evaluated. The device was designed to be compatible for use with MRI guidance and thermometry. The intracavitary applicator increases treatable tissue volume by using an ultrasonic motor to provide a mechanical rotation angle of up to 100 degrees to a 62-element 1D ultrasound array. An aperiodic array geometry was used to reduce grating lobes. In addition, a specially designed Kapton interconnect was used to reduce cable crosstalk and hence also improve the acoustic efficiency of the array. MRI-guided in vivo and ex vivo experiments were performed to verify the array's large-volume ablative capabilities. Ex vivo bovine experiments were performed to assess the focusing range of the applicator. The array generated foci in a 3 cm (2 to 5 cm from the array surface along the axis normal to the array) by 5.5 cm (along the long axis of the array) by 6 cm (along the transverse axis of the array at a depth of 4 cm) volume. In vivo rabbit thigh experiments were performed to evaluate the lesion producing capabilities in perfused tissue. The array generated 3 cm x 2 cm x 2 cm lesions with 8 to 12 half-minute sonications equally spaced in the volume. The results indicate that transrectal ultrasound coagulation of the whole prostate is feasible with the developed device.

Usefulness of MR imaging-derived thermometry and dosimetry in determining the threshold for tissue damage induced by thermal surgery in rabbits.

PURPOSE: To investigate in vivo the feasibility of using magnetic resonance (MR) imaging-derived temperature and thermal dose measurements to find the threshold of thermal tissue damage. MATERIALS AND METHODS: Sonications were delivered in rabbit thigh muscles at varying powers. Temperature-sensitive MR images obtained during the sonications were used to estimate the temperature and thermal dose. The temperature, thermal dose, and applied power were then correlated to the occurrence of tissue damage observed on postsonication images. An eight-element phased-array transducer was used to produce spatially flat temperature profiles that allowed for averaging to reduce the effects of noise and the voxel size. RESULTS: The occurrence of tissue damage correlated well with the MR imaging-derived temperature and thermal dose measurements but not with the applied power. Tissue damage occurred at all locations with temperatures greater than 50.4 degrees C and thermal doses greater than 31.2 equivalent minutes at 43.0 degrees C. No tissue damage occurred when these values were less than 47.2 degrees C and 4.3 equivalent minutes. CONCLUSION: MR imaging thermometry and dosimetry provide an index to predict the threshold for tissue damage in vivo. This index offers improved online control over minimally invasive thermal treatments and should allow for more accurate target volume coagulation.

Determination of the optimal delay between sonications during focused ultrasound surgery in rabbits by using MR imaging to monitor thermal buildup in vivo.

PURPOSE: To use magnetic resonance (MR) imaging to monitor thermal buildup and its effects in treated tissues during sequentially delivered sonications in vivo to optimize the intersonication delay for any set of ultrasound and tissue parameters. MATERIALS AND METHODS: Sequential sonications were delivered next to each other in both thighs in 10 male New Zealand white rabbits. The time between sonications was 11-60 seconds. Phase-difference MR imaging was used to monitor temperature rise, which was used to estimate the thermal dose delivered to the tissue. T2-weighted and contrast agent-enhanced T1-weighted imaging were used to gauge the extent of tissue coagulation. RESULTS: With a short intersonication delay (11-40 seconds), the estimated temperature rise and the extent of tissue coagulation increased dramatically in subsequent sonications. However, when the delay was long (50-60 seconds), the size and shape of the destroyed tissue with subsequent sonications was uniform, and the temperature buildup was substantially lower. CONCLUSION: MR imaging can be used to monitor thermal buildup and its effects due to sequential, neighboring sonications in vivo to produce evenly shaped regions of tissue coagulation. The temperature information obtained from the monitoring can be used to optimize the intersonication delay for any set of ultrasound and tissue parameters.

A phase I study of the toxicity of regional hyperthermia with systemic warming.

This study examines the consequences of allowing moderate systemic hyperthermia during regional heating of the abdomen and pelvis in 29 patients participating in Phase I studies of hyperthermia combined with chemotherapy or radiation therapy. In Group 1 (20 patients, 42 treatments), systemic temperatures were limited by employing surface cooling, while in Group 2 (9 patients, 24 treatments), surface warming and insulation were used so that systemic temperature would rise. Mean time-averaged oral temperatures were 38.4 degrees C and 39.9 degrees C for Groups 1 and 2, respectively. Time-averaged mean regional temperatures were 40.2 +/- 0.7 degrees C and 41.5 +/- 0.2 degrees C for Groups 1 and 2, respectively (p < .001). Regional temperatures > or = 41.0 degrees C were achieved by 64% of Group 1 and all Group 2 patients. The mean time-averaged power required was significantly lower for Group 2 (453 W vs 740 W; p = .032), as was the incidence of pain. Mean maximum pulse rate was significantly higher in Group 2, although this was not associated with symptoms. Allowing systemic temperature to rise decreased power requirements and treatment-related pain, at the cost of an asymptomatic increase in heart rate. The results suggest that regional heating may be more readily achieved in the setting of elevated systemic temperature.

Development of scanned focussed ultrasound hyperthermia: clinical response evaluation.

Selective heating of irregularly shaped tumors at depth can now be accomplished through focussing and controlled scanning of energy deposition patterns by ultrasound. A scanned focussed ultrasound (SFUS) hyperthermia system developed at the University of Arizona has been used to deliver 220 treatments to 87 tumors in 71 patients with extracranial malignancies between October 1986 and May 1990. Patients received an average of three SFUS hyperthermia treatments, spaced weekly, during ongoing fractionated radiotherapy. The most common anatomic sites treated were the pelvis (22 patients), chest wall or breast (14), neck (8), and axilla (7), while the most common histologies were adenocarcinoma (36), squamous cell carcinoma (11), and melanoma (10). Concurrent radiotherapy was delivered (range 1000-7640 cGy, mean 4320 cGy) to 67 SFUS hyperthermia patients; 4 received concomitant chemotherapy. Tumor volumes ranged from 1-2100 cubic centimeters (mean 325 cc), and 75% were located at depths greater than 3 cm from skin. A 62% overall response rate was observed, with 22% of treated tumors demonstrating a complete response (defined as complete disappearance of treated tumor), and 40% exhibiting a partial response (defined as greater than or equal to 50% reduction in tumor volume). Dramatic local pain reduction was achieved in 42% of the tumors treated. The acute tolerance of SFUS hyperthermia was quite good, and chronic toxicities (persistent skin blisters/burns) were identified in two patients. The versatility of the SFUS system is discussed, as well as its future potential for improving control of advanced loco-regional malignancies treated with curative intent.

Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial.

Hyperthermia delivered by scanned focused ultrasound was combined with external beam radiation to treat 15 patients with primary malignant tumors of the brain. A preliminary craniectomy was performed to avoid attenuation of the ultrasound beam by the skull, and multiple thermal sensors were employed to ascertain intratumoral temperatures. The target temperature was 42.5 degrees C at the tumor boundary. This was attained at more than one point during every complete treatment, while a mean temperature in excess of 42 degrees C was achieved within the scanned tumor volume during at least 1 treatment in 11 patients. Technical problems and toxicities are described.

The CDRH helix. A phase I clinical trial.

Seventeen patients have been given regional hyperthermia treatments using the Center for Devices and Radiologic Health (CDRH) Helix, a resonant helical coil unit. Most of these patients had large, clinically advanced tumors, whose mean volume exceeded 1000 cc. Mean maximum, minimum, and average temperatures were 40.6, 38.6, and 39.6 degrees C, respectively, for all sites combined. The pelvic heating capabilities of the CDRH Helix and the BSD-1000 annular phased array were compared, and generally were equivalent. Although the Helix could be used in a wider variety of locations, and was more comfortable and easier to use than the BSD-1000 annular phased array, neither device was particularly effective in generating clinically useful temperatures; the Helix is currently under investigation for use in regional-systemic hyperthermia in combination with antineoplastic drugs and biologic response modifiers.

Scanned focussed ultrasound hyperthermia: initial clinical results.

Between November 1986 and July, 1987, a preliminary study to determine the feasibility of scanned focussed ultrasound for clinical hyperthermia at various sites was conducted. Fourteen patient (17 tumors) have been treated using a microprocessor-controlled apparatus developed at the University of Arizona by modifying a commercially available diagnostic ultrasound unit. We have treated nine pelvic tumors, four extremity tumors, two brain tumors, and two extracranial head and neck tumors for a total of 42 treatments. Multipoint thermometry was achieved for all patients, with 2-25 (mean = 10) points monitored during each treatments within the scanned tumor volume. Average maximum temperature within the scanned tumor volume was 44.2, 44.7, 44.8, and 42.0 degrees C for pelvic, extremity brain, and extracranial head and neck tumors, respectively; similarly, 55%, 45%, 71%, and 0 of monitored points exceeded 42.5 degrees C. Pain limited applied power in 15 of 42 treatments, and bone pain with a periodicity similar to the scanning periodicity was seen in 11 treatments. A non-randomized comparison of temperatures achieved using scanned focussed ultrasound to those achieved using the microwave annular array and the CDRH Helix suggests that scanned focussed ultrasound may have promise and potential advantages in heating selected pelvic tumors.

Diazepam dosage and timing in ketamine combination anaesthesia. A double-blind study.

A form of combination anaesthesia using ketamine, diazepam, alcuronium and nitrous oxide was used in 41 patients over 65 years requiring abdominal surgery. The patients were premedicated with droperidol 2.5-7.5 mg im. At induction the patients received diazepam 5 mg. ketamine 2 mg/kg and alcuronium 0.2 mg/kg. Anaesthesia was maintained with a continuous, steady injection of ketamine 2.5 mg/kg/h and nitrous oxide-oxygen with controlled ventilation. Four minutes before incision the patients received 1 ml of coded solution and at the end of anaesthesia the same solution, which contained either 5 mg/ml diazepam or its solvent only. There were no statistically significant differences between the two groups, i.e. patients receiving either 15 or 5 mg of diazepam. The incidence of bad dreams was 5 per cent, i.e. one patient in each group. Only one patient vomited and one had pronounced nausea in group D5. According to the anaesthesiologist's, the anaesthesia nurse's and the patient's subjective evaluations this type of combination anaesthesia was found to be highly acceptable. Despite there being no statistically significant differences between the patients who received 5 + 5 + 5 mg of diazepam compared to those receiving 5 + 0 + 0 mg, the figures in results per se incline in favour of the use of 5 + 5 + 5 of diazepam.