Transurethral ultrasound applicators with directional heating patterns for prostate thermal therapy: in vivo evaluation using magnetic resonance thermometry.

A catheter-based transurethral ultrasound applicator with angularly directional heating patterns has been designed for prostate thermal therapy and evaluated in canine prostate in vivo using MRI to monitor and assess performance. The ultrasound transducer array (3.5 mm diameter tubular transducers, 180 degrees active sectors, approximately 7.5 MHz) was integrated to a flexible delivery catheter (4 mm OD), and encapsulated within an expandable balloon (35 mm x 10 mm OD, 80 ml min(-1) ambient water) for coupling and cooling of the prostatic urethra. These devices were used to thermally coagulate targeted portions of the canine prostate (n = 2) while using MR thermal imaging (MRTI) to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. MRTI was based upon the complex phase-difference mapping technique using an interleaved gradient echo-planar imaging sequence with lipid suppression. MRTI derived temperature distributions, thermal dose exposures, T1-contrast enhanced MR images, and histology of sectioned prostates were used to define destroyed tissue zones and characterize the three-dimensional heating patterns. The ultrasound applicators produced approximately 180 degrees directed zones of thermal coagulation within targeted tissue which extended 15-20 mm radially to the outer boundary of the prostate within 15 min. Transducer activation lengths of 17 mm and 24 mm produced contiguous zones of coagulation extending axially approximately 18 mm and approximately 25 mm from base to apex, respectively. Peak temperatures around 90 degrees C were measured, with approximately 50 degrees C-52 degrees C corresponding to outer boundary t43 = 240 min at approximately 15 min treatment time. These devices are MRI compatible, and when coupled with multiplanar MRTI provide a means for selectively controlling the length and sector angle of therapeutic thermal treatment in the prostate.

Evaluation of endorectal and urethral cooling devices during MR-guided ultrasound thermal ablation in canine prostate.

High-temperature thermal therapy for the treatment of prostate cancer is currently being applied as a minimally-invasive alternative over traditional forms of treatment. Catheter-based interstitial and transurethral ultrasound applicators are being developed for controlled and selective thermal ablation of prostaric tissues with concurrent MR thermal imaging. As part of this treatment strategy we have devised a transurethral cooling catheter and a cooling jacket to be placed over the endorectal MR imaging coil to protect the urethral mucosa and rectal wall from thermal damage during treatment. The cooling efficiencies and protective abilities of these devices were evaluated in vivo within three canine prostate glands. Invasive and MR derived temperature measurements within the prostate and rectal wall indicate that the protective influence of the endorectal cooling extends 5-10 mm from the rectal wall into the dorsal prostate. The urethral cooling extends approximately 5 mm from the cooling balloon. The protective capabilities were further verified with subsequent histological analysis with TTC stained tissue sections and contrast enhanced T1-weighted MR images post treatment. Both of these cooling devices are compatible with the MR thermometry and can be used to protect the urethral mucosa and rectal wall during prostate thermal ablation with interstitial and transurethral ultrasound devices.

Catheter-based ultrasound applicators for selective thermal ablation: progress towards MRI-guided applications in prostate.

High-temperature thermal therapy is emerging as a feasible treatment option for prostate cancer and benign prostatic hyperplasia. Previous investigations have demonstrated distinct advantages of catheter-based ultrasound technology over other heating modalities for thermal ablation therapies, with significant potential for better spatial control and faster heating times. The purpose of this study was to develop ultrasound devices and techniques specifically for treating prostate cancer in conjunction with magnetic resonance thermal imaging (MRTI) to monitor and control treatment progression. Directional transurethral applicators have been designed with arrays of sectored tubular (90 degrees active acoustic sector) or with narrow planar transducer segments and integrated with a flexible delivery catheter with a cooling balloon. This applicator can be rotated within the prostatic urethra to target specific regions during treatment. MRI compatible catheter-cooled interstitial ultrasound applicators with 180 degrees active acoustic sectors were developed specifically to treat the prostate. These applicators may be implanted through the perineum into the posterior portion of the prostate, with their heating energy directed away from the rectum. Both heating strategies were evaluated via biothermal simulations and in vivo experiments within canine prostate (n = 3). During the in vivo studies, MRTI was used to monitor treatment temperatures, cytotoxic thermal doses (t43 > 240 min) and corresponding maximum temperature thresholds (Tmax > 52 degrees C) within three imaging planes simultaneously. Urethral and endorectal cooling was employed with both treatment strategies to provide further protection of the urethral mucosa and rectum from thermal damage. Results using the transurethral applicators demonstrated that narrow zones of coagulation (approximately 30 degrees sector for planar, approximately 90 degrees for tubular), extending up to 20 mm from the urethra to the periphery of the prostate gland, could be produced within 10-15 min. Further, rotation of the applicator during treatment could be used to destroy larger regions in the prostate. Experiments using multiple interstitial directional applicators (approximately 180 degrees active sectors), implanted within the posterior margin of the prostate with the energy directed away from the rectum, produced contiguous zones of thermal coagulation which extended from the posterior prostate toward the anterior-lateral periphery of the gland. Both transurethral and interstitial treatment strategies demonstrated significant potential for thermal ablation of localized prostate cancer, particularly when MRTI is used to guide and assess treatment.

Acute biomechanical and histological effects of intradiscal electrothermal therapy on human lumbar discs.

STUDY DESIGN: Human cadaver lumbar spines were used to assess the acute effects of intradiscal electrothermal therapy in vitro. OBJECTIVE: To determine whether intradiscal electrothermal therapy produces acute changes in disc histology and motion segment stability. SUMMARY OF BACKGROUND DATA: Intradiscal electrothermal therapy has been introduced as an alternative for the treatment of discogenic low back pain. Several hypothesized mechanisms for the effect of intradiscal electrothermal therapy have been suggested including shrinkage of the nucleus or sealing of the anulus fibrosus by contraction of collagen fibers, and thermal ablation of sensitive nerve fibers in the outer anulus. METHODS: Intradiscal electrothermal therapy was performed with the Spinecath by Oratec on 19 fresh, frozen human lumbar cadaver specimens. In a separate study, eight specimens were tested biomechanically and instrumented to map the thermal distribution, whereas five specimens were tested only biomechanically, both before and after intradiscal electrothermal therapy. Six additional specimens were heated with intradiscal electrothermal therapy, and the resulting canal was backfilled with a silicone rubber compound to allow colocalization of the catheter and anular architecture. RESULTS: A consistent pattern of increased motion and decreased stiffness was observed. For the specimens in which only biomechanical measurements were taken, a 10% increase in the motion, on the average, at 5 Nm torque was observed after intradiscal electrothermal therapy. No apparent alteration of the anular architecture was observed around the catheter site in the intradiscal electrothermal therapy-treated discs. CONCLUSION: The data from this study suggest that the temperatures developed during intradiscal electrothermal therapy are insufficient to alter collagen architecture or stiffen the treated motion segment acutely.

Evaluation of multielement catheter-cooled interstitial ultrasound applicators for high-temperature thermal therapy.

Catheter-cooled (CC) interstitial ultrasound applicators were evaluated for their use in high-temperature coagulative thermal therapy of tissue. Studies in ex vivo beef muscle were conducted to determine the influences of applied electrical power levels (5-20 W per element), catheter flow rate (20-60 ml min(-1)), circulating water temperature (7-40 degrees C), and frequency (7-9 MHz) on temperature distribution and thermal lesion geometry. The feasibility of using multiple interstitial applicators to thermally coagulate a predetermined volume of tissue was also investigated. Results of these studies revealed that the directional shape of the thermal lesions is maintained with increasing time and power. Radial depths of the thermal lesions ranged from 10.7 +/- 0.7 mm after heating for 4 min with an applied power level of 5 W, to 16.2 +/- 1.4 mm with 20 W. The axial length of the thermal lesions is controlled tightly by the number of active transducers. A catheter flow rate of 20 to 40 ml min(-1) (52.2 +/- 5.5 kPa at 40 ml min(-1)) with 22 degrees C water was determined to provide sufficient cooling of the transducers for power levels used in this study. In vivo temperatures measured in the center of a 3-cm-diam peripheral implant of four applicators in pig thigh muscle reached 89.3 degrees C after 4 min of heating, with boundaries of coagulation clearly defined by applicator position and directivity. Conformability of heating in a clinically relevant model was demonstrated by inserting two directional CC applicators with a 2 cm separation within an in vivo canine prostate, and generating a thermal lesion measuring 3.8 cm x 2.2 cm in cross section while directing energy away from, and protecting the rectum. Maximum measured temperatures at midgland exceeded 90 degrees C within 20 min of heating. The results of this study demonstrate the utility of single or multiple CC applicators for conformal thermal coagulation and high temperature thermal therapy, with potential for clinical applications in sites such as prostate, liver, breast, or uterus.

Control of interstitial thermal coagulation: comparative evaluation of microwave and ultrasound applicators.

This study presents a comparative evaluation of the control of heating and thermal coagulation with microwave (MW) and ultrasound (US) interstitial applicators. Helical coil MW antennas (17 mm and 25 mm length radiating antennae) were tested using an external implant catheter (2.2 mm o.d.) with water-cooling. US applicators with tubular transducers (2.2 and 2.5 mm o.d., 10 mm length, single-element and 3-element) were utilized with a direct-coupled configuration and internal water-cooling. Measurements of E-field distributions (for MW) and acoustic beam distributions (for US) were used to characterize the applicator energy output. Thermal performance was evaluated through multiple heating trials in vitro (bovine liver) and in vivo (porcine thigh muscle and liver) at varied levels of applied power (20-40 W for microwave, 15-35 W for ultrasound) and heating times (0.5-5 min). Axial temperature distributions in the tissue were recorded during heating, and dimensions of the resulting lesions of thermal coagulation were measured. Both MW and US applicators produced large volumes of tissue coagulation ranging from 8 to 20 cm3 with singular heating times of 5 min. Radial depth of lesions for both MW and US applicators increased with heating duration and power levels, though US produced notably larger lesion diameters (30-42 mm for US vs 18-26 mm for MW, 5 min heating). Characteristic differences between the applicators were observed in axial energy distribution, tissue temperatures, and thermal lesion shapes. MW lesions increased significantly in axial dimensions (beyond the active applicator length) as applied power level and/or heating duration was increased, and lesion shapes were generally not uniform. US provided greater control and uniformity of heating, with energy deposition and axial extent of thermal lesions corresponding to the length of the active transducer(s). The improved ability to control the extent of thermal coagulation demonstrated by the US applicators provides greater potential to target a specific region of tissue.

Combination of transurethral and interstitial ultrasound applicators for high-temperature prostate thermal therapy.

The purpose of this study was to determine the feasibility of using a transurethral ultrasound applicator in combination with implantable ultrasound applicators for inducing thermal coagulation and necrosis of localized cancer lesions or benign disease within the prostate gland. The potential to treat target zones in the anterior and lateral portions of the prostate with the angularly directive transurethral applicator, while simultaneously treating regions of extracapsular extension and zones in the posterior prostate with the directive implantable applicators in combination with a rectal cooling bolus, is evaluated. Biothermal computer simulations, acoustic characterizations, and in vivo thermal dosimetry experiments with canine prostates were used to evaluate the performance of each applicator type and combinations thereof. Simulations have demonstrated that transurethral applicators with 180-270 degrees acoustic active zones can direct therapeutic heating patterns to the anterior and lateral prostate, implantable needles can isolate heating to the posterior gland while avoiding rectal tissue, and that the combination of applicators can be used to produce conformal heating to the whole gland. Single implantable applicators (1.8 mm OD x 10 mm long, approximately 180 degrees active sector, approximately 7 MHz, direct-coupled type) produced directional thermal lesions within in vivo prostate, with temperatures >50 degrees C extending more than 10 mm radially after 10-15 min. Combination of interstitial applicators (1-2) and a transurethral applicator (3-2.5 mm OD x 6 mm long, approximately 180 degrees active sector, 6.8 MHz, 6 mm OD delivery catheter) produced conforming temperature distributions (48-85 degrees C) and zones of acute thermal damage within 15 min. The preliminary results of this investigation demonstrate that implantable directional ultrasound applicators, in combination with a transurethral ultrasound applicator, have the potential to provide thermal coagulation and necrosis of small or large regions within the prostate gland, while sparing thermally sensitive rectal tissue.

Directional power deposition from direct-coupled and catheter-cooled interstitial ultrasound applicators.

This research represents an experimental investigation of the directional power deposition capabilities of interstitial ultrasound applicators intended for applications in hyperthermia and thermal surgery for cancerous or benign disease. Direct-coupled and catheter-cooled ultrasound applicators were fabricated using cylindrical piezoceramic transducers sectored to produce 90 degrees, 180 degrees or 270 degrees active acoustic zones. The applicators were characterized through measurements of acoustic power output and intensity beam distributions in degassed water, in vitro temperature measurements in a perfused kidney model, and in vivo temperature distributions in pig thigh muscle. The angular power deposition patterns obtained in water were closely correlated to the resultant temperature distributions measured in the perfused kidney and in vivo pig thigh muscle. These sectored catheter-cooled and direct-coupled devices both demonstrated the ability to generate high temperatures (>50 degrees C) at sustained high power output levels (6-12 W) without degradation of the ultrasound transducers. Directional control of the energy deposition from the sectored ultrasound applicators was verified with corresponding temperature profiles in both the in vitro and in vivo experiments, as well as with angularly shaped thermal lesions. This is significant in that it demonstrates that heating in the angular expanse can be controlled with interstitial ultrasound applicators, thus providing more conformal thermal therapy by directing the thermal energy in the targeted tissue while protecting non-targeted tissue from thermal damage.

Measurement of thermal effects on the optical properties of prostate tissue at wavelengths of 1,064 and 633 nm.

BACKGROUND AND OBJECTIVE: The extent of thermal injury during laser prostatectomy is dependent on the light distribution in laser-irradiated tissue. As tissue is irradiated, the optical properties change as a function of temperature due to an alteration of molecular and cellular structure. The purpose of the present study was to determine how the exposure of both fresh and previously frozen canine prostate tissue to elevated temperatures affects the optical properties. STUDY DESIGN/MATERIALS AND METHODS: Optical properties were measured by using a double integrating sphere spectrophotometer with an inverse adding-doubling algorithm. Measurements were made at two wavelengths (1,064 nm and 633 nm) on samples heated in a waterbath in 5 degree-10 degree increments for 10 min through a 50 degrees C temperature range. RESULTS: Upon coagulation, the absorption coefficient of fresh tissue decreased from the baseline measurement for both wavelengths (0.027 +/- 0.003 to 0.019 +/- 0.002 for lambda = 1,064 nm; 0.073 +/- 0.007 to 0.061 +/- 0.006 for lambda = 633 nm). However, the scattering coefficient increased sharply from the baseline measurement following coagulation (3.06 +/- 0.26 to 6.05 +/- 0.29 for lambda = 1,064 nm; 4.89 +/- 0.23 to 7.22 +/- 0.30 for lambda = 633 nm). Thermal coagulation occurred during exposure to temperatures between 60 degrees C and 70 degrees C. CONCLUSION: Data obtained in this study indicate that thermal coagulation of tissue alters the optical properties. The extent to which these changes occur was found to be dependent on wavelength and freshness of tissue. These results are significant because they suggest how thermally induced changes in the optical properties may limit the depth of light penetration in tissue thus compromising treatment.

Ultrasound applicators for interstitial thermal coagulation.

Direct-coupled (DC) and catheter-cooled (CC) ultrasound applicator configurations were evaluated for high-temperature ultrasound interstitial thermal therapy (USITT) using computer simulations, acoustic beam measurements, and in vivo temperature measurements. The DC devices consist of 2.2-mm diameter tubular ultrasound transducers encapsulated within a thin biocompatible plastic coating, which can be inserted directly into the tissue. The CC devices incorporate 1.5-mm diameter tubular transducers, which are inserted within 2.2to 2.4-mm diameter plastic implant catheters and require an integrated water-cooling scheme. Simulated transient temperature profiles and cumulative thermal dose distributions indicate that each of these applicator configurations can produce target temperatures greater than 50 degrees C and corresponding thermal doses greater than 300 to 600 equivalent minutes at 43 degrees C (EM(43 degrees C)) within 5 min at a radial depth of 1 to 1.5 cm in moderately perfused tissues. Theoretical investigations of air-cooling implemented within DC applicators demonstrated a significant enhancement of thermal penetration compared with non-cooled DC applicators, thus approaching performance attainable with CC devices. Temperature distributions achieved with DC and CC applicators in vivo were in agreement with theoretical calculations and further demonstrate that the devices are practical, sufficient power output levels can be obtained, and the angular heating profiles can be shaped or directed to protect non-targeted critical normal tissues. This preliminary study demonstrates that these interstitial ultrasound applicators have potential to provide controlled thermal coagulation and necrosis of small target regions and deserve further investigation and development for possible implementation in the treatment of benign and cancerous lesions in sites such as prostate, liver, and brain.

Air-cooling of direct-coupled ultrasound applicators for interstitial hyperthermia and thermal coagulation.

The feasibility of using air-cooling to improve the thermal penetration of direct-coupled interstitial ultrasound (US) applicators was investigated using biothermal simulations, bench experiments, phantom testing, and in vivo thermal dosimetry. Two applicator configurations using tubular US transducers were constructed and tested. The first design, intended for simultaneous thermobrachy-therapy, utilizes a 2.5 mm OD transducer with a central lumen to accommodate a radiation source from remote afterloaders. The second applicator consists of a 2.2 mm OD transducer designed for coagulative thermal therapy. Both designs provide cooling of the inner transducer surface by the counterflow of chilled air or CO2 gas through the annulus of the enclosed applicator. The average convective heat transfer (ha) associated with each applicator was determined empirically from curve-fits of radial steady-state temperatures measured in a tissue-mimicking phantom. High levels of convective heat transfer (ha > 500 W m-2 degrees C-1) were demonstrated in both designs at relatively low flow rates (< 5 L min-1). Transient and steady-state radial heating profiles were also measured in vivo (pig thigh muscle) with and without cooling. The therapeutic radius for hyperthermia (41-45 degrees C) was extended from 5-6 mm (without cooling) to 11-19 mm with air-cooling (4.8 L min-1, airflow 10 degrees C), effectively doubling and tripling the thermal penetration in vivo. Similar improvements were demonstrated at higher temperatures with the thermal coagulation applicator. Biothermal simulations, which modeled the physical, thermal, and acoustic parameters of the air-cooled applicator and surrounding tissue, were also used to investigate potential improvements in heating patterns. The simulated radial heating profiles with transducer cooling demonstrated significantly enhanced thermal penetration over the experimental range of convective transfer, and also agreed with in vivo results. These theoretical and experimental results clearly show air-cooling controls the transducer surface temperature, significantly increases thermal penetration, and produces a greater treatment volume for direct-coupled US applicators in hyperthermia and thermal coagulation.