Quality assurance guidelines for interstitial hyperthermia.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Correlation of contrast-enhanced MR images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates.

Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

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.

Ultrasound applicators with internal water-cooling for high-powered interstitial thermal therapy.

Internal water-cooling of direct-coupled ultrasound (US) applicators for interstitial thermal therapy (hyperthermia and coagulative thermal therapy) was investigated. Implantable applicators were constructed using tubular US sources (360 angular acoustic emittance, approximately 7 MHz) of 10 mm length and 1.5, 1.8, 2.2, and 2.5 mm outer diameter (OD). Directional applicators were also constructed using 2.2 mm OD tubes sectored to provide active acoustic sectors of 90 degrees and 200 degrees. A water-cooling mechanism was integrated within the inner lumen of the applicator to remove heat from the inner transducer surface. High levels of convective heat transfer (2100-3800 W/m2K) were measured for practical water flow rates of 20-80 mL/min. Comparative acoustic measurements demonstrated that internal water-cooling did not significantly degrade the acoustic intensity or beam distribution of the US transducers. Water-cooling allowed substantially higher levels of applied electrical power (> 45 W) than previous designs (with air-cooling or no cooling), without detriment to the applicators. High-temperature heating trials performed with these applicators in vivo (porcine liver and thigh muscle) and in vitro (bovine liver) showed improved thermal penetration and coagulation. Radial depth of coagulation from the applicator surface ranged from 12 to 20 mm for 1-5 min of sonication with 28-W applied power. Higher powers (41 W) demonstrated increased coagulation depths (approximately 9 mm) at shorter times (15 s). Thermal lesion dimensions (angular and axial expanse) produced with directional applicators were controlled and directed, and corresponded to the active zone of the transducer. These characteristic lesion shapes were also generally unchanged with different sonication times and power, and were found to be consistent with previous coagulation studies using air-cooled applicators. The implementation of water-cooling is a significant advance for the application of ultrasound interstitial thermal therapy (USITT), providing greater treatment volumes, shorter treatment times, and the potential for treatment of highly perfused tissue with shaped lesions.

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.

Thermal and SAR characterization of multielement dual concentric conductor microwave applicators for hyperthermia, a theoretical investigation.

Six aperture array dual concentric conductor (DCO) microwave hyperthermia applicators were studied using theoretical models to characterize power deposition (SAR) and steady state temperature distributions in perfused tissue. SAR patterns were calculated using the finite difference time domain (FDTD) numerical method, and were used as input to a finite difference thermal modeling program based on the Pennes Bio-Heat Equation in order to calculate corresponding temperature distributions. Numerous array configurations were investigated including the use of different size DCC apertures (2, 3, and 4 cm), different spacing between apertures (1.0-2.0 cm), and different water bolus thicknesses (5-15 mm). Thermal simulations were repeated using blood perfusion values ranging from 0.5 to 5 kg/m3 s. Results demonstrate the ability of DCC array applicators to effectively and uniformly heat tissue down to a depth of 7.5-10 mm below the skin surface for a large number of different combinations of DCC element size, spacing, and water bolus thickness. Results also reveal the close correlation between SAR patterns and corresponding temperature distributions, verifying that design studies of the applicator can be performed confidently by analysis of SAR, from which the thermal behavior can be estimated. These simulations are useful in the design optimization of large microwave DCC array applicators for superficial tissue heating and for identifying appropriate aperture spacing and bolus thickness parameters for different size DCC aperture arrays and tissue blood perfusion conditions.

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.

Axial control of thermal coagulation using a multi-element interstitial ultrasound applicator with internal cooling.

A multi-element, direct-coupled ultrasound (US) applicator with internal water cooling was investigated for axial control of interstitial thermal coagulation. A prototype implantable applicator was constructed with a linear array of three tubular PZT ultrasound transducers (each 2.5 mm OD, 10 mm length, 360 degrees emittance). Acoustic beam distributions from each element were measured and found to be collimated within the transducer length. The internally cooled applicator could sustain high levels of applied power to each transducer (0 to 40 W) and maintain acceptable applicator surface temperatures (<100 degrees C). Thermal performance of the applicator was investigated through heating trials in vivo (porcine thigh muscle and liver) and in vitro (bovine liver). The radial depth of thermal lesions produced was dependent on the applied power and sonication time and was controlled independently with power levels to each transducer element. With 18 W per element (applied electrical power) for 3 min, cylindrical thermal lesions were produced with a diameter of ~3 cm and a length ranging from 1.2 cm (with one element) to 3.5 cm (three elements). Higher powers (24 to 30 W) for 3 to 5 min provided increased depths of coagulation (~4 cm diameter lesions). Analysis of axial lesion shapes demonstrated that individual variation of power to each transducer element provided control of axial heating and depth of coagulation (for custom lesion shapes); lesion lengths corresponded to the number of active transducers. This ability to control the heating distribution dynamically along the length of the applicator has potential for improved target localization of thermal coagulation and necrosis in high temperature thermal therapy.

Ultrasound technology for hyperthermia.

Hyperthermia (HT) is used in the clinical management of cancer and benign disease. Numerous biological and clinical investigations have demonstrated that HT in the 41-45 degrees C range can significantly enhance clinical responses to radiation therapy, and has potential for enhancing other therapies, such as chemotherapy, immunotherapy and gene therapy. Furthermore, high-temperature hyperthermia (greater than 50 degrees C) alone is being used for selective tissue destruction as an alternative to conventional invasive surgery. The degree of thermal enhancement of these therapies is strongly dependent on the ability to localize and maintain therapeutic temperature elevations. Due to the often heterogeneous and dynamic properties of tissues, most notably blood perfusion and the presence of thermally significant blood vessels, therapeutic temperature elevations are difficult to spatially and temporally control during these forms of HT therapy. However, ultrasound technology has significant advantages that allow for a higher degree of spatial and dynamic control of the heating compared to other commonly utilized heating modalities. These advantages include a favorable range of energy penetration characteristics in soft tissue and the ability to shape the energy deposition patterns. Thus, heating systems have been developed for interstitial, intracavitary, or external approaches that utilize properties such as multiple transducer arrays, phased arrays, focused beams, mechanical and/or electrical scanning, dynamic frequency control and transducers of various shapes and sizes. This article provides a general review of a selection of ultrasound hyperthermia systems that are either in clinical use or currently under development, that utilize these advantages as a means to better localize and control HT for the aforementioned therapies.

Angular directivity of thermal coagulation using air-cooled direct-coupled interstitial ultrasound applicators.

The performance characteristics and thermal coagulation of tissue produced by directional air-cooled, direct-coupled interstitial ultrasound (US) applicators were evaluated. Prototype applicators (2.2 mm o.d.) were constructed using cylindrical transducers sectored into angular active zones of 90 degrees, 200 degrees, 270 degrees, and 360 degrees. Acoustic characterization of the applicators showed the beam output to be angularly directed from the active sector of the transducer and collimated within the axial extent. Empirical determination of the average convective heat transfer coefficient, resulting from airflow cooling the inner surface of the transducer, showed significantly high levels of transfer (> 700 W m(-2) degrees C(-1)) with a flow rate of 5.6 L min(-1). Thermal performance of the applicators was characterized through high temperature heating in vivo (porcine thigh muscle, 11 trials) and in vitro (bovine liver, 46 trials). Results demonstrated directional coagulation of tissue, with good correlation between the angular extent of the lesions and the active acoustic sector. Radial depth of coagulation with a 200 degrees applicator extended 8-17 mm, with a heating time of 1-10 min, respectively. Angular and axial lesion shape remained similar over the course of 1-10 min heating trials. Implementation of air-cooling within direct-coupled interstitial US applicators provided enhanced directivity of heating in angular and axial dimensions, and significantly increased the power handling and radial depth of tissue coagulation.

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.

Minimax optimization-based inverse treatment planning for interstitial thermal therapy.

The following work represents the development and evaluation of a minimax optimization-based inverse treatment planning approach for interstitial thermal therapy of cancer and benign disease. The goal is to determine a priori optimal applicator placements and power level settings to maintain the minimum tumour temperature, Tmin, and maximum normal tissue temperature, Tmax within a prescribed therapeutic temperature range. The temperature distribution is approximated by a finite element method (FEM) solution of a bioheat transfer equation on a nonuniform finite element mesh. Lower and upper therapeutic temperature thresholds are specified in the tumour and surrounding normal tissues. A constrained minimax optimization problem is formulated to determine optimal applicator positions and power level settings that minimize the maximum (rather than average) temperature errors in the target tumour region and surrounding normal tissues. The optimization problem is formulated for two general classes of interstitial heating applicators, those with and without a surface cooling mechanism. The viability and sensitivity of this approach is investigated in the two-dimensional setting for various tumour shapes and blood perfusion levels using surface-cooled and direct-coupled interstitial ultrasound applicator power deposition models. These preliminary results indicate the utility of this approach for meeting a prescribed Tmin/Tmax-based clinical objective criterion, and its potential for generating optimal treatment plans that can withstand variations or uncertainty in blood perfusion levels.

Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.

PURPOSE: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. METHODS AND MATERIALS: Adults with newly-diagnosed, focal, supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) +/- HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. RESULTS: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ("no heat") and 40 to brachytherapy + HT ("heat"). By intent to treat, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.04 and p = 0.04). For the 33 "no heat" patients and 35 "heat" patients who underwent brachytherapy boost, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to "heat" (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on "no heat" and 6 on the "heat" arm). CONCLUSION: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity.

Effect of practical layered dielectric loads on SAR patterns from dual concentric conductor microstrip antennas.

Radiation patterns of 2 and 4cm square Dual Concentric Conductor (DCC) microstrip antennas were studied theoretically with Finite Difference Time Domain (FDTD) analysis and compared with experimental measurements of power deposition (SAR) in layered lossy dielectric loads. Single and array configurations were investigated with 915 MHz excitation applied across either one, two or four sides, or four corners of the square apertures. FDTD simulations were carried out for realistic models of a muscle tissue load coupled to the DCC antennas with a 5 mm thick bolus of either distilled water or low loss Silicone Oil. This study characterizes the effect on SAR of adding three additional thin dielectric layers which are necessary for clinical use of the applicator. These layers consist of a 0.1 mm thick dielectric coating on the array surface to provide electrical isolation of DCC apertures, and 0.15 mm thick plastic layers above and below the bolus to contain the liquid. Experimental measurements of SAR in a plane 1 cm deep in muscle phantom agree well with theoretical FDTD simulations in the multi-layered tissue models. These studies reveal significant changes in SAR for applicator configurations involving low dielectric constant (Er) layers on either side of a high Er water bolus layer. Prominent changes include a broadening and centring of the SAR under each aperture as well as increased SAR penetration in muscle. No significant differences are noted between the simple and complete load configurations for the low Er Silicone Oil bolus. Both theoretical and measured data demonstrate relatively uniform SAR distributions with > 50% of maximum SAR extending to the perimeter of single and multi-aperture array configurations of DCC applicators when using a thin 5 mm water or Silicone Oil bolus.

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.