The effect of injected dose on localized tumor accumulation and cardiac uptake of doxorubicin in a Vx2 rabbit tumor model using MR-HIFU mild hyperthermia and thermosensitive liposomes.

PURPOSE: When doxorubicin (DOX) is administered via lyso-thermosensitive liposomes (LTLD), mild hyperthermia enhances localized delivery to heated vs. unheated tumors. The optimal LTLD dose and the impact of different doses on systemic drug distribution are unknown.Materials and methods: In this study, we evaluated local and systemic DOX delivery with three LTLD doses (0.1, 0.5, and 2.5 mg/kg) in a Vx2 rabbit tumor model. Temporally and spatially accurate controlled hyperthermia was achieved using a clinical MR-HIFU system for the intended heating duration (40 min).Results: DOX concentration in tissues delivered from LTLD combined with MR-HIFU mild hyperthermia are dose-dependent, including heated/unheated tumor, heart, and other healthy organs. Higher DOX accumulation and tumor-to-heart drug concentration ratio, defined as the ratio of DOX delivered into the tumor vs the heart, were observed in heated tumors compared to unheated tumors in all three tested doses. The DOX uptake efficiency for each mg/kg of LTLD injected IV of heated tumor was significantly higher than that of unheated tumor and heart within the tested dose range (0.1-2.5 mg/kg). The DOX uptake for the heart linearly scaled up as a function of dose while that for the heated tumor showed some evidence of saturation at the high dose of 2.5 mg/kg.Conclusions: These results provide guidance on clinical protocol design of hyperthermia-triggered drug delivery.

Remote acoustic sensing as a safety mechanism during exposure of metal implants to alternating magnetic fields.

Treatment of prosthetic joint infections often involves multiple surgeries and prolonged antibiotic administration, resulting in a significant burden to patients and the healthcare system. We are exploring a non-invasive method to eradicate biofilm on metal implants utilizing high-frequency alternating magnetic fields (AMF) which can achieve surface induction heating. Although proof-of-concept studies demonstrate the ability of AMF to eradicate biofilm in vitro, there is a legitimate safety concern related to the potential for thermal damage to surrounding tissues when considering heating implanted metal objects. The goal of this study was to explore the feasibility of detecting acoustic emissions associated with boiling at the interface between a metal implant and surrounding soft tissue as a wireless safety sensing mechanism. Acoustic emissions generated during in vitro and in vivo AMF exposures were captured with a hydrophone, and the relationship with surface temperature analyzed. The effect of AMF exposure power, surrounding media composition, implant location within the AMF transmitter, and implant geometry on acoustic detection during AMF therapy was also evaluated. Acoustic emissions were reliably identified in both tissue-mimicking phantom and mouse studies, and their onset coincided with the implant temperature reaching the boiling threshold. The viscosity of the surrounding medium did not impact the production of acoustic emissions; however, emissions were not present when the medium was oil due to the higher boiling point. Results of simulations and in vivo studies suggest that short-duration, high-power AMF exposures combined with acoustic sensing can be used to minimize the amount of thermal damage in surrounding tissues. These studies support the hypothesis that detection of boiling associated acoustic emissions at a metal/tissue interface could serve as a real-time, wireless safety indicator during AMF treatment of biofilm on metallic implants.

Temperature-sensitive liposomal ciprofloxacin for the treatment of biofilm on infected metal implants using alternating magnetic fields.

Implants are commonly used as a replacement for damaged tissue. Many implants, such as pacemakers, chronic electrode implants, bone screws, and prosthetic joints, are made of or contain metal. Infections are one of the difficult to treat complications associated with metal implants due to the formation of biofilm, a thick aggregate of extracellular polymeric substances (EPS) produced by the bacteria. In this study, we treated a metal prosthesis infection model using a combination of ciprofloxacin-loaded temperature-sensitive liposomes (TSL) and alternating magnetic fields (AMF). AMF heating is used to disrupt the biofilm and release the ciprofloxacin-loaded TSL. The three main objectives of this study were to (1) investigate low- and high-temperature-sensitive liposomes (LTSLs and HTSLs) containing the antimicrobial agent ciprofloxacin for temperature-mediated antibiotic release, (2) characterise in vitro ciprofloxacin release and stability and (3) study the efficacy of combining liposomal ciprofloxacin with AMF against Pseudomonas aeruginosa biofilms grown on metal washers. The release of ciprofloxacin from LTSL and HTSL was assessed in physiological buffers. Results demonstrated a lower transition temperature for both LTSL and HTSL formulations when incubated in serum as compared with PBS, with a more pronounced impact on the HTSLs. Upon combining AMF with temperature-sensitive liposomal ciprofloxacin, a 3 log reduction in CFU of Pseudomonas aeruginosa in biofilm was observed. Our initial studies suggest that AMF exposure on metal implants can trigger release of antibiotic from temperature sensitive liposomes for a potent bactericidal effect on biofilm.

Employing high-frequency alternating magnetic fields for the non-invasive treatment of prosthetic joint infections.

Treatment of prosthetic joint infection (PJI) usually requires surgical replacement of the infected joint and weeks of antibiotic therapy, due to the formation of biofilm. We introduce a non-invasive method for thermal destruction of biofilm on metallic implants using high-frequency (>100 kHz) alternating magnetic fields (AMF). In vitro investigations demonstrate a >5-log reduction in bacterial counts after 5 minutes of AMF exposure. Confocal and scanning electron microscopy confirm removal of biofilm matrix components within 1 minute of AMF exposure, and combination studies of antibiotics and AMF demonstrate a 5-log increase in the sensitivity of Pseudomonas aeruginosa to ciprofloxacin. Finite element analysis (FEA) simulations demonstrate that intermittent AMF exposures can achieve uniform surface heating of a prosthetic knee joint. In vivo studies confirm thermal damage is confined to a localized region (<2 mm) around the implant, and safety can be achieved using acoustic monitoring for the presence of surface boiling. These initial studies support the hypothesis that AMF exposures can eradicate biofilm on metal implants, and may enhance the effectiveness of conventional antibiotics.

Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

Drift correction for accurate PRF-shift MR thermometry during mild hyperthermia treatments with MR-HIFU.

UNLABELLED: There is growing interest in performing hyperthermia treatments with clinical magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) therapy systems designed for tissue ablation. During hyperthermia treatment, however, due to the narrow therapeutic window (41-45 °C), careful evaluation of the accuracy of proton resonant frequency (PRF) shift MR thermometry for these types of exposures is required. PURPOSE: The purpose of this study was to evaluate the accuracy of MR thermometry using a clinical MR-HIFU system equipped with a hyperthermia treatment algorithm. METHODS: Mild heating was performed in a tissue-mimicking phantom with implanted temperature sensors using the clinical MR-HIFU system. The influence of image-acquisition settings and post-acquisition correction algorithms on the accuracy of temperature measurements was investigated. The ability to achieve uniform heating for up to 40 min was evaluated in rabbit experiments. RESULTS: Automatic centre-frequency adjustments prior to image-acquisition corrected the image-shifts in the order of 0.1 mm/min. Zero- and first-order phase variations were observed over time, supporting the use of a combined drift correction algorithm. The temperature accuracy achieved using both centre-frequency adjustment and the combined drift correction algorithm was 0.57° ± 0.58 °C in the heated region and 0.54° ± 0.42 °C in the unheated region. CONCLUSION: Accurate temperature monitoring of hyperthermia exposures using PRF shift MR thermometry is possible through careful implementation of image-acquisition settings and drift correction algorithms. For the evaluated clinical MR-HIFU system, centre-frequency adjustment eliminated image shifts, and a combined drift correction algorithm achieved temperature measurements with an acceptable accuracy for monitoring and controlling hyperthermia exposures.

Localised hyperthermia in rodent models using an MRI-compatible high-intensity focused ultrasound system.

PURPOSE: Localised hyperthermia in rodent studies is challenging due to the small target size. This study describes the development and characterisation of an MRI-compatible high-intensity focused ultrasound (HIFU) system to perform localised mild hyperthermia treatments in rodent models. MATERIAL AND METHODS: The hyperthermia platform consisted of an MRI-compatible small animal HIFU system, focused transducers with sector-vortex lenses, a custom-made receive coil, and means to maintain systemic temperatures of rodents. The system was integrated into a 3T MR imager. Control software was developed to acquire images, process temperature maps, and adjust output power using a proportional-integral-derivative feedback control algorithm. Hyperthermia exposures were performed in tissue-mimicking phantoms and in a rodent model (n = 9). During heating, an ROI was assigned in the heated region for temperature control and the target temperature was 42 °C; 30 min mild hyperthermia treatment followed by a 10-min cooling procedure was performed on each animal. RESULTS: 3D-printed sector-vortex lenses were successful at creating annular focal regions which enables customisation of the heating volume. Localised mild hyperthermia performed in rats produced a mean ROI temperature of 42.1 ± 0.3 °C. The T10 and T90 percentiles were 43.2 ± 0.4 °C and 41.0 ± 0.3 °C, respectively. For a 30-min treatment, the mean time duration between 41-45 °C was 31.1 min within the ROI. CONCLUSIONS: The MRI-compatible HIFU system was successfully adapted to perform localised mild hyperthermia treatment in rodent models. A target temperature of 42 °C was well-maintained in a rat thigh model for 30 min.

Thermometry and ablation monitoring with ultrasound.

In this review we present the current status of ultrasound thermometry and ablation monitoring, with emphasis on the diverse approaches published in the literature and with an eye on which methods are closest to clinical reality. It is hoped that this review will serve as a guide to the expansion of sonographic methods for treatment monitoring and thermometry since the last brief review in 2007.

Hyperthermia-mediated doxorubicin release from thermosensitive liposomes using MR-HIFU: therapeutic effect in rabbit Vx2 tumours.

PURPOSE: The aim of this study was to determine whether localised drug release using thermosensitive liposomal doxorubicin (TLD) and mild hyperthermia produced by a clinical magnetic resonance high intensity focused ultrasound (MR-HIFU) system improves anti-tumour efficacy over TLD alone in rabbit Vx2 tumours. MATERIALS AND METHODS: Rabbits bearing one Vx2 thigh tumour (n = 6 per group) were administered TLD (1.67 mg/kg) either with or without MR-HIFU mild hyperthermia (20 min, 42.0 °C). Tumour progression was measured using contrast-enhanced T1-weighted MR imaging. Toxicity was evaluated by changes in body weight, blood counts, and blood chemistry. Tumour volume, body weight, and blood data were acquired weekly for the first month and biweekly thereafter. RESULTS: Rabbits treated with TLD plus MR-HIFU mild hyperthermia had target region temperatures with spatial-median, temporal-mean of 41.4° ± 0.6 °C; 10th and 90th percentile temperatures were 40.2 and 42.7 °C. All six rabbits that received TLD alone had rapid tumour progression and reached the tumour size end point (maximum dimension >6 cm) within 24 days. Four of six rabbits treated with TLD plus MR-HIFU mild hyperthermia survived to the study end point of 60 days; one reached tumour size end point, one had hyperthermia-related toxicity, all had at least a transient decrease in tumour volume. Weekly body weight, complete blood counts, and blood chemistry did not reveal additional evidence of drug or hyperthermia-related toxicity. CONCLUSIONS: Rabbit Vx2 tumours treated with a single infusion of TLD during MR-HIFU mild hyperthermia had reduced tumour growth vs. tumours treated with TLD alone. These findings are an important step toward clinical translation of localised drug delivery using MR-HIFU and TLD.

Investigation of power and frequency for 3D conformal MRI-controlled transurethral ultrasound therapy with a dual frequency multi-element transducer.

Transurethral ultrasound therapy uses real-time magnetic resonance (MR) temperature feedback to enable the 3D control of thermal therapy accurately in a region within the prostate. Previous canine studies showed the feasibility of this method in vivo. The aim of this study was to reduce the procedure time, while maintaining targeting accuracy, by investigating new combinations of treatment parameters. Simulations and validation experiments in gel phantoms were used, with a collection of nine 3D realistic target prostate boundaries obtained from previous preclinical studies, where multi-slice MR images were acquired with the transurethral device in place. Acoustic power and rotation rate were varied based on temperature feedback at the prostate boundary. Maximum acoustic power and rotation rate were optimised interdependently, as a function of prostate radius and transducer operating frequency. The concept of dual frequency transducers was studied, using the fundamental frequency or the third harmonic component depending on the prostate radius. Numerical modelling enabled assessment of the effects of several acoustic parameters on treatment outcomes. The range of treatable prostate radii extended with increasing power, and tended to narrow with decreasing frequency. Reducing the frequency from 8 MHz to 4 MHz or increasing the surface acoustic power from 10 to 20 W/cm(2) led to treatment times shorter by up to 50% under appropriate conditions. A dual frequency configuration of 4/12 MHz with 20 W/cm(2) ultrasound intensity exposure can treat entire prostates up to 40 cm(3) in volume within 30 min. The interdependence between power and frequency may, however, require integrating multi-parametric functions in the controller for future optimisations.

Thermally-triggered 'off-on-off' response of gadolinium-hydrogel-lipid hybrid nanoparticles defines a customizable temperature window for non-invasive magnetic resonance imaging thermometry.

For effective and safe thermotherapy, real-time, accurate, three-dimensional tissue thermometry is required. Magnetic resonance imaging (MRI)-based thermometry in combination with current temperature responsive contrast agents only provides an 'off-on' signal at a certain temperature, not indicating temperature increases beyond the desired therapeutic levels. To overcome this limitation, a novel Gd-chelated hydrogel-lipid hybrid nanoparticle (HLN) formulation was developed that provides an 'off-on-off' signal defining a thermometric window for MR thermometry. Novel thermally responsive poly(N-isopropylacrylamide-co-acrylamide) (NIPAM-co-AM) hydrogel nanoparticles (<15 nm) with bisallylamidodiethylenetriaminetriacetic acid, a novel crosslinker with Gd(3+) chelation functionality, were synthesized. The Gd-hydrogel nanoparticles were encapsulated in a solid lipid nanoparticle matrix that prevented T(1)-weighted contrast signal enhancement. Melting of the matrix lipid freed the Gd-hydrogel nanoparticles into the bulk water and an 'off-on' contrast signal enhancement occurred. As the temperature was further increased to temperatures greater than, the volume phase transition temperature of the hydrogel nanoparticles, they collapsed and provided an 'on-off' signal diminution. Both the 'off-on' and the 'on-off' transition temperature could be tailored by changing the lipid matrix and altering the NIPAM/AM ratio in the hydrogel, respectively. This allowed MRI thermometry of different temperature windows using the Gd-HLN system.

Localised drug release using MRI-controlled focused ultrasound hyperthermia.

PURPOSE: Thermosensitive liposomes provide a mechanism for triggering the local release of anticancer drugs, but this technology requires precise temperature control in targeted regions with minimal heating of surrounding tissue. The objective of this study was to evaluate the feasibility of using MRI-controlled focused ultrasound (FUS) and thermosensitive liposomes to achieve thermally mediated localised drug delivery in vivo. MATERIALS AND METHODS: Results are reported from ten rabbits, where a FUS beam was scanned in a circular trajectory to heat 10-15 mm diameter regions in normal thigh to 43°C for 20-30 min. MRI thermometry was used for closed-loop feedback control to achieve temporally and spatially uniform heating. Lyso-thermosensitive liposomal doxorubicin was infused intravenously during hyperthermia. Unabsorbed liposomes were flushed from the vasculature by saline perfusion 2 h later, and tissue samples were harvested from heated and unheated thigh regions. The fluorescence intensity of the homogenised samples was used to calculate the concentration of doxorubicin in tissue. RESULTS: Closed-loop control of FUS heating using MRI thermometry achieved temperature distributions with mean, T90 and T10 of 42.9°C, 41.0°C and 44.8°C, respectively, over a period of 20 min. Doxorubicin concentrations were significantly higher in tissues sampled from heated than unheated regions of normal thigh muscle (8.3 versus 0.5 ng/mg, mean per-animal difference = 7.8 ng/mg, P < 0.05, Wilcoxon matched pairs signed rank test). CONCLUSIONS: The results show the potential of MRI-controlled focused ultrasound hyperthermia for enhanced local drug delivery with temperature-sensitive drug carriers.

MRI-controlled transurethral ultrasound therapy for localised prostate cancer.

Minimally invasive treatments for localised prostate cancer are being developed with the aim of achieving effective disease control with low morbidity. High-temperature thermal therapy aimed at producing irreversible thermal coagulation of the prostate gland is attractive because of the rapid onset of thermal injury, and the immediate visualisation of tissue response using medical imaging. High-intensity ultrasound therapy has been shown to be an effective means of achieving thermal coagulation of prostate tissue using minimally invasive devices inserted into the rectum, urethra, or directly into the gland itself. The focus of this review is to describe the work done in our group on the development of MRI-controlled transurethral ultrasound therapy. This technology utilises high intensity ultrasound energy delivered from a transurethral device to achieve thermal coagulation of prostate tissue. Control over the spatial pattern of thermal damage is achieved through closed-loop temperature feedback using quantitative MR thermometry during treatment. The technology, temperature feedback algorithms, and results from numerical modelling, along with experimental results obtained in animal and human studies are described. Our experience suggests that this form of treatment is technically feasible, and compatible with existing MR imaging systems. Temperature feedback control algorithms using MR thermometry can achieve spatial treatment accuracy of a few millimetres in vivo. Patient-specific simulations predict that surrounding tissues can be spared from thermal damage if appropriate measures are taken into account during treatment planning. Recent human experience has been encouraging and motivates further evaluation of this technology as a potential treatment for localised prostate cancer.

MRI-guided transurethral ultrasound therapy of the prostate gland using real-time thermal mapping: initial studies.

OBJECTIVE: To confirm the correlation between planning and thermal injury of the prostate as determined by magnetic resonance imaging (MRI) and histology in canine and humans treated with transurethral ultrasound. MATERIAL AND METHODS: Canine studies: 2 sets of in vivo studies were performed under general anesthesia in 1.5 T clinical MRI. Nine dogs were treated using single transducer; 8 dogs were treated using urethral applicator with multiple transducers. Rectal cooling was maintained. After initial imaging, a target boundary was selected and high-intensity ultrasound energy delivered. The spatial temperature distribution was measured continuously every 5 seconds with MR thermometry using the proton-resonant frequency shift method. The goal was to achieve 55 °C at the target boundary. After treatment, the prostate was harvested and fixed with adjoining tissue, including rectum. Temperature maps, anatomical images, and histologic sections were registered to each other and compared. Human studies: To date, 5 patients with localized prostate cancer have been treated immediately before radical prostatectomy. Approximately 30% of the gland volume was targeted. RESULTS: A continuous pattern of thermal coagulation was successfully achieved within the target region, with an average spatial precision of 1-2 mm. Radical prostatectomy was routine, with an uncomplicated postoperative course in all patients. The correlation between anatomical, thermal, and histologic images was ≤3 mm. Treatment time was <30 minutes. No thermal damage to rectal tissue was observed. CONCLUSIONS: Thermal ablation within the prescribed target of the prostate has been successfully demonstrated in canine studies. The treatment is also feasible in humans.

Quantitative analysis of 3-D conformal MRI-guided transurethral ultrasound therapy of the prostate: theoretical simulations.

PURPOSE: The capability of MRI-guided transurethral ultrasound therapy to produce continuous regions of thermal coagulation that conform to human prostate geometries was evaluated using 3-D anatomical models of prostate cancer patients. METHODS: Numerical simulations incorporating acoustic and biothermal modeling and a novel temperature control feedback algorithm were used to evaluate treatment accuracy of a rotating dual-frequency multi-element transducer. Treatments were simulated on twenty anatomical models obtained from the manual segmentation of the prostate and surrounding structures on MR images of prostate cancer patients obtained prior to radical prostatectomy. RESULTS: Regions of thermal coagulation could be accurately shaped to predefined volumes within 1 mm across the vast majority of the prostates. Over- and under-treated volumes remained smaller than 4% of the corresponding prostate volumes which ranged from 14 to 60 cc. Treatment times were typically 30 min and remained below 60 min even for large 60 cc prostates. Heating of the rectal wall remained below 30 min(43 degrees C) in half of the patient models with only minor, superficial heating in the other cases. The simulated feedback control algorithm adjusted the ultrasound transducer parameters such that high treatment accuracy was maintained despite variable blood perfusion, changing tissue ultrasound attenuation, and practical temperature measurement noise and sampling rate. CONCLUSIONS: Numerical simulations predict that MRI-guided transurethral ultrasound therapy is capable of producing highly accurate volumes of thermal coagulation that conform to human prostate glands.

Prostate tissue analysis immediately following magnetic resonance imaging guided transurethral ultrasound thermal therapy.

PURPOSE: Preclinical experiments were performed in an acute canine model to analyze the spatial pattern of thermal damage generated in the prostate gland following treatment with a prototype magnetic resonance imaging guided transurethral ultrasound heating system. In particular the boundary of tissue coagulation was analyzed to quantify the treatment margin resulting from this technology. MATERIALS AND METHODS: A heating device incorporating a planar 20 x 3.5 mm transducer operated at 9.1 MHz was used to deliver ultrasound energy to targeted regions in the prostate gland in 7 animals monitored with magnetic resonance imaging thermometry during heating. The animals were sacrificed approximately 45 minutes after treatment. The thermal damage pattern was evaluated using contrast enhanced magnetic resonance imaging, vital tissue staining, and whole mount hematoxylin and eosin stained histological sections. An image warping technique enabled quantitative comparison of these data. RESULTS: Regions of thermal fixation, coagulative necrosis and hemorrhage were observed in the treated prostate glands. The extent of the necrotic region was relatively insensitive to vessel cooling effects. Metabolic enzyme functionality coincided with tissue outside of the treatment area. At the edge of the thermal damage pattern the transition from coagulative necrosis to no visible damage occurred within 3 mm or less. CONCLUSIONS: The narrow extent of the thermal margin suggests that tissue sparing outside of the prostate could be an advantage of this treatment. Histological measurements showed a high level of spatial accuracy, useful for developing accurate control techniques for directional transurethral ultrasound thermal therapy in the treatment of prostate diseases.

Analysis of factors important for transurethral ultrasound prostate heating using MR temperature feedback.

The feasibility of using MR thermometry for temperature feedback to control a transurethral ultrasound heating applicator with planar transducers was investigated. The sensitivity of a temperature-based feedback algorithm to spatial (control point area, slice thickness, angular alignment) and non-spatial (imaging time, temperature uncertainty) parameters was evaluated through numerical simulations. The angular alignment of the control point with the ultrasound beam was an important parameter affecting the average spatial error in heat delivery. The other spatial parameters were less influential, thus providing an opportunity to reduce spatial resolution for increased SNR in the MR imaging. The update time was the most important non-spatial parameter determining the performance of the control algorithm. Combined non-spatial and spatial parameters achieved acceptable performance with a voxel size of 3 mm x 3 mm, a 10 mm slice thickness and a 5 s update time. Temperature uncertainty of up to 2 degrees C had little effect on the performance of the control algorithm but did reduce the average error slightly due to a systematic, noise-induced overestimation of the boundary temperature. These simulations imply that MR thermometry performed on clinical 1.5 T imaging systems is of sufficient quality for use as thermal feedback for conformal prostate thermal therapy with transurethral ultrasound heating applicators incorporating planar transducers.

Method for MRI-guided conformal thermal therapy of prostate with planar transurethral ultrasound heating applicators.

A method for conformal prostate thermal therapy using transurethral ultrasound heating applicators incorporating planar transducers is described. The capability to shape heating patterns to the geometry of the prostate gland from a single element in a multi-element heating applicator was evaluated using Bioheat transfer modelling. Eleven prostate geometries were obtained from patients who underwent MR imaging of the prostate gland prior to radical prostatectomy. Results indicate that ultrasound heating applicators incorporating multi-frequency planar transducers (4 x 20 mm, f = 4.7 MHz, 9.7 MHz) are capable of shaping thermal damage patterns to the geometry of individual prostates. A temperature feedback control algorithm has been developed to control the frequency, rotation rate and applied power level from transurethral heating applicators based on measurements of the boundary temperature during heating. The discrepancy between the thermal damage boundary and the target boundary was less than 5 mm, and the transition distance between coagulation and normal tissue was less than 1 cm. Treatment times for large prostate volumes were less than 50 min, and perfusion did not have significant impact on the control algorithm. Rectal cooling will play an important role in reducing undesired heating near the rectal wall. Experimental validation of the simulations in a tissue-mimicking gel phantom demonstrated good agreement between the predicted and generated patterns of thermal damage.

Multi-modality tissue-mimicking phantom for thermal therapy.

A tissue-mimicking phantom material has been developed for use with thermal therapy devices and techniques. This material has magnetic resonance properties (primarily T2) which change drastically upon thermal coagulation, enabling its use for device characterization and treatment verification using simple T2-weighted imaging techniques. The coagulation temperature of the phantom can be changed from 50-60 degrees C by adjusting the pH from 4.3 to 4.7. The energy absorption properties can be adjusted to match the acoustical and optical properties of tissues. T2 relaxation measurements are provided as a function of temperature, along with T2-weighted MR images to illustrate the visualization of heating patterns. A complete recipe for fabricating phantoms is provided.