Prostate Thermal Therapy Research Articles

Numerical modelling for simulation and treatment planning of prostate thermal therapy

AbstractA 2D transmission line matrix model is used to study thermal transfer in living tissues exposed to laser energy. Damage size because of thermal coagulation in thermal treatment of benign prostate hyperplasia is determined quantitatively. Results show a quasilinear dependency of blood perfusion on temperature at the beginning of coagulation. Immediately thereafter, blood perfusion decreases considerably until it shuts down when the tissue under investigation has been coagulated. Increase in perfusion rate (ω) leads to high values of t100, which is the time required to reach a primary zone temperature of about 100 °C, and reflects the increased cooling created by perfusion. The transmission line matrix numerical model predicts the coagulation damage contours; that way, it has a clinical interest in therapy as an aid for clinicians because damage cannot be easily measured within patients. Results are validated through comparison with other researches. Copyright © 2014 John Wiley & Sons, Ltd.

Transurethral ultrasound applicators with dynamic multi‐sector control for prostate thermal therapy: In vivo evaluation under MR guidance

The purpose of this study was to explore the feasibility and performance of a multi-sectored tubular array transurethral ultrasound applicator for prostate thermal therapy, with potential to provide dynamic angular and length control of heating under MR guidance without mechanical movement of the applicator. Test configurations were fabricated, incorporating a linear array of two multi-sectored tubular transducers (7.8-8.4 MHz, 3 mm OD, 6 mm length), with three 120 degrees independent active sectors per tube. A flexible delivery catheter facilitated water cooling (100 ml min(-1)) within an expandable urethral balloon (35 mm long x 10 mm diameter). An integrated positioning hub allows for rotating and translating the transducer assembly within the urethral balloon for final targeting prior to therapy delivery. Rotational beam plots indicate approximately 90 degrees-100 degrees acoustic output patterns from each 120 degrees transducer sector, negligible coupling between sectors, and acoustic efficiencies between 41% and 53%. Experiments were performed within in vivo canine prostate (n = 3), with real-time MR temperature monitoring in either the axial or coronal planes to facilitate control of the heating profiles and provide thermal dosimetry for performance assessment. Gross inspection of serial sections of treated prostate, exposed to TTC (triphenyl tetrazolium chloride) tissue viability stain, allowed for direct assessment of the extent of thermal coagulation. These devices created large contiguous thermal lesions (defined by 52 degrees C maximum temperature, t43 = 240 min thermal dose contours, and TTC tissue sections) that extended radially from the applicator toward the border of the prostate (approximately15 mm) during a short power application (approximately 8-16 W per active sector, 8-15 min), with approximately 200 degrees or 360 degrees sector coagulation demonstrated depending upon the activation scheme. Analysis of transient temperature profiles indicated progression of lethal temperature and thermal dose contours initially centered on each sector that coalesced within approximately 5 min to produce uniform and contiguous zones of thermal destruction between sectors, with smooth outer boundaries and continued radial propagation in time. The dimension of the coagulation zone along the applicator was well-defined by positioning and active array length. Although not as precise as rotating planar and curvilinear devices currently under development for MR-guided procedures, advantages of these multi-sectored transurethral applicators include a flexible delivery catheter and that mechanical manipulation of the device using rotational motors is not required during therapy. This multi-sectored tubular array transurethral ultrasound technology has demonstrated potential for relatively fast and reasonably conformal targeting of prostate volumes suitable for the minimally invasive treatment of BPH and cancer under MR guidance, with further development warranted.

Recent advances in nonsurgical management of localized prostate cancer

limited to clinical stage T1 or T2, oncological outcomes are believed to be comparable for most men undergoing RP, external-beam radiation, or brachytherapy. Therefore, the basis upon which patients select the primary therapy has shifted toward the consideration of treatment-related morbidity and health-related QOL. Although the probability of eradicating prostate cancer is increased by increasing the radiation dose, classic radiotherapy techniques at doses of more than 70 Gy result in high rates of severe rectal and bladder toxicity. Threedimensional (3D)-conformal radiotherapy and, more recently, IMRT have been shown to improve local control and signifi cantly decrease the side effects, thus improving patient health-related QOL. With recent advances in transrectal ultrasound image-guided and computer-based treatment planning systems, prostate brachytherapy has been widely accepted as a safe and effective treatment for localized prostate cancer. In Japan, the use of iodine-125 as a seed source was legally approved in 2003, and since then the number of these procedures has been increasing dramatically. A number of innovative local therapeutic approaches have been investigated for men with localized prostate cancer, including HIFU, cryotherapy, and thermal therapy. Most of these approaches have not yet suffi ciently matured to be considered as standard therapy for men with prostate cancer, but these investigational treatments appear promising. With continuing technological refi nements, some of these could become established methods of treatment in future. On the other hand, although classical hormonal treatment for men with localized prostate cancer is widely used in clinical practice, its particular role remains to be elucidated, and further study is warranted to establish its clinical signifi cance. In this issue of the International Journal of Clinical Oncology, leaders in the fi eld review the current status and future perspectives of recently developed nonsurgical treatment modalities for localized prostate cancer. I believe these review articles will be useful to aid in our understanding of recent progress in the management of prostate cancer. Received: July 27, 2007

Prostate thermal therapy with high intensity transurethral ultrasound: The impact of pelvic bone heating on treatment delivery

Purpose: This study was designed to assess pelvic bone temperature during typical treatment regimens of transurethral ultrasound thermal ablation of the prostate to establish guidelines for limiting bone heating.Methods: Treatment with transurethral planar, curvilinear, and sectored tubular applicators was simulated using an acoustic and biothermal pelvic model that accommodates applicator sweeping, boundary temperature control, and changes in perfusion and attenuation with thermal dose to more accurately model ultrasound energy penetration. The effects of various parameters including power and frequency (5–10 MHz) on bone heating were assessed for a range of prostate cross-sections (3–5 cm) and bone distances (1–3 cm).Results: All devices can produce significant bone heating (temperatures >50°C, thermal dose >240 EM43°C) without optimization of applied frequency or power for bone <3 cm from the prostate boundary. In small glands (∼3 cm) increasing operating frequency of curvilinear and planar devices can increase bone temperatures, whereas the tubular applicator can be used at 10 MHz to avoid likely bone damage. In larger prostates (4–5 cm wide) increasing frequency reduces bone heating but can substantially increase treatment time. Lowering power can reduce bone temperature but may increase thermal dose by increasing treatment duration. All applicators can be used to treat glands 4–5 cm with limited bone heating by selecting appropriate power and frequency.Conclusions: Pubic bone heating during ultrasound thermal therapy of the prostate can be substantial in certain situations. Successful realization of this therapy will require patient-specific treatment planning to optimally determine power and frequency in order to minimize bone heating.

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 × 3 mm, a 10 mm slice thickness and a 5 s update time. Temperature uncertainty of up to 2 °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 × 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.

In vitro thermal therapy of AT-1 Dunning prostate tumours

To advance the utility of prostate thermal therapy, this study investigated the thermal thresholds (temperature-time) for prostate tissue destructionin vitro. The AT-1 Dunning prostate tumour model was chosen for the study. Three hundred micron thick sections were subjected to controlled temperature-time heating, which ranged from low (40°C, 15 min) to high thermal exposures (70°C, 2 min) (n = 6). After subsequent tissue culture at 37°C, the sections were evaluated for tissue injury at 3, 24 and 72 h by two independent methods: histology and dye uptake. A graded increase in injury was identified between the low and high thermal exposures. Maximum histologic injury occurred above 70°C, 1 min with >95% of the tissue area undergoing significant cell injury and coagulative necrosis. The control and 40°C, 15 min sections showed histologic evidence of apoptosis following 24 and 72 h in culture. Similar signs of apoptosis were minimal or absent at higher thermal histories. Vital-dye uptake quantitatively confirmed complete cell death after 70°C, 2 min. Using the dye data, Arrhenius analysis showed an apparent breakpoint at 50°C, with activation energies of 135.8 kcal/mole below and 4.7 kcal/mole above the threshold after 3 h in culture. These results can be used as a conservative benchmark for thermal injury in the cancerous prostate. Further characterization of the response to thermal therapy in an animal model and in human tissues will be important in establishing the efficacy of the procedure

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.

Theoretical modelling, experimental studies and clinical simulations of urethral cooling catheters for use during prostate thermal therapy

Urethral cooling catheters are used to prevent thermal damage to the urethra during thermal therapy of the prostate. Quantification of a catheter's heat transfer characteristics is necessary for prediction of the catheter's influence on the temperature and thermal dose distribution in periurethral tissue. Two cooling catheters with different designs were examined: the Dornier Urowave catheter and a prototype device from BSD Medical Corp. A convection coefficient, h, was used to characterize the cooling ability of each catheter. The value of the convection coefficient (h = 330 W m−2 °C−1 for the Dornier catheter, h = 160 W m−2 °C−1 for the BSD device) was obtained by comparing temperatures measured in a tissue-equivalent phantom material to temperatures predicted by a finite element method simulation of the phantom experiments. The coefficient was found to be insensitive to the rate of coolant flow inside the catheter between 40 and 120 ml min−1. The convection coefficient method for modelling urethral catheters was incorporated into simulations of microwave heating of the prostate. Results from these simulations indicate that the Dornier device is significantly more effective than the BSD catheter at cooling the tissue surrounding the urethra.

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° 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 (1.8mm ODx10mm long, ∼180° active sector, ∼7MHz, direct-coupled type) produced directional thermal lesions within in vivo prostate, with temperatures >50°C extending more than 10mm radially after 10-15min. Combination of interstitial applicators (1-2) and a transurethral applicator (3-2.5mm ODx6 mm long, 180° active sector, 6.8MHz, 6 mm OD delivery catheter) produced conforming temperature distributions (48-85°C) and zones of acute thermal damage within 15min. 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.