KEYWORDS: Ultrasonography, Magnetic resonance imaging, Prostate, Tissues, In vivo imaging, Thermal modeling, Transducers, Acoustics, Temperature metrology, Magnetism
Thermal ablation is a minimally-invasive treatment option for benign prostatic hyperplasia (BPH) and localized prostate cancer. Accurate spatial control of thermal dose delivery is paramount to improving thermal therapy efficacy and avoiding post-treatment complications. We have recently developed three types of transurethral ultrasound applicators, each with different degrees of heating selectivity. These applicators have been evaluated in vivo in coordination with magnetic resonance temperature imaging, and demonstrated to accurately ablate specific regions of the canine prostate. A finite difference biothermal model of the three types of transurethral ultrasound applicators (sectored tubular, planar, and curvilinear transducer sections) was developed and used to further study the performance and heating capabilities of each these devices. The biothermal model is based on the Pennes bioheat equation. The acoustic power deposition pattern corresponding to each applicator type was calculated using the rectangular radiator approximation to the Raleigh Sommerfield diffraction integral. In this study, temperature and thermal dose profiles were calculated for different treatment schemes and target volumes, including single shot and angular scanning procedures. This study also demonstrated the ability of the applicators to conform the cytotoxic thermal dose distribution to a predefined target area. Simulated thermal profiles corresponded well with MR temperature images from previous in vivo experiments. Biothermal simulations presented in this study reinforce the potential of improved efficacy of transurethral ultrasound thermal therapy of prostatic disease.
Two catheter-based transurethral ultrasound applicators designed for selective thermal coagulation of prostate tissue were evaluated. The first applicator utilized two 3.5 mm piezoelectric sectored tubes with the active transducer surface forming 90°. The second applicator's transducer assembly consisted of a linear array of 3.5 x 10 mm planar transducer elements. Both applicators operated at 8 MHz and were positioned on a 4 mm diameter catheter within an integrated expandable balloon (10 mm). Manual rotation of the transducer assembly within the balloon allowed for angular control and/or sweeping of the treatment volume. Ambient temperature degassed cooling water (~120 ml/min) was circulated inside the balloon to preserve the urethral mucosa. Acoustic efficiencies of 20-54% and acoustic beam distributions were measured. The thermal treatment characteristics of the applicator were investigated in vivo (canine prostate) under MRI guidance in an interventional open magnet (0.5 T). Magnetic resonance thermal imaging (MRTI) monitored the treatments (GRE phase mapping, multiple planes, 15 sec update intervals). Post-treatment imaging (T1 w/contrast) and TTC staining of the prostate were used to verify zones of thermal damage. Single sonications lasting 8-15 min produced coagulated zones of tissue extending to the outer boundary of the prostate while preserving 2-3 mm of urethral mucosa. Multiple sonications in sequence produced larger contiguous sectors of coagulated tissue (~ 3/4 of the gland). In summary, highly directional transurethral applicators under MRI guidance were able to produce selective and controllable thermal coagulation.
Theoretical and experimental approaches were used to develop and evaluate site-specific designs of internally cooled direct coupled (ICDC) and catheter-cooled (CC) ultrasound applicators for thermal coagulation of disease in the prostate, liver, brain, and uterus. The diameter of an interstitial applicator can influence its clinical practicality and effectiveness as well as application site. One purpose of this study was to determine whether the use of larger ultrasound transducers and the inherent increase in applicator size could be justified by potentially producing larger lesion diameters. A second purpose was to explore how the response of tissue acoustic attenuation to heating effects lesion size and preferred applicator configuration. Four applicator configurations and sizes were studied using ex vivo tissue experiments in liver and beef and using acoustic and biothermal simulations. Transmission attenuation measurements showed a 6 to 8 fold increase in baseline tissue attenution inside interstitial ultrasound lesions. Formation of these high attenuation zones in lesions reduced potential lesion size. Larger applicators produced lesions with radial penetration depths superior to their smaller counterparts at power levels in the 20-40W /cm range. The higher cooling rates along the outer surface of the larger diameter applicators due to their greater surface area was a dominant factor in increasing lesion size. The higher cooling rates pushed the maximum temperature farther from the applicator surface and reduced the formation of high acoustic attenuation tissue zones. Acoustic and biothermal simulations matched the experimental data well and were applied to model these applicators within sites of clinical interest such as prostate, uterine fibroid, brain, and normal liver. Lesions of 3.9 to 4.7cm diameter were predicted for moderately perfused tissues such as prostate and fibroid and 2.8 to 3.2cm for highly perfused tissues such as normal liver. Feedback control to reduce maximum tissue temperatures helped to decrease formation of sound-blocking high attenuation zones. This work was supported by a gift from the Oxnard Foundation and Johnson & Johnson.
Theoretical and experimental approaches were used to evaluate Internally-Cooled Direct-Coupled (ICDC) ultrasound applicators for treating disease in the prostate and liver. 2-D and 3-D transient biothermal models, which account for dynamic tissue changes, were used to calculate temperature distributions and zones of coagulation. Experimental evaluations and verification of these models were performed using in vitro tissue and in vivo porcine and canine models. Devices of 2.2 mm outer diameter were evaluated under varied applied power schemes and cooling levels. Both duty cycle power application and PI-controlled power application were found to improve applicator performance by increasing radial depths of lesions with lower maximum temperature. ICDC applicators were found to be able to create 3-5 cm diameter lesions in liver and muscle under 15 minute treatment times using the optimal designs and power application schemes found in this study. From these initial feasibility studies it has been demonstrated that ICDC devices have potential for treating cancerous tumors in prostate, liver and possibly breast.
In this study both transurethral and interstitial ultrasound thermal therapy were applied to thermally coagulate targeted portions of the canine prostate or brain and implanted TVT tumors while using MRI-based thermal mapping techniques to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. The complex phase-difference mapping technique using an iGE-EPI sequence with lipid suppression was used for determining temperature elevations within the in vivo prostate or brain and surrounding structures. Calculated temperature distributions, thermal dose exposures, T2-wieghted & T1-contrast enhanced images, gross inspection, and histology of sectioned prostates and brains were in good agreement with each other in defining destroyed tissue zones. Interstitial and transurethral ultrasound applicators produce directed zones of thermal coagulation within targeted tissue and implanted tumor, which can be accurately monitored and evaluated by MRI.
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