Radiofrequency coil for the creation of large ablations: ex vivo and in vivo testing.

PURPOSE: Various radiofrequency (RF) ablation electrode designs have been developed to increase ablation volume. Multiple heating cycles and electrode positions are often required, thereby increasing treatment time. The objective of this study was to evaluate the performance of a high-frequency monopolar induction coil designed to produce large thermal lesions (>3 cm) with a single electrode insertion in a treatment time of less than 10 minutes. MATERIALS AND METHODS: A monopolar nitinol interstitial coil operated at 27.12 MHz and 200 W was evaluated. Ex vivo performance was tested in excised bovine liver (n = 22). In vivo testing (n = 10) was conducted in livers of seven Yorkshire pigs. Visual inspection, contrast-enhanced computed tomography (CT), and pathologic evaluation of ablation zones were performed. RESULTS: Average ablation volumes in ex vivo and in vivo tests were 60.5 cm(3) ± 14.1 (5.9 × 4.4 × 4.4 cm) and 57.1cm(3) ± 13.8 (6.1 × 4.5 × 4.1cm), with average treatment times of 9.0 minutes ± 3.0 and 8.4 minutes ± 2.7, respectively. Contrast-enhanced CT ablation volume measurements corresponded with findings of gross inspection. Pathologic analysis showed morphologic and enzymatic changes suggestive of tissue death within the ablation zones. CONCLUSIONS: The RF ablation coil device successfully produced large, uniform ablation volumes in ex vivo and in vivo settings in treatment times of less than 10 minutes. Ex vivo and in vivo lesion sizes were not significantly different (P = .53), suggesting that the heating efficiency of this higher-frequency coil device may help to minimize the heat-sink effect of perfusion.

Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer.

With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately +/-2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D(90), was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D(90) less than 23 J cm(-2) had complete biopsy response, while 8/13 (62%) of patients with a D(90) greater than 23 J cm(-2) had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

Fast B-flow imaging: a method for improving frame rate in Golay coded B-flow imaging.

A technique for Golay coded B-flow imaging, called fast B-flow imaging, has been developed. This technique improves the frame rate of Golay coded B-flow imaging. In this technique, three instead of four input pulses are used to produce each scan line. A standard Golay pulse-pair is used as two of the three inputs, and pulse compression is performed upon receive returning the echoes from stationary (tissue) objects in the image. The third input is a repetition of one of the first two inputs. Upon receive, this pulse is cross correlated with an inverted copy of its input pulse. Addition of the cross-correlated signals produced from the identical input pulses results in the cancellation of the strong tissue echoes, and enables visualization of the weaker/moving blood echoes. Combining a small fraction of the tissue echoes with the weaker blood echoes allows both to be visualized in the same gray scale image. By using three instead of four input pulses, this technique can achieve a frame rate improvement of 33% compared with standard Golay coded B-flow imaging, with some loss in signal-to-noise ratio. The impact of axial and lateral motion on these techniques is examined. A quantitative comparison of both techniques is presented.

Characterization of changes in therapeutic ultrasound transducer performance over time using the angular spectrum method.

Strongly focused large aperture transducers used in high-intensity focused ultrasound treatments are prone to manufacturing defects and degradation. Current methods for evaluating transducer quality measure only bulk physical changes of transducers. We have determined the pressure distribution at the transducer surface, using the angular spectrum method, to detect defects of the transducer. Three therapeutic transducers were investigated. The pressure distribution at the focal plane of each transducer was measured and input into a back-projection algorithm to calculate the pressure distribution at the transducer surface. A number of scan window sizes were used for the pressure distribution measurement at the focal plane to determine the effect on the resolution of the calculated pressure distribution at the transducer surface. Results showed that one transducer might have suffered manufacturing defects. The second transducer degraded over 1 year of use with one half of the transducer suffering a partial loss of efficiency. The third transducer remained unchanged over 1 year. The scan window of 40 mm X 40 mm at the focal plane was required to identify defects 6 mm in diameter on the transducer surface. The results demonstrate that the angular spectrum method could be a useful tool for evaluating transducer quality.

Golay pulse encoding for microbubble contrast imaging in ultrasound.

We present a technique that uses Golay phase encoding, pulse inversion, and amplitude modulation (GPIAM) for microbubble contrast agent imaging with ultrasound. This technique improves the contrast-to-tissue ratio (CTR) by increasing the time-bandwidth product of the insonating waveforms. A nonlinear pulse compression algorithm is used to compress the signal energy upon receive. A 6.5-dB improvement in CTR was observed using an 8-chip GPIAM sequence compared to a conventional pulse-inversion amplitude-modulation sequence. The CTR improvement comes at the cost of a reduction in frame rate: GPIAM coding uses four input pulses whereas most contrast imaging sequences require two or three pulses. Our results showed that the microbubble response can be phase encoded and subsequently compressed using a nonlinear matched-filtering algorithm, in order to enhance the signal from the contrast agent, while maintaining resolution and suppressing the tissue signal.

Development of a novel loosely wound helical coil for interstitial radiofrequency thermal therapy.

We have developed a novel, radiofrequency thermal therapy device designed to improve local control of large solid tumours using heat in the range 55-90 degrees C. The device is a solenoid or helical coil designed to be loosely wound inside a tumour and excited with radiofrequency energy. Typically, we associate a uniform axially directed magnetic field with a solenoid coil, which when time varying, results in an electric field inside the coil, which lies mainly in the circumferential direction. In addition to this magnetically induced electric field, there exists a less familiar axially directed electric field inside the coil. Previous investigators have demonstrated the presence of this secondary axial electric field both experimentally and theoretically. Our design exploits the size and uniformity of these electric fields, for heating and coagulating a large tissue volume with a single applicator. The loosely wound solenoid is constructed from Nitinol, an electrically conductive shape memory alloy that permits the minimally invasive percutaneous insertion of the coil through a single cannulating delivery needle. To demonstrate the potential of this device and to determine the optimal frequency of operation, phantom tissue models and finite-element calculation models using COMSOL 3.2 were used to characterize frequency- and geometry-dependent trends in absorption rate density (ARD), which is proportional to electric field intensity. Radial and axial ARD profiles were measured, calculated and evaluated to determine the frequency and geometry best suited for producing large, homogenous coagulation volumes. Based on the trade-off between radial and axial uniformities of the ARD profiles, a 2 cm diameter coil with a 4 cm length and 1 cm pitch, operated at 27.12 MHz, produced the optimal heating pattern, as determined using tissue-mimicking phantom models.

The use of a dispersive ground electrode with a loosely wound helical coil for interstitial radiofrequency thermal therapy.

We have developed a novel, thermal therapy device designed to improve local control of large solid tumours using heat in the range 55-90 degrees C. The device is a helical coil designed to be loosely wound inside a tumour and excited with radiofrequency energy at 27.12 MHz. This design exploits the size and uniformity of the electric fields generated by magnetic induction inside this solenoidal geometry for heating and coagulating a large target volume. The use of the electrically conductive shape memory alloy Nitinol for the coil and an external ground plane permit the minimally invasive percutaneous insertion of the coil through a single cannulating delivery needle. To demonstrate the feasibility of this device, phantom models and finite-element models using COMSOL 3.2 were used to characterize uniformity of the radial and axial ARD (absorption rate density) profiles of different monopolar coil geometries. COMSOL 3.2 was also used to calculate temperature profiles and distributions produced by these coils in a non-perfused tissue-mimicking domain following a 10 min heating period. ARD results showed that optimum radial and axial uniformities were achieved with a 0.75 cm pitch and 3 cm length for a 1.5 cm diameter coil, and a 1.4 cm pitch and 4.2 cm length for a 2 cm diameter coil. These coils were able to produce lesions in excised bovine liver of 4 cm x 4.5 cm and 3.5 cm x 6.5 cm, respectively. Predicted temperature profiles showed similar profile sizes and shapes in a non-perfused domain, with the absolute temperature rise determined by the source input to the coil. These results demonstrate the potential of this interstitial, monopolar induction coil device for heating large tumours using a single applicator delivered through a single needle insertion.

High-frequency ultrasound for monitoring changes in liver tissue during preservation.

Currently the only method to assess liver preservation injury is based on liver appearance and donor medical history. Previous work has shown that high-frequency ultrasound could detect ischemic cell death due to changes in cell morphology. In this study, we use high-frequency ultrasound integrated backscatter to assess liver damage in experimental models of liver ischemia. Ultimately, our goal is to predict organ suitability for transplantation using high-frequency imaging and spectral analysis techniques. To examine the effects of liver ischemia at different temperatures, livers from Wistar rats were surgically excised, immersed in phosphate buffer saline and stored at 4 and 20 degrees C for 24 h. To mimic organ preservation, livers were excised, flushed with University of Wisconsin (UW) solution and stored at 4 degrees C for 24 h. Preservation injury was simulated by either not flushing livers with UW solution or, before scanning, allowing livers to reach room temperature. Ultrasound images and corresponding radiofrequency data were collected over the ischemic period. No significant increase in integrated backscatter (approximately 2.5 dBr) was measured for the livers prepared using standard preservation conditions. For all other ischemia models, the integrated backscatter increased by 4-9 dBr demonstrating kinetics dependent on storage conditions. The results provide a possible framework for using high-frequency imaging to non-invasively assess liver preservation injury.

Optimization of a beam shaping bolus for superficial microwave hyperthermia waveguide applicators using a finite element method.

Temperature inhomogeneity in hyperthermia treatments often limits the total thermal dose that can be delivered to the tumour region. To reduce such inhomogeneities, a prototype dynamically modifiable square array of saline-filled patches which attenuate microwave energy was developed for superficial treatments that use external microwave applicators. The array was situated inside the coupling water bolus that is often used with external applicators. The prototype has been previously tested clinically with promising results. A more complete theoretical analysis of the performance of this new bolus design and improvements to its design by modelling are presented here. The analysis was performed by performing five iterative simulations of the SAR pattern produced inside a tissue structure by a waveguide applicator with a water bolus containing the dynamic patch array attached. Between iterations the patch array configuration was modified in an attempt to improve the ability of the bolus to confine heating to an 'L'-shaped tumour region. These simulations were performed using the finite element method. The steady-state temperature profile was then computed using a finite element method based simulation of heat transfer that assumed a given applicator power level and water bolus temperature. Several iterations of these heat transfer simulations were performed with varying applicator power level and water bolus temperature to improve the confinement of heating to the target region. The analysis showed that the dynamic patch array should be capable of conforming heating to an 'L'-shaped target tumour region while limiting the heating to the surrounding normal tissue to an acceptable level.

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.

Changes in dielectric properties at 460 kHz of kidney and fat during heating: importance for radio-frequency thermal therapy.

We have developed a system to measure the changes due to heating to high temperatures in the dielectric properties of tissues in the radio-frequency range. A two-electrode arrangement was connected to a low-frequency impedance analyser and used to measure the dielectric properties of ex vivo porcine kidney and fat at 460 kHz. This frequency was selected as it is the most commonly used for radio-frequency thermal therapy of renal tumours. Tissue samples were heated to target temperatures between 48 and 78 degrees C in a hot water bath and changes in dielectric properties were measured during 30 min of heating and 15 min of cooling. Results suggest a time-temperature dependence of dielectric properties, with two separate components: one a reversible, temperature-dependent effect and the other a permanent effect due to structural events (e.g. protein coagulation, fat melting) that occur in tissues during heating. We calculated temperature coefficients of 1.3 +/- 0.1% degrees C(-1) for kidney permittivity and 1.6% degrees C(-1) for kidney conductivity, 0.9 +/- 0.1% degrees C(-1) for fat permittivity and 1.7 +/- 0.1% degrees C(-1) for fat conductivity. An Arrhenius model was employed to determine the first-order kinetic rates for the irreversible changes in dielectric properties. The following Arrhenius parameters were determined: an activation energy of 57 +/- 5 kcal mol(-1) and a frequency factor of (6 +/- 1) x 10(34) s(-1) for conductivity of kidney, an activation energy of 48 +/- 2 kcal mol(-1) and a frequency factor of 6 x 10(28) s(-1) for permittivity of kidney. A similar analysis led to an activation energy of 31 +/- 4 kcal mol(-1) and a frequency factor of (4.43 +/- 1) x 10(16) s(-1) for conductivity of fat, and an activation energy of 40 +/- 4 kcal mol(-1) and a frequency factor of 4 x 10(22) s(-1) for permittivity of fat. Structural events occurring during heating at different target temperatures as determined by histological analyses were correlated with the changes in the measured dielectric properties.

Feasibility of salvage interstitial microwave thermal therapy for prostate carcinoma following failed brachytherapy: studies in a tissue equivalent phantom.

Thermal therapy is an experimental treatment to destroy solid tumours by heating them to temperatures ranging from 55 degrees C to 90 degrees C, inducing thermal coagulation and necrosis of the tumour. We are investigating the feasibility of interstitial microwave thermal therapy as a salvage treatment for prostate cancer patients with local recurrence following failed brachytherapy. Due to the electrical and thermal conductivity of the brachytherapy seeds, we hypothesized that the seeds could scatter the microwave energy and cause unpredictable heating. To investigate this, a 915 MHz helical antenna was inserted into a muscle-equivalent phantom with and without brachytherapy seeds. Following a 10 W, 5 s input to the antenna, the temperature rise was used to calculate absorbed power, also referred to as specific absorption rate (SAR). Plane wave models based on Maxwell's equations were also used to characterize the electromagnetic scattering effect of the seeds. In addition, the phantom was heated with 8 W for 5 min to quantify the effect of the seeds on the temperature distribution during extended heating. SAR measurements indicated that the seeds had no significant effect on the shape and size of the SAR pattern of the antenna. However, the plane wave simulations indicated that the seeds could scatter the microwave energy resulting in hot spots at the seed edges. Lack of experimental evidence of these hot spots was probably due to the complex polarization of the microwaves emitted by the helical antenna. Extended heating experiments also demonstrated that the seeds had no significant effect on the temperature distributions and rates of temperature rise measured in the phantom. The results indicate that brachytherapy seeds are not a technical impediment to interstitial microwave thermal therapy as a salvage treatment following failed brachytherapy.

A model based upon pseudo regular spacing of cells combined with the randomisation of the nuclei can explain the significant changes in high-frequency ultrasound signals during apoptosis.

Recent ultrasound (US) experiments on packed myeloid leukaemia cells have shown that, at frequencies from 32 to 40 MHz, significant increases of signal amplitude were observed during apoptosis. This paper is an attempt to explain these signal increases based upon a simulation of the backscattered signals from the cells nuclei. The simulation is an expansion of work in which a condensed sample of cells, with fairly regular sizes, could be considered as an imperfect crystal. Thus, destructive interference could occur and this would be observed as a large reduced value of backscattered signals compared with the values obtained from a similar, but random, scattering source. This current paper explores the possibility that simple changes in the nuclei, such as their observed condensation or the small loss of nuclei scatterers from cells, could cause a significant increase in the observed backscattered signals. This model indicates that the greater backscattered signals can be explained by further randomisation of the average positions of the scattering sources in each cell. When these "microechoes" are added together, so that the destructive interference is reduced, a large increase in the signal is predicted. The simplified model strongly suggests that much of observed large increases of the backscattered signals could be simply explained by the randomisation of the position of the condensed nuclei during apoptosis, and the destruction of the nuclei could produce further signal amplitude changes due to disruption of the cloud of backscattered waves.

Interstitial microwave thermal therapy for prostate cancer.

Thermal therapy is used to kill tumors by heating them to temperatures >50 degrees C for an extended period of time. Cell death results from thermal coagulation. The energy sources available for this approach include radiofrequency electrodes, microwave antennas, laser fiberoptics, and ultrasound transducers. Each of these modalities has the potential to be delivered in a minimally invasive manner, and many theoretical and experimental investigations of these devices have been performed. This review describes current knowledge of interstitial microwave thermal therapy for prostate cancer. Examples are given from an ongoing trial in patients who have recurrent or persistent disease following radiation therapy. Future directions for pretreatment planning and real-time monitoring and control are discussed. These techniques have the potential to optimize treatments on a patient-specific basis and will be instrumental in planned future trials of this therapy as first line for prostate cancer.

Characterization of measurement artefacts in fluoroptic temperature sensors: implications for laser thermal therapy at 810 nm.

BACKGROUND AND OBJECTIVES: Fluoroptic sensors are used to measure interstitial temperatures but their utility for monitoring laser interstitial thermal therapy (LITT) is unclear because these sensors exhibit a measurement artefact when exposed to the near-infrared (NIR) treatment light. This study investigates the cause of the artefact to determine whether fluoroptic sensors can provide reliable temperature measurements during LITT. STUDY DESIGN/MATERIALS AND METHODS: The temperature rise measured by a fluoroptic sensor irradiated in non-absorbing media (air and water) was considered an artefact. Temperature rise was measured as a function of distance from a laser source. Two different sensor designs and several laser powers were investigated. A relationship between fluence rate and measurement artefact in water was determined and coupled with a numerical simulation of LITT in liver to estimate the error in temperature measurements made by fluoroptic sensors in tissue in proximity to the laser source. The effect of ambient light on the performance of sensors capped with a transparent material ("clear-capped sensors") was also investigated. RESULTS: The temperature rise recorded in air by both clear- and black-capped fluoroptic sensors decreased with distance from a laser source in a manner similar to fluence rate. Sensor cap material, laser power, and the thermal properties of the surrounding medium affected the magnitude of the artefact. Numerical simulations indicated that the accuracy of a clear-capped fluoroptic sensor used to monitor a typical LITT treatment in liver is > 1 degrees C provided the sensor is further than approximately 3 mm from the source. It was also shown that clear-capped fluoroptic sensors are affected by ambient light. CONCLUSIONS: The measurement artefact experienced by both black-capped and clear-capped fluoroptic sensors irradiated by NIR light scales with fluence rate and is due to direct absorption of the laser light, which results in sensor self-heating. Clear-capped fluoroptic sensors can be used to accurately monitor LITT in tissue but should be shielded from ambient light.

The uncertainty of radio frequency treatment of renal cell carcinoma: findings at immediate and delayed nephrectomy.

PURPOSE: Radio frequency thermal therapy for the ablation of renal cell carcinoma has been reported. Outcomes are usually measured by imaging alone. We have performed ex vivo and in vivo experiments using radio frequency in porcine models in our laboratory. We now report our early experience in the treatment of renal cell carcinoma in patients who underwent post-radio frequency radical or partial nephrectomy. MATERIALS AND METHODS: We treated 10 patients diagnosed with small renal masses with radio frequency. All masses were biopsied before treatment. In 4 patients 5 renal cell carcinomas were treated with radio frequency after surgical exposure of the tumor followed immediately by partial or radical nephrectomy (acute group). Six other patients were treated percutaneously with ultrasound or computerized tomography guided radio frequency under local anesthesia and intravenous sedation 7 days before partial or radical nephrectomy (delayed group). A median of 2 radio frequency cycles was applied. Mean total heating time was 17 minutes 15 seconds. Specimens were analyzed grossly and histologically. Triphasic contrast-enhanced computerized tomography and/or magnetic resonance imaging was performed before and 7 days after radio frequency treatment in the delayed group. RESULTS: Mean radiological largest diameter of all 11 masses was 2.4 cm. and mean gross diameter was 2.2 cm. Pathological examination demonstrated residual viable tumor in approximately 5% of the volume in 4 of the 5 tumors in the acute group and in 3 of the 6 masses of the delayed group. In 1 delayed case the viable tumor appeared to be in contact with the renal vein. No significant complications were observed in 9 of the 10 patients. In 1 delayed case, a subcapsular hepatic hematoma, biliary fistula and pneumonia developed and resolved. CONCLUSIONS: Based on our experience, we continue to consider percutaneous radio frequency for the treatment of small renal cell carcinomas as a potentially curative therapy. However, complete tumor cell death appears to be difficult to achieve with our current treatment protocol. More phase II testing is indicated to ensure that this technique is an effective and reproducible treatment alternative.