Verena Knappe

Radiation Planning for Thermal Laser Treatment

Summary A dosimetry model was developed for the thermal laser treatment of biological tissue and applied to laser-induced thermotherapy of organ tumors. This model combines a Monte Carlo simulation for calculating photon distribution in the target volume, a finite difference method for computing heat dissipation and the Arrhenius formalism for predicting protein denaturation and subsequent tissue damage. Implementation was carried out on a Windows-based platform and enabled the three-dimensional control of the target volume. An in vitro evaluation in porcine liver revealed a difference of less than 7% with regard to the ablation volume.

The vascular cooling effect in hepatic multipolar radiofrequency ablation leads to incomplete ablation ex vivo

Abstract Purpose: Major limitations of conventional RFA are vascular cooling effects. However, vascular cooling effects are supposed to be less pronounced in multipolar RFA. The objective of this ex vivo study was a systematic evaluation of the vascular cooling effects in multipolar RFA. Materials and methods: Multipolar RFA with three bipolar RFA applicators was performed ex vivo in porcine liver (applicator distance 20 mm, energy input 40 kJ). A saline-perfused glass tube (‘vessel’) was placed parallel to the applicators in order to simulate a natural liver vessel. Five applicator-to-vessel geometries were tested. A liquid-filled glass tube without perfusion was used as a dry run. Ablations were orthogonally cut to the applicators at a defined height. Cooling effects were analysed qualitatively and quantitatively along these cross sectional areas. Results: Thirty-six ablations were performed. A cooling effect could be seen in all ablations with perfused vessels compared to the dry run. While this cooling effect did not have any influence on the ablation areas (859–1072 mm2 versus 958 mm2 in the dry run, p > 0.05), it had a distinctive impact on ablation shape. A vascular cooling effect could be observed in all ablations with perfusion directly around the vessel independent of the applicator position compared to the dry run (p < 0.01). Conclusions: A vascular cooling effect occurred in all multipolar RFA with simulated liver vessels ex vivo independent of the applicator-to-vessel geometry. While the cooling effect did not influence the total ablation area, it had a distinctive impact on the ablation shape.

Bipolar Radiofrequency Ablation for Nodular Thyroid Disease—Ex Vivo and In Vivo Evaluation of a Dose-Response Relationship

BACKGROUND The prevalence of thyroid nodules ranges between 2% and 60% depending on the population studied. However, minimally invasive procedures like radiofrequency ablation (rfA) are increasingly used to treat tumors of parenchymatous organs, and seem to be suitable for singular thyroid nodules as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for rfA of thyroid nodules. MATERIAL AND METHODS Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n=110) and in vivo (n=10) using a bipolar radiofrequency system; rf was applied in a power range of 10-20 watts. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The transversal and axial lesion diameters were measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. RESULTS The inducible lesion volumes were between 0.91±0.71 cm(3) at 20W and 2.80±0.85 cm(3) at 14W. The maximum temperatures after rf ablation were between 44.0±9.7°C and 61.6±13.9°C at a distance of 5 mm and between 30.0±8.6°C and 53.5±8.6°C at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. CONCLUSION This study is the first to demonstrate a dose-response relationship for rfA of thyroid tissue. rfA is suitable for singular thyroid nodules and induces reproducible, clinically relevant lesions with irreversible cell damage in an appropriate application time.

Ex vivo and in vivo evaluation of laser‐induced thermotherapy for nodular thyroid disease

The prevalence of thyroid nodules ranges between 2% and 60% depending on the population studied. However, minimally invasive procedures like laser‐induced thermotherapy (LITT) are increasingly used to treat tumors of parenchymatous organs and seem to be suitable for singular thyroid nodules as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose–response relationship for LITT of thyroid nodules.

New Flexible Applicatorsfor Laser-Induced Thermotherapy

Summary A new scattering applicator for use in laser-induced thermotherapy (LITT) is presented. The applicator is mounted in front of a 400 μm quartz fiber and consists of a temperature stable plastic material with deposited scattering particles. The applicator provides a homogeneous axial scattering profile over an active length of 30 mm. The maximum power settings in porcine liver (in vitro) using a Nd:YAG-Laser and a cooled protective catheter were 31 W over an exposure period of 10 minutes. The resulting thermal lesions showed axial extensions of up to 50 mm and diameters of up to 33 mm, representing a total volume of 28.6 cm 3 .

Experimental study and first clinical results with a cooled applicator system for interstitial laser coagulation (LITT)

Laser-induced interstitial thermotherapy has proven to be an effective method for the treatment of different types of tumors. Until now the attainable coagulation volume was limited by the maximum applicable energy. The limiting factor was the high tissue temperature around the applicator which may have caused applicator damage. Consequently an internally cooled catheter system has been developed in order to reduce the temperature of the applicator surface and to allow for the application of higher laser powers. The optimal treatment parameters for the Nd:YAG laser were determined on the basis of in vitro studies with porcine tissue. Following these experimental studies, 127 patients with liver metastases were treated with the cooled system. The applicator position and the resulting tissue damage were verified using a MRI on-line monitoring system applying a FLASH-2D sequence. The optimal in vivo treatment parameters were found to be 25 watts for an exposure time of 20 minutes, resulting in coagulated volumes of up to 20 cm3. The experimental and clinical results have proven that the combination of a scattering laser applicator with an internally flushed catheter enables a significant increase in the coagulation volume.

Laser-induced Thermotherapy (LITT): Dose-Effect Relation on Lung Tissue

Summary Laser-induced thermotherapy (LITT) is an established minimally invasive technique which has been proven to be successful for many years, especially in the treatment of liver metastases. The lung is the organ most affected by metastases, next to the liver. Many patients do not meet the criteria of inclusion for metastasectomy which is considered the gold standard (3, 4). LITT could be a safe and effective alternative for these inoperable patients. In case of bilateral lung disease, segmental excision or lobectomy can be complemented by LITT of solitary focuses in other lobes. For a successful therapy management of lung metastases, lesion sizes are required for creating situations comparable to RO excision. For this purpose, the dose-effect relation between the applied Nd:YAG laser power and the coagulation size attainable was investigated for a clinically established applicator system. The tests were made ex vivo on porcine lungs using a LITT puncture set for open surgery. The laser power ranging from 20 to 32 watts was applied to the tissue through an internally cooled diffusor-tip applicator. The induced coagulation lesions were measured for volumes and maximum extensions. While the tested LITT system proved to be suitable for application with powers up to 32 watts, its maximum efficacy had been reached already at 25 watts and an exposure time of 20 minutes. Higher powers did not generate substantially larger lesions, but caused a temperature holdup and subsequent carbonisation. The data on the dose-effect relation obtained by this study contribute essentially to clinical application and lay the ground for a safe and validated therapy control.

Experimental study and first clinical results with a cooled applicator system for LITT

Laser-induced interstitial thermotherapy has proven to be an effective method for the treatment of different types of tumors. Until now the attainable coagulation volume was limited by the maximum applicable energy. The limiting factor is the high tissue temperatures around the applicator which may cause applicator damage. Consequently an internally cooled catheter system has been developed in order to reduce the temperature of the applicator surface and therefore enable the application of higher laser powers. The optimal treatment parameters for the Nd:YAG laser were determined on the basis of computer simulations and in vitro studies with porcine liver. Following these experimental studies, 72 patients with liver metastases were treated with the cooled applicator system. The applicator position and the resulting tissue damage were verified using the MRI on- line monitoring system with a FLASH-2D sequence. The optimal treatment parameters were found to be 25 watts for an exposure time of 20 minutes, resulting in coagulated volumes of up to 20 cm3. The experimental and clinical results proved that the combination of a scattering laser applicator with an internally flushed catheter enables a significant increase in the coagulation volume.

Finding Optimal Ablation Parameters for Multipolar Radiofrequency Ablation

Purpose. Radiofrequency ablation (RFA) for primary liver tumors and liver metastases is restricted by a limited ablation size. Multipolar RFA is a technical advancement of RFA, which is able to achieve larger ablations. The aim of this ex vivo study was to determine optimal ablation parameters for multipolar RFA depending on applicator distance and energy input. Methods. RFA was carried out ex vivo in porcine livers with three internally cooled, bipolar applicators in multipolar ablation mode. Three different applicator distances were used and five different energy inputs were examined. Ablation zones were sliced along the cross-sectional area at the largest ablation diameter, orthogonally to the applicators. These slices were digitally measured and analyzed. Results. Sixty RFA were carried out. A limited growth of ablation area was seen in all test series. This increase was dependent on ablation time, but not on applicator distance. A steady state between energy input and energy loss was not observed. A saturation of the minimum radius of the ablation zone was reached. Differences in ablation radius between the three test series were seen for lowest and highest energy input (P < .05). No differences were seen for medium amounts of energy (P > .05). Conclusions. The ablation parameters applicator distance and energy input can be chosen in such a way, that minor deviations of the preplanned ablation parameters have no influence on the size of the ablation area.

Therapie-Planungssystem zur Berechnung des thermischen Destruktionsvolumens der Radiofrequenzablation von Lebertumoren – ex-situ Evaluation unter Einbeziehung des Kühleffektes von Lebergefäßen

Objective: The oncologically safe application of radiofrequency ablation (RFA) is limited by the cooling effect of liver vessels. The aim of the current study was to validate a planning system for RFA of liver tumors with regard to the calculation of thermal lesions including the cooling effect of liver vessels ex-vivo. Methods: A bipolar RFA applicator (diameter: 1.8 mm, electrode length: 30 mm, internal cooling) was inserted parallel at a distance of 5 mm to a perfused glass tube (diameter: 5 mm; flow: 0–500 ml/min) in porcine liver ex-vivo. RFA was performed with 30 W/15 kJ. The liver was cut perpendicular to the applicator after RFA and the thermal lesion was digitally measured. RFA was simulated with the planning system using the aforementioned parameters. A morphometric analysis was carried out in order to assess the correlation between the thermal lesion and the result of the planning system. Results: 40 RFA were carried out. Sensitivity (correct prediction of the destruction volume) was 0.96 ± 0.05. Specificity (correct prediction of non-destructed tissue) was 0.75 ± 0.10. No significant differences for sensitivity and specificity were found for flows of 0 ml/min (glass tube without perfusion) and flows of 1, 5, 10, 100, 250 and 500 ml/min. Conclusions: (1) A computer planning system was developed for predicting thermal lesions resulting from RFA. (2) The calculation of the cooling effect of intrahepatic vessels is possible for the first time with this system. (3) Ex-situ validation showed a high sensitivity of the planning system, but specificity has to be improved (DFG, Ref-No. RI1131/3-2).