Preclinical assessment of a noncooled MR thermometry-based neurosurgical laser therapy system.

OBJECTIVE: MRI-guided laser interstitial thermal therapy (MRgLITT) has recently gained interest as an ablative stereotactic procedure for intractable epilepsy, movement disorders, and brain tumors. Conventionally, a LITT system consists of a laser generator and cooled laser applicator, which is a fiber optic core surrounded by a sheath through which cooled fluid is pumped. However, this footprint can make the system bulky and nonmobile, limit the maximum depth of targeting, and increase the chances of breakdown. Herein, the authors conduct a preclinical assessment of a noncooled MRgLITT system in a porcine model. METHODS: Three-tesla MRI was used to guide the in vivo placement of noncooled laser applicators in the porcine brain. The study consisted of a survival arm and terminal arm. The laser was activated at a power of 4-7 W for ≤ 180 seconds. Temperature changes were monitored using the MR thermometry software ThermoGuide in the survival arm (n = 5) or both ThermoGuide software and adjacently inserted thermal probes in the terminal arm (n = 3). Thermal damage was determined by the software using the temperature-time relationship of cumulative equivalent minutes at 43°C (CEM43). Temperatures calculated by the software were compared with those recorded by the temperature probes. The dimensions of thermal damage thresholds (TDTs; 2-9, 10-59, 60-239, ≥ 240 CEM43 isolines) given by MR thermometry were compared with the dimensions of irreversible damage on histopathological analysis. RESULTS: There was a strong correlation between temperature recordings by ThermoGuide and those by thermal probes at both 4 mm (r = 0.96) and 8 mm (r = 0.80), with a mean absolute error of 0.76°C ± 2.13°C and 0.17°C ± 1.65°C at 4 and 8 mm, respectively. The area of 2-9 CEM43 was larger than the area of irreversible damage seen on histopathological analysis. The dimensions of the 10 and 60 CEM43 correlated well with dimensions of the lesion on histopathological analysis. A well-defined border (≤ 1 mm) was observed between the area of irreversible damage and healthy brain tissue. CONCLUSIONS: This preclinical assessment showed that the noncooled LITT system was able to precisely reach the target and create well-defined lesions within a margin of safety, without any adverse effects. MR thermometry software provided an accurate near-real-time temperature of the brain tissue, and dimensions of the lesion as visualized by the software correlated well with histopathological findings. Further studies to test the system's efficacy and safety in human subjects are in progress.

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.

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

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 mm(2) versus 958 mm(2) 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.

Effectiveness of various thermal ablation techniques for the treatment of nodular thyroid disease--comparison of laser-induced thermotherapy and bipolar radiofrequency ablation.

Alternative minimally invasive treatment options such as radiofrequency ablation (RFA) or laser-induced thermotherapy (LITT) are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. So far, studies have not been able to show a secure advantage for neither LITT nor RFA. The aim of this study was to compare the two ablation procedures in terms of their effectiveness. Thermal lesions were induced in porcine thyroid glands either by LITT or bipolar RFA ex vivo (n = 110 each) and in vivo (n = 10 each) using power settings between 10 and 20 W. Temperature spread during application was documented in 5- and 10-mm distance of the applicator. Postinterventional lesion diameters were measured and lesion size was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed in vivo. Lesion volumes induced by LITT ranged between 0.74 ± 0.18 cm(3) (10 W) and 3.80 ± 0.41 cm(3) (20 W) with a maximum of 5.13 ± 0.16 cm(3) at 18 W. The inducible lesion volumes by RFA were between 2.43 ± 0.68 cm(3) (10 W) and 0.91 ± 0.71 cm(3) (20 W) with a maximum of 2.80 ± 0.85 cm(3) at 14 W. The maximum temperatures were 112.9 ± 9.2°C (LITT) and 61.6 ± 13.9°C (RFA) at a distance of 5 mm and 73.2 ± 6.7°C (LITT) and 53.5 ± 8.6°C (RFA) at a distance of 10 mm. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage both for LITT and RFA. This study is the first to compare the effectiveness of laser-induced thermotherapy and radiofrequency ablation of thyroid tissue. LITT as well as RFA are suitable for singular thyroid nodules and induces reproducible clinically relevant lesions in an appropriate application time. The maximum inducible lesion volumes by LITT are significantly larger than by RFA with the devices used herein.

In vivo validation of a therapy planning system for laser-induced thermotherapy (LITT) of liver malignancies.

PURPOSE: In situ ablation is increasingly being used for the treatment of liver malignancies. The application of these techniques is limited by the lack of a precise prediction of the destruction volume. This holds especially true in anatomically difficult situations, such as metastases in the vicinity of larger liver vessels. We developed a three-dimensional (3D) planning system for laser-induced thermotherapy (LITT) of liver tumors. The aim of the study was to validate the system for calculation of the destruction volume. METHODS: LITT (28 W, 20 min) was performed in close contact to major hepatic vessels in six pigs. After explantation of the liver, the coagulation area was documented. The liver and its vascular structures were segmented from a pre-interventional CT scan. Therapy planning was carried out including the cooling effect of adjacent liver vessels. The lesions in vivo and the simulated lesions were compared with a morphometric analysis. RESULTS: The volume of lesions in vivo was 6,568.3 ± 3,245.9 mm(3), which was not different to the simulation result of 6,935.2 ± 2,538.5 mm(3) (P = 0.937). The morphometric analysis showed a sensitivity of the system of 0.896 ± 0.093 (correct prediction of destructed tissue). The specificity was 0.858 ± 0.090 (correct prediction of vital tissue). CONCLUSIONS: A 3D computer planning system for the prediction of thermal lesions in LITT was developed. The calculation of the directional cooling effect of intrahepatic vessels is possible for the first time. The morphometric analysis showed a good correlation under clinical conditions. The pre-therapeutic calculation of the ablation zone might be a valuable tool for procedure planning.

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.

BACKGROUND AND OBJECTIVE: 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. MATERIALS AND METHODS: Thermal lesions were induced in healthy porcine thyroid glands ex vivo (n = 110) and in vivo (n = 10) using an Nd:YAG laser (1,064 nm). Laser energy was applied for 300 seconds in a power range of 10-20 W. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The lesions were longitudinally and transversally measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. RESULTS: The maximum inducible lesion volumes were between 0.74 +/- 0.18 cm(3) at a laser power of 10 W and 3.80 +/- 0.41 cm(3) at 20 W. The maximum temperatures after ablation were between 72.9 +/- 2.9 degrees C (10 W) and 112.9 +/- 9.2 degrees C (20 W) at a distance of 5 mm and between 49.5 +/- 2.2 degrees C (10 W) and 73.2 +/- 6.7 degrees C (20 W) at a distance of 10 mm from the applicator. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. CONCLUSIONS: This study is the first to demonstrate a dose-response relationship for LITT of thyroid tissue. LITT is suitable for singular thyroid nodules and induces reproducible clinically relevant lesions with irreversible cell damage in an appropriate application time.

Laser-induced thermotherapy for lung tissue--evaluation of two different internally cooled application systems for clinical use.

Thermal ablation techniques like radiofrequency or laser-induced thermotherapy (LITT) are increasingly used to treat tumors of parenchymatous organs. Minimal access, parenchymal preservation, and a low complication rate render them suitable for pulmonary tumors 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 a percutaneous and an intraoperative system for LITT of lung tissue. Thermal lesions were induced in healthy porcine lungs using an Nd:YAG laser (1,064 nm). LITT was performed with a percutaneous application system in group I (n = 18) and an intraoperative application system in group II (n = 90). Laser energy was applied for 600-1,200 s in a power range of 20-32 W (12,000-38,400 J). The lesions were longitudinally and transversally measured, and the volume was calculated after the intervention. Furthermore, an open application system was used to perform LITT under in vivo conditions during lung perfusion and ventilation in domestic pigs. Lesion volumes in both groups showed a plateau-like curve when the laser power increased from an initial level of 25 W. With the percutaneous puncture system (group I), the application of 28 W (16,800 J) for 10 min generated the largest lesions with a volume of 12.54 +/- 1.33 cm(3), an axial diameter of 39.33 +/- 2.52 mm, and a diametrical diameter of 24.67 +/- 1.15 mm. A longer application time was not possible due to thermal instability of the applicator. Moreover, group I started developing extensive carbonizations at a laser power of 22 W (13,200 J). The intraoperative application system (group II) achieved the largest lesion volumes of 11.03 +/- 2.54 cm(3) with diameters of 34.6 +/- 4.22 mm (axial) and 25.6 +/- 2.51 mm (diametrical) by an exposure time of 20 min and a power of 32 W (38,400 J). Here extensive carbonizations only started to occur at 28 W (33,600 J). Under in vivo conditions, all pigs tolerated the LITT procedure well without complications. Besides a typical cooling effect in the vicinity of blood vessels, the thermal lesions were about three times smaller than the ex vivo lesions. Both the percutaneous and the open LITT application system induced reproducible, clinically relevant lung lesions. The percutaneous puncture set generated large relevant lesions, although its usability is limited by its restricted capacity and high carbonization risk. It is suitable for powers up to 22 W. The intraoperative application system allows higher energy exposure to induce larger lesion volumes. This study elucidates the dose-effect relation of two clinically relevant puncture sets.

Principles of lasers and biophotonic effects.

In this review, we discuss how, due to a variety of different interactions between laser radiation and biological tissue, the laser has become an established instrument in most medical fields. Depending on the interaction time and the effective power density, three types of laser tissue interaction can be distinguished: photochemical effects, photothermal effects, and photomechanical and photoionizing effects. After a description of the physical mechanisms, the typical parameters, and the medical applications of these effects, a review of the laser types used in medicine is given. For percutaneous laser disc decompression (PLDD), lasers in the near-infrared region (Nd:YAG, Ho:YAG, and diode lasers) and with visible green radiation (frequency doubled Nd:YAG, called "KTP laser") were reported to be effective.