Synergy effects between organic and inorganic UV filters in sunscreens.

The influence of the synergy effects between organic and inorganic UV filter substances on the sun protection factor (SPF) of topically applied sunscreen formulations is investigated. The medium is considered to have reflection, absorption, and scattering properties. The distribution of photons in this medium is investigated by Monte Carlo calculation. Typical optical parameters of the skin and substances are used to characterize the synergy effect. The results of the model calculation are checked by in vitro and in vivo measurements investigating the influence of different types of scattering microparticles on the absorption efficacy of topically applied formulations. It is found that the inorganic filter substances act as scattering microparticles in the upper skin layers. They increase the optical pathway of the photons in the topically applied absorbing formulation also localized there. In this way, more photons are absorbed, increasing the SPF. The results obtained are important for the optimization of the SPF of sunscreen formulation containing organic and inorganic UV-filter components.

Multipolar radiofrequency ablation: first clinical results.

Common systems of radiofrequency ablation (RFA) are monopolar devices which require grounding pads on the thighs in order to close the electrical circuit. Bipolar RFA does not require grounding pads, because both electrodes are located on one probe and alternating current circuit is confined within the target tissue. In this paper we report on the first clinical application of a new ablation device which enables both, bipolar (1 probe) and multipolar (up to 3 internally cooled probes simultaneously) radiofrequency ablation. We report on bi- and multipolar applications in liver tumors (9 patients), osteoid osteoma (2 patients) and renal cell cancer (1 patient).

Laser-induced thermotherapy: intra- and extralesionary recurrence after incomplete destruction of experimental liver metastasis.

PURPOSE: The aim of this study was to determine the energy (J/mm3 tumor volume) and temperature required for a complete laser-induced thermotherapy (LITT) of experimental liver tumors, and to find out causes and areas of local recurrence followed by incomplete treatment. METHODS: In VX-2 tumor-bearing rabbits LITT was performed using neodymium:yttrium-aluminum-garnet (Nd:YAG) laser (1064 nm) with a diffuser-tip applicator and a temperature feedback system. The animals were randomized into four groups (n = 20) that differed in the target temperature at the tumor border as follows: 45 degrees C, 50 degrees C, 55 degrees C and 60 degrees C. The target temperature was held for 10 min constant. Histologic examination (hematoxylin and eosin [H and E], nicotinamide adenine dinucleotide phosphate [NADPH]-dehydrogenase) was performed at 0 h, 24 h, 96 h, and 14 days after LITT. RESULTS: The pretreatment tumor volume of 2191 +/- 61 mm3 was the same for all groups (p > 0.05). Energy up to target temperature and total energy required, lesion size, and the rate of incomplete tumor ablation (recurrences) are listed below (ap < 0.05, Kruskal-Wallis test). Histologically, two forms of local recurrences could be differentiated intralesionary and extralesionary. CONCLUSIONS: To achieve complete in situ ablation under the given conditions, it is necessary to apply laser energy of 3 J/mm3 tumor volume. A minimum temperature of 60 degrees C on the tumor border presumed an application of 10 min. Recurrence was found outside the coagulation zone (extralesionary) and in high vascularized areas within the coagulation zone (intralesionary).

MR-guided laser-induced thermotherapy in recurrent extrahepatic abdominal tumors.

The aim of this study was to evaluate the feasibility of MR-guided laser-induced thermotherapy (LITT) for treatment of recurrent extrahepatic abdominal tumors. In 11 patients (6 women and 5 men; mean age 53 years, age range 29-67 years) with 14 lesions the following tumors were treated in this study: paravertebral recurrence of hypernephroma (n=1); recurrence of uterus carcinoma (n=1); recurrence of chondrosarcoma of the pubic bone (n=1); presacral recurrence of rectal carcinoma (n=1); recurrent anal cancer (n=1); metastases in the abdominal wall (n=1); and lymph node metastases from colorectal cancer (n=8). A total of 27 laser applications were performed. A fast low-angle shot 2D sequence (TR/TE/flip angle=102 ms/8 ms/70 degrees ) was used for nearly real-time monitoring during treatment. All patients had no other treatment option. Seventeen LITT sessions were performed using a conventional laser system with a mean laser power of 5.2 W (range 4.5-5.7 W), and 10 LITT session were performed using a power laser system with a mean laser power of 28.0 W. In 10 lesions total destruction could be achieved. In the remaining recurrent tumors, significant reduction of tumor volume by 60-80% was obtained. All patients tolerated the procedure well under local anesthesia. No complications occurred during treatment. Laser-induced thermotherapy is a practicable, minimally invasive, well-tolerated technique that can produce large areas of necrosis within recurrent tumors, substantially reducing active tumor volume if not resulting in outright destruction of tumor.

Optical properties of native and coagulated porcine liver tissue between 400 and 2400 nm.

BACKGROUND AND OBJECTIVE: Laser induced thermotherapy (LITT) is a promising treatment for irresectable liver tumors. For predicting the effects of laser applications and optimizing irradiation planning in LITT, knowledge about light distribution in tissue, optical tissue properties (absorption, scattering, anisotropy, penetration depth) and their changes due to thermal denaturation is indispensable. STUDY DESIGN/MATERIALS AND METHODS: The optical parameters in healthy porcine liver were determined in the native state and after thermal coagulation using a double integrating sphere system in the wavelength range of 400-2400 nm. RESULTS: Optical parameters showed significant fluctuations in the examined wavelength range mainly due to the water and hemoglobin content in the tissue. The greatest optical penetration depth of 7.46 mm was achieved at 1070 nm. After thermal coagulation, a clear increase in scattering and a slight decrease in absorption was found, which results in a decreased optical penetration depth. CONCLUSIONS: In order to ensure a safe and effective procedure, an adjustment of the laser power to the decreasing penetration depth is recommended during therapy. These results provide a better understanding of laser-tissue interaction and may be helpful to investigators in the field of light dosimetry in liver tissue.

Percutaneous MR imaging-guided laser-induced thermotherapy of hepatic metastases.

BACKGROUND: Many primary tumors may cause liver metastases, which are generally treated with surgical resection and/or chemotherapy. After resection of liver metastases in patients with colorectal carcinoma, 5-year survival rates are achieved in 25-38%, and two-thirds of patients will experience recurrent metastases. We examined percutaneous, minimally invasive, laser-induced thermotherapy (LITT) as an alternative outpatient procedure. Local tumor control rate and survival data were analyzed prospectively. METHODS: Between June 1993 and August 2000, 7148 laser applications were performed in 1981 lesions in 705 consecutive patients and 1653 treatment sessions. The complications of the procedure were evaluated by clinical examination and magnetic resonance imaging (MRI) and computed tomography. Local tumor control was evaluated by plain and contrast-enhanced follow-up MRI using T1- and T2-weighted spin-echo and gradient-echo sequences every 3 months after treatment. Cumulative survival times were calculated using the Kaplan-Meier method. RESULTS: The overall rate of complications and side effects was 7.5%. The rate of clinically relevant complications was 1.3%. Local tumor control rate after 3 months was 99.3%; 6 months after laser treatment, plain and contrast-enhanced MRI documented a local tumor control rate of 97.9%. In patients treated with MR-guided LITT for unresectable colorectal liver metastases, the mean survival was 41.8 months (95% confidence interval = 37.3-46.4 months). The 1-year survival rate was 93%, the 2-year survival rate was 74%, the 3-year survival rate was 50%, and the 5-year survival was 30%. In patients treated with LITT for liver metastases from breast cancer, the mean survival was 4.3 years (95% confidence interval = 3.6-5.0 years). CONCLUSION: In patients with liver metastases, local tumor destruction using minimally invasive, percutaneous LITT under local anesthesia results in improved clinical outcomes and survival rates and can be a potential alternative to surgical resection.

Ex vivo evaluation of novel miniaturized laser-induced interstitial thermotherapy applicators for effective small-volume tissue ablation.

RATIONALE AND OBJECTIVES: For effective small-volume tissue ablation in clinical and experimental settings, smaller laser-induced interstitial thermotherapy (LITT) applicator designs are required. The aim of this study was to compare the ablation properties of recently developed ultrasmall and small to standard LITT applicators. METHODS: Laser-induced interstitial thermotherapy was performed on liver samples using ultrasmall, small, and standard LITT applicators. Thermotherapy was monitored by magnetic resonance imaging, and lesion sizes were measured for each image. True lesion sizes were then determined macroscopically and by histology. RESULTS: For continuous laser application over 5 minutes, maximum power settings were 5 W for the ultrasmall and small applicators and 10 W for the standard applicator. Given identical LITT settings, lesion volume measured by magnetic resonance imaging was significantly larger and histological tissue damage was more severe with the ultrasmall and small applicators than with the standard applicator. CONCLUSIONS: Small and ultrasmall LITT applicators can be used for effective tissue ablation of small target volumes in experimental and clinical applications.

Continuous changes in the optical properties of liver tissue during laser-induced interstitial thermotherapy.

BACKGROUND AND OBJECTIVE: Laser-induced thermotherapy (LITT) is a promising treatment for irresectable liver tumors. To predict the effects of laser applications and to optimize treatment planning in LITT, it is essential to gain knowledge about light distribution in tissue, tissue optical properties (absorption, scattering, anisotropy, penetration depth), and their continuous changes during therapy. STUDY DESIGN/MATERIALS AND METHODS: Measurements of optical properties were performed with a double integrating-sphere system and a laser diode (830 nm). Porcine liver tissue samples were examined in a native state (35 degrees C) and after exposure to different temperatures (45 degrees C to 80 degrees C). RESULTS: Rising temperature was accompanied by a decrease in the absorption coefficient and anisotropy factor and an increase in the scattering coefficient. These changes were only significant in the temperature range of 50 degrees to 65 degrees C (P < 0.01). The optical penetration depth decreased from 3.1mm in the native state to 1.7mm at 65 degrees C (P < 0.01). Above 65 degrees, there was no significant change in the tissue optical properties. CONCLUSIONS: The optical properties of liver tissue change significantly under the influence of tissue heating, resulting in a decreased optical penetration depth. These changes occur mainly in the temperature range of 50 degrees C to 65 degrees C, corresponding to protein denaturation. To ensure a safe and effective procedure, an adjustment of the laser power to the actual penetration depth is recommended during therapy.

MR-guided interstitial laser-induced thermotherapy of hepatic metastasis combined with arterial blood flow reduction: technique and first clinical results in an open MR system.

The feasibility and safety of percutaneous laser-induced thermotherapy (LITT) of liver metastases in an open low-field magnetic resonance imaging (MRI) system combined with microsphere-modulated blood flow reduction were tested. Nd:YAG laser therapy with an internally cooled laser applicator was performed under local anesthesia on 20 patients with 34 liver metastases. To increase the effectiveness of LITT, degradable starch microspheres were injected into the proper hepatic artery through an MR-visible catheter initially inserted under fluoroscopy. Near real-time imaging was used for positioning the laser applicator. A T1-weighted gradient-echo breath-hold sequence was used for catheter localization and temperature monitoring. The volumes of the liver metastases and the thermonecroses were determined. MRI-guided LITT could be performed in all patients with no clinically relevant complications. Intraprocedural imaging underestimated the extent of thermonecrosis. In conclusion, percutaneous LITT of liver metastases after injection of starch microspheres is both technically feasible and safe in an open MRI system. J. Magn. Reson. Imaging 2001;13:31-36.

[Laser-induced thermotherapy (LITT) for liver metastasis in an open 0.2T MRI]. / Laserinduzierte Thermotherapie (LITT) von Lebermetastasen in einem offenen 0,2T MRT.

OBJECTIVE: To test the feasibility and safety of the laser-induced thermotherapy (LITT) for liver metastases in open MR imaging system operating at 0.2 Tesla. METHOD: Laser therapy using the Nd:YAG laser was performed on 25 patients with a total of 41 liver metastases. An open low-field MRI scanner was used for puncture, positioning of the laser applicator, and monitoring the therapy. A true FISP sequence was used to track the puncture in close to real-time. Localization diagnostics and temperature monitoring were aided by T1-weighted gradient echo sequences in the breath-holding technique. In the first follow up after 24-48 hours, a contrast-enhanced T1-weighted gradient-echo sequence was performed in an MRI scanner at 1.5T. The pre-, intra- and postinterventional volumes of the liver metastases as well as the thermolesions and the thermonecroses were determined. RESULTS: LITT in an open MRI system was technically feasible in all patients with no clinically relevant complications. The mean volumes of the thermolesions measured during intervention in low-field MRI were lower than the volumes of the thermonecroses measured after intervention in high-field MRI. CONCLUSION: The technique presented here of laser-induced thermotherapy for liver metastases in an open MRI system is technically feasible and safe.

[Percutaneous interstitial thermotherapy of malignant liver tumors]. / Perkutane interstitielle Thermotherapie maligner Lebertumoren.

PURPOSE: Description of local ablative techniques such as laser-induced thermotherapy (LITT) and radiofrequency ablation in the percutaneous interstitial thermotherapy for malignant liver tumors. PATIENTS AND METHODS: MR-guided LITT is currently performed by means of implantable percutaneous catheter systems. CT is used to control the insertion of the catheter. Irrigated administration systems are available both for LITT and for radiofrequency therapy. RESULTS: At present LITT enables a local tumor control of 97.2% for localized liver metastases without extrahepatic spreading patterns. In a group of 381 patients the average survival times were 45.7 months for patients with liver metastasis, 42.7 months for those with colorectal liver metastases, and 32 months for HCC tumors. The data for radiofrequency ablation confirm the high value for tumor control of hepatocellular carcinomas with poorer results for liver metastases. CONCLUSIONS: Percutaneous, MR-guided LITT permits good tumor control of liver metastases smaller than 5 cm and less than 5 in number. For HCC, at present percutaneous injection of alcohol, radiofrequency ablation, and LITT are equally effective.

Laser-induced thermotherapy combined with hepatic arterial embolization in the treatment of liver tumors in a rat tumor model.

OBJECTIVE: To assess the effect of combined laser-induced thermotherapy (LITT) and hepatic arterial embolization with degradable starch microspheres (DSM) on tumor response and intrahepatic temperature distribution in rats with liver tumors. SUMMARY BACKGROUND DATA: Laser-induced thermotherapy is a promising in situ ablation technique for malignant liver tumors. However, clinical use is still limited, mainly because of the small size of the inducible coagulation necroses. This results in insufficient tumor destruction. METHODS: Colon carcinoma CC531 was implanted in 60 WAG rat livers. Fourteen days later, a silicon catheter was implanted in the hepatic artery for DSM administration. Tumors were exposed to 1064 nm Nd:YAG laser light at 2 watts for 10 minutes from a diffuser tip applicator placed in the tumor. The animals were randomized into a sham-operated control (group I) and three test groups. Group II received DSM alone, group III received LITT alone, and group IV received DSM + LITT. Tumor control was examined 1, 7, and 14 days after treatment. RESULTS: A complete tumor remission was achieved in all rats treated with LITT + DSM (group IV). In contrast, tumor progression was seen in animals treated with LITT alone (group III) or DSM alone (group II), as well as in the sham-operated controls (group I). CONCLUSIONS: The authors' results suggest that the combination of LITT and DSM considerably increases the efficacy of LITT in the treatment of liver metastases in the rat.

Optical Properties of Circulating Human Blood in the Wavelength Range 400-2500 nm.

Knowledge about the optical properties µa,µs, and g of human blood plays an important role for many diagnostic and therapeutic applications in laser medicine and medical diagnostics. They strongly depend on physiological parameters such as oxygen saturation, osmolarity, flow conditions, haematocrit, etc. The integrating sphere technique and inverse Monte Carlo simulations were applied to measure µa,µs, and g of circulating human blood. At 633 nm the optical properties of human blood with a haematocrit of 10% and an oxygen saturation of 98% were found to be 0.210±0.002 mm-1 for µa,77.3±0.5 mm-1 for µs, and 0.994±0.001 for the g factor. An increase of the haematocrit up to 50% lead to a linear increase of absorption and reduced scattering. Variations in osmolarity and wall shear rate led to changes of all three parameters while variations in the oxygen saturation only led to a significant change of the absorption coefficient. A spectrum of all three parameters was measured in the wavelength range 400-2500 nm for oxygenated and deoxygenated blood, showing that blood absorption followed the absorption behavior of haemoglobin and water. The scattering coefficient decreased for wavelengths above 500 nm with approximately λ-1.7; the g factor was higher than 0.9 over the whole wavelength range. © 1999 Society of Photo-Optical Instrumentation Engineers.

Diffusing Fibre Tip for the Minimally Invasive Treatment of Liver Tumours by Interstitial Laser Coagulation (ILC): An Experimental Ex Vivo Study.

A newly developed diffusing laser applicator was examined for interstitial laser coagulation (ILC) of liver tumours. The applicator consisted of a matted quartz core and a quartz glass dome, also matted on its inner surface and sealed to the fibre. The applicator provided a homogeneous light intensity distribution over an active length of about 20 mm. Lesions were created in an ex-vivo porcine liver model using a Nd-YAG laser comparing the new diffusing tip with a Ringmode(®)-ITT applicator in order to find optimal laser parameters and damage thresholds. The lesions were investigated using macroscopic size measurement, volume calculation and histological examination (H&E, NADPH-dehydrogenase). The damage threshold of the diffusing tip was 6 W at 14 min exposure time whereas the Ringmode(®)-ITT applicator had its limit at 5 W and 12 min exposure. Comparing various exposure times showed that treatment over a time of more than 840 s did not significantly increase the lesion volume. At 5 W and 720 s the mean lesion volume was 6.9±1.1 cm(3) with the diffusing tip and 6.3±0.6 cm(3) with the Ringmode(®)-ITT applicator, both having a slight ellipsoidal shape. Hence, the created lesions were not significantly different for both applicators when the same laser parameters were applied. On the other hand, the new diffusing tip had a higher damage threshold and was therefore capable of producing maximal coagulation volumes of up to 7.9±0.5 cm(3) at 5 W and 20 min. The experiments showed that lesions with a dimension of 31×22 mm can be achieved with the diffusing applicator which seem suitably sized for treating small human liver metastases in a single laser session.

[Laser-induced thermotherapy. Technical prerequisites for treatment of malignant liver tumors]. / Laserinduzierte Thermotherapie. Technische Voraussetzungen zur Behandlung maligner Lebertumoren.

Laser-induced thermotherapy is an in situ ablation method for the local treatment of liver tumors. The basic prerequisite for induction of adequate treatment volumes for clinical use was the development of a thermostable application system. In an ex vivo test series, the specially developed application system (diffuser tip) with 5760 J had a higher thermic loading capacity than the Ringmode applicator with 4200 J, thus enabling the induction of significantly larger lesions with a volume of 7.6 cm3. The results of a further in vivo test series demonstrated that the lesions were subject to a four-phase connective-tissue organization within a 6-month period. Furthermore, the same laser energy (4200 J) was associated with a significantly lower lesion volume of 2.5 cm3 in the in vivo than in the ex vivo test series. The influence of liver perfusion on the inducible lesion volume was examined in a further animal experimental study. By temporarily interrupting hepatic blood perfusion (Pringle's maneuver) during laser application, the effective volume could be increased to 50.3 cm3 (P < 0.01) using an optical beam splitter. These results show that the technical prerequisites for reliable clinical application of laser-induced thermotherapy have been fulfilled.

Optical properties of native and coagulated human liver tissue and liver metastases in the near infrared range.

BACKGROUND AND OBJECTIVE: Knowledge about optical parameters and the resultant light distribution in laser-treated tissue is important for predicting the effects of laser-induced thermotherapy of liver metastases (LITT). MATERIALS AND METHODS: The absorption and scattering coefficients as well as the anisotropy factors and the optical penetration depths of human liver tissue and colorectal liver metastases were determined at 850, 980, and 1,064 nm under native and thermocoagulated conditions. RESULTS: Liver metastases had a lower anisotropy factor, absorption, and scattering coefficient than healthy liver (P < 0.01), resulting in a significantly higher optical penetration depth in metastatic tissue. Coagulation significantly changes the optical parameters by reducing the optical penetration depth in both tissue types (P < 0.01). CONCLUSIONS: A greater optical penetration depth in metastatic tissue is advantageous for LITT, since larger tumor volumes can be coagulated. At the same time, an adjustment of the application parameters during LITT is necessary to achieve optimal therapeutic success.

Internally cooled power laser for MR-guided interstitial laser-induced thermotherapy of liver lesions: initial clinical results.

PURPOSE: To evaluate experimentally and clinically an internally cooled power laser system for percutaneous treatment of liver metastases, with magnetic resonance (MR) imaging guidance, to increase the volume of coagulative necrosis with single laser beam applications. MATERIALS AND METHODS: The power laser system consisted of standard cannulation paraphernalia and a specially designed 7-F protective catheter for cooling the laser tip during treatment to avoid carbonization. A microdome laser beam applicator with a laser tip diameter of 0.95 mm kept the entire device as small as possible. After the unit was tested in 40 porcine livers, 532 laser beam applications (mean power, 27.5 W [range, 22.1-30.0 W]; mean application time, 19.8 minutes [range, 14-30 minutes]) were performed with MR guidance in 127 patients with 318 liver metastases. The safety of the procedure and the volume of induced necrosis were evaluated. RESULTS: In vitro, cuboid areas of coagulative necrosis with a mean greatest diameter of 4.3 cm +/- 0.5 (SD) were demonstrated after single applications. In vivo, MR thermometry allowed accurate demarcation of changes induced by heat, with a mean diameter of necrosis of 3.3 cm +/- 1.4. No carbonization or vaporization of tissue or damage of equipment occurred during treatment. CONCLUSION: This power laser system can increase the volume of laser-induced necrosis in liver metastases with a single application, thereby simplifying and accelerating the treatment of larger lesions.

Laser-induced thermotherapy for the treatment of liver metastasis. Correlation of gadolinium-DTPA-enhanced MRI with histomorphologic findings to determine criteria for follow-up monitoring.

PURPOSE: To evaluate gadolinium (Gd)-diethylenetriamine-pentaacetic-acid (DTPA)-enhanced magnetic resonance imaging (MRI) for follow-up monitoring of laser-induced thermotherapy (LITT) and to determine a useful examination schedule. METHODS: LITT of the liver was performed in 55 rabbits using a neodymium: yttrium-aluminum-garnet (Nd:YAG) laser (4-W power output, 840-s exposure time). Gd-DTPA MRI and histologic examinations were performed at different times (0-168 days). RESULTS: Laser-induced lesions underwent regeneration and volume size reduction (69% after 168 days). The correlation coefficient (MR vs. macroscopic analysis) for the mean lesion diameter was r = 0.96. Histology of lesions comprised the four zones that correlated best with MRI findings. Coagulation necroses immediately after LITT was seen as an area of no enhancement on Gd-DTPA MRI. Circular enhancement was first seen 72-96 h after LITT, which was due to early mesenchymal proliferation. CONCLUSIONS: Gd-DTPA MRI is a good monitoring procedure for LITT. MRI should be performed 24 and 96 h after LITT.