[Survival after laser-induced interstitial thermotherapy of colorectal liver metastases--a comparison of first clinical experiences with current therapy results]. / Langzeitüberleben nach laserinduzierter interstitieller Thermotherapie kolorektaler Lebermetastasen--ein Vergleich erster klinischer Erfahrungen mit aktuellen Behandlungsergebnissen.

PURPOSE: Laser-induced interstitial thermotherapy (LITT) is a minimally invasive procedure for local tumor ablation. This report discusses the long-term results of this therapy in non-surgical patients with colorectal liver metastases. MATERIALS AND METHODS: In total, we treated 163 colorectal liver metastases in 85 patients by MR-guided LITT. RESULTS: The overall lethality was 1.1%. The mean survival period of all treated patients was 3.3+/-0.3 years (CI: 2.8; 3.8; Kaplan-Meier method) with a calculation start date of the diagnosis of the metastases. The mean survival period after LITT was 2.6+/-0.2 years (CI 2.2; 3.0). There was a substantial learning curve with respect to the indication for LITT and the technical procedure of the intervention itself. In the first period (50 patients; 1998-2001), the mean survival period was 2.2+/-0.2 years (CI: 1.8; 2.7). Thereafter (35 patients 2001-2006), the mean survival period increased to 2.9+/-0.3 years (CI: 2.4; 3.4; log rank Test; p=0.0097). In the latter group, the 1-year survival rate was 93% and the 3-year survival rate was 56%. CONCLUSION: MR-guided LITT is a treatment suitable for non-surgical patients suffering from colorectal liver metastases. The complication rate of the procedure is comparatively low. The survival periods after the procedure are longer than those reported for similar patient populations after chemotherapy alone.

[Stereotactic body radiotherapy (SBRT) -- an overview under special consideration of SBRT and LITT in the therapy of liver metastases]. / Extrakranielle stereotaktische Radiotherapie (ESRT) - eine Ubersicht unter besonderer Berücksichtigung von ESRT und LITT in der Behandlung von Lebermetastasen.

Stereotactic body radiotherapy (SBRT) is a high dose radiotherapy, the radiation dose is applicated one-time or in a few fractions exactly to the tumor or metastases under maximal separation from the normal tissue. Because of this a major expenditure of medical and technical efforts are necessary, a detailed description of the proceedings is following in the methodic part of this article. Indications of SBRT are especially medical irresectable lung tumors of early stages, primary liver/biliary tumors and pulmonary or liver metastases if there is an oncological benefit for the patients. The side effects are moderate, the local tumor control rate is between 78 to 100 %. Depending on the primary tumor the overall survival is prolonged statistically significant. In the Klinikum Krefeld indications of SBRT vs chemotherapy, LITT or resection are discussed by an interdisciplinary conference of gastroenterologists/oncologists, radiologists, radiooncologists and surgeons. An example of LITT will be shown also.

Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range.

Medical laser applications require knowledge about the optical properties of target tissue. In this study, the optical properties of selected native and coagulated human brain structures were determined in vitro in the spectral range between 360 and 1100 nm. The tissues investigated included white brain matter, grey brain matter, cerebellum and brainstem tissues (pons, thalamus). In addition, the optical properties of two human tumours (meningioma, astrocytoma WHO grade II) were determined. Diffuse reflectance, total transmittance and collimated transmittance of the samples were measured using an integrating-sphere technique. From these experimental data, the absorption coefficients, the scattering coefficients and the anisotropy factors of the samples were determined employing an inverse Monte Carlo technique. The tissues investigated differed from each other predominantly in their scattering properties. Thermal coagulation reduced the optical penetration depth substantially. The highest penetration depths for all tissues investigated were found in the wavelength range between 1000 and 1100 nm. A comparison with data from the literature revealed the importance of the employed tissue preparation technique and the impact of the theoretical model used to extract the optical coefficients from the measured quantities.

Laser-induced interstitial thermotherapy of liver metastases in an interventional 0.5 Tesla MRI system: technique and first clinical experiences.

Laser-induced interstitial thermotherapy (LITT) surveyed by magnetic resonance imaging (MRI) has been shown to be effective in various applications. The laser treatment of colorectal liver metastases usually requires a separate device (e.g., ultrasound or CT) to position the laser applicator. In this study, we used an interventional 0.5 T MRI system, allowing both the navigation to the target tissue and on-line thermometry. Laser irradiation was performed using a near-infrared laser source combined with a cooled laser light guide. We treated 20 patients exhibiting a total of 58 colorectal liver metastases. Clinically relevant complications did not occur. No residual tumor was observed after laser irradiation in all metastases with a diameter below 2 cm. Metastases with a mean diameter between 2 and 3 cm demonstrated total necrosis in 71%, while in larger tumors this proportion decreased to 46% (diameter, 3-4 cm) and 30% (diameter, >4 cm), respectively. We conclude that LITT, guided by the employed interventional MRI system, is feasible and safe. The results suggest a more aggressive treatment, especially for larger metastases. J. Magn. Reson. Imaging 2001;13:729-737.

Scattering delay time of Mie scatterers determined from steady-state and time-resolved optical spectroscopy.

We have determined the scattering delay time of Mie scatterers (r = 255 nm quartz spheres in polyester resin) from a combination of steady-state (integrating-sphere) and time-resolved (frequency-domain) measurements performed in the multiple-scattering regime. The effective transport velocity of light was derived from intensity and phase measurements at four different wavelengths by using the time-integrated microscopic Beer-Lambert law. We could demonstrate a systematic underestimation of the effective transport velocity compared with the phase velocity in the medium. Assuming that this discrepancy was caused entirely by the transient nature of a single-scattering process, the data presented resulted in time delays of between 18 fs (lambda = 678 nm) and 177 fs (lambda = 1,064 nm) per scattering event. For three out of four wavelengths investigated, the measured values are in excellent agreement with values predicted by a theoretical model for the scattering delay time based on Mie theory.

Quantitative microspectrophotometry in turbid media.

We present a new technique to determine the scattering coefficient, the absorption coefficient, and the anisotropy factor in turbid media on a microscopic level. To this end, a microspectrophotometer was used to obtain transmission measurements at different solid angles. To extract the optical properties from phantom materials (liquid and solid) and biological tissue (bovine liver) an inverse Monte Carlo algorithm was used. The results obtained with the new microspectrophotometric technique agreed within one standard deviation with the values from Mie theory and within less than 10% with the data derived from conventional spectroscopic measurements. The results suggest that this new method is a valid tool to determine the optical properties of turbid media on a microscopic level.

Influence of the scattering phase function approximation on the optical properties of blood determined from the integrating sphere measurements.

We investigated the impact of the scattering phase function approximation on the optical properties of whole human blood determined from integrating sphere measurements using an inverse Monte Carlo technique. The diffuse reflectance Rd and the total transmittance Tt(λ=633 nm) of whole blood samples (Hct=38%) were measured with double-integrating sphere equipment. The scattering phase functions of highly diluted blood samples (Hct=0.1%) were measured using a goniophotometer. We approximated the experimentally determined scattering phase functions with either Henyey-Greenstein (HGPF), Gegenbauer kernel (GKPF), or Mie (MPF) phase functions to preset the anisotropy factor µ¯ for the inverse problem. We have employed HGPF, GKPF, and MPF approximations in the inverse Monte Carlo procedure to derive the absorption coefficient µa and the scattering coefficient µs. To evaluate the obtained data, we calculated the angular distributions of scattered light for optically thick samples and compared the results with goniophotometric measurements. The data presented in this study demonstrate that the employed approximation of the scattering phase function can have a substantial impact on the derived values of µs and µ¯, while µa and the reduced scattering coefficient µs' are much less sensitive to the exact form of the scattering phase function. © 1999 Society of Photo-Optical Instrumentation Engineers.

[Interventional MR tomography. Current status and future perspectives]. / Interventionelle MR-Tomographie. Aktueller Stand und Zukunftsperspektiven.

The concept of MR guidance of invasive diagnostic and minimally invasive therapeutic procedures is based on the excellent morphologic and functional properties of MR imaging. Prerequisites are adequate patient monitoring and adherence to safety guidelines. Fast and ultrafast sequences, temperature quantification, visualization of intravascular devices, thermal stability of contrast media and thermosensitive contrast media are discussed. The spectrum of clinical applications includes biopsies, thermal ablation modalities, vascular applications, MR endoscopy and intraoperative MR imaging. The development of interventional MR imaging is still in its infancy. In the future, MR imaging may play an important role in interventional radiology and minimally invasive therapy.

In vivo MRI thermometry using a phase-sensitive sequence: preliminary experience during MRI-guided laser-induced interstitial thermotherapy of brain tumors.

The purpose of this study was the application of the proton-resonance-frequency method to monitor laser-induced interstitial thermotherapy (LITT) in a patient with an astrocytoma WHO II. A phase-sensitive two-dimensional (2D) fast low-angle shot (FLASH) sequence was used to determine the temperature-related phase shifts during LITT. Temperature maps were displayed during therapy with a temporal resolution of 20 seconds. Irradiation was discontinued as soon as the 60 to 65 degrees C isotherm reached the margin of the tumor. A contrast-enhanced MRI study performed immediately after therapy showed a good correlation of the size of an enhancing rim around the lesion with the 60 to 65 degrees C isotherm. The preliminary results of our study indicate that MRI guidance of LITT may be improved by temperature quantification based on the proton-resonance-frequency method.

Treatment planning for MRI-guided laser-induced interstitial thermotherapy of brain tumors--the role of blood perfusion.

MR techniques have been demonstrated to allow a reliable monitoring of laser-induced interstitial thermotherapy (LITT). However, an adequate on-line control of this coagulation technique requires an exact therapy planning. The latter is mandatory to interpret the MR-monitoring data correctly to guarantee a precise laser irradiation. Moreover, it is a prerequisite for on-line decisions if modifications of the therapeutic regimen are required. In this work, we present a new simulation technique for LITT planning. The model accounts for the specific geometry of the treatment site, the exact configuration of the applicator, and the optical and thermal properties of the tissue, including changes during the heating process. The simulation results were compared with MR scans of laser-induced lesions in three patients with World Health Organization (WHO) grade II astrocytoma. Special interest was directed toward the role of blood perfusion, which was studied parametrically. Good agreement between the simulation results and the MR data was found if the appropriate blood perfusion rates were taken into account. Thus, the model can generate valid therapy plans allowing a precise on-line control of laser irradiation using MR techniques. Neglecting adequate perfusion parameters resulted in substantial errors with respect to the prediction of the final laser lesion.

Laser-induced thermal lesions in the human brain: short- and long-term appearance on MRI.

PURPOSE: The purpose of our study was to investigate with MRI the development of thermal lesions in the human brain up to almost 4 years after laser-induced interstitial thermotherapy (LITT). METHOD: Eighteen patients with brain tumors who underwent LITT entered the study. RESULTS: In all patients the acute lesion comprised five concentric zones that showed reverse signal intensities on T1- versus T2-weighted images. Lesion development over time was uniform in 89% of the lesions. In two cases variations were observed. CONCLUSION: The results of our MR follow-up studies showed that post-LITT, laser-induced lesions will shrink exponentially after an initial expansion without any pseudocystic effects.

[MR tomographic temperature quantification at 1.5 T in vitro: a comparison of fast T1 maps and a phase-sensitive sequence]. / MR-tomographische Temperaturquantifizierung bei 1.5 T in vitro: Vergleich von schnellen T1-Parameterbildern und einer phasensensitiven Sequenz.

PURPOSE: To determine the value of fast T1-maps and a phase-sensitive sequence for temperature quantification with MR imaging. MATERIAL AND METHODS: The experimental setup allowed both homogeneous heating as well as laser-induced interstitial thermotherapy (Nd:YAG, 1064 nm) of tissue specimens (pig brain, liver and muscle) in vitro. A total of 60 experiments were performed. T1-maps were calculated by means of a multi-point-turbo-FLASH sequence. Additionally, the temperature dependent phase shift was determined with a 2D-FLASH sequence. RESULTS: The T1-relaxation times of four different aqueous solutions of gadolinium-DTPA (0.125-1.0 mmol/l) varied by less than 5%. During homogeneous heating, the T1-maps revealed a linear correlation (r > 0.98) between temperature and T1-relaxation times. The temperature coefficients were 11.0 +/- 0.42 ms/degree C. Variations of the linear correlation were observed during laser irradiation. There was only slight variation of the temperature coefficients of the chemical shift during homogeneous heating of different tissues (brain: 0.0098 +/- 0.0002 ppm/degree C; muscle: 0.0109 +/- 0.0003 ppm/degree C; liver: 0.0093 +/- 0.0002 ppm/degree C). The temperatures calculated during laser therapy based on the phase shift correlated strongly (r = 0.99) to the measured temperatures. CONCLUSION: Due to the considerable tissue independence and high accuracy, the phase mapping method is superior to T1-maps for monitoring thermal therapy modalities at 1.5 T in vitro.

Determination of laser-induced temperature distributions using echo-shifted TurboFLASH.

An echo-shifted TurboFLASH sequence implemented on a clinical whole body MR scanner was used to determine thermal changes in tissue. With this snapshot-like data acquisition, temperature-related phase shifts were measured with a temporal resolution of 1.3 s. For different types of tissue (postmortem porcine brain, liver, and muscle) the temperature coefficients of the proton chemical shift were recorded during uniform heating of the specimen in a water bath. The specific temperature-dependent frequency shifts appeared similar to the proton chemical shift of free water (-0.01 ppm/degrees C). With this method, laser-induced ablation in postmortem porcine brain was monitored by temperature mapping. Comparison of the induced temperature profiles measured with NiCrNi-thermocouples with the MR calculated profiles demonstrated excellent temperature sensitivity and accuracy for this method of MR thermometry, with a maximum deviation of the determined temperatures of only 1.8 degrees C. This investigation was designed as a feasibility study for this rapid version of the phase mapping method, and no in vivo studies were performed.

Preliminary experience with the application of gadolinium-DTPA before MR imaging-guided laser-induced interstitial thermotherapy of brain tumors.

The purpose of this study was to investigate the potential value of i.v. gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) applied before MRI-guided laser-induced interstitial thermotherapy (LITT) of brain tumors without original enhancement, especially in defining total lesion size during therapy. MRI-guided LITT was performed on two patients with astrocytoma WHO II. For both patients, Gd-DTPA was administered intravenously after a first irradiation period and LITT was continued after pulling back the light guide to coagulate the upper parts of the tumor. In both patients, the whole irreversible damaged zone of the second irradiation period after Gd-DTPA showed an intense increase of signal intensity. The spatial expansion correlated with the diameter of an enhancing rim after Gd-DTPA on follow-up studies. Our preliminary results indicate that the application of Gd-DTPA before MRI-guided LITT may be of value in defining exactly the size of the irreversible damaged zone during therapy in nonenhancing brain tumors.

Effect of the scattering delay on time-dependent photon migration in turbid media.

We modified the diffusion approximation of the time-dependent radiative transfer equation to account for a finite scattering delay time. Under the usual assumptions of the diffusion approximation, the effect of the scattering delay leads to a simple renormalization of the light velocity that appears in the diffusion equation. Accuracy of the model was evaluated by comparison with Monte Carlo simulations in the frequency domain for a semi-infinite geometry. A good agreement is demonstrated for both matched and mismatched boundary conditions when the distance from the source is sufficiently large. The modified diffusion model predicts that the neglect of the scattering delay when the optical properties of the turbid material are derived from normalized frequency- or time-domain measurements should result in an underestimation of the absorption coefficient and an overestimation of the transport coefficient. These observations are consistent with the published experimental data.

[Laser-induced interstitial induced hyperthermia of cerebral tumors with nuclear magnetic resonance tomography control]. / Laserinduzierte interstitielle Thermotherapie von zerebralen Tumoren unter kernspintomographischer Kontrolle.

PURPOSE: The purpose of our study was to determine the value of MRI in monitoring laser-induced interstitial thermotherapy (LITT) of cerebral neoplasms. MATERIALS AND METHODS: Sixteen patients with brain tumors were treated with LITT. The laser irradiation was performed within the MR unit and monitored with a temperature-sensitive T1-weighted 2D-FLASH sequence. RESULTS: During irradiation a gradually increasing central zone of high signal intensity was surrounded by an increasing area of reduced signal intensity. After therapy, the diameter of an enhancing rim at the outer border of the peripheral zone indicated total lesion size. On T2-weighted images the signal intensities were reversed. Total lesion size decreased during follow-up. CONCLUSION: MRI is suitable for monitoring LITT. However, the role of LITT in the treatment of brain tumors has still to be defined.

Mapping of the cortical motor hand area with functional MR imaging and MR imaging-guided laser-induced interstitial thermotherapy of brain tumors. Work in progress.

PURPOSE: To localize the cortical motor hand area with functional magnetic resonance (MR) imaging before and after MR imaging--guided laser-induced interstitial thermotherapy of tumors in the precentral brain region to control energy delivery and to improve safety. MATERIALS AND METHODS: Functional MR images were obtained in eight patients (five men, three women; aged 27-63 years) while they flexed their fingers. MR imaging--guided laser-induced interstitial thermotherapy was terminated when there was less than 8-12 mm between the border of the laser-induced lesion and the motor hand area anterior aspect. RESULTS: Seven patients had a statistically significant localized change in signal intensity in the central region of the contralateral hemisphere. This area was a spotlike circumscribed focus in three patients and scattered over a larger zone in four patients. Persistent deficits did not occur after thermotherapy in any patient. In three patients, onset of reversible perifocal edema in the motor hand area coincided with the development of hemiparesis, which completely resolved. No patient had activity within the tumor on functional MR images. CONCLUSION: Functional MR imaging findings can be used to prevent neurologic damage during MR imaging--guided laser-induced interstitial thermotherapy.

Inverse hybrid technique for determining the optical properties of turbid media from integrating-sphere measurements.

We have combined the Monte Carlo method with the small-angle approximation of the radiative transfer theory to derive the optical properties (the absorption coefficient, the scattering coefficient, and the anisotropy factor) of turbid materials from integrating-sphere measurements (the total transmittance and the diffuse reflectance) and the collimated transmittance. Unlike one-dimensional models, the technique accounts for the side losses of light at the edges of the sample. In addition, it enables the correction of the measured collimated signal for the contribution of multiply scattered light. On the other hand, the hybrid technique allows a significant reduction in calculation time compared with inverse methods based on a pure Monte Carlo technique. Numerical tests and experimental results from a phantom material (milk) as well as samples of biological tissue (porcine myocardium) confirmed the feasibility of applying this technique to the determination of the optical properties of turbid media.

Magnetic resonance imaging of microwave induced tissue heating.

MR-guided interstitial thermotherapy offers a minimally invasive treatment for localized tumors and tissue structures exhibiting functional abnormalities. In this study, microwaves (2.45 GHz) were used for tissue irradiation to overcome some limitations of the heating sources used so far. To this end, a microwave antenna was positioned in a specimen of porcine myocardium and irradiated for 10 min under MRI control using a T1-weighted FLASH sequence. The heating procedure resulted in a spherical tissue lesion of 26 mm in diameter. Thus, we could demonstrate the feasibility to monitor the microwave-induced coagulation process by MR-imaging in vitro.