Martin Bettag

MRI-guided LASER-induced interstitial thermotherapy of cerebral neoplasms

Objective Laser-induced interstitial thermotherapy (LITT) using a neodymium:yttrium aluminum garnet (Nd: YAG) laser is a new therapeutic approach in the treatment of brain tumors. The purpose of our study was to determine the value of MRI in monitoring LITT. Materials and Methods Eight patients with intracerebral tumors were treated with LITT. The light guide was inserted via an applicator sheath that was implanted stereotaxically with CT guidance. The laser irradiation was performed within the MR unit and monitored by repetitive measurements of a T1-weighted 2D-FLASH sequence. Results During therapy in all patients, typical changes of signal intensity were seen. A gradually increasing central zone of high signal intensity was surrounded by an increasing peripheral area of reduced signal intensity. The diameter of an enhancing rim at the outer border of the peripheral area after Gd-DTPA was considered as the total lesion size. The lesion size as determined on 2D-FLASH scans during LITT accounted for 88–100% (mean 93.5%) of total lesion size on T1-weighted images after Gd-DTPA acquired immediately after therapy. On T2-weighted images the signal intensities of the two zones were vice versa. Follow-up studies showed a decrease of total lesion size (15–87%). Conclusion Our results demonstrate that MRI is feasible and effective in monitoring LITT. However, the role of LITT in the therapeutic workup of brain tumors still has to be defined in future clinical studies.

Stereotactic Laser Therapy in Cerebral Gliomas

The 1.06 micron Nd:YAG laser and a new fiberoptic delivery system, the Interstitial Thermo-Therapy (ITT) laser fibre, allows stereotactic interstitial irradiation of cerebral tumours. In experimental rat brain studies we found typical laser-tissue effects with a central necrosis and a sharply demarcated oedema towards the normal brain. The size of the lesion depended on the energy and exposure time applied. In a pilot series we treated 5 patients with cerebral gliomas WHO grade II-III in functionally important regions and monitored the therapeutic effects by MR imaging and PET scan. Early post-operative results showed irreversible necrotic changes in the tumour centre and reversible oedematous changes at the tumour margin. Long-term results will show if stereotactic interstitial laser therapy is a useful supplementary method in the treatment of malignant cerebral tumours.

Gadolinium-DTPA-enhanced MRI and positron emission tomography of stereotactic laser-induced interstitial thermal therapy in cerebral gliomas

Stereotactic laser-induced interstitial thermal therapy (SLIITT) is a new method for inducing local hyperthermia in cerebral tumours. As pre- and early post-therapeutic evaluations in five patients with cerebral gliomas WHO grade II and III treated by SLIITT we performed ga-dolinium-DTPA-enhanced MRI and positron emission tomography (PET). We found that MRI is a sensitive tool for mapping the spatial and temporal distribution of laser-tissue interactions. PET studies using 2-(18F)fluoro-2-D-de-oxyglucose showed typical changes in glucose metabolism of the glioma. Both investigations seem to reveal irreversible laser effects in the centre of the tumour probably due to a coagulative necrosis and reversible effects at the tumour margin probably caused by reparative processes after SLIITT. It could be demonstrated that laser-tissue interactions progress with time, depending on laser energy and exposure time.

Optical changes of porcine brain tissue after thermal coagulation

Porcine brain tissue is a model for human brain structures in laser induced thermo-therapy. However, its optical properties including possible heat-related changes were basically unknown so far. To simulate laser coagulation, 12 specimens (6 grey and 6 white matter) were heated in a saline bath (80°C, 2 hours) and compared to 11 untreated samples (5 grey and 6 white matter). The optical constants were obtained from transmission (total and collimated) and reflection (diffuse) measurements using the inverse Monte-Carlo method. The absorption coefficient ((mu) a) of untreated grey substance decreased from 0.35 +/- 0.06/mm (340 nm) to 0.03 +/- 0.02/mm (800 nm). The scattering coefficient ((mu) s) varied between 20.42 +/- 3.65/mm (340 nm) and 6.85 +/- 2.07/mm (800 nm). The anisotropy factor (g) increased from 0.848 +/- 0.013 (340 nm) to 0.889 +/- 0.009 (800 nm). Coagulation increased (mu) a up to a factor of 2 (340-540 nm; p < 0.05), and (mu) s by a factor up to 3 (340-800 nm, all data p < 0.001) while g was decreased up to 18% (340-560 nm; p < 0.05). White substance exhibited a (mu) a between 0.24 +/- 0.07/mm (340 nm) and 0.04 +/- 0.02/mm (800 nm) while (mu) s varied between 26.72 +/- 9.10/mm (340 nm) and 21.78 +/- 3.88/mm (800 nm). The g-value increased from 0.561 +/- 0.180 (340 nm) to 0.834 +/- 0.068 (800 nm). Coagulation increased (mu) a by a factor up to 2 (340-800 nm; all data p < 0.05) while (mu) s and g remained unchanged. Thermal denaturation changes the absorption and scattering properties of porcine brain significantly.

MR-guided laser interventions

Low-power interstitial thermal therapy using a 1064 nm Nd:YAG laser and a newly designed fiberoptic transmission system, the ITT laser fiber, is a promising therapeutic approach in the treatment of cerebral tumors. After CT-guided stereotactic implantation of an applicator probe, we performed laser-induced interstitial thermal therapy in a patient with an astrocytomas WHO grade II under simultaneous magnetic resonance imaging (MRI) control. In order to assess the effects of the treatment a 2D-Flash sequence with an acquisition time of 15 sec was used. It could be demonstrated that laser-tissue interactions progressed with duration of irradiation depending on laser powers applied. There was a well-defined area of tissue necrosis with a maximum size of 17 mm in diameter in the center of the tumor and a small zone of transient perifocal edema. With regard to experimental studies, it seems to be possible to define between reversible and irreversible laser-tissue effects.

Somatosensory evoked potentials modified by laser-induced lesions of the rat cortex.

The effect of focal application of laser energy on the modification of somatosensory evoked potentials (SEPs) was studied in sensory cortical fields of the rat. This article describes the methodological set-up for recording of SEPs and for determining location and size of the laser-induced lesion. The results show that both the size of the lesion of the somatosensory cortex, and the suppression and time of recovery of cortical SEPs varied depending on the laser energy dose. It remains to be analyzed by further experiments if the recovery of SEPs is due to a transient dysfunction of the somatosensory cortex or if it reflects cortical plasticity.

Magnetic Resonance Imaging-Guided Interstitial Laser Therapy in Brain Tumors

Laser-induced interstitial thermotherapy (LITT) is a minimally invasive technique of local brain tumor destruction. The concept of interstitial hyperthermia was first evaluated in experimental studies by Bown in 1983 [6]. For a safe clinical application it is mandatory to define the extent of thermally mediated laser-induced damage to the tissue. Jolesz and coworkers studied the sensitivity of magnetic resonance imaging (MRI) to visualize laser-induced tissue changes [7]. MRI proved to be well suited for monitoring LITT due to its high soft-tissue contrast and its sensitivity for temperature changes. In this paper we report our experiences with MRI-guided LITT in eight patients with intracranial tumors.

Positron emission tomography of laser-induced interstitial hyperthermia in cerebral gliomas

Up to the present 5 patients with cerebral gliomas (WHO II-III) were treated by stereotactic, laser-induced, interstitial thermal therapy (SLIITT). Parameters used in SLIITT were 3 watts as continuous wave over 5-10 minutes in single or multiple foci depending on the size of the tumor.