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The goal of the project “stereotactic laser-neurosurgery” is the development of a system for careful and minimal-invasive resection of brain tumors with ultrashort laser pulses through a thin probe. A confocal laser-scanning-microscope is integrated in the probe. In this paper, the simulation of its optical properties by a laboratory setup and the expansion by the ability for fluorescence microscopy are reported. For a valuation of the imaging properties, the point-spread-function in three dimensions and the axial depth-transfer-function were measured and thus, among other things, the resolving power and the capacity for depth discrimination were analysed. The microscope will enable intra-operative detection of tumor cells by the method of immunofluorescence. As a first model of the application in the brain, cell cultures, that fluorescein-labelled antibodies were bound to specifically, were used in this work. Due to the fluorescence signal, it was possible to detect and identify clearly the areas that had been marked in this manner, proving the suitability of the setup for minimal-invasive tumor diagnosis.

Nonthermal in vitro ablation of bovine neural tis- sue by using laser-induced optical breakdown generated by ultrashort laser pulses, with durations from 100 fs to 35 ps and pulse energies of up to 165mJ, has been investigated. The experiments were performed at wavelengths ranging from 630 to 1053 nm by using a femtosecond Ti:Sapphire laser, a femtosecond dye laser, and a picosecond Nd:YLF laser sys- tem. Tissue ablations have been achieved by focusing the laser beam on the surface of the tissue, to a spot diameter of 5- 20mm, resulting in the generation of a microplasma. Laser pulses from the Ti:Sapphire laser with 140 fs duration showed a two times higher efficiency of ablation than the longer 30 ps pulses from a Nd:YLF laser with an identical pulse energy. At pulse energies of 140mJ, single pass excisions deeper than 200mm were generated by the 140 fs pulses. In addition, the fluence at threshold of the ablation was found to be reduced for shorter pulse durations. For 3p slaser pulses at 630 nm, we measured the fluence at threshold to be about 5: 3J =cm 2 ; for 100 fs pulses from the same laser the experimental thresh- old was at 1: 5J =cm 2 . Histopathological examinations and scanning electron micrographs confirm the high quality of the excisions. No sign of significant thermal damage was ob- served.

The basis for most laser applications in neurosurgery is the conversion of laser light into heat when the incident laser beam is absorbed by the tissue. Irradiation of neural tissue with laser light therefore leads to its thermal damage. However, due to the diffusion of heat energy into the surrounding tissue, often there is thermal damage to neural tissue outside the area of the target volume. These are the characteristics of thermal laser/tissue interaction. In this paper we discuss how we used three different short-pulsed lasers to achieve non-thermal ablation of neural tissue. Three different short-pulsed lasers were used to generate ultrashort laser pulses in the picosecond to femtosecond range. The interaction of such laser pulses with tissue was predicted to be nonthermal. The short-pulsed lasers were used for the ablation of neural tissue using an in vitro calf brain model. The histopathological examination of the lesions revealed that the neural tissue had been removed very precisely without any sign of thermal damage to the surrounding tissue.

Plasma-mediated ablations of brain tissue have been performed using picosecond laser pulses obtained from a Nd:YLF oscillator/regenerative amplifier system. The laser pulses had a pulse duration of 35 ps at a wavelength of 1.053 µm. The pulse energy varied from 90 µJ to 550 µJ at a repetition rate of 400 Hz. The energy density at the ablation threshold was measured to be 20 J/cm2. Comparisons have been made to 19 ps laser pulses at 1.68 µm and 2.92 µm from an OPG/OPA system and to microsecond pulse trains at 2.94 µm from a free running Er:YAG laser. Light microscopy and scanning electron microscopy were performed to judge the depth and the quality of the ablated cavities. No thermal damage was induced by either of the picosecond laser systems. The Er:YAG laser, on the other hand, showed 20 µm wide lateral damage zones due to the longer pulse durations and the higher pulse energies.

This study was conducted to assess the long-term safety of fluticasone propionate 50 micrograms twice daily (100 micrograms/day) or 100 micrograms twice daily (200 micrograms/day) administered via a dry powder inhaler in children aged 4-17 years with moderately severe asthma. A total of 257 patients received open treatment for 12 months. Of these, 110 had not received treatment with fluticasone propionate in any prior study. The remaining 147 patients had completed one of two previous short-term inhaled fluticasone propionate studies. In all, 132 patients (51%) reported 273 adverse events, the pattern of which was as expected in an atopic population with asthma; only 26 (10%) of these reports were considered either certainly, probably or possibly related to study treatment. The events most commonly reported either as a single or multiple diagnosis were: asthma and related events (25%), upper respiratory tract infection (13%), and rhinitis (6%). For most patients who reported a worsening of asthma, additional therapy was all that was required to control symptoms, and they continued in the study. There was a low incidence (2%) of pharmacologically predictable adverse events. Eight patients (3%) withdrew from the study because of an adverse event, five of which events (one each of hypertension, hoarseness and asthma and two of oral candidiasis) were recorded as being possibly or probably drug-related. Sixteen adverse events reported by 15 patients (6%) were classified as serious but none was considered to be related to the study drug. Of these reports 10 ( patients; 4%) were exacerbations of asthma requiring hospital admission; the other six adverse events were unrelated to asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrashort laser pulses enable a process of tissue ablation that is of great interest for medical therapy. In contrast to long pulsed or cw lasers, where the applied energy leads to heating and vaporization of irradiated tissue, the ablation process in the ultrashort pulse range is initiated by a plasma formation in the laser focus, resulting in tissue removal.1 Using picosecond pulses this ablation mechanism is already well established in ophthalmology. The accuracy and the absence of undesired thermal side effects made the plasma-mediated ablation a promising technique in other medical fields, e.g., neurosurgery.