Photodynamic therapy for cholangiocarcinoma using low dose mTHPC (Foscan(®)).

BACKGROUND: Photodynamic therapy (PDT) combined with stenting is an effective treatment modality for palliation of nonresectable cholangiocarcinoma (CC). A drawback of standard PDT using Photofrin(®) as photosensitizer is the long lasting skin photosensitivity of up to 3 months. The aim of this study was to show the outcome of PDT of CC, potential side effects and to determine the best drug light interval (DLI) using mTHPC (Foscan(®)) at a low dose. METHODS: 13 patients with nonresectable CC were treated with stenting and PDT (3mg Foscan(®) per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity. RESULTS: The results so far indicate a median survival time of 13 months. Side effects such as perforations or skin phototoxicity could not be observed. Foscan(®) fluorescence within the tumor site was clearly detectable but a significant fluorescence contrast of tumor to adjacent healthy tissue could not be found. The fluorescence kinetics measured in the oral mucosa showed a maximum at 3.85 days (median) after drug administration. CONCLUSION: Combined stenting and PDT performed with a low Foscan(®) dose results in equal and potentially longer survival times compared to standard Photofrin(®) PDT, while lowering the risk of side effects strongly. Thus it may improve the quality of life.

Bandwidth-variable tunable optical filter unit for illumination and spectral imaging systems using thin-film optical band-pass filters.

An optical filter unit is demonstrated, which uses two successively arranged tunable thin-film optical band-pass filters and allows for simultaneous adjustment of the central wavelength in the spectral range 522-555 nm and of the spectral bandwidth in the range 3-16 nm with a wavelength switching time of 8 ms∕nm. Different spectral filter combinations can cover the complete visible spectral range. The transmitted intensity was found to decrease only linearly with the spectral bandwidth for bandwidths >6 nm, allowing a high maximum transmission efficiency of >75%. The image of a fiber bundle was spectrally filtered and analyzed in terms of position-dependency of the transmitted bandwidth and central wavelength.

Protoporphyrin IX fluorescence and photobleaching during interstitial photodynamic therapy of malignant gliomas for early treatment prognosis.

BACKGROUND AND OBJECTIVE: Interstitial photodynamic therapy (iPDT) of non-resectable recurrent glioblastoma using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear, however, to what extent inter- and intra-tumoural differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analysed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intraoperatively. MATERIALS AND METHODS: Five patients harbouring non-resectable glioblastomas were included. ALA (20 or 30 mg/kg body weight) was given 5-8 hours before treatment. Stereotactic biopsies were taken throughout the tumour volume for both histological analysis and determination of PpIX concentrations, which were measured by chemical extraction. Cylindrical light diffusors were stereotactically implanted. Prior to and after irradiation, fluorescence measurements were performed. Outcome measurement was based on clinical and neuro-radiological follow up. RESULTS: In three patients, a strong PpIX fluorescence was seen before treatment, which was completely photobleached after iPDT. High concentrations of PpIX could be detected in viable tumour parts of these patients (mean PpIX uptake per tumour: 1.4-3.0 µM). In the other two patients, however, no or only low PpIX uptake (0-0.6 µM) could be detected. The patients with strong PpIX uptake showed treatment response and long-term clinical stabilisation (no progression in 29, 30 and 36 months), early treatment failure was seen in the remaining two patients (death after 3 and 9 months). CONCLUSIONS: Intra-tumoural PpIX concentrations exhibited pronounced inter- and intra-tumoural variations in glioblastoma, which are directly linked to variable degrees of fluorescence intensity. High intra-tumoural PpIX concentrations with strong fluorescence intensity and complete photobleaching after iPDT seem to be associated with favourable outcome. Real-time monitoring of PpIX fluorescence intensity and photobleaching turned out to be feasible and safe and might be employed for early treatment prognosis of iPDT.

Optical needle endoscope for safe and precise stereotactically guided biopsy sampling in neurosurgery.

Proper treatment of deep seated brain tumors requires correct histological diagnosis which unambiguously necessitates biopsy sampling. Stereotactically guided sampling of biopsies is widely used but bears the danger of incorrect sampling locations and damage to intracerebral blood vessels. Here, we present a minimally invasive contact endoscopic probe that can be inserted into the tissue inside a standard biopsy needle and allows for fluorescence detection of both tumorous tissue and intracerebral blood vessels. Outer diameter of our contact probe is smaller than 1.5 mm, field-of-view in the range of several hundred microns; the optical design allows for simultaneous detection and visualization of tissue autofluorescence and selective fluorescence signals from deep seated brain tumors and vasculature as shown on in vivo animal models. We demonstrate the tumor detection capability during stereotactic needle insertion in a clinical pilot trial. Using our probe, we expect stereotactic interventions to become safer and more precise and the technology might ultimately be used also for various other kinds of applications.