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Background We investigated light attenuation at 664 nm, which is the excitation wavelength of photodynamic therapy (PDT) using talaporfin sodium, in a salted cadaver brain. Estimation of therapeutic lesions is important to ensure the effectiveness and safety of brain tumor PDT. Previously reported optical properties of the human brain vary widely. In this study, we measured the light attenuation in brain tissue using a practical method. We employed a salted cadaver brain, in which the mechanical and optical properties can be maintained as close as possible to those under operative conditions. Methods A neuroendoscope was inserted into the brain until the cerebral ventricle was reached. A thin cylindrical diffuser probe was advanced 10 mm from the endoscope tip. By another path from the brain surface, an optical fiber for measurement was inserted into a puncture needle, and a pair of needles was used to puncture the tissue and reach the same cerebral ventricle in which the endoscope tip was positioned. The attenuation of light intensities in the frontal lobe and cerebellum was measured by varying the bundle tip position. The starting positions of the bundle were confirmed by the endoscopic view. The measured light intensity attenuations were fitted with an exponential curve. Results The following attenuation coefficients were obtained: 0.20 ± 0.05 mm−1 in the cerebrum and 0.27 ± 0.05 mm−1 in the cerebellum. Conclusion As conventional spectroscopic measurement may overestimate attenuation in the whole tissue, in situ measurement using the withdrawal technique might be appropriate for measurement of inhomogeneous biological tissues.

To measure the few millimeter–scale macroscopic optical properties of biological tissue, including the scattering coefficient, while avoiding the instability that originates from sample slicing preparation processes, we performed propagated light intensity measurements through an optical fiber that punctures the bulk tissue while varying the fiber tip depth and the field of view (FOV) at the tip; the results were analyzed using the inverse Monte Carlo method. We realized FOV changes at the fiber tip in the bulk tissue using a variable aperture that was located outside the bulk tissue through a short high-numerical aperture (high-NA) multi-mode fiber with a quasi-straight shape. Using a homogeneous optical model solution, we verified the principle and operation of the constructed experimental system. A 200-μm-core-diameter silica fiber with NA of 0.5 and length of 1 m installed in a 21G needle was used. The detection fiber’s shape was maintained over a radius of curvature of 30 cm. The dependences of the detected light intensity on the FOV and the depth showed better than 1.4% accuracy versus calculated dependences based on the measured optical properties of the solution. Adaptation of the method for use with complex structured biological tissue, particularly in the presence of a thick fascia, was not completely resolved. However, we believe that our specific fiber puncture–based measurement method for use in bulk tissue based on variation of the FOV with inverse Monte Carlo method-based analysis will be useful in obtaining optical coefficients while avoiding sample preparation–related instabilities.

To better understand the mechanism of photodynamic cardiac ablation, we studied the effects of a photosensitization reaction (PR) performed during the first 3 min after rat myocardial cells were exposed to talaporfin sodium. A 3-mm-square microelectrode array with 64 electrodes was used to continuously measure the action potentials of the myocardial cells. A 30 μg/mL talaporfin sodium solution, a chlorine photosensitizer, was used, along with a 663-nm red diode laser (86 mW/cm2 for up to 600 s). The first trough of the measured action potential waveform corresponding to Na+ dynamics decreased exponentially with increasing PR duration. The average decay time of the exponential function from PR onset was 20.1 s. Marked morphological changes in the myocardial cells was observed after the PR. These results indicated that the behavior of the action potential waveform measured by the microelectrode array might be used as a less invasive method to evaluate the electrophysiological effects of a PR on myocardial cells.

In order to study cardiomyocyte electrical conduction damage by a photosensitization reaction (PR) mostly comes from outside of the cells in a few minutes after the PR, we studied propagation delay of contact action potential with cardiomyocyte by the PR. To determine appropriate PR condition for tachyarrhythmia ablation, a precise electrophysiological experiment in vitro has been preferable. We measured the contact action potential using a microelectrode array system of which information may be correct than conventional Ca 2+ measurement. We investigated the propagation delays of an evoked potential to evaluate the electrical conduction damage by the PR. Rat cardiomyocytes were cultivated for 5-7 days on a dish with which 64 electrodes were patterned, in an incubator controlled to 37°C, 5% CO 2 . The following conditions were used for the PR: 40 μg/ml talapordfin sodium and 290 mW/cm 2 , 40-78 J/cm 2 for an irradiation. A 2D map was obtained to visualize the propagation delays of the evoked potential. The propagation speed, which was calculated based on the measured propagation delays, was decreased by about 30-50% on average of all electrodes after the PR. Therefore, we think 2D propagation delays measurement of the evoked potential with contact action potential measuring system might be available to evaluate the acute electrical conduction damage of cardiomyocyte by the PR.