Norihiro Honda

Determination of the tumor tissue optical properties during and after photodynamic therapy using inverse Monte Carlo method and double integrating sphere between 350 and 1000 nm

Photodynamic therapy (PDT) efficacy depends on the amount of light distribution within the tissue. However, conventional PDT does not consider the laser irradiation dose during PDT. The optical properties of biological tissues (absorption coefficient μ(a), reduced scattering coefficient μs), anisotropy factor g, refractive index, etc.) help us to recognize light propagation through the tissue. The goal of this paper is to acquire the knowledge of the light propagation within tissue during and after PDT with the optical property of PDT-performed mouse tumor tissue. The optical properties of mouse tumor tissues were evaluated using a double integrating sphere setup and the algorithm based on the inverse Monte Carlo method in the wavelength range from 350 to 1000 nm. During PDT, the μ(a) and μs were not changed after 1 and 5 min of irradiation. After PDT, the μs in the wavelength range from 600 to 1000 nm increased with the passage of time. For seven days after PDT, the μs increased by 1.7 to 2.0 times, which results in the optical penetration depth decreased by 1.4 to 1.8 times. To ensure an effective procedure, the adjustment of laser parameters for the decreasing penetration depth is recommended for the re-irradiation of PDT.

Photodynamic Therapy Using Systemic Administration of 5-Aminolevulinic Acid and a 410-nm Wavelength Light-Emitting Diode for Methicillin-Resistant Staphylococcus aureus-Infected Ulcers in Mice

Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds.

A novel photodynamic therapy for drug-resistant prostate cancer cells using porphyrus envelope as a novel photosensitizer

BACKGROUND In the clinic, it is often very difficult to treat drug-resistant advanced prostate cancer by conventional treatments. Photodynamic therapy (PDT) is a minimally invasive treatment that takes advantage of photochemical reactions between a photosensitizer and light. On the basis of several of its key characteristics, PDT is considered to be a promising novel method for treating drug-resistant prostate cancer. OBJECTIVES For effective treatment of drug-resistant prostate cancer, we developed a novel agent termed porphyrus envelope, which was produced from PpIX lipid and hemagglutinating virus of Japan envelope (HVJ-E). MATERIALS AND METHODS We inserted PpIX lipid into HVJ-E by centrifugation, and used the resultant porphyrus envelope in PDT of two drug-resistant prostate cancer cell lines, PC-3 and PC-3-DR. RESULTS Porphyrus envelope enhanced uptake of PpIX, and cytotoxicity of PDT, relative to free PpIX lipid or PpIX induced by 5-ALA. CONCLUSION PDT using porphyrus envelope has potential as a method for treating drug-resistant prostate cancer.

Determination of optical property changes by laser treatments using inverse adding-doubling method

It is widely recognized for the realization of the pre-estimated treatment effects that the knowledge about the optical properties of the target tissues used to understanding the prediction of propagation and distribution of light within tissues would suffer from the technical problem such as the kinetic changes of the optical properties in laser irradiation. In this study, the optical properties of normal and laser coagulated chicken breast tissues and porcine intervertebral disks, normal and laser ablation have been determined in vitro in the spectral range between 350 and 1000 nm. In addition, the optical properties of the normal and photodynamic therapy (PDT) treated tumor, Lewis lung carcinoma, tissues have been determined. Diffuse reflectance and total transmittance of the samples are measured using an integrating-sphere technique. From these experimental data, the absorption coefficients and the reduced scattering coefficients of the samples are determined employing an inverse adding-doubling method. Laser coagulations and ablations have clearly increased the reduced scattering coefficient and slightly reduced the absorption coefficient. PDT treatment has increased absorption and reduced scattering coefficient. It is our expectation that these data will provide fundamental understandings on laser irradiation interactions behavior with tissues. The changes of the optical properties should be accounted for while planning the therapeutic procedure for the realization of safe laser treatments.

Ex vivo efficacy evaluation of laser vaporization for treatment of benign prostatic hyperplasia using a 300-W high-power laser diode with a wavelength of 980 nm

BACKGROUND AND OBJECTIVE Laser vaporization of the prostate is considered to be a promising treatment for benign prostatic hyperplasia (BPH), and efficiency of vaporization and hemostasis are both important parameters for such treatment. In this study, we used a high-power laser diode with a wavelength of 980 nm to obtain high vaporization efficiency with good hemostasis. The objective of this study is to evaluate the efficacy of laser vaporization for treatment of BPH in ex vivo experiments using a 300-W high-power laser diode with a wavelength of 980 nm quantitatively. MATERIALS AND METHODS An ex vivo experimental setup simulating clinical treatment situation was constructed. Bovine prostate tissue was used as a sample. The power setting was 100, 150, 200, 250, or 300 W, and the irradiation time was 0.5, 1, or 2 s. After laser irradiation, vaporized and coagulated depths were measured. RESULTS The vaporized depth increased with the laser power and irradiation time, and the results confirmed that the high-power laser diode could efficiently vaporize the prostate tissue. Coagulated depth increased as the laser power became higher. CONCLUSIONS Laser vaporization of prostate tissue using a high-power laser diode with a wavelength of 980 nm represents a promising treatment for BPH; this method exhibits high vaporization efficiency and good hemostasis. However, operators must be aware of the risk of postoperative perforation of the prostatic capsule caused by coagulation of deep regions that cannot be visualized by endoscopic observation.

Optical properties of tumor tissues grown on the chorioallantoic membrane of chicken eggs: tumor model to assay of tumor response to photodynamic therapy

Abstract. Herein, the optical adequacy of a tumor model prepared with tumor cells grown on the chorioallantoic membrane (CAM) of a chicken egg is evaluated as an alternative to the mouse tumor model to assess the optimal irradiation conditions in photodynamic therapy (PDT). The optical properties of CAM and mouse tumor tissues were measured with a double integrating sphere and the inverse Monte Carlo technique in the 350- to 1000-nm wavelength range. The hemoglobin and water absorption bands observed in the CAM tumor tissue (10 eggs and 10 tumors) are equal to that of the mouse tumor tissue (8 animals and 8 tumors). The optical intersubject variability of the CAM tumor tissues meets or exceeds that of the mouse tumor tissues, and the reduced scattering coefficient spectra of CAM tumor tissues can be equated with those of mouse tumor tissues. These results confirm that the CAM tumor model is a viable alternative to the mouse tumor model, especially for deriving optimal irradiation conditions in PDT.

Hemagglutinating virus of Japan envelope (HVJ-E) allows targeted and efficient delivery of photosensitizer for photodynamic therapy against advanced prostate cancer

Selective and efficient photosensitizer delivery was accomplished by utilizing inactivated Sendai virus particle. Drug delivering mechanism was addressed via transmission electron microscope and photocytotoxic activity was investigated thorough performing photodynamic therapy on cultured cells.

Optical properties of tumor tissues grown on the chorioallantoic membrane of chicken eggs measured with a double integrating sphere and inverse Monte Carlo method in the wavelength range of 350–1000 nm

Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is an attractive method because of the shorter decay time of photosensitivity compared with PDT using other drugs. However, the optimum conditions to perform ALA-PDT, e.g., drug dose, wavelength, and irradiation dose have never been clarified. To evaluate the effectiveness of PDT using ALA and its dependence on drug dose, wavelength, and irradiation dose in the treatment of tumors, the usefulness of a tumor model prepared with tumor cells grown on the chorioallantoic membrane of chicken eggs was studied by measuring the optical properties of the tumor model. The optical properties of tumor model were measured with a double integrating sphere optical setup and inverse Monte Carlo technique in the wavelength range from 350 to 1000 nm. The spectra of absorption and reduced scattering coefficients of the tumor model grown in the chicken eggs were compared with those of the other tumor model grown in mice. The measured optical properties of the tumor model using chicken eggs were similar to those of the tumor model using mice. These results indicate that the tumor model using chicken eggs is a suitable system to investigate the effectiveness of ALA-PDT. This in vivo assay system for tumors has advantages for evaluating antitumor effect of ALA-PDT because of its convenience, rapidity, and inexpensiveness.

Optical properties measurement of laser coagulated tissues with double integrating sphere and inverse Monte Carlo technique in the wavelength range from 350 to 2100 nm

In laser medicine, the accurate knowledge about the optical properties (absorption coefficient; μa, scattering coefficient; μs, anisotropy factor; g) of laser irradiated tissues is important for the prediction of light propagation in tissues, since the efficacy of laser treatment depends on the photon propagation within the irradiated tissues. Thus, it is likely that the optical properties of tissues at near-ultraviolet, visible and near-infrared wavelengths will be more important due to more biomedical applications of lasers will be developed. For improvement of the laser induced thermotherapy, the optical property change during laser treatment should be considered in the wide wavelength range. For estimation of the optical properties of the biological tissues, the optical properties measurement system with a double integrating sphere setup and an inverse Monte Carlo technique was developed. The optical properties of chicken muscle tissue were measured in the native state and after laser coagulation using the optical properties measurement system in the wavelength range from 350 to 2100 nm. A CO2 laser was used for laser coagulation. After laser coagulation, the reduced scattering coefficient of the tissue increased. And, the optical penetration depth decreased. For improvement of the treatment depth during laser coagulation, a quantitative procedure using the treated tissue optical properties for determination of the irradiation power density following light penetration decrease might be important in clinic.

Determination of optical property changes during laser therapies

Optical property changes should be considered to realize safe laser treatments. This study shows the optical properties of normal and laser treated tissues in visible to near-infrared wavelength range by using double integrating sphere system.