For a favorable treatment result, early diagnosis of pathological cancerous micro-areas with their subsequent removal is highly important and can be achieved by the development of new modeling techniques and conducting relevant experiments. Various models of the bladder can be developed and applied to provide a platform for studying, processing and improving the signals received from various video systems. Here, in order to study visualization properties at fluorescence endoscopy, 3D optical phantoms of urinary bladder have been developed. The phantoms simulated optical properties of the bladder wall, including localized areas that represent tumor tissues and contained PpIX photosensitizer at various concentrations for fluorescence "diagnostics". To perform bimodal fluorescence imaging, a two-channel video fluorescence system was used. First, intraoperative images of the bladder wall were obtained in a patient with bladder cancer. A video system was used to reveal and image pathological areas with increased fluorescence intensity. Fluorescence indices in tumor tissue were recorded and corresponded to different concentrations of PpIX photosensitizer. Then, a bimodal fluorescence imaging was performed on 3D phantoms. The obtained images and fluorescence intensity measurements showed the ability of the video fluorescence system to register bladder wall structures and accumulated in them photosensitizers in concentrations from 0.25 to 20 mg/kg. The developed models can serve as a useful instrument for test measurements for constructing multimodal mosaic panoramic images of the bladder surface. This will help to advance in solving problems of endoscopic image processing using bimodal imaging, which uses diagnostic (fluorescence) and color channels.
The limited penetration of laser radiation into biological tissue prevents the widespread distribution of photodiagnostics (PD) and photodynamic therapy (PDT) methods to clinical practice. We have investigated several approaches for PD and PDT of deep-seated tumors: 1. Stereotactic biopsy cannula with a laser spectroscopic control. Special fiber ports for long-term installation in the tumor removal area were developed in order to cause tumor cells to migrate not into the depth of brain but along the fibers with occasional laser irradiation for PD and PDT. The fibers are coated with a special compound containing photosensitizer (PS) and nutrients for cancer cells. 2. Neurosurgical aspirator with the function of video-fluorescence and spectroscopic analysis system. More than 500 patients with various types of brain tumors were operated on using fluorescent navigation based on 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (Pp IX) fluorescence under laser excitation in red spectral range. 3. Diagnostics and navigation of tumors when fluorescence is excited in the red and near infrared ranges. We used indocyanine green (ICG) as near infrared dye to observe blood and lymph vasculature of laboratory animals. This method could be useful while examining tumor bed and adjacent area. 4. Joint action of radiopharmaceuticals and PS based on Cherenkov radiation. Cell death by PDT mechanism via Pp IX excitation by Cherenkov radiation in mitochondria during 18F-fludeoxyglucose decay. This idea achieved good results on rats with C6 glioma. The results of using this approach with chlorin e6 PS in comparable doses are negative. 5. Action through photodynamic inactivation of tumor-associated macrophages and microglia. Idea of minimally invasive method for determining macrophage (microglia) phenotype and their polarization in tumors and their immediate vicinity in situ. This would allow evaluating the effectiveness of the treatment, including PDT. The most promising results were obtained with Pp IX and aluminum phthalocyanine nanoparticles. Studies have been conducted on experimental animals with grafted tumors and, in part, on cancer patients in the clinic.
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