Laser fluorescent system for endoscopic tumor diagnostic and irradiation control in photodynamic therapy

The laser fluorescent methods are very promising for photosensitizer distribution control in diagnostics and photodynamic therapy of tumors in intracavital organs. We have developed the laser fluorescent imaging system employing high sensitive CCD-camera. The system is adjusted to the standard endoscope (Olympus), cystoscope and can be also used for surface tumor observations. The high sensitivity of the system makes it possible to evaluate the photosensitizer distribution, its dynamic during PDT treatment and control the irradiation process observing tissues in fluorescent light during endoscopic investigations of stomach and lungs. The ways of improving of fluorescent imaging systems are discussed including the choosing of suitable laser source for fluorescent excitation and special filters for enhancing fluorescent contrast. 2. INRODUCTION One of the most important problems in practical oncology, determining the treatment efficacy is the evaluating of tumor topology. The availability of such information allows the physician to estimate adequately the required extent of surgical or therapeutic intrusion, optimally choose the treatment protocol. At present time a lot of new apparatus methods, particularly fluorescent diagnostic methods, have been employed in practical medicine. These methods are based on the use of photosensitizers, having the ability to accumulate in tumors and fluorescing in the determined spectral range. Among many substances applied for fluorescent diagnostic the phtalocianines are considered as the most perspective ones"2. They have emission and excitation bands in the range of 670-700 nm. This spectral range is characterized by low blood absorption being the transparency window for nonsensibilitized human tissue. This allows first to obtain information from deep tissue layers (0.5-1 cm from the surface) and second to increase the information validity because the influence of local inhomogenities due to the presence of blood vessels in the irradiated zone is diminished. The fluorescent diagnostic observations of malignant tumors with the use of sulphanated aluminium Phtalocyamne as photosensitizer and laser endoscopic spectra analyzer (LESA-5)3 allowing one to control locally fluorescent intensity and emission spectmm showed the perspectivity and high sensibility of this method in the diagnostics (identffication) of surface and intracavity tumors. At the same time for the fluorescent method to be widely applied in the clinical diagnostics the special apparatus is required allowing one to observe and analyze the fluorescent image of the whole tumor in real time and make right decision. This is especially important in endoscopic and intraoperation observations of intracavity organs because the observation time is limited. Another important problem is connected with the need of fluorescent control of pathological part in situ in the process of photodynamic therapy when light irradiation can affect the physical-chemical properties of photosensitizer, 0-8194-2104-9/96/$6.00 SPIE Vol. 2728 / 35 its localization in tissue, the blood supply and tissue properties itself In this case the fluorescent image information can help the physician to correct in situ the photodynamic therapy procedure parameters. The above mentioned facts prove the necessity of development of compact, simple, low price system adapted to standard endoscopes for fluorescent tumor visualization in real time during endoscopic observations. Such system must have high sensitivity so that it would be possible to function under low intensity of exiting irradiation to avoid photosensitizer photobleaching and undesirable additional photodynamic action. It should also have the wide dynamic range and automatic gain to provide the possibility of observation from one side under low photosensitizer concentration and light irradiation during diagnostics and from the other side under high values of these parameters during photodynamic therapy procedure. 3. MATERIALS AND METhODS At present work the fluorescent image analyzer based on the high sensitivity miniature CCD camera Watex902A (Watex, Japan) is described. Optical mechanical adapter of the system consists of the optical system for image transfer from the endoscope lens to the CCD matrix, optical filter cutting of laser irradiation, and mechanical lock adapted to the "Olympus-lO" or "Olympus-20" endoscopes. The total weight of the system is less than 200g. The system modification for fluorescent observations of surface tumors includes the same CCD camera with lenses and filter, its total weight being less than 120g. To choose the optimal excitation laser source and cutoff filter we have measured the dependencies of sensitivity from the wavelength with laser excitation power being fixed. We applied dye laser exited by the copper laser. The output wavelength could be changed from 640 to 685 am. The power density has been controlled by Optometer S 370 (UDT Instruments, USA). In each experimental set power density has been fixed. The special standard samples (Biospec, Russia) based on the suiphanated aluminum Phtalocyanine added to the scattered media have been used in the experiments. The optical parameters of standard samples were close to the photosensitized human tissue. The standard samples imitated the wide photosensitizer concentration range in tissue (from 1 .6* i(i to 6.6* iø mg/cm3). According to our investigations the Phtalocyanine concentration in tumor tissue during PDT procedure is in the range of(2÷5)* 10 mg/cm3 and during diagnostic procedures in the range of(3÷10)* i0 mg/cm3. In the experiment for the every standard sample from the set (for the every value of photosensitizer concentration) the excitation length has been measured when the sample could be seen on the background scattering surface. In our case fluorescent radiation to scattered radiation measured by filtered CCD-camera ratio was 1.2. The experiments have been done by using various cutoff filters. Optical transmittance of all filters has been measured on "Hitachi" spectrophotometer. 4. RESULTS AND DISCUSSION Some results of the experiments are shown on Fig 1. These results show that with optimal choosing of exiting irradiation the system provides the high sensitivity and qualitative visualization of fluorescent image of photosensitized tissues in the wide photosensitizer concentration range (Fig 2). In this case for fluorescence excitation the power density was less than 10 mW/cm2 in endoscopic visualization and less than 1 mW/cm2 in surface visualization. This wide dynamic range is provided by electron shutter in CCD camera. The system operates in real time displaying fluorescent image on standard TV-monitor and saving it on video-recorder or by using frame grabber on personal computer.