Optical-CCD system for imaging light and drug distributions in tumors for phototherapy

Abstract

An optical system for digitized imaging (OSDI) consisting of a computer-controlled charge-coupled-device (CCD) array with 576 x 384 detection elements and 1.4 bits of digitization is used for in-vivo measurements of light distributions from diffusing tips of optical fibers in tumors. A macro lens assembly allows imaging with a spatial resolution of approximately 46 pm. Radiation-induced fibrosarcoma were implanted and grown subcutaneously in C3H mice. A fiber with a cylindrical diffuser tip (1.5 x 5 mm) was inserted into tumors. Tumor light intensity distribution images were made with the OSDI at wavelengths varying from 457.9 to 800 nm with argon, argon-dye and titanium-sapphire lasers. These tumor images show that the volume of tumor exposed to actinic light intensities increases for wavelengths between 400 and 800 run and reaches a maximum at about 800 nm. The uniformity of light distribution also increases at longer wavelengths. At shorter wavelengths, blood vessels in the tumor are clearly delineated as dark lines and networks of lines that might shield sensitized tumor cells from adequate light exposure. The light-acti.vated drug, Photofrin II (PF II), 20 mg/kgbw, was administered intravenously to anesthetized mice. With optical excitation at 457.9 nm consecutive (0, 1., 2.5, 4 hours) fluorescence-only images were made of PF II fluorescence distribution in the tumor and surrounding the diffusing optical fiber. Serial images after PF II injection showed drug fluorescence increasing with time in the tumor around the fiber. The OSDI provides a way to measure actual light intensity distributions and could be used in vivo to guide adjustments in light intensity and drug distributions before and during tumor phototherapy.