Development of an optical fiber applicator for interstitial photodynamic therapy in minimally invasive cancer treatments

Photodynamic therapy (PDT) is a minimally invasive medical treatment that exploits the activation of a drug – the photosensitizer (PS) – by light, usually from a laser. The PS is toxic to the target tissue only when activated by light. Although the elective application of PDT is the killing of malignant cancer cells, it can also be used in the treatment of many other pathologies, such as macular degeneration and skin diseases. Important advancements in PDT have been made possible by recent studies of new PS, which have improved their light absorption and cytotoxicity effect when activated, while simultaneously reducing the side effects. However, activation light delivery remains a primarily problem in PDT, especially in the so-called interstitial PDT in which light must be delivered within deeply seated tumors without damaging other tissues. The PS can be optimized in terms of absorption and required power density, but to improve the aspects related to light delivery a suitable tool is necessary. Optical fibers can constitute an effective solution because they can be inserted in the human body through natural apertures or through thin needles, exploiting their small dimension combined with high flexibility, good mechanical resistance and all-dielectric composition. The aim of this master’s thesis is the development of a fiber optic light diffuser that can be then combined with fiber Bragg gratings for sensing the induced temperature and obtain a smart applicator for interstitial photodynamic therapy. Effective interstitial PDT treatments require a uniform diffusion of light in the entire tumor mass. In turn, this implies that light must be irradiated not only from the tip of the delivery fiber but also from the side walls, dissipating the optical power gradually along the fiber length and isotropically around the fiber. This can be obtained by mechanical processing of the fiber, with the downside of weakening the fiber and affecting the fiber strength to bending and stress. Therefore, in this thesis an alternative approach based on the selective modification of the fiber refractive index through a femto-second laser has been studied. The uniformity characterization of the fabricated diffusers has been performed by measuring the emissions in a phantom made of ink-loaded agar gel designed to mimic the behavior of biological tissue. The laser delivery diffuser has been placed in the center of the gel block and the uniformity of the light distribution evaluated at 3 mm from the fiber along two perpendicular axes, with four optical fiber temperature sensors based on arrays of fiber Bragg gratings (FBG-array). The light emitted by the diffuser is absorbed by the black agar that heats up, while the FBG arrays monitor the temperature change in the agar block. Reading the results collected by the sensors and relating them to the position of the arrays, it is possible to create a 3D map of the temperature in the agar block and analyze its changes in real time. The uniformity is achieved when all the FBG-based sensors indicate the same temperature across the whole volume at every time instant. These preliminary results show good uniformity and isotropy of the light emission, opening the possibility for extending the same fabrication method to more suitable fibers in medical applications. The results are also promising to develop future upgrades of the diffuser, such as an FBG temperature sensor addition in a smart and integrated applicator for simultaneous therapeutic and monitoring purpose.