Spatially Resolved Frequency Domain Phosphorescence Lifetime-Based Oxygen Sensing for Photodynamic Therapy

摘要

Photodynamic Therapy (PDT) is a minimally invasive treatment that uses a photosensitive drug into convert triplet state oxygen (~3O_2) to singlet oxygen (~1O_2) to destroy malignant tissue. A fiber-optic system based on frequency domain detection of phosphorescence quenching by ~3O_2 is described which optically measures the distribution of ~3O_2 in the treatment volume during PDT to permit adjustments of treatment parameters to improve outcome. A specially designed fiber optic probe containing phosphorescent sensors embedded along its length permit spatially resolved measurements. Each sensor is composed of a phosphorescent metalloporphyrin compound that emits a characteristic spectrum. Four candidate sensors with high absorption at the excitation wavelength of 405nm and emission in the 650nm to 700nm region are considered. The dependence of phosphorescence lifetime (τ) on ~3O_2 concentration is described by the linearized Stern-Volmer relationship as being inversely proportional. Determination of i, and hence ~3O_2 concentration, is accomplished in the frequency domain by means of phase-modulation detection of the phosphorescence signal due to an amplitude modulated excitation. The t's of each sensor are recovered by performing global non-linear least squares fit on the measured phase and modulation index over a range of frequencies and wavelengths. With the t of each sensor known, the oxygen concentration at each sensor's location can be determined with the Stern-Volmer relationship.