Fiber Optic Spectroscopy for the Optimization of Photodynamic Therapy

__Abstract__ Photodynamic therapy (PDT) is a treatment modality for cancer and premalignant lesions that utilizes a photoactive drug, the photosensitizer, in combination with light. PDT has become the treatment of choice for various malignancies. Furthermore, PDT is under investigation as a potential (palliative) treatment in situations where the possibilities of chemo-­ and radiotherapy are limited or exhausted. Since both photosensitizer and light have to be present to cause tissue damage, selective damage to the lesion can be achieved by controlling the presence of either one of them to the treatment area. Selective damage can be reached by i) choosing a photosensitizer that is mainly present in the lesion, or ii) preventing normal tissue from being illuminated. However, the success of PDT in reducing/removing (pre-­‐)malignant lesions has been variable. Treatment efficacy can range form non-‐observable effects to severe damage to normal tissue. Considering the complexity of both the execution of the treatment and damage pathways involved in PDT, some variability in treatment efficacy is not unexpected. However, given the fact that clinical applications of PDT that have proved successful remain small in number, more work is necessary to optimize therapeutic efficacy

Extraction of Intrinsic Fluorescence from Single Fiber Fluorescence Measurements on a Turbid Medium: Experimental Validation

Abstract The detailed mechanisms associated with the influence of scattering and absorption properties on the fluorescence intensity sampled by a single optical fiber have recently been elucidated based on Monte Carlo simulated data. Here we develop an experimental single fiber fluorescence (SFF) spectroscopy setup and validate the Monte Carlo data and semi-empirical model equation that describes the SFF signal as a function of scattering. We present a calibration procedure that corrects the SFF signal for all system-related, wavelength dependent transmission efficiencies to yield an absolute value of intrinsic fluorescence. The validity of the Monte Carlo data and semi-empirical model is demonstrated using a set of fluorescent phantoms with varying concentrations of Intralipid to vary the scattering properties, yielding a wide range of reduced scattering coefficients (μ′s = 0–7 mm −1). We also introduce a small modification to the model to account for the case of μ′s = 0 mm −1 and show its relation to the experimental, simulated and theoretically calculated value of SFF intensity in the absence of scattering. Finally, we show that our method is also accurate in the presence of absorbers by performing measurements on phantoms containing red blood cells and correcting for their absorption properties

Intrinsic photosensitizer fluorescence measured using multi-diameter single-fiber spectroscopy in vivo

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Microscopic analysis of the localization of two chlorin-based photosensitizers in OSC19 tumors in the mouse oral cavity

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

In vivo quantification of the scattering properties of tissue using multi-diameter single fiber reflectance spectroscopy

Multi diameter single fiber reflectance (MDSFR) spectroscopy is a non-invasive optical technique based on using multiple fibers of different diameters to determine both the reduced scattering coefficient (μs') and a parameter ? that is related to the angular distribution of scattering, where λ = (1-g2)/(1-g1) and g1 and g2 the first and second moment of the phase function, respectively. Here we present the first in vivo MDSFR measurements of μs'(λ) and γ(λ) and their wavelength dependence. MDSFR is performed on nineteen mice in four tissue types including skin, liver, normal tongue and in an orthotopic oral squamous cell carcinoma. The wavelength-dependent slope of μs'(λ) (scattering power) is significantly higher for tongue and skin than for oral cancer and liver. The reduced scattering coefficient at 800 nm of oral cancer is significantly higher than of normal tongue and liver. Gamma generally increases with increasing wavelength; for tumor it increases monotonically with wavelength, while for skin, liver and tongue γ(λ) reaches a plateau or even decreases for longer wavelengths. The mean γ(γ) in the wavelength range 400-850 nm is highest for liver (1.87 ± 0.07) and lowest for skin (1.37 ± 0.14). Gamma of tumor and normal tongue falls in between these values where tumor exhibits a higher average γ(λ) (1.72 ± 0.09) than normal tongue (1.58 ± 0.07). This study shows the potential of using light scattering spectroscopy to optically characterize tissue in vivo