KEYWORDS: Oxygen, Photodynamic therapy, Dosimetry, Signal detection, Picosecond phenomena, Tissues, Luminescence, In vivo imaging, In vitro testing, Algorithm development
This study presents our implementation of a multi-channel device for continuous singlet oxygen luminescent dosimetry (CSOLD) signal acquisition using multiple InGaAs detectors connected to individual narrow band filters (1200 nm, 1240 nm, 1250 nm, 1270 nm, and 1300 nm) during PDT. An algorithm is developed to extrapolate various components from the raw multi-channel data.
Direct detection of singlet-state oxygen ([1O2]) is a crucial objective in type II photodynamic therapy (PDT), achievable through the implementation of multispectral singlet oxygen dosimetry (MSOLD). To accurately assess the amount of reactive singlet oxygen, the Singlet Oxygen Explicit Dosimetry (SOED) model was developed, incorporating parameters such as light fluence rate, photosensitizer concentration, and ground-state oxygen concentration. This study focuses on comparing the results obtained from MSOLD and SOED by measuring the singlet oxygen signal via a commercial InGaAs spectrometer and subsequently calculating reactive singlet oxygen based on the SOED theory. A continuous-wave laser emitting at 630nm is employed to excite Protoporphyrin IX (PPIX) in methanol, varying the concentration from 10mg/kg to 100mg/kg. Utilizing the Singular Value Decomposition (SVD) algorithm, the measured singlet oxygen spectrum is fitted to extract the singlet oxygen signal. To simulate clinical PDT scenarios, real-time singlet oxygen spectra are collected over 1200 seconds, employing a 1.5mm diameter optic fiber for signal collection. Ground-state oxygen concentration is measured using a commercial oxygen probe while the laser is inactive, and photosensitizer concentration is assessed via a custom-made contact probe. Additionally, the fluence rate of the laser is measured using an isotropic detector. The Reactive Singlet Oxygen is then calculated using the SOED model, incorporating the photosensitizer concentration, oxygen concentration, and photon fluence rate. Detailed comparisons between MSOLD and SOED results are presented, offering valuable insights into the accuracy and reliability of both methods in quantifying singlet-state oxygen during PDT.
KEYWORDS: Oxygen, Monte Carlo methods, Optical properties, Signal detection, Absorption, Photodynamic therapy, Luminescence, Singular value decomposition
Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the administration of a photosensitizing agent followed by light activation at a specific wavelength. Upon activation, the photosensitizer generates reactive oxygen species, including singlet-state oxygen ([1O2]), which causes cellular damage leading to cancer cell death. Direct detection of singlet-state oxygen constitutes the holy grail dosimetric method for type II PDT, a goal that can be quantified using multispectral singlet oxygen dosimetry (MSOLD). The optical properties of tissues, specifically their scattering and absorption coefficients, play a crucial role in determining how light interacts within a medium. Variations in these optical properties can significantly impact various aspects, including the distribution of treatment laser, the generation of singlet oxygen, and the detection of singlet oxygen signals using the MSOLD device. In this study, we have investigated the influence of optical properties variation on the spatial distribution of treatment laser energy in tissue simulated phantom and the distribution of generated singlet oxygen signals using Monte Carlo simulations (MC). Additionally, we conducted a comparative analysis by examining singlet oxygen signals generated by Photofrin in MeOH, as detected by an InGaAs spectrometer in vitro, and compared these results to our Monte Carlo simulations. The experimental findings validate the accuracy of our Monte Carlo simulations, further affirming the robustness of our research. Our research advanced the comprehension of singlet oxygen generation and enhanced the accuracy of singlet oxygen detection using the MSOLD device, especially when optical properties undergo changes.
Imaging Cherenkov photons emitted during radiation therapy can provide real-time information of the external beam field. It is well established that Cherenkov emission is correlative to dose deposited; however, differential photon energies and tissue attenuation properties, along with complicated camera geometries, entangle this relationship and introduce variability in the Cherenkov emission-to-dose ratio from patient-to-patient. This study aims to better understand the effects of optical properties, skin color, and patient-specific geometries (i.e. angle of camera incidence and curvature) on the Cherenkov emission-to-dose relationship. To do so, a series of phantom experiments were conducted with tissuesimulating optical phantoms and an andromorphic breast phantom in which optical properties, curvature, and camera angle of incidence were all examined as a function of normalized Cherenkov emission-to-dose. To acquire clinical Cherenkov data along with patient skin color, Cherenkov images and OSLD measurements for the ground-truth surface dose were collected weekly on 13 whole-breast radiotherapy patients, alongside high-resolution 3D color and texture scans. Phantom results suggest there to be a moderately strong correlation between dose percent error and patient curvature (R2 = 0.57), as well as angle of camera incidence (R2 = 0.56). Initial patient results suggest there to be a correlation between the redness of a patient’s skin, and the Cherenkov emission-to-dose ratio, with higher amounts of redness correlating to lower Cherenkov signal. By better characterizing these trends, we are potentially able to find generalizable optics-based corrections that improve the accuracy in mapping Cherenkov emission to real-time skin dose.
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