Total Skin Electron Therapy (TSET) utilizes high-energy electrons to treat cancers on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interaction between the high-energy electron beam and tissue. Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real-time using a time-gated intensified camera system. Each patient was monitored during TSET by in-vivo detectors (IVD) as well as Scintillators. Patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. A rigorous methodology for converting Cherenkov intensity to surface dose as products of correction factors, including camera vignette correction factor, incident radiation correction factor, and tissue optical properties correction factor. A comprehensive study has been carried out by inspecting various positions on the patients such as vertex, chest, perineum, shins, and foot relative to the umbilicus point (the prescription point).

Tissue optical properties are crucial for determining the light dose delivered to the tumor. Two probes are compared: the two-catheter probe is based on transmittance measurement between one point source and one isotropic detector inside parallel catheters spaced at 0.5 cm along a 1-inch diameter transparent cylinder; and a 1-inch trans-rectal diffuse optical tomography (DOT) probe designed for prostate measurements, using a multiple fiber-array with source-detector separations of 1.4-10 mm. The two-catheter probe uses an empirical model for primary and scatter light fluence rates in the cylindrical cavity condition for anal PDT to determine optical properties along the source catheter using dual motors to move the source and detector along the catheters. The DOT probe uses finite element method (FEM) to obtain distribution of optical properties in 3D. Validations for the two probes were performed in liquid and solid phantoms. For each method, validation was performed in tissue-mimicking liquid phantoms for a range of known optical properties (μ_a between 0.05 and 0.9 cm^-1 and μ_s’ between 5.5 and 16.5 cm^-1). To cross-check the two methods, solid phantoms were created of known optical properties at the University of Pennsylvania and sent for measurement to Princess Margaret Cancer Centre (PMH) to mimic realistic patient simulating conditions. Measurements were taken and optical properties were then recovered without knowing the expected values to cross-validate each probe. The results show modest agreement between the measured μ_a and μ_s’values, but high degree of agreement between the measured μ_eff performed independently using the two methods.

Photosensitizer fluorescence emission during photodynamic therapy (PDT) can be used to estimate for in vivo photosensitizer concentration. We built a surface contact probe with 405nm excitation light source to obtain Photofrin fluorescence signal during clinical PDT. The probe was equipped with multiple detector fibers that were located at distances between 0.14 to 0.87 cm laterally from the excitation source fiber. In this study, we investigated the probing depth of fluorescence in biological tissue with different source-detector separation using our contact probe setup. We used Monte Carlo method to simulate the 405nm excitation light and 630nm fluorescence probing depth at various source and detector (SD) separations. The results provided insight to the most probable depth of origin of detected fluorescence at each SD separation and help to understand the in vivo depth distribution of clinically measured Photofrin concentration.

Malignant tissues can be effectively treated by Total Skin Electron Therapy (TSET) over the entire body surface using 6 MeV electron beams. During the radiation treatment, Cherenkov photons are emitted from the patient’s skin, and can potentially be used for in-vivo imaging of the radiation dose distribution. A Monte Carlo (MC) simulation toolkit TOPAS is used to study the generation and propagation of Cherenkov photons that are generated from the interaction of electron radiation with human tissues, and to understand the relationship between the dose distributions and the Cherenkov photon distributions. Validation of MC simulations with experiments are performed at 100 SSD and 500 SSD, and simulations of a patient phantom in realistic clinical treatment setups have been done. These simulations with TOPAS show that the emitted Cherenkov distributions at phantom surfaces closely follow their corresponding dose distributions.

PDT efficacy depends on the availability and dynamic interactions of photosensitizer, light, and oxygen. Tissue optical properties influence the delivered light dose and impact PDT outcome. In-vivo measurements of tissue optical properties and photosensitizer concentration enable determination of explicit and implicit dose factors affecting PDT and helps to understand the underlying biophysical mechanism of PDT. In this study, we measure tissue optical properties (absorption μa (λ) and scattering μs’ (λ) coefficients) and PpIX concentration in tissue simulating liquid phantoms with a geometry that resembles anal canal. In-vivo light fluence rate and photosensitizer fluorescence of 405nm excitation light source were acquired using a dual-motor continuous wave transmittance spectroscopy system. We characterized the tissue optical properties correction factor of fluorescence signal using a series of tissue simulating phantoms with known PpIX concentrations and with absorption coefficient between 0.1 – 0.9 cm^-1 and reduced scattering coefficient between 5 – 40 cm^-1. The results demonstrated that our spectroscopy system could determine the distribution of tissue optical properties and PPIX concentration during anal PDT.

Characterizing an administered drug’s pathway from initial systemic uptake, to targeted tissue accumulation, and the eventual excretion route is an important component of clinical translation. For mapping such pharmacokinetic behaviors in a biologically-relevant system, fluorescently-tagged drugs are commonly administered and examined in preclinical animal models. Broadband fluorescence cryo-imaging offers a high-resolution, whole-animal technique for recovering such fluorescently-tagged biodistributions, although agent-specificity remains a challenge due to unknown levels of heterogeneous tissue autofluorescence. Herein, we report on a new hyperspectral multichannel fluorescence cryo-imaging system and demonstrate higher agent-specificity and signal-sensitivity compared to conventional broadband fluorescence.

Dental fluorosis is an increasing problem in the U.S. due to excessive exposure to fluoride from the environment. Fluorosis causes hypomineralization of the enamel during tooth development and mild fluorosis is visible as faint white lines on the tooth surface while the most severe fluorosis can result in pitted surfaces. It is difficult to quantify the severity of fluorosis and assessments are limited to subjective visual assessments. Dental fluorosis appears with very high contrast at short wavelength infrared (SWIR) wavelengths beyond 1400-nm and we hypothesize that these wavelengths may be better suited for detecting mild fluorosis and for estimating the severity. In this study the contrast of fluorosis of varying severity on extracted human permanent teeth was measured at SWIR wavelengths ranging from 1300-2000-nm using an extended range InGaAs camera and broadband light sources. Cross polarization optical coherence tomography was used to measure the depth of hypomineralization.

Changes in the reflectivity of lesions on the proximal surfaces of extracted human teeth were measured at SWIR wavelengths from 1300-2000 nm as they were dried with air to assess lesion activity. An extended range tungsten-halogen lamp with bandpass filters of varying wavelength (bandwidth) 1300 nm (90), 1460 nm (85), 1535 nm (80), and 1675 nm (90) along with a broadband ASE source centered near the peak of the water-absorption band at 1950-nm were used as light sources and an extended range InGaAs camera (1000-2340 nm) was used to acquire reflected light images as the samples were dried with air. MicroCT images were used as a gold standard for comparison. SWIR light at 1950 nm yields extremely high contrast of demineralization and appears to be the optimum wavelength for the assessment of lesion activity on tooth coronal surfaces.

Several studies have demonstrated the potential of short wavelength infrared (SWIR) reflectance, thermal imaging and optical coherence tomography for the nondestructive assessment of the activity of caries lesions. The purpose of this study was to test the hypothesis that the activity of arrested caries lesions on the coronal surfaces of extracted teeth would be changed by reducing the thickness of the highly mineralized transparent surface layer, which was measured using polarization sensitive optical coherence tomography (PS-OCT). The lesion activity was assessed using SWIR reflectance and thermal imaging during forced air drying of the lesion before and after mechanical removal of a surface layer ~ 50-μm thick covering the lesion. Both the intensity change in SWIR reflectance images at 1500- 1750-nm wavelengths after drying the lesions and the change in thermal emission measured with a thermal camera at 8-13-μm wavelengths increased significantly (P<0.05) after reducing the thickness of the mineralized surface layer in the lesions indicating the permeability of the lesion to fluids increased. These results provide further evidence that the presence of a highly mineralized outer surface layer is a key indicator of lesion arrest.

Intraoral imaging of teeth with near-IR light provides increased contrast of dental caries and restorative materials compared to visible inspection and digital radiography. The objective of this study was to investigate the near-IR optical properties of the dental pulp-chamber floor, walls and canal orifices. We imaged in vitro extracted human posterior teeth at 1300-nm and 1500-1700-nm in reflectance and transillumination and compared the tissues properties with visible light images and quantitative light fluorescence. Transillumination of posterior teeth at both 1300-nm and 1500-1700-nm yielded significantly higher contrast between the pulp-chamber floor and walls than all other methods.