Cherenkov light emission from tissue undergoing radiation therapy is a complex function of the dose deposition and is reduced by the optical attenuation of the tissue. A diffusion theory based integral of the remitted light is presented, using the assumption that only Cherenkov photons from the first 8 mm of tissue are able to appreciably escape from the surface. This depth restriction falls within the linear build-up region for both electron and photon beams used in radiotherapy. The resulting expression for Cherenkov light fluence formulated here indicates that the outgoing intensity is dependent upon the quasi-linear dose build up gradient (k2) in the first 8 mm of tissue, is inversely proportional to the optical absorption (μa), and is relatively independent of the scattering coefficient (μs/ ). Numerical evaluation suggests that the diffuse component of Cherenkov light emission dominates over any unscattered photons, suggesting that the radiation build-up factor dominates what is imaged off the surface. This observation could allow for linear corrections to Cherenkov images with knowledge of tissue optical properties and for better interpretation of the origin of Cherenkov from tissue.
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. Using a specialized camera-system, the Cherenkov emission can thus be used to evaluate the dose uniformity on the surface of the patient in real-time. Each patient was also monitored during TSET via in-vivo detectors (IVD) in nine locations. Patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed, and the viability of the system to provide clinical feedback was established.
Cherenkov imaging during radiation therapy has been developed as a tool for dosimetry, which could have applications in patient delivery verification or in regular quality audit. The cameras used are intensified imaging sensors, either ICCD or ICMOS cameras, which allow important features of imaging, including: (1) nanosecond time gating, (2) amplification by 103-104, which together allow for imaging which has (1) real time capture at 10-30 frames per second, (2) sensitivity at the level of single photon event level, and (3) ability to suppress background light from the ambient room. However, the capability to achieve single photon imaging has not been fully analyzed to date, and as such was the focus of this study. The ability to quantitatively characterize how a single photon event appears in amplified camera imaging from the Cherenkov images was analyzed with image processing. The signal seen at normal gain levels appears to be a blur of about 90 counts in the CCD detector, after going through the chain of photocathode detection, amplification through a microchannel plate PMT, excitation onto a phosphor screen and then imaged on the CCD. The analysis of single photon events requires careful interpretation of the fixed pattern noise, statistical quantum noise distributions, and the spatial spread of each pulse through the ICCD.
Imaging of Cherenkov light emission from patient tissue during fractionated radiotherapy has been shown to be a possible way to visualize beam delivery in real time. If this tool is advanced as a delivery verification methodology, then a sequence of image processing steps must be established to maximize accurate recovery of beam edges. This was analyzed and developed here, focusing on the noise characteristics and representative images from both phantoms and patients undergoing whole breast radiotherapy. The processing included temporally integrating video data into a single, composite summary image at each control point. Each image stack was also median filtered for denoising and ultimately thresholded into a binary image, and morphologic small hole removal was used. These processed images were used for day-to-day comparison computation, and either the Dice coefficient or the mean distance to conformity values can be used to analyze them. Systematic position shifts of the phantom up to 5 mm approached the observed variation values of the patient data. This processing algorithm can be used to analyze the variations seen in patients being treated concurrently with daily Cherenkov imaging to quantify the day-to-day disparities in delivery as a quality audit system for position/beam verification.
External beam radiotherapy utilizes high energy radiation to target cancer with dynamic, patient-specific treatment plans. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interaction between the high energy beam and tissue. Using a specialized camera-system, the Cherenkov emission can thus be used to track the radiation beam on the surface of the patient in real-time, even for complex cases such as volumetric modulated arc therapy (VMAT). Two patients undergoing VMAT of the head and neck were imaged and analyzed, and the viability of the system to provide clinical feedback was established.
Cherenkov radiation has emerged as a novel source of light with a number of applications in the biomedical sciences. It’s unique properties, including its broadband emission spectrum, spectral weighting in the ultraviolet and blue wavebands, and local generation of light within a given tissue have made it an attractive source of light for techniques ranging from widefield imaging to oximetry and phototherapy. To help guide the future development of this field in the context of molecular imaging, quantitative estimates of the light fluence rates of Cherenkov radiation from a number of radionuclide and external radiotherapy beams in tissue was explored for the first time. Using Monte Carlo simulations, these values were found to be on the order of 0.1 – 1 nW/cm2 per MBq/g for radionuclides and 1 – 10 μW/cm2 per Gy/sec for external radiotherapy beams, dependent on the given waveband and optical properties. For phototherapy applications, the total light fluence was found to be on the order of nJ/cm2 for radionuclides, and mJ/cm2 for radiotherapy beams. To validate these findings, experimental validation was completed with an MV x-ray photon beam incident onto a tissue phantom, confirming the magnitudes of the simulation values. The results indicate that diagnostic potential is reasonable for Cherenkov excitation of molecular probes, but phototherapy may remain elusive at these relatively low fluence values.
Photodynamic therapy (PDT) and radiotherapy are non-systemic cancer treatment options with different mechanisms of damage. So combining these techniques has been shown to have some synergy, and can mitigate their limitations such as low PDT light penetration or radiotherapy side effects. The present study monitored the induced tissue changes after PDT, radiotherapy, and a combination protocol in normal rat skin, using an optical spectroscopy system to track the observed biophysical changes. The Wistar rats were treated with one of the protocols: PDT followed by radiotherapy, PDT, radiotherapy and radiotherapy followed by PDT. Reflectance spectra were collected in order to observe the effects of these combined therapies, especially targeting vascular response. From the reflectance, information about oxygen saturation, met-hemoglobin and bilirubin concentration, blood volume fraction (BVF) and vessel radius were extracted from model fitting of the spectra. The rats were monitored for 24 hours after treatment. Results showed that there was no significant variation in the vessel size or BVF after the treatments. However, the PDT caused a significant increase in the met-hemoglobin and bilirubin concentrations, indicating an important blood breakdown. These results may provide an important clue on how the damage establishment takes place, helping to understand the effect of the combination of those techniques in order to verify the existence of a known synergistic effect.
Radiation therapy is often used as the preferred clinical treatment for control of localized head and neck cancer.
However, during the course of treatment (6-8 weeks), feedback about functional and/or physiological changes within
impacted tissue are not obtained, given the onerous financial and/or logistical burdens of scheduling MRI, PET or CT
scans. Diffuse optical sensing is well suited to address this problem since the instrumentation can be made low-cost and
portable while still being able to non-invasively provide information about vascular oxygenation in vivo. Here we report
results from studies that employed an optical fiber-based portable diffuse reflectance spectroscopy (DRS) system to
longitudinally monitor changes in tumor vasculature within two head and neck cancer cell lines (SCC-15 and FaDu)
xenografted in the flanks of nude mice, in two separate experiments. Once the tumor volumes were 100mm3, 67% of
animals received localized (electron beam) radiation therapy in five fractions (8Gy/day, for 5 days) while 33% of the
animals served as controls. DRS measurements were obtained from each animal on each day of treatment and then for
two weeks post-treatment. Reflectance spectra were parametrized to extract total hemoglobin concentration and blood
oxygen-saturation and the resulting time-trends of optical parameters appear to be dissimilar for the two cell-lines.
These findings are also compared to previous animal experiments (using the FaDu line) that were irradiated using a
photon beam radiotherapy protocol. These results and implications for the use of fiber-based DRS measurements made
at local (irradiated) tumor site as a basis for identifying early radiotherapy-response are presented and discussed.
Cherenkov imaging during radiotherapy is a method by which an optical analog for the high-energy radiation beam can
be observed directly on the surface of the patient. While simple geometries and volumes demonstrate a strong
correlation between Cherenkov emission intensity and surface dose, in vivo data collected from 14 whole-breast patients
has not exhibited the same correlation. The purpose of this anthropomorphic phantom study was to investigate a new
method for improving the in vivo correlation based on a pixel-by-pixel correction from a reference reflectance image.
The pixel intensities in Cherenkov images of a phantom were correlated with the surface dose measured from
thermoluminescent dosimeters (TLDs) placed on the phantom’s surface. Because the phantom had homogeneous optical
properties, results show a no appreciable change in correlation between Cherenkov intensity and surface dose when
using the correction method on images of an anthropomorphic solid silicone phantom, nor a change in the dose fall-off at
the edges of the phantom. The method may improve correlation with in vivo data.
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