Jacqueline M. Andreozzi

Video‐rate optical dosimetry and dynamic visualization of IMRT and VMAT treatment plans in water using Cherenkov radiation

PURPOSE A novel technique for optical dosimetry of dynamic intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans was investigated for the first time by capturing images of the induced Cherenkov radiation in water. METHODS A high-sensitivity, intensified CCD camera (ICCD) was configured to acquire a two-dimensional (2D) projection image of the Cherenkov radiation induced by IMRT and VMAT plans, based on the Task Group 119 (TG-119) C-Shape geometry. Plans were generated using the Varian Eclipse treatment planning system (TPS) and delivered using 6 MV x-rays from a Varian TrueBeam Linear Accelerator (Linac) incident on a water tank doped with the fluorophore quinine sulfate. The ICCD acquisition was gated to the Linac target trigger pulse to reduce background light artifacts, read out for a single radiation pulse, and binned to a resolution of 512 × 512 pixels. The resulting videos were analyzed temporally for various regions of interest (ROI) covering the planning target volume (PTV) and organ at risk (OAR), and summed to obtain an overall light intensity distribution, which was compared to the expected dose distribution from the TPS using a gamma-index analysis. RESULTS The chosen camera settings resulted in 23.5 frames per second dosimetry videos. Temporal intensity plots of the PTV and OAR ROIs confirmed the preferential delivery of dose to the PTV versus the OAR, and the gamma analysis yielded 95.9% and 96.2% agreement between the experimentally captured Cherenkov light distribution and expected TPS dose distribution based upon a 3%/3 mm dose difference and distance-to-agreement criterion for the IMRT and VMAT plans, respectively. CONCLUSIONS The results from this initial study demonstrate the first documented use of Cherenkov radiation for video-rate optical dosimetry of dynamic IMRT and VMAT treatment plans. The proposed modality has several potential advantages over alternative methods including the real-time nature of the acquisition, and upon future refinement may prove to be a robust and novel dosimetry method with both research and clinical applications.

Cherenkoscopy based patient positioning validation and movement tracking during post-lumpectomy whole breast radiation therapy

To investigate Cherenkov imaging (Cherenkoscopy) based patient positioning and movement tracking during external beam radiation therapy (EBRT). In a phase 1 clinical trial, including 12 patients undergoing post-lumpectomy whole breast irradiation, Cherenkov emission was imaged with a time-gated ICCD camera synchronized to the LINAC pulse output, during different fractions of the treatment. Patients were positioned with the aid of the AlignRT system in the beginning of each treatment session. Inter-fraction setup variation was studied by rigid image registrations between images acquired at individual treatments to the average image from all imaged treatment fractions. The amplitude of respiratory motion was calculated from the registration of each frame of Cherenkov images to the reference. A Canny edge detection algorithm was utilized to highlight the beam field edges and biological features provided by major blood vessels apparent in the images. Real-time Cherenkoscopy can monitor the treatment delivery, patient motion and alignment of the beam edge to the treatment region simultaneously. For all the imaged fractions, the patient positioning discrepancies were within our clinical tolerances (3 mm in shifts and 3 degree in pitch angle rotation), with 4.6% exceeding 3 mm but still within 4 mm in shifts. The average discrepancy of repetitive patient positioning was 1.22 mm in linear shift and 0.34 degrees in rotational pitch, consistent with the accuracy reported by the AlignRT system. The edge detection algorithm enhanced features such as field edges and blood vessels. Patient positioning discrepancies and respiratory motion retrieved from rigid image registration were consistent with the edge enhanced images. Besides positioning discrepancies caused by globally inaccurate setups, edge enhanced blood vessels indicate the existence of deformations within the treatment region, especially for large patients. Real-time Cherenkoscopy imaging during EBRT is a novel imaging tool that can be used for treatment monitoring, patient positioning and motion tracking.

Cherenkov radiation fluence estimates in tissue for molecular imaging and therapy applications.

Cherenkov radiation has recently emerged as an interesting phenomenon for a number of applications in the biomedical sciences. Its unique properties, including broadband emission spectrum, spectral weight in the ultraviolet and blue wavebands, and local generation of light within a given tissue, have made it an attractive new source of light within tissue for molecular imaging and phototherapy applications. While several studies have investigated the total Cherenkov light yield from radionuclides in units of [photons/decay], further consideration of the light propagation in tissue is necessary to fully consider the utility of this signal in vivo. Therefore, to help further guide the development of this novel field, quantitative estimates of the light fluence rate of Cherenkov radiation from both radionuclides and radiotherapy beams in a biological tissue are presented for the first time. Using Monte Carlo simulations, these values were found to be on the order of 0.01-1 nW cm(-2) per MBq g(-1) for radionuclides, and 1-100 μW cm(-2) per Gy s(-1) for external radiotherapy beams, dependent on the given waveband, optical properties, and radiation source. For phototherapy applications, the total light fluence was found to be on the order of nJ cm(-2) for radionuclides, and mJ cm(-2) for radiotherapy beams. The results indicate that diagnostic potential is reasonable for Cherenkov excitation of molecular probes, but phototherapy may remain elusive at such exceedingly low fluence values. The results of this study are publicly available for distribution online at www.dartmouth.edu/optmed/.

Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy

PURPOSE A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). METHODS Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1° increments, from 239.5° to 300.5°). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. RESULTS As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R(2) = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5° and 284.5° at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5° and 287.5° (+6° increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35° at 441 cm, to 39° at 300 cm, with no significant variation in percent-depth dose at midline (R(2) = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. CONCLUSIONS Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments.

Camera selection for real-time in vivo radiation treatment verification systems using Cherenkov imaging

PURPOSE To identify achievable camera performance and hardware needs in a clinical Cherenkov imaging system for real-time, in vivo monitoring of the surface beam profile on patients, as novel visual information, documentation, and possible treatment verification for clinicians. METHODS Complementary metal-oxide-semiconductor (CMOS), charge-coupled device (CCD), intensified charge-coupled device (ICCD), and electron multiplying-intensified charge coupled device (EM-ICCD) cameras were investigated to determine Cherenkov imaging performance in a clinical radiotherapy setting, with one emphasis on the maximum supportable frame rate. Where possible, the image intensifier was synchronized using a pulse signal from the Linac in order to image with room lighting conditions comparable to patient treatment scenarios. A solid water phantom irradiated with a 6 MV photon beam was imaged by the cameras to evaluate the maximum frame rate for adequate Cherenkov detection. Adequate detection was defined as an average electron count in the background-subtracted Cherenkov image region of interest in excess of 0.5% (327 counts) of the 16-bit maximum electron count value. Additionally, an ICCD and an EM-ICCD were each used clinically to image two patients undergoing whole-breast radiotherapy to compare clinical advantages and limitations of each system. RESULTS Intensifier-coupled cameras were required for imaging Cherenkov emission on the phantom surface with ambient room lighting; standalone CMOS and CCD cameras were not viable. The EM-ICCD was able to collect images from a single Linac pulse delivering less than 0.05 cGy of dose at 30 frames/s (fps) and pixel resolution of 512 × 512, compared to an ICCD which was limited to 4.7 fps at 1024 × 1024 resolution. An intensifier with higher quantum efficiency at the entrance photocathode in the red wavelengths [30% quantum efficiency (QE) vs previous 19%] promises at least 8.6 fps at a resolution of 1024 × 1024 and lower monetary cost than the EM-ICCD. CONCLUSIONS The ICCD with an intensifier better optimized for red wavelengths was found to provide the best potential for real-time display (at least 8.6 fps) of radiation dose on the skin during treatment at a resolution of 1024 × 1024.

Optical cone beam tomography of Cherenkov-mediated signals for fast 3D dosimetry of x-ray photon beams in water

PURPOSE To test the use of a three-dimensional (3D) optical cone beam computed tomography reconstruction algorithm, for estimation of the imparted 3D dose distribution from megavoltage photon beams in a water tank for quality assurance, by imaging the induced Cherenkov-excited fluorescence (CEF). METHODS An intensified charge-coupled device coupled to a standard nontelecentric camera lens was used to tomographically acquire two-dimensional (2D) projection images of CEF from a complex multileaf collimator (MLC) shaped 6 MV linear accelerator x-ray photon beam operating at a dose rate of 600 MU/min. The resulting projections were used to reconstruct the 3D CEF light distribution, a potential surrogate of imparted dose, using a Feldkamp-Davis-Kress cone beam back reconstruction algorithm. Finally, the reconstructed light distributions were compared to the expected dose values from one-dimensional diode scans, 2D film measurements, and the 3D distribution generated from the clinical Varian ECLIPSE treatment planning system using a gamma index analysis. A Monte Carlo derived correction was applied to the Cherenkov reconstructions to account for beam hardening artifacts. RESULTS 3D light volumes were successfully reconstructed over a 400 × 400 × 350 mm(3) volume at a resolution of 1 mm. The Cherenkov reconstructions showed agreement with all comparative methods and were also able to recover both inter- and intra-MLC leaf leakage. Based upon a 3%/3 mm criterion, the experimental Cherenkov light measurements showed an 83%-99% pass fraction depending on the chosen threshold dose. CONCLUSIONS The results from this study demonstrate the use of optical cone beam computed tomography using CEF for the profiling of the imparted dose distribution from large area megavoltage photon beams in water.

Cherenkov imaging in the potential roles of radiotherapy QA and delivery

Cherenkov emission has a direct proportionality to the deposited dose at the local level, and capture of these emitted light signals allows visualization of real time maps of dose in vivo. Mapping the Cherenkov signals through water tanks illustrates how 3D Cherenkov can be achieved, either as 2D plus time, or 3D in static imaging. Imaging Cherenkov from patients shows how signals can be acquired which map out radiation dose in real time. The signals are affected by several factors, each of which will take some calibration to resolve, yet intrinsically the signal is shown to be a linear reporter of dose delivered. Development of calibration methodologies is ongoing in both research and development work.

Beam and tissue factors affecting Cherenkov image intensity for quantitative entrance and exit dosimetry on human tissue

This studys goal was to determine how Cherenkov radiation emission observed in radiotherapy is affected by predictable factors expected in patient imaging. Factors such as tissue optical properties, radiation beam properties, thickness of tissues, entrance/exit geometry, curved surface effects, curvature and imaging angles were investigated through Monte Carlo simulations. The largest physical cause of variation of the correlation ratio between of Cherenkov emission and dose was the entrance/exit geometry (˜50%). The largest human tissue effect was from different optical properties (˜45%). Beyond these, clinical beam energy varies the correlation ratio significantly (˜20% for X-ray beams), followed by curved surfaces (˜15% for X-ray beams and ˜8% for electron beams), and finally, the effect of field size (˜5% for X-ray beams). Other investigated factors which caused variations less than 5% were tissue thicknesses and source to surface distance. The effect of non-Lambertian emission was negligible for imaging angles smaller than 60 degrees. The spectrum of Cherenkov emission tends to blue-shift along the curved surface. A simple normalization approach based on the reflectance image was experimentally validated by imaging a range of tissue phantoms, as a first order correction for different tissue optical properties.

Monitoring longitudinal changes in irradiated head and neck cancer xenografts using diffuse reflectance spectroscopy

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.

Using a reflectance-based correction on Cherenkov images to strengthen correlation with radiation surface dose in an anthropomorphic breast phantom

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.