Technical Note: A novel dosimeter improves total skin electron therapy surface dosimetry workflow.

PURPOSE: The novel scintillator-based system described in this study is capable of accurately and remotely measuring surface dose during Total Skin Electron Therapy (TSET); this dosimeter does not require post-exposure processing or annealing and has been shown to be re-usable, resistant to radiation damage, have minimal impact on surface dose, and reduce chances of operator error compared to existing technologies e.g. optically stimulated luminescence detector (OSLD). The purpose of this study was to quantitatively analyze the workflow required to measure surface dose using this new scintillator dosimeter and compare it to that of standard OSLDs. METHODS: Disc-shaped scintillators were attached to a flat-faced phantom and a patient undergoing TSET. Light emission from these plastic discs was captured using a time-gated, intensified, camera during irradiation and converted to dose using an external calibration factor. Time required to complete each step (daily QA, dosimeter preparation, attachment, removal, registration, and readout) of the scintillator and OSLD surface dosimetry workflows was tracked. RESULTS: In phantoms, scintillators and OSLDs surface doses agreed within 3% for all data points. During patient imaging it was found that surface dose measured by OSLD and scintillator agreed within 5% and 3% for 35/35 and 32/35 dosimetry sites, respectively. The end-to-end time required to measure surface dose during phantom experiments for a single dosimeter was 78 and 202 sec for scintillator and OSL dosimeters, respectively. During patient treatment, surface dose was assessed at 7 different body locations by scintillator and OSL dosimeters in 386 and 754 sec, respectively. CONCLUSION: Scintillators have been shown to report dose nearly twice as fast as OSLDs with substantially less manual work and reduced chances of human error. Scintillator dose measurements are automatically saved to an electronic patient file and images contain a permanent record of the dose delivered during treatment.

Initial Clinical Experience of Cherenkov Imaging in External Beam Radiation Therapy Identifies Opportunities to Improve Treatment Delivery.

PURPOSE: The value of Cherenkov imaging as an on-patient, real-time, treatment delivery verification system was examined in a 64-patient cohort during routine radiation treatments in a single-center study. METHODS AND MATERIALS: Cherenkov cameras were mounted in treatment rooms and used to image patients during their standard radiation therapy regimen for various sites, predominantly for whole breast and total skin electron therapy. For most patients, multiple fractions were imaged, with some involving bolus or scintillators on the skin. Measures of repeatability were calculated with a mean distance to conformity (MDC) for breast irradiation images. RESULTS: In breast treatments, Cherenkov images identified fractions when treatment delivery resulted in dose on the contralateral breast, the arm, or the chin and found nonideal bolus positioning. In sarcoma treatments, safe positioning of the contralateral leg was monitored. For all 199 imaged breast treatment fields, the interfraction MDC was within 7 mm compared with the first day of treatment (with only 7.5% of treatments exceeding 3 mm), and all but 1 fell within 7 mm relative to the treatment plan. The value of imaging dose through clear bolus or quantifying surface dose with scintillator dots was examined. Cherenkov imaging also was able to assess field match lines in cerebral-spinal and breast irradiation with nodes. Treatment imaging of other anatomic sites confirmed the value of surface dose imaging more broadly. CONCLUSIONS: Daily radiation therapy can be imaged routinely via Cherenkov emissions. Both the real-time images and the posttreatment, cumulative images provide surrogate maps of surface dose delivery that can be used for incident discovery and/or continuous improvement in many delivery techniques. In this initial 64-patient cohort, we discovered 6 minor incidents using Cherenkov imaging; these otherwise would have gone undetected. In addition, imaging provides automated, quantitative metrics useful for determining the quality of radiation therapy delivery.

Tracking tumor radiotherapy response in vivo with Cherenkov-excited luminescence ink imaging.

This study demonstrates remote imaging for in vivo detection of radiation-induced tumor microstructural changes by tracking the diffusive spread of injected intratumor UV excited tattoo ink using Cherenkov-excited luminescence imaging (CELI). Micro-liter quantities of luminescent tattoo ink with UV absorption and visible emission were injected at a depth of 2 mm into mouse tumors prior to receiving a high dose treatment of radiation. X-rays from a clinical linear accelerator were used to excite phosphorescent compounds within the tattoo ink through Cherenkov emission. The in vivo phosphorescence was detected using a time-gated intensified CMOS camera immediately after injection, and then again at varying time points after the ink had broken down with the apoptotic tumor cells. Ex vivo tumors were imaged post-mortem using hyperspectral cryo-fluorescence imaging to quantify necrosis and compared to Cherenkov-excited light imaging of diffusive ink spread measured in vivo. Imaging of untreated control mice showed that ink distributions remained constant after four days with less than 3% diffusive spread measured using full width at 20% max. For all mice, in vivo CELI measurements matched within 12% of the values estimated by the high-resolution ex vivo sliced luminescence imaging of the tumors. The tattoo ink spread in treated mice was found to correlate well with the nonperfusion necrotic core volume (R2 = 0.92) but not well with total tumor volume changes (R2 = 0.34). In vivo and ex vivo findings indicate that the diffusive spread of the injected tattoo ink can be related to radiation-induced necrosis, independent of total tumor volume change. Tracking the diffusive spread of the ink allows for distinguishing between an increase in tumor size due to new cellular growth and an increase in tumor size due to edema. Furthermore, the imaging resolution of CELI allows for in vivo tracking of subtle microenvironmental changes which occur earlier than tumor shrinkage and this offers the potential for novel, minimally invasive radiotherapy response assay without interrupting a singular clinical workflow.

Experimentally Observed Cherenkov Light Generation in the Eye During Radiation Therapy.

PURPOSE: Patients have reported sensations of seeing light flashes during radiation therapy, even with their eyes closed. These observations have been attributed to either direct excitation of retinal pigments or generation of Cherenkov light inside the eye. Both in vivo human and ex vivo animal eye imaging was used to confirm light intensity and spectra to determine its origin and overall observability. METHODS AND MATERIALS: A time-gated and intensified camera was used to capture light exiting the eye of a patient undergoing stereotactic radiosurgery in real time, thereby verifying the detectability of light through the pupil. These data were compared with follow-up mechanistic imaging of ex vivo animal eyes with thin radiation beams to evaluate emission spectra and signal intensity variation with anatomic depth. Angular dependency of light emission from the eye was also measured. RESULTS: Patient imaging showed that light generation in the eye during radiation therapy can be captured with a signal-to-noise ratio of 68. Irradiation of ex vivo eye samples confirmed that the spectrum matched that of Cherenkov emission and that signal intensity was largely homogeneous throughout the entire eye, from the cornea to the retina, with a slight maximum near 10 mm depth. Observation of the signal external to the eye was possible through the pupil from 0° to 90°, with a detected emission near 2500 photons per millisecond (during peak emission of the ON cycle of the pulsed delivery), which is over 2 orders of magnitude higher than the visible detection threshold. CONCLUSIONS: By quantifying the spectra and magnitude of the signal, we now have direct experimental observations that Cherenkov light is generated in the eye during radiation therapy and can contribute to perceived light flashes. Furthermore, this technique can be used to further study and measure phosphenes in the radiation therapy clinic.

Technical Note: Quality assurance and relative dosimetry testing of a 60 Co total body irradiator using optical imaging.

PURPOSE: The aim of this study was to create an optical imaging-based system for quality assurance (QA) testing of a dedicated Co-60 total body irradiation (TBI) machine. Our goal is to streamline the QA process by minimizing the amount time necessary for tests such as verification of dose rate and field homogeneity. METHODS: Plastic scintillating rods were placed directly on the patient treatment couch of a dedicated TBI 60 Co irradiator. A tripod-mounted intensified camera was placed directly adjacent to the couch. Images were acquired over a 30-s period once the cobalt source was fully exposed. Real-time image filtering was used; cumulative images were flatfield corrected as well as background and darkfield subtracted. Scintillators were used to measure light-radiation field correspondence, dose rate, field homogeneity, and symmetry. Dose rate effects were measured by modifying the height of the treatment couch and scintillator response was compared to ionization chamber (IC) measurements. Optically stimulated luminesce detector (OSLD) used as reference dosimeters during field symmetry and homogeneity testing. RESULTS: The scintillator-based system accurately reported changes in dose rate. When comparing normalized output values for IC vs scintillators over a range of source-to-surface distances, a linear relationship (R2  = 0.99) was observed. Normalized scintillator signal matched OSLD measurements with <1.5% difference during field homogeneity and symmetry testing. Beam symmetry across both axes of the field was within 2%. The light field was found to correspond to 90 ± 3% of the isodose maximum along the longitudinal and latitudinal axis, respectively. Scintillator imaging output results using a single image stack requiring no postexposure processing (needed for OSLD) or repeat manual measurements (needed for IC). CONCLUSION: Imaging of scintillation light emission from plastic rods is a viable and efficient method for carrying out TBI 60 Co irradiator QA. We have shown that this technique can accurately measure field homogeneity, symmetry, light-radiation field correspondence, and dose rate effects.

Improvements to an optical scintillator imaging-based tissue dosimetry system.

Previous work has shown that capturing optical emission from plastic discs attached directly to the skin can be a viable means to accurately measure surface dose during total skin electron therapy. This method can provide accurate dosimetric information rapidly and remotely without the need for postprocessing. The objective of this study was to: (1) improve the robustness and usability of the scintillators and (2) enhance sensitivity of the optical imaging system to improve scintillator emission detection as related to tissue surface dose. Baseline measurements of scintillator optical output were obtained by attaching the plastic discs to a flat tissue phantom and simultaneously irradiating and imaging them. Impact on underlying surface dose was evaluated by placing the discs on-top of the active element of an ionization chamber. A protective coating and adhesive backing were added to allow easier logistical use, and they were also subjected to disinfection procedures, while verifying that these changes did not affect the linearity of response with dose. The camera was modified such that the peak of detector quantum efficiency better overlapped with the emission spectra of the scintillating discs. Patient imaging was carried out and surface dose measurements were captured by the updated camera and compared to those produced by optically stimulated luminescence detectors (OSLD). The updated camera was able to measure surface dose with < 3 % difference compared to OSLD­Cherenkov emission from the patient was suppressed and scintillation detection was enhanced by 25 × and 7 × , respectively. Improved scintillators increase underlying surface dose on average by 5.2 ± 0.1 % and light output decreased by 2.6 ± 0.3 % . Disinfection had < 0.02 % change on scintillator light output. The enhanced sensitivity of the imaging system to scintillator optical emission spectrum can now enable a reduction in physical dimensions of the dosimeters without loss in ability to detect light output.

Characterization of a non-contact imaging scintillator-based dosimetry system for total skin electron therapy.

Surface dosimetry is required for ensuring effective administration of total skin electron therapy (TSET); however, its use is often reduced due to the time consuming and complex nature of acquisition. A new surface dose imaging technique was characterized in this study and found to provide accurate, rapid and remote measurement of surface doses without the need for post-exposure processing. Disc-shaped plastic scintillators (1 mm thick × 15 mm [Formula: see text]) were chosen as optimal-sized samples and designed to attach to a flat-faced phantom for irradiation using electron beams. Scintillator dosimeter response to radiation damage, dose rate, and temperature were studied. The effect of varying scintillator diameter and thickness on light output was evaluated. Furthermore, the scintillator emission spectra and impact of dosimeter thickness on surface dose were also quantified. Since the scintillators were custom-machined, dosimeter-to-dosimeter variation was tested. Scintillator surface dose measurements were compared to those obtained by optically stimulated luminescence dosimeters (OSLD). Light output from scintillator dosimeters evaluated in this study was insensitive to radiation damage, temperature, and dose rate. Maximum wavelength of emission was found to be 422 nm. Dose reported by scintillators was linearly related to that from OSLDs. Build-up from placement of scintillators and OSLDs had a similar effect on surface dose (4.9% increase). Variation among scintillator dosimeters was found to be 0.3 ± 0.2%. Scintillator light output increased linearly with dosimeter thickness (~1.9 × /mm). All dosimeter diameters tested were able to accurately measure surface dose. Scintillator dosimeters can potentially improve surface dosimetry-associated workflow for TSET in the radiation oncology clinic. Since scintillator data output can be automatically recorded to a patient medical record, the chances of human error in reading out and recording surface dose are minimized.

Assessment of imaging Cherenkov and scintillation signals in head and neck radiotherapy.

The goal of this study was to test the utility of time-gated optical imaging of head and neck (HN) radiotherapy treatments to measure surface dosimetry in real-time and inform possible interfraction replanning decisions. The benefit of both Cherenkov and scintillator imaging in HN treatments is direct daily feedback on dose, with no change to the clinical workflow. Emission from treatment materials was characterized by measuring radioluminescence spectra during irradiation and comparing emission intensities relative to Cherenkov emission produced in phantoms and scintillation from small plastic targets. HN treatment plans were delivered to a phantom with bolus and mask present to measure impact on signal quality. Interfraction superficial tumor reduction was simulated on a HN phantom, and cumulative Cherenkov images were analyzed in the region of interest (ROI). HN human patient treatment was imaged through the mask and compared with the dose distribution calculated by the treatment planning system. The relative intensity of radioluminescence from the mask was found to be within 30% of the Cherenkov emission intensity from tissue-colored clay. A strong linear relationship between normalized cumulative Cherenkov intensity and tumor size was established ([Formula: see text]). The presence of a mask above a scintillator ROI was found to decrease mean pixel intensity by >40% and increase distribution spread. Cherenkov imaging through mask material is shown to have potential for surface field verification and tracking of superficial anatomy changes between treatment fractions. Imaging of scintillating targets provides a direct imaging of surface dose on the patient and through transparent bolus material. The first imaging of a patient receiving HN radiotherapy was achieved with a signal map which qualitatively matches the surface dose plan.

Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy.

Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool.

Time-gated scintillator imaging for real-time optical surface dosimetry in total skin electron therapy.

The purpose of this study was to measure surface dose by remote time-gated imaging of plastic scintillators. A novel technique for time-gated, intensified camera imaging of scintillator emission was demonstrated, and key parameters influencing the signal were analyzed, including distance, angle and thickness. A set of scintillator samples was calibrated by using thermo-luminescence detector response as reference. Examples of use in total skin electron therapy are described. The data showed excellent room light rejection (signal-to-noise ratio of scintillation SNR ≈ 470), ideal scintillation dose response linearity, and 2% dose rate error. Individual sample scintillation response varied by 7% due to sample preparation. Inverse square distance dependence correction and lens throughput error (8% per meter) correction were needed. At scintillator-to-source angle and observation angle <50°, the radiant energy fluence error was smaller than 1%. The achieved standard error of the scintillator cumulative dose measurement compared to the TLD dose was 5%. The results from this proof-of-concept study documented the first use of small scintillator targets for remote surface dosimetry in ambient room lighting. The measured dose accuracy renders our method to be comparable to thermo-luminescent detector dosimetry, with the ultimate realization of accuracy likely to be better than shown here. Once optimized, this approach to remote dosimetry may substantially reduce the time and effort required for surface dosimetry.

Improving treatment geometries in total skin electron therapy: Experimental investigation of linac angles and floor scatter dose contributions using Cherenkov imaging.

PURPOSE: The purpose of this study was to identify the optimal treatment geometry for total skin electron therapy (TSET) using a new optimization metric from Cherenkov image analysis, and to investigate the sensitivity of the Cherenkov imaging method to floor scatter effects in this unique treatment setup. METHODS: Cherenkov imaging using an intensified charge coupled device (ICCD) was employed to measure the relative surface dose distribution as a 2D image in the total skin electron treatment plane. A 1.2 m × 2.2 m × 1 cm white polyethylene sheet was placed vertically at a source to surface distance (SSD) of 300 cm, and irradiated with 6 MeV high dose rate TSET beams. The linear accelerator coordinate system used stipulates 0° is the bottom of the gantry arc, and progresses counterclockwise so that gantry angle 270° produces a horizontal beam orthogonal to the treatment plane. First, all unique pairs of treatment beams were analyzed to determine the performance of the currently recommended symmetric treatment angles (±20° from the horizontal), compared to treatment geometries unconstrained to upholding gantry angle symmetry. This was performed on two medical linear accelerators (linacs). Second, the extent of the floor scatter contributions to measured surface dose at the extended SSD required for TSET were imaged using three gantry angles of incidence: 270° (horizontal), 253° (-17°), and 240° (-30°). Images of the surface dose profile at each angle were compared to the standard concrete floor when steel plates, polyvinyl chloride (PVC), and solid water were placed on the ground at the base of the treatment plane. Postprocessing of these images allowed for comparison of floor material-based scatter profiles with previously published simulation results. RESULTS: Analysis of the symmetric treatment geometry (270 ± 20°) and the identified optimal treatment geometry (270 + 23° and 270 - 17°) showed a 16% increase in the 90% isodose area for the latter field pair on the first linac. The optimal asymmetric pair for the second linac (270 + 25° and 270 - 17°) provided a 52% increase in the 90% isodose area when compared to the symmetric geometry. Difference images between Cherenkov images captured with test materials (steel, PVC, and solid water) and the control (concrete floor) demonstrated relative changes in the two-dimensional (2D) dose profile over a 1 × 1.9 m region of interest (ROI) that were consistent with published simulation data. Qualitative observation of the residual images demonstrates localized increases and decreases with respect to the change in floor material and gantry angle. The most significant changes occurred when the beam was most directly impinging the floor (gantry angle 240°, horizontal -30°), where the PVC floor material decreased scatter dose by 1-3% in 7.2% of the total ROI area, and the steel plate increased scatter dose by 1-3% in 7.0% of the total ROI area. CONCLUSIONS: An updated Cherenkov imaging method identified asymmetric, machine-dependent TSET field angle pairs that provided much larger 90% isodose areas than the commonly adopted symmetric geometry suggested by Task Group 30 Report 23. A novel demonstration of scatter dose Cherenkov imaging in the TSET field was established.