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Purpose In mono-isocentric radiation therapy treatment plans designed to treat the whole breast and supraclavicular lymph nodes, the fields meet at isocenter, forming the match line. Insufficient coverage at the match line can lead to recurrence, and overlap over weeks of treatment can lead to increased risk of healthy tissue toxicity. Cherenkov imaging was used to assess the accuracy of delivery at the match line and identify potential incidents during patient treatments. Methods and materials A controlled calibration was constructed from the deconvolved Cherenkov images from the delivery of a modified patient treatment plan to an anthropomorphic phantom with introduced separation and overlap. The trend from this calibration was then used to evaluate the field match line for accuracy and inter-fraction consistency for two patients. Results The intersection point between matching field profiles was directly correlated to the distance (gap/overlap) between the fields (anthropomorphic phantom R2 = 0.994 “breath hold” and R2 = 0.990 “free breathing”). The profile intersection points from two patients’ imaging sessions yielded an average of +1.40 mm offset (overlap) and −1.32 mm offset (gap), thereby introducing roughly a 25.0% over-dose and a −23.6% under-dose (R2 = 0.994). Conclusions This study shows that field match regions can be detected and quantified by taking deconvolved Cherenkov images and using their product image to create steep intensity gradients, causing match lines to stand out. These regions can then be quantitatively translated into a dose consequence. This approach offers a high sensitivity detection method which can quantify match line variability and errors in vivo.

PURPOSE: This study demonstrates a robust Cherenkov imaging-based solution to MR-Linac daily QA, including mechanical-imaging-radiation isocenter coincidence verification. METHODS: A fully enclosed acrylic cylindrical phantom was designed to be mountable to the existing jig, indexable to the treatment couch. An ABS plastic conical structure was fixed inside the phantom, held in place with 3D-printed spacers and filled with water allowing for high edge contrast on MR imaging scans. Both a star shot plan and a four-angle sheet beam plan were delivered to the phantom; the former allowed for radiation isocenter localization in the x-z plane (A/P and L/R directions) relative to physical landmarks on the phantom, and the latter allowed for the longitudinal position of the sheet beam to be encoded as a ring of Cherenkov radiation emitted from the phantom, allowing for isocenter localization on the y-axis (S/I directions). A custom software application was developed to perform near-real-time analysis of the data by any clinical user. RESULTS: Calibration procedures show that linearity between longitudinal position and optical ring diameter is high (R(2) > 0.99), and that RMSE is low (0.184 mm). The star shot analysis showed a minimum circle radius of 0.34 mm. The final isocenter coincidence measurements were in the lateral, longitudinal, and vertical directions were −0.61 mm, 0.55 mm, and −0.14 mm respectively, and the total 3D distance coincidence was 0.83 mm, with each of these being below the 2 mm tolerance. CONCLUSION: This novel system provided an efficient, MR safe, all in one method for acquisition and near-real-time analysis of isocenter coincidence data. This represents a direct measurement of the 3D isocentricity. The combination of this phantom and the custom analysis application makes this solution readily clinically deployable after longitudinal analysis of performance consistency.

Purpose High dose-rate conditions, coupled with problems related to small field dosimetry, make dose characterization for FLASH-RT challenging. Most conventional dosimeters show significant dependence on dose rate at ultra-high dose rate conditions or fail to provide sufficiently fast temporal data for pulse to pulse dosimetry. Here fast 2D imaging of radioluminescence from a water and quinine phantom was tested for dosimetry of individual 4 μs linac pulses. Methods A modified clinical linac delivered an electron FLASH beam of >50 Gy/s to clinical isocenter. This modification removed the X-ray target and flattening filter, leading to a beam that was symmetric and gaussian, as verified with GafChromic EBT-XD film. Lateral projected 2D dose distributions for each linac pulse were imaged in a quinine-doped water tank using a gated intensified camera, and an inverse Abel transform reconstruction provided 3D images for on-axis depth dose values. A total of 20 pulses were delivered with a 10 MeV, 1.5 cm circular beam and beam with jaws wide open (40 × 40 cm2 ), and a 3D dose distribution was recovered for each pulse. Beam output was analyzed on a pulse by pulse basis. Results The Rp , Dmax and the R50 measured with film and optical methods agreed to within 1 mm for the 1.5 cm circular beam and the beam with jaws wide open. Cross beam profiles for both beams agreed with film data with > 95 % passing rate (2%/2mm gamma criteria). The optical central axis depth dose agreed with film data, except for near the surface. A temporal pulse analysis revealed a ramp-up period where the dose per pulse increased for the first few pulses and then stabilized. Conclusions Optical imaging of radioluminescence was presented as a valuable tool for establishing a baseline for the recently initiated electron FLASH beam at our institution.

Color vision is used throughout medicine to interpret the health and status of tissue. Ionizing radiation used in radiation therapy produces broadband white light inside tissue through the Cherenkov effect, and this light is attenuated by tissue features as it leaves the body. In this study, a novel time-gated three-channel camera was developed for the first time and was used to image color Cherenkov emission coming from patients during treatment. The spectral content was interpreted by comparison with imaging calibrated tissue phantoms. Color shades of Cherenkov emission in radiotherapy can be used to interpret tissue blood volume, oxygen saturation and major vessels within the body., A novel three-channel intensified camera capable of imaging Cherenkov emission in full color was developed, allowing for sensitivity to in vivo biological tissue information during radiotherapy.

Significance: The Cherenkov emission spectrum overlaps with that of ambient room light sources. Choice of room lighting devices dramatically affects the efficient detection of Cherenkov emission during patient treatment. Aim: To determine optimal room light sources allowing Cherenkov emission imaging in normally lit radiotherapy treatment delivery rooms. Approach: A variety of commercial light sources and long-pass (LP) filters were surveyed for spectral band separation from the red to near-infrared Cherenkov light emitted by tissue. Their effects on signal-to-noise ratio (SNR), Cherenkov to background signal ratio, and image artifacts were quantified by imaging irradiated tissue equivalent phantoms with an intensified time-gated CMOS camera. Results: Because Cherenkov emission from tissue lies largely in the near-infrared spectrum, a controlled choice of ambient light that avoids this spectral band is ideal, along with a camera that is maximally sensitive to it. An RGB LED light source produced the best SNR out of all sources that mimic room light temperature. A 675-nm LP filter on the camera input further reduced ambient light detected (optical density > 3), achieving maximal SNR for Cherenkov emission near 40. Reduction of the room light signal reduced artifacts from specular reflection on the tissue surface and also minimized spurious Cherenkov signals from non-tissue features such as bolus. Conclusions: LP filtering during image acquisition for near-infrared light in tandem with narrow band LED illuminated rooms improves image quality, trading off the loss of red wavelengths for better removal of room light in the image. This spectral filtering is also critically important to remove specular reflection in the images and allow for imaging of Cherenkov emission through clear bolus. Beyond time-gated external beam therapy systems, the spectral separation methods can be utilized for background removal for continuous treatment delivery methods including proton pencil beam scanning systems and brachytherapy.

Significance: Optical imaging of Cherenkov emission during radiation therapy could be used to verify dose delivery in real-time if a more comprehensive quantitative understanding of the factors affecting emission intensity could be developed. Aim: This study aims to explore the change in diffuse Cherenkov emission intensity with x-ray beam energy from irradiated tissue, both theoretically and experimentally. Approach: Derivation of the emitted Cherenkov signal was achieved using diffusion theory, and experimental studies with 6 to 18 MV energy x-rays were performed in tissue phantoms to confirm the model predictions as related to the radiation build-up factor with depth into tissue. Results: Irradiation at lower x-ray energies results in a greater surface dose and higher build-up slope, which results in a ∼46% greater diffusely emitted Cherenkov signal per unit dose at 6 MV relative to 18 MV x-rays. However, this phenomenon competes with a decrease in signal from less Cherenkov photons being generated at lower energies, a ∼44% reduction at 6 versus 18 MV. The result is an emitted Cherenkov signal that is nearly constant with beam energy. Conclusions: This study explains why the observed Cherenkov emission from tissue is not a strong function of beam energy, despite the known strong correlation between Cherenkov intensity and particle energy in the absence of build-up and scattering effects.

Background Total skin electron therapy (TSET) utilizes high-energy electrons to treat malignancies on the entire body surface. The otherwise invisible radiation beam can be observed via the optical Cherenkov photons emitted from interactions between the high-energy electron beam and tissue. Methods and materials With a time-gated intensified camera system, the Cherenkov emission can be used to evaluate the dose uniformity on the surface of the patient in real time. Fifteen patients undergoing TSET in various conditions (whole body and half body) were imaged and analyzed. Each patient was monitored during TSET via in vivo detectors (IVD) in nine locations. For accurate Cherenkov imaging, a comparison between IVD and Cherenkov profiles was conducted using a polyvinyl chloride board to establish the perspective corrections. Results and discussion With proper corrections developed in this study including the perspective and inverse square corrections, the Cherenkov imaging provided two-dimensional maps proportional to dose and projected on patient skin. The results of ratio between chest and umbilicus points were in good agreement with in vivo point dose measurements, with a standard deviation of 2.4% compared to OSLD measurements. Conclusions Cherenkov imaging is a viable tool for validating patient-specific dose distributions during TSET.

PURPOSE: We demonstrate the feasibility of optical imaging as a quality assurance tool for static small beamlets, and pre-treatment verification tool for radiosurgery and VMAT plans. METHODS: Small static beams and clinical Volumetric-modulated arc therapy (VMAT) plans were simulated in a treatment planning system (TPS) and delivered to a cylindrical tank filled with water-based liquid scintillator. Emission was imaged using a blue-sensitive, intensified CMOS camera time-gated to the linac pulses. For static beams, percentage depth and cross beam profiles of projected intensity distribution were compared to treatment planning system (TPS) data. 2D gamma analysis was performed on all clinical plans, and the technique was tested for sensitivity against common errors (multileaf collimator position, gantry angle) by inducing deliberate errors in the VMAT plans control points. The technique’s detection limits for spatial resolution and the smallest number of control points that could be imaged reliably was also tested. The sensitivity to common delivery errors was also compared against a commercial 2.5D diode array dosimeter. RESULTS: A spatial resolution of 1 mm was achieved with our imaging setup. The optical projected percentage depth intensity profiles agreed to within 2% relative to the TPS data for small static square beams (5, 10 and 50mm(2)). For projected cross beam profiles, a gamma pass rate >99% was achieved for a 3%/1mm criteria. All clinical plans passed the 3%/3mm criteria with >95% passing rate. A static 5 mm beam with 20 Monitor Units could be measured with an average percent difference of 5.5 ±3% relative to the TPS. The technique was sensitive to multileaf collimator errors down to 1 mm and gantry angle errors of 1°. CONCLUSIONS: Optical imaging provides ample spatial resolution for imaging small beams. The ability to faithfully image down to 20 MU of 5 mm, 6 MV beamlets prove the ability to perform quality assurance for each control point within dynamic plans. The technique is sensitive to small offsets errors in gantry angles and Multi-leaf collimator (MLC) leaf positions, and at certain scenario it exhibits higher sensitivity than a commercial 2.5D diode array.

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

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).

Purpose: In this study, procedures were developed to achieve efficient reversible conversion of a clinical linear accelerator (LINAC) and deliver electron FLASH (eFLASH) or conventional beams to the treatment room isocenter. Material & Methods: The LINAC was converted to deliver eFLASH beam within 20 minutes by retracting the x-ray target from the beam's path, positioning the carousel on an empty port, and selecting 10 MV photon beam energy in the treatment console. Dose per pulse and average dose rate were measured in a solid water phantom at different depths with Gafchromic film and OSLD. A pulse controller counted the pulses via scattered radiation signal and gated the delivery for preset pulse count. A fast photomultiplier tube-based Cherenkov detector measured per pulse beam output at 2 ns sampling rate. After conversion back to clinical mode, conventional beam output, flatness, symmetry, field size and energy were measured for all clinically commissioned energies. Results: Dose per pulse of 0.86 +/- 0.01 Gy (310 +/- 7 Gy/s average dose rate) were achieved at isocenter. The dose from simultaneous irradiation of film and OSLD were within 1%. The PMT showed the LINAC required about 5 pulses before the output stabilized and its long-term stability was within 3% for measurements performed at 3 minutes intervals. The dose, flatness, symmetry, and photon energy were unchanged from baseline and within tolerance (1%, 3%, 2%, and 0.1% respectively) after reverting to conventional beams. Conclusion: 10 MeV FLASH beams were achieved at the isocenter of the treatment room. The beam output was reproducible but requires further investigation of the ramp up time in the first 5 pulses, equivalent to, Manuscript: 21 Pages, 1 Table, 8 Figures; Supplementary Material A: 2 Pages, 2 Figures; Appendix: Film Dosimetry: 2 Pages, 2 Tables

Fluorescence imaging is severely limited by the background and autofluorescence of tissues for in vivo detection of circulating tumor cells (CTCs). Time-gated luminescence (TGL) imaging, in combination with luminescent probes that possess hundreds of microsecond emission lifetimes, can be used to effectively suppress this background, which has predominantly nanosecond lifetimes. This Letter demonstrates the feasibility of TGL imaging using luminescent probes for the in vivo real time imaging and tracking of single CTCs circulating freely in the blood vessels with higher accuracy given by substantially higher signal-to-noise ratio. The luminescent probe used in this Letter was a commercial E u 3 + chelate (EuC) nanosphere with a super-long lifetime of near 800 µs, which enabled TGL imaging to achieve background-free detection with ∼ 5 times higher SNR versus steady state. Phantom and in vivo mouse studies indicated that EuC labeled tumor cells moving in medium or bloodstream at the speed of 1–2 mm/s could be captured in real time.

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.

Biomedical imaging techniques are often limited by the loss of resolution with depth due to light scattering in biological tissue. Beyond a few millimeters in depth, diffuse transport dominates and makes high resolution imaging impossible using conventional techniques. In this work, light sheet imaging using x-ray photons was developed with a keV x-ray source. This partially overcomes this scattering by generating light within tissue at depth. The light excites fluorescent probes that can be used for tumor tracking based upon molecular targeting. Most of the fluorescent probes have a lifetime in the nanosecond range. In this study, the use of a portable linear accelerator delivering 30-ns x-ray pulses was explored. Using x-ray excitable fluorophores, light was generated within a tissue phantom. Image stacks were acquired using an intensified camera (PiMAX4 – Princeton Instrument – USA) placed perpendicularly to the slicing direction of the sample. A solid-state silicon photomultiplier was used to gate acquisition. Although this delayed acquisition slightly, it improved the fluorescence signal-to-noise ratio (SNR). A deconvolution algorithm counteracted the blurring effects of tissue, and image stacks were converted to 3D reconstructions. In summary, nanosecond x-ray pulses can be used to excite fluorophores through radioluminescence phenomenon. Combined with slice imaging, this approach shows promise for time-resolved x-ray luminescence.

Purpose A remote imaging system tracking Cherenkov emission was analyzed to verify that the linear accelerator (linac) beam shape could be quantitatively measured at the irradiation surface for Quality Audit (QA). Methods The Cherenkov camera recorded 2D dose images delivered on a solid acrylonitrile butadiene styrene (ABS) plastic phantom surface for a range of square beam sizes, and 6 MV photons. Imaging was done at source to surface distance (SSD) of 100 cm and compared to GaF film images and linac light fields of the same beam sizes, ranging over 5 × 5 cm2 up to 20 × 20 cm2 . Line profiles of each field were compared in both X and Y jaw directions. Each measurement was repeated on two different Clinac2100 machines. An interreader comparison of the beam width interpretation was completed using procedures commonly employed for beam to light field coincidence verification. Cherenkov measurements are also done for beams of complex treatment plan and isocenter QA. Results The Cherenkov image widths matched with the measured GaF images and light field images, with accuracy in the range of ±1 mm standard deviation. The differences between the measurements were minor and within tolerance of geometrical requirement of standard linac QA procedures conducted by human setup verification, which had a similar error range. The measurement made by the remote imaging system allowed for beam shape extraction of radiation fields at the SSD location of the beam. Conclusions The proposed Cherenkov image acquisition system provides a valid way to remotely confirm radiation field sizes and provides similar information to that obtained from the linac light field or GaF film estimates of the beam size. The major benefit of this approach is that with a fixed installation of the camera, testing could be done completely under software control with automated image analysis, potentially simplifying conventional QA procedures with appropriate calibration of boundary definitions, and the natural extension to capturing dynamic treatment beamlets at SSD could have future value, such as verification of beam plans with complex beam shapes, like IMRT or "star-shot" QA for the isocenter.

PURPOSE: CCD cameras are employed to image scintillation and Cherenkov radiation in external beam radiotherapy. This is achieved by gating the camera to the linear accelerator (Linac) output. While a direct output signal line from the target current can be used, this approach can induce delay in the trigger signal, and potentially alter Linac performance through electrical feedback. A scintillating detector for stray radiation inside the Linac room was developed to act as an untethered trigger for camera-based dosimetry, thereby overcoming the issues of time delay and altered Linac performance. METHODS: A scintillator coupled silicon photomultiplier detector was optimized and systematically tested for location sensitivity and for use with both X-rays and electron beams, at different energies and field sizes. Two different scintillator sizes were used for the study. Images captured using the physical trigger were compared to the stray radiation trigger. The issue of false positive event detection, due to additional neutron activated products with high energy beams, was addressed. RESULTS: For X-ray beams, the detector module triggered 130–80 ns before the Linac target current signal output line. The designed circuit provided ample output voltage for the camera to trigger for distances up to 3m from the isocenter with a 6MV, 5×5cm beam, using a Ø3×20 mm(3) crystal. With a larger scintillator size, the detector could be placed even beyond 3m distance. False positive triggering was reduced by a coincidence detection scheme. Negligible fluctuations were seen in time-gated imaging of Cherenkov intensity on a body phantom, when comparing directly connected vs this remote triggering approach. CONCLUSION: This scintillator-diode trigger can be used for remote Cherenkov imaging or remote scintillator dosimetry imaging during radiotherapeutic procedures. Moreover, the module overcomes the delay caused by wire-based triggering and solves the issue of false triggering from stray radiation.

Purpose/Objective(s) In the last decade, Cherenkov imaging has been demonstrated as a useful clinical technique both for real-time surface dose visualization during patient treatment and for various high-resolution QA measurements. However there remains much work to be done in the development of Cherenkov-based in vivo dosimetry. In this work, the concept of in vivo color Cherenkov imaging is introduced. It is hypothesized that Cherenkov images with sensitivity to the spectral quality of Cherenkov emission induced inside tissue can provide increased information about tissue composition as opposed to monochromatic, red-weighted images used in prior work. Materials/Methods A custom Color Cherenkov camera was created from three time-gated intensified CMOS cameras, each with varying spectral sensitivity of the photocathode, and sharing one imaging lens. A dichroic mirror assembly allowed for incoming Cherenkov light signals to be redirected according to wavelength to the appropriate camera resulting in three raw image stacks for each acquisition. These images were then reconstructed into three-channel color images via color calibration, summed, and background subtracted. In vivo color Cherenkov images of three right-sided breast patients were acquired for one treatment fraction each as part of an IRB-approved clinical trial. These images were interpreted alongside images of liquid tissue-simulating phantoms that matched tissue optical properties. Variations in oxygenation and blood volume were mimicked in this way, and the data was used to interpret the clinical images. Impacts on Cherenkov emission spectra from tissue under these various conditions were also estimated. Results The presence of oxygenated vs deoxygenated blood in tissue has a visible impact on the color of Cherenkov emission, leading to a redder hue due to decreased attenuation of red wavelengths by oxyhemoglobin, similar to erythema or blush of tissue. This was verified in the tissue phantoms. Variations in blood concentration produce a strong blue-red trend in color space (R2 = 0.96), as verified by detailed analysis. Color Cherenkov images of right breast radiotherapy treatments displayed pink regions across the breast coincident with the treated area for all three patients, and the variations in color were interpreted relative to the phantom data. Conclusion This first investigation of color Cherenkov imaging uncovered the natural relationship between tissue composition and the spectral quality of emitted Cherenkov light. The correlation between blood content and color will be translated in future work to in vivo sensing of variations in fat and fibroglandular content in irradiated tissues. These findings will allow for the correction of Cherenkov images to produce accurate in vivo surface dose maps during patient treatments.

We realized subsurface fluorescence LiDAR with a large format single-photon avalanche diode array capable of localizing and quantifying concentration of fluorescent molecules in heavily scattering media, such as tissue, with submillimeter depth accuracy. (C) 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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.

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 ) 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.

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 with3 % difference compared to OSLD–Cherenkov 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 had0.02 % 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.

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with a clinical linear accelerator during External Beam Radiotherapy, to map out molecular luminescence intensity or lifetime in tissue. In order to realize a deeper imaging depth with a reasonable spatial resolution in CELSI, we optimized the original scanning procedure to complete this in a similar way to x-ray computed tomography and with image reconstruction from Maximum-likelihood expectation maximization and multi-pinhole irradiation for parallelization. Resolution phantom studies showed that a 0.3 mm diameter capillary tube containing 0.01 nM luminescent nanospheres could be recognized at a depth of 21 mm into tissue-like media. Small animal imaging with a 1 mm diameter cylindrical target demonstrated that fast 3D data acquisition can be achieved by this multi-pinhole collimator approach to image high resolution luminescence through a whole animal.

Cherenkov-excited luminescence scanned imaging (CELSI) is achieved with External Beam Radiotherapy, to map out molecular luminescence intensity or lifetime in tissue. In order to realize a deeper imaging depth with a reasonable spatial resolution, we optimized the original scanning gesture to do in a similar way to computed tomography (CT) and the image reconstruction was instead used a customized Maximum-likelihood expectation maximization (ML-EM) for CELSI. In tomographic CELSI (TCELSI), tomographic images are generated by irradiating the subject using a sequence of programmed X-ray beams at a fixed projection angle, while sensitive measurement is to take a sum for all image pixels from an intensified charge-coupled device. By restricting the X-ray excitation to a single, narrow beam of radiation, the origin of the optical photons can be inferred regardless of where these photons were detected, and how many times they scattered in tissue. Measurement geometry was designed for clinical expectation: CT scanning was achieved by a clinical linear accelerator (LINAC), where X-ray beam sequence and multiple projections were realized with multi leaf collimator (MLC) and gantry movement, respectively. Furthermore, in most modern External Beam Radiotherapy, MLC movement is synchronized with gantry angle to release a uniform radiation, and some of treatment plans, e.g., Intensity Modulated Radiation Therapy (IMRT), have a potential to match the scanning way mentioned. By including Cherenkov imaging results, medium surface profile can be additionally acquired, which can be used as boundary reference to do depth correction and co-register with molecular images. Resolution phantom studies showed that a 0.3 mm diameter capillary tube containing 0.01 nM luminescent nanospheres could be recognized at a depth of 21 mm into tissue-like media. Small animal imaging with a 1 mm diameter cylindrical target demonstrated that fast 3D data acquisition was achieved by a multi-pinhole collimator to image local luminescence 20mm deep.

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 is used to evaluate the dose uniformity on the surface of the patient in real-time. We have utilized a structured light sensor to determine the surface contour of each patient. Each patient was also monitored during TSET via in-vivo detectors (IVD) and/or scintillating discs in nine locations. The Cherenkov image is converted to dose distribution after a two-dimensional perspective geometry correction and the IVD measured dose at umbilicus. Cumulative dose on patient surface is obtained by projecting the two-dimensional dose distribution onto a cylindrical geometry representing the patient anatomic geometry. Patients undergoing TSET in various conditions (whole body and half body) were imaged and analysed, and the cumulative dose based on Cherenkov imaging was evaluated on various patients.

Purpose.In this study, spatio-temporal beam profiling for electron ultra-high dose rate (UHDR; >40 Gy s-1) radiation via Cherenkov emission and radioluminescence imaging was investigated using intensified complementary metal-oxide-semiconductor cameras.Methods.The cameras, gated to FLASH optimized linear accelerator pulses, imaged radioluminescence and Cherenkov emission incited by single pulses of a UHDR (>40 Gy s-1) 10 MeV electron beam delivered to the isocenter. Surface dosimetry was investigated via imaging Cherenkov emission or scintillation from a solid water phantom or Gd2O2S:Tb screen positioned on top of the phantom, respectively. Projected depth-dose profiles were imaged from a tank filled with water (Cherenkov emission) and a 1 g l-1quinine sulfate solution (scintillation). These optical results were compared with projected lateral dose profiles measured by Gafchromic film at different depths, including the surface.Results.The per-pulse beam output from Cherenkov imaging agreed with the photomultiplier tube Cherenkov output to within 3% after about the first five to seven ramp-up pulses. Cherenkov emission and scintillation were linear with dose (R2 = 0.987 and 0.995, respectively) and independent of dose rate from ∼50 to 300 Gy s-1(0.18-0.91 Gy/pulse). The surface dose distribution from film agreed better with scintillation than with Cherenkov emission imaging (3%/3 mm gamma pass rates of 98.9% and 88.8%, respectively). Using a 450 nm bandpass filter, the quinine sulfate-based water imaging of the projected depth optical profiles agreed with the projected film dose to within 5%.Conclusion.The agreement of surface dosimetry using scintillation screen imaging and Gafchromic film suggests it can verify the consistency of daily beam quality assurance parameters with an accuracy of around 2% or 2 mm. Cherenkov-based surface dosimetry was affected by the target's optical properties, prompting additional calibration. In projected depth-dose profiling, scintillation imaging via spectral suppression of Cherenkov emission provided the best match to film. Both camera-based imaging modalities resolved dose from single UHDR beam pulses of up to 60 Hz repetition rate and 1 mm spatial resolution.

In this study the metric of detective quantum efficiency (DQE) was applied to Cherenkov imaging systems for the first time, and results were compared for different detector hardware, gain levels and with imaging processing for noise suppression. Intensified complementary metal oxide semiconductor cameras using different image intensifier designs (Gen3 and Gen2+) were used to image Cherenkov emission from a tissue phantom in order to measure the modulation transfer function (MTF) and noise power spectrum (NPS) of the systems. These parameters were used to calculate the DQE for varying acquisition settings and image processing steps. MTF curves indicated that the Gen3 system had superior contrast transfer and spatial resolution than the Gen2+ system, with f 10 values of 0.52 mm−1 and 0.31 mm−1, respectively. With median filtering for noise suppression, these values decreased to 0.50 mm−1 and 0.26 mm−1. The maximum NPS values for the Gen3 and Gen2+ systems at high gain were 1.3 × 106 mm2 and 9.1 × 104 mm2 respectively, representing a 14x decrease in noise power for the Gen2+ system. Both systems exhibited increased NPS intensity with increasing gain, while median filtering lowered the NPS. The DQE of each system increased with increasing gain, and at the maximum gain levels the Gen3 system had a low-frequency DQE of 0.31%, while the Gen2+ system had a value of 1.44%. However, at a higher frequency of 0.4 mm−1, these values became 0.54% and 0.03%. Filtering improved DQE for the Gen3 system and reduced DQE for the Gen2+ system and had a mix of detrimental and beneficial qualitative effects by decreasing the spatial resolution and sharpness but also substantially lowering noise. This methodology for DQE measurement allowed for quantitative comparison between Cherenkov imaging cameras and improvements to their sensitivity, and yielded the first formal assessment of Cherenkov image formation efficiency.

Cherenkov light induced from megavolt (MV) X-rays during external beam radiotherapy serves as an internal light source to excite phosphors or fluorophores within biological tissues for molecular imaging. The broad spectrum of Cherenkov light leads to significant spectral overlap with any luminescence emission and, to overcome this problem, a single pixel hyperspectral imaging methodology was demonstrated here by coupling the detection with light sheet scanning and filtered back projection reconstruction of hyperspectral images. Thin scanned sheets of MV X-rays produce Cherenkov light to illuminate the planes deep within the tissue-simulating media. A fluorescence probe was excited by Cherenkov light, and a complete hyperspectral sinogram of the data was obtained through translation and rotation of the beam. Hyperspectral 2D images finally were reconstructed. Through this approach of spectral unmixing, it was possible to resolve hyperspectral images of both the Cherenkov and resulting fluorescence intensity from molecular sensors.

Cherenkov emission induced by external beam radiation therapy from a clinical linear accelerator (LINAC) can be used to excite phosphors deep in biological tissues. As with all luminescence imaging, there is a desire to minimize the spectral overlap between the excitation light and emission wavelengths, here between the Cherenkov and the phosphor. Cherenkov excited short-wavelength infrared (SWIR, 1000 to 1700 nm) fluorescence imaging has been demonstrated for the first time, using long Stokes-shift fluorophore PdSe quantum dots (QD) with nanosecond lifetime and an optimized SWIR detection. The 1/λ2 intensity spectrum characteristic of Cherenkov emission leads to low overlap of this into the fluorescence spectrum of PdSe QDs in the SWIR range. Additionally, using a SWIR camera itself inherently ignores the stronger Cherenkov emission wavelengths dominant across the visible spectrum. The SWIR luminescence was shown to extend the depth sensitivity of Cherenkov imaging, which could be used for applications in radiotherapy sensing and imaging in human tissue with targeted molecular probes.

PURPOSE: To measure surface dose by remote time-gated imaging of plastic scintillators. METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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 time and effort required for surface dosimetry.

Cherenkov-excited luminescence scanned imaging (CELSI) has been proposed for radiation-dose determination in medical physics due to its high spatial-resolution over centimeters of tissue. However, dense line-scanning illumination in typical CELSI is time-cost owing to the mechanical movement of the leaves in multi leaf collimator (MLC), resulting into increased radiation exposure. As a result, a scanningless Cherenkov luminescence imaging modality is herein proposed through structuring epi-illumination with MLC-based Hadamard-patterns, which utilizes a reduced radiation does by limiting illumination patterns, extremely shortening the sampling process. In order to effectively reconstruct unknowns from the resultant underdetermined linear system with sparse samplings, a compressed sensing-based reconstruction methodology with l1-norm regularization is adopted. Numerical and phantom experiments show that the proposed methodology achieves the same image quality as the traditional CELSI does.

Nature photonics 12(3), 150 - 153 (2018). doi:10.1038/s41566-018-0110-y, Ultrafast X-ray imaging on individual fragile specimens such as aerosols1, metastable particles2, superfluid quantum systems3 and live biospecimens4 provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined4,5. Here, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolution so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale., Published by Nature Publ. Group, London [u.a.]

Online acquisition of Cherenkov and portal imaging data was combined with a reconstruction scheme called EC3D, providing a full 3D dosimetry of megavoltage X-ray beams in a water tank. The methodology was demonstrated and quantified in a single static beam. Furthermore, the dynamics and visualization of the 3D dose reconstruction were demonstrated with a volumetric modulated arc therapy (VMAT) plan for TG-119 C-Shape geometry. The developed algorithm combines depth dose information, provided by Cherenkov images, with the lateral dose distribution, provided by the electronic portal imaging device (EPID). The strength of our approach lies in the acquisition of both imaging data-streams with sub-millimeter theoretical resolution at 5 Hz frame-rate, which can be concurrently processed by Fast Fourier Transform-based analysis, thus providing means for an efficient real-time 3D dosimetry.

A tomographic reconstruction algorithm for Cherenkov-excited luminescence scanned imaging (CELSI) is proposed and demonstrated for the first time, to reconstruct distributions of luminescent source. Coupled continuous wave (CW) diffusion equations are used to model luminescent photon propagation in biological tissues. The CELSI reconstruction was achieved by minimizing the difference between measured and computed data based on Tikhonov regularization technique. The feasibility and effectiveness of the algorithm were tested with numerical simulations on noisy data. In addition, comparisons between conventional diffuse optical fluorescence tomography (DOFT) and CELSI were also performed. Contrast-detail analysis was also used to evaluate the imaging performance of CELSI.

This publisher’s note contains corrections to Opt. Lett. 45, 284 (2020)OPLEDP0146-959210.1364/OL.45.000284.

We present the applications of time-resolved spectrometer for soft X-ray (SXR) excited luminescence measurements. We use the spectrometer to monitor the delayed recombination phenomena in the scintillation response of ZnO:Ga nanoparticles, SrHfO3 microcrystalline powder, and rare-earth doped LiCaAlF6 single crystals in an extended time and dynamic range. The nanosecond soft X-ray (E ≈ 0.4 keV) pulse plasma source is used for excitation of a scintillation process. High sensitivity of our experiment is enabled by an intense nanosecond SXR pulse with a very short absorption length (

The observed behavior of short-wave infrared (SWIR) light in tissue, characterized by relatively low scatter and subdiffuse photon transport, has generated considerable interest for the potential of SWIR imaging to produce high-resolution, subsurface images of fluorescence activity in vivo. These properties have important implications for fluorescence-guided surgery and preclinical biomedical research. Until recently, translational efforts have been impeded by the conventional understanding that fluorescence molecular imaging in the SWIR regime requires custom molecular probes that do not yet have proven safety profiles in humans. However, recent studies have shown that two readily available near-infrared (NIR-I) fluorophores produce measurable SWIR fluorescence, implying that other conventional fluorophores produce detectable fluorescence in the SWIR window. Using SWIR spectroscopy and wide-field SWIR imaging with tissue-simulating phantoms, we characterize and compare the SWIR emission properties of eight commercially available red/NIR-I fluorophores commonly used in preclinical and clinical research, in addition to a SWIR-specific fluorophore. All fluorophores produce measurable fluorescence emission in the SWIR, including shorter wavelength dyes such as Alexa Fluor 633 and methylene blue. This study is the first to report SWIR fluorescence from six of the eight conventional fluorophores and establishes an important comparative reference for developing and evaluating SWIR imaging strategies for biomedical applications.

Cherenkov emission induced by external beam radiation from a clinical linear accelerator has been shown in preclinical molecular imaging and clinical imaging. The broad spectrum Cherenkov emission should have a short wavelength infrared (SWIR, 1000-1700 nm) component, as predicted theoretically. To the best of our knowledge, this Letter is the first experimental observation of this SWIR Cherenkov emission induced by external beam radiation. The measured spectrum of SWIR Cherenkov emission matches the theoretical prediction, with a fluence rate near one-third of the visible and near-infrared red emissions (Vis-NIR, 400-900 nm). Imaging in water-based phantoms and biological tissues indicates that there is a sufficient fluence rate for radiotherapy dosimetry applications. The spatial resolution is improved approximately 5.3 times with SWIR Cherenkov emission detection versus Vis-NIR Cherenkov emission, which provides some improvement in the potential for higher resolution Cherenkov emission dosimetry and molecular sensing during clinical radiotherapy by imaging with SWIR wavelengths.

Radiation therapy produces Cherenkov optical emission in tissue, and this light can be utilized to activate molecular probes. The feasibility of sensing luminescence from a tissue molecular oxygen sensor from within a human body phantom was examined using the geometry of the axillary lymph node region. Detection of regions down to 30-mm deep was feasible with submillimeter spatial resolution with the total quantity of the phosphorescent sensor PtG4 near 1 nanomole. Radiation sheet scanning in an epi-illumination geometry provided optimal coverage, and maximum intensity projection images provided illustration of the concept. This work provides the preliminary information needed to attempt this type of imaging in vivo.

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.

Purpose: To investigate the viability of using Cherenkov imaging as a fast and robust method for quality assurance tests in the presence of a magnetic field, where other instruments can be limited. Methods: Water tank measurements were acquired from a clinically utilized adaptive magnetic resonance image guided radiation therapy (MR-IGRT) machine with three multileaf-collimator equipped 60Co sources. Cherenkov imaging used an intensified charge coupled device (ICCD) camera placed 3.5m from the treatment isocenter, looking down the bore of the 0.35T MRI into a water tank. Images were post-processed to make quantitative comparison between Cherenkov light intensity with both film and treatment planning system predictions, in terms of percent depth dose curves as well as lateral beam profile measurements. A TG-119 commissioning test plan (C4: C-Shape) was imaged in real-time at 6.33 frames per second to investigate the temporal and spatial resolution of the Cherenkov imaging technique. Results: A .33mm/pixel Cherenkov image resolution was achieved across 1024×1024 pixels in this setup. Analysis of the Cherenkov image of a 10.5×10.5cm treatment beam in the water tank successfully measured the beam width at the depth of maximum dose within 1.2% of the film measurement at the same point. The percent depth dose curve for the same beam was on average within 2% of ionization chamber measurements for corresponding depths between 3–100mm. Cherenkov video of the TG-119 test plan provided qualitative agreement with the treatment planning system dose predictions, and a novel temporal verification of the treatment. Conclusions: Cherenkov imaging was successfully used to make QA measurements of percent depth dose curves and cross beam profiles of MRI-IGRT radiotherapy machines after only several seconds of beam-on time and data capture; both curves were extracted from the same data set. Video-rate imaging of a dynamic treatment plan provided new information regarding temporal dose deposition. This study has been funded by NIH grants R21EB17559 and R01CA109558, as well as Norris Cotton Cancer Center Pilot funding.

Purpose: To recover a three-dimensional density distribution of luminescent molecular probes located several centimeters deep within a highly scattering tissue. Methods: We developed a novel sheet beam Cherenkov-excited luminescence scanned imaging (CELSI) methodology. The sample was irradiated by a horizontally oriented, vertically scanned 6 MV X-ray sheet beam (200mm × 5mm, 0.2mm vertical step) from a radiotherapy linear accelerator. The resulting Cherenkov light emission – and thus luminescent probe excitation – occurred exclusively along the irradiation plane due to a short diffusion path of secondary particles and Cherenkov photons. Cherenkov-excited luminescence was detected orthogonally to the sheet beam by gated, intensified charge coupled device camera. Analogously to light sheet microscopy, a series of luminescence images was taken for varied axial positions (depths) of the Cherenkov light sheet in sample. Knowledge of the excitation plane position allowed a 3D image stack deconvolution and depth-variant attenuation correction. The 3D image post-processing yielded a true spatial density distribution of luminescent molecules in highly scattering tissue. Results: We recovered a three-dimensional shape and position of 400 µL lesion-mimicking phantom tubes containing 25 µM solution of PtG4 molecular probe from 3 centimeter deep tissue-like media. The high sensitivity of CELSI also allowed resolving 100 micron capillaries of test solution. Functional information of partial oxygen pressure at the site of PtG4 molecular probe was recovered from luminescence lifetime CELSI. Finally, in-vivo sheet beam CELSI localized milimeter-sized PtG4-labelled tumor phantoms in multiple biological objects (hairless mice) from single scan. Conclusion: Presented sheet beam CELSI technique greatly extended the useful depth range of luminescence molecular imaging. More importantly, the light sheet microscopy approach was successfully adapted to CELSI, providing means to recover a completely attenuation-corrected 3D image of luminescent probe distribution. Gated CELSI acquisition yielded functional information of a spatially resolved oxygen concentration map of deep lying targets. This work was supported by NIH research grant R01CA109558 and R21EB017559, as well as by Pilot Grant Funds from the Norris Cotton Cancer Center.

The hybrid semiconductor pixel device Timepix consists of a sensor (e.g. silicon 300 µm thick) bump-bonded to a pixelated ASIC readout chip (256 × 256 square pixels with pitch of 55 µm). In the Time-over-Threshold mode (TOT) the detector enables the direct energy measurement in each pixel. The advantage of noiseless position sensitive detection combined with per pixel spectroscopic capability opens many new applications, which were till now, however, restricted to detection of radiation which is basically above the detector threshold (typically 4 keV). This limitation excludes application of the hybrid technology to highly interesting fields such as plasma diagnostics or X-ray microscopy. In this contribution we demonstrate how the Timepix detector working in TOT mode can be operated as a detector for soft X-ray photons with energy typically 0.5 keV (i.e. for particles which are in principle below the detector threshold). The approach is based on the detection of a larger number of photons incoming in the pixel read-out chain in a time significantly shorter than the shaping time of the pixel electronics. The proposed approach enables a CCD-like operation with many advantages of the hybrid counting technology (high sensitivity, dark-current free operation, enhanced signal-to-noise ratio). Using the proposed approach we demonstrate single-shot soft X-ray imaging with a laser-induced plasma source and the characterization of the source itself.

The hybrid semiconductor pixel detector Timepix operated in the Time-over-Threshold mode (ToT) enables direct energy measurement in each pixel. The advantage of noiseless position sensitive detection combined with per pixel spectroscopic capability opens the way to numerous new applications, which were till now, however, restricted to detection of radiation which is basically above the detector energy threshold (typically 3–4 keV). This limitation excludes application of the hybrid pixel technology to highly interesting fields such as plasma diagnostics or X-ray microscopy. In this contribution we demonstrate how the Timepix detector working in ToT mode can be operated as a detector for particles which are in principle below the detector threshold, namely for soft X-ray photons with energy typically 0.5 keV. The approach is based on the detection of a larger number of photons incoming in the pixel signal processing chain in a time significantly shorter than the shaping time of the pixel electronics, i.e. forming signal pile-up. The proposed approach enables a CCD-like integrating operation with the many advantages of the hybrid counting technology (direct conversion, high sensitivity, dark-current free, room temperature operation, fully digital output and possibility to utilize various read-out architectures). Using the proposed approach we performed single-shot X-ray radiography with a laser-induced plasma source in the spectral region of water window. The same technique was used for the characterization of the source itself.