FLASH radiotherapy delivered at ultrahigh dose-rates (UHDR) has shown promise in reducing normal tissue toxicity while maintaining tumor control, which could revolutionize cancer treatment. In this talk, some of the current research aimed towards clinical translation of FLASH and its challenges will be discussed. The history of FLASH radiotherapy from first in vitro experiments to the ongoing clinical trials will be presented. The engineering challenges of UHDR radiation sources and the need for accurate online dose measurements, where optical dosimetry might play an important role, will be discussed. Radiobiological hypotheses responsible for the FLASH effect will be briefly discussed.
Ultra-high dose-rate radiotherapy (FLASH-RT) shows the potential to eliminate tumors while sparing healthy tissues. Current FLASH-RT preclinical animal studies either euthanize animals for histological assessment or use blood tests and cytokine assays to evaluate normal tissue complications. Assessing the progression of complications in situ in live animals with a non-invasive, high-resolution, and sensitive diagnostic method is desired. This study demonstrated using in vivo respiratory-gated micro-computed tomography (micro-CT) to characterize the progression of irradiation-induced pulmonary complications caused by conventional and FLASH-RT in free-breathing mice. Twelve healthy male C57BL/6 mice completed baseline micro-CT scans. Mice were equally separated into three groups that received different treatments targeting the lungs. Treatments administered included no irradiation, 10 MV x-ray FLASH-RT, and 10 MV conventional radiotherapy with a single fraction 15 Gy prescribed dose. Post-treatment, chest cavities of mice were imaged by noninvasive in vivo prospective respiratory-gated micro-CT at 2, 4, 6, 9, and 12 weeks. The image acquisition was triggered using the measured respiratory signal to produce images representing end expiration and peak inspiration. Lung volume and lung CT number were measured for both respiratory phases to evaluate functional residual capacity and tidal volume. Micro-CT images revealed that two mice developed pneumonitis post-treatment after receiving radiotherapy. Here we demonstrated an imaging method to characterize the progression of radiation-induced pulmonary side effects in free-breathing animals.
FLASH-Radiotherapy (FLASH-RT) is an emerging radiotherapy technique delivering ionizing radiation beam at ultrahigh dose rates (UHDR), typically ≥40 Gy/s. Animal studies have demonstrated the safety and efficacy of the technique in killing tumor cells while significantly reducing radiation toxicity in normal tissues, compared to conventional radiotherapy (dose-rate exposure <0.03 Gy/s). A reliable real-time dosimeter system is crucial for the characterization of the so-called ‘FLASH-effect’ and an accurate beam delivery. Standard dosimeters for conventional radiotherapy saturate at this high-intensity field or cannot provide real-time measurements. In previous work, optical fiber inorganic scintillating detectors (ISDs) showed excellent linearity with shutter exposure time and tube current, indicating scintillating signals independent of the dose and dose rate, respectively. This study aims to benchmark the performance of the ISD with plastic scintillating detectors (PSDs) for an ultrahigh dose-rate x-ray beam irradiation. Relative scintillator output, signal linearity with dose and dose rate, signal-to-noise ratio (SNR), signal stability and reliability were evaluated for all detectors. In a UHDR x-ray beam irradiation, the ISDs produced a larger SNR than the PSDs. All detectors showed good linearity with tube current (R2 < 0.975) and shutter exposure (R2 >0.999). Gd2O2S:Tb showed excellent repeatability (coefficient of variation (CV) <0.1%) compared to other detectors, while the PSDs resulted in the highest reliability for a UHDR beam measurement with a CV of <0.1%. A further investigation regarding the positioning uncertainty of the ISDs during irradiation due to the detector’s angular dependency and the optimal design of the scintillator detectors for UHDR applications are required.
Purpose: We present photon-counting computed tomography (PCCT) imaging of contrast agent triplets similar in atomic number (Z) achieved with a high-flux cadmium zinc telluride (CZT) detector.
Approach: The table-top PCCT imaging system included a 330-μm-pitch CZT detector of size 8 mm × 24 mm2 capable of using six energy bins. Four 3D-printed 3-cm-diameter phantoms each contained seven 6-mm-diameter vials with water and low and high concentration solutions of various contrast agents. Lanthanum (Z = 57), gadolinium (Gd) (Z = 64), and lutetium (Z = 71) were imaged together and so were iodine (Z = 53), Gd, and holmium (Z = 67). Each phantom was imaged with 1-mm aluminum-filtered 120-kVp cone beam x rays to produce six energy-binned computed tomography (CT) images.
Results:K-edge images were reconstructed using a weighted sum of six CT images, which distinguished each contrast agent with a root-mean-square error (RMSE) of <0.29 % and 0.51% for the 0.5% and 5% concentrations, respectively. Minimal cross-contamination in each K-edge image was seen, with RMSE values <0.27 % in vials with no contrast.
Conclusion: This is the first preliminary demonstration of simultaneously imaging three similar Z contrast agents with a difference in Z as low as 3.
KEYWORDS: Sensors, Monte Carlo methods, Gadolinium, Zinc, Optical fibers, Animal model studies, Modeling, 3D modeling, Absorption, Polymethylmethacrylate
In the field of radiation therapy, optical fiber dosimeters (OFD) offer several advantages over conventional dosimeters for real-time dosimetry. Their sensing tips can be small in size affording them the potential for high spatial resolution capabilities. In previous work, a novel inorganic scintillating detector (ISD) based on Gadolinium Oxysulfide (gadox) was fabricated for in vivo optical fiber dosimetry of conformal small animal irradiators. The performance of this detector was evaluated for 40 and 80 kVp imaging beams and the 220 kVp therapy beam of the Small Animal Research Platform (SARRP). The purpose of this study was to use a validated Monte Carlo (MC) model of the SARRP to investigate (i) dose absorption in the ISD active volume and (ii) dose perturbation by the inorganic scintillating phosphor volume. A comparison was also drawn between the perturbation by the gadox phosphor and a ZnS-based phosphor. The gadox-based detector was seen to cause high levels of dose perturbation in the radiation field, leaving significant dose shadows in the irradiated media. The use of ZnS:Ag phosphor reduces the perturbations with just over half as much dose absorbed relative to the gadox phosphor. An optimized ISD design which utilizes the higher light yield of the less perturbing ZnS:Ag phosphor to allow for a smaller high-density active volume, and significantly mitigating kV dose perturbation, has been proposed.
The system presented herein consists of a custom 200 kV electron tube with deflection magnets and stationary water-cooled targets for radiotherapy (RT) and imaging. The electron beam is deflected and dwelled along 41 discrete anode locations equally spaced by 1 cm in a line, at equivalent speeds of 1000 cm/s, to create a focused radiotherapy source. The treatment beam is collimated into a triangular polyhedron shape, producing a 4 cm focal spot at the isocenter and corresponding planning-treatment-volume (PTV). This beam shape would allow entry dose to be distributed over large areas for skin sparing. The source is mounted on a ring gantry that rotates at speeds up to 1.5 rpm. Preliminary dose rate measurements were collected in air at 140 kV beam energy, up to 80 mA beam current. Radiographic film was used to collect an image of the treatment beam at isocenter. Results are presented and can be extrapolated to a dose rate of 2 Gy/min for a 140 kV, 200 mA beam. The electron beam can be deflected within 1 ms from therapy path to an additional array of 19 imaging targets, which provides hardware capabilities for real-time tomosynthesis and image-guided RT. Onboard cone beam CT for patient positioning is also available. The utilization of 200 kV beam treatment energies compared to MV greatly reduces the required shielding (4-6 mm lead vs. 1-2 m concrete) and the cost of radiotherapy system installations. Systems can be mounted onto standard mobile trailers for use at remote locations.
Thanks to the current advances in nanoscience, molecular biochemistry, and x-ray detector technology, x-ray fluorescence computed tomography (XFCT) has been considered for molecular imaging of probes containing high atomic number elements, such as gold nanoparticles. The commonly used XFCT imaging performed with K-shell x rays appears to have insufficient imaging sensitivity to detect the low gold concentrations observed in small animal studies. Low energy fluorescence L-shell x rays have exhibited higher signal-to-background ratio and appeared as a promising XFCT mode with greatly enhanced sensitivity. The aim of this work was to experimentally demonstrate the feasibility of L-shell XFCT imaging and to assess its achievable sensitivity. We built an experimental L-shell XFCT imaging system consisting of a miniature x-ray tube and two spectrometers, a silicon drift detector (SDD), and a CdTe detector placed at ±120 deg with respect to the excitation beam. We imaged a 28-mm-diameter water phantom with 4-mm-diameter Eppendorf tubes containing gold solutions with concentrations of 0.06 to 0.1% Au. While all Au vials were detectable in the SDD L-shell XFCT image, none of the vials were visible in the CdTe L-shell XFCT image. The detectability limit of the presented L-shell XFCT SDD imaging setup was 0.007% Au, a concentration observed in small animal studies.
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