Automated multi-parameter high-dose-rate brachytherapy quality assurance via radioluminescence imaging.

The purpose of this study is to leverage radioluminescence imaging for the development of an automated high-dose-rate (HDR) brachytherapy quality assurance (QA) system that enables simultaneous measurements of dwell position, dwell time, wire velocity, and relative source strength in a single test. The system consists of a radioluminescence phosphor sheet (a mixture of Gd2O2S:Tb and PDMS) positioned atop a HDR needle applicator, a complementary metal-oxide-semiconductor digital camera used to capture the emitted radioluminescence signals from the scintillator sheet, and an in-house graphical user interface for signal processing. The signal processing was used to extract source intensity, location, and elapsed time, yielding the final measurements on dwell position, dwell time, and wire velocity. The source strength relative to the well chamber calibration (in unit of Air-Kerma strength, Sk ) is measured by establishing a calibration curve that correlates Sk with the detector response. Validation experiments are performed using three customized treatment plans. With these plans, the dwell position and dwell time are verified for a range of 110.0 cm-117.5 cm and 2 s-16 s, respectively, and the linear correlation with Sk is demonstrated for the source strength varying between 28 348 U (cGy cm2 h-1) and 41 906 U. The wire velocity, i.e. the speed of the radioactive source averaged over the distance in between dwell positions, is calculated for various distances ranging from 5 mm to 50 mm. Results show that the mean deviations of the measured dwell position and dwell time are 0.1 mm (range from 0 to 0.2 mm) and 32.5 ms (range from 0 to 60.0 ms) with respect to the planned values, respectively, and the system response is highly linear with Sk ( R2 = 0.998). Moreover, the measured wire velocities are comparable to previously reported values. Benefitting from the compact hardware design and image processing algorithms, the system provides a practical, reliable, and comprehensive solution for HDR QA.

Synergistically Enhancing the Therapeutic Effect of Radiation Therapy with Radiation Activatable and Reactive Oxygen Species-Releasing Nanostructures.

Nanoparticle-based radio-sensitizers can amplify the effects of radiation therapy on tumor tissue even at relatively low concentrations while reducing the potential side effects to healthy surrounding tissues. In this study, we investigated a hybrid anisotropic nanostructure, composed of gold (Au) and titanium dioxide (TiO2), as a radio-sensitizer for radiation therapy of triple-negative breast cancer (TNBC). In contrast to other gold-based radio sensitizers, dumbbell-like Au-TiO2 nanoparticles (DATs) show a synergistic therapeutic effect on radiation therapy, mainly because of strong asymmetric electric coupling between the high atomic number metals and dielectric oxides at their interfaces. The generation of secondary electrons and reactive oxygen species (ROS) from DATs triggered by X-ray irradiation can significantly enhance the radiation effect. After endocytosed by cancer cells, DATs can generate a large amount of ROS under X-ray irradiation, eventually inducing cancer cell apoptosis. Significant tumor growth suppression and overall improvement in survival rate in a TNBC tumor model have been successfully demonstrated under DAT uptake for a radio-sensitized radiation therapy.

Synthesis, Characterization, and Biomedical Applications of a Targeted Dual-Modal Near-Infrared-II Fluorescence and Photoacoustic Imaging Nanoprobe.

Our development of multifunctional dual-modal imaging probes aims to integrate the benefits from both second near-infrared (NIR-II) fluorescence (1000-1700 nm) and photoacoustic imaging with an ultimate goal of improving overall cancer diagnosis efficacy. Herein we designed a donor-acceptor chromophore based nanoparticle (DAP) as a dual-modal image contrast agent has strong absorption in the NIR-I window and a strong fluorescence emission peak in the NIR-II region. The dual-modal DAPs composed of D-π-A-π-D-type chromophores were PEGylated through nanoprecipitation. The multifunctional DAP surface was thus available for subsequent bioconjugation of EGFR Affibody (Ac-Cys-ZEGFR:1907) to target EGFR-positive cancers. The Affibody-conjugated DAPs appeared as highly monodisperse nanoparticles (∼30 nm) with strong absorption in the NIR-I window (at ca. 680 nm) and an extremely high fluorescence in the NIR-II region (maximum peak at 1000 nm). Consequently, the Affibody-DAPs show significantly enhanced photoacoustic and NIR-II fluorescence contrast effects in both in vitro and in vivo experiments. Moreover, the Affibody-DAPs have the capability to selectively target EGFR-positive tumors in an FTC-133 subcutaneous mouse model with relatively high photoacoustic and fluorescent signals. By taking advantage of high spatial resolution and excellent temporal resolution, photoacoustic/NIR-II fluorescence imaging with targeted dual-modal contrast agents allows us to specifically image and detect various cancers and diseases in an accurate manner.

Radiosurgical Treatment Verification Using Removable Megavoltage Radiation Detectors.

Introduction Accurate dose delivery is critical to the success of stereotactic radiosurgery. Unfortunately, verification of the accuracy of treatment delivery remains a challenging problem. Existing radiosurgery delivery paradigms are limited in their ability to verify the accurate delivery of radiation beams using data sampled from the beam after it has traversed the patient. The Zap-X Radiosurgery System (Zap Surgical Systems, San Carlos, CA) addresses this issue by implementing a fully integrated treatment delivery system that utilizes a factory commissioned megavoltage (MV) imager to measure the transmitted beam. The measured intensity is then compared with an expected value in order to confirm that treatment is proceeding as expected. The purpose of this study was to evaluate a prototype system and investigate the accuracy of an attenuation model used in generating the expected transmitted intensity values. Methods A prototype MV imager was used to measure transmitted beam intensities at various exposure levels and through several thicknesses of solid water. The data were used to evaluate imager linearity and model accuracy. Results Experimental results indicate that a quadratic attenuation model is appropriate for predicting beam attenuation and that the imager exhibits excellent dose linearity. Conclusions The MV imager system is shown to be capable of accurately acquiring the data needed to confirm treatment validity.

Flexible radioluminescence imaging for FDG-guided surgery.

PURPOSE: Flexible radioluminescence imaging (Flex-RLI) is an optical method for imaging 18F-fluorodeoxyglucose (FDG)-avid tumors. The authors hypothesize that a gadolinium oxysulfide: terbium (GOS:Tb) flexible scintillator, which loosely conforms to the body contour, can enhance tumor signal-to-background ratio (SBR) compared with RLI, which utilizes a flat scintillator. The purpose of this paper is to characterize flex-RLI with respect to alternative modalities including RLI, beta-RLI (RLI with gamma rejection), and Cerenkov luminescence imaging (CLI). METHODS: The photon sensitivity, spatial resolution, and signal linearity of flex-RLI were characterized with in vitro phantoms. In vivo experiments utilizing 13 nude mice inoculated with the head and neck (UMSCC1-Luc) cell line were then conducted in accordance with the institutional Administrative Panel on Laboratory Animal Care. After intravenous injection of 18F-FDG, the tumor SBR values for flex-RLI were compared to those for RLI, beta-RLI, and CLI using the Wilcoxon signed rank test. RESULTS: With respect to photon sensitivity, RLI, beta-RLI, and flex-RLI produced 1216.2, 407.0, and 98.6 times more radiance per second than CLI. Respective full-width half maximum values across a 0.5 mm capillary tube were 6.9, 6.4, 2.2, and 1.5 mm, respectively. Flex-RLI demonstrated a near perfect correlation with 18F activity (r = 0.99). Signal uniformity for flex-RLI improved after more aggressive homogenization of the GOS powder with the silicone elastomer during formulation. In vivo, the SBR value for flex-RLI (median 1.29; interquartile range 1.18-1.36) was statistically greater than that for RLI (1.08; 1.02-1.14; p < 0.01) by 26%. However, there was no statistically significant difference in SBR values between flex-RLI and beta-RLI (p = 0.92). Furthermore, there was no statistically significant difference in SBR values between flex-RLI and CLI (p = 0.11) in a more limited dataset. CONCLUSIONS: Flex-RLI provides high quality images with SBRs comparable to those from CLI and beta-RLI in a single 10 s acquisition.

Automating quality assurance of digital linear accelerators using a radioluminescent phosphor coated phantom and optical imaging.

Performing mechanical and geometric quality assurance (QA) tests for medical linear accelerators (LINAC) is a predominantly manual process that consumes significant time and resources. In order to alleviate this burden this study proposes a novel strategy to automate the process of performing these tests. The autonomous QA system consists of three parts: (1) a customized phantom coated with radioluminescent material; (2) an optical imaging system capable of visualizing the incidence of the radiation beam, light field or lasers on the phantom; and (3) software to process the captured signals. The radioluminescent phantom, which enables visualization of the radiation beam on the same surface as the light field and lasers, is placed on the couch and imaged while a predefined treatment plan is delivered from the LINAC. The captured images are then processed to self-calibrate the system and perform measurements for evaluating light field/radiation coincidence, jaw position indicators, cross-hair centering, treatment couch position indicators and localizing laser alignment. System accuracy is probed by intentionally introducing errors and by comparing with current clinical methods. The accuracy of self-calibration is evaluated by examining measurement repeatability under fixed and variable phantom setups. The integrated system was able to automatically collect, analyze and report the results for the mechanical alignment tests specified by TG-142. The average difference between introduced and measured errors was 0.13 mm. The system was shown to be consistent with current techniques. Measurement variability increased slightly from 0.1 mm to 0.2 mm when the phantom setup was varied, but no significant difference in the mean measurement value was detected. Total measurement time was less than 10 minutes for all tests as a result of automation. The system's unique features of a phosphor-coated phantom and fully automated, operator independent self-calibration offer the potential to streamline the QA process for modern LINACs.

Monitoring external beam radiotherapy using real-time beam visualization.

PURPOSE: To characterize the performance of a novel radiation therapy monitoring technique that utilizes a flexible scintillating film, common optical detectors, and image processing algorithms for real-time beam visualization (RT-BV). METHODS: Scintillating films were formed by mixing Gd2O2S:Tb (GOS) with silicone and casting the mixture at room temperature. The films were placed in the path of therapeutic beams generated by medical linear accelerators (LINAC). The emitted light was subsequently captured using a CMOS digital camera. Image processing algorithms were used to extract the intensity, shape, and location of the radiation field at various beam energies, dose rates, and collimator locations. The measurement results were compared with known collimator settings to validate the performance of the imaging system. RESULTS: The RT-BV system achieved a sufficient contrast-to-noise ratio to enable real-time monitoring of the LINAC beam at 20 fps with normal ambient lighting in the LINAC room. The RT-BV system successfully identified collimator movements with sub-millimeter resolution. CONCLUSIONS: The RT-BV system is capable of localizing radiation therapy beams with sub-millimeter precision and tracking beam movement at video-rate exposure.