Objective.Secondary electron bremsstrahlung (SEB) imaging, along with prompt gamma (PG) and positron emission tomography (PET) imaging, has been proposed as anin vivorange verification tool for proton therapy. This study presents the first simulation based on patient computed tomography (CT) data to investigate the feasibility of SEB imaging for range verification in proton therapy, while comparing the characteristics of SEB imaging with those of PG and PET imaging.Approach.A Monte Carlo simulation was performed using patient CT data for the irradiation of monoenergetic pencil beams and spread-out Bragg peak proton beams. The physical characteristics of SEB imaging were analyzed at three different anatomical sites and compared with those of PG and PET imaging.Main results. In all the treatment cases, SEB imaging exhibited higher production rates than PG and PET imaging, particularly in the regions with high CT values along the beam path. Although the SEB signal was more affected by scattering and absorption than the PET or PG signals, sufficient statistical counts for range verification (∼3 × 10-3SEBs/proton) could potentially be detected outside the patient geometry. For pencil beam cases, the SEB and PET fall-offs were located 4-5 mm proximal to the dose fall-off, while the PG fall-off was located 0-1 mm distal to it.Significance.Results suggest that SEB imaging has the potential to offer a real-time range verification tool (by comparing measured and expected images), particularly for treating shallow-seated tumors using proton pencil-beam scanning delivery. Thus, this study represents a significant step towards the clinical application of range verification based on SEB imaging and promotes future efforts in this direction.

Bremsstrahlung radiation imaging may play an important role in the quantitative evaluation of the spatial-temporal distribution of the β − radioactive emitters in order to optimize and personalize the methodology and dosage of radiopharmaceuticals in radiometabolic therapy. The present work is an attempt to investigates quantitative bremsstrahlung imaging aspects, using a configurable phantom based experimental apparatus with corresponding simulated model, to highlight critical issues and pitfalls, and to identify, whenever possible, directions to overcome, mitigate or likely take advantage of some of them. Procedure for precise phantom activity determination by portable counter, Monte Carlo fine tuning, definition of figures of merit for the choice of optimal image reconstruction parameters, and correction factors for the activity estimation are some of the main explored details to end up with a preliminary quantitative imaging obtained by simulation-measurement comparison.

Geant4 simulation of fast-electron bremsstrahlung imaging at the HL-3 tokamak

Abstract Targeted alpha (α) therapy (TAT) is an emerging therapeutic strategy for cancer treatment. To evaluate the safety and efficacy of targeted α‐therapy, the biodistribution and internal radiation dose of α‐emitting radionuclides should be determined. In vivo imaging of these radionuclides often involves the detection of gamma rays, X‐rays, and positrons generated during their complex decay processes. This review aims to classify the α‐emitting radionuclides (astatine‐211, actinium‐225, radium‐223, bismuth‐212, bismuth‐213, thorium‐227, and terbium‐149) according to their imageable signals. Additionally, this study summarizes various imaging modalities, including gamma camera imaging, single‐photon emission computed tomography, positron emission tomography, Compton imaging, bremsstrahlung imaging, and Cerenkov luminescence imaging, which hold potential for imaging α‐emitting radionuclides, to explore their biomedical applications in qualitative nuclide tracing and diagnosis, quantifying pharmacokinetics, and assessing prognosis and response to therapy.

In imaging of Yttrium-90 patients treated hepatic primary and metastatic cancers, bremsstrahlung photons produced in a wide energy range is used. However, the image quality depends on acquisition energy window. This research aimed energy window optimization for Yttrium-90 bremsstrahlung imaging and 48 patients with various types of cancer received radioembolization therapy were investigated. Patients were imaged using a GE Healthcare Optima NM/CT 640 series gamma camera system with a medium energy general-purpose (MEGP) collimator and planar images were acquired with 8 different energy windows in the 55–400 keV energy range. The data set, formed with the % FOV, contrast, and spatial resolution of image quality parameters calculated from these images, was statistically examined with ANOVA and Tukey tests. According to the visual evaluations and ANOVA/Tukey test results, it was statistically concluded that energy window of 90–110 keV is the optimal energy window while 60–400 keV energy ranges show the lowest image quality for Y-90 bremsstrahlung imaging.

We developed a picosecond photodetector based on our Bridgman-grown and specially engineered cadmium magnesium telluride (Cd <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$_{\mathrm {1-x}}$ </tex-math></inline-formula> MgxTe) single crystal that is sensitive to both optical and X-ray pulses for coarse timing in free-electron laser applications. Cd <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$_{\mathrm {1-x}}$ </tex-math></inline-formula> MgxTe is a widebandgap semiconductor with potential applications, not only in optoelectronics, but also in particle physics as an intense pulse radiation detector for bremsstrahlung, X-ray/gamma-ray radiation, thermal neutrons, and medical imaging. For femtosecond optical and X-ray cross-correlation, the material must have a very short lifetime, a condition that is opposite to that required for nuclear spectroscopy applications. At the same time, the material also needs to have a very low bulk leakage current, in the 10–90 nA range for voltages to even 1000 V. Hence, the ability to tailor or engineer the material is very crucial. Picosecond response and the crystal growth of this specially engineered Cd <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$_{\mathrm {1-x}}$ </tex-math></inline-formula> MgxTe material are presented. Other characterization and transient measurements are discussed along with room-temperature semiconductor detector performance for other nuclear radiation detection applications.

Yttrium-90 (90Y) is an almost pure beta emitter used in Transarterial Radioembolization (TARE). Post-TARE 90Y bremsstrahlung imaging is employed for quantification of the delivered dose. 90Y bremsstrahlung imaging is the most challenging issue in nuclear medicine because of the low photon yield, the continuous and non-pronounced peak of the bremsstrahlung spectrum. GATE Monte Carlo code was employed to find the most proper imaging protocol for 90Y bremsstrahlung imaging. Images were acquired using Medium-Energy Medium-Resolution (MEMR) and High-Energy Medium-Resolution (HEMR) in nine energy windows widths (50 to 500 keV). The quality of images was evaluated using contrast, resolution, sensitivity, Signal-to-Background Ratio (SBR), percentage of total counts in useful field of view, and Contrast-to-Noise Ratio (CNR). The HEMR collimator performed better than the MEMR collimator on all imaging criteria except for the sensitivity. The CNR values were equal in both collimators. Based on the measured parameters, images acquired by the HEMR collimator with the energy window of 50–200 keV are the best protocol for 90Y bremsstrahlung imaging. The findings in this study suggest the imaging protocol for 90Y bremsstrahlung imaging that can be practically used in the clinic.

Transarterial Radioembolization (TARE) with 90Y-loaded glass microspheres is a locoregional treatment option for Hepatocellular Carcinoma (HCC). Post-treatment 90Y bremsstrahlung imaging using Single-Photon Emission Tomography (SPECT) is currently a gold-standard imaging modality for quantifying the delivered dose. However, the nature of bremsstrahlung photons causes difficulty for dose estimation using SPECT imaging. This work aimed to investigate the possibility of using glass microspheres loaded with 90Y and Nanoparticles (NPs) to improve the quantification of delivered doses. The Monte Carlo codes were used to simulate the post-TARE 90Y planar imaging. Planar images from bremsstrahlung photons and characteristic X-rays are acquired when 0, 1.2mol/L, 2.4mol/L, and 4.8mol/L of Gold (Au), Hafnium (Hf), and Gadolinium (Gd) NPs are incorporated into the glass microspheres. We evaluated the quality of acquired images by calculating sensitivity and Signal-to-Background Ratio (SBR). Therapeutic effects of NPs were evaluated by calculation of Dose Enhancement Ratio (DER) in tumoral and non-tumoral liver tissues. The in silico results showed that the sensitivity values of bremsstrahlung and characteristic X-ray planar images increased significantly as the NPs concentration increased in the glass microspheres. The SBR values decreased as the NPs concentration increased for the bremsstrahlung planar images. In contrast, the SBR values increased for the characteristic X-ray planar images when Hf and Gd were incorporated into the glass microspheres. The DER values decreased in the tumoral and non-tumoral liver tissues as the NPs concentration increased. The maximum dose reduction was observed at the NPs concentration of 4.8mol/L (≈7%). The incorporation of Au, Hf, and Gd NPs into the glass microspheres improved the quality and quantity of post-TARE planar images. Also, treatment efficiency was decreased significantly at NPs concentration > 4.8mol/L.

To determine the realized tumor to normal ratios (TNRs) in patients undergoing radiation segmentectomies (RS); determine the relationship between TNRs and particle load in transarterial radioembolization (TARE). In total, 148 patients who underwent 184 TARE procedures for hepatocellular carcinoma were evaluated. Post treatment SPECT CT bremsstrahlung imaging was analyzed utilizing Simplicit90y™ to determine realized TNR. A model which normalized activity across all RS treatments to a level that would achieve 400Gy by unicompartmental dosing was created to determine the affect realized TNR would have on tumor absorbed dose. The mean TNR in the setting of RS was 2.88 ± 1.60 and was higher for glass as compared to resin microspheres (3.07 ± 1.68 vs 2.24 ± 1.21, p = 0.01). The TNR was significantly greater in the RS as compared to the lobar deliveries (2.88 ± 1.60 vs 2.16 ± 1.12, p < 0.01). When normalizing the activity of RS treatments to the level required to achieve 400Gy by unicompartmental calculations, there was found to be significant differences in the predicted tumor absorbed dose when separated by the median tumor dose (601.2 ± 133.3 vs 1146.9 ± 297.5, p < 0.01) or median realized TNR (1119.2 ± 341Gy vs 635.7 ± 160.2Gy, p < 0.01). Particle load was found to be associated with TNR on univariate (p < 0.01) and multivariate (p < 0.01) analysis. Significant TNRs are seen in RS and perhaps argue for the use of multi-compartmental dosimetry techniques in this setting and particle load may affect TNR. •Tumor to normal ratios were significantly higher in radiation segmentectomies than lobar deliveries. •Tumor to normal ratios were significantly higher when utilizing glass, as compared to resin microspheres. •When creating a model that prescribed the activity required to reach 400Gy by MIRD, realized tumor dose varied significantly in radiation segmentectomies.

An estimate of 90Y dosimetry for bremsstrahlung SPECT/CT imaging in liver therapy with 90Y microspheres

Introduction: The quality control parameters of in-house-produced 90Y-Acetate from high-level liquid waste (HLLW) using supported liquid membrane (SLM) technology were validated and compared with the pharmacopeia standard. The radiolabeling of DOTATATE yielding 90Y-DOTATATE in acceptable radiochemical purity (RCP), with expected pharmacological behavior in in vivo models, establish the quality of 90Y-Acetate. Clinical translation of 90Y-Acetate in formulation of 90Y-DOTATATE adds support toward its use as clinical-grade radiochemical. Methods: Quality control parameters of 90Y-Acetate, namely radionuclide purity (RNP), were evaluated using β- spectrometry, γ-spectroscopy, and liquid scintillation counting. RCP and metallic impurities were established using high-performance liquid chromatography and inductively coupled plasma optical emission spectrometry, respectively. The suitability of 90Y-Acetate as an active pharmaceutical ingredient radiochemical was ascertained by radiolabeling with DOTATATE. In vivo biodistribution of 90Y-DOTATATE was carried out in nude mice bearing AR42J xenografted tumor. Clinical efficacy of 90Y-DOTATATE was established after using in patients with large-volume neuroendocrine tumors (NET). Bremsstrahlung imaging was carried out in dual-head gamma camera with a wide energy window setting (100-250 keV). Results: In-house-produced 90Y-Acetate was clear, colorless, and radioactive concentration (RAC) in the range of 40-50 mCi/mL. RCP was >98%. 90Sr content was <0.85 μCi/Ci of 90Y. Gross λ content was <0.8 nCi/Ci of 90Y and no γ peak was observed. Fe3+, Cu2+, Zn2+, Cd2+, and Pb2+ contents were <1.7 μg/Ci. The radiolabeling yield (RLY) of 90Y-DOTATATE was >94%, RCP was >98%. The in vitro stability of 90Y-DOTATATE was up to 72 h postradiolabeling, upon storage at -20°C. Post-therapy (24 h) Bremsstrahlung image of patients with large NET exhibit complete localization of 90Y-DOTATATE in tumor region. Conclusions: This study demonstrates that the in-house-produced 90Y-Acetate from HLLW can be used for the formulation of various therapeutic 90Y-based radiopharmaceuticals. Since 90Y is an imported radiochemical precursor available at a high cost in India, this study which demonstrates the suitability of indigenously sourced 90Y, ideally exemplifies the recovery of "wealth from waste." The Clinical Trial Registration number: (P17/FEB/2019).

Abstract Quiet Sun meterwave emission arises from thermal bremsstrahlung in the MK corona, and can potentially be a rich source of coronal diagnostics. On its way to the observer, it gets modified substantially due to propagation effects—primarily refraction and scattering—through the magnetized and turbulent coronal medium, leading to the redistribution of the intensity in the image plane. By comparing the full-disk meterwave solar maps during a quiet solar period and the modeled thermal bremsstrahlung emission, we characterize these propagation effects. The solar radio maps between 100 MHz and 240 MHz come from the Murchison Widefield Array. The FORWARD package is used to simulate thermal bremsstrahlung images using the self-consistent Magnetohydrodynamic Algorithm outside a Sphere coronal model. The FORWARD model does not include propagation effects. The differences between the observed and modeled maps are interpreted to arise due to scattering and refraction. There is a good general correspondence between the predicted and observed brightness distributions, though significant differences are also observed. We find clear evidence for the presence of significant propagation effects, including anisotropic scattering. The observed radio size of the Sun is 25–30% larger in area. The emission peak corresponding to the only visible active region shifts by 8–11ʹ and its size increases by 35–40%. Our simple models suggest that the fraction of scattered flux density is always larger than a few tens of percent, and varies significantly between different regions. We estimate density inhomogeneities to be in the range 1–10%.

177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) alone has lesser potential in the clinical setting of neuroendocrine tumor (NET) with large bulky disease and nonhomogeneous somatostatin receptors (SSTR) distribution, owing to lower energy (Eβmax 0.497 MeV) and a shorter particle penetration range (maximum 2–4 mm) of 177Lu. In large bulky NETs, 90Yttrium (90Y) has the theoretical advantages because of a longer beta particle penetration range (a maximum soft tissue penetration of 11 mm). Therefore, a combination of 177Lu and 90Y is a theoretically sound concept that can result in better response in metastatic NET with large-bulky lesion and non-homogeneous SSTR distribution. The aim of the study was to determine the feasibility of combining 90Y-DOTATATE with 177Lu-DOTATATE PRRT as sequential duo-PRRT in metastatic NET with (≥5 cm) including the post 90Y-DOTATATE-PRRT imaging and also to determine early toxicity of the duo-PRRT approach. A total of 9 patients received combination of 177Lu-DOTATATE with 90Y-DOTATATE (indigenously prepared and approved) through sequential duo-PRRT approach. These 9 NET patients were included and analyzed in this study. All 9 patients had undergone post-PRRT 90Y-DOTATATE imaging, including a whole-body planar bremsstrahlung imaging followed by regional single-photon emission computed tomography (SPECT)-computed tomography (CT) imaging and also a regional positron emission tomography–computed tomography imaging. Grading of 90Y-DOTATATE and 177Lu-DOTATATE uptake was done on post-PRRT imaging by both modalities. The size of the lesions ranged from 5.5 cm to 16 cm with average size of 10 cm before sequential duo-PRRT was decided. Sequential duo-PRRT was administered because of stable, unresponsive disease following 177Lu-DOTATATE in 5 patients (55.6%), progressive disease after 177Lu-DOTATATE in 2 patients (22.2%), and with neoadjuvant intent in 2 patients (22.2%). The total cumulative dose of 177Lu-DOTATATE before duo-pRRT ranged from 11.84 GBq to 37 GBq per patient and average administered dose of 27.21 GBq per patient in this study. Out of 9 patients, 8 patients received single cycle of 90Y-DOTATATE (ranging from 2.66 GBq to 3.4 GBq per patient with average administered dose of 3.12 GBq per patient). One patient received two cycles of 90Y-DOTATATE (total dose of 6.2 GBq). Out of 9 patients, 8 patients showed excellent tracer concentration in lesions on post-PRRT 90Y-DOTATATE imaging and the remaining 1 patient showed fairly adequate 90Y-DOTATATE tracer uptake in lesion on visual analysis. There was matched 90Y-DOTATATE uptake with 68Ga-DOTATATE and also with 177LuDOTATATE in all 9 patients. The sequential duo-PRRT was well tolerated by all patients. Two patients (22.2%) developed mild nausea, one patient (11.1%) developed transient mild-grade hemoglobin toxicity, and one patient (11.1%) developed mild-grade gastrointestinal symptoms (loose motion and abdominal pain). No nephrotoxicity, hepatotoxicity, and other hematological toxicity was observed. The combination of the indigenous 90Y-DOTATATE with 177Lu-DOTATATE PRRT in NET as sequential duo-PRRT was well tolerated, feasible and safe in stable, unresponsive/progressive disease following single isotope 177Lu-DOTATATE therapy and also in neoadjuvant PRRT setting with large bulky lesion (≥≥5cm). Post-PRRT 90Y-DOTATATE imaging showed excellent 90Y-DOTATATE uptake in nearly all NET patients. Mild-grade early adverse effects were easily manageable and controllable in this sequential duo-PRRT approach.

Collimator and energy window optimization for YTTRIUM-90 bremsstrahlung SPECT imaging

Imaging of the secondary electron bremsstrahlung (SEB) x rays emitted during particle-ion irradiation is a promising method for beam range estimation. However, the SEB x-ray images are not directly correlated to the dose images. In addition, limited spatial resolution of the x-ray camera and low-count situation may impede correctly estimating the beam range and width in SEB x-ray images. To overcome these limitations of the SEB x-ray images measured by the x-ray camera, a deep learning (DL) approach was proposed in this work to predict the dose images for estimating the range and width of the carbon ion beam on the measured SEB x-ray images. To prepare enough data for the DL training efficiently, 10,000 simulated SEB x-ray and dose image pairs were generated by our in-house developed model function for different carbon ion beam energies and doses. The proposed DL neural network consists of two U-nets for SEB x ray to dose image conversion and super resolution. After the network being trained with these simulated x-ray and dose image pairs, the dose images were predicted from simulated and measured SEB x-ray testing images for performance evaluation. For the 500 simulated testing images, the average mean squared error (MSE) was 2.5×10-5 and average structural similarity index (SSIM) was 0.997 while the error of both beam range and width was within 1mm FWHM. For the three measured SEB x-ray images, the MSE was no worse than 5.5×10-3 and SSIM was no worse than 0.980 while the error of the beam range and width was 2mm and 5mm FWHM, respectively. We have demonstrated the advantages of predicting dose images from not only simulated data but also measured data using our deep learning approach.

Introduction: In yttrium-90 imaging, image quality is highly dependent on the selection of energy window and collimator design becausetheY-90 bremsstrahlung photons have a continuous and broad energy distribution. The current study aimed to optimize the bremsstrahlung energy window setting and collimator for the improvement of both resolution and sensitivity. Material and Methods: In the present study, simulation of medical imaging nuclear detectors (SIMIND) Monte Carlo program was used to simulate Siemens Medical System Symbia. The SIMIND was utilized to generate the Y-90 bremsstrahlung single-photon emission computed tomography (SPECT) projection of the point source. Six energy windows settings and two collimators denoting medium energy and high energy were used in order to assess the effect of the energy window on the resolution. Results: The experimental measurements and simulation results showed a similar pattern in the point spread functions with the energy window. The simulation data indicated that the geometric component reached 73%for the energy window within the range of51-120keVusingthe high-energy (HE) collimator. In addition, the obtained results showed that the full width at half maximum (FWHM) and full width at tenth maximum (FWTM)(FWHM=7mm and FWTM=35mm)were higher in this window in comparison to those reported for other windows. Conclusion: According to the obtained results of the present study, the optimal energy window for Y-90 bremsstrahlung SPECT imaging was within the range of 51-120 keV. The obtained optimal energy window and optimal HE collimator had the potential to improve the image resolution and sensitivity of Y-90 SPECT images

Tritium (H-3) is a pure beta-emitting radionuclide and beta particles have extremely low energy (maximum energy: 18.6 keV). Thus the in-vivo imaging of H-3 is thought to be impossible. However, beta particles emit bremsstrahlung X-rays in subjects that may be imaged from outside of the subjects. We tried to image the bremsstrahlung X-rays from H-3 water using a newly developed radiation imaging system. The developed imaging system used a pixelated Ce-doped (Gd, La)2Si2O7 (LaGPS) scintillator plate optically coupled to a flat-panel position-sensitive photomultiplier tube (FP-PMT). Using the imaging system, we conducted bremsstrahlung X-ray imaging from H-3 water in a plastic bag with 37-MBq radioactivity. We obtained tungsten slit mask images with a spatial resolution of ∼3 mm full width at half maximum (FWHM). The energy spectrum of the bremsstrahlung X-rays from the H-3 water showed a broad distribution with an average energy of ∼10 keV. The measured sensitivities of the LaGPS imaging system for bremsstrahlung X-rays from H-3 water in a plastic bag were 1.8 × 10−7. We conclude that the imaging of bremsstrahlung X-rays from H-3 water was really possible and it has a potential to be a new method for the in-vivo H-3 imaging of small animals, plants, or materials.

Abstract No. 557 Overestimation of Y-90 lung shunt fraction by Tc99m-MAA scans: preliminary results

The treatment efficiency of 90Y and providing reliable estimates of activity are evaluated by SPECT imaging of bremsstrahlung radiation released during beta therapy. In this technique, the resulting spectrum from 90Y is very complex and continuous, which creates difficulties on the imaging protocol. Moreover, collimator geometry has an impressive effect on the spatial resolution, system sensitivity, image contrast, and the signal-to-noise ratio (SNR), which should be optimized. We evaluated the effect of energy window width, reconstruction algorithms, and different geometries of a medium-energy (ME) parallel-hole collimator on the image contrast and SNR of 90Y SPECT images. The Siemens E.Cam gamma camera equipped with a ME collimator and a digital Jaszczak phantom were simulated by SIMIND Monte Carlo program to generate the 90Y bremsstrahlung SPECT images. Our results showed that optimal image quality can be acquired by the reconstruction algorithm of OS-EM in the energy window width of 60 to 400 keV for 90Y bremsstrahlung SPECT imaging. Furthermore, the optimal values of the hole diameter and hole length of a ME collimator were obtained 0.235 and 4.4 cm, respectively. The acquired optimal ME collimator and energy window along with using a suitable reconstruction algorithm lead to improved contrast and SNR of 90Y bremsstrahlung images of hot spheres of the digital Jaszczak phantom. This can improve the accuracy and precision of the 90Y activity distribution estimation after radioembolization in targeted radionuclide therapy.

Experiments and modeling of x-ray radiography of millimeter diameter solid Al wires with laser-produced broadband x rays are reported. Experiments were performed using the 50-TW Leopard short-pulse laser in a laser and pulsed power chamber at the Nevada Terawatt Facility. To characterize broadband x rays and demonstrate a radiographic capability, bremsstrahlung, escaping electrons, and radiograph images of Al wires were simultaneously measured. The angularly resolved x-ray spectra are modeled by comparing measured bremsstrahlung signals in the range between 10 and ∼500 keV with hybrid particle-in-cell simulations. Transmission of Al wires from the radiograph images is further simulated with a Monte Carlo code. The measured transmission profiles of Al wires with three different diameters agree with calculations when a simulated x-ray spectrum composed of line emissions and bremsstrahlung is used with a source size of 600 ± 200 μm. Transmission calculations with only 22 keV Ag Kα or an exponential x-ray spectrum do not reproduce the measurement, suggesting that the accurate determination of an x-ray source spectrum, as well as the inclusion of the photon sensitivity of the detector, is critical in transmission calculations to infer the density of an object. The laser-based broadband x-ray radiography that was developed has been successfully implemented in a pulsed power chamber for future laser-pulsed-power coupled experiments.