kVp Beam Research Articles

An Optimized Method for Evaluating the Potential Gd-Nanoparticle Dose Enhancement Produced by Electronic Brachytherapy.

This work reports an optimized method to experimentally quantify the Gd-nanoparticle dose enhancement generated by electronic brachytherapy. The dose enhancement was evaluated considering energy beams of 50 kVp and 70 kVp, determining the Gd-nanoparticle concentration ranges that would optimize the process for each energy. The evaluation was performed using delaminated radiochromic films and a Poly(methyl methacrylate) (PMMA) phantom covered on one side by a thin 2.5 μm Mylar filter acting as an interface between the region with Gd suspension and the radiosensitive film substrate. The results for the 70 kVp beam quality showed dose increments of 6±6%, 22±7%, and 9±7% at different concentrations of 10, 20, and 30 mg/mL, respectively, verifying the competitive mechanisms of enhancement and attenuation. For the 50 kVp beam quality, no increase in dose was recorded for the concentrations studied, indicating that the major contribution to enhancement is from the K-edge interaction. In order to separate the contributions of attenuation and enhancement to the total dose, measurements were replicated with a 12 μm Mylar filter, obtaining a dose enhancement attributable to the K-edge of 29±7% and 34±7% at 20 and 30 mg/mL, respectively, evidencing a significant additional dose proportional to the Gd concentration.

Determination of intrinsic energy dependence of point-like inorganic scintillation detector in brachytherapy.

Inorganic scintillation detectors (ISDs) are promising for in vivo dosimetry in brachytherapy (BT). ISDs have fast response, providing time resolved dose rate information, and high sensitivity, attributed to high atomic numbers. However, the conversion of the detector signal to absorbed dose-to-water is highly dependent on the energy spectrum of the incident radiation. This dependence is comprised of absorbed dose energy dependence, obtainable with Monte Carlo (MC) simulation, and the absorbed dose-to-signal conversion efficiency or intrinsic energy dependence requiring measurements. Studies have indicated negligible intrinsic energy dependence of ZnSe:O-based ISDs in Ir-192 BT. A full characterization has not been performed earlier. This study characterizes the intrinsic energy dependence of ZnSe:O-based ISDs for kV X-ray radiation qualities, with energies relevant for BT. Three point-like ISDs made from fiber-coupled cuboid ZnSe:O-based scintillators were calibrated at the Swedish National Metrology Laboratory for ionizing radiation. The calibration was done in terms of air kerma free-in-air, , in 13 X-ray radiation qualities, , from 25 to 300 kVp (CCRI 25-250kV and ISO 4037 N-series), and in terms of absorbed dose to water, , in a Co-60 beam, . The mean absorbed dose to the ISDs, relative to and , were obtained with the MC code TOPAS (Geant4) using X-ray spectra obtained with SpekPy software and laboratory filtration data and a generic Co-60 source. The intrinsic energy dependence was determined as a function of effective photon energy, , (relative to Co-60). The angular dependence of the ISD signal was measured in a 25 kVp (0.20mm Al HVL) and 135 kVp beam (0.48mm Cu HVL), by rotating the ISDs 180° around the fiber's longitudinal axis (perpendicular to the beam). A full 360° was not performed due to setup limitations. The impact of detector design was quantified with MC simulation. Above 30keV the intrinsic energy dependence varied with less than 5±4% from unity for all detectors (with the uncertainty expressed as the mean of all expanded measurement uncertainties for individual above 30keV, k=2). Below 30keV, it decreased with up to 17% and inter-detector variations of 13% were observed, likely due to differences in detector geometry not captured by the simulations using nominal geometry. In the 25 kVp radiation quality, the ISD signal varied with 24% over a ∼45° rotation. For 135 kVp, the corresponding variation was below 3%. Assuming a 0.05mm thicker layer of reflective paint around the sensitive volume changed the absorbed dose with 6.3% at the lowest , and with less than 2% at higher energies. The study suggests that the ISDs have an intrinsic energy dependence relative to Co-60 lower than 5±4% in radiation qualities with >30keV. Therefore, they could in principle be calibrated in a Co-60 beam quality and transferred to such radiation qualities with correction factors determined only by the absorbed dose energy dependence obtained from MC simulations. This encourages exploration of the ISDs' applications in intensity modulated BT with Yb-169 or other novel intermediate energy isotopes.

Towards Clinical Translation of Microbeam Radiation Therapy (MRT) with a Compact Source

MRT is an innovative concept of spatially fractionated radiation therapy that has demonstrated substantially improved normal tissue tolerance while achieving local tumor control in a wealth of preclinical studies. In MRT a collimator shapes a few micrometers wide planar x-ray beams with a spacing of a few 100 µm. MRT has the potential to improve cancer treatment substantially. However, until now, only a few large 3rd generation synchrotrons provide beam parameters that would allow patient treatments and therefore, MRT has not yet become clinically available. For a clinical translation, compact x-ray sources are required, that produce high dose rate orthovoltage x-rays from a micrometer sized emitter. We developed and built a first prototype of a line focus x-ray tube (LFxT) dedicated to preclinical MRT research. By exploiting the heat capacity limit, the LFxT can deliver dose rates above 100 Gy/s from a just 50 µm-wide focal spot without destroying the rapidly (>200 Hz) rotating x-ray target. A bespoke collimator splits the homogeneous x-ray field into 50 µm wide high-dose peaks separated by 350 µm wide low-dose troughs (valleys). While the prototype in our lab is restricted to a power of 90 kW and 10 Gy/s at 300 kVp, we have started the development of the first clinically usable LFxT-2 at 1.5 MW power and >100 Gy/s at 600 kVp beam quality. We investigated the clinical applicability of the LFxT-2 by performing retrospective treatment planning studies. In particular, we were examining, whether 600 kVp photons would suffice to meet clinical dose constraints in MRT treatments treatment scenarios for first clinical use of MRT. We coupled the open source platform 3D Slicer with an in-house developed dose calculation algorithm for MRT treatment planning. For comparability of spatially fractionated MRT doses with conventional broad beam treatments, the MRT dose was converted to equivalent uniform dose (EUD) and equivalent doses in 2-Gy-fractions (EQD2). The 3D Slicer RT toolkit enabled the dosimetric analysis based on dose volume histograms (DVHs). We installed a preclinical prototype of the LFxT that is currently put into operation and commissioned. Simulations show the feasibility of the next generation LFxT-2 with more than 100 Gy/s peak dose rate. Planned MRT dose distributions with the LFxT-2 meet established radiotherapy dose constraints in many of the investigated clinical cases. However, treatment planning procedures are not yet optimal and require improvement. In a next step, we will build the LFxT-2 and aim for first clinical MRT trials at this source. In order to further improve calculated MRT dose distributions, we will implement inverse treatment planning techniques.

Theoretical comparison and optimization of cadmium telluride and gallium arsenide photon-counting detectors for contrast-enhanced spectral mammography.

Most photon-counting detectors (PCDs) being developed use cadmium telluride (CdTe), which has nonoptimal characteristic x-ray emission with energies in the range used for breast imaging. New PCD using a gallium arsenide (GaAs) has been developed. Since GaAs has characteristic x-rays lower in energy than those of CdTe, it is hypothesized that this new PCD might be beneficial for spectral x-ray breast imaging. We performed simulations using realistic mammography x-ray spectra with both CdTe and GaAs PCDs. Five different experiments were conducted, each comparing the performance of CdTe and GaAs: (1) sensitivity of iodine quantification to charge cloud size and electronic noise, (2) effect of photon spectrum on iodine quantification, (3) effect of varying the number of energy bins, (4) a dose analysis to assess any possible dose reduction from using either detector, and (5) spectral performance of ideal CdTe and GaAs PCDs. For each study, 3 sets of 5000 noise realizations were used to calculate the Cramer-Rao lower bound (CRLB) of iodine quantification. For all spectra studied, GaAs gave a lower CRLB for iodine quantification, with 10 of the 12 spectra showing a statistically significant difference ( ). The photon energy spectrum that optimized iodine detection for both detector materials was the 40 kVp beam with 2-mm Al filtration, which produced CRLBs of and for CdTe and GaAs, respectively, when using five energy bins. GaAs is a promising detector material for contrast-enhanced spectral mammography that offers better spectral performance than CdTe.

In silico analysis of optimum photon energy spectra and beam parameters for iodine nanoparticle–aided orthovoltage radiation therapy of brain tumors

In this study, the effect of photon energy spectra on the dose enhancement factor (DEF) and other influencing parameters such as skull–tumor dose ratios were estimated for a confined tumor loaded with iodine nanoparticles (INPs). A mathematical brain phantom with a brain tumor was simulated by the MCNP6 Monte Carlo code. A validated commercial computed tomography model consisting of an X-ray tube, Al–Cu filters, and collimators was used to simulate the rotational conformal treatment of the tumor. INPs with a diameter of 20 nm and concentrations of 10–50 mg/g were introduced inside the tumor as homogenously distributed spherical particles. The dose distribution inside the phantom was scored for several orthovoltage beams with the peak voltages of 140, 200, and 320 kVp as well as two 3.5 and 6 MV megavoltage beams. A significant rise of DEF values with nanoparticle (NP) concentration for orthovoltage beams is revealed; no significant dose enhancement was obtained for megavoltage beams. The highest DEF and skull–tumor dose ratio were obtained for the 140 kVp beam which decreased with the number of directional fields. The clinically optimal plan for a brain tumor, with high DEFs of 2.81–2.24 and acceptable skull–tumor dose ratios of 0.61–0.51, would be feasible for treatment using 200 and 320 kVp beams, an iodine concentration of 20 mg/g, and 8–15 fields. Our calculations show that clinically significant radiation dose enhancements can be obtained for tumors loaded with INPs using orthovoltage beams. Optimal treatment regimens are feasible using a proper selection of photon beam spectrum and sufficient numbers of cross-firing beams. The limiting effect of skull bone could be minimized by increasing the number of radiation fields and the use of higher quality of orthovoltage beams.

Feasibility and early toxicity of intraoperative radiotherapy for breast cancer using the papillon + system: First results

Background and PurposeBreast intra operative radiation therapy has been evaluated with different systems delivering 20–21 Gy with treatment times around 30 min. Papillon + TM Contact X-ray machine was designed to produce a 50 kVp beam with a high dose rate ≥ 15 Gy/minute. A pilot study with the first prototype was conducted in Nice. Materials and methodsThe inclusion criteria were age ≥ 60 years, unifocal ductal breast adenocarcinoma ≤ 2.5 cm, grade 1–2. Surgical local excision with sentinel node dissection was performed and the applicator was placed in the tumor bed after excision with a prescribed dose of 20 Gy. The main end point of the study was the doses measured with the Gafchromic films; two were located at the skin surface and two in the excision cavity. Secondary endpoints were early toxicity and relapse free survival. ResultsBetween 10/2018 and 09/2019, 26 patients were included. Mean Gafchromic doseswere 18.8 Gy ± 2 Gy at the south pole, 15.6 Gy ± 2.81 Gy at the equator and 2.5 Gy ± 1.67 Gy at the skin. With a median follow-up time of 12 months, no skin or subcutaneous toxicity > grade 2, no local relapse and no metastasis were observed. ConclusionThis is the first phase II study testing the Papillon + tm system for breast IORT with in vivo dosimetry measurements and reassuring clinical data.

Abstract 2598: AZD1390 radio-sensitizes p53-mutant GBM via disrupting homology directed DNA repair

Abstract The ATM inhibitor AZD1390 disrupts cellular responses to ionizing radiation (IR) and is a potent radiosensitizer being tested in clinical trials. Here, we evaluated, the effects of AZD1390 on radiation sensitivity and DNA damage repair pathways in glioblastoma (GBM) cells and patient derived xenografts (PDXs). AZD1390 (30 nM and higher) suppressed IR (5 Gy)-induced phosphorylation of ATM-Serine1981 and downstream phosphorylation sites on Kap1, Chk2 and H2AX in U251 cells and multiple PDXs. Consistent with enhanced DNA damage, AZD1390 increased IR induced G2/M arrest in U251 (80.6% with AZD1390/IR vs. 64.6% with IR, p= 0.01), GBM43 (61.9% vs. 25.7%, p= 0.01) and GBM39 (40.9% vs. 25.4%, p= 0.01). Moreover, in a clonogenic survival assay, AZD1390 sensitized U251 cells to 5 Gy IR (0.24% survival with AZD1390/IR vs. 2.3% with IR alone, p=0.01). In a reporter-based analysis of DNA repair capacity, ATM inhibition resulted in a 40 to 60% reduction in homologous recombination (HR) and modest but significant decrease in micro-homology mediated end joining (MMEJ) and gap fill-in synthesis in U251 cells but had no effect on non-homologous end joining, translesion synthesis, nucleotide or base excision repair pathways. Comparing effects of AZD1390 on repair in GBM14 (TP53-wt) and GBM43 (TP53-mutant), similar results were observed except that decreased MMEJ was seen only in GBM43 (0.03± 0.01% vs. 0.07± 0.01% in control, p=0.002). Intriguingly, RAD51 knockdown (to disrupt HR) sensitized U251 and GBM43 but not GBM14. The efficacy of AZD1390 ± IR was studied in vivo in 10 PDXs. IR was delivered to orthotopic tumors using opposed lateral 225 kVp beams. AZD1390 (20 mg/kg PO) was given just prior to each radiation dose (2 Gy x 5 fractions). AZD1390 monotherapy was mostly ineffective, IR alone was reasonably efficacious with an average 1.8 ± 0.1-fold-increase in survival relative to sham radiation (survival ratio) across all 10 models. IR/AZD1390 treatment resulted in significant survival extension relative to IR alone in 6 of 10 models. Analysis of the survival benefit of combination therapy compared to IR alone across the entire cohort of PDXs was statistically marginal (average survival ratio 2.3± 0.3 vs. 1.8 ± 0.1 with IR, p=0.08). However, when stratified by TP53 status, combination therapy was significantly more effective than IR (mean survival ratio 2.3 ± 0.1 vs. 1.6 ± 0.2 with IR alone, p=0.02) in TP53-mutant PDXs, where all 5 models benefited. In contrast, TP53-wt group had no benefit (mean survival ratio 2.2 ± 0.5 vs. 2.0 ± 0.2, p=0.61), GBM39 was only TP53-wt PDX that benefited from the combination. In conclusion, AZD1390 is an effective radio-sensitizer that causes disruption in HR and potentially other DNA repair pathways. Interestingly, in vivo radiosensitizing effects are mostly restricted to TP53-mutant GBM PDXs. Understandingmechanism of resistance in the context of different TP53 backgrounds remains an important future direction. Citation Format: Shiv K. Gupta, Jiajia Chen, Daniel J. Laverty, Surabhi Talele, Brett L. Carlson, Ann C. Mladek Tuma, Danielle Burgenske, Gaspar J. Kitange, Petra Hamerlik, Zachary D. Nagel, Stephen T. Durant, William F. Elmquist, Jann N. Sarkaria. AZD1390 radio-sensitizes p53-mutant GBM via disrupting homology directed DNA repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2598.

Quality control test of fixed x-ray units at Bir hospital and National trauma center

One of the important goals of the use of X-rays is to diagnose a disease and its extent and minimizing the adverse effect. In diagnostic X-ray, there is an important issue concerning the quality of the image and the exposure of radiation to the patient. Regular practice of quality control in diagnostic X-ray is essential to provide good quality images, decrease hazard to patients, and enhance the appropriate diagnosis. Quality control tests were carried out at six fixed X-ray units at National Academy of Medical Sciences, Bir Hospital and National Trauma Center. Parameters like kVp accuracy, timer accuracy, Reproducibility of kV, time and dose, variable mA and radiation output Linearity with the acceptance limits were checked. Radiation leakage, spatial resolution, contrast resolution and field alignment tests were also carried out. Quality control tests of kVp dose, dose rate, HVL, mAs, beam alignment and leakage radiation shows mixed results. The measured values were within limit in four X-ray units. Until now we do not have any regulations in Nepal on acceptance testing of x-ray units after installation. The need for quality assurance of X-ray needs to be taken to avert detrimental effects to patients and staff. Institutes must introduce a mandatory system for acceptance tests of X-ray when installed and alongside regular quality control programs.

An evaluation of solid state detectors for the relative dosimetry of kilovoltage X-ray beams.

Kilovoltage (kV) X-ray beams are an essential modality in radiotherapy. Solid state detectors are widely available in radiotherapy departments, but their use for kV dosimetry has been limited to date. This study aimed to evaluate the dosimetric performance of a range of solid state detectors for kV dosimetry. Percentage depth doses (PDDs) and relative output factors (ROFs) were measured on an XStrahl 300 unit (XStrahl-Ltd., UK) using 60, 100, 150, and 300 kVp X-ray beams. The fields were defined by circular applicators with field sizes of 2, 5, 8, and 10 cm diameter and square applicators of field sizes 10 × 10 and 20 × 20 cm2 . The following Physikalisch-Technische Werkstätten (PTW) dosimeters were used for measurements: Advanced Markus, PinPoint 3D and Semiflex ionization chambers; photon, electron, and stereotactic radiosurgery (SRS) diodes plus the microDiamond detector. All PDDs were normalized at 5mm depth, and ROFs were measured at 3mm depth to avoid collisions with the end of the applicators. ROFs measured using chambers were corrected for polarity and ion-recombination effects. PDD measurements for 60, 100, and 150 kVp beams exhibited good agreement between all diodes and the ionization chambers over the entire range of depths except in the first few millimeters near the surface. However, for the 300 kVp, all diode detectors exhibited an overresponding behavior compared to reference depth dose data measured with the Advanced Markus chamber. ROFs with the diodes were higher than the Advanced Markus chamber at low energy, and the magnitude of these differences is inversely proportional to the field sizes. The PTW P diode showed the highest variation of up to 15% in the output factor compared to the Advanced Markus chamber. This study evaluated the dosimetric performance of a range of solid state detectors in kV relative dosimetry. This study showed that diode detectors are a suitable replacement for ionization chambers for the PDD measurement of low energy kV beams (60-150 kVp) except for the PDD of 60 kVp with the smaller field sizes. However, an overresponding behavior of diode detectors at 300 kVp beams shows that diode detectors are not suitable for the PDD measurement of high energy kV beams. Generally, all solid state detectors overresponded to ROF measurements, indicating that it is not suitable for ROF measurements. In general, both shielded and unshielded diodes produced a similar dosimetric response, which demonstrates that the energy dependence of solid state detectors should be considered before they are used for any kV relative dosimetric measurements.

Investigation of image quality of MV and kV CBCT with low-Z beams and high DQE detector.

To investigate cone beam computed tomography (CBCT) image quality using novel combinations of kilovoltage (kV) and megavoltage (MV) beams and detectormaterials. MV and kV CBCT imaging was simulated using the Fastcat hybrid Monte Carlo application. CBCT imaging with various beam energies was investigated: 2.5 and 6 MV photon beams generated with carbon, aluminum, and tungsten targets and a 120 kVp x-ray tube beam based off of a Varian Truebeam on-board imager (OBI). Cadmium tungstate (CWO), gadolinium oxysulfide (GOS), and cesium iodide (CsI) detectors with identical pixel pitch of 0.784 mm were evaluated. Modulation transfer functions (MTF) for all detector/beam combinations were calculated. MV and kV CBCT images for each detector/beam combination of a contrast phantom containing inserts with rib and spongiosa bone, lung, and adipose tissues were simulated with an imaging dose of 7 mGy. Contrast to noise ratio (CNR) of all inserts were compared for all detector/beam combinations. CBCT images of an anthropomorphic head phantom with silver amalgam fillings were also generated. The CWO/120 kVp beam combination resulted in the highest MTF at low frequencies and the CsI detector showed the highest MTF for all other beams and at high frequencies. The CWO/120 kVp beam combination showed the highest CNR for all tissues. The unoptimized CWO/2.5 MV carbon target beam showed the highest CNR of the MV beam/detector combinations with CNR 4% and 17% worse than the optimized Truebeam CsI 120 kVp setup with a bowtie filter and antiscatter grid. Additionally, the CWO 2.5 MV setup showed qualitative reduction of metal artifacts surrounding silver amalgam fillings in an anthropomorphic headphantom. This finding makes a compelling case that further optimization of this CWO carbon target setup could produce CBCT images with similar CNR to current OBI CBCT for equivalent dose with added resilience to metalartifacts.

Dose calculations for preclinical radiobiology experiments conducted with single-field cabinet irradiators.

To provide percentage depth dose (PDD) data along the central axis for dosimetry calculations in small-animal radiation biology experiments performed in cabinet irradiators. The PDDs are provided as a function of source-to-surface distance (SSD), field size, and animal size. The X-ray tube designs for four biological cabinet irradiators, the RS2000, RT250, MultiRad350, and XRAD320, were simulated using the BEAMnrc Monte Carlo code to generate 160, 200, 250, and 320kVp photon beams, respectively. The 320kVp beam was simulated with two filtrations: a soft F1 aluminium filter and a hard F2 thoraeus filter made of aluminium, tin, and copper. Beams were collimated into circular fields with diameters of 0.5-10cm at SSDs of 10-60cm. Monte Carlo dose calculations in 1-5-cm diameter homogeneous (soft tissue) small-animal phantoms as well as in heterogeneous phantoms with 3-mm diameter cylindrical lung and bone inserts (rib and cortical bone) were performed using DOSXYZnrc. The calculated depth doses in three test-cases were estimated by applying SSD, field size, and animal size correction factors to a reference case (40-cm SSD, 1-cm field, and 5-cm animal size), and these results were compared with the specifically simulated (i.e., expected) doses to assess the accuracy of this method. Dosimetry for two test-case scenarios of 160 and 250 kVp beams (representative of end-user beam qualities) was also performed, whereby the simulated PDDs at two different depths were compared with the results based on the interpolation from reference data. The depth doses for three test-cases calculated at 200, 320kVp F1, and 320kVp F2 with half value layers (HVLs) ranging from ∼0.6to 3.6mm Cu, agreed well with the expected doses, yielding dose differences of 1.2%, 0.1%, and 1.0%, respectively. The two end-user test-cases for 160 and 250 kVp beams with respective HVLs of ∼0.8 and 1.8mm Cu yielded dose differences of 1.4% and 3.2% between the simulated and the interpolated PDDs. The dose increase at the bone-tissue proximal interface ranged from 1.2 to 2.5 times the dose in soft tissue for rib and 1.3 to 3.7 times for cortical bone. The dose drop-off at 1-cm depth beyond the bone ranged from 1.3% to 6.0% for rib and 3.2% to 11.7% for cortical bone. No drastic dose perturbations occurred in the presence of lung, with lung-tissue interface dose of>99% of soft tissue dose and<3% dose increase at 1-cm depth beyond lung. The developed dose estimation method can be used to translate the measured dose at a point to dose at any depth in small-animal phantoms, making it feasible for preclinical calculation of dose distributions in animals irradiated with cabinet-style irradiators. The dosimetric impact of bone must be accurately quantified as dramatic dose perturbations at and beyond the bone interfaces can occur due to the relative importance of the photoelectric effect at kilovoltage energies. These results will help improve dosimetric accuracy in preclinical experiments.

Bomb Model of Radiosensitization by Metallic Nanoparticles

Metallic nanoparticles (NPs) have been shown to be effective in enhancing radiotherapy through photoelectric effect due to the large photoelectric interaction cross-sections of high atomic number atoms. Experiments, however, demonstrated a strong radiosensitizing effect of Gold and Gadoliniums NPs in vivo that is beyond the calculated macroscopic dose enhancement, and even beyond the microdosimetric properties of the Auger electrons following a photoelectric interaction. We propose to describe NPs in cells as a bomb to kill the cell at a probability during a photoelectric event, depending on biological properties of the cell.The biological damage caused by NPs may be categorized into local and non-local. The non-local part corresponds approximately to the macroscopic dose enhancement. Based on the reported in vivo NP concentration, the calculated contribution of this part is negligibly small, especially for MV beams. The local part of the damage is caused by the electron cascade near the NP surface following a photoelectric interaction. We model this effect as a bomb, which gives an upper limit of cell killing for a known NP concentration inside a cell or cell nucleus. We performed a Monte Carlo simulation of irradiating a Gd-based NP with a 250 kVp beam and a 6 MV FFF beam, and calculated the photoelectric interaction probability of GdNP per gray of dose to surrounding medium (water) and the distribution of the number of Auger cascade electrons generated per ionization. The increase in α of the Linear-Quadratic survival model can be calculated using the following equation for the mean number of lethal lesions due to local damage: Nlocal = Nionization·p = NNp·p1Gy·D·p = Δα·D where Δα = NNp·p1Gy·p, Nionization is the total number of NP ionizations that occur in the target (e.g., the nucleus), p is the probability of killing which is set to a value ≤1 when the number of electrons generated per ionization is > 1, and 0 otherwise, NNP is the average number of NPs in the target, D is the dose to the surrounding water due to the X-rays without NPs, and p1Gy is the probability of ionizing an NP when D is 1 Gy.Based on reported in vivo GdNP concentrations of ∼5.5 ppm, for 250 kVp X-rays, the upper limit on the increase in α will be 0.0008 Gy-1 for a 100 μm3 effective DNA volume. If the entire cell of a typical volume of 1000 μm3 is taken to be the target, the upper limit on the increase in α will be 0.008 Gy-1 and 9e-6 Gy-1, respectively for a typical 250kVp beam and a 6MV FFF beam. Radiosensitization may be predicted based on the NP concentrations in cells and the cell properties.The NP radiosensitization effect, which cannot be accounted for by macroscopic dose enhancement alone and has been failed to be described by many other microdosimetry studies, could be potentially described using a bomb model of NP. One of the consequences of this model is that the β does not change due to the presence of NP, which fits most experimental observations.

Experimental validation of Fastcat kV and MV cone beam CT (CBCT) simulator.

To experimentally validate the Fastcat cone beam computed tomography (CBCT) simulator against kV and MV CBCT images acquired with a Varian Truebeamlinac. kV and MV CBCT images of a Catphan 504 phantom were acquired using a 100 kVp beam with the on-board imager (OBI) and a 6 MV treatment beam with the electronic portal imaging device (EPID), respectively. The kV Fastcat simulation was performed using detailed models of the x-ray source, bowtie filter, a high resolution voxelized virtual Catphan phantom, anti-scatter grid, and the CsI scintillating detector. Likewise, an MV Fastcat CBCT was simulated with detailed models for the beam energy spectrum, flattening filter, a high-resolution voxelized virtual Catphan phantom, and the gadolinium oxysulfide (GOS) scintillating detector. Experimental and simulated CBCT images of the phantom were compared with respect to HU values, contrast to noise ratio (CNR), and dose linearity. Detector modulation transfer function (MTF) for the two detectors were also experimentally validated. Fastcat's dose calculations were compared to Monte Carlo (MC) dose calculations performed with Topas. For the kV and MV simulations, respectively: Contrast agreed within 14 and 9 HUs and detector MTF agreed within 4.2% and 2.5%. Likewise, CNR had a root mean squared error (RMSE) of 2.6% and 1.4%. Dose agreed within 2.4% and 1.6% of MC values. The kV and MV CBCT images took 71 and 72 s to simulate in Fastcat with 887 and 493 projections, respectively. We present a multienergy experimental validation of a fast and accurate CBCT simulator against a commercial linac. The simulator is open source and all models found in this work can be downloaded from https://github.com/jerichooconnell/fastcat.git.

Characterization of an x-ray tube-based ultrahigh dose-rate system for in vitro irradiations.

To present an x-ray tube system capable of in vitro ultrahigh dose-rate (UHDR) irradiation of small<0.3mm samples and to characterize it by means of a plastic scintillation detector (PSD). A conventional x-ray tube was modified for the delivery of short UHDR irradiations. A beam shutter system with a sample holder was designed and installed in a close proximity of an x-ray tube window to enable<1 s irradiations at UHDR. The dosimetry was performed with a small 0.5-mm long 0.5-mm in diameter PSD irradiated with 80, 100, and 120 kVp beams and beam currents of 1-37.5mA. The PSD signal was recorded at frame rates of 20 and 50 fps for shutter exposure between 100 and 1125ms. Irradiation reproducibility was studied with the PSD. The x-ray tube irradiation setup was modeled with Monte Carlo (MC) and dose on a surface of a phantom was also measured with films. The effect of dose delivery uncertainty to 300-μm spheroids due to positioning and spheroid size was evaluated. MC simulations showed good agreement with PSD measurements acquired at both frame rates of 20 and 50 fps in terms of beam temporal profile. PSD-measured dose exhibited excellent linearity as a function of instantaneous dose rate from 3.1 to 118.0Gy/s as well as shutter exposure time from 100 and 1125ms for all investigated beam energies. PSD absorbed dose for the 80, 100, and 120 kVp beams agreed with MC simulations to within 5%. The total delivered doses ranged from 0.4Gy for a 1-mA, 80 kVp beam, and 100ms shutter exposure to 166.9Gy for a 37.5-mA, 80 kVp beam, and a 1125ms exposure. PSD irradiation reproducibility was<0.5%. Simulated and measured dose fall off agreed and it was steep along the axis of the shutter slit (1%/0.1mm) and with depth (2%/0.1mm at 1-mm depth). Spheroid positioning uncertainty of 300μm resulted in dose difference of<3% for x and y shifts but up to 7% uncertainty for a z-shift parallel to the beam axis. A 16% difference in spheroid size resulted in<5% dose difference in spheroid absorbed dose. We have presented a cost-effective x-ray tube-based system with a beam shutter designed for in vitro UHDR delivery and reaching dose rates of up to 118.0Gy/s. The described shutter system can be easily implemented at other institutions, which might enable new researchers to investigate the radiobiology of UHDR irradiations in vitro.

Method to measure the size of a radiographic field larger than a detector by imaging fluorescence X‐rays with a slit camera

PurposeX‐ray imaging devices contain a collimator system that defines a rectangular irradiation field on the detector plane. The size and position of the X‐ray field, and its congruence with the corresponding light field, must be regularly tested for quality control. We propose a new method to estimate how far the x‐ray field extends beyond the detector which does not require the use of external detectors.MethodsA metallic foil is inserted perpendicularly between the source and the detector. A slit camera, a linear extension of a pinhole camera, is used to project onto the detector the fluorescence X‐rays emitted by the irradiated foil. The location where the fluorescence signal inside the camera vanishes is used to extrapolate the location of the field boundary. Monte Carlo simulations were performed to determine the optimal composition and thickness of the foil. A prototype camera with a 1‐mm‐wide slit was built and tested in a clinical mammography and digital breast tomosynthesis (DBT) system.ResultsThe simulations estimated that a foil made of 25 µm of Molybdenum provided the maximum signal inside the camera for a 39 kVp beam. The boundary of the X‐ray fields in mammography and DBT views were experimentally measured. With the camera along the chest wall side, the measured field in multiple DBT views had a variability of only 0.4 ± 0.1 mm compared to mammography. A difference in the measured boundary position of 2.4 and –1.0 mm was observed when comparing to measurements with a fluorescent ruler and self‐developing film.ConclusionThe introduced technique provides a practical alternative method to detect the boundary of an X‐ray field. The method can be combined with other testing methods to assess the congruence of the X‐rays and light fields, and to determine if the X‐ray field extends beyond the detector more than permitted.

Development and characterization of an LED-based detector for dosimetry in diagnostic radiology

Light-emitting diodes (LEDs) could be a potential dosimetry candidate because they are radiation hard, spectrally selective, direct band gap, and low-cost devices. Thus, an LED-based detector prototype was designed and characterized for dosimetry. A 20 × 20 cm2 array of surface mount device LED chips was sandwiched in photovoltaic mode between two intensifying screens to form a dosimetric system. The system was enclosed in a light-tight air cavity using black vinyl tape. The screens converted diagnostic x-ray beams into fluorescent blue light. LEDs, applied in detector mode, converted the fluorescent light into radiation-induced currents. A digital multimeter converted the analog currents into digital voltage signals. Prototype characterization was executed using (a) IEC 61267’s RQR 7 (90 kVp) and RQR 8 (100 kVp) beam qualities, and (b) low (25 mAs) and high (80 mAs) beam quantities. A standard dosimeter probe was simultaneously exposed with the prototype to measure the prototype’s absorbed dose. In all exposures, the x-ray beams were perpendicularly incident on both the dosimeter and prototype, at a fixed source to detector distance-60 cm. The LED array prototype’s minimum detectable dose was 0.139 mGy, and the maximum dose implemented herein was ∼13 mGy. The prototype was 99.18% and 98.64% linearly sensitive to absorbed dose and tube current–time product (mAs), respectively. The system was ±4.69% energy, ±6.8% dose, and ±7.7% dose rate dependent. Two prototype data sets were 89.93% repeatable. We fabricated an ultrathin (5 mm), lightweight (130 g), and a relatively low-cost LED-based dosimetric prototype. The prototype executed a simple, efficient, and accurate real-time dosimetric mechanism. It could thus be an alternative to the current passive dosimetric systems.

Monte Carlo determination of a nanoDot OSLD response using quality index for diagnostic kilovoltage X-ray beams.

This study aims to investigate the energy response of an optically stimulated luminescent dosimeter known as nanoDot for diagnostic kilovoltage X-ray beams via Monte Carlo calculations. The nanoDot response is calculated as a function of X-ray beam quality in free air and on a water phantom surface using Monte Carlo simulations. The X-ray fluence spectra are classified using the quality index (QI), which is defined as the ratio of the effective energy to the maximum energy of the photons. The response is calculated for X-ray fluence spectra with QIs of 0.4, 0.5, and 0.6 with tube voltages of 50-137.6kVp and monoenergetic photon beams. The surface dose estimated using the calculated response is verified by comparing it with that measured using an ionization chamber. The nanoDot response in free air for monoenergetic photon beams (QI=1.0) varies significantly at photon energies below 100keV and reaches a factor of 3.6 at 25-30keV. The response differs by up to approximately 6% between QIs of 0.4 and 0.6 for the same half-value layer (HVL). The response at the phantom surface decreases slightly owing to the backscatter effect, and it is almost independent of the field size. The agreement between the surface dose estimated using the nanoDot and that measured using the ionization chamber for assessing X-ray beam qualities is less than 2%. The nanoDot response is indicated as a function of HVL for the specified QIs, and it enables the direct surface dose measurement.

Impact of bowtie filter and detector collimation on multislice CT scatter profiles: A simulation study

To investigate via Monte Carlo simulations, the impact of scan subject size, antiscatter grid (ASG), collimator size, and bowtie filter on the distribution of scatter radiation in a typical realistically modeled third generation 16 slice diagnostic computed tomography (CT) scanner. Full radiation transport was simulated with Geant4 in a realistic CT scanner geometric model, including the imaging phantom, bowtie filter (BTF), collimators and detector assembly, except for the ASGs. An analytical method was employed to quantify the probable transmission through the ASG of each photon intersecting the detector array. Normalized scatter profiles (NSP) and scatter-to-primary-ratio (SPR) profiles were simulated for 90 and 140kVp beams for different size phantoms and slice thicknesses. The impact of CT scatter on the reconstructed attenuation coefficient factor was also studied as were the modulating effects of phantom- and patient-tissue heterogeneities on scatter profiles. A method to characterize the relative spatial frequency content of sinogram signals was developed to assess the latter. For the 21.4-cm diameter phantom, NSP and SPR increase linearly with collimator opening for both tube potentials, with the 90kVp scan exhibiting slightly larger NSP and SPR. The BTF modestly modulates scatter under the phantom center, reducing the prominent off-axis lobes by factors of 1.1-1.3. The ASG reduces scatter on the central axis NSP threefold, and reduces scatter at the detectors outside the phantom shadow by factors of 25 to 500. For the phantoms with diameters of 27 and 32cm, the scatter increases roughly three- and fourfold, respectively, demonstrating that scatter monotonically increases with phantom size, despite deployment of the ASG and BTF. In the absence of a scan subject, the ASG reduces the signal profile arising photons scattered by the BTF. Without ASG, the in-air scatter profile is relatively flat compared to the scatter profile when the ASG is present. For both 90 and 140 kVp photon spectra, the calculated attenuation coefficient decreases linearly with increasing collimation size. For both homogeneous and heterogeneous objects, NSPs are dominated by low spatial frequency content compared to the primary signal. However, the SPR, which quantifies the local magnitude of nonlinear detector response and is dominated by the high frequency content of the primary profile, can contribute strongly to high-spatial frequency streaking artifacts near high-density structures in reconstructed image artifacts. Public-domain Monte Carlo codes, Geant-4 in particular, is a feasible method for characterizing CT detector response to scattered- and off-focal radiation. Our study demonstrates that the ASG substantially reduces the scatter radiation and reshapes scatter-radiation profiles and affects the accuracy with which the detector array can measure narrow-beam attenuation due its inability to distinguish between true uncollided primary and narrow-angle coherently scattered photons. Hence, incorporating the impact of detector array collimation into the forward-projection signal formation models used by iterative reconstruction algorithms is necessary to use CT for accurately characterizing material properties. While tissue heterogeneities exercise a modest influence on local NPS shape and magnitude, they do not add significant high spatial frequency content.

Monte Carlo simulations of EBT3 film dose deposition for percentage depth dose (PDD) curve evaluation.

PurposeTo use Monte Carlo (MC) calculations to evaluate the effects of Gafchromic EBT3 film orientation on percentage depth dose (PDD) curves.MethodsDose deposition in films placed in a water phantom, and oriented either parallel or perpendicular with respect to beam axis, were simulated with MC and compared to PDDs scored in a homogenous water phantom. The effects of introducing 0.01–1.00 mm air gaps on each side of the film as well as a small 1°‐3° tilt for film placed in parallel orientation were studied. PDDs scored based on two published EBT3 film compositions were compared. Three photon beam energies of 120 kVp, 220 kVp, and 6 MV and three field sizes between 1 × 1 and 5 × 5 cm2 were considered. Experimental PDDs for a 6‐MV 3 × 3 cm2 beam were acquired.ResultsPDD curves for films in perpendicular orientation more closely agreed to water PDDs than films placed in parallel orientation. The maximum difference between film and water PDD for films in parallel orientation was −12.9% for the 220 kVp beam. For the perpendicular film orientation, the maximum difference decreased to 5.7% for the 120 kVp beam. The inclusion of an air gap had the largest effect on the 6‐MV 1 × 1 cm2 beam, for which the dose in the buildup region was underestimated by 21.2% compared to the simulation with no air gap. A 2° film tilt decreased the difference between the parallel film and homogeneous water phantom PDDs from −5.0% to −0.5% for the 6 MV 3 × 3 cm2 beam. The “newer” EBT3 film composition resulted in larger PDD discrepancies than the previous composition. Experimental film data qualitatively agreed with MC simulations.ConclusionsPDD measurements with films should either be performed with film in perpendicular orientation to the beam axis or in parallel orientation with a ~ 2º tilt and no air gaps.

Dose simulations of an early 20th century kilovoltage pneumonia radiotherapy technique performed with a modern fluoroscope

To simulate an early 20th century viral pneumonia radiotherapy treatment using modern fluoroscopy and evaluated it according to current dose guidelines. Monte Carlo was used to assess the dose distribution on an anthropomorphic phantom. Critical organs were: skin, breasts, esophagus, ribs, vertebrae, heart, thymus, and spinal cord. A 100 kVp beam with 3 mm Al HVL, 25 × 25 cm2 posterior-anterior (PA) field and 50 cm source-to-surface distance were simulated. Simulations had a resolution of 0.4 × 0.4 × 0.06 cm3 and a 6% uncertainty. Hundred percent dose was normalized to the skin surface and results were displayed in axial, coronal, and sagittal planes. Dose volume histograms were generated in MATLAB for further analysis. Prescription doses of 0.3, 0.5, and 1.0 Gy were applied to the 15% isodose for organ-dose comparison to current tolerances and potential risk of detriment. Ninety-five and ninety-seven percent of the right and left lung volumes, respectively, were well-covered by the 15% isodose line. For the 0.3, 0.5, and 1.0 Gy prescriptions, the maximum skin doses were 2.9, 4.8, and 9.6 Gy compared to a 2.0 Gy transient erythema dose threshold; left/right lung maximum doses were 1.44/1.46, 2.4/2.4, and 4.8/4.9 Gy compared to a 6.5 Gy pneumonitis and 30 Gy fibrosis thresholds; maximum heart doses were 0.5, 0.9, and 1.8 Gy compared to the 0.5 Gy ICRP-recommendation; maximum spinal cord doses were 1.4, 2.3, and 4.6 Gy compared to 7.0 Gy single fraction dose threshold. Maximum doses to other critical organs were below modern dose thresholds. A 100 kVp PA field could deliver a 0.3 Gy or 0.5 Gy dose without risk of complications. However, a 1.0 Gy dose treatment could be problematic. Critical organ doses could be further reduced if more than one treatment field is used.