The present study aimed to investigate the dosimetric impact of metal stent for photon and proton treatment plans in hepatocellular carcinoma.With computed tomography data of a water-equivalent solid phantom, dose perturbation caused by a metal stent included in the photon and proton treatment of hepatocellular carcinoma was evaluated by comparing Eclipse and RayStation treatment planning system (TPS) to a Monte Carlo (MC) based dose calculator. Photon and proton plans were created with anterior–posterior/posterior-anterior (AP/PA) fields using a 6 MV beam and AP/PA fields of a wobbling beam using 150 MeV and a 10 cm ridge filter. The difference in dose distributions and dosimetric parameters were compared depending on the stent's positions (the bile duct (GB) and intestinal tract (GI)) and angles . Additionally, the dose variation in the target volume including the stent was comparatively evaluated through dose volume histogram (DVH) analysis. And the comparison of clinical cases was carried out in the same way.min), which was observed in both photon and proton plans in the GB and GI stents deployed at a 90° incidence angle. The parameter differences were greater in the proton plan than in photon plan. The target volume showed various dose variations depending on positions and angles of stent for both beams. Compared with no-stent, the doses within the target volume containing the GI and GB stents for the photon beam were overestimated in the high-dose area at 0°, nearly equal within 1% at 45°, and underestimated at 90°. These doses to the proton beam were underestimated at all angles, and the amount of underdose to the target volume increased with an increase in the stent angle. However, the difference was significantly greater with the proton plan than the photon plan.Percentage differences in the dosimetric parameters calculated by MC ranged from − 7.0 to 3.9% for the photon plan and − 33.7 to 4.3% for the proton plan, depending on the angle at which the GB and GI stents were placed, compared to those without the stent. The maximum difference was observed at the minimum dose (DDose perturbations within the target volume due to the presence of the metal stent were not observed in the TPS calculations for photon and proton beams, but MC was used to confirm that there are dose variations within the target volume. The MC results found that delivery of the treatment beam avoiding the stent was the best method to prevent target volume underdose. Hepatocellular carcinoma (HCC), a malignant tumour of the liver, is one of the most difficult cancers to detect and has a poor prognosis. Depending on the patient's condition, it is treated with surgical resection, radiofrequency ablation, transarterial chemoembolization (TACE), and radiotherapy (RT) –3. Among3; however, the thickness of the stent used in clinic is 0.16 mm, which is relatively small, resulting in image artefacts such as blurring [HCC patients are treated with VMAT or PBT, depending on the particular case . Few of blurring . In addiblurring , 12, 15.This study aimed to understand the volumetric effect of dose perturbations induced during RT using photon and proton beams, by metal stents used in HCC patients. The dose coverage of the target volume was evaluated at the location of the stent (GB and GI stents) according to different beam incident directions , and the effect of dose perturbation by the stent was evaluated in clinical practice.3. Two types of stents were used to determine the effect of the stent size: one in the bile duct (the GB stent) and another in the gastrointestinal tract (the GI stent). The diameter of the metal wire constituting the metal stent was 0.16 mm; when constructed in cross-section, the stent consisted of 28 wires for the bile duct and 36 wires for the gastrointestinal tract. The material composition was the same for the bile duct and gastrointestinal tract, and the diameter of each stent was between 1 and 2 cm when not inserted into the body.In this study, dose perturbation caused by metal stents was evaluated using MC simulations and TPSs for photon and proton beams. For the evaluation of dose calculation with TPS, CT data were obtained for 1.25 mm thick slices in a water-equivalent solid phantom containing a metal stent. Subsequently, MC simulations were performed to evaluate the dose perturbation due to the metal stent in three dimensions . Geant4 A Truebeam  linear accelerator and a proton therapy system (Sumitomo Heavy Industries Ltd.) were used to study the dose difference caused by metal stents in a photon beam and proton beam, respectively. The virtual machine system completed in previous studies –19 was uFigure 3. The physics list library for the calculation of the photon and proton beams used the QuarkGluonStrongG4Precompound-BInaryCascade-HighPrecision neutron-ElectroMagnetic opt Z (QGSP-BIC-HP-EMZ) reference physics list [The range cut value of the water phantom was 0.01 mm with respect to the size of the wire, and the dose value calculated by the DoseActor function was reconstructed into a voxel size of 1 mmics list .The calculated results were sent to a system that had been programmed to be converted into a digital imaging and communications in medicine (DICOM) format compatible with the TPS. Because the digital value in the uncorrected simulation required a tool for analysis, we set the configuration to import the frame ID value into the TPS and performed the dose analysis using the TPS function. The output values calculated in the MC simulation were compared and analysed as relative values. For evaluation, a contour was made for dose analysis by expanding 5 mm, based on the metal stent.max), minimum dose (Dmin), mean dose (Dmean), and dose of 1% volume (D1%) for target volume were evaluated to investigate the effect in the coverage of target volume due to the metal stent. In addition, the difference in dose volume histograms (DVHs) were compared according to the type of the metal stent for the photon and proton beams.For AP/PA field technique, VMAT, and double scattering plans, dosimetric parameters such as the maximum dose  and GI stent (0.7%). The differences in the dosimetric parameters (compared to not using the stent) were large for both the GB stent and the GI stent located at 90°.The differences in dosimetric parameters on photon and proton plans calculated using TPS and MC simulation for GI and GB stents according to the incident beam angle are listed in Tables max were 0.7 to 4.4% higher than the value without the stent because of the interaction between the proton beam and metal stent. Compared to not using the stent, Dmax showed the maximum difference (4.4%) for the GB stent located at 90°. The Dmin showed the maximum difference in dose perturbation value according to the stent from − 5.9 to − 31.8%. The differences in the values of Dmin were relatively large, − 31.8% and − 30.2% in the GB and GI stents, respectively, for stent locations at 90°. The values of Dmean were within 1% of the no-stent values for the GI and GB stents located at 0° and 45° (as in the photon beam), whereas there was a slightly higher difference with the GB and GI stents located at 90°. The comparison of dose using VMAT and double scattering technique was shown to be 0.0–0.5% in Table For the proton beam, the values of DComparisons of the DVHs at various position angles  of the stent with those without the stent are shown in Figs. For the photon beam, the DVHs for the GB and GI stents positioned at 0° showed a difference with respect to the volume of the high-dose region. For the GB and GI stents positioned at 45°, the DVHs were similar to those without the stent. In contrast, the DVHs for the GI and GB stents positioned at 90° showed significant differences, indicating underdoses for the target volume.For the proton beam, the DVHs indicated underdoses in the target volume for the GI and GB stents at all angles, as compared with the DVHs obtained without stents. The underestimated volume seen in the DVHs was exacerbated as the stent angle was increased. The GI and GB stents positioned at 90° were accompanied by differences in the high-dose region, indicating that high-dosing increased in accordance with the use of the stent. This trend was similar for the photon and proton beams; however, the difference was significantly larger for the proton beam than for the photon beam.Film dosimetry is often used to evaluate the effect of radiation distribution by artefacts during RT . However3, a range of densities considerably lower than the actual density of the stent [To perform an appropriate simulation using TPS and MC, a metal stent was inserted into the intensity modulated radiation therapy (IMRT) phantom, and CT scan was performed with the phantom. The wire thickness of the used stent was 0.1 mm, which was smaller than the size of the CT detector. Consequently, the stent did not appear clearly on the CT image, producing a blurry image instead. The stent density was assigned an average value corresponding to the densities of the surrounding materials, which amounted to 1.08–1.3 g/cmhe stent . Therefomax, Dmean, Dmin, and D1%, the dose enhancement was observed in Dmax because of the multiple Coulomb scattering caused by the interactions with the high-density material. Compared to the no-stent case, the maximum difference in Dmax was found when the stent was positioned at 0° for the photon beam and at 90° for the proton beam. Values of Dmin were lower for both the GB and the GI stents positioned at all angles, except for the stents positioned at 45°. The value of Dmin indicated that the degree of underdose increased as the angle of the positioned stent increased. In addition, the differences observed for the proton beam were more pronounced than those observed for the photon beam. Both the photon and proton beams showed a more significant reduction when the GB and GI stents were positioned at 90° than when they were positioned at 0° and 45°. This was because both the photon and proton beams interacted more intensively with the stent when they were incident on the stents positioned at 90°, due to the overlapping effect. However, it is expected that the differences observed in this study will not be replicated in the clinical situation because the positioning of a stent at 90° is rarely applied. In the MC simulation for clinical practice, very small dose differences were observed. The values of Dmean for both the photon and proton beams also indicated reduced doses for the stents located at all angles, compared with those obtained without a stent.To analyse the dosimetric parameters such as DThe analysis of the DVHs indicated that there was an underdose to the target volume when the stent was positioned at the specified angles, as compared with the no-stent dose, for both the photon and proton beams. The largest dose reduction in the DVHs occurred with the stent located at 90°, for both the photon and proton beams. In addition, the proton beam displayed a greater dose reduction for the target volume than the photon beam. This may have occurred because of the influence of the dose shadow on the proton beam . A compaThis study has two limitations. One limitation is that the stent modelling for the MC calculation consisted of only nitinol wire. However, the tip of the nitinol wire attached to the stent was gold. Because this part occupies a relatively small proportion of the entire stent composition, it was excluded from the stent modelling for MC simulation. In this gold portion of the stent, the effect of the dose difference on the overall volume was very small. However, there was a 5% difference for the point dose in the MC simulation. In future studies, a simulation using accurate stent modelling which includes the complete composition of the stent will lead to a more accurate dose analysis. The second limitation of the study is that dose perturbations by the stent for the proton and photon plans were evaluated through simulations based on a single fraction with AP/PA fields, VMAT, and double scattering technique. Treatment plans used in actual clinical practice are complex creations with various beam numbers and incident beam angles. However, the dosimetric results of this study obtained under few conditions may have shown a relatively large difference. Therefore, it is expected that clinical plans that can use a variety of beam incidence direction and numbers will produce reduced results rather than differences of our results obtained in this study. To obtain more accurate results, we will include more patient data and different treatment technique in our future studies of proton beams and photon beams which include the use of stents.This study confirmed that there was a difference in the dose delivered within the target volume by using MC simulation, which could not confirm the dose perturbation in the target volume even in the presence of the metal stent in the TPS calculation. Through MC simulations of photon and proton plans, we demonstrated that there are differences in the dosimetric parameters of the target volume as compared with those without a stent, for the positions and angles of the stent inserted into the phantom. Furthermore, we found that the stent caused a dose reduction rather than a dose increase of the target volume. This phenomenon appeared more clearly in the proton beam than in the photon beam.Based on the results obtained from the MC simulation, we believe that delivery of the treatment beam avoiding the stent is the best method to prevent underdose and overdose in the target volume. However, we recommend that it is important to reduce the effect by using as many fractions and beams as possible, to reduce the effect of the stent when the beam is delivered.


To investigate the usefulness and effectiveness of a dual beam‐current transformer (BCTs) design to monitor and record the beam dosimetry output and energy of pulsed electron FLASH (eFLASH) beams in real‐time, and to inform on the usefulness of this design for future eFLASH beam control.Two BCTs are integrated into the head of a FLASH Mobetron system, one located after the primary scattering foil and the other downstream of the secondary scattering foil. The response of the BCTs was evaluated individually to monitor beam output as a function of dose, scattering conditions, and ability to capture physical beam parameters such as pulse width (PW), pulse repetition frequency (PRF), and dose per pulse (DPP), and in combination to determine beam energy using the ratio of the lower‐to‐upper BCT signal.R2 > 0.99). A linear relationship was also observed in the BCT signals as a function of the number of pulses delivered regardless of the PW, DPP, or PRF (R2 > 0.99). The lower‐to‐upper BCT ratio was found to correlate strongly with the energy of the eFLASH beam due to differential beam attenuation caused by the secondary scattering foil. The BCTs were also able to provide accurate information about the PW, PRF, energy, and DPP for each individual pulse delivered in real‐time.A linear relationship was observed between the absorbed dose measured on Gafchromic film and the BCT signals for both the upper and lower BCT (The dual BCT system integrated within the FLASH Mobetron was shown to be a reliable monitoring system able to quantify accelerator performance and capture all essential physical beam parameters on a pulse‐by‐pulse basis, and the ratio between the two BCTs was strongly correlated with beam energy. The fast signal readout and processing enables the BCTs to provide real‐time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams. The use of beam current transformers (BCTs) for eFLASH beam monitoring is advantageous over transmission ion chambers because they allow real‐time monitoring of the beam output without beam perturbation and saturation effectsBCTs consist of a conducting wire wrapped around a donut‐shaped object, typically made of iron, and attached to a readout or circuit. The movement of a charged particle through the center of the BCT induces a signal through the electromagnetic principle of inductionThe purpose of this work is to introduce a novel use for dual BCTs integrated in the Mobetron unit,22.1The FLASH Mobetron  Figure  is a comOur unique Mobetron head design contains built‐in BCTs capable of collecting beam information at different locations in the beam path. The BCTs used in the Mobetron are alternating‐current (AC) current transformers (ACCTs) from Bergoz Instrumentation ; they are BCT sensors constructed from a cobalt‐based alloyBefore irradiations are delivered with the eFLASH Mobetron, the accelerator performs a 10‐min self‐warmup, and the user then delivers 8000 monitor units (MUs) from the beam in CONV mode as part of the daily protocol. Machine output constancy is then evaluated by delivering a set number of MUs (CONV mode) or a set number of pulses (FLASH mode) to an Advanced Markus ionization chamber , which has a reported uncertainty of 2.8% for the saturation model in UHDR modes2.21) and after (t2) the two locations of the threshold value as shown in Figure 1 and t2. The integral of the BCT signal related to the individual pulses is modified by subtracting the baseline noise before and after the pulse delivery received from each BCT to consider changes in noise  and the repetition frequency for each pulse . Here, the signal from each BCT after a pulsed delivery was acquired by using a PicoScope 5000 Series FlexRes Oscilloscope  operating with 14‐bit resolution and sampling rate of 125 MS/s (Mega Samples per second) in rapid acquisition mode based on vendor recommendations. Data collected from the BCTs underwent multi‐tier processing, as described below, to assist with characterization of the signals. The signals were forward‐backward filtered by passing a Bessel functionMraw is the integrated signal S′(t) obtained from the BCT, Mbef is the integrated noise before the pulse, and Maftis the integrated noise after the pulse. The bounds on Mraw are set by using an in‐house‐written peak‐finding algorithm. The bounds on Mbef and Maft are chosen based on the results of the pulse‐finding algorithm and scaled to the window of the Mraw signal.This process is described in Equations  and 2),,2), wher2.312 Gy/s.max) in solid water for a 9‐MeV eFLASH beam. The PW and PRF were kept constant at 1.2 µs and 120 Hz, with a DPP of 0.75 Gy. To evaluate the linearity of dose delivered from the eFLASH beam with the measured BCT signal, we delivered 1, 5, 10, 20, 30, 40, and 50 pulses to the EBT3 films placed at dmax. This experiment was repeated three times at all of the above pulse numbers. A summary of the fixed and variable experimental parameters performed are described and tabulated in Table Dosimetric evaluations were performed using GafChromic EBT3 film  to measure dose in a fixed geometry under the following reference conditions: a source‐to‐surface distance (SSD) of 42 cm, using an applicator with a 10‐cm diameter insert and a 5‐cm air gap between the insert and the surface (thereafter referred to as our standard dosimetric setup). Film was selected as the dosimeter for dose measurements owing to its dose‐rate independence up to 9 × 10Pixelbackground, with the averaged mean pixel reading from the films irradiated to an absorbed dose, Pixeldose:At 24 h after irradiation, EBT3 films, stored in the dark at a 22°C ambient temperature environment, were scanned with an Epson 10000XL flatbed scanner in transmission mode, landscape orientation, 48‐bit color, 72 dpi, and without color correction. Film placement on the scanner was made consistent with the aid of a cardboard cutout. The scanned film data were analyzed by measuring the net optical density (netOD) of the irradiated films relative to an unirradiated (0 Gy) film from the same batch. The red channel component of the scanned image was analyzed by using ImageJ and MATLAB in acquiring the mean pixel value for each irradiated film used. The mean pixel value measured for the three films in each dose group were averaged to acquire an averaged mean pixel reading. The netOD reading was acquired by taking the base‐10 logarithmic ratio of the averaged mean pixel reading from the unirradiated films, The change in netOD of the film was correlated to dose by using a dose calibration curve from the same batch of film irradiated to known doses ranging from 0.5 to 50 Gy,2.4To determine whether the BCT response was influenced by PW, the signal measured from the BCTs were collected during deliveries of 1, 2, 5, 10, 20, 50, 100, and 200 pulses of a 9‐MeV eFLASH beam at PWs of 1, 1.2, 2, 3, and 3.6 µs, with a constant PRF of 120 Hz (Table 2) in a water tank with a film holder at a 2‐degree tilt, using the dosimetric setup described by Arjomandy et al.,max was obtained from each scanned film corresponding to their PW and were normalized to the number of pulses delivered. The DPP values were plotted against the BCT response per pulse.The relationship between BCT response and DPP was investigated by modifying all the aforementioned PWs at a constant PRF of 120 Hz and comparing the response to what was measured on EBT3 film. The irradiation set‐up involved percent depth dose (PDD) measurements with the eFLASH beams by placing EBT3 film  and depth of 50% of maximum dose (R50) were obtained from each scanned film, corresponding to their incremental modification of the grid level. These values were then plotted against the lower‐to‐upper BCT ratio values. Moreover, the upper BCT signal from each irradiation was normalized to the dose delivered at dmax from the PDD measured on film and was plotted as a function of the measured R50.To investigate the response of the BCT as a function of the energy, the energy of the beam was modified by manipulating the electron gun grid and the RF shorts position in the waveguide  while keeping other settings constant; the pulse flatness was recovered by tuning the automatic frequency control voltage Table . Modifyi50 using these BCT observations, we first fit linear and quadratic models using R50 as the covariate and the BCT ratio as the outcome. The absolute mean prediction error for the quadratic model (0.016) was smaller than the linear model (0.021), and thus we used the quadratic model as the final predictive model. Because the observation error of BCT ratio depends on the value of R50, we designed a simulation study to compute the actual statistical power. In the simulation study, we first estimated the association of the BCT ratio with the R50 level by using a quadratic linear regression model. We then resampled the BCT ratio and incorporated normally distributed measurement noises to the observation with the mean and variance estimated from the k‐nearest neighboring observed noises, with k = 3 to mimic the noise in each location. This was performed by generating 10 repeated measurements in adding the prediction from the quadratic linear regression model with the simulated observation noise for each R50 of interest. Two‐sample t‐tests were performed at each R50 level to compute the p‐values between the values of R50 and the BCT ratio. Any p‐values smaller than 0.05 were deemed to be statistically significant and the scenario was counted towards the power calculation. To provide robust conclusions, the results were averaged from 1000 Monte Carlo datasets for final statistical power estimations.To understand the statistical power of detecting a shift in R2.8To examine how the effects of electron scatter may influence the BCT signal and to determine the need for output correction factors, BCT measurements were collected for different dosimetric setups and configurations for the 9‐MeV eFLASH beam Table . Seven d33.1R2 of >0.999.The measured signals from the upper and lower BCTs as a function of absorbed dose are shown in Figure 3.2Figure R2 of ≥ 0.999  with the 6 and 9 MeV eFLASH R50 values for reference. The BCT signal per dose is shown to decrease with increasing energy. Figure 50, with possible distance shifts ranging from 2‐mm to 3‐mm. The detection ability of BCT ratio depends on the R50 values of interest. The middle range of the R50 values in particular tend to be associated with higher observation errors and thus have less power to detect a fixed distance shift in R50. Next, the results show that statistical power was sufficient (>90%) to detect an R50 distance shift of 2‐mm at the lower and upper ends of the range of interest, that is, R50 < 3 cm and R50 > 4 cm. For the middle range of R50 values, the statistical power was >80% for detecting a distance shift of 2.5 mm or more.Figure 3.6Figure 4Previous studies have described the response of a single BCT placed at the exit/exterior of the accelerator as a function of the measured charge delivered to an Advanced Markus chamber; these reports demonstrated linearity in the BCT signal with the measured charge‐dose from the ion chamber.The current study builds on this previous work by investigating the utility of dual‐BCTs incorporated into the interior of the eFLASH accelerator, designed for preclinical and clinical use, for redundant monitoring of a variety of modifiable beam parameters and beam energy. Because the eFLASH Mobetron was designed for a clinical context, it is important to evaluate the number of pulses delivered, the beam energies, PW, PRF, and DPP for a variety of potential irradiation sites and prescription doses in the context of beam monitoring with BCTs. The ideal settings for a given clinical setup have yet to be determined, because this research is ongoing; for that reason we evaluated all the relevant beam settings available and provided a comprehensive investigation of the utility of BCTs as a beam monitoring solution for eFLASH beams. The BCT signals were found to be linear with respect to the dose and DPP delivered, and the two BCTs were demonstrated to be capable of functioning as beam monitors independent of one another to monitor the dose delivery of an eFLASH beam after each pulsed delivery, thereby taking on the role of the traditional transmission chambers embedded in standard clinical linear accelerators.Moreover, the BCTs demonstrated their utility in evaluating the performance of the eFLASH accelerator on a pulse‐by‐pulse basis. This was validated in Figures k = 2),Given that we have established the linearity of the cumulative BCT signal for a given number of delivered pulses with absorbed dose, we were also able to demonstrate linearity in the BCT signal from a given number of pulses for different PW and PRF parameters. These results provide a more thorough picture of the pulse structure of an eFLASH beam by using BCTs as opposed to any other commercially available detector. From this we can see that BCTs are a useful tool for evaluating the performance of the eFLASH accelerator in terms of pulse‐by‐pulse stability, PW, PRF, and scatter. Small deviations in the individual and in the cumulative pulse signal at different beam parameters were also thoroughly visualized with the BCT, allowing the user to observe any instabilities attributed to the accelerator performance and account for these instabilities. Our findings further show that the signal from each individual pulse can be correlated to dose given the proper calibration, demonstrating the utility of BCTs for providing real‐time dose monitoring of an eFLASH beam without the effects of beam perturbation or detector saturation. We further found that the BCTs have an uncertainty on par with EBT3 film, which does limit the current study, as the ideal case would be to test a new instrument against an instrument with greater accuracy and reproducibility. The uncertainty of film for dose measurements in UHDR beams has been reported as being 2%50.50 from 2‐mm to 3‐mm with sufficient statistical power. However, the statistical power for detecting shifts of 2‐mm was <90% for R50 values of 3–4 cm. This is most likely associated with limitations in how the energy of the beam was manipulated to acquire this data which was performed mainly through manipulating the gun grid voltage and the RF shorts position. With improved beam energy tuning and energy optimization, the data presented in Figure 50 values of 3–4 cm than what we observed; On par with the high statistical power observed at both lower and higher R50 values, where the energy of the beam was closer to the nominal values and therefore better optimized. Daily energy monitoring using the BCT ratio for short‐ and long‐term stability, and further optimization in evaluating the energy of the beam with the BCT ratio, is currently being done to evaluate the full utility of BCT ratios as a means of energy monitoring in real time. It is important to note that individual BCT signals are shown to be dependent on the energy of the beam  situated in between the upper and lower BCTs in the eFLASH Mobetron head. The lower‐to‐upper BCT ratio were found to provide detailed information regarding the energy of the eFLASH beam. This relationship can be used to evaluate the potential energy fluctuations on a pulse‐by‐pulse basis for both the 6‐MeV and 9‐MeV eFLASH beams. Even though individual variations in the BCT ratio were observed for each individual pulse in a 200‐pulse delivery, the pulse distribution tended to center on some nominal BCT ratio. Thus, the BCT ratio can be considered for the cumulative signal measured in the lower and upper BCT at a given pulse delivery, because the individual pulse values tended to be close together in their respective output with minimal variation. In AAPM TG‐72, recommendations for energy constancy in mobile electron accelerators were defined by an upper limit of 2‐mm in the shift in the Rm Figure  as evideIn this work, all data were acquired with the Mobetron situated in a room designed to shield for 18‐MV photons. A full radiation shielding survey, according to the recommendations in TG‐45One effect that must be taken under consideration in the use of BCTs for beam monitoring and control is the scatter and collimation conditions of the measurement setup. We found that differential contribution in electron scatter influences both the upper and lower BCT signal. More specifically, having a collimator with a smaller field size or having a scattering medium situated closer to the exit window of the beam influenced both the upper and lower BCT signal due to electrons backscatter, with the upper BCT signal being less sensitive to differences in the setup conditions. The lower BCT signal was observed to decrease (by as much as 12% relative to the open beam configuration), whereas the upper BCT signal was observed to vary slightly (by as much as 1.4% relative to the open beam configuration) when more material was obstructing the path of the FLASH electron beam, such as greater collimation restricting the beam‐path or when the exit window was moved closer to a scattering surface to facilitate electron scatter back into the head of the Mobetron. The reduction in signal in the lower BCT is most likely due to the greater backscatter with electrons traveling in the opposite direction of the beam delivered, thereby decreasing the net magnetic flux of the incident beam measured by the lower BCT. However, the reason for the increase in the signal from the upper BCT is unknown as the output of the eFLASH beam in its current configuration is not influenced by what is measured by the lower or upper BCT, thus requiring further investigation in future studies. The phenomenon of differential backscatter between different measurement setups is not specific to BCTs but is also highly prevalent in standard clinical linear accelerators, and the effects of electron backscatter on the measured BCT signal resemble the effects of monitor backscattering as reported in TG‐745This is the first detailed investigation of a dual‐BCT system design for monitoring and recording the individual pulse structure of an eFLASH beam and how this system is influenced by dose, dose rate, PW, PRF, scatter conditions, and DPP. It is important to emphasize that BCTs are a beam monitoring device that can measure the output of the eFLASH beam, and that their utility is in their use for relative dosimetry calibrated to specific dosimetric setups. We found that the BCTs’ responses were linear with respect to dose and DPP and no dependence on dose‐rate or PRF was found. The BCTs provided detailed information regarding the individual and cumulative pulse structure in a single delivery, which, when correlated with dose, can provide real‐time dosimetric information in a manner similar to the transmission ionization chambers in a conventional linear accelerator. Moreover, we found that the BCT ratio provided correlative information regarding the beam energy characteristics and can thus also be used for beam energy monitoring. Overall, the use of BCTs allow the beam to be monitored in real time without perturbation or saturation effects, which collectively allows highly detailed determinations of the physical beam parameters for each individual pulse delivered by UHDR FLASH irradiation. The fast signal readout and processing enables the BCTs to provide real‐time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams.All authors were involved in the conceptualization, writing, editing, and figure visualization. Kevin Liu took the lead in data acquisition and initial data analyses. Emil Schüler and Sam Beddar were jointly responsible for project oversight, administration, and funding acquisition. All authors have read and agreed to the published version of the manuscript.NoneSupporting InformationClick here for additional data file.


Dementia is considered a global health priority with projections of the disease set to increase dramatically across the world. Current support for persons living with dementia (PLWD) relies on long-term care and local service centers to provide education and support. Augmented reality-based programs continue to gain momentum across health sectors, becoming an innovative approach that provides an opportunity to have a visceral experience, which can deepen understanding and provide an embodied perspective of other groups within a relatively short time frame. There is increasing interest in developing approaches to aid patient care outcomes for PLWD and their caregivers. Hence, healthcare providers (HCPs) who are appropriately trained and equipped to provide quality care to PLWD areessential and of international concern. The purpose of this research program is to develop an augmented reality (AR) education experience (AREduX), a proof of concept prototype in the form of a digital resource that uses AR to simulate the physical and cognitive symptoms that PLWD experience. The findings from a stakeholder focus group will allow for the preliminary development of the AREduX. Dementia is a devastating disorder for sufferers and their families, and it imposes a substantial burden on caregivers, healthcare providers (HCPs) and the health care system. The estimated cost to the Canadian economy of caring for persons living with dementia (PLWD) is $10.4 billion per year, and rising ,3. MoreoTo date, there are limited programs that train HCPs or caregivers to develop empathy . ResearcSimulation in medical education is a well-established pedagogical practice . It provIn contrast, in an AR environment, digital information overlays the physical surroundings leading to an environment that is both real and virtual . This isThis report describes the first phase of a project with the eventual goal of developing innovative approaches to enhance the education and training of HCPs working with PLWD, with a particular emphasis on improving empathy. To accomplish this goal, we plan to develop a prototype of an AR education experience (AREduX) that will offer experiential learning that simulates some of the effects of dementia and challenges experienced by PLWD. The immersive experience will be used for training, to give HCPs and caregivers of PLWD a sense of what it is like to live with dementia, to make them more empathetic and, therefore, more likely to deliver compassionate care.In this report, we describe the preliminary stage in developing the AREduX, which involved consultation with relevant stakeholders using a focus group. The goal was to obtain caregivers’ and HCPs’ opinions and knowledge. We expected that their input would provide insight into, and understanding of, the lived experiences of PLWD and their caregivers. This insight will guide the design of the digital educational resource, and inform the elements that will be incorporated.Focus group The focus group session was held in December 2021. Due to the ongoing COVID-19 pandemic, it was not possible to hold the focus group in person as initially planned and the focus group session was therefore held virtually via the Zoom video conferencing software . Conducting the focus group virtually was advantageous for the caregivers because they could participate without arranging alternative care for their family members with dementia. The Zoom software was also used to transcribe the audio resulting from the session. The focus group session was facilitated by a research assistant working on the project. To ensure that the facilitator was not distracted by any technical issues, another research team member assisted with hosting and recording the Zoom meeting. The transcription was subsequently reviewed by the team member who had assisted with the meeting, and errors in the automated transcription were corrected. The duration of the focus group discussion was 95 minutes.Most of the questions included in the script were targeted at particular subgroups of participants. To ensure that input was obtained from everyone, if a participant from the group targeted by a question did not volunteer a response, they were asked if they had anything they would like to add. The facilitator used a script which is provided in Table ParticipantsA total of 12 participants joined the focus group. A range of stakeholders was included among the participants ensuring various perspectives, but they broadly represented two subgroups. The first subgroup (n=7) comprised participants with experience living with dementia or caring for PLWD, while the second subgroup comprised educational developers and experts in computer science. All participants met the following inclusion criteria: able to understand, read and speak basic English; willing to participate in a focus group; able to access the internet.Recruitment process Participants who had experience with PLWD were recruited through Baycrest, an academic health sciences centre providing a continuum of care for older adults. This subgroup included one HCP, four caregivers, and two PLWDs. HCPs were recruited by word-of-mouth and fliers posted at Baycrest, which detailed the study. Caregivers and PLWD were recruited via the Baycrest Client Registry.HCPs were individuals who care for PLWD in some professional capacity. Caregivers were carers for a person with any type of dementia who did not necessarily live with the person for whom they care. PLWD had been diagnosed with any type of dementia. We aimed to recruit PLWD who had scores from 18 to 25 (out of 30) on the Montreal Cognitive Assessment . This raThe second subgroup of participants (n=5) was recruited through purposive sampling and included two educational developers, two game development students, and one participant who was a software developer and research assistant.Focus group challengesThere were some challenges with recruitment. The focus group was intended to be larger, but one HCP, four caregivers, and two PLWD agreed to participate and then withdrew shortly before the focus group started, or failed to show up. The high drop-out rate may have been due to caregivers being under much pressure due to the demands of caregiving. Recruitment of HCPs was made difficult by the COVID-19 pandemic. When the focus group was held, HCPs were overworked and seemed to have little spare time to participate in research. Despite these difficulties with recruitment, there were sufficient participants to enable us to obtain reliable and fulsome information.In addition, the two participants with dementia were limited by their disease in their ability to contribute to the discussion. One had aphasia with empty speech and obvious word-finding difficulty, and when she spoke her intended message was often unclear. The other participant with dementia had fluent speech but frequently did not answer the question asked and instead spoke off-topic. Nevertheless, both participants with dementia were able to make some relevant and valuable points. The observed difficulty with communication enhanced our understanding of the experiences of PLWD and will contribute to our prototype development. However, the questions did provoke discussion which was relevant and informative for our purposes.Some minor but unexpected events led to reduced participation from three participants. The HCP chose to participate while at work and appeared to experience numerous interruptions in the latter half of the session, hence participating only in the first half. Furthermore, one of the student game development participants had to leave before the session ended. Finally, the participant who was a software developer and research assistant contributed little and said she was just there to listen.Qualitative analysis of resultsThe focus group transcription was qualitatively coded on a sentence-by-sentence basis using an open coding process that was not based upon a pre-existing theory. The coding was done using the NVivo qualitative data analysis software , which facilitates the analysis of unstructured text such as focus group results. The software provides tools for classifying and sorting data, leading themes or patterns to become apparent. In the present analysis, categories of information (or nodes) were developed as part of the open coding process. Next, the relationships between the codes were examined and connections were made between them where relevant. Ultimately,following an iterative process of refining the codes and their interconnections, we were able to identify central themes within the data. These themes are detailed below and are listed in Table Qualitative findings There were seven themes generated via the qualitative coding, and these are elaborated upon in this section. The first six themes relate to experiences associated with dementia, while the seventh theme arose from a discussion of experiences with AR.Theme 1: Hurdles and Challenges in CaregivingThis theme included any mention of something which increases the difficulty of caregiving. Elements of this theme were mentioned by all of the caregivers and by the HCP. In particular, they described the relentlessness of caregiving, and the three caregivers who live (or lived) with a PLWD emphasized this strongly. They noted how fatiguing caregiving is because it is perpetual, and happens around the clock.Another significant challenge in caregiving was noted to be problems with communication, mainly comprising difficulty understanding what is said or meant by the PLWD. Two of the caregivers described particular problems in this regard. In one case, the PLWD had aphasia with word-finding difficulty and was mostly unable to generate meaningful speech. In the other case, the PLWD suffered from dementia associated with Parkinson’s Disease (PD), for which hypophonic speech is an established feature; as a result, this person was not able to speak, loudly enough to be heard, and this was a substantial barrier to communication that was frustrating and difficult for the caregiver. Another area that seemed to particularly add to the challenge is the fact that other people don’t understand the inherent difficulty of caregiving. The lack of acknowledgment and understanding from others was stressed by all of the caregivers. This relates to their perceptions about lack of support, which is further addressed as part of Theme 2.Other difficulties included how hard it is to accept the situation, the fact that the PLWD can no longer do things that they used to, and that the PLWD is different from how they used to be.Theme 2: Help From Others (or Lack of it)This theme refers to any acknowledgment of professional or other (mostly family) help with caring for a PLWD. Caregivers were generally appreciative of professional support and particularly liked Personal Support Workers (PSWs). The caregivers seemed to agree, however, that the help they receive is insufficient and that ultimately they shoulder the responsibility and burden of caregiving all on their own. Lack of help from other family members seemed to be a sore point for caregivers and was mentioned by the HCP as well.Theme 3: Description of PLWDThis theme included a description of the capabilities of the PLWD (activities they can and cannot do and perform), as well as signs and symptoms of dementia and of co-occurring morbidities. Tasks and activities the PLWD can no longer do at all, or can no longer do without help, including driving, traveling alone, bathing, grooming, feeding, getting into bed, taking others into consideration, remembering to do things, and following directions. Participants did mention things the PLWD is still capable of doing, but these seemed rather limited . Things that the PLWD can no longer do outnumbered the things they have retained the ability to do. The signs and symptoms of dementia that were mentioned by the caregivers and the HCP included problems with memory , problems with speaking and understanding, and loss of the ability to take another’s perspective (resulting in selfishness and not taking their caregiver’s needs into account). Anxiety was also reported, and this is a common concomitant of dementia. The caregivers’ comments indicated that the people they care for are suffering from comorbidities. This was reflected in comments describing non-dementia signs and symptoms, such as fatigue, hearing loss, inability to speak loudly enough to be heard, difficulty walking, and pain. For two of the caregivers, these additional problems seemed to substantially increase their burden. In one case, the PLWD had PD, and the concomitant quiet speech, fatigue, and difficulty walking added considerably to the workload, while in another case there was a significant problem with pain as well as difficulty walking.Theme 4: Goals in CaregivingThis theme refers to anything caregivers or the HCP aim to do which will benefit the PLWD for whom they care. They all seemed highly motivated to do their best in caregiving, and this theme comprises the things they do to help their PLWD, as well as their stated objectives for helping. Safety was a primary objective and was mentioned by all four caregivers and the HCP, with particular emphasis on keeping the environment safe. Strategies used to safeguard PLWD included arranging for a medical alert system so the PLWD can summon help, not allowing the PLWD to go out on their own, ensuring extra care is taken when bathing, and setting-up handrails, and ensuring the floor is kept clear of trip hazards. Keeping the PLWD happy, comfortable, and stimulated also seemed to be an important goal for these participants, as well as encouraging independence as much as possible, and keeping a routine.Theme 5: Strategies and Other Things That Help With CaregivingThis theme comprises caregiver characteristics and strategies which were described as necessary or beneficial for caregiving. The most frequently mentioned requirement in a caregiver was patience. Empathy and caring were also perceived to be important, as was the ability of the caregiver to adapt to the PLWD’s needs. The caregivers and HCP mentioned a range of useful strategies. One that was mentioned frequently was the differentiation between the person and the disease; the idea is that it is easier to cope when the difficulties are blamed on the disease rather than the PLWD. Other useful strategies included distraction, reassurance, acknowledgment of the feelings of the PLWD, and in one case, medication. Caregivers also mentioned that it is important that they look after themselves to ensure that they remain able to care for their family members with dementia.Theme 6: Technology and EquipmentThis theme includes any mention of technology and equipment, whether helpful or not, including technology that participants would like to see developed. Equipment that was noted to be helpful included monitoring devices, such as a GPS tracker, a medical alert system, and an emergency call button, as well as basic equipment such as proper shoes, a cane, and a hearing aid. Helpful technology was mentioned by only one (caregiver) participant who noted that the PLWD for whom he cares can be kept occupied by, and obtains significant enjoyment from, playing Lumosity which is proprietary “brain-training” software.Other equipment was tried but not found to be useful. Participants often noted that the PLWD was incapable of using devices that were intended to help. The person who cared for an individual who had both dementia and PD was very vocal about how frustrated she was that the person for whom she cared was unable or unwilling to use various devices which she purchased . One of the participants with dementia noted that she was unable to use a walker and found it dangerous, although she found a cane helpful. The only technology that was mentioned in this regard was that one participant had tried using Siri  with his wife (he didn’t specify for what purpose), but it wasn’t helpful. The caregiver participants had several suggestions for technology that they would like to see developed. Some of the items on this “wish list” were also discussed by participants who are educational developers or computer science experts (see Theme 7). Caregivers expressed a need for technology that would enable a PLWD to better communicate, either by making quiet speech audible or by helping with word-finding and/or generating a message. Other potentially helpful technology would be something that could calm or reassure a distressed PLWD who is on their own, something that would light up when a hazard is present, such as a tripping hazard, and something to keep the PLWD safe if they go near a stove.Theme 7: AR Design RecommendationsThis theme comprises a discussion about experiences with AR and about ways AR could be incorporated into Long Term Care settings. In contrast with the above themes, most of what was said on this topic were contributed by the educational developers and computer science experts. At the time that AR was discussed, these participants had already listened to the caregivers’ ideas. The suggestions made by the educational developers and computer science experts included ideas for technology that could be developed within an AR framework, as well as potentially useful design features. Suggestions for technology that could be developed in the future included a device to label and actively amplify audio, as well as using AR to develop something to provide fulfillment, engagement, and even companionship for PLWD. In addition, it was suggested that technology capable of sensing the emotions and reactions of a PLWD could ultimately be used to help PLWD. Guidance for the development of such technology was offered. In particular, it was felt that the user interface should be kept simple, and be thoroughly tested.A summary of the themes is illustrated in Table A focus group meeting was held to obtain stakeholders’ inputs to inform the development of an AREduX prototype which will ultimately be used to increase empathy for PLWD, among HCPs and caregivers of PLWD. We were able to obtain inputs from various stakeholders with various perspectives, which provided insight into the lived experiences of PLWD and caregivers. Caregivers described their struggles with caregiving. They find it relentless and exhausting, and they feel that they receive insufficient help or acknowledgment from others. Nevertheless, they were clearly motivated to do the best they could. Problems experienced by PLWD were also described. PLWD may experience difficulty undertaking simple tasks such as grooming, feeding, and getting into bed. They also suffer from memory loss and problems with communication, both in language production and comprehension. The communication problems seemed to present more of a hurdle in caring than did the memory loss. The PLWD who were described in the focus group suffered from comorbidities that caused symptoms in addition to dementia, such as hearing loss, mobility issues, hypophonic speech, and pain. Some of the elements mentioned in the focus group could be incorporated into the AREduX. Since the aim of the AREduX is to create a digital resource in the form of AR and expose users to an experience that gives them a sense of what it is like to live with dementia using the latest AR game development technology, our team will create a unique experience that simulates the effects of dementia for training purposes with the goal of making users more empathetic. The experience itself is intended to draw the user into the imagined world of PLWD.The educational developers and computer science experts had little to no experience with AR in a health care setting. This lack of experience indicates that our project is valid and demonstrates a need for more work in this area. Further, the findings from data collected through the focus group will substantially contribute to the scientific literature on the development of empathy; address the knowledge gap that exists aligned with an evidence-based understanding of empathy as a construct and its associated dimensions from the perspective of HCPs and caregivers of PLWD; impact how empathy is conceptualized and taught within our curriculum and community; finally, contribute to guiding further research aligned with implementing AR as an experiential education to enhance empathy among HCPs and caregivers of PLWD.The focus group results have laid the foundation for designing and developing a platform that will be used in the later stages of our research. The results will be used to generate a plan of action for designing the AREduX prototype. The AREduX will allow end-users to build an understanding of the symptoms experienced by PLWD and will enable us to evaluate how the medium impacts empathy levels among HCPs and caregivers of PLWD.


Quantitative measurements of activity in SPECT are important for radioisotope therapy planning and disease diagnosis. The aim of this manuscript is to develop a robust method to quantify the total activity in a volume‐of‐interest (VOI) of different quantitative SPECT reconstructions and validate the estimation accuracy.We customized an IEC body phantom using 3D printing technology and made six sphere inserts of 1–6 cm in diameter with at least 3 cm separation. The activity concentration within the spheres was in the range of patient lesion/organ activity. The background activity was then increased from zero to a sphere/background activity concentration of 8:1, 4:1, and 2:1. SPECT data were acquired with Philips Brightview and GE Discovery 670 SPECT/computed tomography (CT) systems under clinical acquisition protocols. Quantitative SPECT images were reconstructed with Hermes SUV‐SPECT (both Philips and GE data) and GE Q.Metrix (GE data only). The quantitative SPECT reconstructions are iterative with scatter, CT attenuation correction, and resolution recovery. We quantified the total activity by expanding the sphere VOI to include a spill‐out region. Background correction was applied by sampling a region outside the spill‐out region. The true fractions (TFs)  were measured for all six spheres for all SPECT acquisitions.The TF is close to 100% for 2–6 cm spheres for zero background, 8:1 and 4:1 sphere/background activity ratios. The TF was found to be unreliable for the 1‐cm sphere because of the limit of phantom design. TF accuracy for 2:1 sphere/background ratio was degraded due to significantly large background, inadequate scatter correction and detector count loss.The results demonstrated that the proposed quantification method is accurate for objects of different sizes in currently clinical quantitative reconstruction and has the potential for improving the accuracy for therapeutic treatment planning or radiation dosimetry calculations. Emission tomography uses various radionuclide‐labeled compounds for imaging, and quantitative emission tomography can be a powerful investigation tool for both clinical and research practices. The two principal forms of emission tomography are SPECT and PET. Unlike SPECT, PET systems from the early development have been designed to produce reconstructed images that are inherently quantitative mainly because the attenuation correction for PET is relatively straightforward to apply, and in early two‐dimensional PET scanners, the amount of scattered radiation detected was low. Modern PET scanners are always paired with CT scanners for both attenuation and scatter correction, and clinically, there are almost no stand‐alone PET scanners. PET images have since been used quantitatively, and there are manufacture procedures to validate the quantitative accuracy of PET images.In SPECT, attenuation correction and scatter correction have been more challenging. The accurate correction of attenuation and scatter also requires that transmission data (CT) is available. However, the incorporation of CT into SPECT is not as widely available as PET/CT. Nevertheless, new SPECT systems come with CT. With the combined SPECT/CT scanners and more robust iterative image reconstruction algorithms , quantitative SPECT has been under development for a long time.For both PET and SPECT images, quantitative means pixel values in the concentration of the radioactivity in a volume (Bq/ml). From a quantitative PET/SPECT image, either a SUV (which is used to quantify metabolic state of tissues and tumors) or the total activity within a volume‐of‐interest (VOI) can be calculated. The SUV is a ratio of the radioactivity concentration in a VOI to the average concentration in the whole patient volume. An SUV greater than one implies active tissue incorporation of the radiotracer. Often the peak SUV in a VOI is reported. The total activity in an organ VOI is used to perform internal radiation absorbed dose calculations for a patient's whole body, organ, and/or tumors.Both PET and SPECT systems suffer from partial volume effectsIn this manuscript, we focus on the total activity estimation by expanding the VOI to include both the object region and the spill‐out region so that all of the spill‐out activities are captured. By doing so, we eliminate the need to obtain recovery coefficients to estimate the total activity of the object. The activity can then be assigned to the true volume of the object and be used for dosimetry purposes or to calculate an activity concentration for diagnostic purposes.22.1Considering SPECT has relatively poor resolution compared to PET and that therapeutic application generally involves large objects such as the whole organ, we modified the IEC body phantom designed for PET system evaluation to include objects of larger size for our experiment. The IEC phantom cover is customized using 3D printing to hold six hollow spheres from 1 to 6 cm of diameters. The spheres are arranged so that all sphere surfaces are a minimum of 3 cm apart from one another. The 3 cm spacing was chosen with a consideration of the spatial resolution of SPECT systems to ensure the measurements of one sphere would not interfere with another. In order to meet this requirement, the placement of the spheres at depth inside the phantom had to be staggered because of space limit. Hollow stems are fitted for filling the spheres and inserting inside the IEC phantom. We used a 3D printer to make the cover, stems, and the spheres. The advantage of using 3D printer for the phantom is the low cost and more freedom in design. The phantom we customized is shown in Figure Tc‐99m activity was prepared so that the Tc‐99m concentrations in the spheres are approximately 12 μCi/ml, which is about the same concentration as specified in IEC SPECT test documents.The phantom data acquisitions were performed on a clinical GE Discovery 670 SPECT/CT and Philips Brightview SPECT/CT systems. The crystal thicknesses of the two systems are both 9 mm. For both studies, SPECT data were acquired using the LEHR collimator, a noncircular orbit under step‐and‐shoot mode. The projection view settings are 30 s per view, 128 views (for Philips) or 120 views (for GE) with a matrix size of 128 × 128, and a zoom factor 1.46. The resulted SPECT reconstruction image pixel size is about 3.2 mm with the same array dimension as the detector matrix size. The GE SPECT/CT system is incorporated with a 16‐slice diagnostic CT scanner, whereas the Philips Brightview SPECT/CT system uses a flat‐panel‐based cone‐beam CT system. The Philips Brightview does not have a quantitative reconstruction package. The Hermes SUV‐SPECT reconstruction software was used for quantitative reconstruction of Brightview data. For the GE Discovery system, both the manufacture‐provided Q.Metrix quantitative package and the Hermes SUV‐SPECT reconstruction tools were used to reconstruct quantitative SPECT images. The Q.Metrix quantification was performed on the Xeleris workstation. All the SPECT reconstructions use OSEM  with CT attenuation correction, scatter correction, and resolution recovery.The quantification of the SPECT reconstruction requires the measurement of sensitivity coefficient that will be used to convert the counts into activity concentration. This coefficient is usually available from the SPECT system annual physics surveys. The details about the measurement of this coefficient have been described by Gnesin et al.,We then measured the total activity within the spheres by placing VOI's at the boundaries of the spheres using VOI tools provided by Hermes or GE Xeleris workstation. To include the spill‐out of activity outside the boundaries of the spheres, we overlaid enlarged VOI's over each sphere. Altogether, 8 data acquisitions  were performed with the two clinical systems, and 12 sets of reconstruction images were reconstructed from the 8 data sets using Hermes and GE Q.Metrix quantitative SPECT reconstruction .2.2Our proposed quantification method is as follows: We first co‐registered the SPECT images with the CT image using either Hermes or GE Xeleris. We placed six VOIs that match the diameters for the hot spheres on the reconstructed SPECT images using CT images as references. This set of VOIs is called VOI1 (sphere 1). We then expanded the diameter of each sphere in VOI1 by a fixed distance (sphere 2). The volume between the two VOI's for each sphere is called VOI2. VOI2 essentially captures the spill‐out regions of Tc‐99m activities. We then expanded the diameter further by about 1 cm (sphere 3). The volume between the sphere 2 and sphere 3 is called VOI3. VOI3 will be used to estimate mean background activity concentration. Total activity is the sum of the activities within VOI1 and VOI2 minus background activity. The background activity is estimated using the mean activities within VOI3 multiplied by the volume of VOI2. The assumption here is that the background activity is only significant for the activity within VOI2. The whole quantification method can be summarized by the following equation:corrA is the final estimated total activity within the sphere, A is the total activity within VOI1, SPA is the total activity within VOI2, which is the spill‐out activity, SPV is the volume of VOI2, and B(v)¯ is the mean background activity concentration.In which 33.1We first performed a study to determine the expansion size of the VOI using data without any background. We studied the effect of expansion size on the total activity estimation accuracy by using different size of expansions. Figure Based on this study, the expansion of diameter was set to be 2 cm for different spheres for our proposed methodology. The 2 cm expansion is possibly related to the spatial resolution of the SPECT system, which include the effects of the system hardware , acquisition protocol (detector radius of rotation and acquisition pixel size), and the reconstruction . Both systems studied had very similar characteristics. It can be observed that the 1 cm sphere is an outlier among the six spheres. After further examination, we found that two factors contribute to this. The first factor is the limitation of 3D printing. The opaque stem and sphere made it difficult to observe the liquid level in the sphere, especially for the 1 cm sphere. This has resulted large portion of residual activity in the stem during filling of 1‐cm sphere. The second factor is the small volume of 1‐cm sphere. The small volume makes the activity in the stem a significant portion of the total activity. Because of the previous limitation of our 3D printing, meaningful conclusions can only be drawn from the other five spheres.3.2The proposed quantification method described in Section In Figure In Figure 4This manuscript demonstrates a robust method to estimate the total activity for objects of different sizes across different quantitative SPECT reconstructions. The advantage of the proposed method over sphere‐based recovery coefficients is that the latter heavily depends on the size of the objects and also varies slightly from system to system. The proposed method is consistent across objects of different sizes and for the two clinical systems that were studied. From the total activity, the average activity can be estimated by dividing the total activity with the volume. However, the quantitative accuracy of activity distribution (or SUV) within the volume still needs further validation.Although resolution recovery improved the overall image quality of the SPECT image, significant edge enhancement effects can be observed in the reconstruction images. In Figure The accuracy of the proposed method will depend on how well the VOI can be delineated. The spherical objects in our experiment have relatively simple shapes, and we are able to accurately position the VOIs, and we know the activity is confined in the spheres. Expansion of the VOI's is simply accomplished by increasing the VOI diameter. For irregular‐shaped objects, the delineation will be more difficult. With the available CT images, we can always use the CT images as a reference in the segmentation process as long as the object boundary is visualized. Accurate expansion of an irregularly shaped VOI may be more difficult. The existing visualization tools incorporate an expansion VOI tool but only by increasing the VOI size by adding one voxel at a time at its periphery. This may be reasonably accurate for large objects, but not for small objects. This was the case in our experiment using the GE Xeleris by which we were only able to expand VOI's using the voxel approach. The results in Figures Sometimes two lesions may be close to each other, and there may not be enough space for expansion between the lesions. This situation will need further study. Either the expansion size needs to be reduced or the two lesions can be included in one VOI.The expansion method requires a background correction applied to the expanded volume used to capture all of the spill‐out activity. For our experiment, it was easy to enlarge the sphere an additional cm to measure the background concentration. It is not expected that the same method would be always appropriate for patient images. What is required is a proper sampling of the patient background in the vicinity of the object or tumor. A VOI off to the side may be sufficient. Likewise in quantifying activity in planar imaging studies, a background is drawn near or adjacent to the ROI surrounding the object of interest. The most accurate background sampling is by drawing a background ROI almost encircling the drawn ROI. The same principle can be applied in 3D or tomographic image quantification.The main purpose of this manuscript is to develop a method to quantify the total activity in a quantitative SPECT reconstruction and validate the activity estimation accuracy with known truth values. That is why we focused on phantom studies in this manuscript. The same method can be extended to patient studies as well with the addition of segmentation tools.It seems even though the CT image quality of the Brightview system is not as good as a diagnostic CT system such as GE Discovery, that did not affect the overall total activity estimation accuracy. This is mainly because we used CT images for attenuation correction and segmentation reference. The CT image quality of the Brightview system seems to be sufficient for these two purposes.5The results demonstrate that the proposed quantitative method is robust for objects of different sizes. This method has the potential to be robust in performing quantitative analysis of organ and lesion activity in patients for clinical SPECT/CT images using the expanded VOI technique. The results also demonstrated that the current quantitative SPECT packages (Hermes SUV‐SPECT and GE Q.Metrix) are reasonably accurate when used for estimating the total activity of VOIs with the proposed technique.Junguo Bian, experiment design, data acquisition and analysis, conceptualization, results analysis, writing‐original draft, writing‐revision and response; Judy James, data analysis, conceptualization, editing the original draft; Robert Wagner, phantom design, editing original draft and revision; James Halama, phantom design, experiment design, data acquisition and analysis, conceptualization, data analysis, critical editing the original draft and revision.The authors have no potential conflict of interest to disclose.


There was an error in the original publication . We mistA correction was implemented in Section 1 in the second paragraph of the Introduction:“…an estimated 100,000 pet ferrets in the UK [13]”.The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated.