Objective To compare the dosimetric effects of systematic MLC leaf position errors on flattening filter (FF) and flattening filter-free (FFF) IMRT for nasopharyngeal carcinoma (NPC).Methods In totaly of ten patients with NPC were enrolled in the current study.FF IMRT and FFF IMRT plans were designed for each patient, and in-house software was developed to modify the corresponding MLC files.Briefly, three kinds of systematic MLC error presented with 0.5 and 1 mm magnitudes error were simulated.The modified MLC files were re-imported into IMRT plans for dose recalculation, and differences in the dosimetry trends between FF-IMRT and FFF-IMRT plans were analyzed using a dosevolume histogram.Results Upon closed MLC, the average changes in D95％ of PTV and D of parotid glands in FFF-IMRT plans were more sensitive than in FF-IMRT plans (t =3.298-4.793, P ＜ 0.05).Otherwise, when MLC are shifted in the same direction, changes in D95％of PTV, D of PGTV, PTV as well as D of left parotid gland in FFF-IMRT plans were also more sensitive (t =2.372-6.844, P ＜ 0.05), whereas average changes in D of right parotid gland presented with less sensitivity (t =-4.049,-3.378, P ＜ 0.05).Conclusions For out-of-field or large organs, FFF-IMRT plans are more sensitive to leaf position error than FF-IMRT plans.

Objective To verify the dose delivery accuracy of volumetric-modulated arc therapy plan by log-file analysis of linear accelerator that can be created when a dynamic delivery occurs.Methods Accelerator log file in binary format recorded the accelerator execution plan for each control point corresponding to the gantry angle,multi-leaf collimator leave position,cumulative machine monitor units ( MU).These information were read from the accelerator log file with Matlab7.1,then the original control points in the plan file replaced the corresponding information for the log,which generated a new plan.New plan was exported into the planning system to reculculate the dose.The volume dose histogram (DVH) and dose distribution was contrasted to determine the accuracy of the accelerator plan of implementation between two plans.Results Compared with the original plan,antry angle difference over ± 1° accounted for about 35％ of the entire arc of control points in 4 of 12 arcs and the percentage of the leave error of ±0.5 mm was about 95％.MU error of a single control point was larger,but the cumulative MU for each are was small which was located between-0.09％ to 0.11％ in the selected 12 arcs.Between the targets,the maximum dose,minimum dose,the mean dose differences were from-0.07％ to 0.42％,-0.38％ to 0.40％,0.03％ to 0.08％,respectively.The maximum dose and mean dose differences of organs at risks were located from-1.16％ to 2.51％,-1.21％ to 3.12％,respectively.Conclusions Accelerator log-file analysis to verify the VMAT plan nan be supplyed to the experimental method supplement.

Objective To compare the dosimetric verification results of Varian Portal Dosimetry and Matrixx,and to assess the reliability of the clinical application of electronic portal imaging device (EPID) verification.Methods Varian TrueBeam linear accelerator,which was equipped with a 120-leaf multileaf collimator and an amorphous silicon EPID,as well as portal dose prediction software.IBA I′mRT Matrixx ion chamber array was used.EPID algorithm configuration,dose calibration,and testing before use were performed.The sliding-window protocol was used.There were 77 patients with tumors involving the head and neck (mainly nasopharyngeal carcinoma),mediastinum,abdomen,and pelvic cavity were selected.The verification plan of the portal dose was created with a source-detector distance of 100 cm,and the gantry angle was kept the same as the treatment plan.The verification plan was carried out in the TrueBeam machine,and the data were collected at the same time by EPID.Comparison between the measured and calculated dose images was performed,and the evaluation standard was gamma index (3%/3 mm).The paired t-test was used for difference analysis.Results For the 77 patients,the Gamma passing rates of both methods were above 97%.Except for head and neck carcinoma were a significant difference between the results of dosimetric results using EPID and Matrixx in intensity-modulated radiotherapy (P=0.018) other remaining all P> 0.05.Conclusions The dosimetric verification results of EPID are consistent with those of Matrixx.EPID can be used for dosimetric verification,and Matrixx ion chamber array can be used only in case of a low Gamma passing rate.

Objective:To evaluate the combined effect of an trajectory log field based(LBF)and two commercial dose reconstruction systems on volume-modulated arc therapy(VMAT)dose verification of lung cancer.Methods:An in-house program was developed to introduce errors in trajectory log of TrueBeam to the origin plan and recalculate the dose of the error plan in treatment planning system(TPS). A total of 18 lung cancer cases treated by two-arc VMAT were selected to perform on LINAC and measured by ArcCheck simultaneously. Then, the reconstructed doses were obtained by 3DVH. The mode of reconstruction was calculated by LFB and Compass. Five of the 18 cases were performed on LINAC two times in four hours and measured by ArcCheck to evaluate the stability of the TrueBeam performance. The 18 plans were recalculated and performed on LINAC with a solid water phantom with 5 cm build-up, 4 cm back scattering thickness and a FC65-G detector in the center. The measured dose by detector was compared with the reconstructed dose by three systems.Results:TheTruebeam performance was stable. For all of the 18 cases, the point dose measured by FC65-G and reconstructed by three systems had a deviation of less than 2% to the TPS calculated. For all of the organs reconstructed by LBF and most organs reconstructed by 3DVH and Compass, the γ pass rate between them and TPS all exceeded 90% under all criteria, as well as the ArcCheck measured results. For all the organ dose difference between reconstructed and TPS, LBF system had the smallest difference, followed by the Compass system except the lung, and the 3DVH had the highest difference.Conclusions:LBF, 3DVH and Compass can reflect the VMAT dose verification results of lung cancer from different perspectives. The combined application of three systems can demonstrate the verification results in an intuitive manner, which is beneficial for subsequent analysis.

Objective:To evaluate the positive rate of the bronchodilation test (BDT) in asthmatic children with normal forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC) and FEV 1/FVC, so as to improve the recognition of the importance of the BDT test in asthmatic children with normal FEV 1, FVC and FEV 1/FVC. Methods:Children aged 5-14 who were diagnosed with asthma in the outpatient clinic of Shandong Provincial Hospital Affiliated to Shandong University from September 2018 to August 2019 and willing to receive pulmonary function and BDT examinations were enrolled.Data of pulmonary function of children with normal FEV 1, FVC and FEV 1/FVC were collected to analyze the rate of positive BDT results and the status of small airway function. Results:A total of 1 631 asthmatic children with normal FEV 1, FVC and FEV 1/FVC were enrolled in this study, including 1 414 children with normal pulmonary function and 217 children with small airway dysfunction.Fifteen minutes after the bronchodilator was inhaled, 127 children (87 males and 40 females) showed positive BDT results, accounting for 7.8%.Among these children, 62 cases (28.6%) with co-existing small airway dysfunction showed positive BDT results.The improvement rate of FEV 1 was 8.0% to 11.9% in 132 cases (8.1%). The FEV 1 before bronchodilator inhalation accounted for (98.5±10.3)% of the predicted value.Fifteen minutes after terbutaline sulfate inhalation, the improvement rate was 13.5% (12.5%, 16.2%). The improvement rates of forced expiratory flow at 50% of FVC exhaled (FEF 50, r=-0.339, P<0.01), forced expiratory flow at 75% of forced vital capacity exhaled (FEF 75, r=-0.400, P<0.01), maximum mid-expiratory flow(MMEF, r=-0.375, P<0.01) were negatively correlated with their baseline values.The improvement rate of FEV 1 was not associated with its baseline value ( r=-0.128, P=0.153), but negatively correlated with the baseline value of MMEF ( r=-0.231, P<0.01). Conclusions:BDT results are positive in some asthmatic children with normal FEV 1, FVC and FEV 1/FVC.It is recommended that BDT testing should be conducted as much as possible in the diagnosis and follow-up of children with typical or atypical asthma.In this way, the diagnosis can be confirmed and the current optimal results can be obtained.Meanwhile, small airway function testing is helpful for comprehensive assessment of asthma and its control level.

Objective: To achieve quantitative analysis of image quality parameters and establish warning and action thresholds for the on-board imaging (OBI) system of linear accelerator. Methods: The Catphan604 phantom was repeatedly scanned in the Full-Fan and Half-Fan CBCT scanning modes on a Varian EDGE linear accelerator, and the software based on Python language development in-house was utilized to analyze image quality parameters, such as CT number linearity, geometric consistency, slice thickness, spatial resolution, uniformity and low-contrast resolution. The quantitative analysis results of each image quality parameter obtained from 16 times of scanning within 16 months were normalized to the mean and the standard deviations were recorded. A run chart analysis was created to determine the warnings and action thresholds. Results: The software built in-house can quantitatively analyze the image parameters of the two scanning modes of OBI system. The low-contrast resolution of Half-Fan was better than that of Full-Fan, whereas the spatial resolution of Full-Fan was superior to that of Half-Fan. One standard deviation (1σ) was set as the warning threshold and 2 standard deviations (2σ) as the action threshold, respectively. The tolerance level of Half-Fan was smaller than that of Full-Fan. Conclusion Self-developed software enables quantitative analysis of accelerator image quality parameters, establishes warning and action tolerance of quality assurance and provides guidance for image quality assurance under image-guided radiotherapy specification.

Objective:To perform testing and clinical application of a volumetric-modulated arc therapy (VMAT) dosimetry verification system based on three-dimensional dose reconstruction of patient anatomical structures.Methods:ArcCheck array calibration was performed. Then, 200 MU was delivered with a 10 cm×10 cm field when the source to center of ArcCheck was 100 cm to calibrate the absolute dose and the dose was simultaneously measured by a FC65-G detector in the center of the ArcCheck. The absolute dose calibration value or the CT value of ArcCheck was adjusted to minimize the differences between the planning and measurement values of FC65-G, reconstructed value by 3DVH and reconstructed percent depth dose by 3DVH. 10 lung and 10 cervical cancer VMAT cases were selected and measured by ArcCheck and FC65-G under the delivery of a TrueBeam LINAC. The three-dimensional doses of all cases were reconstructed by 3DVH and compared with the planning and measurement values.Results:Different array calibration files of ArcCheck exerted different effect upon the two-dimensional dose measured by ArcCheck and three-dimensional dose reconstructed by 3DVH. The optimal reconstructed dose was obtained when self-calibration file was adopted and 249.96 cGy was regarded as the absolute dose calibration value. The deviations of the mean dose (D mean) and D 95% of the target were within ±4.2% and parameters of some organs at risk significantly differed compared with the reconstructed and planning dose for all cases. A negative mean point dose difference was obtained and the reconstructed dose was closer to the measured value. The γ-passing rate of the target for some cases was low, the proportion of regions irradiated by 50% prescription dose was slightly higher and the proportion of other organs was relatively high. Conclusion:The 3DVH model can be accurately established and tested with the acceptance test method in the present study, which can provide detailed information for dose verification.

Objective:To explore the difference in the complexity of different treatment planning systems, multi-leaf collimator (MLC) types and treatment sites of volume-modulated arc therapy (VMAT), and propose a complexity score for plan quality control.Methods:Statistical analysis of 12 complexity metrics including Monaco and Eclipse, Agility, Millennium and High-definition MLC, nasopharyngeal, lung and cervical cancer was performed. Spearman correlation coefficient between complexity metrics was calculated. Principal component analysis was conducted to reduce the dimensionality of the original data set to the first two principal components and explain its physical meaning. Complexity score based on the principal components was calculated to establish warning and action thresholds for plan quality control. The correlation between complexity metrics and γ pass rate was analyzed.Results:Except cervical cancer aperture sub-regions metric, other metrics had significant differences between Monaco and Eclipse. Monaco MLC had a more regular field but higher MU, smaller leaf gap, and longer leaf travel distance. High-definition MLC with smaller leaf width significantly added MLC aperture-related metrics. The first two principal components explained over 80% of the total variance of the original dataset, complexity score was weighted average of first two principal components. The distribution of complexity score for different equipment and sites was different. The warning threshold was expressed as the average plus standard deviation, and the action threshold was expressed as the average plus 2 standard deviations. Complexity metrics and complexity scores had small correlation with γ pass rate, showing weak or irrelevant but statistically significant. Conclusions:Different planning systems, MLC types, and treatment site complexity metrics are significantly different. The complexity score is a useful tool for plan quality control.

Objective:To evaluate the volumetric modulated arc therapy (VMAT) dose verification of cervical cancer based on γ rule and dose volume histogram (DVH) and to perform correlation analysis between the evaluation results and the dose differences.Methods:Twenty cervical cancer VMAT plans were selected and performed on TrueBeam Linac. The delivered point and surface dose was measured by FC-65 G and ArcCheck and the results were compared to those calculated by Eclipse. The dose of patients was reconstructed by 3DVH. Then, differences between the reconstructed and plan value of D mean, D 95%, D 98% and D 2% of PTV, V 20Gy of left and right femoral head, V 40Gy of rectum, D 1cm 3 of cord, D 98%, D 2% and D 50% of the 50% prescription iso-dose volume (IDV), were evaluated and 3-dimensional (3D) γ was assessed for each organ. Lastly, Pearson’s correlation coefficient was used to analyze the relationship between point dose difference, 2D γ pass-rate (γ%), γ mean and 3D γ% of each organ and the dose difference. Results:Small differences were found between the point dose measured, reconstructed and the plan value. Differences between D mean of PTV, all dose parameters of IDV and plan values were all within 3% and V 40Gy of rectum showed the largest difference. As for the 3D γ%, the maximum pass rate was found for the left and right femoral head and the maximum variance for cord D 1cm 3. There was a moderate correlation between measured and reconstructed point dose deviation and dose difference of each organ, while no significant correlation was found for 2D γ%. Strong correlation was found between 3D γ% of target and D 50% of PTV/IDV and no correlation was found for other organs. Conclusion:The performance of both γ-and DVH-based evaluation can reveal dose error for dose verification, but both of them have some limitations and should be combined in clinical practice.

BACKGROUND:Inherited heart disease has a high prevalence and mortality rate,but its pathogenesis has not yet been clarified.Although relevant animal models have been established to provide a foundation for the pathogenesis research of inherited heart disease,the value of these research results has been significantly reduced due to differences among species.Therefore,a new model is needed to explore its occurrence and development. OBJECTIVE:To review the current role of induced pluripotent stem cells in disease modeling and potential application prospects in various inherited heart diseases. METHODS:The first author searched the relevant articles published nearly 13 years in PubMed from January to March 2023.The search terms were"induced pluripotent stem cell,inherited heart disease,congenital heart disease".Finally,76 articles were included for analysis. RESULTS AND CONCLUSION:Since 2007,when induced pluripotent stem cells were induced from human somatic cells,many studies have been reported on disease-specific induced pluripotent stem cells.Due to the ability of disease-specific induced pluripotent stem cells to reproduce disease phenotypes,they are expected to become a new research tool for in vitro disease modeling,used to analyze pathogenesis and develop auxiliary drugs.In the research of cardiovascular genetic diseases,cardiomyocytes derived from patient-specific induced pluripotent stem cells contain gene mutations that are involved in cardiac dysplasia.Therefore,it can be used as a new tool to study the potential mechanisms of inherited heart disease.Up to now,induced pluripotent stem cells-derived cardiomyocytes have been widely used to study the molecular mechanisms of various genetic heart diseases,such as cardiac electrophysiological diseases,cardiomyopathy,and some syndromic inherited heart diseases.