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Background and aims Liver metastasis is a frequent occurrence in patients with colorectal cancer (CRC), with 15%-25% of CRC patients having liver metastases at the time of initial diagnosis. Specifically, some regional-stage patients with mild symptoms (stage 1 or 2) will also advance to liver metastases rapidly, even if the CRC lesion in situ is resected in time. Nevertheless, the precise mechanism of liver metastasis is still unclear. Approach and results Fresh tumor tissues from patients with CRC, adjacent noncancerous tissues, and colorectal adenoma tissues were subjected to microarray analysis to identify differentially expressed microRNA. Exosomes from human serum and cell culture medium were separated, quantitated, and verified by transmission electronic microscopy and Zetasizer Nano. Luciferase reporter assay, real-time quantitative PCR, western blot, immunoprecipitation, chromatin and re-chromatin immunoprecipitation, migration and invasion assay, PDX mouse model, flow cytometry, immunohistochemistry, and immunofluorescence staining were employed to explore the regulation among CRC liver metastases, immunosuppression, and cell adhesion. In this study, we demonstrated that the hypoxic microenvironment in primary CRC lesions boosted exosome release, selectively initiated favorable premetastatic niche formation in the liver but not in other organs. Mechanistically, Kupffer cells (KCs) can phagocytose exosomes containing highly expressed miR-135a-5p from the blood circulation into the liver. Exosomal miR-135a-5p initiated the large tumor suppressor kinase 2-yes-associated protein-matrix metalloproteinase 7 axis to promote the occurrence of CRC liver metastasis, and cluster of differentiation 30-TNF receptor-associated factor 2-p65-mediated immunosuppression signaling also contributed to this process. Conclusions Hypoxia-induced exosomal miR-135a-5p correlates with the development, clinical severity, and prognosis of CRC liver metastases through the premetastatic niche; and our findings revealed that miR-135a-5p might be a promising target in halting CRC liver metastases.

The application of reservoir computing (RC) is for the first time studied in a class of forecasting tasks in which signals are under random physical perturbations, meaning that the data-baring waveform distortions are versatile, and the process is not repeatable. Tumor movement caused by respiratory motion is such a problem and real-time prediction of tumor motion is required by the clinical radiotherapy. In this work, a true-time delay (TTD) respiration monitor based on photonic RC with adjustable nodes connection is developed specifically for this task. A breathing data set from a total of 76 patients with breathing speeds ranging from 3 to 20 breath per minute (BPM) are studied. A double-sliding window technology is demonstrated to enable the real-time establishment of an individually trained model for each patient and the real-time processing of live-streamed tumor position data. Motion prediction of look-ahead times of 66.6 ms, 166.6 ms and 333 ms are investigated. With a 333 ms look-ahead time, the real-time RC model achieves an average normalized mean square error (NMSE) of 0.0246, an average mean absolute error (MAE) of 0.338 mm, an average therapeutic beam exposure efficiency of 94.14% for an absolute error (AE) < 1mm and 99.89% for AE < 3mm. This study demonstrates that real-time RC is an efficient computing framework for high precision respiratory motion prediction.

Background A range pull-back device, such as a machine-related range shifter (MRS) or a universal patient-related range shifter (UPRS), is needed in pencil beam scanning technique to treat shallow tumors. Methods Three UPRS made by QFix (Avondale, PA, USA) allow treating targets across the body: U-shaped bolus (UB), anterior lateral bolus (ALB), and couch top bolus. Head-and-neck (HN) patients who used the UPRS were tested. The in-air spot sizes were measured and compared in this study at air gaps: 6 cm, 16 cm, and 26 cm. Measurements were performed in a solid water phantom using a single-field optimization pencil beam scanning field with the ALB placed at 0, 10, and 20 cm air gaps. The two-dimensional dose maps at the middle of the spread-out Bragg peak were measured using ion chamber array MatriXX PT (IBA-Dosimetry, Schwarzenbruck, Germany) located at isocenter and compared with the treatment planning system. Results A UPRS can be consistently placed close to the patient and maintains a relatively small spot size resulting in improved dose distributions. However, when a UPRS is non-removable (e.g. thick couch top), the quality of volumetric imaging is degraded due to their high Z material construction, hindering the value of Image-Guided Radiation Therapy (IGRT). Limitations of using UPRS with small air gaps include reduced couch weight limit, potential collision with patient or immobilization devices, and challenges using non-coplanar fields with certain UPRS. Our experience showed the combination of a U-shaped bolus exclusively for an HN target and an MRS as the complimentary device for head-and-neck targets as well as for all other treatment sites may be ideal to preserve the dosimetric advantages of pencil beam scanning proton treatments across the body. Conclusion We have described how to implement UPRS and MRS for various clinical indications using the PBS technique, and comprehensively reviewed the advantage and disadvantages of UPRS and MRS. We recommend the removable UB only to be employed for the brain and HN treatments while an automated MRS is used for all proton beams that require RS but not convenient or feasible to use UB.

Purpose This review article aims to consolidate information regarding existing and emerging implanted devices used in patients undergoing radiation therapy and to categorize levels of attention needed for each device, including which devices require monitoring throughout treatment. Methods and Materials Based on the collective information from scholar searches, manufacturers’ technical reports, and institutional experiences in the past years, commonly present devices in patients with cancer are compiled. This work summarizes cardiac pacemaker, implanted cardiac defibrillator, hepatic pump, intrathecal pain pump, neurostimulator, shunt, loop recorder, and mediport. Three different classifications of implanted devices can be made based on the potential effect of radiation: life-dependent, nonlife-dependent but with adverse effects if overdosed, and devices without electronic circuits. Implanted devices that contain electronic circuits that would be life-dependent or have adverse effects if overdosed, include cardiac pacemakers, implanted cardiac defibrillators, programmable hepatic pumps, pain pumps, neurostimulators, and loop recorders. Results Dose exposure to these devices need to be calculated or measured in vivo, especially for cardiac implanted devices, and they should be minimized to assure continued healthy functioning. Treatment planning techniques should be chosen to reduce entry, exit and internal scatter dose. Lower energy photon beams should be used to decrease potential neutron contamination. Implanted devices without electronic circuits are less of a concern. If a patient is life-dependent on the implanted device, it is not recommended to treat the patient with proton therapy. Conclusions This study reviewed the management of patients with commonly seen implanted devices and summarized a workflow for identifying and planning when a patient has implanted devices. Classifications of implanted devices could help clinicians make proper decisions in regard to patients with specific implanted devices. Lastly, the management of such devices in the era of the pandemic is also discussed in this review article.

The Daily Quality Assurance (DQA) for a proton modality is not standardized. The modern pencil beam scanning proton system is becoming a trend and an increasing number of proton centers with PBS are either under construction or in planning. The American Association of Physicists in Medicine has a Task Group 224 report published in 2019 for proton modality routine QA. Therefore, there is a clinical need to explore a DQA procedure to meet the TG 224 guideline. The MatriXX PT and a customized phantom were used for the dosimetry constancy checking. An OBI box was used for imaging QA. The MyQA(TM) software was used for logging the dosimetry results. An in‐house developed application was applied to log and auto analyze the DQA results. Another in‐house developed program "DailyQATrend" was used to create DQA databases for further analysis. All the functional and easy determined tasks passed. For dosimetry constancy checking, the outputs for four gantry rooms were within ±3% with room to room baseline differences within ±1%. The energy checking was within ±1%. The spot location checking from the baseline was within 0.63 mm and the spot size checking from the baseline was within −1.41 ± 1.27 mm (left–right) and −0.24 ± 1.27 mm (in–out) by averaging all the energies. We have found that there was also a trend for the beam energies of two treatment rooms slowly going down (0.76% per month and 0.48 per month) after analyzing the whole data trend with linear regression. A DQA program for a PBS proton system has been developed and fully implemented into the clinic. The DQA program meets the TG 224 guideline and has web‐based logging and auto treading functions. The clinical data show the DQA program is efficient and has the potential to identify the PBS proton system potential issue.

Background Although diabetes mellitus has been reported to aggravate liver ischaemia and reperfusion (IR) injury, the basic mechanism remains largely unknown. The object of the present study was to determine the role of oxidative stress and hepatocellular pyroptosis in liver IR injury in diabetic mice. Methods Db/db and C57BL/6 mice at 8 weeks of age were subjected to liver IR injury. Liver injury and hepatocyte cell death were analyzed. A NOD-like receptor family pyrin domain-containing 3 protein (NLRP3) inflammasome antagonist (CY09) and a reactive oxygen species (ROS) antagonist (N-Acetyl-L-cysteine, NAC) were used to determine the role of ROS-mediated hepatocellular pyroptosis in diabetic mice post-IR. Results Aggravated liver IR injury was found in db/db mice compared to C57BL/6 control mice, as demonstrated by increased serum alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) levels, liver architecture damage and Suzuki scores. Interestingly, IR induces the pyroptosis of hepatocytes in db/db mice, as evidenced by enhanced NLRP3 inflammasome activation, increased numbers of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive hepatocytes and increased gene expression of interleukin-1β (IL-1β) and IL-18 in livers post-IR. The inhibitory effect of CY09, an NLRP3 antagonist, efficiently abrogated the exacerbation effects of diabetes on liver IR injury in db/db mice. Furthermore, increased ROS expression was detected in db/db mice compared to control mice after IR. ROS scavenging by NAC pretreatment markedly inhibited hepatocellular NLRP3 inflammasome activation and pyroptosis in the db/db mice post-IR, indicating that ROS play an essential role in mediating hepatocyte pyroptosis in the setting of diabetes mellitus. Conclusions Our results demonstrate that diabetes induces hepatocyte pyroptosis by promoting oxidative stress-mediated NLRP3 inflammasome activation during liver IR injury. Strategies targeting ROS and NLRP3 inflammasome activation would be beneficial for preventing liver IR injury in diabetic patients.

A pulse transformer has advantages of compactness and long lifetime achievability, and is considered an important candidate for the development of high voltage pulse generators. In this paper, a fast rise time high voltage pulse transformer with a compact structure is studied numerically and experimentally. Specifically, the structure of the pulse transformer was designed with paralleled winding groups. The response and insulation characteristics of the pulse transformer are investigated numerically. After that, a fast rise time high voltage pulse transformer was built, and scaling experiments were performed to analyze the influence of the feed structure of the pulse transformer. Importantly, the pulse transformer was successfully used in a low impedance generator, and high voltage pulses with a peak voltage of about 260 kV, a pulse duration of 170 ns, and a rise time of 65 ns were achieved on a resistive load of 32 Ω. The ratio of the transformer is approximately 1:3. Experiments show reasonable agreement with the numerical analysis.

Deformable image registration (DIR) is the key process for contour propagation and dose accumulation in adaptive radiation therapy (ART). However, currently, ART suffers from a lack of understanding of “robustness” of the process involving the image contour based on DIR and subsequent dose variations caused by algorithm itself and the presetting parameters. The purpose of this research is to evaluate the DIR caused variations for contour propagation and dose accumulation during ART using the RayStation treatment planning system. Ten head and neck cancer patients were selected for retrospective studies. Contours were performed by a single radiation oncologist and new treatment plans were generated on the weekly CT scans for all patients. For each DIR process, four deformation vector fields (DVFs) were generated to propagate contours and accumulate weekly dose by the following algorithms: (a) ANACONDA with simple presetting parameters, (b) ANACONDA with detailed presetting parameters, (c) MORFEUS with simple presetting parameters, and (d) MORFEUS with detailed presetting parameters. The geometric evaluation considered DICE coefficient and Hausdorff distance. The dosimetric evaluation included D95, Dmax, Dmean, Dmin, and Homogeneity Index. For geometric evaluation, the DICE coefficient variations of the GTV were found to be 0.78 ± 0.11, 0.96 ± 0.02, 0.64 ± 0.15, and 0.91 ± 0.03 for simple ANACONDA, detailed ANACONDA, simple MORFEUS, and detailed MORFEUS, respectively. For dosimetric evaluation, the corresponding Homogeneity Index variations were found to be 0.137 ± 0.115, 0.006 ± 0.032, 0.197 ± 0.096, and 0.006 ± 0.033, respectively. The coherent geometric and dosimetric variations also consisted in large organs and small organs. Overall, the results demonstrated that the contour propagation and dose accumulation in clinical ART were influenced by the DIR algorithm, and to a greater extent by the presetting parameters. A quality assurance procedure should be established for the proper use of a commercial DIR for adaptive radiation therapy.

The deep inspiration breath hold (DIBH) and prone (P) position are two common heart‐sparing techniques for external‐beam radiation treatment of left‐sided breast cancer patients. Clinicians select the position that is deemed to be better for tissue sparing based on their experience. This approach, however, is not always optimum and consistent. In response to this, we develop a quantitative tool that predicts the optimal positioning for the sake of organs at risk (OAR) sparing. Sixteen left‐sided breast cancer patients were considered in the study, each received CT scans in the supine free breathing, supine DIBH, and prone positions. Treatment plans were generated for all positions. A patient was classified as DIBH or P using two different criteria: if that position yielded (1) lower heart dose, or (2) lower weighted OAR dose. Ten anatomical features were extracted from each patient's data, followed by the principal component analysis. Sequential forward feature selection was implemented to identify features that give the best classification performance. Nine statistical models were then applied to predict the optimal positioning and were evaluated using stratified k‐fold cross‐validation, predictive accuracy and receiver operating characteristic (AUROC). For heart toxicity‐based classification, the support vector machine with radial basis function kernel yielded the highest accuracy (0.88) and AUROC (0.80). For OAR overall toxicities‐based classification, the quadratic discriminant analysis achieved the highest accuracy (0.90) and AUROC (0.84). For heart toxicity‐based classification, Breast volume and the distance between Heart and Breast were the most frequently selected features. For OAR overall toxicities‐based classification, Heart volume, Breast volume and the distance between ipsilateral lung and breast were frequently selected. Given the patient data considered in this study, the proposed statistical model is feasible to provide predictions for DIBH and prone position selection as well as indicate important clinical features that affect the position selection.

International Journal of Medical Physics, Clinical Engineering and Radiation Oncology: Editorial

The purpose of this study is to investigate the potential use of Ir-192 as the source for real time imaging during HDR (High Dose Rate) brachytherapy treatment. Phantom measurement was performed to determine outside of the body dose. Monte Carlo code, EGSnrcMP egs_inprz, was used for the simulation to calculate the outside of the body x-ray signal for CT reconstruction. Matlab code was developed to reconstruct the Ir-192 source and for 3D visualization in order to assess reconstructed CT resolution, signal-to-noise ratio, and imaging dose information. The measured dose was 0.67 ± 0.04 cGy, which was comparable to the Monte Carlo simulation result 0.71 ± 0.20 cGy. The reconstructed source diameter dimension was 1.3 mm compared with 1.1 mm for the real source dimension. The signal-to-noise ratio was 19.91 db following de-noising. Source position was within a 1 mm difference between programmed and simulated results. Although the Ir-192 signal is weak for CT imaging, it is possible to use it as a CT imaging x-ray source for HDR treatment localization, verification and dosimetry purposes. Further study is needed for the detailed design of an outside of the body CT-like device for use in brachytherapy imaging.

Segmentation of prostate Cone Beam CT (CBCT) images is an essential step towards real-time adaptive radiotherapy (ART). It is challenging for Calypso patients, as more artifacts generated by the beacon transponders are present on the images. We herein propose a novel wavelet-based segmentation algorithm for rectum, bladder, and prostate of CBCT images with implanted Calypso transponders. For a given CBCT, a Moving Window-Based Double Haar (MWDH) transformation is applied first to obtain the wavelet coefficients. Based on a user defined point in the object of interest, a cluster algorithm based adaptive thresholding is applied to the low frequency components of the wavelet coefficients, and a Lee filter theory based adaptive thresholding is applied on the high frequency components. For the next step, the wavelet reconstruction is applied to the thresholded wavelet coefficients. A binary (segmented) image of the object of interest is therefore obtained. 5 hypofractionated Calypso prostate patients with daily CBCT were studied. DICE, Sensitivity, Inclusiveness and ΔV were used to evaluate the segmentation result.

Radiochromic film for spot-scanning QA provides high spatial resolution and efficiency gains from one-shot irradiation for multiple depths. However, calibration can be a tedious procedure which may limit widespread use. Moreover, since there may be an energy dependence, which manifests as a depth dependence, this may require additional measurements for each patient. We present a one-scan protocol to simplify the procedure. A calibration using an EBT3 film, exposed by a 6-level step-wedge plan on a Proteus®PLUS proton system (IBA, Belgium), was performed at depths of 18, 20, 24 cm using Plastic Water® (CIRS, Norfolk, VA). The calibration doses ranged from 65 - 250 cGy (RBE) (relative biological effectiveness) for proton energies of 170 - 200 MeV. A clinical prostate + nodes plan was used for validation. The planar doses at selected depths were measured with EBT3 films and analyzed using one-scan protocol (one-scan digitization of QA film and at least one film exposed to a known dose). The gamma passing rates, dose-difference maps, and profiles of 2D planar doses measured with EBT3 film and IBA MatriXX-PT, versus the RayStation TPS calculations were analyzed and compared. The EBT3 film measurement results matched well with the TPS calculation data with an average passing rate of ~95% for 2%/2 mm and slightly lower passing rates were obtained from an ion chamber array detector. We were able to demonstrate that the use of a proton step-wedge provided clinically acceptable results and minimized variations between film-scanner orientation, inter-scan, and scanning conditions. Furthermore, for relative dosimetry (calibration is not done at the time of experiment), it could be derived from no more than two films exposed to known doses (one could be zero) for rescaling the master calibration curve at each depth. The sensitivity of the calibration to depth variations has been explored. One-scan protocol results appear to be comparable to that of the ion chamber array detector. The use of a proton step-wedge for calibration of EBT3 film potentially increases efficiency in patient-specific QA of proton beams.

Purposes: The newly released Protura 6 degrees-of-freedom couch (CIVCO) has limited quality assurance protocols and pertinent publications. Herein, we report our experiences of the Protura system acceptance, commissioning, and quality assurance. Methods: The Protura system integration was tested with peripheral equipment on the following items: couch movement range limit, 6 degrees-of-freedom movement accuracy, weight test and couch sagging, system connection with Linac, isocentricity of couch and rotation alignment, kV and cone-beam computed tomography imaging of HexaCHECK with MIMI phantom (Standard Imaging), and an in-house custom 6 degrees-of-freedom quality assurance phantom. A couch transmission measurement was also performed. Results: The vertical, longitudinal, and lateral ranges of the 6 degrees-of-freedom couch pedestal are 43.9 to 0.0 cm, 24.6 to 149.5 cm, −20.6 to 20.7 cm, respectively. The couch movement accuracy was within 1 mm in all directions. The couch sagging with a 200 lbs (∼91 kg) evenly distributed object is 1.0 cm and 0.4° pitch in the distal end of the couch. The isocentricity of the couch was about 0.5 mm in diameter of all crosshair projections on the couch isocenter level, and the largest couch rotation alignment observed was (0.3°) at the couch angle of 90°. The deviation from the reference position (zero position) of the HexaCHECK phantom, measured by matching the cone-beam computed tomography with the reference planning computed tomography, was found to be below 0.2 mm in the anterior–posterior and right–left dimensions, 0.4 mm in superior–inferior dimension, and 0.1° in roll, pitch, and yaw directions. Conclusions: A 6 degrees-of-freedom quality assurance phantom is helpful for the commissioning and routine quality assurance tests. Due to the third-party integration with Linac, the system is prone to “double-correction” errors. A rigorous quality assurance program is the key to a successful clinical implementation of the Protura system.

Purpose: To compare plan quality and delivery efficiency of noncoplanar volumetric modulated arc therapy with coplanar volumetric modulated arc therapy, intensity-modulated radiation therapy, and CyberKnife for multiple brain metastases. Methods: For 15 patients with multiple brain metastases, noncoplanar volumetric modulated arc therapy, coplanar volumetric modulated arc therapy, intensity-modulated radiation therapy, and CyberKnife plans with a prescription dose of 30 Gy in 3 fractions were generated. Noncoplanar volumetric modulated arc therapy and coplanar volumetric modulated arc therapy plans consisted of 4 noncoplanar arcs and 2 full coplanar arcs, respectively. Intensity-modulated radiation therapy plans consisted of 7 coplanar fields. CyberKnife plans used skull tracking to ensure accurate position. All plans were generated to cover 95% target volume with prescription dose. Gradient index, conformity index, normal brain tissue volume ( V 3Gy − V 24Gy), monitor units, and beam on time were evaluated. Results: Gradient index was the lowest for CyberKnife (3.49 ± 0.65), followed by noncoplanar volumetric modulated arc therapy (4.21 ± 1.38), coplanar volumetric modulated arc therapy (4.87 ± 1.35), and intensity-modulated radiation therapy (5.36 ± 1.98). Conformity index was the largest for noncoplanar volumetric modulated arc therapy (0.87 ± 0.03), followed by coplanar volumetric modulated arc therapy (0.86 ± 0.04), CyberKnife (0.86 ± 0.07), and intensity-modulated radiation therapy (0.85 ± 0.05). Normal brain tissue volume at high-to-moderate dose spreads ( V 24Gy − V 9Gy) was significantly reduced in noncoplanar volumetric modulated arc therapy over that of intensity-modulated radiation therapy and coplanar volumetric modulated arc therapy. Normal brain tissue volume for noncoplanar volumetric modulated arc therapy was comparable with noncoplanar volumetric modulated arc therapy at high-dose level ( V 24Gy − V 15Gy) and larger than CyberKnife at moderate-to-low dose level ( V 12Gy − V 3Gy). Monitor units was highest for CyberKnife (28 733.59 ± 7197.85), followed by intensity-modulated radiation therapy (4128.40 ± 1185.38), noncoplanar volumetric modulated arc therapy (3105.20 ± 371.23), and coplanar volumetric modulated arc therapy (2997.27 ± 446.84). Beam on time was longest for CyberKnife (30.25 ± 7.32 minutes), followed by intensity-modulated radiation therapy (2.95 ± 0.85 minutes), noncoplanar volumetric modulated arc therapy (2.61 ± 0.07 minutes), and coplanar volumetric modulated arc therapy (2.30 ± 0.23 minutes). Conclusion: For brain metastases far away from organs-at-risk, noncoplanar volumetric modulated arc therapy generated more rapid dose falloff and higher conformity compared to intensity-modulated radiation therapy and coplanar volumetric modulated arc therapy. Noncoplanar volumetric modulated arc therapy provided a comparable dose falloff with CyberKnife at high-dose level and a slower dose falloff than CyberKnife at moderate-to-low dose level. Noncoplanar volumetric modulated arc therapy plans had less monitor units and shorter beam on time than CyberKnife plans.

Liver fibrosis is an important pathologic process in injured liver tissues. A protein kinase, receptor-interacting protein (RIP)3, plays a crucial role in mediating different diseases. However, the role of RIP3 in macrophages in liver fibrosis has not yet been studied. In our study, we found that RIP3 expression was up-regulated in liver tissues and macrophages of humans and mice with liver fibrosis. Absence of RIP3 in macrophages could alleviate inflammation and macrophage or neutrophil accumulation in mice after carbon tetrachloride (CCl4) or bile duct ligation (BDL) treatment. Importantly, RIP3 deficiency in macrophages could decrease CCl4-induced and BDL-induced liver fibrosis in mice. Moreover, RIP3 deficiency could inhibit the TLR4-NF-κB pathway through suppressing Rho-associated coiled-coil containing protein kinase (ROCK)1 in macrophages. To explore the connection of ROCK1 and RIP3 in macrophages of mice with liver fibrosis in vivo, ROCK1-overexpressed macrophages were infused to RIP3-deficient mice, which resulted in increased inflammation and liver fibrosis. In conclusion, our findings suggest that RIP3 plays a crucial proinflammatory role in liver fibrosis by regulating the ROCK1-TLR4-NF-κB signaling pathway in macrophages and therefore may be a potential therapeutic target for immune-mediated liver fibrosis.-Wei, S., Zhou, H., Wang, Q., Zhou, S., Li, C., Liu, R., Qiu, J., Shi, C., Lu, L. RIP3 deficiency alleviates liver fibrosis by inhibiting ROCK1-TLR4-NF-κB pathway in macrophages.

In this paper, a compact solid-state high voltage pulse generator, composed of a pulse transformer and a magnetic pulse compressor, is investigated numerically and experimentally. The generator can achieve pulses with a peak voltage over several tens of kilovolts and a rise-time in the microsecond level, which can be widely used in plasma physics research, high power microwave generation, and material treatment. Specifically, PSpice software is used to analyze the performance of the generator. Then, the generator was constructed in our laboratory. The experimental results illustrate that when the charging voltage of the generator was changing from 10 kV to 14 kV, typical pulses with a peak voltage ranging from 67 kV to 95 kV and rise-time between 10 µs and 12 µs were obtained on a dummy load. The generator can continually work over 10 min with a repetitive rate of 20 Hz, and until now, it has been successfully achieving over 1 × 106 high voltage pulses. Experiments show reasonable agreement with numerical analysis.

Purpose: To evaluate the efficacy and safety of the accelerated partial breast irradiation brachytherapy with a combination of applicators at a community hospital cancer center. Methods and Materials: Between 2005 and 2009, 120 patients with early-stage breast cancer were being followed after treatment with accelerated partial breast irradiation brachytherapy using MammoSite, single or multilumen balloon, or Contura multilumen balloon. After their lumpectomy surgery, each patient was treated with Ir-192 high-dose rate unit following radiation therapy oncology group 0413 guidelines. The patients had multiple follow-ups at 6 months, 1 year, 2 years, 3 years, or more. Results: Based on the Harvard Breast Cosmesis Scale, 95.00% of patients described their cosmetic evaluation as the treated breast essentially the same as the opposite side (excellent) or minimal but identifiable effects were noticed from radiation (good). After a median follow-up of 36 months, the local recurrence rate was 1.66% and a disease-free survival is 98.3%. Forty-two patients reported 85 adverse events, which were fibrosis: 24.70%, hyperpigmentation: 20.00%, radiation skin reaction: 7.05%, seroma: 7.05%, breast pain: 7.05%, erythema: 5.88%, and other events were less than 5.00%. Of all the adverse events recorded, grade 1 to 3 events are 95.29% (n = 81), 2.35% (n = 2), and 2.35% (n = 2). There was no grade 4 or 5 events recorded. Conclusions: Our study has shown promising results for delivering radiation with MammoSite, single or multilumen balloon, or Contura multilumen balloon and has been successful in achieving local control in patients with early-stage breast cancer.

This study is to investigate three common potential setup uncertainties during Linac commissioning and annual QA and to evaluate how these uncertainties propagate into the quality of beam profiles and patient dosimetry using gamma analysis. Three uncertainty scenarios were purposely introduced for gantry position tilted from 0r - 3r (scenario 1), isocenter position misaligned from 0 - 6 mm (scenario 2) and SAD changed from 99.5 - 103 cm (scenario 3). A 60 × 60 × 60 cm3 water phantom cube was created to replicate a 3D water tank in VarianEclipse (V.11) treatment planning system (Varian Medical Systems, Palo Alto, CA). For each scenario, beam data profiles (crossline and diagonal) and PDD curves were calculated at different field sizes and depths for three energies: 6 MV, 6 MV-FFF and 10 MV-FFF. Gamma analysis method was used to compare a total of 263 profiles to baseline using a 1%/1mm parameter with 90% gamma passing rate criteria. For scenario 1, a ≥90% gamma passing rate and ≤1% dose difference were seen on both crossline and diagonal profiles, and PDD curves for gantry tilted up to 2r. For 3r degree tilt, the gamma passing rate decreased to ≤90% at depth of ≥20 cm for 6MV/6MV-FFF and depth of ≥12 cm for 10MV-FFF. For scenario 2, a ≤90% gamma passing rate and ≥1% dose difference were seen at depths from dmax to 20 cm for all energies. For depths ≥20 cm, mostly ≥90% gamma passing rate and ≤1% dose difference were seen. For scenario 3, a ≥90% gamma passing rate and ≤1% dose difference were seen on ≤4 mm isocenter misalignments for all energies. In summary, gamma analysis of the beam profiles is a very sensitive test for SAD deviation scenarios and can reveal issues of sub millimeter setup uncertainty. However, it is not as sensitive for isocenter misalignment scenarios. The test is also more sensitive for FFF beams than flattening filter beams.

Objective The newly released Respiratory Gating for Scanners (RGSC; Varian Medical Systems, Palo Alto, CA, USA) system has limited existing quality assurance (QA) protocols and pertinent publications. Herein, we report our experiences of the RGSC system acceptance and QA. Methods The RGSC system integration was tested with peripheral equipment, spatial reproducibility, and dynamic localization accuracy for regular and irregular breathing patterns, respectively. A QUASAR Respiratory Motion Phantom and a mathematical fitting method were used for data acquisition and analysis. Results The results showed that the RGSC system could accurately measure regular motion periods of 3–10 s. For irregular breathing patterns, differences from the existing Real‐time Position Management (RPM; Varian Medical Systems, Palo Alto, CA) system were observed. For dynamic localization measurements, the RGSC system showed 76% agreement with the programmed test data within ±5% tolerance in terms of fitting period. As s comparison, the RPM system showed 66% agreement within ±5% tolerance, and 65% for the RGSC versus RPM measurements. Conclusions New functions and positioning accuracy improve the RGSC system's ability to achieve higher dynamic treatment precision. A 4D phantom is helpful for the QA tests. Further investigation is required for the whole RGSC system performance QA.

Liver stereotactic body radiation therapy (SBRT) is a feasible treatment method for the nonoperable, patient with early-stage liver cancer. Treatment planning for the SBRT is very important and has to consider the simulation accuracy, planning time, treatment efficiency effects etc. The modified dynamic conformal arc (MDCA) technique is a 3-dimensional conformal arc planning method, which has been proposed for liver SBRT planning at our center. In this study, we compared the MDCA technique with the RapidArc technique in terms of planning target volume (PTV) coverage and sparing of organs at risk (OARs). The results show that the MDCA technique has comparable plan quality to RapidArc considering PTV coverage, hot spots, heterogeneity index, and effective liver volume. For the 5 PTVs studied among 4 patients, the MDCA plan, when compared with the RapidArc plan, showed 9% more hot spots, more heterogeneity effect, more sparing of OARs, and lower liver effective volume. The monitor unit (MU) number for the MDCA plan is much lower than for the RapidArc plans. The MDCA plan has the advantages of less planning time, no-collision treatment, and a lower MU number.

PurposeThe accuracy of dose delivery and the evaluation of differences between calculated and delivered dose distributions, has been studied by several groups. The aim of this investigation is to extend the gamma index by including radiobiological information and to propose a new index that we will here forth refer to as the gamma plus (γ+). Furthermore, to validate the robustness of this new index in performing a quality control analysis of an IMRT treatment plan using pure radiobiological measures such as the biologically effective uniform dose ( D ? ? ) and complication-free tumor control probability (P+). Material and methodsA new quality assurance index, the (γ+), is proposed based on the theoretical concept of gamma index presented by Low et al. (1998). In this study, the dose difference, including the radiobiological dose information (biological effective dose, BED) is used instead of just the physical dose difference when performing the γ+ calculation. An in-house software was developed to compare different dose distributions based on the γ+ concept. A test pattern for a two-dimensional dose comparison was built using the in-house software platform. The γ+ index was tested using planar dose distributions (exported from the treatment planning system) and delivered (film) dose distributions acquired in a solid water phantom using a test pattern and a theoretical clinical case. Furthermore, a lung cancer case for a patient treated with IMRT was also selected for the analysis. The respective planar dose distributions from the treatment plan and the film were compared based on the γ+ index and were evaluated using the radiobiological measures of P+ and D ? ? . ResultsThe results for the test pattern analysis indicate that the γ+ index distributions differ from those of the gamma index since the former considers radiobiological parameters that may affect treatment outcome. For the theoretical clinical case, it is observed that the γ+ index varies for different treatment parameters (e.g. dose per fraction). The dose area histogram (DAH) from the plan and film dose distributions are associated with P+ values of 50.8% and 49.0%, for a D ? ? to the target of 54.0Gy and 53.3Gy, respectively. ConclusionThe γ+ index shows advantageous properties in the quantitative evaluation of dose delivery and quality control of IMRT treatments because it includes information about the expected responses and radiobiological doses of the individual tissues.

A software program [MU-EPID], has been developed to perform patient specific pre-treatment quality assurance (QA) verification for intensity modulated radiation therapy (IMRT) using fluence maps measured with an electronic portal imaging device (EPID). The software converts the EPID acquired images of each IMRT beam, to fluence maps that are equivalent to those calculated by the treatment planning system (TPS). The software has the capability to process Varian, Elekta and Siemens EPID DICOM images. In the present investigation, several IMRT plans for different treatment sites were used to validate the software using the Varian a-Si 1000 EPID with the Pinnacle TPS. A total of 20 IMRT plans of different treatment sites were analyzed. Isodose distributions, dose profiles, dose volume histograms (DVH's) and gamma analysis comparisons were performed to evaluate the accuracy of our method. A gamma index analysis of the isocenter coronal plane was done for each plan and showed an average of 97.44% of gamma passing rate using a 3% and 3 mm gamma criterion. Isodose, DVH and dose profile comparisons were conducted between the original calculated plan and the measured reconstructed plan from the EPID images processed through the MU-EPID software. The results suggest that MU-EPID can be used clinically for patient specific IMRT QA, providing a comprehensive 3D dosimetric evaluation through DVH comparison as well as an option for a 2D gamma analysis.

A new generation of reference computational phantoms, based on image-based models tied to the reference masses defined by the International Commission on Radiological Protection (ICRP) for dose calculations, is presented. Methods: Anatomic models based on nonuniform rational b-spline modeling techniques were used to define reference male and female adults, 15-y-olds, 10-y-olds, 5-y-olds, 1-y-olds, newborns, and pregnant women at 3 stages of gestation, using the defined reference organ masses in ICRP publication 89. Absorbed fractions and specific absorbed fractions for internal emitters were derived using standard Monte Carlo radiation transport simulation codes. Results: Differences were notable between many pairs of organs in specific absorbed fractions because of the improved realism of the models, with adjacent organs usually closer and sometimes touching. Final estimates of absorbed dose for radiopharmaceuticals, for example, were only slightly different overall, as many of the differences were small and most pronounced at low radiation energies. Some new important organs were defined (salivary glands, prostate, eyes, and esophagus), and the identity of a few gastrointestinal tract organs changed. Conclusion: A new generation of reference models for standardized internal and external dose calculations has been defined. The models will be implemented in standardized software for internal dose calculations and be used to produce new standardized dose estimates for radiopharmaceuticals and other applications.

A Monte Carlo model of the Novalis Tx linear accelerator equipped with high‐definition multileaf collimator (HD‐120 HD‐MLC) was commissioned using ionization chamber measurements in water. All measurements in water were performed using a liquid filled ionization chamber. Film measurements were made using EDR2 film in solid water. Open rectangular fields defined by the jaws or the HD‐MLC were used for comparison against measurements. Furthermore, inter‐ and intraleaf leakage calculated by the Monte Carlo model was compared against film measurements. The statistical uncertainty of the Monte Carlo calculations was less than 1% for all simulations. Results for all regular field sizes show an excellent agreement with commissioning data (percent depth‐dose curves and profiles), well within 1% of difference in the relative dose and 1 mm distance to agreement. The computed leakage through HD‐MLCs shows good agreement with film measurements. The Monte Carlo model developed in this study accurately represents the new Novalis Tx Varian linac with HD‐MLC and can be used for reliable patient dose calculations. PACS number: 87.10.Rt

Novalis Tx ExacTrac X‐ray system has the 6D adjustment ability for patient setup. Limited studies exist about the setup uncertainty with ExacTrac X‐ray system for IMRT prostate treatment with fiducial markers implanted. The purpose of this study is to investigate the marker‐based prostate IMRT treatment setup uncertainty using ExacTrac 6D IGRT ability for patient setup. Forty‐three patients with prostate cancers and markers implanted have been treated on the Novalis Tx machine. The ExacTrac X‐ray system has been used for the patient pretreatment setup and intratreatment verification. In total, the shifts data for 1261 fractions and 3504 correction times (the numbers of X‐ray images were taken from tube 1 and tube 2) have been analyzed. The setup uncertainty has been separated into uncertainties in 6D. Marker matching uncertainty was also analyzed. Correction frequency probability density function was plotted, and the radiation dose for imaging was calculated. The minimum, average, and maximum translation shifts were: −5.12±3.89 mm, 0.20±2.21 mm, and 6.07±4.44 mm, respectively, in the lateral direction; −6.80±3.21 mm, −1.09±2.21 mm, and 3.12±2.62 mm, respectively, in the longitudinal direction; and −7.33±3.46 mm, −0.93±2.70 mm, and 5.93±4.85 mm, respectively, in the vertical direction. The minimum, average, and maximum rotation shifts were: −1.23° ± 1.95°, −0.25° ± 1.30°, and −2.38° ± 2.91°, respectively, along lateral direction; −0.67° ± 0.91°, −0.10° ± 0.61°, and −1.51° ± 2.04°, respectively, along longitudinal direction; and −0.75° ± 1.01°, −0.02° ± 0.50°, and −0.82° ± 1.13°, respectively, along vertical direction. On average, each patient had three correction times during one fraction treatment. The radiation dose is about 3 mSv per fraction. With the ExacTrac 6D X‐ray system, the prostate IMRT treatment with marker implanted can achieve less than 2 mm setup uncertainty in translations, and less than 0.25° in rotations as overall interfraction mean error. The imaging dose is less than kV (CBCT) for setup verification. PACS number: 87.55.km, 87.55.Qr, 87.56.bd

In this study, a clinical evaluation of the Body Pro-Lok™ System combined with the TomoTherapy megavoltage computed tomography (MVCT) was performed for lung and liver stereotactic body radiotherapy (SBRT) to reduce interfractional setup uncertainty. Twenty patients treated with 3–5 fractions of SBRT were analyzed retrospectively. The Body Pro-Lok™ system was used in both CT simulation and during patient treatment setup. Patients were immobilized with a vacuum cushion placed posteriorly over the thoracic region, an abdominal compression plate, and a knee and foot sponge. Pretreatment MVCT scans of the TomoTherapy HI-ART II unit were fused with the planning kVCT before delivery of each fraction to determine the interfractional setup error. A total of 84 shifts were analyzed to assess the interfractional setup accuracy. Results showed that the mean interfractional setup errors and standard deviations were –0.9 ± 3.1 mm, 1.2 ± 5.5 mm, and 6.5 ± 2.6 mm for lateral (IEC-X), longitudinal (IEC-Y), and vertical (IEC-Z) variations, respectively. The maximum motion was 17.1 mm in the longitudinal direction. When all 3 translational coordinates were analyzed, a mean composite displacement vector of 8.2 ± 2.0 mm (range 4.1–11.7 mm) was obtained for all patients. Based on the findings, image-guided SBRT using the Body Pro-Lok™ system in conjunction with the MVCT of TomoTherapy is capable of minimizing interfractional setup error and improving treatment accuracy.

Purpose: To develop a novel four-dimensional (4D) intensity modulated radiation therapy(IMRT)treatment planning methodology based on dynamic virtual patient models. Methods: The 4D model-based planning (4DMP) is a predictive tracking method which consists of two main steps: (1) predicting the 3D deformable motion of the target and critical structures as a function of time during treatment delivery; (2) adjusting the delivery beam apertures formed by the dynamic multi-leaf collimators (DMLC) to account for the motion. The key feature of 4DMP is the application of a dynamic virtual patient model in motion prediction, treatment beam adjustment, and dose calculation. A lung case was chosen to demonstrate the feasibility of the 4DMP. For the lung case, a dynamic virtual patient model (4D model) was first developed based on the patient’s 4DCT images. The 4D model was capable of simulating respiratory motion of different patterns. A model-based registration method was then applied to convert the 4D model into a set of deformation maps and 4DCT images for dosimetric purposes. Based on the 4D model, 4DMP treatment plans with different respiratory motion scenarios were developed. The quality of 4DMP plans was then compared with two other commonly used 4D planning methods: maximum intensity projection (MIP) and planning on individual phases (IP). Results: Under regular periodic motion, 4DMP offered similar target coverage as MIP with much better normal tissue sparing. At breathing amplitude of 2 cm, the lung V20 was 23.9% for a MIP plan and 16.7% for a 4DMP plan. The plan quality was comparable between 4DMP and IP: PTV V97 was 93.8% for the IP plan and 93.6% for the 4DMP plan. Lung V20 of the 4DMP plan was 2.1% lower than that of the IP plan and Dmax to cord was 2.2 Gy higher. Under a real time irregular breathing pattern, 4DMP had the best plan quality. PTV V97 was 90.4% for a MIP plan, 88.6% for an IP plan and 94.1% for a 4DMP plan. Lung V20 was 20.1% for the MIP plan, 17.8% for the IP plan and 17.5% for the 4DMP plan. The deliverability of the real time 4DMP plan was proved by calculating the maximum leaf speed of the DMLC. Conclusions: The 4D model-based planning, which applies dynamic virtual patient models in IMRTtreatment planning, can account for the real time deformable motion of the tumor under different breathing conditions. Under regular motion, the quality of 4DMP plans was comparable with IP and superior to MIP. Under realistic motion in which breathing amplitude and period change, 4DMP gave the best plan quality of the three 4D treatment planning techniques.

Objectives: The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. Methods: Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P+) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. Results: The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P+ of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average DP+ of 27.0% for a D effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average DP+ of 23.8% for a D effective uniform dose of 11.6 Gy. Conclusion: A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose–response relations of the irradiated tumours and normal tissues. The use of P – effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans.

The pulsed power technology has been applied to many defense and industrial fields. Different applications have different demands on the parameters of the pulsed power systems. However, the parameters of the current pulsed power systems are usually fixed and cannot be changed easily. As a special nonlinear device, metal-oxide varistor was considered to be applied for generating square pulses. Moreover, the magnetic switches are widely used in the field of the pulsed power technology due to the special switching characteristic. This paper proposed a high voltage pulse generator with pulse width adjustable based on the magnetic switch and metal-oxide varistor. The pulse forming network and metal-oxide varistor were combined to generate quasi-square pulses, the magnetic switch was used as a crowbar switch to sharpen the falling edge and the pulse width was adjusted by changing the reset current. The paper carried on theoretical analysis as well as simulation study, and developed preliminary experiment based on the simulation results. In the preliminary experiment, the falling edge of the voltage waveforms obtained on a dummy water load is less than 50 ns, the flat-top is about 7 kV and the pulse width is adjustable within 200 ns-900 ns. This kind of pulse generator with pulse width adjustable can be applied to many fields such as corona plasma generation, industrial dedusting and medical disinfection.

A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95.2% in water phantoms without RBE enhancement (planned BED). About 10% increase in the source output is required to raise BED PTV V(100) to 95%. As a conclusion, the composite effect of dose reduction in the target due to heterogeneities and RBE enhancement results in a net effect of 5.3% target BED coverage loss for electronic brachytherapy. Therefore, it is suggested that about 10% increase in the source output may be necessary to achieve sufficient target coverage higher than 95%.

This paper introduces the development and experiments of a 100 kV-level pulse generator based on a metal-oxide varistor (MOV). MOV has a high energy handling capacity and nonlinear voltage-current (V-I) characteristics, which makes it useful for high voltage pulse shaping. Circuit simulations based on the measured voltage-current characteristics of MOV verified the shaping concept and showed that a circuit containing a two-section pulse forming network (PFN) will result in better defined square pulse than a simple L-C discharging circuit. A reduced-scale experiment was carried out and the result agreed well with simulation prediction. Then a 100 kV-level pulse generator with multiple MOVs in a stack and a two-section pulse forming network (PFN) was experimented. A pulse with a voltage amplitude of 90 kV, rise time of about 50 ns, pulse width of 500 ns, and flat top of about 400 ns was obtained with a water dummy load of 50 Ω. The results reveal that the combination of PFN and MOV is a practical way to generate high voltage pulses with better flat top waveforms, and the load voltage is stable even if the load's impedance varies. Such pulse generator can be applied in many fields such as surface treatment, corona plasma generation, industrial dedusting, and medical disinfection.

A software program, MU-Tomo, has been developed to perform an independent point dose calculation and compare it to the dose calculated from the TomoTherapy (TomoTherapy, Inc., Madison, WI) treatment planning system (TPS). Input parameters required for this software include: archived tomotherapy patient files, QA plan image coordinates, tomotherapy-calculated point dose and machine-specific dosimetric parameters such as the off-axis ratios (OARx and OARy), tissue phantom ratios (TPR) and output functions (Scp). The software was validated on four phantom models and fifty tomotherapy patient plans representing various anatomical sites. Our results indicate that MU-Tomo can perform in a few seconds an independent dose calculation accurately and provide a secondary check for a point dose validation of helical tomotherapy plans.

The specific absorbed fraction (Phi), defined by the Medical Internal Radiation Dose Committee, is generally applied to evaluate the average absorbed dose in a target organ as a result of radioactive materials deposited in a source organ. This paper reports a new set of Phi values for internal electron emitters ranging from 10 keV to 4 MeV from various internal organs of the mother to the fetus based on three newly developed pregnant female tomographic models, called RPI-P3, RPI-P6 and RPI-P9. The results show a linear log relationship between Phi values and electron energy. The linear log coefficients have been derived and reported. The relationship between Phi values and mean distances between source organs and the fetus were also determined to allow for individual dosimetry. Since the RPI-P models have finer details of human anatomy and more realistic organ volumes and geometries, which follow the latest ICRP reference values, the newly derived Phi values could be used as reference values in determination of the dose to the fetus from internal electron emitters.

The purpose of this study was to commission a first-of-its-kind dual-layer micro multileaf collimator (mMLC) system by using Monte Carlo dose calculations. The mMLC is attached on a Varian 600C linac. Having a lower and an upper layer of MLC leaves, this mMLC allows for field shaping in two orthogonal directions. The commissioning of the system was performed in two steps: without and with the mMLC attached on the linac. The treatment head without and with the mMLC was modeled in the BEAMnrc Monte Carlo (MC) code. The scoring planes for the phase space files were specified below the linac's secondary collimators (jaws) and above and below the mMLC. With the mMLC attached to the linac the field size was defined by the jaws as 10 × 10 cm2, which is also the maximum possible field size that can be shaped by the mMLC. For the commissioning of the linac, several fields of various sizes were simulated and compared against ionization chamber measurements in a water phantom. Output factors for several field sizes, as well as percent depth dose curves and dose profiles for rectangular and irregular shape fields, were calculated and compared against measurements in water. Agreement between measured and calculated data was better than 1% and less than 1.0 mm in the penumbra region for open fields. With the mMLC attached, the agreement between measurements and MC calculations is within 1.0% or 1.0 mm in the penumbra region.

Yaxi Liu, Ph.D. 11.9999 Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Normal 0 false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} Respiratory motion has been considered a clinical challenge for lung tumor treatments due to target motion. In this study, we aimed to perform an experimental evaluation based on dynamic phantoms using MLC-based beam tracking. TrackBeam TM , a prototype real-time beam tracking system, has been assembled and evaluated in our clinic. TrackBeam TM includes an orthogonal dual-layer micro multi-leaf collimator (DmMLC), an on-board mega-voltage (MV) portal imaging device, and an image processing workstation. With a fiducial marker implanted in a moving target, the on-board imaging device can capture the motion. The TrackBeam TM workstation processes the online MV fluence and detects and predicts tumor motion. The DmMLC system then dynamically repositions each leaf to form new beam apertures based on the movement of the fiducial marker. In this study, a dynamic phantom was used for the measurements. Three delivery patterns were evaluated for dosimetric verification based on radiographic films: no-motion-lung-tumor (NMLT), three-dimensional conformal radiotherapy (3DCRT), and four-dimensional tracking radiotherapy (4DTRT). The displacement between the DmMLC dynamic beam isocenter and the fiducial marker was in the range of 0.5 mm to 1.5 mm. With radiographic film analysis, the planar dose histogram difference between 3DCRT and NLMT was 48.6% and 38.0% with dose difference tolerances of 10% and 20%. The planar dose histogram difference between 4DTRT and NLMT was 15.2% and 4.0% respectively. Based-on dose volume histogram analysis, 4DTRT reduces the mean dose for the surrounding tissue from 35.4 Gy to 19.5 Gy, reduces the relative volume of the total lung from 28% to 18% at V 20 , and reduces the amount of dose from 35.2 Gy to 15.0 Gy at D 20 . The experimental results show that MLC-based real-time beam tracking delivery provides a potential solution to respiratory motion control. Beam tracking delivers a highly conformal dose to a moving target, while sparing surrounding normal tissue.

The investigation of the clinical efficacy and effectiveness of Intensity Modulated Radiotherapy (IMRT) using Multileaf Collimators (MLC) and Helical Tomotherapy (HT) has been an issue of increasing interest over the past few years. In order to assess the suitability of a treatment plan, dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean, and standard deviation of the dose distribution are typically used. Nevertheless, the radiobiological parameters of the different tumors and normal tissues are often not taken into account. The use of the biologically effective uniform dose (D̿) together with the complication-free tumor control probability ( P+) were applied to evaluate the two radiation modalities. Two different clinical cases of brain and cranio-spinal axis cancers have been investigated by developing a linac MLC-based step-and-shoot IMRT plan and a Helical Tomotherapy plan. The treatment plans of the MLC-based IMRT were developed on the Philips treatment planning station using the Pinnacle 7.6 software release while the dedicated Tomotherapy treatment planning station was used for the HT plan. With the use of the P+ index and the D̿ concept as the common prescription point, the different treatment plans were compared based on radiobiological measures. The tissue response probabilities were plotted against D̿ for a range of prescription doses. The applied plan evaluation method shows that in the brain cancer, the HT treatment gives slightly better results than the MLC-based IMRT in terms of optimum expected clinical outcome ( P+ of 66.1% and 63.5% for a D̿ to the PTV of 63.0 Gy and 62.0 Gy, respectively). In the cranio-spinal axis cancer, the HT plan is significantly better compared to the MLC-based IMRT plan over the clinically useful dose prescription range ( P+ of 84.1% and 28.3% for a D̿ to the PTV of 50.6 Gy and 44.0 Gy, respectively). If a higher than 5% risk for complications could be allowed, the complication-free tumor control could be increased by almost 30% compared to the initial dose prescription. In comparison to MLC based-IMRT, HT can better encompass the often large PTV while minimizing the volume of the OARs receiving high dose. A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumors and normal tissues. The use of P — D̿ diagrams can complement the traditional tools of evaluation such as DVHs, in order to compare and effectively evaluate different treatment plans.

Intensity modulated radiotherapy (IMRT) is an advanced treatment technology for radiation therapy. There are several treatment planning systems (TPS) that can generate IMRT plans. These plans may show different inhomogeneity indices to the planning target volume (PTV) and integral dose to organs at risk (OAR). In this study, we compared clinical cases covering different anatomical treatment sites, including head and neck, brain, lung, prostate, pelvis, and cranio-spinal axis. Two treatment plans were developed for each case using Pinnacle 3 and helical tomotherapy (HT) TPS. The inhomogeneity index of the PTV and the non-tumor integral dose (NTID) were calculated and compared for each case. Despite the difference in the number of effective beams, in several cases, NTID did not increase from HT as compared to the step-and-shoot delivery method. Six helical tomotherapy treatment plans for different treatment sites have been analyzed and compared against corresponding step-and-shoot plans generated with the Pinnacle 3 planning system. Results show that HT may produce plans with smaller integral doses to healthy organs, and fairly homogeneous doses to the target as compared to linac-based step-and-shoot IMRT planning in special treatment site such as cranio-spinal.

During helical tomotherapy, gantry angle accuracy is one of the vital geometric factors that assure accurate dose delivery to the target and organs at risk adjacent to it. The purpose of this study is to investigate the dosimetric impact of gantry angle misalignment on the target volume and critical organs during helical tomotherapy treatment. Five prostate cases were chosen to calculate the effects of gantry angle deviations on both patient-specific delivery quality assurance (DQA) and helical tomotherapy treatment plans. For DQA plans, the cheese phantom was rotated for up to +/-5 degrees from the preset position to simulate the gantry angle deviations during tomotherapy. Point doses at 5 mm below the isocenter and the dose distribution for each gantry angle were measured and reconstructed, respectively. For helical tomotherapy treatment plans, the same gantry misalignment effect was simulated by adjusting the automatic roll correction for up to +/-5 degrees using Planned Adaptive software. Variations of dose volume histograms (DVHs) and isodose lines were evaluated for both target and critical organs. There was no significant difference found, however, among the point dose measurements for gantry rotation up to +/-5 degrees in DQA plans. Shifts of isodose lines could be observed for gantry rotations larger than +/-27 degrees. Dosimetric discrepancies (less than 2%) were also found among DVHs of the PTV in the cases when gantry angle misalignment was larger than +/-2 degrees. However, for DVHs of either bladder or rectum under different gantry rotations, no significant differences were detected when gantry angle errors were up to +/-5 degrees. In summary, point dose measurements alone cannot reveal the dosimetric deviation due to gantry angle misalignment in DQA plans. For a 5 degrees gantry deviation, the dose to PTV increased by 0.5% comparing to the planned dose. The influence on organs at risk, i.e., rectum and bladder, is also negligible. Further studies are needed on the dosimetric impacts of gantry angle deviations for other treatment sites.

Estimates of radiation absorbed doses from radionuclides internally deposited in a pregnant woman and her fetus are very important due to elevated fetal radiosensitivity. This paper reports a set of specific absorbed fractions (SAFs) for use with the dosimetry schema developed by the Society of Nuclear Medicine’s Medical Internal Radiation Dose (MIRD) Committee. The calculations were based on three newly constructed pregnant female anatomic models, called RPI-P3, RPI-P6, and RPI-P9, that represent adult females at 3-, 6-, and 9-month gestational periods, respectively. Advanced Boundary REPresentation (BREP) surface-geometry modeling methods were used to create anatomically realistic geometries and organ volumes that were carefully adjusted to agree with the latest ICRP reference values. A Monte Carlo user code, EGS4-VLSI, was used to simulate internal photon emitters ranging from 10 keV to 4 MeV. SAF values were calculated and compared with previous data derived from stylized models of simplified geometries and with a model of a 7.5-month pregnant female developed previously from partial-body CT images. The results show considerable differences between these models for low energy photons, but generally good agreement at higher energies. These differences are caused mainly by different organ shapes and positions. Other factors, such as the organ mass, the source-to-target-organ centroid distance, and the Monte Carlo code used in each study, played lesser roles in the observed differences in these. Since the SAF values reported in this study are based on models that are anatomically more realistic than previous models, these data are recommended for future applications as standard reference values in internal dosimetry involving pregnant females.

Temporal and spatial anatomic changes caused by respiration during radiation treatment delivery can lead to discrepancies between prescribed and actual radiation doses. The present paper documents a study to construct a respiratory‐motion‐simulating, four‐dimensional (4D) anatomic and dosimetry model for the study of the dosimetric effects of organ motion for various radiation treatment plans and delivery strategies. The non‐uniform rational B‐splines (NURBS) method has already been used to reconstruct a three‐dimensional (3D) VIP‐Man (“visible photographic man”) model that can reflect the deformation of organs during respiration by using time‐dependent equations to manipulate surface control points. The EGS4 (Electron Gamma Shower, version 4) Monte Carlo code is then used to apply the 4D model to dose simulation. We simulated two radiation therapy delivery scenarios: gating treatment and 4D image‐guided treatment. For each delivery scenario, we developed one conformal plan and one intensity‐modulated radiation therapy plan. A lesion in the left lung was modeled to investigate the effect of respiratory motion on radiation dose distributions. Based on target dose–volume histograms, the importance of using accurate gating to improve the dose distribution is demonstrated. The results also suggest that, during 4D image‐guided treatment delivery, monitoring of the patient's breathing pattern is critical. This study demonstrates the potential of using a “standard” motion‐simulating patient model for 4D treatment planning and motion management. PACS numbers: 87.53.Bn, 87.53.Kn, 87.53.Tf, 87.53.Wz, 87.57.Gg, 89.80.+h

To investigate the impact of prone versus supine patient set-up and use of various image-guidance protocols on residual set-up error for radiation therapy of pelvic malignancies. We aim to identify an optimal frequency and protocol for image-guidance.Using daily online image-guidance mega-voltage CT data from 30 patients (829 MVCT; 299 prone set-up on belly board, 530 supine set-up), we retrospectively assessed the impact of various image-guidance protocols on residual set-up error. We compared daily image-guidance with three different No Action Level protocols (NAL), alternate day image-guidance with running mean and weekly image-guidance.Of 5 IGRT protocols analyzed, the protocol with the highest imaging frequency, alternate day imaging with a running mean (50% imaging frequency), provided the best set-up error reduction. This protocol would have reduced the average length of 3D corrective vector shifts derived from daily image-guidance from 15.2 and 13.5 mm for prone and supine set-up, to 5 and 5.4 mm, respectively. A NAL protocol, averaging shifts of the first 3 fractions (NAL3), would have reduced the respective set-up variability to 6.3 (prone), and 7.5 mm (supine). An extended NAL (eNAL) protocol, averaging shifts of the first 3 fractions plus weekly imaging, would have reduced the daily positioning variability to 6 mm for both prone and supine set-ups. Daily image-guidance yielded set-up corrections10 mm in 64.3% for prone and 70.3% for supine position. Use of the NAL3 protocol would have reduced the respective frequency to 14.4%, and 21.2% for prone, and supine positioning. In comparison, the alternate day running mean protocol would have reduced the frequency of shifts10 mm to 5.5% (prone), and 8.3% (supine), respectively.In this comparison, high frequency image-guidance provided the highest benefit with respect to residual set-up errors. However, both NAL and eNAL protocols provided significant set-up error reduction with lowered imaging frequency. While the mean 3D vector of corrective shifts was longer for prone set-up compared to the supine set-up, using any image-guidance protocol would have reduced shifts for prone set-up to a greater extent than for the supine set-up. This indicates a greater risk for systematic set-up errors in prone set-up, and larger random errors using a supine patient set-up.

For the last 50 years, high-energy electron beams have been used mainly for treatment of superficial targets. Accordingly, two-dimensional (2D) measurements are required to determine the margin between the surface and protected normal tissues in high-dose-gradient regions. As recommended by the AAPM, 2D electron beam dosimetry should be conducted primarily with films because of their high spatial resolution and because of the fact that they produce permanent records. In this work, the dosimetric characteristics of a newly developed radiochromic film, GAFCHROMIC EBT film were used to study treatment parameters for therapeutic electron beams. The dose-response curve was found to be weakly dependent on the electron beam energy (within +/-4%). The effect of fractionation, as well as electron beam dose rate, had small influence on the calibration curve of EBT films (+/-2.5% and 2%, respectively). For the investigated range of depth, dose-response curves are nearly independent of the calibration depth. As for the cone size dependence, we found that it is accurate to calibrate GAFCHROMIC EBT films using a 10 x 10 cm(2) cone and apply this calibration to other cone sizes.

Quality assurance (QA) of the multileaf collimator (MLC) is a critical step for the delivery of intensity modulated radiation therapy treatment plan. While QA procedures for motor-driven MLC have been published extensively, those for binary MLCs such as the one used for helical tomotherapy have not been presented in the literature, as this is still a fairly new technology. In this study, seven test patterns for the MLC QA of a helical tomotherapy unit have been designed and implemented. The seven test patterns check the MLC alignment, MLC leakage, MLC timing and MLC leaf position error in detail. Those patterns can be easily implemented in any center with a helical tomotherapy unit as part of the routine QA. The QA procedures can be performed using existing QA resources such as solid water phantom and EDR2 film. A software toolkit called "Tomo MLC QA" has been developed to assist in generating the QA procedures and analyzing the results. Our results showed that the helical tomotherapy MLC is very robust, exhibiting interleaf leakage of 0.53% +/-0.09%. Several issues with the MLC have been found and discussed. The QA results also illustrate the utilization and usefulness of the proposed QA procedures.

In recent years, mobile robots are playing an increasingly important role in the rescue work. Relative research has been widely attention. Mapping of the environment and navigation research become more important when robots need to move in a complex environment. Two-dimensional(2D) mapping can not be remarkable in robot navigation due to the limitation of information access, while laser-based 3D mapping always owns high cost. Besides, the accuracy of ordinary 3D mapping cannot meet requirement. In this paper, a method is presented to realize the low cost 3D-environment-mapping. We combine the two-dimensional navigation algorithm based on extended Kalman filtering with the three-dimensional mapping based on SIFT algorithm. The 2D laser ranger cooperates with Kinect sensor. Experimental result shows that the method can guide the robot to explore independently in the unknown environment with good performance for mapping and navigation.

In our institution, patient‐specific quality assurance (QA) for intensity‐modulated radiation therapy (IMRT) is usually performed by measuring the dose to a point using an ion chamber and by measuring the dose to a plane using film. In order to perform absolute dose comparison measurements using film, an accurate calibration curve should be used. In this paper, we investigate the film response curve uncertainty factors, including film batch differences, film processor temperature effect, film digitization, and treatment unit. In addition, we reviewed 50 patient‐specific IMRT QA procedures performed in our institution in order to quantify the sources of error in film‐based dosimetry. Our study showed that the EDR2 film dosimetry can be done with less than 3% uncertainty. The EDR2 film response was not affected by the choice of treatment unit provided the nominal energy was the same. This investigation of the different sources of uncertainties in the film calibration procedure can provide a better understanding of the film‐based dosimetry and can improve quality control for IMRT QA. PACS numbers: 87.86.Cd, 87.53.Xd, 87.57.Nk

Presentation and comparison of tomotherapeutic intensity-modulated techniques for planning and delivery of stereotactic body radiation therapy. Serial tomotherapeutic SBRT has been planned and delivered at our institution since 8/2001. Since 12/2005, 12 patients have been treated using a helical tomotherapy unit. For these 12 patients both helical and serial tomotherapy plans were computed and clinically approved. Techniques and considerations of tomotherapy SBRT planning, associated image-guidance, and delivery are presented. The respective treatment plans were compared based on dosimetric parameters as well as time to develop a treatment plan and delivery times. Also the associated quality of megavoltage CT (MVCT) image-guidance inherent to the helical tomotherapy unit was assessed. Tumor volumes averaged 9.3, 9.8, and 58.7 cm3 for liver, lung, and spinal targets. Helical and serial tomotherapy plans showed comparable plan quality with respect to maximum and average doses to the gross tumor and planning target volumes. Time to develop helical tomotherapy plans averaged 3.5 h while serial tomotherapy planning consistently required less than one hour. Treatment delivery was also slower using helical tomotherapy, with differences of less than 10 min between modalities. MVCT image-guidance proved satisfactory for bony and lung targets, but failed to depict liver lesions, owing to poor soft-tissue contrast. SBRT planning and delivery is clinically feasible using either tomotherapeutic modality. While treatment planning time was consistently shorter and more readily accomplished in a standardized approach using the serial tomotherapy modality, actual plan quality and treatment delivery times are grossly comparable between the modalities. MVCT volumetric image-guidance, was observed to be valuable for thoracic and spinal target volumes, whereas it proved challenging for liver targets.

Assessment of radiation dose and risk to a pregnant woman and her fetus is an important task in radiation protection. Although tomographic models for male and female patients of different ages have been developed using medical images, such models for pregnant women had not been developed to date. This paper reports the construction of a partial-body model of a pregnant woman from a set of computed tomography (CT) images. The patient was 30 weeks into pregnancy, and the CT scan covered the portion of the body from above liver to below pubic symphysis in 70 slices. The thickness for each slice is 7 mm, and the image resolution is 512x512 pixels in a 48 cm x 48 cm field; thus, the voxel size is 6.15 mm3. The images were segmented to identify 34 major internal organs and tissues considered sensitive to radiation. Even though the masses are noticeably different from other models, the three-dimensional visualization verified the segmentation and its suitability for Monte Carlo calculations. The model has been implemented into a Monte Carlo code, EGS4-VLSI (very large segmented images), for the calculations of radiation dose to a pregnant woman. The specific absorbed fraction (SAF) results for internal photons were compared with those from a stylized model. Small and large differences were found, and the differences can be explained by mass differences and by the relative geometry differences between the source and the target organs. The research provides the radiation dosimetry community with the first voxelized tomographic model of a pregnant woman, opening the door to future dosimetry studies.