TomoMQA: Automated analysis program for MVCT quality assurance of helical tomotherapy.

PURPOSE: In this study, we developed a simple but useful computer program, called TomoMQA, to offer an automated quality assurance for mega-voltage computed tomography (MVCT) images generated via helical tomotherapy. METHODS: TomoMQA is written in MATLAB and contains three steps for analysis: (a) open the DICOM dataset folder generated via helical tomotherapy (i.e., TomoTherapy® and Radixact™), (b) call the baseline data for the consistency test and click the "Analysis" button (or click the "Analysis" button without the baseline data and export the results as the baseline data), and (c) print an analyzed report. The overall procedure for the QA analysis included in TomoMQA is referred from the TG-148 recommendation. Here, the tolerances for MVCT QA were implemented from TG-148 recommended values as default; however, it can be modified by a user manually. RESULTS: To test the performance of the TomoMQA program, 15 MVCTs were prepared from five helical tomotherapy machines (1 of TomoTherapy® HD, 2 of TomoTherapy® HDA, and 2 of Radixact™) in 3 months and the QA procedures were performed using TomoMQA. From our results, the evaluation revealed that the developed program can successfully perform the MVCT QA analysis irrespective of the type of helical tomotherapy equipment. CONCLUSION: We successfully developed a new automated analysis program for MVCT QA of a helical tomotherapy platform, called TomoMQA. The developed program will be made freely downloadable from the TomoMQA-dedicated website.

Preliminary study for dose evaluation depending on dose range with optically stimulated luminescence dosimeter considering individual dosimeter sensitivity.

The purpose of this study was to investigate dose evaluation depending on dose range using optically stimulated luminescence dosimeter (OSLD) and evaluate the possibility of high dose evaluation. This study investigated a commercial OSLD and used a Co-60 gamma irradiator for irradiation. The OSLDs (N = 26) were sampled in total OSLDs (N = 46) depending on the radiation sensitivity for this study. After irradiating doses from 0.5 to 40 Gy at fixed intervals in a standard environment, the dose response of a reference OSLD (N = 5) was determined through the reading process at each dose. The dose-response curves obtained from the reference OSLD were fitted according to the dose. In the dose range below 3 Gy, a linear function was used to determine the relationship between dose and the OSLD response. Quadratic and cubic functions were applied for dose ranges of up to 15 Gy and 40 Gy, respectively. Test OSLDs (N = 21) were evaluated at various doses (2.5 to 30 Gy) using different fitting functions, according to dose ranges. When doses from 0.5 Gy to 3.0 Gy were curve-fitted to the linear function, the relationship was y = 70278.0x - 3125.3 (r2 = 0.999). When doses of up to 15 Gy were curve-fitted to the quadratic function, the relationship was y = 628.6x2 + 70444.6x - 6142.3 (r2 = 0.999). Furthermore, when doses of up to 40 Gy were curve-fitted to the cubic function, the relation was y = -15.5x3 + 527.3x2 + 75059.6x - 16260.3 (r2 = 0.998). Test OSLDs were evaluated for various dose ranges based on the above equation. It was confirmed that the average difference was 0.86 ± 0.27%, and it was evaluated that the largest difference occurred at 30 Gy (2.24 ± 0.24%). In this study, we prove that measurements using the OSLD at various dose ranges, including high doses, will be possible through the application of an in-house software program and a correction process.

Performance Evaluation of Deformable Image Registration Algorithms Using Computed Tomography of Multiple Lung Metastases.

Purpose: Various deformable image registration (DIR) methods have been used to evaluate organ deformations in 4-dimensional computed tomography (4D CT) images scanned during the respiratory motions of a patient. This study assesses the performance of 10 DIR algorithms using 4D CT images of 5 patients with fiducial markers (FMs) implanted during the postoperative radiosurgery of multiple lung metastases. Methods: To evaluate DIR algorithms, 4D CT images of 5 patients were used, and ground-truths of FMs and tumors were generated by physicians based on their medical expertise. The positions of FMs and tumors in each 4D CT phase image were determined using 10 DIR algorithms, and the deformed results were compared with ground-truth data. Results: The target registration errors (TREs) between the FM positions estimated by optical flow algorithms and the ground-truth ranged from 1.82 ± 1.05 to 1.98 ± 1.17 mm, which is within the uncertainty of the ground-truth position. Two algorithm groups, namely, optical flow and demons, were used to estimate tumor positions with TREs ranging from 1.29 ± 1.21 to 1.78 ± 1.75 mm. With respect to the deformed position for tumors, for the 2 DIR algorithm groups, the maximum differences of the deformed positions for gross tumor volume tracking were approximately 4.55 to 7.55 times higher than the mean differences. Errors caused by the aforementioned difference in the Hounsfield unit values were also observed. Conclusions: We quantitatively evaluated 10 DIR algorithms using 4D CT images of 5 patients and compared the results with ground-truth data. The optical flow algorithms showed reasonable FM-tracking results in patient 4D CT images. The iterative optical flow method delivered the best performance in this study. With respect to the tumor volume, the optical flow and demons algorithms delivered the best performance.

Effect of Interleukin-7 on Radiation-Induced Lymphopenia and Its Antitumor Effects in a Mouse Model.

PURPOSE: Local ionizing radiation (IR) can lead to systemic lymphocyte depletion, which is associated with poor survival outcomes in patients with cancer. Interleukin-7 (IL-7) plays an important role in lymphocyte homeostasis; however, its role in alleviating radiation-induced lymphopenia remains unclear. Hence, we established a radiation-induced lymphopenia animal model and evaluated the effect of exogenous IL-7 administration. METHODS: C3H/HeN mice underwent x-ray irradiation of 30 Gy in 10 fractions at the right hind limbs. Next, 10 mg/kg of IL-7 was injected subcutaneously, and the lymphocyte count in blood was measured. Murine hepatocellular carcinoma (HCa-1) cells were inoculated subcutaneously into the right thighs of tumor model mice, which underwent the same treatment. RESULTS: In the naïve mouse model, the decreased CD45+ cell count after irradiation gradually recovered to the initial level over 3 weeks in the IR group, whereas it markedly increased to 373% of the initial level in 1 week in the IR+IL-7 group. Similar trends were observed for the CD3+, CD8+, CD4+, regulatory T cells, and CD19+ B cell counts. Similar findings were observed in the tumor mouse model. CD8+ and CD4+ T cell infiltration in tumor specimens was higher in the IL-7 and IR+IL-7 groups than in the nontreated and IR groups. Tumor growth was significantly more suppressed in the IR+IL-7 group than in the IR group. The median survival time was significantly longer in the IR+IL-7 group (not reached) than in the IR (56 days; P = .0382), IL-7 (36 days; P = .0004), or nontreated groups (36 days; P < .0001). CONCLUSIONS: Administration of exogenous IL-7 after IR not only restored lymphocyte counts but also enhanced the antitumor effect. Exogenous IL-7 can be beneficial in overcoming radiation-induced lymphopenia and in enhancing the treatment outcome in combination with radiation therapy, which needs validation through future clinical studies.

TomoEQA: Dose verification for patient-specific quality assurance in helical tomotherapy using an exit detector.

PURPOSE: Existing phantom-less quality assurance (QA) platforms does not provide patient-specific QA for helical tomotherapy (HT). A new system, called TomoEQA, is presented to facilitate this using the leaf open time (LOT) of a binary multi-leaf collimator, as measured by an exit detector. METHODS: TomoEQA was designed to provide measurement-based LOTs based on detector data and to generate a new digital imaging and communication in medicine (DICOM) dataset that includes the measured LOTs for use by secondary check platforms. To evaluate the system, 20 patient-specific QAs were performed using the program in Mobius3D software, and the results were compared to conventional phantom-based QA results. RESULTS: From our assessment, most of the differences between the planned and measured (or calculated) data, excluding one case, were within the acceptance criteria comparing with those of conventional QA. Regarding the gamma analysis, all results considered in this study were within the acceptance criteria. In addition, the developed system was performed for a failed case and showed approximately the same trends as the conventional approach. CONCLUSIONS: TomoEQA could perform patient-specific QAs of HT using Mobius3D and provide reliable patient-specific QAs results by evaluating point dose errors and 3D gamma passing rates. TomoEQA could also distinguish whether an intensity-modulated radiation therapy plan failed or not.

Monitoring beam-quality constancy considering uncertainties associated with ionization chambers in Daily QA3 device.

This study evaluates the changes occurring in the X-ray energy of a linear accelerator (LINAC) using a Daily QA3 detector system. This is accomplished by comparing the Daily QA3 results against those obtained using a water phantom. The X-energy levels of a LINAC were monitored over a duration of 1 month using the Daily QA3 system. Moreover, to account for the uncertainty, the reproducibility of the Daily QA3 ionization-chamber results was assessed by performing repeated measurements (12 per day). Subsequently, the energy-monitoring results were compared with the energy-change results calculated using the water-phantom percentage depth dose (PDD) ratio. As observed, the 6- and 10-MV beams experienced average daily energy-level changes of (-0.30 ± 0.32)% and (0.05 ± 0.38)%, respectively, during repeated measurements. The corresponding energy changes equaled (-0.30 ± 0.55)% and (-0.05 ± 0.48)%, respectively, when considering the measurement uncertainty. The Daily QA3 measurements performed at 6 MV demonstrated a variation of (2.15 ± 0.81)% (i.e., up to 3%). Meanwhile, the corresponding measurements performed using a water phantom demonstrated an increase in the PDD ratio from 0.577 to 0.580 (i.e., approximately 0.5%). At 10 MV, the energy variation in the Daily QA3 measurements equaled (-0.41 ± 0.82)% (i.e., within 1.5%), whereas the corresponding water phantom PDD ratio remained constant at 0.626. These results reveal that the Daily QA3 system can be used to monitor small energy changes occurring within radiotherapy machines. This demonstrates its potential for use as a secondary system for monitoring energy changes as part of the daily quality-assurance workflow.

Pharmacologic Inhibition of HIF-1α Attenuates Radiation-Induced Pulmonary Fibrosis in a Preclinical Image Guided Radiation Therapy.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a long-term side effect of thoracic radiation therapy. Hypoxia-induced vascular endothelial mesenchymal transition (EndMT) can occur during the development of RIPF. Here, we examined the direct contribution of endothelial HIF-1α (EC-HIF1α) on RIPF. METHODS AND MATERIALS: An inducible Cre-lox-mediated endothelial Hif1a deletion mouse line was used to evaluate the potential of HIF-1α inhibition to suppress RIPF. To evaluate the effects of a pharmacologic HIF-1α inhibitor on RIPF after image guided radiation therapy (IGRT) for spontaneous lung adenocarcinoma, we generated conditional tdTomato; K-RasG12D; and p53 flox/flox mice to facilitate tracking of tumor cells expressing tdTomato. RESULTS: We found that vascular endothelial-specific HIF-1α deletion shortly before radiation therapy inhibited the progression of RIPF along with reduced EndMT, whereas prolonged deletion of endothelial HIF-1α before irradiation did not. Moreover, we revealed that postirradiation treatment with the novel HIF-1α inhibitor, 2-methoxyestradiol (2-ME) could efficiently inhibit RIPF and EndMT. In addition, IGRT using primary mouse models of non-small cell lung cancer showed that combined treatment of 2-ME with ablative high-dose radiation therapy efficiently inhibited RIPF and the growth of both multifocal and single tumors, concomitantly reducing radiation-induced EndMT of normal as well as tumor regions. CONCLUSION: These results suggest that a negative regulator of HIF-1α-mediated EndMT, such as 2-ME, may serve as a promising inhibitor of RIPF in radiation therapy.

Assessment of dosimetric leaf gap correction factor in Mobius3D commissioning affected by couch top.

This study assesses the dosimetric leaf gap (DLG) correction factor in Mobius3D commissioning affected by a couch top platform and calculates the optimal DLG value according to the point dose difference function. DLG optimizations were performed for 3 LINAC machines and a total of 30 patient volumetric modulated arc therapy plans (i.e., 10 plans per each LINAC). Point dose calculations were performed using an automatic dose calculation system in Mobius3D as well as Mobis3D calculation using a Mobius Verification Phantom (MVP)-based quality assurance plan with a carbon fiber couch top. Subsequently, the results were compared with measurement data. The averaged point dose measured for the MVP with a couch top decreased by approximately 2% relative to that without the couch top. The average of the optimal DLG factors increased by 1.153 mm due to the couch top effect for a dose decrease of 2% at the measured point. In the procedure of Mobius beam commissioning, users should adjust the DLG correction factor using a specific phantom (including MVP) with a couch top structure. If the DLG optimization were performed by using MVP automatic dose calculation system, the factor should be increased by approximately 1.2 mm per 2% dose difference considering user's couch top effect.

Sensitivity of radio-photoluminescence glass dosimeters to accumulated doses.

BACKGROUND: This study investigated the effect of accumulated doses on radio-photoluminescence glass dosimeters (RPLGDs) from measurements involving mega-voltage photons. METHODS: Forty-five commercially available RPLGDs were irradiated to estimate their dose responses. Photon beams of 6, 10, and 15 MV were irradiated onto the RPLGDs inside a phantom, which were divided into five groups with different doses and energies. Groups 1 and 2 were irradiated at 1, 5, 10, 50, and 100 Gy in a sequential manner; Group 3 was irradiated 10 times with a dose of 10 Gy; and Groups 4 and 5 followed the same method as that of Group 3, but with doses of 50 Gy and 100 Gy, respectively. Each device was subjected to a measurement reading procedure each time irradiation. RESULTS: For the annealed Group 1, RPLGD exhibited a linearity response with variance within 5%. For the non-annealed Group 2, readings demonstrated hyperlinearity at 6 MV and 10 MV, and linearity at 15 MV. Following the 100 Gy irradiation, the readings for Group 2 were 118.7 ± 1.9%, 112.2 ± 2.7%, and 101.5 ± 2.3% at 6, 10, and 15 MV, respectively. For Groups 3, 4, and 5, the responsiveness of the RPLGDs gradually decreased as the number of repeated irradiations increased. The percentage readings for the 10th beam irradiation with respect to the readings for the primary beam irradiation were 84.6 ± 1.9%, 87.5 ± 2.4%, and 93.0 ± 3.0% at 6 MV, 10 MV, and 15 MV, respectively. CONCLUSIONS: The non-annealed RPLGD response to dose was hyperlinear for the 6 MV and 10 MV photon beams but not for the 15 MV photon beam. Additionally, the annealed RPLGD exhibited a fading phenomenon when the measurement was repeated several times and demonstrated a relatively large fading effect at low energies than at high energies.

Plasma Fibrinogen-Like 1 as a Potential Biomarker for Radiation-Induced Liver Injury.

Liver damage upon exposure to ionizing radiation, whether accidental or because of therapy can contribute to liver dysfunction. Currently, radiation therapy is used for various cancers including hepatocellular carcinoma; however, the treatment dose is limited by poor liver tolerance to radiation. Furthermore, reliable biomarkers to predict liver damage and associated side-effects are unavailable. Here, we investigated fibrinogen-like 1 (FGL1)-expression in the liver and plasma after radiation exposure. We found that 30 Gy of liver irradiation (IR) induced cell death including apoptosis, necrosis, and autophagy, with fibrotic changes in the liver occurring during the acute and subacute phase in mice. Moreover, FGL1 expression pattern in the liver following IR was associated with liver damage represented by injury-related proteins and oxidative stress markers. We confirmed the association between FGL1 expression and hepatocellular injury by exposing human hepatocytes to radiation. To determine its suitability, as a potential biomarker for radiation-induced liver injury, we measured FGL1 in the liver tissue and the plasma of mice following total body irradiation (TBI) or liver IR. In TBI, FGL1 showed the highest elevation in the liver compared to other major internal organs including the heart, lung, kidney, and intestine. Notably, plasma FGL1 showed good correlation with radiation dose by liver IR. Our data revealed that FGL1 upregulation indicates hepatocellular injury in response to IR. These results suggest that plasma FGL1 may represent a potential biomarker for acute and subacute radiation exposure to the liver.

COMPARISON OF SURFACE DOSES FROM INDIRECT AND DIRECT DIGITAL RADIOGRAPHY USING OPTICALLY STIMULATED LUMINESCENCE DOSEMETERS.

An optically stimulated luminescence dosemeter was used to compare the surface dose to both eyes from an X-ray delivered frontally to the skull, and the dose could be reduced depending on image acquisition. The detectors were analysed in advance according to each image acquisition method, and the irradiation condition (mA) was obtained to equate the detective quantum efficiency of the two detectors. The surface doses to both eyes were measured in a human phantom. In the detector using the direct conversion method, the surface doses to both eyes were 0.29 ± 0.01 mSv (Rt. eye) and 0.28 ± 0.01 mSv (Lt. eye). In the detector using the indirect conversion method, the surface doses to both eyes were 0.23 ± 0.01 mSv (Rt. eye) and 0.23 ± 0.01 mSv (Lt. eye). Dose reduction by 18.00 ± 8.9% was permitted by the indirect method as compared with the direct method.

ASSESSMENT OF DIAGNOSTIC MULTILEAF COLLIMATOR FOR CEPHALOMETRIC EXPOSURE REDUCTION USING OPTICALLY STIMULATED LUMINESCENT DOSEMETERS.

A diagnostic multileaf collimator (MLC) was developed for diagnostic radiography dose reduction. Optically stimulated luminescent dosemeters (OSLDs) were used to evaluate the efficacy of this device for dental radiography cephalometric exposure reduction. The OSLD dosimetric characteristics for 80 kVp cephalometric exposure were first obtained. The batch homogeneity and reproducibility were 1.67 % and 0.18-1.58, respectively. Good linearity was obtained between the OSLD dose and response, and the angular dependence was within ±4 %. The equivalent organ doses for the left eye, right eye and thyroid were 41.20±6.58, 178.86±1.71 and 171.12±8.78 µSv and 36.80±0.33, 156.63±0.22 and 22.04±0.13 µSv for the open and MLC fields, respectively. The MLC-induced dose reductions for the left and right eyes of in field were 10.67±16.78 and 12.42±8.84 %, respectively, and that of the thyroid gland of out of field was 87±8.82 %, considering combined uncertainty. Therefore, use of diagnostic MLC for dose reduction during dental radiography cephalometric exposure is both feasible and effective.

Radiation dose reduction to the critical organ with bismuth shielding during endovascular coil embolisation for cerebral aneurysms.

This study evaluated certified dose reduction with bismuth shielding during an endovascular coiling procedure for cerebral aneurysms using a thermoluminescent dosemeter-100 H. A total of 60 patients were enrolled in the study and randomised into two groups (shielding group and unshielded group). In the unshielded group, the total dose-area product was 286.46 Gy cm(2), the fluoroscopy time was 61.57 min and the procedure time was 96.57 min. In the shielding group, those values were 256.36 Gy cm(2), 51.10 min and 91.00 min, respectively. The reductions in the organ-equivalent doses in the right eye, left eye and thyroid were 32.9 % (11.43 mSv), 28.9 % (17.58 mSv) and 68.1 % (20.48 mSv), respectively. The reductions in the relative organ doses were 21.6, 20.8, and 64.4 %, respectively. Bi shielding was feasible and effective for dose reduction during this neurointerventional procedure.

Suppression of phase transition in LiTb(0.01)Mn(1.99)O4 cathodes with fast Li+ diffusion.

The structural characteristics of terbium-doped spinel LiTb(x)Mn(2-x)O(4) related to the electrochemical performance were studied as the cathode in lithium-ion batteries. We chose terbium as the dopant, which is a well-known mixed-valent cation (3+/4+), expecting that it would provide structural stabilization and improve the power density. LiTb(x)Mn(2-x)O(4) revealed that terbium doping significantly affected the lattice structure and lithium-ion diffusion during charge-discharge cycles, resulting in an enhanced capacity retention and rate capability at an extremely small amount of terbium doping (LiTb(0.01)Mn(1.99)O(4)). The absence of two-cubic phase formation in the delithiated state and a tetragonal phase in the overlithiated state, along with a reduced dimensional change of the main cubic phase during charge-discharge, provided LiTb(0.01)Mn(1.99)O(4) with structural stability at both room temperature and 60 °C. The fast lithium-ion diffusion resulted in reduced polarization, which became more conspicuous as the C rates increased. As a result, the power density of LiTb(0.01)Mn(1.99)O(4), which was similar to that of LiMn(2)O(4) at 1C (476.1 W·kg(-1) for LiMn(2)O(4) vs 487.0 W·kg(-1) for LiTb(0.01)Mn(1.99)O(4)), was greatly improved at higher C rates. For example, the power density of LiTb(0.01)Mn(1.99)O(4) was improved to 4000 and 6000 W·kg(-1) at 10 and 20, respectively, compared with 3120 and 3320 W·kg(-1) for pristine LiMn(2)O(4).