Monte Carlo-based dose calculation engine for minibeam radiation therapy

Minibeam radiation therapy (MBRT) is an innovative radiotherapy approach based on the well-established tissue sparing effect of arrays of quasi-parallel micrometre-sized beams. In order to guide the preclinical trials in progress at the European Synchrotron Radiation Facility (ESRF), a Monte Carlo-based dose calculation engine has been developed and successfully benchmarked with experimental data in anthropomorphic phantoms. Additionally, a realistic example of treatment plan is presented. Despite the micron scale of the voxels used to tally dose distributions in MBRT, the combination of several efficiency optimisation methods allowed to achieve acceptable computation times for clinical settings (approximately 2 h). The calculation engine can be easily adapted with little or no programming effort to other synchrotron sources or for dose calculations in presence of contrast agents.     

Prevention of Transfusion-Associated Graft-versus-Host Disease by Irradiation: Technical Aspect of a New Ferrous Sulphate Dosimetric System

Irradiation of whole blood and blood components before transfusion is currently the only accepted method to prevent Transfusion-Associated Graft-Versus-Host-Disease (TA-GVHD). However, choosing the appropriate technique to determine the dosimetric parameters associated with blood irradiation remains an issue. We propose a dosimetric system based on the standard Fricke Xylenol Gel (FXG) dosimeter and an appropriate phantom. The modified dosimeter was previously calibrated using a ⁶⁰Co teletherapy unit and its validation was accomplished with a ¹³⁷Cs blood irradiator. An ionization chamber, standard FXG, radiochromic film and thermoluminescent dosimeters (TLDs) were used as reference dosimeters to determine the dose response and dose rate of the ⁶⁰Co unit. The dose distributions in a blood irradiator were determined with the modified FXG, the radiochromic film, and measurements by TLD dosimeters. A linear response for absorbed doses up to 54 Gy was obtained with our system. Additionally, the dose rate uncertainties carried out with gel dosimetry were lower than 5% and differences lower than 4% were noted when the absorbed dose responses were compared with ionization chamber, film and TLDs.     

A review of dose calculation approaches with cone beam CT in photon and proton therapy

Background and purposeThe use of cone beam computed tomography (CBCT) for performing dose calculations in radiation therapy has been widely investigated as it could provide a quantitative analysis of the dosimetric impact of changes in patients during the treatment. The aim of this review was to classify different techniques adopted to perform CBCT dose calculation and to report their dosimetric accuracy with respect to the metrics used.Methods and materialsA literature search was carried out in PubMed and ScienceDirect databases, based upon the following keywords: “cone beam computed tomography”, “CBCT”, “cone beam CT”, “dose calculation”, “accuracy”. Sixty-nine peer-reviewed relevant articles were included in this review: thirty-one patient studies, fifteen phantom studies and twenty-three patient & phantom studies. Most studies were found to have focused on head and neck, lung and prostate cancers.ResultsThe techniques adopted to perform CBCT dose calculation have been grouped in six categories labelled as (1) pCT calibration, (2) CBCT calibration, (3) HU override, (4) Deformable image registration, (5) Dose deformation, and (6) Combined techniques. Differences between CBCT dose and reference dose were reported both for target volumes and OARs.ConclusionsA comparison among the available techniques for CBCT dose calculations is challenging as many variables are involved. Therefore, a set of reporting standards is recommended to enable meaningful comparisons among different studies. The accuracy of the results was strongly dependent on the image quality, regardless of the methods used, highlighting the need for dose validation and quality assurance standards.     

Accuracy of dose calculation on iterative CBCT for head and neck radiotherapy

PurposeTo evaluate the feasibility of the use of iterative cone-beam computed tomography (CBCT) for dose calculation in the head and neck region.MethodsThis study includes phantom and clinical studies. All acquired CBCT images were reconstructed with Feldkamp–Davis–Kress algorithm-based CBCT (FDK-CBCT) and iterative CBCT (iCBCT) algorithm. The Hounsfield unit (HU) consistency between the head and body phantoms was determined in both reconstruction techniques. Volumetric modulated arc therapy (VMAT) plans were generated for 16 head and neck patients on a planning CT scan, and the doses were recalculated on FDK-CBCT and iCBCT with Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB). As a comparison of the accuracy of dose calculations, the absolute dosimetric difference and 1%/1 mm gamma passing rate analysis were analyzed.ResultsThe difference in the mean HU values between the head and body phantoms was larger for FDK-CBCT (max value: 449.1 HU) than iCBCT (260.0 HU). The median dosimetric difference from the planning CT were <1.0% for both FDK-CBCT and iCBCT but smaller differences were found with iCBCT (planning target volume D_50%: 0.38% (0.15–0.59%) for FDK-CBCT, 0.28% (0.13–0.49%) for iCBCT, AAA; 0.14% (0.04–0.19%) for FDK-CBCT, 0.07% (0.02–0.20%) for iCBCT). The mean gamma passing rate was significantly better in iCBCT than FDK-CBCT (AAA: 98.7% for FDK-CBCT, 99.4% for iCBCT; AXB: 96.8% for FDK_CBCT, 97.5% for iCBCT).ConclusionThe iCBCT-based dose calculation in VMAT for head and neck cancer was accurate compared to FDK-CBCT.     

Effect of anode angle on photon beam spectra and depth dose characteristics for X-RAD320 orthovoltage unit

Background

In radiation therapy with orthovoltage units, the tube design has a crucial effect on its dosimetric features.

Aim

In this study, the effect of anode angle on photon beam spectra, depth dose and photon fluence per initial electron was studied for a commercial orthovoltage unit of X-RAD320 biological irradiator.

Materials and methods

The MCNPX MC code was used for modeling in the current study. We used the Monte Carlo method to model the X-RAD320 X-ray unit based on the manufacturer provided information. The MC model was validated by comparing the MC calculated photon beam spectra with the results of SpekCalc software. The photon beam spectra were calculated for anode angles from 15 to 35 degrees. We also calculated the percentage depth doses for some angles to verify the impact of anode angle on depth dose. Additionally, the heel effect and its relation with anode angle were studied for X-RAD320 irradiator.

Results

Our results showed that the photon beam spectra and their mean energy are changed significantly with anode angle and the optimum anode angle of 30 degrees was selected based on less heel effect and appropriate depth dose and photon fluence per initial electron.

Conclusion

It can be concluded that the anode angle of 30 degrees for X-RAD320 unit used by manufacturer has been selected properly considering the heel effect and dosimetric properties.     

Deep learning-based metal artifact reduction using cycle-consistent adversarial network for intensity-modulated head and neck radiation therapy treatment planning

PurposeTo develop a deep learning-based metal artifact reduction (DL-MAR) method using unpaired data and to evaluate its dosimetric impact in head and neck intensity-modulated radiation therapy (IMRT) compared with the water density override method.MethodsThe data set comprised the data of 107 patients who underwent radiotherapy. Fifteen patients with dental fillings were used as the test data set. The computed tomography (CT) images of the remaining 92 patients were divided into two domains: the metal artifact and artifact-free domains. CycleGAN was used for domain translation. The artifact index of the DL-MAR images was compared with that of the original uncorrected (UC) CT images. The dose distributions of the DL-MAR and UC plans were created by comparing the reference clinical plan with the water density override method (water plan) in each dataset. Dosimetric deviation in the oral cavity from the water plan was evaluated.ResultsThe artifact index of the DL-MAR images was significantly smaller than that of the UC images in all patients (13.2 ± 4.3 vs. 267.3 ± 113.7). Compared with the reference water plan, dose differences of the UC plans were greater than those of the DL-MAR plans. DL-MAR images provided dosimetric results that were more similar to those of the water plan than the UC plan.ConclusionsWe developed a fast DL-MAR method using CycleGAN for head and neck IMRT. The proposed method could provide consistent dose calculation against metal artifact and improve the efficiency of the planning process by eliminating manual delineation.     

A Threshold Dose of Heavy Ion Radiation that Decreases the Oxidative Enzyme Activity of Spinal Motoneurons in Rats

The effect of heavy ion radiation exposure of the spinal cord on the properties of the motoneurons innervating the slow soleus and fast plantaris muscles was investigated. A 15-, 20-, 40-, 50-, or 70-Gy dose of carbon ions (5 Gy/min) was applied to the 2nd to the 6th lumbar segments of the spinal cord in rats. After a 1-month recovery period, the number and cell body size of the irradiated motoneurons innervating the soleus and plantaris muscles did not differ from that of the non-irradiated controls, irrespective of the dose received. However, the oxidative enzyme activity of these motoneurons was decreased by heavy ion radiation at doses of 40, 50, and 70 Gy compared to that of the non-irradiated controls. This decrease in oxidative enzyme activity levels in the motoneurons returned to that of the non-irradiated controls after a 6-month recovery period. We conclude that heavy ion radiation at doses of 40–70 Gy reversibly decreases the oxidative enzyme activity of motoneurons in the spinal cord of rats.     

Exosomes Derived from Squamous Head and Neck Cancer Promote Cell Survival after Ionizing Radiation

Exosomes are nanometer-sized extracellular vesicles that are believed to function as intercellular communicators. Here, we report that exosomes are able to modify the radiation response of the head and neck cancer cell lines BHY and FaDu. Exosomes were isolated from the conditioned medium of irradiated as well as non-irradiated head and neck cancer cells by serial centrifugation. Quantification using NanoSight technology indicated an increased exosome release from irradiated compared to non-irradiated cells 24 hours after treatment. To test whether the released exosomes influence the radiation response of other cells the exosomes were transferred to non-irradiated and irradiated recipient cells. We found an enhanced uptake of exosomes isolated from both irradiated and non-irradiated cells by irradiated recipient cells compared to non-irradiated recipient cells. Functional analyses by exosome transfer indicated that all exosomes (from non-irradiated and irradiated donor cells) increase the proliferation of non-irradiated recipient cells and the survival of irradiated recipient cells. The survival-promoting effects are more pronounced when exosomes isolated from irradiated compared to non-irradiated donor cells are transferred. A possible mechanism for the increased survival after irradiation could be the increase in DNA double-strand break repair monitored at 6, 8 and 10 h after the transfer of exosomes isolated from irradiated cells. This is abrogated by the destabilization of the exosomes. Our results demonstrate that radiation influences both the abundance and action of exosomes on recipient cells. Exosomes transmit prosurvival effects by promoting the proliferation and radioresistance of head and neck cancer cells. Taken together, this study indicates a functional role of exosomes in the response of tumor cells to radiation exposure within a therapeutic dose range and encourages that exosomes are useful objects of study for a better understanding of tumor radiation response.     

Imbalance between apoptosis and proliferation causes late radiation damage of salivary gland in mouse

Severe xerostomia is a common late radiation consequence, which occurs after irradiation of head and neck malignancies. The aim of the present study was to analyze apoptosis and proliferation and their relationship during the late post-irradiation phase. C57BL/6 mice were locally irradiated in head and neck region with a single dose of 7.5 or 15 Gy and their submandibular glands were collected at 40 and 90 days after irradiation. To identify apoptotic cells, the TUNEL method was employed and immunohistochemistry with proliferating cell nuclear antigen (PCNA) was used for detecting proliferation. Histological changes at day 40 were mild in contrast to day 90 when glands of irradiated mice showed severe atrophy, vacuolization and mononuclear infiltration. Acinar cells, granular and intercalated duct cells of mice irradiated with 7.5 and 15 Gy expressed higher apoptotic index than cells of non-irradiated, control glands at both examined time points. At 40 days, a higher proliferation index in granular and intercalated duct cells was detected only in group irradiated with 7.5 Gy. At 90 days, proliferation index for all cell types in both irradiated groups was similar to the controls. According to our results, the imbalance between apoptosis and proliferation caused by X-irradiation may be the reason for gland impairment during the late post-irradiation phase.     

Detecting demineralization of enamel and cementum after gamma irradiation using radiographic densitometry

The purpose of this study was to evaluate the ability of radiographic densitometry in detecting the early demineralization of human enamel and cementum in irradiated and non-irradiated teeth. Sixty extracted teeth were divided into two groups: irradiated group and non-irradiated group. After irradiation, the groups were subjected to demineralization–remineralization (PH) cycling. Radiographic densitometric measurements (gray values) of a selected area of interest in the enamel and in the cementum of each tooth were performed at baseline and after PH cycling. After PH cycling, there was a significant reduction in gray values for both groups. The difference between “baseline” and “after PH cycling” values represents the reduction in the mineral content of the hard tissue, i.e., the demineralization. Results show that the demineralization of irradiated tooth enamel and cementum was significantly higher compared to that of non-irradiated tissues as determined by gray-level values. It is concluded that densitometric measurements by means of digital radiographs allow for the detection of demineralization of enamel and cementum, and can be used successfully for diagnosis of the early carious lesions in patients who received head and neck radiotherapy. This will allow implementation of remineralizing therapy and avoid the risk of progression of radiation caries. Furthermore, it is concluded that gamma irradiation with typical therapeutic doses for head and neck carcinoma is a direct cause of demineralization of tooth enamel and cementum.     

Optimization of dose distributions in intraoperative HDR brachytherapy

The authors present their initial experience in physical aspects of treatment planning in HDR intraoperative brachytherapy. The examples are given of implantations in various tumour localizations: head and neck, pancreas, soft tissue sarcomas in the abdomen. The technical and dosimetric problems which may occur in such situations are discussed. The capabilities of dose distribution optimization by the Abacus HDR treatment planning system are presented.     

Antioxidant tolerance of kidney after irradiation

Different doses of irradiation were performed in which group 1 (non-irradiated), group 2 (8 Gy/single dose/whole body) and group 3 (15 Gy/single dose/whole body) were formed of guinea pigs. After 24 hr of radiation exposure the levels of lipid peroxidation product, malondialdehyde, (MDA), glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured in the whole kidney. The MDA content increased in animals irradiated with 8 and 15 Gy. And group 3 showed an increase the level of MDA. GSH contents of kidney in group 2 and 3 increased. The activity of SOD decreased markedly in group 3 when compared with control group. The activity of GSH-Px decreased significantly in group 2 and group 3 in comparison to controls. It may be concluded that a high dose of ionizing irradiation cause excessive oxidative stress in kidney.     

ELF MAGNETIC FIELD EFFECTS ON FATTY ACID COMPOSITION OF PHOSPHOLIPID FRACTION AND REPRODUCTION OF RATS' TESTES

In this study, we investigated how rat reproductive cells, testosterone, and the fatty acid composition of the phospholipid fraction of rats' testis cells are affected by extremely low frequency magnetic field (ELFMF). The change in fatty acid composition of the membrane phospholipid fraction can be the mechanism for this effect. We used a total of 26 male Wistar Albino rats, 14 experimental, and 12 controls. The experimental group rats were exposed to a magnetic field (0.8 mT) for 5 weeks, 3 hr per day. The control group rats were kept between inactive coils. After 5 weeks, the testis tissues and sperm cells of all rats were histopathologically investigated and sperm counts determined. Epididymal sperm count did not change compared to the control group (p>.05). Besides this, amorphous head, banana-like head, hammer head, coiled tail, abnormal mid-piece and tail, multiple, and cytoplasmic-droplet type cell numbers did not change in either group (p>.05). However, a statistical difference was found between the control and experimental groups with respect to head with lack of hook and isolated head type sperm (p<.05). In addition, testosterone levels were also found to be altered (p<.05). In the histopathologic investigation of testis tissue, decreased spermatogenesis in some seminiferous tubules, congestion in blood vessels of the interstitium, and increases in interstitial edema and Sertoli cells were observed. Leydig cells were found to be normal in appearance. The fatty acid of the testis cell membrane phospholipids was decreased in the experimental group with respect to the control group.     

Phantom design and dosimetric characterization for multiple simultaneous cell irradiations with active pencil beam scanning

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LET_d distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LET_d, where higher LET_d leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE₁₀). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

     

The "shielding" effect of the guide wire during coronary brachytherapy with P-32 source

Intracoronary beta irradiation (use of beta radiation for intracoronary irradiation) is an effective method in reducing neointimal proliferation after successful angioplasty and stent implantation. However, long-term results may be influenced by absolute dose and by the homogeneity in dose distribution. In our study, we investigated dose perturbation due to the presence of a conventional guide wire during irradiation. The Galileo III centering catheter and P-32 beta source were used. The 55 MD GAF Chromic foil was positioned within a phantom made of PMMA. The dose distribution at cylindrical surfaces has been assessed using GAF Chromic dosimetric foil MD55 (Nuclear Associates, USA). Our study demonstrated the significant dose reduction of 46% in the most "shaded" area. The dose reduction to 80% or less occupy the 60 degrees sector. This phenomenon can cause progression of late restenosis. In conclusion, the results suggest that technical improvements in centering catheter construction should be made to eliminate the "shielding" effect of the guide wire.     

Ionizing radiation effects on the secretory-stage ameloblasts and enamel organic extracellular matrix

This study assessed the effects of high doses of ionizing radiation on eruption rate, odontogenic region morphology, secretory-stage ameloblasts, and enamel organic extracellular matrix (EOECM) of rat maxillary incisors. For the study, 30 male rats were divided into three experimental groups: control (non-irradiated), irradiated by 15 Gy, and irradiated by 25 Gy. Irradiated groups received a single dose of 15 or 25 Gy of X-rays in the head and neck region. The maxillary incisor eruption rate was measured. Sections of 5-µm thickness of the maxillary incisor odontogenic regions were evaluated using bright field light microscopy. Ultrathin sections of secretory ameloblasts and their EOECM were analyzed by transmission electron microscopy (TEM). Irradiated groups showed significantly diminished eruption rate values at the 4th and at the 6th day after irradiation. Reduced optical retardation values were observed in the irradiated groups. The odontogenic region of maxillary incisors from irradiated rats exhibited altered and poorly organized preameloblasts. TEM showed degeneration areas in the secretory-stage EOECM and several autophagosomes in the secretory ameloblasts from irradiated animals. In conclusion, high radiation doses delay eruption and induce disturbances in secretory ameloblasts and EOECM of rat maxillary incisors. These findings may be associated with structural defects of mature enamel.     

A practical methodology to improve the dosimetric accuracy of MR-based radiotherapy simulation for brain tumors

PurposeTo investigate the dosimetric accuracy of synthetic computed tomography (sCT) images generated by a clinically-ready voxel-based MRI simulation package, and to develop a simple and feasible method to improve the accuracy.Methods20 patients with brain tumor were selected to undergo CT and MRI simulation. sCT images were generated by a clinical MRI simulation package. The discrepancy between planning CT and sCT in CT number and body contour were evaluated. To resolve the discrepancies, an sCT specific CT-relative electron density (RED) calibration curve was used, and a layer of pseudo-skin was created on the sCT. The dosimetric impact of these discrepancies, and the improvement brought about by the modifications, were evaluated by a planning study. Volumetric modulated arc therapy (VMAT) treatment plans for each patient were created and optimized on the planning CT, which were then transferred to the original sCT and the modified-sCT for dose re-calculation. Dosimetric comparisons and gamma analysis between the calculated doses in different images were performed.ResultsThe average gamma passing rate with 1%/1 mm criteria was only 70.8% for the comparison of dose distribution between planning CT and original sCT. The mean dose difference between the planning CT and the original sCT were −1.2% for PTV D₉₅ and −1.7% for PTV D_max, while the mean dose difference was within 0.7 Gy for all relevant OARs. After applying the modifications on the sCT, the average gamma passing rate was increased to 92.2%. Mean dose difference in PTV D₉₅ and D_max were reduced to −0.1% and −0.3% respectively. The mean dose difference was within 0.2 Gy for all OAR structures and no statistically significant difference were found.ConclusionsThe modified-sCT demonstrated improved dosimetric agreement with the planning CT. These results indicated the overall dosimetric accuracy and practicality of this improved MR-based treatment planning method.