Comparative analysis of two dose-volume histogram prediction tools for treatment planning in volumetric-modulated arc therapy: A multi-planner study


Influence of Pitch on Surface Dose Distribution and Image Noise of Computed Tomography Scans

This study evaluated the effect of pitch on 256-slice helical computed tomography (CT) scans. Cylindrical water phantoms (CWP) were measured using axial and helical scans with various pitch values. The surface dose distributions of CWP were measured, and reconstructed images were obtained using filtered back-projection (FBP) and iterative model reconstruction (IMR). The image noise in each reconstructed image was decomposed into a baseline component and another component that varied along the z-axis. The baseline component of the image noise was highest at the center of the reconstructed image and decreased toward the edges. The normalized 2D power spectra for each pitch were almost identically distributed. Furthermore, the ratios of the 2D power spectra for IMR and FBP at different pitch values were obtained. The magnitudes of the components varying along the z-axis were smallest at the center of the reconstructed image and increased toward the edge. The ratios of the 3D power spectra on the fx axis for IMR and FBP at different pitch values were obtained. The results showed that the effect of the pitch was related to the component that varied along the z-axis. Furthermore, the pitch had a smaller effect on IMR than on FBP.


3D Shape Reconstruction of Japanese Traditional Puppet Head from CT images


Estimation of imaging intervals and intra-fraction displacement in CyberKnife image-guided radiotherapy for intracranial lesions


Influence of distant scatterer on air kerma measurement in the evaluation of diagnostic X-rays using Monte Carlo simulation

The evaluation of the entrance surface dose (ESD) ensures safe radiation doses for X-ray imaging patients. The air kerma free-in-air value used to estimate ESD may be affected by those X-rays that scatter from the scatterer placed behind the chamber at the time of measurement, thereby leading to assessment errors. Therefore, the influence of scattered radiation on air kerma measurements was investigated. Monte Carlo simulations were performed for various detector-to-scatterer distances and scatterer materials. The simulation results were compared with actual measurements to confirm the simulation accuracy. The source-chamber distance was set to 50 and 100 cm for the experimental measurements and simulation, respectively, and the chamber-scatterer distance was varied. The Monte Carlo simulation results reproduced the actual measurements with an accuracy of 3.5%. The effect of backscattering varied with the tube voltage and irradiation field size. The effect was observed in the order of prominence for the following scatterer materials: water-equivalent phantom, acrylic, concrete, lead, and iron. Furthermore, this effect decreased exponentially with increasing chamber-scatterer distance. For a field size of 10 × 10 cm, the finite-distance backscatter factor decreased with an increasing chamber-scatterer distance for all materials. The cause of backscattering in diagnostic X-ray energy regions differs depending on the scatterer material, as well as the photon energy and field size. Backscattering decreases exponentially as the distance between the detector and scatterer increases.


Usability of detecting delivery errors during treatment of prostate VMAT with a gantry-mounted transmission detector

Volumetric-modulated arc therapy (VMAT) requires highly accurate control of multileaf collimator (MLC) movement, rotation speed of linear accelerator gantry, and monitor units during irradiation. Pretreatment validation and monitoring of these factors during irradiation are necessary for appropriate VMAT treatment. Recently, a gantry mounted transmission detector "Delta Discover® (D4D)" was developed to detect errors in delivering doses and dose distribution immediately after treatment. In this study, the performance of D4D was evaluated. Simulation plans, in which the MLC position was displaced by 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 mm from the clinically used original plans, were created for ten patients who received VMAT treatment for prostate cancer. Dose deviation (DD), distance-to-agreement (DTA), and gamma index analysis (GA) for each plan were evaluated by D4D. These results were compared to the results (DD, DTA and GA) measured by Delta Phantom + (D4P). We compared the deviations between the planned and measured values of the MLC stop positions A-side and B-side in five clinical cases of prostate VMAT during treatment and measured the GA values. For D4D, when the acceptable errors for DD, DTA, and GA were determined to be ≤3%, ≤2 mm, and ≤3%/2 mm, respectively, the minimum detectable errors in the MLC position were 2.0, 1.5, and 1.5 mm based on DD, DTA, and GA respectively. The corresponding minimum detectable MLC position errors were 2.0, 1.0, and 1.5 mm, respectively, for D4P. The deviation between the planned and measured position of MLC stopping point of prostate VMAT during treatment was stable at an average of -0.09 ± 0.05 mm, and all GA values were above 99.86%. In terms of delivering doses and dose distribution of VMAT, error detectability of D4D was comparable to that of D4P. The transmission-type detector "D4D" is thus suitable for detecting delivery errors during irradiation.

Journal of Applied Clinical Medical Physics


Estimation of X-ray Energy Spectrum of Cone-Beam Computed Tomography Scanner Using Percentage Depth Dose Measurements and Machine Learning Approach

Journal of the Physical Society of Japan


Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice.

International Journal of Radiation Biology


Development of a novel acetyl glucose-modified gefitinib derivative to enhance the radiosensitizing effect

Various radiosensitizers are being developed to increase the radiation sensitivity of hypoxic cancer cells, which show resistance to radiation. Previously, we demonstrated that an acetyl glucose-modified nitroimidazole derivative showed a high radiosensitizing effect by inhibiting glucose uptake and glycolysis. Based on this finding, we designed and synthesized novel sugar hybrid radiosensitizers, wherein acetyl glucose was introduced into gefitinib. Among them, UTX-114 had higher autophosphorylation and radiosensitizing activity than gefitinib and inhibited glucose uptake. This result supports our hypothesis that an acetyl glucose moiety improves the radiosensitizing effect of the drug, and UTX-114 can be expected to be a leading compound with a radiosensitizing effect.


Epigallocatechin-3-gallate Enhances Radiation Sensitivity in Colorectal Cancer Cells Through Nrf2 Activation and Autophagy.

Epigallocatechin-3-gallate (EGCG) is a major polyphenolic component of green tea. EGCG plays a potential role in radio-sensitizing cancer cells. The combined effect of EGCG and radiation was investigated in a colorectal cancer cell line, focusing on nuclear factor (erythroid-derived 2)-like 2 (Nrf2) autophagy signalling. HCT-116 cells were treated with 12.5 μM EGCG for different periods of time, 2 Gy radiation, or both. Cell viability was determined with the WST-8 assay. The number of colonies was determined with the colony formation assay. mRNA expression of LC3 and caspase-9 was analyzed with quantitative real-time polymerase chain reaction. Combination treatment with EGCG and radiation significantly decreased the growth of HCT-116 cells. The number of colonies was reduced to 34.2% compared to the control group. Immunofluorescence microscopy images showed that nuclear translocation of Nrf2 was significantly increased when cells were treated with the combination of EGCG and radiation compared to the control and single-treatment groups. Combined treatment with EGCG and radiation significantly induced LC3 and caspase-9 mRNA expression. EGCG increased the sensitivity of colorectal cancer cells to radiation by inhibiting cell proliferation and inducing Nrf2 nuclear translocation and autophagy.


Radiosensitizing Effect of 5-Aminolevulinic Acid and Protoporphyrin IX on Carbon-ion Beam Irradiation

Carbon-ion beam is one of the most advanced radiations used for cancer treatment. However, there are tumors that are difficult to suppress with carbon-ion beam alone, thus necessitating development of drugs that can enhance its therapeutic effect. In this regard, the radiosensitizing effect of 5-aminolevulinic acid (ALA) and protoporphyrin IX (PpIX), that is a metabolic intermediate of ALA, on carbon-ion beam was investigated. Radiosensitizing activity, mitochondrial ROS and DNA double-strand break production of ALA and PpIX were evaluated by irradiation with 1.0 or 1.5-Gy carbon-ion beam to mouse mammary EMT6 tumor cells. Combination of carbon-ion beam and ALA or PpIX showed a significant enhancement of its cytotoxic activity through a significant increase in ROS production in mitochondria. Furthermore, the combined activity of carbon-ion beam and ALA resulted in a significant increase in DNA double-strand breakage. ALA selectively accumulates in the mitochondria and PpIX synthesized from ALA reacts with carbon-ion beam to produce ROS that exert antitumor activity.


Development of a novel Schiff base derivative for enhancing the anticancer potential of 5-aminolevulinic acid-based photodynamic therapy.

5-Aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX), is now widely used for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various cancers. Recently, we found that treatment of cancer cells with the Schiff base derivative TX-816 along with ALA could significantly increase the efficacy of ALA-PDT. This enhancing effect of TX-816 on ALA-PDT is attributed to 3,5-dichlorosalicylaldehyde (DCSA), a molecule produced by the degradation of TX-816. Similar to TX-816, DCSA significantly enhances the effect of ALA-PDT. Furthermore, DCSA could restore the sensitivity of cancer cells that acquired resistance to ALA-PDT. These results indicate that DCSA, as well as TX-816, is a potent lead compound for the development of an ALA-PDT sensitizer. TX-816 might be a useful compound for designing prodrug-type ALA-PDT enhancers.


Influence of multi-leaf collimator leaf transmission on head and neck intensity-modulated radiation therapy and volumetric-modulated arc therapy planning.

The aim of this study was to quantify the effect of multi-leaf collimators (MLCs) with different leaf widths on the planning of intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT). Toward this objective, dose transmission through a high-definition 120-leaf MLC (HD120MLC) and 120-leaf Millennium MLC (M120MLC) was investigated, using it with a test case and clinical case studies. In test case, studies with IMRT and VMAT plans, the difference in MLC leaf width had a limited effect on planning target volumes (PTVs). Organs at risk (OARs) were more affected by a reduction in dose transmission through the MLC than by a reduction in MLC leaf width. The results of the test case studies and clinical case studies were mostly similar. In the latter, the different MLCs had no effect on the PTV regardless of the treatment method; however, the HD120MLC plans achieved dose reductions to OARs similar to or larger than the dose reduction of the M120MLC plans. The similar results of the test case and clinical case studies showed that despite a limitation of the irradiation field size, the HD120MLC plans were superior.


Uncertainty evaluation of absorbed dose measurements by means of small-type OSL dosimeter for radiotherapeutic X-ray region

For Quality Assurance of clinical radiation therapy, it is necessary to accurately measure multiple doses, and evaluate and compare the results to the radiation treatment system. Based on the measurements using multiple dosimeters, there is no uncertainty estimation of the delivered dose for accurate analysis. In this study, we focused attention on small-type optically stimulated luminescence (OSL) dosimeters, and clarified the relationship of uncertainties between the experimental variance associated with multiple data points and the variance predicted by Poisson distribution. The experiments were carried out as follows: fifteen dosimeters were placed in a water equivalent phantom, they were irradiated with X-rays having an acceleration voltage of 10-MV with 167.2 cGy (200 MU) and 2,090 cGy (2,500 MU). Each dosimeter was read ten times and the experimental variance and predicted variance were analyzed. As a result, we found that the experimental uncertainties were 3.9 and 6.2 times higher than predicted uncertainty when irradiated at 167.2 cGy and 2,090 cGy, respectively. We discuss the relationship of measurement uncertainties. Then, we concluded that the uncertainty of OSL dosimeters was found to be 3%. We also conclude that the OSL dosimeter can be used to measure the absorbed dose in the radiation therapy region.

Medical Imaging and Information Sciences


RADIOSENSITIZING EFFECT OF PROTOPORPHYRIN IX WITH CARBON ION BEAM AGAINST MOUSE MAMMARY BREAST TUMOR CELL.

5-Aminolevulinic acid (ALA), a precursor ofprotoporphyrin IX (PpIX), has been utilized as a potent sensitizerfor photodynamic therapy (PDT) of cancer through productionof reactive oxygen species (ROS). ALA also has been proposed asa possible radiosensitizer with low linear energy transfer (LET)radiation because antitumor activity of low-LET radiation dependson ROS mainly. In this paper, we investigated the radiosensitizingactivity of PpIX in carbon ion irradiation as a high LET radiation.PpIX was detected in an EMT6 mouse mammary breast tumor cellseven at 24 h post treatment. The cytotoxicity of PpIX against EMT6cells was IC50 = 48.0 m. The combined treatment of 1.0 m of PpIXwith 2 Gy of carbon ion irradiation (290 MeV/nucleon, 85.1 keV/m)showed a more potent antitumor activity than carbon ion irradiationalone. We demonstrated that PpIX showed a radiosensitizing effectwith carbon ion beam against mouse mammary breast tumor cells.

Journal of Advanced Manufacturing Technology


Practical method for determination of air-kerma by using an ionization chamber toward the construction of secondary X-ray field to be used in clinical examination rooms


Dose impact of rectal gas on prostatic IMRT and VMAT

In this study, we compared the dose impact of the heterogeneity caused by rectal gas using two methods of treatment planning for intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). In addition to the structure set used for the standard treatment plan, we created a structure set for evaluation for each patient. These sets were transferred to the same isocenter as the respective treatment plans for IMRT and VMAT that were to become the standard. Values were then recalculated. During the standard prostatic IMRT and VMAT treatment planning, all study participants met dose restrictions in place at our hospital. Dose restrictions were fulfilled in treatment plans for evaluation, excluding those with a clinical target volume (CTV) of V(100%) and planning target volume (PTV) of D95 when the rectum was excluded. However, in treatment plans for evaluation, IMRT was shown to have a higher concordance rate with standard treatment plans than VMAT. If rectal gas is present during either IMRT or VMAT, a dose decrease will occur in relation to CTV and PTV, suggesting that a plan does not eliminate adverse effects on organs at risk.


Radiosensitivity Uncertainty Evaluation for the In Vitro Biophysical Modeling of EMT6 Cells

The aims of this study were to evaluate the cell survival uncertainty distribution of radiation and to assess the accuracy of predictions of tumor response by using three different in vitro experimental cell cultures with radiosensitizers (including etanidazole). Using EMT6 cells and X-rays, the cell survival fraction was obtained from 15, 34, and 21 different experiments under normoxic, hypoxic, and hypoxic-plus-radiosensitizer culture, respectively. The α coefficients were 0.257 ± 0.188, 0.078 ± 0.080, and 0.182 ± 0.116 Gy(-1), respectively. The β coefficients were 0.0159 ± 0.0208, 0.0076 ± 0.0113, and 0.0062 ± 0.0077 Gy(-2), respectively. The α coefficient and the dose that killed half of the clonogens population (D50) were significantly different between normoxic cell and hypoxic cell cultures (p<0.01), respectively. The use of radiosensitizers under hypoxic conditions improved radiosensitivity. Our results suggest that parameter value distributions are required for biophysical modeling of applications for radiotherapy.


Clinical evaluation of automatic contours for head and neck region using deformable image registration software

The purpose of this study was to clinically evaluate the automatic outline extraction properties using general-purpose deformable image registration (DIR) software for the head and neck region. To this end, we evaluated the following: (1) the difference between manual outline extraction carried out by a radiation therapy specialist and automatic outline extraction using the DIR software, and (2) the precision of the automatic outline extraction for the diachronic figure change and change in the organ shape. The manually-extracted outline and that extracted using the DIR software closely resembled each other at 0.70. Further, in the same case, the automatic outline extraction precision of the DIR software was greater at about 0.80. Our findings suggest DIR software to be useful for lessening the work involved in outline extraction.

Japanese Journal of Radiological Technology


Changes of tumor and normal structures of the neck during radiation therapy for head and neck cancer requires adaptive strategy.

The treatment period over which radiation therapy is administered extends over several weeks. Since tumor shrinkage in response to radiation therapy and weight loss due to radiation-induced mucositis may impact on the dose distribution in both target and organ at risk in patients with head and neck cancer, the anatomical changes of tumor and neck volumes during this period should be taken into consideration. We investigated the anatomical changes that occurred in the target and normal structure of the neck during radiation therapy for pharyngeal cancer, and evaluated the necessity of an adaptive strategy. Ten patients with pharyngeal cancer who underwent radical chemoradiation therapy using 3-dimensional conformal radiation therapy RT (66-70 Gy in 33-35 fractions) between April 2009 and September 2010 were enrolled in the study. Patients underwent CT scans every week during their course of treatment. We analyzed the CT data in the radiation treatment planning system and measured changes of tumor, organ at risk, and neck volume. Gross tumor volume (GTV) was rapidly reduced by 28% of the original volume on average in the first 3 weeks. The right and left submandibular glands volume decreased to 70% and 63% of their initial volumes on average, respectively. The volume of the neck in the radiation fields decreased to 89% of its initial volume on average by the sixth week mainly caused by body weight loss due to acute radiation morbidity. Considerable anatomical change in the radiation filed that will affect dose distribution of the target and organ at risk was observed during radiation therapy for head and neck cancer.

The Journal of Medical Investigation : JMI


Development of a pin-hole camera using a phosphor plate, and visualization of the scattered X-ray distribution and optical image

輝尽性蛍光体プレートを用いたピンホールカメラの開発と散乱X線分布および可視光画像の撮影

In order to obtain an image of scattered X-ray in the diagnosis domain, we have newly developed a pin-hole camera. Because of the necessity of the X-ray shielding, the pin-hole part has a depth corresponding to that of the shielded material. As a result, efficiencies of obliquely incident X-rays are reduced. To decrease the descent of the efficiencies, we developed a large camera using a 10×12 inch size phosphor plate as an X-ray detector. A phantom was irradiated by X-rays with conditions of 500 mAs and 5000 mAs, and images of scattered X-rays were obtained. The former image showed scattered X-rays from the phantom. The latter image showed those from the air of beam axis as well as from the phantom. Moreover, we made a new proposal to obtain an optical image using the fading effect.


Impact of multileaf collimator leaf positioning accuracy on intensity modulated radiation therapy.

マルチリーフコリメータの位置精度が強度変調放射線治療に及ぼす影響

In multileaf collimator (MLC)-based intensity modulated radiation therapy (IMRT), the dose is influenced by the uncertainty of MLC driving control. In this study, we examined the influence of MLC driving control accuracy on dose evaluation (gamma analysis) by evaluating 60-day MLC driving control accuracy (stationary positioning accuracy and positioning reproducibility) once a week as well as measuring IMRT dose distribution. The MLC positioning accuracy accompanied variation over time and tended to expand by 0.1 to 0.15 mm in one week and about 1 mm in 60 days. In terms of reproducibility, errors were within 0.2 mm for more than 95%. For prostate IMRT, when MLC stationary positioning accuracy was around 1 mm, no significant difference was observed in the pass rate in gamma analysis. Therefore, the results suggest that regular maintenance by setting a permissible value determined by the MLC positioning accuracy test can be an effective indicator in the future for maintaining the safety of IMRT.


Measurements of multi-detector CT surface dose distributions using a film dosimeter and chest phantom

This paper uses film dosimetry to investigate the relationship between multiple scan parameters of multidetector CT with automatic exposure control (AEC) and the surface dose distribution produced on a chest phantom. The characteristics of the film used in the film dosimeter were evaluated with regard to linearity, relative film response, and directional dependence. Measurements with an ionization chamber dosimeter and a water phantom were used to evaluate the accuracy of the film dosimeter measurements and to validate the dose profile measurements while changing the tube current, detector dimensions and pitch. When using AEC, the surface dose distribution on the chest phantom was analyzed while changing the detector dimensions and pitch. The linearity, relative film response, and directional dependence of the film were established. The measurement difference between the film dosimeter and ionization chamber dosimeter was within +/- 5% and the dose profile measurement results were validated. It was found that the surface dose distribution changed helically in the direction of the body axis depending on the scan parameters and the phantom. Using a film dosimeter, the relationship between various multidetector CT scan parameters and the surface dose distribution on a chest phantom was investigated and clarified.


強度変調放射線治療におけるradiographic filmと radiochromic filmの比較評価

Purpose: Radiographic film is generally used for inspection of dose distribution in intensity modulated radiation therapy (IMRT) at many institutions. However, the distribution of filmless systems can be expected to be used increasingly in the future. Therefore, we confirmed the utility of radiochromic film by comparing it with radiographic film that does not need an automatic processor. Result: Difference in does measured by radiographic film and radiochromic film tended to increase in the low does area, but it was limited in a range of 1.5%. Conclusion: When the dose distribution was verified in a highly accurate radiation therapy such as IMRT, the results suggested that radiochromic film can be useful in addition to radiographic film.


Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers

We have designed sugar-hybrid TX-1877 derivatives conjugated with sugar moieties including β-glucose (β-Glc), β-galactose (β-Gal), α-mannose (α-Man) and N-acetyl-β-galactosamine (β-GalNAc). Compound 1 (TX-1877) was glycosylated with appropriate peracetylated sugars using BF3-OEt2 to give acetylated sugar-hybrids, 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), and 10 (TX-2243). Removal of the acetyl groups afforded the sugar-hybrids having free hydroxyl groups, 11 (TX-2141), 12 (TX-2218), 13 (TX-2217) and 14 (TX-2068). We evaluated their radiosensitizing activities by an in vitro radiosensitization assay. All free hydroxyl hybrids have lower enhancement ratio (ER) values (ER 1.43) and lower n-octanol/water partition coefficient (Poct) values (Poct < 1.00 × 10-2) than does 1 (TX-1877, ER = 1.75, Poct: 5.60 × 10-2). All acetylated hybrids have similar Poct values (3.55 × 10-2 1.05 × 10-1) to 1 (TX-1877) and have improved ER values (ER 1.47) compared to the hybrids having free hydroxyl groups. Among these, 5 (TX-2244) is the most active radiosensitizer (ER = 2.30). We found a good correlation (r = 0.866) between the magnitude of Poct (logPoct) and the ER value of 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), 10 (TX-2243) and 1 (TX-1877), suggesting that increasing the hydrophobicity is reflected in increased in vitro radiosensitizing activity. In the present study, we have succeeded in producing sugar-hybrid hypoxic cell radiosensitizers that have an increased radiosensitizing activity that does not depend on increased hydrophobicity.


Bulletin of School of Medical Sciences, the University of Tokushima

徳島大学医療技術短期大学部紀要


徳島大学医療技術短期大学部紀要