Synergistic Effect of Ferroptosis-Inducing Nanoparticles and X-Ray Irradiation Combination Therapy.

Ferroptosis, characterized by the induction of cell death via lipid peroxidation, has been actively studied over the last few years and has shown the potential to improve the efficacy of cancer nanomedicine in an iron-dependent manner. Radiation therapy, a common treatment method, has limitations as a stand-alone treatment due to radiation resistance and safety as it affects even normal tissues. Although ferroptosis-inducing drugs help alleviate radiation resistance, there are no safe ferroptosis-inducing drugs that can be considered for clinical application and are still in the research stage. Here, the effectiveness of combined treatment with radiotherapy with Fe and hyaluronic acid-based nanoparticles (FHA-NPs) to directly induce ferroptosis, considering the clinical applications is reported. Through the induction of ferroptosis by FHA-NPs and apoptosis by X-ray irradiation, the therapeutic efficiency of cancer is greatly improved both in vitro and in vivo. In addition, Monte Carlo simulations are performed to assess the physical interactions of the X-rays with the iron-oxide nanoparticle. The study provides a deeper understanding of the synergistic effect of ferroptosis and X-ray irradiation combination therapy. Furthermore, the study can serve as a valuable reference for elucidating the role and mechanisms of ferroptosis in radiation therapy.

A Study on the Performance of a Silicon Photodiode Sensor for a Particle Dosimeter and Spectrometer.

A lunar vehicle radiation dosimeter (LVRAD) has been proposed for studying the radiation environment on the lunar surface and evaluating its impact on human health. The LVRAD payload comprises four systems: a particle dosimeter and spectrometer (PDS), a tissue-equivalent dosimeter, a fast neutron spectrometer, and an epithermal neutron spectrometer. A silicon photodiode sensor with compact readout electronics was proposed for the PDS. The PDS system aims to measure protons with 10-100 MeV of energy and assess dose in the lunar space environment. The manufactured silicon photodiode sensor has an effective area of 20 mm × 20 mm and thickness of 650 µm; the electronics consist of an amplifier, analog pulse processor, and a 12-bit analog-to-digital converter for signal readout. We studied the responses of silicon sensors which were manufactured with self-made electronics to gamma rays with a wide range of energies and proton beams.

A Monte Carlo simulation study for the gamma-ray/neutron dual-particle imager using rotational modulation collimator (RMC).

The aim of this work is to develop a gamma-ray/neutron dual-particle imager, based on rotational modulation collimators (RMCs) and pulse shape discrimination (PSD)-capable scintillators, for possible applications for radioactivity monitoring as well as nuclear security and safeguards. A Monte Carlo simulation study was performed to design an RMC system for the dual-particle imaging, and modulation patterns were obtained for gamma-ray and neutron sources in various configurations. We applied an image reconstruction algorithm utilizing the maximum-likelihood expectation-maximization method based on the analytical modeling of source-detector configurations, to the Monte Carlo simulation results. Both gamma-ray and neutron source distributions were reconstructed and evaluated in terms of signal-to-noise ratio, showing the viability of developing an RMC-based gamma-ray/neutron dual-particle imager using PSD-capable scintillators.

Confidence limits for patient-specific IMRT dose QA: a multi-institutional study in Korea.

This study aims to investigate tolerance levels for patient-specific IMRT dose QA (DQA) using the confidence limits (CL) determined by a multi-institutional study. Eleven institutions participated in the multi-institutional study in Korea. A total of 155 DQA measurements, consisting of point-dose differences (high- and low-dose regions) and gamma passing rates (composite and per-field) for IMRT patients with brain, head and neck (H&N), abdomen, and prostate cancers were examined. The Shapiro-Wilk test was used to evaluate the normality of data grouped by the treatment sites and the DQA methods. The confidence limit coefficients in cases of the normal distribution, and the two-sided Student's t-distribution were applied to determine the confidence limits for the grouped data. The Spearman's test was applied to assess the sensitivity of DQA results within the limited groups. The differences in CLs between the two confidence coefficients based on the normal and t-distributions were negligible for the point-dose data and the gamma passing rates with 3%/3 mm criteria. However, with 2%/2 mm criteria, the difference in CLs were 1.6% and 2.2% for composite and per-field measurements, respectively. This resulted from the large standard deviation and the more sensitive criteria of 2%/2 mm. There was no noticeable correlation among the different QA methods. Our multi-institutional study suggested that the CL was not a suitable metric for defining the tolerance level when the statistics of the sample group did not follow the normality and had a large standard deviation.

Dosimetric effects of immobilization devices on SABR for lung cancer using VMAT technique.

The purpose of this study was to investigate the dosimetric effects of immobilization devices on the dose distributions of stereotactic ablative radiotherapy (SABR) for lung cancer using volumetric-modulated arc therapy (VMAT) technique. A total of 30 patients who underwent SABR for lung cancer were selected retrospectively. Every patient was immobilized using Body Pro-Lok with a vacuum bag customized for each patient body shape. Structure sets were generated to include the patient body inside the body structure with and without the immobilization device. Dose distributions, with and without the immobilization device, were calculated using identical VMAT plans for each patient. Correlations between the change in dose-volumetric parameters and the MU fraction of photon beams penetrating through the immobilization device were analyzed with Pearson correlation coefficients (r). The maximum change in D95%, D100%, and the minimum, maximum and mean dose to the planning target volume (PTV) due to the immobilization device were 5%, 7%, 4%, 5%, and 5%, respectively. The maximum changes in the maximum dose to the spinal cord, esophagus, heart, and trachea were 1.3 Gy, 0.9 Gy, 1 Gy, and 1.7 Gy, respectively. Strong correlations were observed between the changes in PTV D95%, the minimum, the maximum, and the mean dose to the PTV, the maximum dose to the esophagus and heart, and the MU fractions, showing values of r higher than 0.7. The decrease in dose to the target volume was considerable for lung SABR using VMAT technique, especially when MU fraction was large.

The effect of body contouring on the dose distribution delivered with volumetric-modulated arc therapy technique.

The purpose of the study was to investigate the dosimetric effect defining the body structure with various Hounsfield unit (HU) threshold values on the dose distributions of volumetric-modulated arc therapy (VMAT) plans. Twenty patients with prostate cancer and twenty patients with head and neck (H&N) cancer were retrospectively selected. For each patient, the body structure was redefined with HU threshold values of -180 (Body180), -350 (Body350), -700 (Body700), and -980 (Body980). For each patient, dose-volumetric parameters with those body structures were calculated using identical VMAT plans. The differences in dose-volumetric parameters due to the varied HU threshold values were calculated. For the prostate boost target volume, the maximum dose, mean dose, D95%, and D5% with Body180 were higher than those with Body980 by approximately 0.7% (p < 0.001). For H&N target volumes, the changes in D95% of the targets receiving 67.5 Gy, 54 Gy, and 48 Gy between Body180 and Body980 were -1.2%, -0.9%, and -1.2%, respectively (p < 0.001). The differences were larger for H&N VMAT plans than for prostate VMAT plans due to the inclusion of an immobilization device in the irradiated region in H&N cases. To apply all attenuating materials to dose calculation, the body structure would be defined with -980 HU. Otherwise, systematic error of about 1%, resulting in underdosage of the target volume, can occur.

Evaluation of treatment plans using various treatment techniques for the radiotherapy of cutaneous Kaposi's sarcoma developed on the skin of feet.

The purpose of this study was to investigate the plan qualities of various treatment modalities for the radiotherapy of cutaneous Kaposi's sarcoma developed on the skin of the foot. A total of six virtual targets were generated on the skin of the foot in CT images. Five types of treatment plans were generated using photon beams (PB), electron beams (EB), high-dose-rate (HDR) brachytherapy with a Freiburg flap applicator, intensity-modulated radiation therapy (IMRT), and volumetric- modulated arc therapy (VMAT) techniques. Plans for each of the six targets (single-target plans) and also for the combined target consisting of the six single targets combined (multitarget plans) were generated. Dose-volumetric analysis was performed for the targets and normal tissues. The averaged conformity index (CI) and homogeneity index (HI) values for each single target using PB, EB, HDR, IMRT, and VMAT techniques were 1.97, 2.39, 1.60, 4.60, and 0.80 and 1.05, 1.11, 1.52, 1.04, and 1.04, respectively. For the multitarget, the CI values were 3.99, 5.08, 1.38, 1.95, and 0.84, and the values of HI were 1.10, 1.36, 1.43, 1.06, and 1.04, respectively. The averaged mean doses to normal tissue were 2.5, 2.7, 3.6, 1.7, and 2.9 Gy for single-target plans, and 21.3, 14.6, 14.2, 14.3, and 13.0 Gy for the multitarget plans, respectively. The VMAT demonstrated dosimetric advantages and better treatment efficiency over other techniques for the radiotherapy of multifocal skin disease of the feet. 

Assessment of potential jaw-tracking advantage using control point sequences of VMAT planning.

This study aims to evaluate the potential jaw-tracking advantage using control point sequences of volume volumetric modulated arc therapy (VMAT) planning. VMAT plans for patients with prostate and head and neck (H&N) cancers were converted into new static arc (SA) plans. The SA plan consisted of a series of static fields at each control point of the VMAT plan. All other machine parameters of the SA plan were perfectly identical to those of the original VMAT plan. The jaw-tracking static arc (JTSA) plans were generated with fields that closed the jaws of each SA field into the multileaf collimators (MLCs) aperture. The dosimetric advantages of JTSA over SA were evaluated in terms of a dose-volume histogram (DVH) of organ at risk (OAR) after renormalizing both plans to make the same target coverage. Both plans were delivered to the MatriXX-based COMPASS system for 3D volume dose verification. The average jaw size reduction of the JTSA along the X direction was 3.1 ± 0.9 cm for prostate patients and 6.9 ± 1.9 cm for H&N patients. For prostate patients, the organs far from the target showed larger sparing (3.7%-8.1% on average) in JTSA than the organs adjacent to the target (1.1%-1.5%). For the H&N plans, the mean dose reductions for all organs ranged from 4.3% to 11.9%. The dose reductions were more significant in the dose regions of D80, D90, and D95 than the dose regions of D5, D10, and D20 for all patients. Likewise, the deliverability and reproducibility of jaw-tracking plan were validated. The measured dosimetric advantage of JTSA over SA coincided with the calculated one above.

A GPU-accelerated Monte Carlo code, RT2for coupled transport of photon, electron/positron, and neutron.

Objective.This work aims to develop a graphics processing unit (GPU)-accelerated Monte Carlo code for the coupled transport of photon, electron/positron and neutron over a broad range of energies for medical applications.Approach.By separating the MC evolution of radiation into source, transport, and interaction kernels, the branch divergence was alleviated. The memory coalescence was achieved by vectorizing the access pattern in which the secondary particles were archived. To accelerate further particle tracking, ray-tracing hardware acceleration in the Nvidia OptiXTMframework was applied. For photon and electron/positron, the EGSnrc interaction modules were ported as a GPU-optimized configuration. For neutron, a group-wised transport based on NJOY21 preprocessed data was implemented. The developed code was validated against CPU-based FLUKA. Neutron, x-ray and electron beams incident on water and ICRP phantoms were simulated. The neutron energy group and the transport parameters of photon and electron were set to be the same in both codes. A single Nvidia RTX 4090 card was used in this code while all 20 threads of a single Intel Core i9-10900K node were used in FLUKA.Main results.The number of histories was set to ensure that statistical uncertainties lower than 2% for all voxels whose doses were larger than 20% of the maximum. In all cases, the dose differences in the voxels between the codes were within 2.5%. For photons and electrons, the developed code was 150-300 times faster than FLUKA in both geometries. For neutrons, the code was respectively 80 and 135 times faster in the water and ICRP phantoms than FLUKA.Significance.This study offers an appropriate solution for uncoalesced memory access and branch divergence commonly encountered in coupled MC transport on the GPU architecture. The formidable acceleration in computing times and accuracy shown in this study can promise a routine clinical use of MC simulations.

Enhancing Precision in L-band Electron Paramagnetic Resonance Tooth Dosimetry: Incorporating Digital Image Processing and Radiation Therapy Plans for Geometric Correction.

ABSTRACT: Following unforeseen exposure to radiation, quick dose determination is essential to prioritize potential patients that require immediate medical care. L-band electron paramagnetic resonance tooth dosimetry can be efficiently used for rapid triage as this poses no harm to the human incisor, although geometric variations among human teeth may hinder accurate dose estimation. Consequently, we propose a practical geometric correction method using a mobile phone camera. Donated human incisors were irradiated with calibrated 6-MV photon beam irradiation, and dose-response curves were developed by irradiation with a predetermined dose using custom-made poly(methyl methacrylate) slab phantoms. Three radiation treatment plans for incisors were selected and altered to suit the head phantom. The mean doses on tooth structures were calculated using a commercial treatment planning system, and the electron paramagnetic resonance signals of the incisors were measured. The enamel area was computed from camera-acquired tooth images. The relative standard uncertainty was rigorously estimated both with and without geometric correction. The effects on the electron paramagnetic resonance signal caused by axial and rotational movements of tooth samples were evaluated through finite element analysis. The mean absolute deviations of mean doses both with and without geometric correction showed marginal improvement. The average relative differences without and with geometric correction significantly decreased from 21.0% to 16.8% (p = 0.01). The geometric correction method shows potential in improving dose precision measurement with minimal delay. Furthermore, our findings demonstrated the viability of using treatment planning system doses in dose estimation for L-band electron paramagnetic resonance tooth dosimetry.

Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Development of real-time motion verification system using in-room optical images for respiratory-gated radiotherapy.

Phase-based respiratory-gated radiotherapy relies on the reproducibility of patient breathing during the treatment. To monitor the positional reproducibility of patient breathing against a 4D CT simulation, we developed a real-time motion verification system (RMVS) using an optical tracking technology. The system in the treatment room was integrated with a real-time position management system. To test the system, an anthropomorphic phantom that was mounted on a motion platform moved on a programmed breathing pattern and then underwent a 4D CT simulation with RPM. The phase-resolved anterior surface lines were extracted from the 4D CT data to constitute 4D reference lines. In the treatment room, three infrared reflective markers were attached on the superior, middle, and inferior parts of the phantom along with the body midline and then RMVS could track those markers using an optical camera system. The real-time phase information extracted from RPM was delivered to RMVS via in-house network software. Thus, the real-time anterior-posterior positions of the markers were simultaneously compared with the 4D reference lines. The technical feasibility of RMVS was evaluated by repeating the above procedure under several scenarios such as ideal case (with identical motion parameters between simulation and treatment), cycle change, baseline shift, displacement change, and breathing type changes (abdominal or chest breathing). The system capability for operating under irregular breathing was also investigated using real patient data. The evaluation results showed that RMVS has a competence to detect phase-matching errors between patient's motion during the treatment and 4D CT simulation. Thus, we concluded that RMVS could be used as an online quality assurance tool for phase-based gating treatments.

A multi-institutional study for tolerance and action levels of IMRT dose quality assurance measurements in Korea.

The purpose of this study was to suggest tolerance levels for IMRT DQA measurements using confidence limits determined by a multi-institutional study in Korea. Ten institutions were grouped into LINAC (seven linear accelerators) and TOMO (three tomotherapy machines). The DQA processes consisted of point (high- and low-dose regions) and planar (per-field and composite-field) dose measurements using an ion chamber and films (or 2D detector array) inserted into a custom-made acryl phantom (LINAC) or a cheese phantom (TOMO). The five mock structures developed by AAPM TG-119 were employed, but the prostate as well as the H&N structures were modified according to Korean patients' anatomy. The point measurements were evaluated in a ratio of measured and planned doses, while the planar dose distributions were assessed using two gamma criteria of 2 mm/2% and 3 mm/3%. The confidence limit (|mean + 1.96 σ|) for point measurements was determined to be 3.0% in high-dose regions and 5.0% in low-dose regions. The average percentage of points passing the gamma criteria of 2 mm/2% and 3mm/3% for per-field measurements was 92.7 ± 6.5% and 98.2 ± 2.8%, respectively. Thus, the corresponding confidence limit was 79.1% and 92.7%, respectively. The gamma passing rate averaged over all mock tests and institutions for composite-field measurements was 86.1 ± 6.5% at 2 mm/2% and 95.3 ± 3.8% at 3 mm/3%, leading to the confidence limit of 73.3% and 87.9%, respectively. There was no significant difference in the tolerance levels of point dose measurements between LINAC and TOMO groups. In spite of the differences in mock structures and dosimetry tools, our tolerance levels were comparable to those of AAPM and ESTRO guidelines.

Development of an advanced velocity modulator for a portable Mössbauer spectrometer.

Mössbauer spectroscopy is a nuclear spectroscopic technique that measures changes in energy on an atomic scale. In a Mössbauer spectrometer, a velocity modulator oscillates a radioactive source to vary the energy of gamma rays. Conventional velocity modulators use wires primarily as motion guides; however, the tension state of these wires may change over time. Membrane springs are thus used as an alternative to wires; however, they also present certain challenges related to their design, manufacturing, and assembly. Instead of wires or membrane springs, this study used a linear bearing with preloaded compression springs. The advantage of this mechanism is that permanent deformation or changes in spring stiffness minimally occur during spring assembly and operation. The developed velocity modulator is compact and light, making it ideal for portable applications. A digital controller is used to easily modify and customize control parameters and the supporting algorithm, which is not easily achieved with conventional analog controllers. Moreover, by applying a switching amplifier, low-power operation is also achieved. Feedforward control values are calculated by an iterative learning method that is robust to the control of repeated motion. Using finite element method simulations and experiments, the performance of the developed prototype was evaluated. The velocity signal demonstrated linearity with a correlation with a straight line of approximately 0.996 for a triangular velocity profile (satisfactory performance).

Dual imaging modality of fluorescence and transmission X-rays for gold nanoparticle-injected living mice.

BACKGROUND: X-ray fluorescence (XRF) imaging for metal nanoparticles (MNPs) is a promising molecular imaging modality that can determine dynamic biodistributions of MNPs. However, it has the limitation that it only provides functional information. PURPOSE: In this study, we aim to show the feasibility of acquiring functional and anatomic information on the same platform by demonstrating a dual imaging modality of pinhole XRF and computed tomography (CT) for gold nanoparticle (GNP)-injected living mice. METHODS: By installing a transmission CT detector in an existing pinhole XRF imaging system using a two-dimensional (2D) cadmium zinc telluride (CZT) gamma camera, XRF and CT images were acquired on the same platform. Due to the optimal X-ray spectra for XRF and CT image acquisition being different, XRF and CT imaging were performed by 140 and 50 kV X-rays, respectively. An amount of 40 mg GNPs (1.9 nm in diameter) suspended in 0.20 ml of phosphate-buffered saline were injected into the three BALB/c mice via a tail vein. Then, the kidney and tumor slices of mice were scanned at specific time points within 60 min to acquire time-lapse in vivo biodistributions of GNPs. XRF images were directly acquired without image reconstruction using a pinhole collimator and a 2D CZT gamma camera. Subsequently, CT images were acquired by performing CT scans. In order to confirm the validity of the functional information provided by the XRF image, the CT image was fused with the XRF image. After the XRF and CT scan, the mice were euthanized, and major organs (kidneys, tumor, liver, and spleen) were extracted. The ex vivo GNP concentrations of the extracted organs were measured by inductively coupled plasma mass spectrometry (ICP-MS) and L-shell XRF detection system using a silicon drift detector, then compared with the in vivo GNP concentrations measured by the pinhole XRF imaging system. RESULTS: Time-lapse XRF images were directly acquired without rotation and translation of imaging objects within an acquisition time of 2 min per slice. Due to the short image acquisition time, the time-lapse in vivo biodistribution of GNPs was acquired in the organs of the mice. CT images were fused with the XRF images and successfully confirmed the validity of the XRF images. The difference in ex vivo GNP concentrations measured by the L-shell XRF detection system and ICP-MS was 0.0005-0.02% by the weight of gold (wt%). Notably, the in vivo and ex vivo GNP concentrations in the kidneys of three mice were comparable with a difference of 0.01-0.08 wt%. CONCLUSIONS: A dual imaging modality of pinhole XRF and CT imaging system and L-shell XRF detection system were successfully developed. The developed systems are a promising modality for in vivo imaging and ex vivo quantification for preclinical studies using MNPs. In addition, we discussed further improvements for the routine preclinical applications of the systems.

Frequency-fixed motion compensation system for in-vivo electron paramagnetic resonance tooth dosimetry.

This article describes the design process for a motion compensation system that can suppress the spectral distortion caused by human motion and breathing during in-vivo electron paramagnetic resonance (EPR) spectroscopy on an intact incisor. The developed system consists of two elements: an electronically controlled tunable resonator and an automatic control circuit (ACC). The resonator can modify the resonant frequency and impedance by tuning and matching the voltage, while the ACC can generate a feedback signal using phase-sensitive detection (PSD). The signal is transferred into the resonator to maintain the critical coupling state. The tunable frequency range of the resonator was measured at over 10 MHz, offering approximately eight times the required range. The bandwidth of the resonator fluctuated in a negligible range (0.14% relative standard error) following the resonant frequency. With the feedback signal on, in-vivo EPR measurements were demonstrated to be a stable baseline with 35% higher signal-to-noise ratio (SNR). When one incisor sample was irradiated by an X-ray instrument, the EPR signal responses to the absorbed doses of 0-10 Gy exhibited high linearity (R2 = 0.994). In addition, the standard error of inverse prediction was estimated to be 0.35 Gy. The developed system achieved a discrimination ability of 2 Gy, which is required for triage in large-scale radiation accidents. Moreover, the compensation is fully automated, meaning that the system can be operated with simple training in an emergency.

Calibration and simulation of a silicon dosemeter for ambient dose equivalent in low-earth orbit space.

A particle dosemeter (PD) is a payload of NEXTSat-2 in the low-earth orbit (LEO). The absorbed dose in LEO needs to be converted into the ambient dose equivalent (H*(10)). Due to a mixed field in LEO, the calibration factors (klow and khigh) should be determined for the low-and high-linear energy transfers (LET) (below and above 1.5 keV/µm), respectively. The PD was irradiated with a 137Cs source at the Korea Radiation Solution facility to obtain H*(10) and absorbed doses. However due to the lack of sources for the high-LET calibration, H*(10) and an absorbed dose were calculated by simulating PD for the high-energy neutron field at CERN-EU high-energy Reference Field. The measured klow of PD had a difference of 5.1% and 9.5% from the calculated value of PD and the measured value of Liulin detectors, respectively. However, a difference in khigh between PD and Liulin was explained by the contribution of non-neutron components to Liulin in the measurements.

Enhanced Dosimetric Accuracy Using Quality Factor Compensation Method for In Vivo Electron Paramagnetic Resonance Tooth Dosimetry.

ABSTRACT: We aim to develop a dose assessment method compensating for quality factors (Q factor) observed during in vivo EPR tooth dosimetry. A pseudo-in-vivo phantom made of tissue-equivalent material was equipped with one each of four extracted human central incisors. A range of Q factors was measured at tooth-depths of -2, 0, and 2 mm in the pseudo-in-vivo phantom. In addition, in vivo Q factors were measured from nine human volunteers. For the dose-response data, the above four sample teeth were irradiated at 0, 1, 2, 5, and 10 Gy, and the radiation-induced signals were measured at the same tooth-depths using an in vivo EPR tooth dosimetry system. To validate the method, the signals of two post-radiotherapy patients and three unirradiated volunteers were measured using the same system. The interquartile range of the Q factors measured in the pseudo-in-vivo phantom covered that observed from the human volunteers, which implied that the phantom represented the Q factor distribution of in vivo conditions. The dosimetric sensitivities and background signals were decreased as increasing the tooth-depth in the phantom due to the decrease in Q factors. By compensating for Q factors, the diverged dose-response data due to various Q factors were converged to improve the dosimetric accuracy in terms of the standard error of inverse prediction (SEIP). The Q factors of patient 1 and patient 2 were 98 and 64, respectively, while the three volunteers were 100, 92, and 99. The assessed doses of patient 1 and patient 2 were 2.73 and 12.53 Gy, respectively, while expecting 4.43 and 13.29 Gy, respectively. The assessed doses of the unirradiated volunteers were 0.53, 0.50, and - 0.22 Gy. We demonstrated that the suggested Q factor compensation could mitigate the uncertainty induced by the variation of Q factors.

Dosimetric perturbations due to an implanted cardiac pacemaker in MammoSite(®) treatment.

PURPOSE: To investigate dose perturbations for pacemaker-implanted patients in partial breast irradiation using high dose rate (HDR) balloon brachytherapy. METHODS: Monte Carlo (MC) simulations were performed to calculate dose distributions involving a pacemaker in Ir-192 HDR balloon brachytherapy. Dose perturbations by varying balloon-to-pacemaker distances (BPD = 50 or 100 mm) and concentrations of iodine contrast medium (2.5%, 5.0%, 7.5%, and 10.0% by volume) in the balloon were investigated for separate parts of the pacemaker (i.e., battery and substrate). Relative measurements using an ion-chamber were also performed to confirm MC results. RESULTS: The MC and measured results in homogeneous media without a pacemaker agreed with published data within 2% from the balloon surface to 100 mm BPD. Further their dose distributions with a pacemaker were in a comparable agreement. The MC results showed that doses over the battery were increased by a factor of 3, compared to doses without a pacemaker. However, there was no significant dose perturbation in the middle of substrate but up to 70% dose increase in the substrate interface with the titanium capsule. The attenuation by iodine contrast medium lessened doses delivered to the pacemaker by up to 9%. CONCLUSIONS: Due to inhomogeneity of pacemaker and contrast medium as well as low-energy photons in Ir-192 HDR balloon brachytherapy, the actual dose received in a pacemaker is different from the homogeneous medium-based dose and the external beam-based dose. Therefore, the dose perturbations should be considered for pacemaker-implanted patients when evaluating a safe clinical distance between the balloon and pacemaker.

Photon energy-modulated radiotherapy: Monte Carlo simulation and treatment planning study.

PURPOSE: To demonstrate the feasibility of photon energy-modulated radiotherapy during beam-on time. METHODS: A cylindrical device made of aluminum was conceptually proposed as an energy modulator. The frame of the device was connected with 20 tubes through which mercury could be injected or drained to adjust the thickness of mercury along the beam axis. In Monte Carlo (MC) simulations, a flattening filter of 6 or 10 MV linac was replaced with the device. The thickness of mercury inside the device varied from 0 to 40 mm at the field sizes of 5 × 5 cm(2) (FS5), 10 × 10 cm(2) (FS10), and 20 × 20 cm(2) (FS20). At least 5 billion histories were followed for each simulation to create phase space files at 100 cm source to surface distance (SSD). In-water beam data were acquired by additional MC simulations using the above phase space files. A treatment planning system (TPS) was commissioned to generate a virtual machine using the MC-generated beam data. Intensity modulated radiation therapy (IMRT) plans for six clinical cases were generated using conventional 6 MV, 6 MV flattening filter free, and energy-modulated photon beams of the virtual machine. RESULTS: As increasing the thickness of mercury, Percentage depth doses (PDD) of modulated 6 and 10 MV after the depth of dose maximum were continuously increased. The amount of PDD increase at the depth of 10 and 20 cm for modulated 6 MV was 4.8% and 5.2% at FS5, 3.9% and 5.0% at FS10 and 3.2%-4.9% at FS20 as increasing the thickness of mercury from 0 to 20 mm. The same for modulated 10 MV was 4.5% and 5.0% at FS5, 3.8% and 4.7% at FS10 and 4.1% and 4.8% at FS20 as increasing the thickness of mercury from 0 to 25 mm. The outputs of modulated 6 MV with 20 mm mercury and of modulated 10 MV with 25 mm mercury were reduced into 30%, and 56% of conventional linac, respectively. The energy-modulated IMRT plans had less integral doses than 6 MV IMRT or 6 MV flattening filter free plans for tumors located in the periphery while maintaining the similar quality of target coverage, homogeneity, and conformity. CONCLUSIONS: The MC study for the designed energy modulator demonstrated the feasibility of energy-modulated photon beams available during beam-on time. The planning study showed an advantage of energy-and intensity modulated radiotherapy in terms of integral dose without sacrificing any quality of IMRT plan.