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.

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.

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.

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).

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.

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.

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.

Deep Radiomics-based Approach to the Diagnosis of Osteoporosis Using Hip Radiographs.

Purpose: To develop and validate deep radiomics models for the diagnosis of osteoporosis using hip radiographs. Materials and Methods: A deep radiomics model was developed using 4924 hip radiographs from 4308 patients (3632 women; mean age, 62 years ± 13 [SD]) obtained between September 2009 and April 2020. Ten deep features, 16 texture features, and three clinical features were used to train the model. T score measured with dual-energy x-ray absorptiometry was used as a reference standard for osteoporosis. Seven deep radiomics models that combined different types of features were developed: clinical (model C); texture (model T); deep (model D); texture and clinical (model TC); deep and clinical (model DC); deep and texture (model DT); and deep, texture, and clinical features (model DTC). A total of 444 hip radiographs obtained between January 2019 and April 2020 from another institution were used for the external test. Six radiologists performed an observer performance test. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic performance. Results: For the external test set, model D (AUC, 0.92; 95% CI: 0.89, 0.95) demonstrated higher diagnostic performance than model T (AUC, 0.77; 95% CI: 0.70, 0.83; adjusted P < .001). Model DC (AUC, 0.95; 95% CI: 0.92, 0.97; adjusted P = .03) and model DTC (AUC, 0.95; 95% CI: 0.92, 0.97; adjusted P = .048) showed improved diagnostic performance compared with model D. When observer performance without and with the assistance of the model DTC prediction was compared, performance improved from a mean AUC of 0.77 to 0.87 (P = .002). Conclusion: Deep radiomics models using hip radiographs could be used to diagnose osteoporosis with high performance.Keywords: Skeletal-Appendicular, Hip, Absorptiometry/Bone Densitometry© RSNA, 2022.

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.

Microdosimetric-Kinetic Model for Radio-enhancement of Gold Nanoparticles: Comparison with LEM.

Numerous studies have strongly supported the application of gold nanoparticles (GNPs) as radio-enhanced agents. In our previous study, the local effect model (LEM I) was adopted to predict the cell survival for MDA-MB-231 cells exposed to 150 kVp X rays after 500 µg/ml GNPs treatment. However, microdosimetric quantities could not be obtained, which were correlated with biological effects on cells. Thus, we developed microdosimetric kinetic model (MKM) for GNP radio-enhancement (GNP-MKM), which uses the microdosimetric quantities such as dose-mean lineal energy with subcellular domain size. Using the Monte Carlo simulation tool Geant4, we estimated the dose-mean lineal energy with secondary radiations from GNPs and absorbed dose in the nucleus. The variations in MKM parameters for different domain sizes, and GNP concentrations, were calculated to compare the survival fractions predicted by both models. With a domain radius of 500 nm and a threshold dose of 20 Gy, the sensitizer enhancement ratio predicted by GNP-MKM and GNP-LEM was 1.41 and 1.29, respectively. The GNP-MKM predictions were much more strongly dependent on the domain size than were the GNP-LEM on the threshold dose. These findings provide another method to predict survival fraction for the GNP radio-enhancement.

Dependence of Radiation-induced Signals on Geometry of Tooth Enamel Using a 1.15 GHz Electron Paramagnetic Resonance Spectrometer: Improvement of Dosimetric Accuracy.

ABSTRACT: We aim to improve the accuracy of electron paramagnetic resonance (EPR)-based in vivo tooth dosimetry using the relationship between tooth geometry and radiation-induced signals (RIS). A homebuilt EPR spectrometer at L-band frequency of 1.15 GHz originally designed for non-invasive and in vivo measurements of intact teeth was used to measure the RIS of extracted human teeth. Twenty human central incisors were scanned by microCT and irradiated by 220 kVp x-rays. The RISs of the samples were measured by the EPR spectrometer as well as simulated by using the finite element analysis of the electromagnetic field. A linear relationship between simulated RISs and tooth geometric dimensions, such as enamel area, enamel volume, and labial enamel volume, was confirmed. The dose sensitivity was quantified as a slope of the calibration curve (i.e., RIS vs. dose) for each tooth sample. The linear regression of these dose sensitivities was established for each of three tooth geometric dimensions. Based on these findings, a method for the geometry correction was developed by use of expected dose sensitivity of a certain tooth for one of the tooth geometric dimensions. Using upper incisors, the mean absolute deviation (MAD) without correction was 1.48 Gy from an estimated dose of 10 Gy; however, the MAD corrected by enamel area, volume, and labial volume was reduced to 1.04 Gy, 0.77 Gy, and 0.83 Gy, respectively. In general, the method corrected by enamel volume showed the best accuracy in this study. This homebuilt EPR spectrometer for the purpose of non-invasive and in vivo tooth dosimetry was successfully tested for achieving measurements in situ. We demonstrated that the developed correction method could reduce dosimetric uncertainties resulting from the variations in tooth geometric dimensions.

Radiosensitization by Au-nanofilm at micrometer level using confocal Raman spectroscopy.

PURPOSE: To measure the radiosensitization by an Au-nanofilm (GNF) at a micrometer level on a radiochromic film (RCF) using confocal Raman spectroscopy (CRS). METHODS: Unlaminated radiochromic films were irradiated by 200 kVp x-ray from 0.3 to 50 Gy to obtain a calibration curve. Raman spectra of these films were measured by positioning the postirradiated RCF perpendicular to the CRS monochromatic beam and reading a depth profile of the film along the lateral axis. The Raman peak corresponding to the C ≡ C peak was obtained from a region of interest of 100 × 5 µm2 . To investigate the radiosensitization by GNF, two sets of RCF, one attached to a 100-nm thick GNF and the other without GNF were irradiated at 0.5 Gy by 50 and 120 kVp X-rays. The spatial resolution of the CRS on the RCF was quantified by the modulation transfer function method (MTF). Thus, in the spatial resolution determined by MTF, the doses deposited on the films were evaluated. The dose enhancement factor (DEF) was obtained in the measurable micro-size by comparing doses deposited on the RCFs with and without GNF. To verify the experimental results, Monte Carlo simulations following the experimental set up were performed using Geant4. In addition, analytical calculations for the radiosensitization by GNF were carried out. RESULTS: The confocal Raman spectroscopy on the RCF achieved a spatial resolution of ~6 µm. An experimental DEF within the first 6 µm depth from the surface of RCF was found to be 17.9 for 50 kVp and 14.7 for 120 kVp. The DEF for the same depth obtained by MC and analytical calculations was 13.53 and 9.75 for 50 kVp, and 10.63 and 6.67 for 120 kVp, respectively. CONCLUSIONS: The experimental DEF as a function of the distance from GNF was consistent with data from previous studies and the MC simulations, supporting that CRS in conjunction with the RCF is a feasible micrometer-resolution dosimeter.

Europium-Diethylenetriaminepentaacetic Acid Loaded Radioluminescence Liposome Nanoplatform for Effective Radioisotope-Mediated Photodynamic Therapy.

Photodynamic therapy (PDT) is an effective anticancer strategy with a higher selectivity and fewer adverse effects than conventional therapies; however, shallow tissue penetration depth of light has hampered the clinical utility of PDT. Recently, reports have indicated that Cerenkov luminescence-induced PDT may overcome the tissue penetration limitation of conventional PDT. However, the effectiveness of this method is controversial because of its low luminescence intensity. Herein, we developed a radiolabeled diethylenetriaminepentaacetic acid chelated Eu3+ (Eu-DTPA)/photosensitizer (PS) loaded liposome (Eu/PS-lipo) that utilizes ionizing radiation from radioisotopes for effective in vivo imaging and radioluminescence-induced PDT. We utilized Victoria blue-BO (VBBO) as a PS and observed an efficient luminescence resonance energy transfer between Eu-DTPA and VBBO. Furthermore, 64Cu-labeled Eu lipo demonstrated a strong radioluminescence with a 2-fold higher intensity than Cerenkov luminescence from free 64Cu. In our radioluminescence liposome, radioluminescence energy transfer showed a 6-fold higher energy transfer efficiency to VBBO than Cerenkov luminescence energy transfer (CLET). 64Cu-labeled Eu/VBBO lipo (64Cu-Eu/VBBO lipo) showed a substantial tumor uptake of up to 19.3%ID/g by enhanced permeability and retention effects, as revealed by in vivo positron emission tomography. Finally, the PDT using 64Cu-Eu/VBBO lipo demonstrated significantly higher in vitro and in vivo therapeutic effects than Cerenkov luminescence-induced PDT using 64Cu-VBBO lipo. This study envisions a great opportunity for clinical PDT application by establishing the radioluminescence liposome which has high tumor targeting and efficient energy transfer capability from radioisotopes.

Artifact-free CT images for electron beam therapy using a patient-specific non metallic shield.

Patient's CT images taken with metallic shields for radiotherapy suffer from artifacts. Furthermore, the treatment planning system (TPS) has a limitation on accurate dose calculations for high density materials. In this study, a Monte Carlo (MC)-based method was developed to accurately evaluate the dosimetric effect of the metallic shield. Two patients with a commercial tungsten shield of lens and two patients with a custom-made lead shield of lip were chosen to produce their non-metallic dummy shields using 3D scanner and printer. With these dummy shields, we generated artifact-free CT images. The maximum CT number allowed in TPS was assigned to metallic shields. MC simulations with real material information were carried out. In addition, clinically relevant dose-volumetric parameters were calculated for the comparison between MC and TPS. Relative dosimetry was performed using radiochromic films. The dose reductions below metallic structures were shown on MC dose distributions, but not evident on TPS dose distributions. The differences in dose-volumetric parameters of PTV between TPS and MC for eye shield cases were not clearly shown. However, the mean dose of lens from TPS and MC was different. The MC results were in superior agreement with measured data in relative dosimetry. The lens dose could be overestimated by TPS. The differences in dose-volumetric parameters of PTV between TPS and MC were generally larger in lip cases than in eye cases. The developed method is useful in predicting the realistic dose distributions around the organs blocked by the metallic shields.

Reduced-dose whole-brain radiotherapy with tumor bed boost after upfront high-dose methotrexate for primary central nervous system lymphoma.

PURPOSE: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. RESULTS: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. CONCLUSION: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.

Dynamic In Vivo X-ray Fluorescence Imaging of Gold in Living Mice Exposed to Gold Nanoparticles.

Dynamic in vivo biodistribution of gold nanoparticles (GNPs) in living mice was first successfully acquired by a pinhole X-ray fluorescence (XRF) imaging system using polychromatic X-rays. The system consisted of fan-beam X-rays to stimulate GNPs and a 2D cadmium zinc telluride (CZT) gamma camera to collect K-shell XRF photons emitted from the GNPs. 2D XRF images of kidney slices of three Balb/C mice were obtained within 2 minutes of irradiation per slice. 40 mg of GNPs suspended in a 0.2 mL phosphate-buffered saline was injected into the mice via a tail vein. The mice were scanned over a 60 min period after the injection of GNPs in order to acquire a dynamic biodistribution of GNPs. The concentrations of GNPs measured by the CZT gamma camera were then validated by inductively coupled plasma atomic emission spectroscopy and ex vivo L-shell XRF measurements using a silicon drift detector. The GNP concentrations in the right-side kidneys were 1.58% by weight (wt%) at T =0 min and 0.77 wt% at T=60 min after the injection. This investigation showed a dramatically reduced scan time and imaging dose. Hence, we conclude that dynamic in vivo XRF imaging of GNPs is technically feasible in a benchtop system. The developed pinhole XRF imaging system can be a potential molecular imaging modality for metal nanoparticles to emerge as a radiosensitizer and a drug-delivery agent.

Measuring radioenhancement by gold nanofilms: Comparison with analytical calculations.

PURPOSE: To measure radioenhancement by gold nanoparticles (GNPs) using gold nanofilms (GNFs). METHODS: GNFs of 20-100 nm thicknesses were prepared. The GNF attached to radiochromic film (RCF) was irradiated using 50, 220 kVp, and 6 MV X-rays. The radiation doses to the active layer of RCF with and without GNF were measured using an optical flatbed scanner and Raman spectrometer to estimate the dose enhancement factor (DEF). For verification, analytical calculations of DEF within the thickness of active layer and the ranges of secondary electrons were carried out. RESULTS: The DEFs for GNFs of 20 to 100 nm thicknesses measured by an optical scanner ranged from 2.1 to 6.1 at 50 kVp and 1.6 to 4.9 at 220 kVp. Similarly, the DEFs measured by Raman spectroscopy ranged from 2.6 to 4.6 at 50 kVp and 2.2 to 4.8 at 220 kVp. The calculated DEFs ranged from 1.5 to 3.6 at 50 kVp and from 1.7 to 4.7 at 220 kVp. Almost no dose enhancement was observed in 6 MV X-ray. The analytical DEFs seemed to be underestimated by averaging local enhancement over the entire active layer. However, analytical DEFs within the ranges of secondary electrons was much higher than the measured macroscopic DEFs. CONCLUSIONS: The experimental and analytical approaches developed in this study could quantitatively estimate radioenhancement by GNPs. Due to a short range of low-energy electrons emitted from gold, the microscopic radioenhancement within the ranges of low-energy electrons would be particularly important in a cell.

Dose perturbation and inhomogeneity of multi-arrays of 125I seed-loaded stent for treatment of portal vein tumor thrombosis.

PURPOSE: To investigate the dosimetry of 125I seed-loaded stent system currently used for an adjuvant treatment of portal vein tumor thrombosis (PVTT). METHODS: The stent system consisted of an inner metallic stent and outer seed-loaded capsules. Four arrays of 125I seeds were attached longitudinally to the outer surface of the stent at 90° separation. 145 Gy was prescribed at 5 mm from the axes of seed-arrays. For the geometries of the 4-array, and potential 6- and 8-array configurations, treatment planning system (TPS) and Monte Carlo (MC) calculations were performed to evaluate 3D dose distributions and dosimetric impact of the metallic stent. RESULTS: The MC simulations indicated the metallic stent reduced a dose to the prescription points by over 10%, compared to the water-based TPS results. The total activity calculated by the water-based TPS to deliver the prescription dose should compensate for this amount of reduction. The MC- and TPS-calculated doses normalized to the prescription points for the current configuration were in agreements within 4.3% on a cylindrical surface along 5 mm from the axes of seed-arrays. The longitudinal underdosage worsened as approaching the edge of arrays, and ranged from 2.8% to 25.5%. The angular underdosage between neighboring arrays was 2.1%-8.9%. CONCLUSIONS: With this compensation and a special care of near-edge underdosage, the current 4-array system can provide adequate dose coverage for treatment of PVTT. Further dosimetric homogeneity can be achieved using 6-or 8-array configurations.

Characterization of radiochromic films as a micrometer-resolution dosimeter by confocal Raman spectroscopy.

PURPOSE: Micrometer spatial resolution dosimetry has become inevitable for advanced radiotherapy techniques. A new approach using radiochromic films was developed to measure a radiation dose at a micrometer spatial resolution by confocal Raman spectroscopy. METHODS: The commercial radiochromic films (RCF), EBT3 and EBT-XD, were irradiated with known doses using 50, 100, 200, and 300 kVp, and 6-MV x rays. The dose levels ranged from 0.3 to 50 Gy. The Raman mapping technique developed in our early study was used to readout an area of 100 × 100 µm2 on RCF with improved lateral and depth resolutions with confocal Raman spectrometry. The variation in Raman spectra of C-C-C deformation and C≡C stretching modes of diacetylene polymers around 676 and 2060 cm-1 , respectively, as a function of therapeutic x-ray doses, was measured. The single peak (SP) of C≡C and the peak ratio (PR) of C≡C band height to C-C-C band height with a spatial resolution of 10 µm on both types of RCF were evaluated, averaged, and plotted as a function of dose. An achievable spatial resolution, clinically useful dose range, dosimetric sensitivity, dose uniformity, and postirradiation stability as well as the orientation, energy, and dose rate dependence, of both types of RCFs, were characterized by the technique developed in this study. RESULTS: A spatial resolution on RCF achieved by SP and PR methods was ~4.5 and ~2.9 µm, respectively. Raman spectroscopy data showed dose nonuniformity of ~11% in SP method and <3% in PR method. The SP method provided dose ranges of up to ~10 and ~20 Gy for EBT3 and EBT-XD films, respectively while the PR method up to ~30 and ~50 Gy. The PR method diminished the orientation effect. The percent difference between landscape and portrait orientations for the EBT3 and the EBT-XD films at 4 Gy had an acceptable level of 1.2% and 2.4%, respectively. With both SP and PR methods, the EBT3 and the EBT-XD films showed weak energy (within ~10% and ~3% for SP and PR methods, respectively) and dose rate dependence (within ~5% and ~3% for SP and PR methods, respectively) and had a stable response after 24-h postirradiation. CONCLUSIONS: A technique for micrometer-resolution dosimetry was successfully developed by detecting radiation-induced Raman shift on EBT3 and EBT-XD. Both types of RCFs were suitable for micrometer-resolution dosimetry using CRS. With CRS both lateral and depth resolutions on RCF were improved. The PR method provided superior characteristics in dose uniformity, dose ranges, orientation dependence, and laser effect for both types of RCFs. The overall dosimetric characteristics of the RCFs determined by this technique were similar to those known by optical density scanning. The CRS with the PR method is advantageous over other the traditional scanning systems as a spatial resolution of <10 µm on RCF can be achieved with less deviations.