Inhomogeneously distributed ferroptosis with a high peak-to-valley ratio may improve the antitumor immune response.

Combined radiotherapy (RT) and mild hyperthermia have been used clinically for decades to increase local control. Both modalities tend to achieve a homogeneous dose distribution within treatment targets to induce immunogenic cell death. However, marked, and long-lasting abscopal effects have not usually been observed. We proposed a hypothesis to emphasize the importance of the peak-to-valley ratio of the dose distribution inside the tumor to induce immunogenic ferrroptosis in peak area while avoid nonimmunogenic ferroptosis in valley area. Although inhomogeneous distributed energy absorption has been noted in many anticancer medical fields, the idea of sedulously created dose inhomogeneity related to antitumor immunity has not been discussed. To scale up the peak-to-valley ratio, we proposed possible implications by the combination of nanoparticles (NP) with conventional RT or hyperthermia, or the use of a high modulation depth of extremely low frequency hyperthermia or high resolution spatially fractionated radiotherapy (SFRT) to enhance the antitumor immune reactions.

Parameter configuration of the electrical spark discharge method for preparing graphene copper nanocomposite colloids and the analysis of product characteristics.

The electrical spark discharge method was used to prepare graphene copper nanocomposite (GNS-Cu) colloids under normal temperature and pressure. Cu and graphite were mixed in deionized water at a Cu : C mass ratio of 9 : 1 (99% purity), and the mixture was used to produce composite rods as the electrodes for spark machining. An electrical discharge machine with five settings of pulse cycle turn-on and turn-off times, namely 10-10, 30-30, 50-50, 70-70, and 90-90 µs, was used to prepare five different types of GNS-Cu colloids. The ultraviolet-visible spectroscopy results revealed that the highest absorbance (2.441) was observed when the turn-on and turn-off times were 30-30 µs, indicating that this configuration was most efficient for preparing GNS-Cu colloids. Transmission electron microscopy and X-ray diffraction analysis were also conducted to examine the surface characteristics and crystal structure of GNS-Cu colloids. The transmission electron microscopy results revealed that Cu particles in the GNS-Cu colloids were located within or on top of graphene sheets. The Cu particle size varied with the discharge efficiency, and the lattice spacing of the Cu particles was approximately 0.218 nm. The results of X-ray diffraction analysis revealed that no byproducts were formed from the preparation of GNS-Cu colloids, which had complete crystal structures.

Deriving Optimized PID Parameters of Nano-Ag Colloid Prepared by Electrical Spark Discharge Method.

Using the electrical spark discharge method, this study prepared a nano-Ag colloid using self-developed, microelectrical discharge machining equipment. Requiring no additional surfactant, the approach in question can be used at the ambient temperature and pressure. Moreover, this novel physical method of preparation produced no chemical pollution. This study conducted an in-depth investigation to establish the following electrical discharge conditions: gap electrical discharge, short circuits, and open circuits. Short circuits affect system lifespan and cause electrode consumption, resulting in large, non-nanoscale particles. Accordingly, in this study, research for and design of a new logic judgment circuit set was used to determine the short-circuit rate. The Ziegler-Nichols proportional-integral-derivative (PID) method was then adopted to find optimal PID values for reducing the ratio between short-circuit and discharge rates of the system. The particle size, zeta potential, and ultraviolet spectrum of the nano-Ag colloid prepared using the aforementioned method were also analyzed with nanoanalysis equipment. Lastly, the characteristics of nanosized particles were analyzed with a transmission electron microscope. This study found that the lowest ratio between short-circuit rates was obtained (1.77%) when PID parameters were such that Kp was 0.96, Ki was 5.760576, and Kd was 0.039996. For the nano-Ag colloid prepared using the aforementioned PID parameters, the particle size was 3.409 nm, zeta potential was approximately -46.8 mV, absorbance was approximately 0.26, and surface plasmon resonance was 390 nm. Therefore, this study demonstrated that reducing the short-circuit rate can substantially enhance the effectiveness of the preparation and produce an optimal nano-Ag colloid.

Fast Fourier transform combined with phase leading compensator for respiratory motion compensation system.

BACKGROUND: The reduction of the delaying effect in the respiratory motion compensation system (RMCS) is still impossible to completely correct the respiratory waveform of the human body due to each patient has a unique respiratory rate. In order to further improve the effectiveness of radiation therapy, this study evaluates our previously developed RMCS and uses the fast Fourier transform (FFT) algorithm combined with the phase lead compensator (PLC) to further improve the compensation rate (CR) of different respiratory frequencies and patterns of patients. METHODS: In this study, an algorithm of FFT automatic frequency detection was developed by using LabVIEW software, uisng FFT combined with PLC and RMCS to compensate the system delay time. Respiratory motion compensation experiments were performed using pre-recorded respiratory signals of 25 patients. During the experiment, the respiratory motion simulation system (RMSS) was placed on the RMCS, and the pre-recorded patient breathing signals were sent to the RMCS by using our previously developed ultrasound image tracking algorithm (UITA). The tracking error of the RMCS is obtained by comparing the encoder signals of the RMSS and RMCS. The compensation effect is verified by root mean squared error (RMSE) and system CR. RESULTS: The experimental results show that the patient's respiratory patterns compensated by the RMCS after using the proposed FFT combined with PLC control method, the RMSE is between 1.50-5.71 and 3.15-8.31 mm in the right-left (RL) and superior-inferior (SI) directions, respectively. CR is between 72.86-93.25% and 62.3-83.81% in RL and SI, respectively. CONCLUSIONS: This study used FFT combined with PLC control method to apply to RMCS, and used UITA for respiratory motion compensation. Under the automatic frequency detection, the best dominant frequency of the human respiratory waveform can be determinated. In radiotherapy, it can be used to compensate the tumor movement caused by respiratory motion and reduce the radiation damage and side effects of normal tissues nearby the tumor.

Tumor motion tracking based on a four-dimensional computed tomography respiratory motion model driven by an ultrasound tracking technique.

BACKGROUND: An ultrasound image tracking algorithm (UITA) was combined with four-dimensional computed tomography (4DCT) to create a real-time tumor motion-conversion model. The real-time position of a lung tumor phantom based on the real-time diaphragm motion trajectories detected by ultrasound imaging in the superior-inferior (SI) and medial-lateral (ML) directions were obtained. METHODS: Three different tumor motion-conversion models were created using a respiratory motion simulation system (RMSS) combined with 4DCT. The tumor tracking error was verified using cone-beam computed tomography (CBCT). The tumor motion-conversion model was produced by using the UITA to monitor the motion trajectories of the diaphragm phantom in the SI direction, and using 4DCT to monitor the motion trajectories of the tumor phantom in the SI and ML directions over the same time period, to obtain parameters for the motion-conversion model such as the tumor center position and the amplitude and phase ratios. RESULTS: The tumor movement was monitored for 90 s using CBCT to determine the real motion trajectories of the tumor phantom and using ultrasound imaging to simultaneously record the diaphragm movement. The absolute error of the motion trajectories of the real and estimated tumor varied between 0.5 and 2.1 mm in the two directions. CONCLUSIONS: This study has demonstrated the feasibility of using ultrasound imaging to track diaphragmatic motion combined with a 4DCT tumor motion-conversion model to track tumor motion in the SI and ML directions. The proposed method makes tracking a lung tumor feasible in real time, including under different breathing conditions.

Simulating the approximate irregular field dose distribution in radiotherapy using an ultrasound tracking technique.

PURPOSE: This study used an ultrasound image tracking algorithm (UITA) in combination with a proposed simulation program for the approximate irregular field dose distribution (SPAD) to assess the feasibility of performing dose distribution simulations for two-dimensional radiotherapy. METHODS: This study created five different types of multileaf collimator openings, and applied a SPAD to analyze the matrix position parameters for each regular field to generate a static program-simulation dose distribution map (PDDM), whose similarity was then compared with a static radiochromic film experimental-measurement dose distribution map (EDDM). A two-dimensional respiration motion simulation system (RMSS) was used to reproduce the respiration motion, and the UITA was used to capture the respiration signals. Respiration signals were input to the SPAD to generate two dynamic PDDMs, which were compared for similarity with the dynamic EDDM. RESULTS: In order to verify the dose distribution between different dose measurement techniques, the gamma passing rate with 2%/2 mm criterion was used for the EDDM and PDDM, the passing rates were between 94.31% and 99.71% in the static field analyses, and between 84.45% and 96.09% for simulations with the UITA signal input and between 89.35% and 97.78% for simulations with the original signal input in the dynamic field analyses. CONCLUSIONS: Static and dynamic dose distribution maps can be simulated based on the proposed matrix position parameters of various fields and by using the UITA to track respiration signals during radiation therapy. The present findings indicate that it is possible to develop a reusable and time-saving dose distribution measurement tool.

Parameter control and property analysis in the preparation of platinum iodide nanocolloids through the electrical spark discharge method.

This study employed the electrical spark discharge method to prepare platinum iodide nanocolloids at normal temperature and pressure. Wires composed of 99.5% platinum were applied as the electrodes, and 250 ppm liquid iodine was employed as the dielectric fluid. An electric discharge machine was applied to generate cyclic direct current pulse power between the electrodes. Five sets of turn-on and turn-off time (T on-T off) parameters, namely 10-10, 30-30, 50-50, 70-70, and 90-90 µs, were implemented to identify the optimal nanocolloid preparation conditions. An ultraviolet-visible spectroscope, a Zetasizer, and a transmission electron microscope were used to examine the nanocolloids' properties. The results revealed that the T on-T off parameter set of 10-10 µs was the most ideal setting for platinum iodide nanocolloid preparation. With this parameter set, the characteristic wavelengths of the nanocolloid were 285 and 350 nm, respectively; its absorbance values were 0.481 and 0.425, respectively; and its zeta potential and particle size were -30.3 mV and 61.88 nm, respectively. This parameter set yielded maximized absorbance, satisfactory suspension stability, and minimized nanoparticle sizes for the nanocolloid.

Novel Preparation of Reduced Graphene Oxide-Silver Complex using an Electrical Spark Discharge Method.

This study used an electrical discharge machine (EDM) to perform an electrical spark discharge method (ESDM), which is a new approach for reducing graphene oxide (GO) at normal temperature and pressure, without using chemical substances. A silver (Ag) electrode generates high temperature and high energy during gap discharge. Ag atoms and Ag nanoparticles (AgNP) are suspended in GO, and ionization generates charged Ag+ ions in the Ag plasma with a strong reducing property, thereby carrying O away from GO. A large flake-like structure of GO was simultaneously pyrolyzed to a small flake-like structure of reduced graphene oxide (rGO). When Ag was used as an electrode, GO was reduced to rGO and the exfoliated AgNP surface was coated with rGO, thus forming an rGOAg complex. Consequently, suspensibility and dispersion were enhanced.

Adaptive control of phase leading compensator parameters applied to respiratory motion compensation system.

PURPOSE: This study evaluates the feasibility of our previously developed Respiratory Motion Compensation System (RMCS) combined with the Phase Lead Compensator (PLC) to eliminate system delays during the compensation of respiration-induced tumor motion. The study objective is to improve the compensation effect of RMCS and the efficay of radiation therapy to reduce its side effects to the patients. MATERIAL AND METHODS: In this study, LabVIEW was used to develop the proposed software for calculating real-time adaptive control parameters, combined with PLC and RMCS for the compensation of total system delay time. Experiments of respiratory motion compensation were performed using 6 pre-recorded human respiration patterns and 7 sets of different sine waves. During the experiments, a respiratory simulation device, Respiratory Motion Simulation System (RMSS), was placed on the RMCS, and the detected target motion signals by the Ultrasound Image Tracking Algorithm (UITA) were transmitted to the RMCS, and the compensation of respiration induced motion was started. Finally, the tracking error of the system is obtained by comparing the encoder signals bwtween RMSS and RMCS. The compensation efficacy is verified by the root mean squared error (RMSE) and the system compensation rate (CR). RESULTS: The experimental results show that the calcuated CR with the simulated respiration patterns is between 42.85% ∼3.53% and 33.76% ∼2.62% in the Right-Left (RL) and Superior-Inferior (SI), respectively, after the RMCS compensation of using the adaptive control parameters in PLC. For the compensation results of human respiration patterns, the CR is between 58.95% ∼8.56% and 62.87% ∼9.05% in RL and SI, respectively. CONCLUSIONS: During the respiratory motion compensation, the influence of the delay time of the entire system (RMCS+RMSS+UITA) on the compensation effect was improved by adding an adaptive control PLC, which reduces compensation error and helps improve efficacy of radiation therapy.

Experimental verification of a two-dimensional respiratory motion compensation system with ultrasound tracking technique in radiation therapy.

This study proposed respiratory motion compensation system (RMCS) combined with an ultrasound image tracking algorithm (UITA) to compensate for respiration-induced tumor motion during radiotherapy, and to address the problem of inaccurate radiation dose delivery caused by respiratory movement. This study used an ultrasound imaging system to monitor respiratory movements combined with the proposed UITA and RMCS for tracking and compensation of the respiratory motion. Respiratory motion compensation was performed using prerecorded human respiratory motion signals and also sinusoidal signals. A linear accelerator was used to deliver radiation doses to GAFchromic EBT3 dosimetry film, and the conformity index (CI), root-mean-square error, compensation rate (CR), and planning target volume (PTV) were used to evaluate the tracking and compensation performance of the proposed system. Human respiratory pattern signals were captured using the UITA and compensated by the RMCS, which yielded CR values of 34-78%. In addition, the maximum coronal area of the PTV ranged from 85.53 mm2 to 351.11 mm2 (uncompensated), which reduced to from 17.72 mm2 to 66.17 mm2 after compensation, with an area reduction ratio of up to 90%. In real-time monitoring of the respiration compensation state, the CI values for 85% and 90% isodose areas increased to 0.7 and 0.68, respectively. The proposed UITA and RMCS can reduce the movement of the tracked target relative to the LINAC in radiation therapy, thereby reducing the required size of the PTV margin and increasing the effect of the radiation dose received by the treatment target.

Development of an in vitro diaphragm motion reproduction system.

This study developed an in vitro diaphragm motion reproduction system (IVDMRS) based on noninvasive and real-time ultrasound imaging to track the internal displacement of the human diaphragm and diaphragm phantoms with a respiration simulation system (RSS). An ultrasound image tracking algorithm (UITA) was used to retrieve the displacement data of the tracking target and reproduce the diaphragm motion in real time using a red laser to irradiate the diaphragm phantom in vitro. This study also recorded the respiration patterns in 10 volunteers. Both simulated and the respiration patterns in 10 human volunteers signals were input to the RSS for conducting experiments involving the reproduction of diaphragm motion in vitro using the IVDMRS. The reproduction accuracy of the IVDMRS was calculated and analyzed. The results indicate that the respiration frequency substantially affects the correlation between ultrasound and kV images, as well as the reproduction accuracy of the IVDMRS due to the system delay time (0.35s) of ultrasound imaging and signal transmission. The utilization of a phase lead compensator (PLC) reduced the error caused by this delay, thereby improving the reproduction accuracy of the IVDMRS by 14.09-46.98%. Applying the IVDMRS in clinical treatments will allow medical staff to monitor the target displacements in real time by observing the movement of the laser beam. If the target displacement moves outside the planning target volume (PTV), the treatment can be immediately stopped to ensure that healthy tissues do not receive high doses of radiation.

Tracking and compensation of respiration pattern by an automatic compensation system.

PURPOSE: This study aimed to determine the feasibility of using an ultrasound image tracking algorithm (UITA) combined with a respiration compensating system (RCS) to track and compensate the respiration pattern of the diaphragm in real time. METHODS: Diaphragm motions and various respiration patterns were tracked and captured in volunteers using our previously developed UITA (Kuo et al., J Xray Sci Technol, 2016:875). A diaphragm phantom was placed on a respiration simulation system (RSS) that received signals with different respiration patterns to simulate actual human respiration signals. The RSS was mounted on the RCS, which is 180 cm long and driven by inputting a compensating signal to a linear actuator underneath with and without using a phase-lead compensator (PLC) (Chuang et al., J Xray Sci Technol, 2015:503). The target displacement was calculated automatically by the UITA and compensated by the RCS. The phantom displacements were observed using a fluoroscopic imaging system on the linear accelerator at the Department of Radiation Oncology, Taipei Medical University Hospital, and the results were also compared with the displacements measured by the UITA and the RSS for correlation verification. In addition, the compensating effect was analyzed after activating the RCS. RESULTS: The experimental results indicate a significant correlation between the UITA-calculated and actual displacements, with a correlation coefficient of up to 91% for the simulated respiration patterns. After activating the RCS, the obtained compensating effect was more than 65%, and even up to 85% if a PLC was used. Moreover, the compensation of 10 extreme respiration patterns of diaphragm was improved significantly through the use of a PLC, with a peak compensating rate of 88.92% being achieved. Finally, compensation effects ranging from 52% to 74% were obtained in 10 human volunteers. CONCLUSIONS: This study combined ultrasound imaging tracking technology with the RCS to offset the respiration-induced diaphragm displacement and compensate the various respiration patterns, even including those with baseline-shift phenomenon in real time with the aid of a noninvasive ultrasound imaging system.

An autotuning respiration compensation system based on ultrasound image tracking.

The purpose of this study was to develop an ultrasound image tracking algorithm (UITA) for extracting the exact displacement of internal organs caused by respiratory motion. The program can track organ displacements in real time, and analyze the displacement signals associated with organ displacements via a respiration compensating system (RCS). The ultrasound imaging system is noninvasive and has a high spatial resolution and a high frame rate (around 32 frames/s), which reduces the radiation doses that patients receive during computed tomography and X-ray observations. This allows for the continuous noninvasive observation and compensation of organ displacements simultaneously during a radiation therapy session.This study designed a UITA for tracking the motion of a specific target, such as the human diaphragm. Simulated diaphragm motion driven by a respiration simulation system was observed with an ultrasound imaging system, and then the induced diaphragm displacements were calculated by our proposed UITA. These signals were used to adjust the gain of the RCS so that the amplitudes of the compensation signals were close to the target movements. The inclination angle of the ultrasound probe with respect to the surface of the abdomen affects the results of ultrasound image displacement tracking. Therefore, the displacement of the phantom was verified by a LINAC with different inclination-angle settings of the ultrasound probe. The experimental results indicate that the best inclination angle of the ultrasound probe is 40 degrees, since this results in the target displacement of the ultrasound images being close to the actual target motion. The displacement signals of the tracking phantom and the opposing displacement signals created by the RCS were compared to assess the positioning accuracy of our proposed ultrasound image tracking technique combined with the RCS.When the ultrasound probe was inclined by 40 degrees in simulated respiration experiments using sine waves, the correlation between the target displacement on the ultrasound images and the actual target displacement was around 97%, and all of the compensation rates exceeded 94% after activating the RCS. Furthermore, the diaphragm movements on the ultrasound images of three patients could be captured by our image tracking technique. The test results show that our algorithm could achieve precise point locking and tracking functions on the diaphragm. This study has demonstrated the feasibility of the proposed ultrasound image tracking technique combined with the RCS for compensating for organ displacements caused by respiratory motion.This study has shown that the proposed ultrasound image tracking technique combined with the RCS can provide real-time compensation of respiratory motion during radiation therapy, without increasing the overall treatment time. In addition, the system has modest space requirements and is easy to operate.

The feasibility of the auto tuning respiratory compensation system with ultrasonic image tracking technique.

The purpose of this study is to assess the feasibility of using the analytical technique of ultrasound images in combination with an auto tumor localization system. During respiration, the activity of breathing in and out causes organs displacement at the lower lobe of the lung, and the maximum displacement range happens in the Superior-Inferior (SI) direction. Therefore, in this study all the tumor positioning is in SI direction under respiratory compensation, in which the compensations are carried out to the organs at the lower lobe and adjacent to the lower lobe of lung.In this research, due to the processes of ultrasound imaging generation, image analysis and signal transmission, when the captured respiratory signals are sent to auto tumor localization system, there was a signal time delay. The total delay time of the entire signal transmission process was 0.254 ± 0.023 seconds (with the lowest standard deviation) after implementing a series of analyses. To compensate for this signal delay time (0.254 ± 0.023 sec), a phase lead compensator (PLC) was designed and built into the auto tumor localization system. By analyzing the impact of the delay time and the respiratory waveforms under different frequencies on the phase lead compensator, an overall system delay time can be configured. Results showed as the respiratory frequency increased, variable value ``a'' and the subsequent gain ``k'' in the controller becomes larger. Moreover, value ``a'' and ``k'' increased as the system delay time increased when the respiratory frequency was fixed. The relationship of value ``a'' and ``k'' to the respiratory frequency can be obtained by using the curve fitting method to compensate for the respiratory motion for tumor localization. Through the comparison of the uncompensated signal and the compensated signal performed by the auto tumor localization system on the simulated respiratory signal, the feasibility of using ultrasound image analysis technology combined with the developed auto tumor localization system can be evaluated. The results show that the simulated respiratory signals under different frequencies of 0.5, 0.333, 0.25, 0.2 and 0.167 Hz with phase lead compensators were improved and stabilized. The compensation rate increased to the range of 7.04$∼ $18.82%, and the final compensation rate is about 97%. Therefore the auto tumor localization system combined with the ultrasound image analysis techniques is feasible.In this study, the developed ultrasound image analysis techniques combined into the auto tumor localization system has the following four advantages: (1) It is a non-invasive way (ultrasonic images) to monitor the entire compensating process of the active respiration instead of using a C-arm (invasive) to observe the organs motion. (2) During radiation therapy, the whole treatment process can be continuous, which can save the overall treatment time. (3) It is an independent system, which can be mounted onto any treatment couch. (4) Users can operate this system easily without the need of prior complicated training process.

Verification and compensation of respiratory motion using an ultrasound imaging system.

PURPOSE: The purpose of this study was to determine if it is feasible to use ultrasound imaging as an aid for moving the treatment couch during diagnosis and treatment procedures associated with radiation therapy, in order to offset organ displacement caused by respiratory motion. A noninvasive ultrasound system was used to replace the C-arm device during diagnosis and treatment with the aims of reducing the x-ray radiation dose on the human body while simultaneously being able to monitor organ displacements. METHODS: This study used a proposed respiratory compensating system combined with an ultrasound imaging system to monitor the compensation effect of respiratory motion. The accuracy of the compensation effect was verified by fluoroscopy, which means that fluoroscopy could be replaced so as to reduce unnecessary radiation dose on patients. A respiratory simulation system was used to simulate the respiratory motion of the human abdomen and a strain gauge (respiratory signal acquisition device) was used to capture the simulated respiratory signals. The target displacements could be detected by an ultrasound probe and used as a reference for adjusting the gain value of the respiratory signal used by the respiratory compensating system. This ensured that the amplitude of the respiratory compensation signal was a faithful representation of the target displacement. RESULTS: The results show that performing respiratory compensation with the assistance of the ultrasound images reduced the compensation error of the respiratory compensating system to 0.81-2.92 mm, both for sine-wave input signals with amplitudes of 5, 10, and 15 mm, and human respiratory signals; this represented compensation of the respiratory motion by up to 92.48%. In addition, the respiratory signals of 10 patients were captured in clinical trials, while their diaphragm displacements were observed simultaneously using ultrasound. Using the respiratory compensating system to offset, the diaphragm displacement resulted in compensation rates of 60%-84.4%. CONCLUSIONS: This study has shown that a respiratory compensating system combined with noninvasive ultrasound can provide real-time compensation of the respiratory motion of patients.

Biological characterization of cetuximab-conjugated gold nanoparticles in a tumor animal model.

Gold nanoparticles (AuNPs) are widely applied to the diagnosis and treatment of cancer and can be modified to contain target-specific ligands via gold-thiolate bonding. This study investigated the pharmacokinetics and microdistribution of antibody-mediated active targeting gold nanoparticles in mice with subcutaneous lung carcinoma. We conjugated AuNPs with cetuximab (C225), an antibody-targeting epidermal growth factor receptor (EGFR), and then labeled with In-111, which created EGFR-targeted AuNPs. In vitro studies showed that after a 2 h incubation, the uptake of C225-conjugated AuNPs in high EGFR-expression A549 cells was 14.9-fold higher than that of PEGylated AuNPs; furthermore, uptake was also higher at 3.8-fold when MCF7 cells with lower EGFR-expression were used. MicroSPECT/CT imaging and a biodistribution study conducted by using a A549 tumor xenograft mouse model provided evidence of elevated uptake of the C225-conjugated AuNPs into the tumor cells as a result of active targeting. Moreover, the microdistribution of PEGylated AuNPs revealed that a large portion of AuNPs remained in the tumor interstitium, whereas the C225-conjugated AuNPs displayed enhanced internalization via antibody-mediated endocytosis. Our findings suggest that the anti-EGFR antibody-conjugated AuNPs are likely to be a plausible nano-sized vehicle for drug delivery to EGFR-expressing tumors.

A respiratory compensating system: design and performance evaluation.

This study proposes a respiratory compensating system which is mounted on the top of the treatment couch for reverse motion, opposite from the direction of the targets (diaphragm and hemostatic clip), in order to offset organ displacement generated by respiratory motion. Traditionally, in the treatment of cancer patients, doctors must increase the field size for radiation therapy of tumors because organs move with respiratory motion, which causes radiation-induced inflammation on the normal tissues (organ at risk (OAR)) while killing cancer cells, and thereby reducing the patient's quality of life. This study uses a strain gauge as a respiratory signal capture device to obtain abdomen respiratory signals, a proposed respiratory simulation system (RSS) and respiratory compensating system to experiment how to offset the organ displacement caused by respiratory movement and compensation effect. This study verifies the effect of the respiratory compensating system in offsetting the target displacement using two methods. The first method uses linac (medical linear accelerator) to irradiate a 300 cGy dose on the EBT film (GAFCHROMIC EBT film). The second method uses a strain gauge to capture the patients' respiratory signals, while using fluoroscopy to observe in vivo targets, such as a diaphragm, to enable the respiratory compensating system to offset the displacements of targets in superior-inferior (SI) direction. Testing results show that the RSS position error is approximately 0.45 ~ 1.42 mm, while the respiratory compensating system position error is approximately 0.48 ~ 1.42 mm. From the EBT film profiles based on different input to the RSS, the results suggest that when the input respiratory signals of RSS are sine wave signals, the average dose (%) in the target area is improved by 1.4% ~ 24.4%, and improved in the 95% isodose area by 15.3% ~ 76.9% after compensation. If the respiratory signals input into the RSS respiratory signals are actual human respiratory signals, the average dose (%) in the target area is improved by 31.8% ~ 67.7%, and improved in the 95% isodose area by 15.3% ~ 86.4% (the above rates of improvements will increase with increasing respiratory motion displacement) after compensation. The experimental results from the second method suggested that about 67.3% ~ 82.5% displacement can be offset. In addition, gamma passing rate after compensation can be improved to 100% only when the displacement of the respiratory motion is within 10 ~ 30 mm. This study proves that the proposed system can contribute to the compensation of organ displacement caused by respiratory motion, enabling physicians to use lower doses and smaller field sizes in the treatment of tumors of cancer patients.

Evaluation of EGFR-targeted radioimmuno-gold-nanoparticles as a theranostic agent in a tumor animal model.

This study evaluated the tumor targeting and therapeutic efficacy of a novel theranostic agent (131)I-labeled immuno-gold-nanoparticle ((131)I-C225-AuNPs-PEG) for high epidermal growth factor receptor (EGFR)-expressed A549 human lung cancer. Confocal microscopy demonstrated the specific uptake of C225-AuNPs-PEG in A549 cells. (131)I-C225-AuNPs-PEG induced a significant reduction in cell viability, which was not observed when incubated with AuNPs-PEG and C225-AuNPs-PEG. MicroSPECT/CT imaging of tumor-bearing mice after intravenous injection of (123)I-C225-AuNPs-PEG revealed significant radioactivity retention in tumor suggested that (131)I-labeled C225-conjugated radioimmuno-gold-nanoparticles may provide a new approach of targeted imaging and therapy towards high EGFR-expressed cancers.

A compensating system of respiratory motion for tumor tracking: design and verification.

Using the reverse motion of the treatment couch, this study offset the organ displacement generated by respiratory motion to solve the current clinical problem of increasing field sizes and safety margin expansions. This study used the self-designed simulated respiratory system (SRS) coupled with radiochromic EBT film to verify the self-developed respiratory compensation system. Pressure signals were generated from SRS to simulate abdomen movements during respiratory motion. The respiratory compensation system takes the phase of the pressure signals as the respiratory motion phase and adjusts the pressure signal gain to make the compensation signal amplitude close to the displacement of the target region. A linear accelerator is used to irradiate a 300 cGy dose on the EBT film. The experimental results suggested that the average dose percentage in the target region for the sine-wave amplitudes of 5, 10 and 15 mm with compensation improved by 6.9 ∼ 20.3% over the cases without compensation. The 80% isodose area with compensation improved by 22.8 ∼ 77.2% over the cases without compensation. The average dose percentage in the target region with compensation for respiratory motion distances of 5, 10 and 15 mm improved by 10.3 ∼ 18.7%. The 80% isodose area improved by 22.4 ∼ 55.1% after compensation. The average dose percentage of the compensated target region indicates that the proposed respiratory compensation system could improve the issue of the inability to constantly irradiate the target region caused by respiratory motion.

Control release of bactericidal ion by an electronically driven system.

There is a dramatic proliferation of research related to electronically generated metallic bactericidal ions. Unfortunately, there are no literature reviews or discussions concerning metallic-nanoparticle suspension as a drug reservoir for iontophoretic applications. Heavy metals, especially silver, are frequently used to treat infection before the development of systemic antimicrobial agents. For medical applications, the conversion of colloidal silver into its ionic form is required; however, it does not directly use silver salts to provide the silver ions, due to the counter-ion (e.g., NO3-, SO4-) content of silver salts, which may cause severe problems to the body as the silver ion is consumed. The goal of this research is to develop an electronic dissociation system (EDS), which can provide a relatively safe bactericidal ion (Ag+) solution from the silver nanoparticles that has a controllable electric field. In this study, an ionic selective electrode (ISE) was used to observe and identify the details of the system activity throughout the course of the experiment. Both qualitative and quantitative data analyses were performed. The experimental data indicated that EDS can control the parameters of ion-releasing profiles, including the area under curve (AUC, dosage), rate of profile rise and fall, total dissociation time, peak time, and peak level concentration by a constant voltage (CV) mode or constant current (CC) mode. However, the CC mode was proved to be more controllable (an increase of 200 microA, equal to an increase of 1 ppm/hour), as the premeditated driving force is more precise, and relies on the current not voltage. This technology will be used to develop a chemical residue-free administration of control-released medical devices for iontophoretic applications.