The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis.

Akt kinase plays a central role in cell growth, metabolism, and tumorigenesis. The TRAF6 E3 ligase orchestrates IGF-1-mediated Akt ubiquitination and activation. Here, we show that Akt ubiquitination is also induced by activation of ErbB receptors; unexpectedly, and in contrast to IGF-1 induced activation, the Skp2 SCF complex, not TRAF6, is a critical E3 ligase for ErbB-receptor-mediated Akt ubiquitination and membrane recruitment in response to EGF. Skp2 deficiency impairs Akt activation, Glut1 expression, glucose uptake and glycolysis, and breast cancer progression in various tumor models. Moreover, Skp2 overexpression correlates with Akt activation and breast cancer metastasis and serves as a marker for poor prognosis in Her2-positive patients. Finally, Skp2 silencing sensitizes Her2-overexpressing tumors to Herceptin treatment. Our study suggests that distinct E3 ligases are utilized by diverse growth factors for Akt activation and that targeting glycolysis sensitizes Her2-positive tumors to Herceptin treatment.

A Point Cloud Data-Driven Pallet Pose Estimation Method Using an Active Binocular Vision Sensor.

Pallet pose estimation is one of the key technologies for automated fork pickup of driverless industrial trucks. Due to the complex working environment and the enormous amount of data, the existing pose estimation approaches cannot meet the working requirements of intelligent logistics equipment in terms of high accuracy and real time. A point cloud data-driven pallet pose estimation method using an active binocular vision sensor is proposed, which consists of point cloud preprocessing, Adaptive Gaussian Weight-based Fast Point Feature Histogram extraction and point cloud registration. The proposed method overcomes the shortcomings of traditional pose estimation methods, such as poor robustness, time consumption and low accuracy, and realizes the efficient and accurate estimation of pallet pose for driverless industrial trucks. Compared with traditional Fast Point Feature Histogram and Signature of Histogram of Orientation, the experimental results show that the proposed approach is superior to the above two methods, improving the accuracy by over 35% and reducing the feature extraction time by over 30%, thereby verifying the effectiveness and superiority of the proposed method.

A Low-Delay Dynamic Range Compression and Contrast Enhancement Algorithm Based on an Uncooled Infrared Sensor with Local Optimal Contrast.

Real-time compression of images with a high dynamic range into those with a low dynamic range while preserving the maximum amount of detail is still a critical technology in infrared image processing. We propose a dynamic range compression and enhancement algorithm for infrared images with local optimal contrast (DRCE-LOC). The algorithm has four steps. The first involves blocking the original image to determine the optimal stretching coefficient by using the information of the local block. In the second, the algorithm combines the original image with a low-pass filter to create the background and detailed layers, compressing the background layer with a dynamic range of adaptive gain, and enhancing the detailed layer for the visual characteristics of the human eye. Third, the original image was used as input, the compressed background layer was used as a brightness-guided image, and the local optimal stretching coefficient was used for dynamic range compression. Fourth, an 8-bit image was created (from typical 14-bit input) by merging the enhanced details and the compressed background. Implemented on FPGA, it used 2.2554 Mb of Block RAM, five dividers, and a root calculator with a total image delay of 0.018 s. The study analyzed mainstream algorithms in various scenarios (rich scenes, small targets, and indoor scenes), confirming the proposed algorithm's superiority in real-time processing, resource utilization, preservation of the image's details, and visual effects.

A Novel Pallet Detection Method for Automated Guided Vehicles Based on Point Cloud Data.

Automated guided vehicles are widely used in warehousing environments for automated pallet handling, which is one of the fundamental parts to construct intelligent logistics systems. Pallet detection is a critical technology for automated guided vehicles, which directly affects production efficiency. A novel pallet detection method for automated guided vehicles based on point cloud data is proposed, which consists of five modules including point cloud preprocessing, key point extraction, feature description, surface matching and point cloud registration. The proposed method combines the color with the geometric features of the pallet point cloud and constructs a new Adaptive Color Fast Point Feature Histogram (ACFPFH) feature descriptor by selecting the optimal neighborhood adaptively. In addition, a new surface matching method called the Bidirectional Nearest Neighbor Distance Ratio-Approximate Congruent Triangle Neighborhood (BNNDR-ACTN) is proposed. The proposed method overcomes the problems of current methods such as low efficiency, poor robustness, random parameter selection, and being time-consuming. To verify the performance, the proposed method is compared with the traditional and modified Iterative Closest Point (ICP) methods in two real-world cases. The results show that the Root Mean Square Error (RMSE) is reduced to 0.009 and the running time is reduced to 0.989 s, which demonstrates that the proposed method has faster registration speed while maintaining higher registration accuracy.

A Novel Analytical Modeling Approach for Quality Propagation of Transient Analysis of Serial Production Systems.

Production system modeling (PSM) for quality propagation involves mapping the principles between components and systems. While most existing studies focus on the steady-state analysis, the transient quality analysis remains largely unexplored. It is of significance to fully understand quality propagation, especially during transients, to shorten product changeover time, decrease quality loss, and improve quality. In this paper, a novel analytical PSM approach is established based on the Markov model, to explore product quality propagation for transient analysis of serial multi-stage production systems. The cascade property for quality propagation among correlated sequential stages was investigated, taking into account both the status of the current stage and the quality of the outputs from upstream stages. Closed-form formulae to evaluate transient quality performances of multi-stage systems were formulated, including the dynamics of system quality, settling time, and quality loss. An iterative procedure utilizing the aggregation technique is presented to approximate transient quality performance with computational efficiency and high accuracy. Moreover, system theoretic properties of quality measures were analyzed and the quality bottleneck identification method was investigated. In the case study, the modeling error was 0.36% and the calculation could clearly track system dynamics; quality bottleneck was identified to decrease the quality loss and facilitate continuous improvement. The experimental results illustrate the applicability of the proposed PSM approach.

Dual-Polarity SiPM Readout Electronics Based on 1-bit Sigma-Delta Modulatiom Circuit for PET Detector Applications.

We investigated a simple and effective method to extend 1-bit sigma-delta modulation (SDM) circuit based charge-to-digital converter (QDC) to read dual-polarity silicon photomultiplier (SiPM) output signals. With the same QDC circuit but different voltage biases to the circuit components, the new circuit can read and process both positive and negative polarity signals. We conducted experimental studies to validate its ability to read and process dual-polarity signals and evaluated its performance for Positron Emission Tomography (PET) detector applications. The results, based on energy, coincidence timing and crystal identification measurements, show that the circuit provides equal electronics capability for readout of both polarity signals and good performance for SiPM array-based PET imaging detector applications. Overall, the dual-polarity QDC readout electronics can be easily implemented to extend the range of signal polarity and to provide effective and flexible detector front-end electronics for reading single- or dual-polarity SiPM output signals.

Investigation of intra-fractionated range guided adaptive proton therapy (RGAPT): II. Range-shift compensated on-line treatment adaptation and verification.

We previously proposed range-guided adaptive proton therapy (RGAPT) that uses mid-range treatment beams as probing beams and intra-fractionated range measurements for online adaptation. In this work, we demonstrated experimental verification and reported the dosimetric accuracy for RGAPT. A STEEV phantom was used for the experiments, and a 3 × 3 × 3 cm3cube inside the phantom was assigned to be the treatment target. We simulated three online range shift scenarios: reference, overshoot, and undershoot, by placing upstream Lucite sheets, 4, 0, and 8 that corresponded to changes of 0, 6.8, and -6.8 mm, respectively, in water-equivalent path length. The reference treatment plan was to deliver single-field uniform target doses in pencil beam scanning mode and generated on the Eclipse treatment planning system. Different numbers of mid-range layers, including single, three, and five layers, were selected as probing beams to evaluate beam range (BR) measurement accuracy in positron emission tomography (PET). Online plans were modified to adapt to BR shifts and compensate for probing beam doses. In contrast, non-adaptive plans were also delivered and compared to adaptive plans by film measurements. The mid-range probing beams of three (5.55MU) and five layers (8.71MU) yielded accurate range shift measurements in 60 s of PET acquisition with uncertainty of 0.5 mm while the single-layer probing (1.65MU) was not sufficient for measurements. The adaptive plans achieved an average gamma (2%/2 mm) passing rate of 95%. In contrast, the non-adaptive plans only had an average passing rate of 69%. RGAPT planning and delivery are feasible and verified by the experiments. The probing beam delivery, range measurements, and adaptive planning and delivery added a small increase in treatment delivery workflow time but resulted in substantial dose improvement. The three-layer mid-range probing was most suitable considering the balance of high range measurement accuracy and the low number of probing beam layers.

Yield compensation among plant regions improves soybean adaptation to short-term high-temperature stress during the reproductive period.

Extreme heat events prolong the reproductive period and threaten soybean yield, whereas the specific stage at which individual fruits growth is delayed, and yield/yield components at the node, region, and plant levels under short-term heat stress in the reproductive stage are elusive. In this study, heat treatments (40/30 °C) were applied at 0-6 days (HTF0-6), 6-12 days (HTF6-12), 12-18 days (HTF12-18), and 0-12 days (HTF0-12) after the plant's first flower opened, and a control treatment (32/22 °C) was performed. The influences of heat stress on fruit development and yield/yield components at the node, region, and plant levels were investigated. As a result, the growth of individual fruits at nodes was delayed by HTF0-6 and HTF0-12, which was primarily caused by the prolongation of flowering to pods with a length of 2 cm. Interestingly, there were no significant differences in yield between the control treatment and the various high-temperature stress treatments at the plant level. Further analysis of the regional yield of soybean showed that the yield in the bottom and top regions of plants played significant roles in compensating for yield loss in the middle region after HTF0-12. Moreover, the delayed growth of individual fruits in the middle region was negatively correlated with yield. Our results indicate that the prolongation of fruit development induced by HTF0-6 and HTF0-12 may adversely affect soybean yield. However, the spatial compensation of plants could help maintain soybean yield under various short-term high temperature stress treatments during the reproductive period, which should be considered when breeding for and selecting heat-tolerant varieties.

Investigation of intra-fractionated range guided adaptive proton therapy: I. On-line PET imaging and range measurement.

Objective.Develop a prototype on-line positron emission tomography (PET) scanner and evaluate its capability of on-line imaging and intra-fractionated proton-induced radioactivity range measurement.Approach.Each detector consists of 32 × 32 array of 2 × 2 × 30 mm3Lutetium-Yttrium Oxyorthosilicate scintillators with single-scintillator-end readout through a 20 × 20 array of 3 × 3 mm2Silicon Photomultipliers. The PET can be configurated with a full-ring of 20 detectors for conventional PET imaging or a partial-ring of 18 detectors for on-line imaging and range measurement. All detector-level readout and processing electronics are attached to the backside of the system gantry and their output signals are transferred to a field-programable-gate-array based system electronics and data acquisition that can be placed 2 m away from the gantry. The PET imaging performance and radioactivity range measurement capability were evaluated by both the offline study that placed a radioactive source with known intensity and distribution within a phantom and the online study that irradiated a phantom with proton beams under different radiation and imaging conditions.Main results.The PET has 32 cm diameter and 6.5 cm axial length field-of-view (FOV), ∼2.3-5.0 mm spatial resolution within FOV, 3% sensitivity at the FOV center, 18%-30% energy resolution, and ∼9 ns coincidence time resolution. The offline study shows the PET can determine the shift of distal falloff edge position of a known radioactivity distribution with the accuracy of 0.3 ± 0.3 mm even without attenuation and scatter corrections, and online study shows the PET can measure the shift of proton-induced positron radioactive range with the accuracy of 0.6 ± 0.3 mm from the data acquired with a short-acquisition (60 s) and low-dose (5 MU) proton radiation to a human head phantom.Significance.This study demonstrated the capability of intra-fractionated PET imaging and radioactivity range measurement and will enable the investigation on the feasibility of intra-fractionated, range-shift compensated adaptive proton therapy.

Integrated Small Animal PET/CT/RT with Onboard PET/CT Image Guidance for Preclinical Radiation Oncology Research.

We have integrated a compact and lightweight PET with an existing CT image-guided small animal irradiator to enable practical onboard PET/CT image-guided preclinical radiation therapy (RT) research. The PET with a stationary and full-ring detectors has ~1.1 mm uniform spatial resolution over its imaging field-of-view of 8.0 cm diameter and 3.5 cm axial length and was mechanically installed inside the irradiator in a tandem configuration with CT and radiation unit. A common animal bed was used for acquiring sequential dual functional and anatomical images with independent PET and CT control and acquisition systems. The reconstructed dual images were co-registered based on standard multi-modality image calibration and registration processes. Phantom studies were conducted to evaluate the integrated system and dual imaging performance. The measured mean PET/CT image registration error was ~0.3 mm. With one-bed and three-bed acquisitions, initial tumor focused and whole-body [18F]FDG animal images were acquired to test the capability of onboard PET/CT image guidance for preclinical RT research. Overall, the results have shown that integrated PET/CT/RT can provide advantageous and practical onboard PET/CT image to significantly enhance the accuracy of tumor delineation and radiation targeting that should enhance the existing and enable new and potentially breakthrough preclinical RT research and applications.

Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout.

PURPOSE: Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. METHODS: The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 × 1.5 and 2.0 × 2.0 mm(2) cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. RESULTS: All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. CONCLUSIONS: The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems.

Real-time marker-less tumor tracking with TOF PET:in silicofeasibility study.

Purpose.Although positron emission tomography (PET) can provide a functional image of static tumors for RT guidance, it's conventionally very challenging for PET to track a moving tumor in real-time with a multiple frame/s sampling rate. In this study, we developed a novel method to enable PET based three-dimension (3D) real-time marker-less tumor tracking (RMTT) and demonstrated its feasibility with a simulation study.Methods.For each line-of-response (LOR) acquired, its positron-electron annihilation position is calculated based on the time difference between the two gamma interactions detected by the TOF PET detectors. The accumulation of these annihilation positions from data acquired within a single sampling frame forms a coarsely measured 3D distribution of positron-emitter radiotracer uptakes of the lung tumor and other organs and tissues (background). With clinically relevant tumor size and sufficient differential radiotracer uptake concentrations between the tumor and background, the high-uptake tumor can be differentiated from the surrounding low-uptake background in the measured distribution of radiotracer uptakes. With a volume-of-interest (VOI) that closely encloses the tumor, the count-weighted centroid of the annihilation positions within the VOI can be calculated as the tumor position. All these data processes can be conducted online. The feasibility of the new method was investigated with a simulated cardiac-torso digital phantom and stationary dual-panel TOF PET detectors to track a 28 mm diameter lung tumor with a 4:1 tumor-to-background18FDG activity concentration ratio.Results.The initial study shows TOF PET based RMTT can achieve <2.0 mm tumor tracking accuracy with 5 frame s-1sampling rate under the simulated conditions. In comparison, using reconstructed PET images to track a similar size tumor would require >30 s acquisition time to achieve the same tracking accuracy.Conclusion.With the demonstrated feasibility, the new method may enable TOF PET based RMTT for practical RT applications.

Development of an Eight-Channel Time-Based Readout ASIC for PET Applications.

An eight-channel readout ASIC has been developed for reading output signals from solid-state photomultipliers for positron emission tomography applications. This ASIC converts both the signal charge and occurring time to digital timing pulses so that only a time-to-digital converter is required for further signal processing. This provides the advantages of simplified circuit design, reduced power consumption, and suitability for applications that have a large number of readout channels. The ASIC uses a fully current mode preamplifier to achieve high bandwidth (> 100 MHz), high time resolution (better than ~1 ns FWHM), and low power consumption (a few mW/ch). The linear dynamic range of charge measurement is adjustable and can be extended up to 103 pC. The chip has been fabricated with 0.35 µm 2P4M CMOS technology. A test prototype board has been developed and used for ASIC functionality and performance evaluation. Our preliminary studies show that the targets have been successfully achieved.

A compact and lightweight small animal PET with uniform high-resolution for onboard PET/CT image-guided preclinical radiation oncology research.

OBJECTIVE: In contrast to clinical radiation therapy (RT) that ubiquitously uses PET/CT image to accurately guide RT, all current commercial animal irradiators can only provide CT image-guided preclinical RT that severely limits their capability for preclinical and compatibility for translational radiation oncology research. To address this problem, we have developed a compact and lightweight PET with uniform, high spatial resolution that is suited to be installed inside an existing animal irradiator for potential onboard PET/CT image-guided preclinical RT research. APPROACH: The design focused on the balance of achieving sufficient imaging performance for practical preclinical RT guidance with constrained size and weight. The detector head consists of a ring of 12 detector panels in a dodecagon configuration and 12 front-end electronics boards that are closely attached to the detector panels. The overall size and weight of the detector head are 33.0 cm diameter, 11.0 cm axial length and ∼6.5 kg weight that can be installed inside an existing irradiator. Each detector panel has a 30 × 30 array of 1 × 1 × 20 mm3LYSO scintillators with depth-of-interaction (DOI) measurement. The front-end electronics boards process and convert detected signals to digital signals and transfer them to system electronics and data acquisition located outside the irradiator through low-voltage-differential-signaling cables. MAIN RESULTS: The typical energy, DOI and coincidence timing resolutions are around 22.1%, 3.1 mm, and 1.92 ns. The imaging field-of-view (FOV) is 8.0 cm diameter and 3.5 cm axial length. The performance evaluations show a 1.8% sensitivity at the center FOV, uniform ∼1.1 mm resolution within 6 cm diameter FOV, and all rods of 1.0 mm diameter can be clearly resolved from the image of an ultra-micro hot-rods phantom. SIGNIFICANCE: Overall, this compact and lightweight PET has demonstrated its designed capability and performance sufficient for providing onboard functional/biological/molecular image to guide the preclinical RT research.

Field-programable-gate-array-based distributed coincidence processor for high count-rate online positron emission tomography coincidence data acquisition.

For positron emission tomography (PET) online data acquisition, a centralized coincidence processor (CCP) with single-thread data processing has been used to select coincidence events for many PET scanners. A CCP has the advantages of highly integrated circuit, compact connection between detector front-end and system electronics and centralized control of data process and decision making. However, it also has the drawbacks of data process delay, difficulty in handling very high count-rates of single and coincidence events and complicated algorithms to implement. These problems are exacerbated when implementing a CCP on a field-programable-gate-array (FPGA) due to increased routing congestion and reduced data throughput. Industry companies have applied non-centralized or distributed data processing to solve these problems, but those solutions remain either proprietary or lack full disclosure of technical details that make the techniques unclear and difficult to adapt for most research communities. In this study, we investigated the use of a set of distributed coincidence processors (DCP) that can address the CCP problems and be implemented relatively easily. Each coincidence processor exclusively connects one detector pair and selects coincidence events from this detector pair only, which breaks a centralized coincidence process to a collection of independent and parallel processes. DCP can significantly minimize the data process delay, maximize count-rates of coincidence events and simplify implementation by implementing a single coincidence processor with one detector pair and replicating it to the rest. A prototype DCP with 42 coincidence processors was implemented on an off-the-shelf FPGA development board for a small PET with 12 detectors configured with 42 detector pairs. DCP performances were tested with both pulsed signals and gamma ray interactions. There was no coincidence data loss up to the detector's maximum singles count-rate (250 k s-1). Approximately 1.2 k registers were utilized for each coincidence processor and the FPGA resource utilization was proportional to the number of coincidence processors. Coincidence timing spectra showed the results from accurately acquired coincidence events. In conclusion: complementary to CCP, DCP can provide high count-rate capability, with a simplified algorithm for implementation and potentially a practical solution for online acquisition of a PET with a larger number of detector pairs or for ultrahigh-throughput imaging.

Factors affecting the duration of coronary artery lesions in patients with the Kawasaki disease: a retrospective cohort study.

BACKGROUND: Coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD). Approximately 9-20% of the patients with KD develop CAL despite receiving regular treatment (intravenous immunoglobulin [IVIG] and aspirin). Some patients develop coronary aneurysms, leading to coronary artery stenosis or thrombosis, resulting in ischaemic heart disease and significantly affect the patients' lives. The purpose of this study was to investigate the factors associated with the duration of CAL in patients with KD. METHODS: The data of 464 patients with KD and CAL admitted to the Children's Heart Centre, The Second Affiliated Hospital and Yuying Children's Hospital from 2010 to 2018 were retrospectively analysed. Demographic and clinical information and echocardiographic follow-up data were collected. Kaplan-Meier curves were used to estimate the overall CAL duration, and the log-rank test was used to compare statistical differences. Univariate and multivariate Cox regression models were used to identify variables related to the CAL duration. RESULTS: The median CAL duration was 46 days (95% confidence interval: 41-54 days). CALs were observed in 61.5, 41.5, 33.3, 22.3, 10.3, and 7.7% of the patients at 1 month, 2 months, 3 months, 6 months, 1 year, and 2 years after the onset of KD, respectively. Univariate Cox regression model showed that sex (p = 0.016), rash symptoms (p = 0.035), delayed IVIG treatment (p = 0.022), CAL type (p < 0.001), degree of CAL (p < 0.001), white blood cell count before IVIG treatment (p = 0.019), and platelet count after IVIG treatment (p = 0.003) were statistically significant factors associated with the overall CAL duration. Multivariable Cox regression showed that delayed IVIG treatment (p = 0.020), multiple dilatations (p < 0.001), a greater degree of dilatation (p < 0.001), and higher platelet count after IVIG treatment (p = 0.007) were positively related to CAL duration. CONCLUSIONS: CAL duration was affected by delayed IVIG treatment, type of CAL, degree of CAL, and platelet count after IVIG treatment. These factors should be monitored carefully during the follow-up and management of patients with KD and CAL.

Clinical follow-up study of 166 cases of children with hypertension.

BACKGROUND: Childhood hypertension is a challenge for pediatricians to discover and diagnose. We sought to analyze its clinical characteristics and related risk factors in patients at a single center. METHODS: From 2009 to 2019, 166 children with hypertension were retrospectively analyzed, and their clinical manifestations and relevant laboratory data were collected for statistical analysis. RESULTS: A total of 120 males and 46 females were included in this study. Males were more common than females (P=0.012), and 86.7% were from rural areas. Hypertension appeared in all age groups, but most of them were puberty (52.4%). Most primary hypertension cases (57/91) had no obvious clinical symptoms, and BMI (OR 1.085, 95% CI: 1.004-1.173, P=0.038) and a family history of hypertension (OR 5.605, 95% CI: 2.229-14.092, P<0.001) were the risk factors. In the 75 secondary hypertension cases, renal hypertension (62.7%) was the main cause and headache and dizziness were the most common symptoms, and the serum urea is a risk factor (OR 1.524, 95% CI: 1.037-2.239, P=0.032). CONCLUSIONS: BMI and a family history of hypertension were associated with primary hypertension. The serum urea was related to secondary hypertension. Emphasis on family history, strengthening family health management and education and publicity of hypertension, were important for diagnosis and detection of children with hypertension.

Experimental and numerical studies on kV scattered x-ray imaging for real-time image guidance in radiation therapy.

Motion management is a critical component of image guided radiotherapy for lung cancer. We previously proposed a scheme using kV scattered x-ray photons for marker-less real-time image guidance in lung cancer radiotherapy. This study reports our recent progress using the photon counting detection technique to demonstrate potential feasibility of this method and using Monte Carlo (MC) simulations and ray-tracing calculations to characterize the performance. In our scheme, a thin slice of x-ray beam was directed to the target and we measured the outgoing scattered photons using a photon counting detector with a parallel-hole collimator to establish the correspondence between detector pixels and scatter positions. Image corrections of geometry, beam attenuation and scattering angle were performed to convert the raw image to the actual image of Compton attenuation coefficient. We set up a MC simulation system using an in-house developed GPU-based MC package modeling the image formation process. We also performed ray-tracing calculations to investigate the impacts of imaging system geometry on resulting image resolution. The experiment demonstrated feasibility of using a photon counting detector to measure scattered x-ray photons and generate the proposed scattered x-ray image. After correction, x-ray scattering image intensity and Compton scattering attenuation coefficient were linearly related, with R 2 greater than 0.9. Contrast to noise ratios of different objects were improved and the values in experimental results and MC simulation results agreed with each other. Ray-tracing calculations revealed the dependence of image resolution on imaging geometry. The image resolution increases with reduced source to object distance and increased collimator height. The study demonstrated potential feasibility of using scattered x-ray imaging as a real-time image guidance method in radiation therapy.

Carbon-11 and Carbon-12 beam range verifications through prompt gamma and annihilation gamma measurements: Monte Carlo simulations.

Range uncertainty remains a big concern in particle therapy, as it may cause target dose degradation and normal tissue overdosing. Positron emission tomography (PET) and prompt gamma imaging (PGI) are two promising modalities for range verification. However, the relatively long acquisition time of PET and the relatively low yield of PGI pose challenges for real-time range verification. In this paper, we explore using the primary Carbon-11 (C-11) ion beams to enhance the gamma yield compared to the primary C-12 ion beams to improve PET and PGI by using Monte Carlo simulations of water and PMMA phantoms at four incident energies (95, 200, 300, and 430 MeV u-1). Prompt gammas (PGs) and annihilation gammas (AGs) were recorded for post-processing to mimic PGI and PET imaging, respectively. We used both time-of-flight (TOF) and energy selections for PGI, which boosted the ratio of PGs to background neutrons to 2.44, up from 0.87 without the selections. At the lowest incident energy (100 MeVu-1), PG yield from C-11 was 0.82 times of that from C-12, while AG yield from C-11 was 6 ∼ 11 folds higher than from C-12 in PMMA. At higher energies, PG differences between C-11 and C-12 were much smaller, while AG yield from C-11 was 30%∼90% higher than from C-12 using minute-acquisition. With minute-acquisition, the AG depth distribution of C-11 showed a sharp peak coincident with the Bragg peak due to the decay of the primary C-11 ions, but that of C-12 had no such one. The high AG yield and distinct peaks could lead to more precise range verification of C-11 than C-12. These results demonstrate that using C-11 ion beams for potentially combined PGI and PET has great potential to improve online single-spot range verification accuracy and precision.