Predicting patient-specific organ doses from thoracic CT examinations using support vector regression algorithm.

PURPOSE: This study aims to propose and develop a fast, accurate, and robust prediction method of patient-specific organ doses from CT examinations using minimized computational resources. MATERIALS AND METHODS: We randomly selected the image data of 723 patients who underwent thoracic CT examinations. We performed auto-segmentation based on the selected data to generate the regions of interest (ROIs) of thoracic organs using the DeepViewer software. For each patient, radiomics features of the thoracic ROIs were extracted via the Pyradiomics package. The support vector regression (SVR) model was trained based on the radiomics features and reference organ dose obtained by Monte Carlo (MC) simulation. The root mean squared error (RMSE), mean absolute percentage error (MAPE), and coefficient of determination (R-squared) were evaluated. The robustness was verified by randomly assigning patients to the train and test sets of data and comparing regression metrics of different patient assignments. RESULTS: For the right lung, left lung, lungs, esophagus, heart, and trachea, results showed that the trained SVR model achieved the RMSEs of 2 mGy to 2.8 mGy on the test sets, 1.5 mGy to 2.5 mGy on the train sets. The calculated MAPE ranged from 0.1 to 0.18 on the test sets, and 0.08 to 0.15 on the train sets. The calculated R-squared was 0.75 to 0.89 on test sets. CONCLUSIONS: By combined utilization of the SVR algorithm and thoracic radiomics features, patient-specific thoracic organ doses could be predicted accurately, fast, and robustly in one second even using one single CPU core.

Radiation levels outside a patient undergoing177Lu-PSMA radioligand therapy.

Understanding the spatial distribution of radiation levels outside of a patient undergoing177Lu radioligand therapy is not only helpful for conducting correct tests for patient release, but also useful for estimation of its potential exposure to healthcare workers, caregivers, family members, and the general public. In this study, by mimicking the177Lu-labeled prostate-specific membrane antigen radioligand therapy for prostate cancers in an adult male, the spatial distribution of radiation levels outside of the phantom was simulated based on the Monte Carlo software of Particle and Heavy Ion Transport System, and verified by a series of measurements. Moreover, the normalized dose rates were further formulized on the three transverse planes representing the heights of pelvis, abdomen and chest. The results showed that the distributions of radiation levels were quite complex. Multi-directional and multi-height measurements are needed to ensure the external dose rate to meet the release criteria. In general, the radiation level was higher at the horizontal plane where the source was located, and the levels in front and behind of the body were higher than those of the left and right sides at the same height. The ratio of simulated dose rates to measured ones ranged from 0.82 to 1.19 within 1 m away from the body surface in all directions. Based on the established functions, the relative root mean square deviation between the calculated and simulated values were 0.21, 0.25 and 0.23 within a radius of 1 m on the pelvis, abdomen and chest transverse planes, respectively. It is expected that the results of this study would be helpful for guiding the test of extracorporeal radiation to determine the patient's release, and of benefit to estimate the radiation exposure to others.

Fast prediction of patient-specific organ doses in brain CT scans using support vector regression algorithm.

Objectives. This study aims to develop a method for predicting patient-specific head organ doses by training a support vector regression (SVR) model based on radiomics features and graphics processing unit (GPU)-calculated reference doses.Methods. In this study, 237 patients who underwent brain CT scans were selected, and their CT data were transferred to an autosegmentation software to segment head regions of interest (ROIs). Subsequently, radiomics features were extracted from the CT data and ROIs, and the benchmark organ doses were computed using fast GPU-accelerated Monte Carlo (MC) simulations. The SVR organ dose prediction model was then trained using the radiomics features and benchmark doses. For the predicted organ doses, the relative root mean squared error (RRMSE), mean absolute percentage error (MAPE), and coefficient of determination (R2) were evaluated. The robustness of organ dose prediction was verified by changing the patient samples on the training and test sets randomly.Results. For all head organs, the maximal difference between the reference and predicted dose was less than 1 mGy. For the brain, the organ dose was predicted with an absolute error of 1.3%, and theR2reached up to 0.88. For the eyes and lens, the organ doses predicted by SVR achieved an RRMSE of less than 13%, the MAPE ranged from 4.5% to 5.5%, and theR2values were more than 0.7.Conclusions. Patient-specific head organ doses from CT examinations can be predicted within one second with high accuracy, speed, and robustness by training an SVR using radiomics features.

Circulating Regulatory T Cells: A Novel Marker Associated with Liver Metastasis and the Treatment Response of Transarterial Embolization in Gastroenteropancreatic Neuroendocrine Tumors.

INTRODUCTION: To investigate the role of circulating regulatory T cells (Tregs) as a novel marker associated with liver metastases and treatment response to transarterial embolization (TAE) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: Circulating Tregs, defined as the CD4+CD25+CD127low/- population, were examined by flow cytometry in peripheral blood mononuclear cells (PBMCs) from patients with GEP-NETs. Clinicopathological parameters, radiologic response, and hepatic progression-free survival (hPFS) data were collected. RESULTS: The association between circulating Tregs and clinicopathological parameters was analyzed in 139 GEP-NET patients. Higher Treg levels were significantly associated with more progressive clinical features, including a higher WHO grade, more advanced TNM stage, and the presence of liver metastases. A Treg level ≥ 8.015% distinguished between patients with and without liver metastases. Among a cohort of 51 GEP-NET patients who were subjected to TAE for reducing liver metastasis burden, patients with higher Treg levels depicted unfavorable responses and significantly reduced hPFS after TAE treatment. We also revealed that patients with Treghigh (≥8.975%) displayed significantly shorter median hPFS than patients with Treglow (< 8.975%). Additionally, after adjusting for other confounding clinical parameters, the association between Tregs and treatment response as well as hPFS remained significant, suggesting that Tregs may have a strong and independent prognostic impact in GEP-NETs. CONCLUSIONS: Our data suggest that circulating Tregs are a novel immunological marker associated with liver metastases and treatment response to TAE in patients with GEP-NETs.

Guided block matching and 4-D transform domain filter projection denoising method for dynamic PET image reconstruction.

PURPOSE: Dynamic PET is an essential tool in oncology due to its ability to visualize and quantify radiotracer uptake, which has the potential to improve imaging quality. However, image noise caused by a low photon count in dynamic PET is more significant than in static PET. This study aims to develop a novel denoising method, namely the Guided Block Matching and 4-D Transform Domain Filter (GBM4D) projection, to enhance dynamic PET image reconstruction. METHODS: The sinogram was first transformed using the Anscombe method, then denoised using a combination of hard thresholding and Wiener filtering. Each denoising step involved guided block matching and grouping, collaborative filtering, and weighted averaging. The guided block matching was performed on accumulated PET sinograms to prevent mismatching due to low photon counts. The performance of the proposed denoising method (GBM4D) was compared to other methods such as wavelet, total variation, non-local means, and BM3D using computer simulations on the Shepp-Logan and digital brain phantoms. The denoising methods were also applied to real patient data for evaluation. RESULTS: In all phantom studies, GBM4D outperformed other denoising methods in all time frames based on the structural similarity and peak signal-to-noise ratio. Moreover, GBM4D yielded the lowest root mean square error in the time-activity curve of all tissues and produced the highest image quality when applied to real patient data. CONCLUSION: GBM4D demonstrates excellent denoising and edge-preserving capabilities, as validated through qualitative and quantitative assessments of both temporal and spatial denoising performance.

Identification of BRD7 by whole-exome sequencing as a predictor for intermediate-stage hepatocellular carcinoma in patients undergoing TACE.

OBJECTIVE: In the present study, we aimed to identify potential predictors of intermediate-stage hepatocellular carcinoma (HCC) using whole-exome sequencing (WES) in patients undergoing transarterial chemoembolization (TACE). MATERIALS AND METHODS: In A total of 51 patients, newly diagnosed with intermediate-stage HCC between January 2013 and December 2020, were enrolled. Prior to treatment, histological samples were collected for western blotting and immunohistochemistry. The predictive roles of clinical indicators and genes in patient prognosis were analyzed using univariate and multivariate analyses. Finally, the correlation between imaging features and gene signatures was examined. RESULTS: Using WES, we identified that bromodomain-containing protein 7 (BRD7) was significantly mutated in patients with different TACE responses. No significant difference in BRD7 expression was observed between patients with and without BRD7 mutations. HCC tumors exhibited higher BRD7 than normal liver tissues. Multivariate analysis revealed that alpha-fetoprotein (AFP), BRD7 expression, and BRD7 mutations were independent risk factors for progression-free survival (PFS). In addition, Child-Pugh class, BRD7 expression, and BRD7 mutations were independent risk factors for overall survival (OS). Patients with wild-type BRD7 and high BRD7 expression had worse PFS and OS, whereas those with mutated BRD7 and low BRD7 expression exhibited the best PFS and OS. The Kruskal-Wallis test revealed that wash-in enhancement on computed tomography might be an independent risk factor for high BRD7 expression. CONCLUSION: BRD7 expression may be an independent risk factor for prognosis in patients with HCC undergoing TACE. Imaging features such as wash-in enhancement are closely related to BRD7 expression.

Patient-specific fetal radiation dosimetry for pregnant patients undergoing abdominal and pelvic CT imaging.

BACKGROUND: Accurate estimation of fetal radiation dose is crucial for risk-benefit analysis of radiological imaging, while the radiation dosimetry studies based on individual pregnant patient are highly desired. PURPOSE: To use Monte Carlo calculations for estimation of fetal radiation dose from abdominal and pelvic computed tomography (CT) examinations for a population of patients with a range of variations in patients' anatomy, abdominal circumference, gestational age (GA), fetal depth (FD), and fetal development. METHODS: Forty-four patient-specific pregnant female models were constructed based on CT imaging data of pregnant patients, with gestational ages ranging from 8 to 35 weeks. The simulation of abdominal and pelvic helical CT examinations was performed on three validated commercial scanner systems to calculate organ-level fetal radiation dose. RESULTS: The absorbed radiation dose to the fetus ranged between 0.97 and 2.24 mGy, with an average of 1.63 ± 0.33 mGy. The CTDIvol -normalized fetal dose ranged between 0.56 and 1.30, with an average of 0.94 ± 0.25. The normalized fetal organ dose showed significant correlations with gestational age, maternal abdominal circumference (MAC), and fetal depth. The use of ATCM technique increased the fetal radiation dose in some patients. CONCLUSION: A technique enabling the calculation of organ-level radiation dose to the fetus was developed from models of actual anatomy representing a range of gestational age, maternal size, and fetal position. The developed maternal and fetal models provide a basis for reliable and accurate radiation dose estimation to fetal organs.

Automatic organ completion with image stitching for personalized radiation dosimetry in CT examinations.

PURPOSE: Computed tomography (CT) image-based patient-specific voxel-based dosimetry has difficulties complementing missing tissues for organs located partially inside or completely outside the image volume. Previous studies constructed patient-specific whole-body models by rescaling reference phantoms or extending regional CT images with manually adjusted phantoms. This study proposes a methodology for automatic organ completion of regional CT images for CT dosimetry using a stitching approach. METHODS: Virtual clinical trials were performed by truncating whole-body CT images to generate virtual clinical chest and abdominopelvic CT images. Corresponding anchor images for each patient were selected according to sex and similarity of the axial length and water equivalent diameter of the virtual regional CT images. Automatic image stitching was performed by transformation initialization and iteration, while the stitched CT images and organ atlas were used in GPU-based Geant4 Monte Carlo simulations to generate a radiation dose map and absorbed organ dose. To evaluate the performance of the stitching model in radiation dosimetry, organ mass differences and Jaccard's coefficient of stitched and rescaled anchor images were calculated, and the radiation doses were compared among the corresponding values from the VirtualDose®, original whole-body CT, stitching model, regional CT, registration-based rescaling method, and WED-based rescaling method. RESULTS: The anatomical accuracy of stitched images was significantly improved. For organs partially inside the image volume, organ dose estimation from the stitching model could be more accurate than that reported in previous studies. The absolute differences in effective dose from the stitched images were 6.55% and 4.81% for chest and abdominopelvic CT scans, respectively. CONCLUSION: The proposed automatic stitching model partially complements organs inside or outside the CT scan range and provides more accurate anatomical representations for radiation dosimetry than traditional phantom rescaling methods.

Identification and Validation of Novel Immunogenic Cell Death- and DNA Damage Response-Related Molecular Patterns Correlated with Immune Status and Prognosis in Hepatocellular Carcinoma.

Immunogenic cell death (ICD) and DNA damage response (DDR) are involved in cancer progression and prognosis. Currently, chemotherapy is the first-line treatment for intermediate or advanced hepatocellular carcinoma (HCC), which is mostly based on platinum and anthracyclines that induce DNA damage and ICD. With the treatment of HCC with immune checkpoint inhibitors (ICIs), it is important to understand the molecular characteristics and prognostic values of ICD and DDR-related genes (IDRGs). We aimed to explore the characteristics of ICD and DDR-related molecular patterns, immune status, and the association of immunotherapy and prognosis with IDRGs in HCC. We identified IDRGs in HCC and evaluated their differential expression, biological behaviors, molecular characteristics, immune cell infiltration, and prognostic value. Prognostic IDRGs and subtypes were identified and validated. FFAR3, DDX1, POLR3G, FANCL, ADA, PI3KR1, DHX58, TPT1, MGMT, SLAMF6, and EIF2AK4 were determined as risk factors for HCC, and the biological experiments indicated that high FANCL expression is harmful to the treatment and prognosis. HCC was classified into high- and low-risk groups based on the median values of the risk factors to construct a predictive nomogram. These findings provide novel insights into the treatment and prognosis of HCC and provide a new research direction for HCC.

Prolonged progression-free survival achieved by octreotide LAR plus transarterial embolization in low-to-intermediate grade neuroendocrine tumor liver metastases with high hepatic tumor burden.

OBJECTIVE: To evaluate the efficacy and outcome of transarterial embolization (TAE) plus octreotide long-acting repeatable (LAR) on patients with low-to-intermediate neuroendocrine tumor liver metastases (NETLM). METHODS: One hundred and sixteen patients with G1/G2 NETLM treated with TAE plus octreotide LAR at the First Affiliated Hospital, Sun Yat-sen University between January 12, 2016 and September 24, 2020 were reviewed. Radiological response was evaluated according to response evaluation criterion in solid tumor version 1.1. Overall progression-free survival (PFS) was assessed. Intrahepatic and extrahepatic PFS were evaluated in the whole cohort and in patients with the extrahepatic disease (EHD), respectively. Factors affecting treatment response and overall PFS were analyzed using the logistic regression model and Cox proportional hazard model. Adverse events were recorded and evaluated according to Common Terminology Criteria for Adverse Events 5.0. RESULTS: The median overall PFS of the whole cohort was 13.6 months. For the patients with EHD, the median intrahepatic PFS and extrahepatic PFS were 13.6 and 26.1 months, respectively. The median overall PFS of patients with hepatic tumor burden (HTB) <10%, 10%-25%, 25%-50%, and >50% were 25.2, 13.6, 11.2, and 12.3 months, respectively. Ki67 >10%, HTB >50%, and bone metastasis were independently associated with overall PFS. The objective response rate was 78.4%. In patients with HTB 25%-50% and >50%, responders (complete response or partial response) had significant prolonged PFS compared with nonresponders (stable disease or progression disease). Ki67 >10%, bone metastasis, and clear tumor margin were independently associated with response to TAE. The most frequent adverse events that occurred after TAE were postembolization syndrome, and no treatment-associated death occurred during the perioperative period. CONCLUSION: Transarterial embolization plus octreotide LAR can significantly prolong the PFS of neuroendocrine tumor liver metastases, especially with high HTB over 50%. Selected patients with HTB >25% (ki67 ≤10%, absence of bone metastasis, clear tumor margin) could derive prognostic advantage from the combined treatment.

Internal dosimetry in F-18 FDG PET examinations based on long-time-measured organ activities using total-body PET/CT: does it make any difference from a short-time measurement?

PURPOSE: A 2-m axial field-of-view, total-body PET/CT scanner (uEXPLORER) has been recently developed to provide total-body coverage and ultra-high sensitivity, which together, enables opportunities for in vivo time-activity curve (TAC) measurement of all investigated organs simultaneously with high temporal resolution. This study aims at quantifying the cumulated activity and patient dose of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18 FDG ) imaging by using delayed time-activity curves (TACs), measured out to 8-h post-injection, for different organs so that the comparison between quantifying approaches using short-time method (up to 75 min post-injection) or long-time method (up to 8 h post-injection) could be performed. METHODS: Organ TACs of 10 healthy volunteers were collected using total-body PET/CT in 4 periods after the intravenous injection of F-18 FDG. The 8-h post-injection TACs of 6 source organs were fitted using a spline method (based on Origin (version 8.1)). To compare with cumulated activity estimated from spline-fitted curves, the cumulated activity estimated from multi-exponential curve was also calculated. Exponential curve was fitted with shorter series of data consistent with clinical procedure and previous dosimetry works. An 8-h dynamic bladder wall dose model considering 2 voiding were employed to illustrate the differences in bladder wall dose caused by the different measurement durations. Organ absorbed doses were further estimated using Medical Internal Radiation Dose (MIRD) method and voxel phantoms. RESULTS: A short-time measurement could lead to significant bias in estimated cumulated activity for liver compared with long-time-measured spline fitted method, and the differences of cumulated activity were 18.38% on average. For the myocardium, the estimated cumulated activity difference was not statistically significant due to large variation in metabolism among individuals. The average residence time differences of brain, heart, kidney, liver, and lungs were 8.38%, 15.13%, 25.02%, 23.94%, and 16.50% between short-time and long-time methods. Regarding effective dose, the maximum differences of residence time between long-time-measured spline fitted curve and short-time-measured multi-exponential fitted curve was 9.93%. When using spline method, the bladder revealed the most difference in the effective dose among all the investigated organs with a bias up to 21.18%. The bladder wall dose calculated using a long-time dynamic model was 13.79% larger than the two-voiding dynamic model, and at least 50.17% lower than previous studies based on fixed bladder content volume. CONCLUSIONS: Long-time measurement of multi-organ TACs with high temporal resolution enabled by a total-body PET/CT demonstrated that the clinical procedure with 20 min PET scan at 1 h after injection could be used for retrospective dosimetry analysis in most organs. As the bladder content contributed the most to the effective dose, a long-time dynamic model was recommended for the bladder wall dose estimation.

A new phantom developed to test the ATCM performance of chest CT scanners.

In this study, a new ATCM phantom was developed to test the performance of the automatic tube current modulation (ATCM) of computed tomography (CT) scanners.. Based on the Chinese reference man and Monte Carlo simulations of x-ray attenuation, a more realistic ATCM phantom made of polymethyl methacrylate was developed. The phantom has a length of 20 cm, and it can be used to measure the dose profile along the central axis using 19 real-time MOSFET detectors. The image noise can be calculated slice by slice in the phantom's center. Test experiments showed that the phantom could initiate tube current modulation under different modulation levels of CT scans, and the actual effects of ATCM could be evaluated with the aid of the dose profile measurements. Using the measured dose profiles and image noise, the preferred dose can easily be identified from a choice of different modulation levels. The new phantom developed in this study can be used to test the ATCM performance of CT scanners, and is useful for further studies of the optimization of CT scan protocols with ATCM.

Kinase Partner Protein Plays a Key Role in Controlling the Speed and Shape of Pollen Tube Growth in Tomato.

The rapid and responsive growth of a pollen tube requires delicate coordination of membrane receptor signaling, Rho-of-Plants (ROP) GTPase activity switching, and actin cytoskeleton assembly. The tomato (Solanum lycopersicum) kinase partner protein (KPP), is a ROP guanine nucleotide exchange factor (GEF) that activates ROP GTPases and interacts with the tomato pollen receptor kinases LePRK1 and LePRK2. It remains unclear how KPP relays signals from plasma membrane-localized LePRKs to ROP switches and other cellular machineries to modulate pollen tube growth. Here, we biochemically verified KPP's activity on ROP4 and showed that KPP RNA interference transgenic pollen tubes grew slower while KPP-overexpressing pollen tubes grew faster, suggesting that KPP functions as a rheostat for speed control in LePRK2-mediated pollen tube growth. The N terminus of KPP is required for self-inhibition of its ROPGEF activity, and expression of truncated KPP lacking the N terminus caused pollen tube tip enlargement. The C-terminus of KPP is required for its interaction with LePRK1 and LePRK2, and the expression of a truncated KPP lacking the C-terminus triggered pollen tube bifurcation. Furthermore, coexpression assays showed that self-associated KPP recruited actin-nucleating Actin-Related Protein2/3 (ARP2/3) complexes to the tip membrane. Interfering with ARP2/3 activity reduced the pollen tube abnormalities caused by overexpressing KPP fragments. In conclusion, KPP plays a key role in pollen tube speed and shape control by recruiting the branched actin nucleator ARP2/3 complex and an actin bundler to the membrane-localized receptors LePRK1 and LePRK2.

Quantitative Pretreatment CT Parameters as Predictors of Tumor Response of Neuroendocrine Tumor Liver Metastasis to Transcatheter Arterial Bland Embolization.

PURPOSE: To assess whether parameters on preprocedural CT can be utilized to predict the response of NETLM to transcatheter arterial bland embolization (TAE). METHODS: We retrospectively reviewed 135 target lesions from 48 NETLM patients who underwent TAE and with complete preprocedural multiphasic CT. Parameters on preprocedural CT including the longest diameter, mean attenuation value in nonenhanced, arterial, and portal-venous phases were collected from each target lesion. Radiological responses were assessed according to RECIST 1.1. The parameters of responder lesions and nonresponder lesions were compared. Arterial enhancement index (AEI) and portal-venous enhancement index (PEI) were calculated. The predictive function of AEI and PEI on tumor response was analyzed by receiver operating characteristic (ROC) curve. RESULTS: A total of 72.6% target lesions had a partial response. For patients, the objective response rate was 72.9%. Mean attenuation values of responder lesions were significantly higher than nonresponder lesions in both arterial and portal-venous phases (105.36 ± 37.24 vs. 76.01 ± 19.19, p < 0.001; 96.61 ± 24.04 vs. 82.12 ± 21.37, p = 0.002). ROC curve showed that both AEI and PEI were effective in predicting tumor response (area under the curve [AUC] 0.757, p < 0.001; AUC 0.655, p = 0.005). CONCLUSION: AEI and PEI, parameters from evaluation of CT pretreatment attenuation of NETLMs, could predict response to TAE treatment.

Monte Carlo simulation of eye lens dose reduction from CT scan using organ based tube current modulation.

PURPOSE: To investigate lens dose reduction with organ based tube current modulation (TCM) using the Monte Carlo method. METHODS: To calculate lens dose with organ based TCM, 36 pairs of X-ray sources with bowtie filters were placed around the patient head using a projection angle interval of 10° for one rotation of Computed Tomography (CT). Each projection was simulated respectively. Both voxelized and stylized eye models and Chinese reference male phantoms were used in the simulation, and tube voltages 80, 100, 120 and 140 kVp were used. RESULTS: Dose differences between two eye models were less than 20%, but large variations were observed among dose results from different projections of all tube voltages investigated. Dose results from 0° (AP) directions were 60 times greater than those from 180° (PA) directions, which enables organ based TCM reduce lens doses by more than 47%. CONCLUSIONS: Organ based TCM may be used to reduce lens doses. Stylized eye models are more anatomically realistic compared with voxelized eye models and are more reliable for dose evaluation.

Shielding Effect of Lead Glasses on Radiologists' Eye Lens Exposure in Interventional Procedures.

To study the shielding effect of radiologists' eye lens with lead glasses of different equivalent thicknesses and sizes in interventional radiology procedures. Using the human voxel phantom with a more accurate model of the eye and MCNPX software, eye lens doses of the radiologists who wearing different kinds of lead glasses were simulated, different beam projections were taken into consideration during the simulation. Measurements were also performed with the physical model to verify simulation results. Simulation results showed that the eye lens doses were reduced by a factor from 3 to 9 when wearing a 20 cm2-sized lead glasses with the equivalent thickness ranging from 0.1 to 1.0 mm Pb. The increase of dose reduction factor (DRF) was not significant whenever increase the lead equivalent of glasses of which larger than 0.35 mm. Furthermore, the DRF was proportional to the size of glass lens from 6 to 30 cm2 with the same lead equivalent. The simulation results were in well agreements with the measured ones. For more reasonable and effective protection of the eye lens of interventional radiologists, a pair of glasses with a lead equivalent of 0.5 mm Pb and large-sized (at least 27 cm2 per glass) lens are recommended.

VirtualDose: a software for reporting organ doses from CT for adult and pediatric patients.

This paper describes the development and testing of VirtualDose--a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the 'software as a service (SaaS)' delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose's functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT-two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations.

The profound effects of patient arm positioning on organ doses from CT procedures calculated using Monte Carlo simulations and deformable phantoms.

The purpose of this study was to evaluate the organ dose differences caused by the arms-raised and arms-lowered postures for multidetector computed tomography procedures. Organ doses were calculated using computational phantoms and Monte Carlo simulations. The arm position in two previously developed adult male and female human phantoms was adjusted to represent 'raised' and 'lowered' postures using advanced BREP-based mesh surface geometries. Organ doses from routine computed tomography (CT) scan protocols, including the chest, abdomen-pelvis, and chest-abdomen-pelvis scans, were simulated at various tube voltages and reported in the unit of mGy per 100 mAs. The CT scanner model was based on previously tested work. The differences in organ dose per unit tube current between raised and lowered arm postures were studied. Furthermore, the differences due to the tube current modulation (TCM) for these two different postures and their impact on organ doses were also investigated. For a given scan parameter, a patient having lowered arms received smaller doses to organs located within the chest, abdomen or pelvis when compared with the patient having raised arms. As expected, this is caused by the attenuation of the primary X rays by the arms. However, the skin doses and bone surface doses in the patient having lowered arms were found to be 3.97-32.12% larger than those in a patient having raised arms due to the fact that more skin and spongiosa were covered in the scan range when the arms are lowered. This study also found that dose differences become smaller with the increase in tube voltage for most of organs or tissues except the skin. For example, the liver dose differences decreased from -15.01 to -11.33% whereas the skin dose differences increased from 21.53 to 25.24% with tube voltage increased from 80 to 140 kVp. With TCM applied, the organ doses of all the listed organs in patient having lowered arms are larger due to the additional tube current necessary to overcome the presence of the arms while maintaining sufficient image quality Arm position affects the dose to internal organs from CT scans by as much as 25.3%. The presence of arms in the scan range results in a dose increase for the skin and bone surface, but a dose decrease for organs located in the torso. Considering the use of TCM, which is common in many clinics, the patient having lowered arms may receive 50% higher radiation dose to most of the organs because of the increased tube current. The use of higher tube voltage might narrow such dose differences between patients of these two postures due to the greater penetration of higher-energy X rays. Therefore, when calculating or reporting patient doses from CT scans, it is prudent to select an appropriate phantom that accurately represents the patient posture.

Overexpression of the tomato pollen receptor kinase LePRK1 rewires pollen tube growth to a blebbing mode.

The tubular growth of a pollen tube cell is crucial for the sexual reproduction of flowering plants. LePRK1 is a pollen-specific and plasma membrane-localized receptor-like kinase from tomato (Solanum lycopersicum). LePRK1 interacts with another receptor, LePRK2, and with KINASE PARTNER PROTEIN (KPP), a Rop guanine nucleotide exchange factor. Here, we show that pollen tubes overexpressing LePRK1 or a truncated LePRK1 lacking its extracellular domain (LePRK1ΔECD) have enlarged tips but also extend their leading edges by producing "blebs." Coexpression of LePRK1 and tomato PLIM2a, an actin bundling protein that interacts with KPP in a Ca(2+)-responsive manner, suppressed these LePRK1 overexpression phenotypes, whereas pollen tubes coexpressing KPP, LePRK1, and PLIM2a resumed the blebbing growth mode. We conclude that overexpression of LePRK1 or LePRK1ΔECD rewires pollen tube growth to a blebbing mode, through KPP- and PLIM2a-mediated bundling of actin filaments from tip plasma membranes. Arabidopsis thaliana pollen tubes expressing LePRK1ΔECD also grew by blebbing. Our results exposed a hidden capability of the pollen tube cell: upon overexpression of a single membrane-localized molecule, LePRK1 or LePRK1ΔECD, it can switch to an alternative mechanism for extension of the leading edge that is analogous to the blebbing growth mode reported for Dictyostelium and for Drosophila melanogaster stem cells.

Tomato Pistil Factor STIG1 Promotes in Vivo Pollen Tube Growth by Binding to Phosphatidylinositol 3-Phosphate and the Extracellular Domain of the Pollen Receptor Kinase LePRK2.

The speed of pollen tube growth is a major determinant of reproductive success in flowering plants. Tomato (Solanum lycopersicum) STIGMA-SPECIFIC PROTEIN1 (STIG1), a small Cys-rich protein from the pistil, was previously identified as a binding partner of the pollen receptor kinase LePRK2 and shown to promote pollen tube growth in vitro. However, the in vivo function of STIG1 and the underlying mechanism of its promotive effect were unknown. Here, we show that a 7-kD processed peptide of STIG1 is abundant in the stigmatic exudate and accumulates at the pollen tube surface, where it can bind LePRK2. Antisense LePRK2 pollen was less responsive than wild-type pollen to exogenous STIG1 in an in vitro pollen germination assay. Silencing of STIG1 reduced both the in vivo pollen tube elongation rate and seed production. Using partial deletion and point mutation analyses, two regions underlying the promotive activity of the STIG1 processed peptide were identified: amino acids 80 to 83, which interact with LePRK2; and amino acids 88 to 115, which bind specifically to phosphatidylinositol 3-phosphate [PI(3)P]. Furthermore, exogenous STIG1 elevated the overall redox potential of pollen tubes in both PI(3)P-dependent and LePRK2-dependent manners. Our results demonstrate that STIG1 conveys growth-promoting signals acting through the pollen receptor kinase LePRK2, a process that relies on the external phosphoinositide PI(3)P.