Automated Dual-Mode Cell Monitoring To Simultaneously Explore Calcium Dynamics and Contraction-Relaxation Kinetics within Drug-Treated Stem Cell-Derived Cardiomyocytes.

This manuscript proposes a new dual-mode cell imaging system for studying the relationships between calcium dynamics and the contractility process of cardiomyocytes derived from human-induced pluripotent stem cells. Practically, this dual-mode cell imaging system provides simultaneously both live cell calcium imaging and quantitative phase imaging based on digital holographic microscopy. Specifically, thanks to the development of a robust automated image analysis, simultaneous measurements of both intracellular calcium, a key player of excitation-contraction coupling, and the quantitative phase image-derived dry mass redistribution, reflecting the effective contractility, namely, the contraction and relaxation processes, were achieved. Practically, the relationships between calcium dynamics and the contraction-relaxation kinetics were investigated in particular through the application of two drugs─namely, isoprenaline and E-4031─known to act precisely on calcium dynamics. Specifically, this new dual-mode cell imaging system enabled us to establish that calcium regulation can be divided into two phases, an early phase influencing the occurrence of the relaxation process followed by a late phase, which although not having a significant influence on the relaxation process affects significantly the beat frequency. In combination with cutting-edge technologies allowing the generation of human stem cell-derived cardiomyocytes, this dual-mode cell monitoring approach therefore represents a very promising technique, particularly in the fields of drug discovery and personalized medicine, to identify compounds likely to act more selectively on specific steps that compose the cardiomyocyte contractility.

Automated phase unwrapping in digital holography with deep learning.

Digital holography can provide quantitative phase images related to the morphology and content of biological samples. After the numerical image reconstruction, the phase values are limited between -π and π; thus, discontinuity may occur due to the modulo 2π operation. We propose a new deep learning model that can automatically reconstruct unwrapped focused-phase images by combining digital holography and a Pix2Pix generative adversarial network (GAN) for image-to-image translation. Compared with numerical phase unwrapping methods, the proposed GAN model overcomes the difficulty of accurate phase unwrapping due to abrupt phase changes and can perform phase unwrapping at a twice faster rate. We show that the proposed model can generalize well to different types of cell images and has high performance compared to recent U-net models. The proposed method can be useful in observing the morphology and movement of biological cells in real-time applications.

Noise-free quantitative phase imaging in Gabor holography with conditional generative adversarial network.

This paper shows that deep learning can eliminate the superimposed twin-image noise in phase images of Gabor holographic setup. This is achieved by the conditional generative adversarial model (C-GAN), trained by input-output pairs of noisy phase images obtained from synthetic Gabor holography and the corresponding quantitative noise-free contrast-phase image obtained by the off-axis digital holography. To train the model, Gabor holograms are generated from digital off-axis holograms with spatial shifting of the real image and twin image in the frequency domain and then adding them with the DC term in the spatial domain. Finally, the digital propagation of the Gabor hologram with Fresnel approximation generates a super-imposed phase image for the C-GAN model input. Two models were trained: a human red blood cell model and an elliptical cancer cell model. Following the training, several quantitative analyses were conducted on the bio-chemical properties and similarity between actual noise-free phase images and the model output. Surprisingly, it is discovered that our model can recover other elliptical cell lines that were not observed during the training. Additionally, some misalignments can also be compensated with the trained model. Particularly, if the reconstruction distance is somewhat incorrect, this model can still retrieve in-focus images.

Secure storage and retrieval schemes for multiple encrypted digital holograms with orthogonal phase encoding multiplexing.

Recent developments in 3D computational optical imaging such as digital holographic microscopy has ushered in a new era for biological research. Therefore, efficient and secure storage and retrieval of digital holograms is a challenging task for future cloud computing services. In this study, we propose a novel scheme to securely store and retrieve multiple encrypted digital holograms by using phase encoding multiplexing. In the proposed schemes, an encrypted hologram can only be accessed using a binary phase mask, which is the key to retrieve the image. In addition, it is possible to independently store, retrieve, and manage the encrypted digital holograms without affecting other groups of the encrypted holograms multiplexed using different sets of binary phase masks, due to the orthogonality properties of the Hadamard matrices with high autocorrelation and low cross-correlation. The desired encrypted holograms may also be searched for, removed, and added independently of other groups of the encrypted holograms. More and more 3D images or digital holograms can be securely and efficiently stored, retrieved, and managed.

Low serum complement 3 level is associated with severe ANCA-associated vasculitis at diagnosis.

OBJECTIVES: We investigated whether low serum C3 level can cross-sectionally estimate severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in immunosuppressive drug-naïve patients at diagnosis. METHODS: We retrospectively reviewed the medical records of 139 patients with AAV, who were first classified as AAV at Severance Hospital. We obtained clinical and laboratory data including serum complement 3 (C3) level and calculated Birmingham vasculitis activity score (BVAS) at diagnosis. We stratified AAV patients into three groups according to the tertile of BVAS and defined the lower limit of the highest tertile as the cutoff for severe AAV (BVAS at diagnosis ≥ 16) at diagnosis. Low serum C3 level was defined as C3 < 90 mg/dL. The odds ratio (OR) was assessed using the multivariable logistic regression. RESULTS: The mean age at diagnosis was 56.3 years and 41 patients were men (29.5%). The mean initial BVAS was 12.8. The mean serum C3 and C4 levels were 110.6 and 26.8 mg/dL. Thirty-one patients (22.3%) exhibited low serum C3 level at diagnosis. In the multivariable analysis, serum C3 level at diagnosis < 90 mg/dL (OR 2.963) exhibited the significant association with severe AAV at diagnosis. Patients with low serum C3 level exhibited a significantly high relative risk (RR) for severe AAV at diagnosis compared to those without (RR 3.600). Patients with low serum C3 level at diagnosis exhibited poor renal prognosis than those without. CONCLUSION: Low serum C3 level can estimate severe AAV and predict poor renal outcome in immunosuppressive drug-naïve patients at diagnosis.

Systemic immune-inflammation index could estimate the cross-sectional high activity and the poor outcomes in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: We investigated whether systemic immune-inflammation index (SII) at diagnosis can estimate the cross-sectional high activity and predict the poor outcomes in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively reviewed the medical records of 163 patients with AAV and obtained clinical and laboratory data. We calculated Birmingham vasculitis activity score (BVAS) as well as five-factor score (FFS) (2009) at diagnosis. SII at diagnosis was calculated by the equation of (SII at diagnosis = platelet count × neutrophil count/lymphocyte count at diagnosis). Severe AAV was defined as BVAS at diagnosis ≥16. The odds ratio was assessed using the multivariable logistic regression analysis and cumulative survival rates were compared by the Kaplan-Meier survival analysis. RESULTS: The median age at diagnosis was 58.0 years old and 51 patients were men. The median BVAS was 12.0. Fifty-seven patients had severe AAV. The median SII at diagnosis was 1349.6. In the multivariable analysis, only SII exhibited a significant odds ratio for the cross-sectional severe AAV (P = 0.043). We obtained the cut-off of SII at diagnosis for severe AAV as 1573.56. Patients with SII at diagnosis ≥1573.56 exhibited a significantly high relative risk of the cross-sectional severe AAV compared to those without (relative risk 4.625). Furthermore, patients with SII at diagnosis ≥1573.56 exhibited significantly the lower cumulative relapse free and renal survivals than those without. CONCLUSION: Systemic immune-inflammation index at diagnosis could estimate the cross-section severe AAV and predict the poor outcomes in AAV patients.

Highly efficient blue organic light-emitting diodes using quantum well-like multiple emissive layer structure.

In this study, the properties of blue organic light-emitting diodes (OLEDs), employing quantum well-like structure (QWS) that includes four different blue emissive materials of 4,4'-bis(2,2'-diphenylyinyl)-1,1'-biphenyl (DPVBi), 9,10-di(naphth-2-yl)anthracene (ADN), 2-(N,N-diphenyl-amino)-6-[4-(N,N-diphenyl amine)styryl]naphthalene (DPASN), and bis(2-methyl-8-quinolinolate)-4-(phenyl phenolato) aluminum (BAlq), were investigated. Conventional QWS blue OLEDs composed of multiple emissive layers and charge blocking layer with lower highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy level, and devices with triple emissive layers for more significant hole-electron recombination and a wider region for exciton generation were designed. The properties of triple emissive layered blue OLEDs with the structure of indium tin oxide (ITO) /N,N'-diphenyl-N,N'-bis(1-naphthyl-phenyl)-(1,1'-biphenyl)-4,4'-diamine (NPB) (700 Ǻ)/X (100 Ǻ)/BAlq (100 Ǻ)/X (100 Ǻ)/4,7-diphenyl-1,10-phenanthroline (Bphen) (300 Ǻ)/lithium quinolate (Liq) (20 Ǻ)/aluminum (Al) (1,200 Ǻ) (X = DPVBi, ADN, DPASN) were examined. HOMO-LUMO energy levels of DPVBi, ADN, DPASN, and BAlq are 2.8 to 5.9, 2.6 to 5.6, 2.3 to 5.2, and 2.9 to 5.9 eV, respectively. The OLEDs with DPASN/BAlq/DPASN QWS with maximum luminous efficiency of 5.32 cd/A was achieved at 3.5 V.

Effects of electron transport material on blue organ light-emitting diode with fluorescent dopant of BCzVBi.

High efficiency blue organic light emitting diodes (OLEDs), based on 2-me-thyl-9,10-di(2-naphthyl) anthracene (MADN) doped with 4,4'-bis(9-ethyl-3-carbazovinylene)-1,1'-biphenyl (BCzVBi), were fabricated using two different electron transport layers (ETLs) of tris(8-hydroxyquinolino)-aluminum (Alq3) and 4,7-di-phenyl-1,10-phenanthroline (Bphen). Bphen ETL layers favored the efficient hole-electron recombination in the emissive layer of the BCzVBi-doped blue OLEDs, leading to high luminous efficiency and quantum efficiency of 8.34 cd/A at 100 mA/cm2 and 5.73% at 100 cd/m2, respectively. Maximum luminance of blue OLED with Bphen ETL and Alq3 ETL were 10670 cd/m2, and CIExy coordinates of blue OLEDs were (0.180, 0279) and (0.155, 0.212) at 100 cd/m2.

Estimation of absorbed organ doses and effective dose based on body mass index in digital radiography.

With the introduction of digital radiography, patients undergoing radiographic procedures are subject to being overexposed to radiation. Therefore, it is necessary to estimate the absorbed organ dose and the effective dose, which are significant for patient health, along with body type. During chest radiographic examinations conducted in 899 patients for screening, the absorbed dose of the 13 major organs, the average whole-body dose, and two effective doses weighted by factors published in ICRP 60 and ICRP 103 were calculated on the basis of patient information such as height, weight and examination condition, including kilovolt potential, focus-skin distance and entrance surface dose (ESD), using a PC-based Monte Carlo program simulation. It was found that dose per unit ESD had a tendency to decrease with body mass index (BMI). In particular, the absorbed dose for most organs was larger at high voltages (140 kVp) than at low voltages (120 kVp, 100 kVp). In addition, the effective dose which was based on ICRP 60 and ICRP 103 also represented the same tendency in respect of BMI and tube voltage.

High contrast blue organic light-emitting diodes using inorganic multilayers of Al and ZnSe.

High contrast blue organic light-emitting diodes were fabricated using an inorganic multilayer of NPB (700 Å)/MADN (200 Å)/Alq3 (300 Å)/LiF (10 Å)/Al (70 Å)/ZnSe (300 Å)/Al (1000 Å). The optical and electrical characteristics were measured and compared to conventional organic light-emitting devices (OLEDs) and OLEDs with polarizers. OLEDs with the metal multilayer cathodes had an improved contrast ratio of 135∶1 compared to 104∶1 for OLEDs with polarizers. In addition, the multilayer OLEDs had a low turn-on voltage of 3.5 V due to energy band fitting of ZnSe with Al and the electron transport layer.

Radiobiological model-based bio-anatomical quality assurance in intensity-modulated radiation therapy for prostate cancer.

A bio-anatomical quality assurance (QA) method employing tumor control probability (TCP) and normal tissue complication probability (NTCP) is described that can integrate radiobiological effects into intensity-modulated radiation therapy (IMRT). We evaluated the variations in the radiobiological effects caused by random errors (r-errors) and systematic errors (s-errors) by evaluating TCP and NTCP in two groups: patients with an intact prostate (G(intact)) and those who have undergone prostatectomy (G(tectomy)). The r-errors were generated using an isocenter shift of ±1 mm to simulate a misaligned patient set-up. The s-errors were generated using individual leaves that were displaced inwardly and outwardly by 1 mm on multileaf collimator field files. Subvolume-based TCP and NTCP were visualized on computed tomography (CT) images to determine the radiobiological effects on the principal structures. The bio-anatomical QA using the TCP and NTCP maps differentiated the critical radiobiological effects on specific volumes, particularly at the anterior rectal walls and planning target volumes. The s-errors showed a TCP variation of -40-25% in G(tectomy) and -30-10% in G(intact), while the r-errors were less than 1.5% in both groups. The r-errors for the rectum and bladder showed higher NTCP variations at ±20% and ±10%, respectively, and the s-errors were greater than ±65% for both. This bio-anatomical method, as a patient-specific IMRT QA, can provide distinct indications of clinically significant radiobiological effects beyond the minimization of probable physical dose errors in phantoms.

Comparison of operator radiation exposure between C-arm and O-arm fluoroscopy for orthopaedic surgery.

The O-arm system has recently been introduced and has the capability of combined two-dimensional (2-D) fluoroscopy imaging and three-dimensional computed tomography imaging. In this study, an orthopaedic surgical procedure using C-arm and O-arm systems in their 2-D fluoroscopy modes was simulated and the radiation doses to susceptible organs to which operators can be exposed were investigated. The experiments were performed in four configurations of the location of the X-ray source and detector. Shielding effects on the thyroid surface and the direct exposure delivered to the surgeon's hands were also compared. The results obtained show that the O-arm delivered higher doses to the sensitive organs of the operator in all configurations. The thyroid shield cut-off 89 % of the dose in the posteroanterior configuration of both imaging systems. Thus, the operators need to pay more attention to managing radiation exposure, especially when using the O-arm system.

Dose evaluation of selective collimation effect in cephalography by measurement and Monte Carlo simulation.

Recently, simulations based on the Monte Carlo code have been increasingly applied for physics phenomena, patient dose and quality assurance of radiation systems. The objective of this study was to use Monte Carlo simulation and measurement to verify dose and dose reduction in cephalography. The collimator was constructed with 3-mm thick lead plate, and attached to the tube head to remove regions of disinterest in the radiation field. A digital phantom patient was constructed to evaluate patient dose. In addition, detectors of pixel size 1×1 cm² and 0.1×0.1 cm² were constructed to check collimator location. The effective dose according to International Commission on Radiological Protection 103 was calculated with and without collimation. The effective doses for simulation with and without collimation were 5.09 and 11.32 µSv, respectively. The results of the calculated effective dose show 61.7 % reduction of field area and 55 % of effective dose. The Monte Carlo simulation is a good evaluation tool for patient dose.

Dose area product measurement for diagnostic reference levels and analysis of patient dose in dental radiography.

In this study, diagnostic reference levels (DRLs) were suggested and patient doses were analysed through the dose-area product value in dental radiography. In intraoral radiography, at three sites, i.e. molar, premolar and incisor on the maxilla and acquired third quartile values: 55.5, 46 and 36.5 mGy cm(2), respectively, were measured. In panoramic, cephalometric and cone beam computed tomography, the values were 120.3, 146 and 3203 mGy cm(2) (16 × 18 cm), respectively. It has been shown that, in intraoral radiography, the patient dose changes proportionally to the value of mA s, but the change in extraoral radiography in response to mA s could not be confirmed. The authors could confirm, however, the difference in dose according to the manufacturer in all dental radiography examinations, except for panoramic radiography. Depending on the size of hospital, there were some differences in patient dose in intraoral radiography, but no difference in patient dose in extraoral radiography.

Development of a novel quality assurance system based on rolled-up and rolled-out radiochromic films in volumetric modulated arc therapy.

PURPOSE: To develop a cylindrical phantom with rolled-up radiochromic films and dose analysis software in the rolled-out plane for quality assurance (QA) in volumetric modulated arc therapy (VMAT). METHODS: The phantom consists of an acrylic cylindrical body wrapped with radiochromic film inserted into an outer cylindrical shell of 5 cm thickness. The rolled-up films with high spatial resolution enable detection of specific dose errors along the arc trajectory of continuously irradiated and modulated beams in VMAT. The developed dose analysis software facilitates dosimetric evaluation in the rolled-up and rolled-out planes of the film; the calculated doses on the corresponding points where the rolled-up film was placed were reconstructed into a rectangular dose matrix equivalent to that of the rolled-out plane of the film. The VMAT QA system was implemented in 3 clinical cases of prostate, nasopharynx, and pelvic metastasis. Each calculated dose on the rolled-out plane was compared with measurement values by modified gamma evaluation. Detected positions of dose disagreement on the rolled-out plane were also distinguished in cylindrical coordinates. The frequency of error occurrence and error distribution were summarized in a histogram and in an axial view of rolled-up plane to intuitively identify the corresponding positions of detected errors according to the gantry angle. RESULTS: The dose matrix reconstructed from the developed VMAT QA system was used to verify the measured dose distribution along the arc trajectory. Dose discrepancies were detected on the rolled-out plane and visualized on the calculated dose matrix in cylindrical coordinates. The error histogram obtained by gamma evaluation enabled identification of the specific error frequency at each gantry angular position. The total dose error occurring on the cylindrical surface was in the range of 5%-8% for the 3 cases. CONCLUSIONS: The developed system provides a practical and reliable QA method to detect dosimetric errors according to the gantry angle. Film dosimetry based on rolled-up and rolled-out techniques leads to dose verification in the subspaces of the 3D dose volume. The system can be employed as an alternative tool to detect the pitfalls of planar dose verification.

Application of a novel dose-uncertainty model for dose-uncertainty analysis in prostate intensity-modulated radiotherapy.

PURPOSE: To analyze dose uncertainty using a previously published dose-uncertainty model, and to assess potential dosimetric risks existing in prostate intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: The dose-uncertainty model provides a three-dimensional (3D) dose-uncertainty distribution in a given confidence level. For 8 retrospectively selected patients, dose-uncertainty maps were constructed using the dose-uncertainty model at the 95% CL. In addition to uncertainties inherent to the radiation treatment planning system, four scenarios of spatial errors were considered: machine only (S1), S1 + intrafraction, S1 + interfraction, and S1 + both intrafraction and interfraction errors. To evaluate the potential risks of the IMRT plans, three dose-uncertainty-based plan evaluation tools were introduced: confidence-weighted dose-volume histogram, confidence-weighted dose distribution, and dose-uncertainty-volume histogram. RESULTS: Dose uncertainty caused by interfraction setup error was more significant than that of intrafraction motion error. The maximum dose uncertainty (95% confidence) of the clinical target volume (CTV) was smaller than 5% of the prescribed dose in all but two cases (13.9% and 10.2%). The dose uncertainty for 95% of the CTV volume ranged from 1.3% to 2.9% of the prescribed dose. CONCLUSIONS: The dose uncertainty in prostate IMRT could be evaluated using the dose-uncertainty model. Prostate IMRT plans satisfying the same plan objectives could generate a significantly different dose uncertainty because a complex interplay of many uncertainty sources. The uncertainty-based plan evaluation contributes to generating reliable and error-resistant treatment plans.

The characteristics of dental X-ray fluoroscopic equipment 'DreamRay 60F'.

This study examined the characteristics of the dental X-ray fluoroscopic equipment, 'DreamRay 60F', which was recently developed in Korea. The output linearity, output reproducibility, half-value layer (HVL), leakage radiation and scattered radiation were measured using an ionisation chamber. The surface dose equivalent rate and estimated dose equivalent of the operator were also calculated. The output linearity was 0.0015-0.0175 and the coefficient of variation for the output reproducibility was 0.0013-0.0074. The experimental HVL was 2.1 mm Al, and the leakage dose rate at 100 cm from the X-ray focus ranged from 2.70 to 19.66 microGy h (-1) depending on the direction. The scattered radiation doses differed significantly (1.7-16.8 times) depending on the distance and direction. If an operator is exposed for 10 min per procedure, 5 procedures a day at 5 days a week, he/she sitting at a 90 degrees direction will receive an annual dose equivalent of 13.0 mSv (at 30 cm) and 63.7 mSv (at 50 cm) in the trunk and face surface, respectively.

Dose reduction in CT using bismuth shielding: measurements and Monte Carlo simulations.

In this research, using direct measurements and Monte Carlo calculations, the potential dose reduction achieved by bismuth shielding in computed tomography was evaluated. The patient dose was measured using an ionisation chamber in a polymethylmethacrylate (PMMA) phantom that had five measurement points at the centre and periphery. Simulations were performed using the MCNPX code. For both the bare and the bismuth-shielded phantom, the differences of dose values between experiment and simulation were within 9%. The dose reductions due to the bismuth shielding were 1.2-55% depending on the measurement points, X-ray tube voltage and the type of shielding. The amount of dose reduction was significant for the positions covered by the bismuth shielding (34 - 46% for head and 41 - 55% for body phantom on average) and negligible for other peripheral positions. The artefact on the reconstructed images were minimal when the distance between the shielding and the organs was >1 cm, and hence the shielding should be selectively located to protect critical organs such as the eye lens, thyroid and breast. The simulation results using the PMMA phantom was compared with those using a realistically voxelised phantom (KTMAN-2). For eye and breast, the simulation results using the PMMA and KTMAN-2 phantoms were similar with each other, while for thyroid the simulation results were different due to the discrepancy of locations and the sizes of the phantoms. The dose reductions achieved by bismuth and lead shielding were compared with each other and the results showed that the difference of the dose reductions achieved by the two materials was less than 2-3%.

The development of a guidance level for patient dose for CT examinations in Korea.

The primary goal of this study was to analyse the state of patient doses in the field of computed tomography (CT) examinations in the Republic of Korea. All survey data including the CT applications and patient dose details were obtained from general hospitals registered in the Korean Hospital Association. The systematic analysis of the patient dose survey gives target values of the weighted computed tomography dose index (CTDI(w)) and the dose-length product (DLP). The targeted CTDI(w) values were 69, 69, 31, 19, 44, 25, 24, 20, 2, 19 and 19 mGy for the brain non-contrast enhancement (BNCE), brain contrast enhancement (BCE), neck, chest, spine, liver, pancreas, stomach, kidneys, abdomen routine and abdomen trauma protocols, respectively. The targeted DLP values were 1056, 2112, 762, 1234, 1338, 2794, 2742, 2378, 2836, 1844 and 1939 mGy cm for the BNCE, BCE, neck, chest, spine, liver, pancreas, stomach, kidneys, abdomen routine and abdomen trauma protocols, respectively. Comparing with the EUR recommendation, especially in the DLP, the adjustment of the total scan phase frequency and the shortening of the scan phase in each scan phase are needed to reduce the patients radiation exposure to international standards.

High efficient white organic light-emitting diodes using BCzVBi as blue fluorescent dopant.

Efficiency improvement and color optimization of white organic light-emitting diodes (WOLEDs) were achieved via employing blue host DPVBi doped with blue fluorescent, BCzVBi. The structure of high efficient WOLED device was composed of ITO/NPB/DPVBi:BCzVBi-6%/MADN:DCM2-0.5%/Bphen/Liq/Al. WOLED doped by blue fluorescent BCzVBi exhibits 6.19 cd/A of luminous efficiency and 15400 cd/m2 of maximum luminescence. It also performs 480 cd/m2 of luminance at 5.7 V and 15400 cd/m2 at 12.9 V with CIE(x,y) coordinates of (0.33, 0.32) and (0.32, 0.32), respectively. Hole carrier and energy transfer from DPVBi to BCzVBi are proposed to explain the observed phenomena.