Publications by authors named "Sa Yu"

24 Publications

  • Page 1 of 1

HOXA11-AS induces cisplatin resistance by modulating the microRNA-98/PBX3 axis in nasopharyngeal carcinoma.

Oncol Lett 2021 Jun 26;21(6):493. Epub 2021 Apr 26.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China.

Long non-coding RNA homeobox A11-antisense RNA (HOXA11-AS) has been implicated in cisplatin (DDP) resistance in multiple types of cancer. The purpose of the present study was to investigate the role of HOXA11-AS in DDP-resistant nasopharyngeal carcinoma (NPC) cells. The expression levels of HOXA11-AS were examined using reverse transcription-quantitative PCR. Cell viability was measured using a Cell Counting Kit-8 assay, and a TUNEL assay was utilized to assess cell apoptosis. The expression levels of apoptosis-related factors (Bax and Bcl-2) were detected by western blot analysis. The interaction between microRNA-98 (miR-98) and HOXA11-AS or pre-B-cell leukemia homeobox 3 (PBX3) was demonstrated using bioinformatics analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. HOXA11-AS and PBX3 expressions levels were upregulated, whereas miR-98 levels were downregulated in DDP-resistant NPC tissues. Patients with NPC with high HOXA11-AS expression had a low survival rate. Knockdown of HOXA11-AS enhanced the DDP sensitivity of DDP-resistant NPC (5-8F/DDP and SUNE1/DDP) cells, which was demonstrated by the accelerated apoptosis. In addition, HOXA11-AS inhibited the expression levels of miR-98 through direct interaction. Furthermore, miR-98 inhibition counteracted the inductive effect of HOXA11-AS-knockdown on the DDP sensitivity of NPC cells. PBX3 was a target of miR-98 and was positively modulated by HOXA11-AS. Overexpression of PBX3 reversed the suppressive effect of HOXA11-AS silencing on the DDP resistance of NPC cells. The data demonstrated that HOXA11-AS enhanced DDP resistance in NPC via the miR-98/PBX3 axis, providing a potential therapeutic target for patients with DDP-resistant NPC.
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http://dx.doi.org/10.3892/ol.2021.12754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100958PMC
June 2021

Clinic Reopening Post-Coronavirus Disease 2019: Precaution of a Plastic Surgery Clinic in China.

Plast Reconstr Surg Glob Open 2020 May 29;8(5):e2936. Epub 2020 May 29.

Department of Plastic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

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http://dx.doi.org/10.1097/GOX.0000000000002936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572124PMC
May 2020

Long non-coding RNA HOXA-AS2 promotes the expression levels of hypoxia-inducible factor-1α and programmed death-ligand 1, and regulates nasopharyngeal carcinoma progression via miR-519.

Oncol Lett 2020 Nov 15;20(5):245. Epub 2020 Sep 15.

Department of Otorhinolaryngology, Head and Neck Surgery, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang 311800, P.R. China.

Nasopharyngeal carcinoma (NPC) is a rare malignancy arising from the nasopharyngeal epithelium and belongs to the group of head and neck cancer types, which are usually associated with viral and/or environmental influences, as well as heredity causes. A recent study reported that the long non-coding RNA (lncRNA) HOXA cluster antisense RNA 2 (HOXA-AS2) may be a prognostic biomarker in NPC; however, the specific mechanisms underlying NCP progression are yet to be determined. The aim of the present study was to investigate the biological role of HOXA-AS2 in NPC. In the present study, the gene expression levels of HOXA-AS2, miR-519, hypoxia-inducible factor (HIF-1α) and programmed death-ligand 1 (PD-L1) were detected using reverse transcription-quantitative PCR (RT-qPCR) analysis and western blotting. Bioinformatics analysis and a dual luciferase reporter assay were performed to predict and confirm the direct interactions between HOXA-AS2 and microRNA (miR)-519, as well as between miR-519 and HIF-1α. A MTT assay was used to detect the cell viability, while cell migratory and invasive abilities were assessed using wound healing and Transwell assays. HOXA-AS2 and HIF-1α were found to be significantly upregulated in NPC tumor tissues, as well as in NPC cell lines. The overexpression of HOXA-AS2 significantly enhanced NPC progression, including the cell proliferative, migratory and invasive abilities. HOXA-AS2 was identified to directly bind to miR-519, whereas a miR-519 inhibitor significantly rescued the HOXA-AS2 knockdown-attenuated progression of NPC. Moreover, miR-519 could bind to HIF-1α and PD-L1. Overexpression of HIF-1α and PD-L1 significantly promoted NPC progression and partially recovered the phenotype of NPC cells attenuated by HOXA-AS2 knockdown. In conclusion, the present study demonstrated that HOXA-AS2/miR-519/HIF-1α and/or HOXA-AS2/miR-519/PD-L1 may be a novel mechanism regulating the progression of NPC, which may facilitate the development of targeted clinical therapy.
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http://dx.doi.org/10.3892/ol.2020.12107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509505PMC
November 2020

KIF9-AS1 promotes nasopharyngeal carcinoma progression by suppressing miR-16.

Oncol Lett 2020 Nov 15;20(5):241. Epub 2020 Sep 15.

Department of Otorhinolaryngology-Head and Neck Surgery, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang 311800, P.R. China.

Long non-coding RNAs (lncRNAs) have been reported to serve a crucial role in the progression of nasopharyngeal carcinoma (NPC); however, the underlying molecular mechanisms of lncRNA KIF9-AS1 in the tumorigenesis of NPC remains poorly understood. Reverse transcription-quantitative PCR was used to analyze the expression levels of KIF9-AS1 and microRNA (miR)-16, and Cell Counting Kit-8, wound healing and Transwell assays were used to determine the cell viability, invasion and migration, respectively, of NPC cells. In addition, a dual-luciferase reporter assay was used to analyze the direct interaction between KIF9-AS1 and miR-16. NPC stage was classified according to the seventh edition of the AJCC staging system. The results revealed that KIF9-AS1 expression levels were upregulated in NPC tissues and cell lines. In addition, miR-16 was demonstrated to directly interact with KIF9-AS1 and inhibit KIF9-AS1 expression levels, whereas the miR-16 inhibitor rescued the effects of the KIF9-AS1-knockdown in NPC cells. Furthermore, the expression levels of KIF9-AS1 were upregulated, while those of miR-16 were downregulated in NPC tissues. Notably, the expression levels of KIF9-AS1 were observed to be significantly more upregulated in advanced tumors (III-IV vs. I-II) and patients with high KIF9-AS1 expression levels exhibited a worse prognosis. In conclusion, the findings of the present study suggested that KIF9-AS1 may promote the progression of NPC by targeting miR-16, thus KIF9-AS1 may be a novel molecular target for NPC therapy.
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http://dx.doi.org/10.3892/ol.2020.12104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509506PMC
November 2020

Social Media Impact on a Plastic Surgery Clinic During Shutdown due to COVID-19 in China.

Facial Plast Surg Aesthet Med 2020 May/Jun;22(3):162-163. Epub 2020 Apr 16.

Department of Plastic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.

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http://dx.doi.org/10.1089/fpsam.2020.0173DOI Listing
May 2020

Long Non-Coding RNA DLEU1 Up-Regulates BIRC6 Expression by Competitively Sponging miR-381-3p to Promote Cisplatin Resistance in Nasopharyngeal Carcinoma.

Onco Targets Ther 2020 9;13:2037-2045. Epub 2020 Mar 9.

Department of Otolaryngology, Zhuji People's Hospital, Zhuji 311800, People's Republic of China.

Background: Cisplatin (DDP) resistance has become an obstacle to chemotherapy for nasopharyngeal carcinoma (NPC) patients. Recent evidences indicate that long noncoding RNAs (lncRNAs) are involved in tumorigenesis and chemoresistance. However, the potential role of lncRNAs in NPC progression remains largely unknown.

Methods: First, lncRNA expression profiling in NPC was performed via microarray analysis. To explore the involvement of DLEU1 in DDP resistance, loss-of-function experiments were employed in vitro and in vivo. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, and Western blot assays were used to investigate the underlying mechanisms.

Results: Here, we identified 153 differentially expressed lncRNAs. Among them, DLEU1 was remarkably up-regulated in NPC tissues and associated with worse outcome. Knock-down of DLEU1 could sensitize NPC cells to DDP in vitro and in vivo. Further investigations revealed that DLEU1 positively regulated BIRC6 expression via its competing endogenous RNA (ceRNA) activity on miR-381-3p. We also observed that BIRC6 overexpression or miR-381-3p silence could significantly reverse DLEU1-dependent DDP resistance.

Conclusion: Our data suggest that DLEU1 acts as an oncogene to promote DDP resistance and BIRC6 expression in NPC through interacting with miR-381-3p, which may help to develop new strategy against NPC chemoresistance.
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http://dx.doi.org/10.2147/OTT.S237456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082798PMC
March 2020

A potential field segmentation based method for tumor segmentation on multi-parametric MRI of glioma cancer patients.

BMC Med Imaging 2019 06 17;19(1):48. Epub 2019 Jun 17.

Department of Biomedical Engineering, Tianjin University, 92 Weijin Road, Tianjin, 300072, China.

Background: Accurate segmentation of brain tumors is vital for the gross tumor volume (GTV) definition in radiotherapy. Functional MR images like apparent diffusion constant (ADC) and fractional anisotropy (FA) images can provide more comprehensive information for sensitive detection of the GTV. We synthesize anatomical and functional MRI for accurate and semi-automatic segmentation of GTVs and improvement of clinical efficiency.

Methods: Four MR image sets including T1-weighted contrast-enhanced (T1C), T2-weighted (T2), apparent diffusion constant (ADC) and fractional anisotropy (FA) images of 5 glioma patients were acquired and registered. A new potential field segmentation (PFS) method was proposed based on the concept of potential field in physics. For T1C, T2 and ADC images, global potential field segmentation (global-PFS) was used on user defined region of interest (ROI) for rough segmentation and then morphologically processed for accurate delineation of the GTV. For FA images, white matter (WM) was removed using local potential field segmentation (local-PFS), and then tumor extent was delineated with region growing and morphological methods. The individual segmentations of multi-parametric images were ensembled into a fused segmentation, considered as final GTV. GTVs were compared with manually delineated ground truth and evaluated with segmentation quality measure (Q), Dice's similarity coefficient (DSC) and Sensitivity and Specificity.

Results: Experimental study with the five patients' data and new method showed that, the mean values of Q, DSC, Sensitivity and Specificity were 0.80 (±0.07), 0.88 (±0.04), 0.92 (±0.01) and 0.88 (±0.05) respectively. The global-PFS used on ROIs of T1C, T2 and ADC images can avoid interferences from skull and other non-tumor areas. Similarity to local-PFS on FA images, it can also reduce the time complexity as compared with the global-PFS on whole image sets.

Conclusions: Efficient and semi-automatic segmentation of the GTV can be achieved with the new method. Combination of anatomical and functional MR images has the potential to provide new methods and ideas for target definition in radiotherapy.
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http://dx.doi.org/10.1186/s12880-019-0348-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580466PMC
June 2019

Feasibility study of stain-free classification of cell apoptosis based on diffraction imaging flow cytometry and supervised machine learning techniques.

Apoptosis 2018 06;23(5-6):290-298

Department of Biomedical Engineering, Tianjin University, 92 Weijin Rd., Tianjin, 300072, China.

This study was to explore the feasibility of prediction and classification of cells in different stages of apoptosis with a stain-free method based on diffraction images and supervised machine learning. Apoptosis was induced in human chronic myelogenous leukemia K562 cells by cis-platinum (DDP). A newly developed technique of polarization diffraction imaging flow cytometry (p-DIFC) was performed to acquire diffraction images of the cells in three different statuses (viable, early apoptotic and late apoptotic/necrotic) after cell separation through fluorescence activated cell sorting with Annexin V-PE and SYTOX® Green double staining. The texture features of the diffraction images were extracted with in-house software based on the Gray-level co-occurrence matrix algorithm to generate datasets for cell classification with supervised machine learning method. Therefore, this new method has been verified in hydrogen peroxide induced apoptosis model of HL-60. Results show that accuracy of higher than 90% was achieved respectively in independent test datasets from each cell type based on logistic regression with ridge estimators, which indicated that p-DIFC system has a great potential in predicting and classifying cells in different stages of apoptosis.
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http://dx.doi.org/10.1007/s10495-018-1454-yDOI Listing
June 2018

A novel automatic quantification method for high-content screening analysis of DNA double strand-break response.

Sci Rep 2017 08 29;7(1):9581. Epub 2017 Aug 29.

Department of Biomedical Engineering, Tianjin University, Tianjin, 300072, China.

High-content screening is commonly used in studies of the DNA damage response. The double-strand break (DSB) is one of the most harmful types of DNA damage lesions. The conventional method used to quantify DSBs is γH2AX foci counting, which requires manual adjustment and preset parameters and is usually regarded as imprecise, time-consuming, poorly reproducible, and inaccurate. Therefore, a robust automatic alternative method is highly desired. In this manuscript, we present a new method for quantifying DSBs which involves automatic image cropping, automatic foci-segmentation and fluorescent intensity measurement. Furthermore, an additional function was added for standardizing the measurement of DSB response inhibition based on co-localization analysis. We tested the method with a well-known inhibitor of DSB response. The new method requires only one preset parameter, which effectively minimizes operator-dependent variations. Compared with conventional methods, the new method detected a higher percentage difference of foci formation between different cells, which can improve measurement accuracy. The effects of the inhibitor on DSB response were successfully quantified with the new method (p = 0.000). The advantages of this method in terms of reliability, automation and simplicity show its potential in quantitative fluorescence imaging studies and high-content screening for compounds and factors involved in DSB response.
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http://dx.doi.org/10.1038/s41598-017-10063-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574919PMC
August 2017

Solely lung-involved IgG4-related disease : a case report and review of the literature.

Sarcoidosis Vasc Diffuse Lung Dis 2016 Dec 23;33(4):398-406. Epub 2016 Dec 23.

Department of Respirology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.

By analyzing the clinical data of 1 case of IgG4-related lung disease(IgG4-RLD) and the review of literature, the author investigated the clinical characteristics of IgG4-RLD. IgG4-RLD is a rare disease characterized by significant elevation of serum IgG4 and infiltration of a large number of IgG4+ plasma cells. The clinical manifestations of the disease were nonspecific, and the imaging features were mixed with several types. The disease can only be involved in the lung, but also multiple organ involvement. Solely lung-involved IgG4-RD is not only extremely rare but also easily misdiagnosed as tuberculosis, lung cancer, lymphoma and other common pulmonary diseases. Histopathological examination is the key to the diagnosis of the disease. Corticosteroids are the first choice of treatment, and the overall prognosis is good.
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December 2016

Comparison of contourlet transform and gray level co-occurrence matrix for analyzing cell-scattered patterns.

J Biomed Opt 2016 08;21(8):86013

Distribution of scattered image patterns hinges on morphological and optical characteristics of cells. This paper applied a numerical method to simulate scattered images of real cell morphologies, which were reconstructed from confocal image stacks dyed by fluorescent stains. Two approaches, contourlet transform (CT) and gray level co-occurrence matrix (GLCM), were then used to analyze the simulated scattered images. The results showed that features extracted using GLCM contained more information than those extracted using CT. Higher classification accuracy could be achieved with a single GLCM parameter than CT and GLCM could achieve higher accuracy with fewer parameters than CT when using multiple parameters. Meanwhile, GLCM requires less computational cost. Thus, GLCM is more suitable and efficient than CT for the analysis of cell-scattered images.
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http://dx.doi.org/10.1117/1.JBO.21.8.086013DOI Listing
August 2016

Original Research: Label-free detection for radiation-induced apoptosis in glioblastoma cells.

Exp Biol Med (Maywood) 2016 10 5;241(16):1751-6. Epub 2016 May 5.

Department of Biomedical Engineering, Tianjin University, Tianjin 300072, China Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China Department of Radiation Oncology, East Carolina University, Greenville, NC 27834, USA

Current flow cytometry (FCM) requires fluorescent dyes labeling cells which make the procedure costly and time consuming. This manuscript reports a feasibility study of detecting the cell apoptosis with a label-free method in glioblastoma cells. A human glioma cell line M059K was exposed to 8 Gy dose of radiation, which enables the cells to undergo radiation-induced apoptosis. The rates of apoptosis were studied at different time points post-irradiation with two different methods: FCM in combination with Annexin V-FITC/PI staining and a newly developed technique named polarization diffraction imaging flow cytometry. Totally 1000 diffraction images were acquired for each sample and the gray level co-occurrence matrix (GLCM) algorithm was used in morphological characterization of the apoptotic cells. Among the feature parameters extracted from each image pair, we found that the two GLCM parameters of angular second moment (ASM) and sum entropy (SumEnt) exhibit high sensitivities and consistencies as the apoptotic rates (Pa) measured with FCM method. In addition, no significant difference exists between Pa and ASM_S, Pa and SumEnt_S, respectively (P > 0.05). These results demonstrated that the new label-free method can detect cell apoptosis effectively. Cells can be directly used in the subsequent biochemical experiments as the structure and function of cells and biomolecules are well-preserved with this new method.
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http://dx.doi.org/10.1177/1535370216648024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027936PMC
October 2016

A new assessment model for tumor heterogeneity analysis with [18]F-FDG PET images.

EXCLI J 2016 28;15:75-84. Epub 2016 Jan 28.

Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Department of Biomedical Engineering, Tianjin University, Tianjin, China.

It has been shown that the intratumor heterogeneity can be characterized with quantitative analysis of the [18]F-FDG PET image data. The existing models employ multiple parameters for feature extraction which makes it difficult to implement in clinical settings for the quantitative characterization. This article reports an easy-to-use and differential SUV based model for quantitative assessment of the intratumor heterogeneity from 3D [18]F-FDG PET image data. An H index is defined to assess tumor heterogeneity by summing voxel-wise distribution of differential SUV from the [18]F-FDG PET image data. The summation is weighted by the distance of SUV difference among neighboring voxels from the center of the tumor and can thus yield increased values for tumors with peripheral sub-regions of high SUV that often serves as an indicator of augmented malignancy. Furthermore, the sign of H index is used to differentiate the rate of change for volume averaged SUV from its center to periphery. The new model with the H index has been compared with a widely-used model of gray level co-occurrence matrix (GLCM) for image texture characterization with phantoms of different configurations and the [18]F-FDG PET image data of 6 lung cancer patients to evaluate its effectiveness and feasibility for clinical uses. The comparison of the H index and GLCM parameters with the phantoms demonstrate that the H index can characterize the SUV heterogeneity in all of 6 2D phantoms while only 1 GLCM parameter can do for 1 and fail to differentiate for other 2D phantoms. For the 8 3D phantoms, the H index can clearly differentiate all of them while the 4 GLCM parameters provide complicated patterns in the characterization. Feasibility study with the PET image data from 6 lung cancer patients show that the H index provides an effective single-parameter metric to characterize tumor heterogeneity in terms of the local SUV variation, and it has higher correlation with tumor volume change after radiotherapy (R(2) = 0.83) than the 4 GLCM parameters (R(2) = 0.63, 0.73, 0.59 and 0.75 for Energy, Contrast, Local Homogeneity and Entropy respectively). The new model of the H index has the capacity to characterize the intratumor heterogeneity feature from 3D [18]F-FDG PET image data. As a single parameter with an intuitive definition, the H index offers potential for clinical applications.
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http://dx.doi.org/10.17179/excli2015-723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822048PMC
April 2016

Spectrophotometric determination of turbid optical parameters without using an integrating sphere.

Appl Opt 2016 Mar;55(8):2079-85

Spectrophotometric quantification of turbidity by multiple optical parameters has wide-ranging applications in material analysis and life sciences. A robust system design needs to combine hardware for precise measurement of light signals with software to accurately model measurement configuration and rapidly solve a sequence of challenging inverse problems. We have developed and validated a design approach and performed system validation based on radiative transfer theory for determination of absorption coefficient, scattering coefficient, and anisotropy factor without using an integrating sphere. Accurate and rapid determination of parameters and spectra is achieved for microsphere suspension samples by combining photodiode-based measurement of four signals with the Monte Carlo simulation and perturbation-based inverse calculations. The three parameters of microsphere suspension samples have been determined from the measured signals as functions of wavelength from 400 to 800 nm and agree with calculated results based on the Mie theory. It has been shown that the inverse problems in the cases of microsphere suspension samples are well posed with convex cost functions to yield unique solutions, and it takes about 1 min to obtain the three parameters per wavelength.
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http://dx.doi.org/10.1364/AO.55.002079DOI Listing
March 2016

Realistic optical cell modeling and diffraction imaging simulation for study of optical and morphological parameters of nucleus.

Opt Express 2016 Jan;24(1):366-77

Coherent light scattering presents complex spatial patterns that depend on morphological and molecular features of biological cells. We present a numerical approach to establish realistic optical cell models for generating virtual cells and accurate simulation of diffraction images that are comparable to measured data of prostate cells. With a contourlet transform algorithm, it has been shown that the simulated images and extracted parameters can be used to distinguish virtual cells of different nuclear volumes and refractive indices against the orientation variation. These results demonstrate significance of the new approach for development of rapid cell assay methods through diffraction imaging.
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http://dx.doi.org/10.1364/OE.24.000366DOI Listing
January 2016

Comparison study of distinguishing cancerous and normal prostate epithelial cells by confocal and polarization diffraction imaging.

J Biomed Opt 2016 Jul;21(7):71102

East Carolina University, Department of Physics, Greenville, North Carolina 27858, United States.

Accurate classification of malignant cells from benign ones can significantly enhance cancer diagnosis and prognosis by detection of circulating tumor cells (CTCs). We have investigated two approaches of quantitative morphology and polarization diffraction imaging on two prostate cell types to evaluate their feasibility as single-cell assay methods toward CTC detection after cell enrichment. The two cell types have been measured by a confocal imaging method to obtain their three-dimensional morphology parameters and by a polarization diffraction imaging flow cytometry (p-DIFC) method to obtain image texture parameters. The support vector machine algorithm was applied to examine the accuracy of cell classification with the morphology and diffraction image parameters. Despite larger mean values of cell and nuclear sizes of the cancerous prostate cells than the normal ones, it has been shown that the morphologic parameters cannot serve as effective classifiers. In contrast, accurate classification of the two prostate cell types can be achieved with high classification accuracies on measured data acquired separately in three measurements. These results provide strong evidence that the p-DIFC method has the potential to yield morphology-related “fingerprints” for accurate and label-free classification of the two prostate cell types.
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http://dx.doi.org/10.1117/1.JBO.21.7.071102DOI Listing
July 2016

Acquisition of cross-polarized diffraction images and study of blurring effect by one time-delay-integration camera.

Appl Opt 2015 Jun;54(16):5223-8

Blurred diffraction images acquired from flowing particles affect the measurement of fringe patterns and subsequent analysis. An imaging unit with one time-delay-integration (TDI) camera has been developed to acquire two cross-polarized diffraction images. It was shown that selected elements of Mueller matrix of single scatters can be imaged with pixel matching precision in this configuration. With the TDI camera, the effect of blurring on imaging of scattered light propagating along the side directions was found to be much more significant for biological cells than microspheres. Despite blurring, classification of MCF-7 and K562 cells is feasible since the effect has similar influence on extracted image parameters. Furthermore, image blurring can be useful for analysis of the correlations among texture parameters for characterization of diffraction images from single cells. The results demonstrate that with one TDI camera the polarization diffraction imaging flow cytometry can be significantly improved and angular distribution of selected Mueller matrix elements can be accurately measured for rapid and morphology-based assay of particles and cells without fluorescent labeling.
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http://dx.doi.org/10.1364/AO.54.005223DOI Listing
June 2015

Analysis of diffraction imaging in non-conjugate configurations.

Opt Express 2014 Dec;22(25):31568-74

Diffraction imaging of scattered light allows extraction of information on scatterer's morphology. We present a method for accurate simulation of diffraction imaging of single particles by combining rigorous light scattering model with ray-tracing software. The new method has been validated by comparison to measured images of single microspheres. Dependence of fringe patterns on translation of an objective based imager to off-focus positions has been analyzed to clearly understand diffraction imaging with multiple optical elements. The calculated and measured results establish unambiguously that diffraction imaging should be pursued in non-conjugate configurations to ensure accurate sampling of coherent light distribution from the scatterer.
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http://dx.doi.org/10.1364/OE.22.031568DOI Listing
December 2014

A quantitative method for measurement of HL-60 cell apoptosis based on diffraction imaging flow cytometry technique.

Biomed Opt Express 2014 Jul 11;5(7):2172-83. Epub 2014 Jun 11.

Department of Physics, East Carolina University, Greenville, NC 27858, USA.

A quantitative method for measurement of apoptosis in HL-60 cells based on polarization diffraction imaging flow cytometry technique is presented in this paper. Through comparative study with existing methods and the analysis of diffraction images by a gray level co-occurrence matrix algorithm (GLCM), we found 4 GLCM parameters of contrast (CON), cluster shade (CLS), correlation (COR) and dissimilarity (DIS) exhibit high sensitivities as the apoptotic rates. It was further demonstrated that the CLS parameter correlates significantly (R(2) = 0.899) with the degree of nuclear fragmentation and other three parameters showed a very good correlations (R(2) ranges from 0.69 to 0.90). These results demonstrated that the new method has the capability for rapid and accurate extraction of morphological features to quantify cellular apoptosis without the need for cell staining.
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http://dx.doi.org/10.1364/BOE.5.002172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102357PMC
July 2014

Automatic lung tumor segmentation on PET/CT images using fuzzy Markov random field model.

Comput Math Methods Med 2014 29;2014:401201. Epub 2014 May 29.

Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

The combination of positron emission tomography (PET) and CT images provides complementary functional and anatomical information of human tissues and it has been used for better tumor volume definition of lung cancer. This paper proposed a robust method for automatic lung tumor segmentation on PET/CT images. The new method is based on fuzzy Markov random field (MRF) model. The combination of PET and CT image information is achieved by using a proper joint posterior probability distribution of observed features in the fuzzy MRF model which performs better than the commonly used Gaussian joint distribution. In this study, the PET and CT simulation images of 7 non-small cell lung cancer (NSCLC) patients were used to evaluate the proposed method. Tumor segmentations with the proposed method and manual method by an experienced radiation oncologist on the fused images were performed, respectively. Segmentation results obtained with the two methods were similar and Dice's similarity coefficient (DSC) was 0.85 ± 0.013. It has been shown that effective and automatic segmentations can be achieved with this method for lung tumors which locate near other organs with similar intensities in PET and CT images, such as when the tumors extend into chest wall or mediastinum.
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http://dx.doi.org/10.1155/2014/401201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4058834PMC
January 2015

Automatic quantitative analysis of morphology of apoptotic HL-60 cells.

EXCLI J 2014 29;13:19-27. Epub 2014 Jan 29.

Department of Biomedical Engineering, Tianjin University, Tianjin, China ; Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin China ; Department of Radiation Oncology, East Carolina University, Greenville, NC/USA.

Morphological identification is a widespread procedure to assess the presence of apoptosis by visual inspection of the morphological characteristics or the fluorescence images. The procedure is lengthy and results are observer dependent. A quantitative automatic analysis is objective and would greatly help the routine work. We developed an image processing and segmentation method which combined the Otsu thresholding and morphological operators for apoptosis study. An automatic determination method of apoptotic stages of HL-60 cells with fluorescence images was developed. Comparison was made between normal cells, early apoptotic cells and late apoptotic cells about their geometric parameters which were defined to describe the features of cell morphology. The results demonstrated that the parameters we chose are very representative of the morphological characteristics of apoptotic cells. Significant differences exist between the cells in different stages, and automatic quantification of the differences can be achieved.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464453PMC
September 2015

Analysis of cellular objects through diffraction images acquired by flow cytometry.

Opt Express 2013 Oct;21(21):24819-28

It was found that the diffraction images acquired along the side scattering directions with objects in a cell sample contain pattern variations at both the global and local scales. We show here that the global pattern variation is associated with the categorical size and morphological heterogeneity of the imaged objects. An automated image processing method has been developed to separate the acquired diffraction images into three types of global patterns. Combined with previously developed method for quantifying local texture pattern variations, the new method allows fully automated analysis of diffraction images for rapid and label-free classification of cells according to their 3D morphology.
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http://dx.doi.org/10.1364/OE.21.024819DOI Listing
October 2013

Study of low speed flow cytometry for diffraction imaging with different chamber and nozzle designs.

Cytometry A 2013 Nov 9;83(11):1027-33. Epub 2013 Jul 9.

Department of Biomedical Engineering, Tianjin University, Tianjin, 300072, China.

Achieving effective hydrodynamic focusing and flow stability at low speed presents a challenging design task in flow cytometry for studying phenomena such as cell adhesion and diffraction imaging of cells with low-cost cameras. We have developed different designs of flow chamber and sheath nozzle to accomplish the above goal. A 3D computational model of the chambers has been established to simulate the fluid dynamics in different chamber designs and measurements have been performed to determine the velocity and size distributions of the core fluid from the nozzle. Comparison of the simulation data with experimental results shows good agreement. With the computational model significant insights were gained for optimization of the chamber design and improvement of the cell positioning accuracy for study of slow moving cells. The benefit of low flow speed has been demonstrated also by reduced blurring in the diffraction images of single cells. Based on these results, we concluded that the new designs of chamber and sheath nozzle produce stable hydrodynamic focusing of the core fluid at low speed and allow detailed study of cellular morphology under various rheological conditions using the diffraction imaging method.
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http://dx.doi.org/10.1002/cyto.a.22332DOI Listing
November 2013

A novel method of diffraction imaging flow cytometry for sizing microspheres.

Opt Express 2012 Sep;20(20):22245-51

Department of Biomedical Engineering, Tianjin University, Tianjin 300072, China.

We report a novel method of diffraction imaging flow cytometry to measure and analyze size distribution of microspheres. An automated and robust image processing software based on the short-time-Fourier-transform algorithm has been developed to analyze the characteristic and spatially varying oscillations of side scatters recorded as a diffraction image. Our results demonstrate that the new method allows accurate and rapid determination of single microspheres' diameters ranging from 1 to 100 μm. The capacity for analysis of light scattering by two-sphere aggregates has been demonstrated but analytical tools for characterization of aggregates by multiple microspheres remain to be developed.
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http://dx.doi.org/10.1364/OE.20.022245DOI Listing
September 2012