Xulei Qin
Instructor, Surgery - General Surgery
All Publications
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Image-level supervised segmentation for human organs with confidence cues.
Physics in medicine and biology
2021
Abstract
Image segmentation for human organs is an important task for diagnosis and treatment of diseases. Current deep learning-based methods are fully supervised that need pixel-level labels. Since the medical images are highly specialized and complex, the work of delineating pixel-level segmentation masks is very time-consuming. Weakly supervised methods are then chosen to lighten the workload, which only needs physicians to determine whether an image contains the organ regions of interest. While these weakly supervised methods have a common drawback. They do not incorporate prior knowledge that alleviates the lack of pixel-level information for segmentation. In this work, we propose a weakly supervised method based on prior knowledge for the segmentation of human organs. The proposed method was validated on three data sets of human organ segmentation. Experimental results show that the proposed image-level supervised segmentation method outperforms several state-of-the-art methods.
View details for DOI 10.1088/1361-6560/abde98
View details for PubMedID 33477123
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Molecular Imaging of Infective Endocarditis With 6''-[18F]Fluoromaltotriose Positron Emission Tomography-Computed Tomography.
Circulation
2020; 141 (21): 1729–31
View details for DOI 10.1161/CIRCULATIONAHA.119.043924
View details for PubMedID 32453662
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The left ventricle undergoes biomechanical and gene expression changes in response to increased right ventricular pressure overload.
Physiological reports
2020; 8 (9): e14347
Abstract
Pulmonary hypertension (PH) results in right ventricular (RV) pressure overload and eventual failure. Current research efforts have focused on the RV while overlooking the left ventricle (LV), which is responsible for mechanically assisting the RV during contraction. The objective of this study is to evaluate the biomechanical and gene expression changes occurring in the LV due to RV pressure overload in a mouse model. Nine male mice were divided into two groups: (a) pulmonary arterial banding (PAB, N=4) and (b) sham surgery (Sham, N=5). Tagged and steady-state free precision cardiac MRI was performed on each mouse at 1, 4, and 7weeks after surgery. At/week7, the mice were euthanized following right/left heart catheterization with RV/LV tissue harvested for histology and gene expression (using RT-PCR) studies. Compared to Sham mice, the PAB group revealed a significantly decreased LV and RV ejection fraction, and LV maximum torsion and torsion rate, within the first week after banding. In the PAB group, there was also a slight but significant increase in LV perivascular fibrosis, which suggests elevated myocardial stress. LV fibrosis was also accompanied with changes in gene expression in the hypertensive group, which was correlated with LV contractile mechanics. In fact, principal component (PC) analysis of LV gene expression effectively separated Sham and PAB mice along PC2. Changes in LV contractile mechanics were also significantly correlated with unfavorable changes in RV contractile mechanics, but a direct causal relationship was not established. In conclusion, a purely biomechanical insult of RV pressure overload resulted in biomechanical and transcriptional changes in both the RV and LV. Given that the RV relies on the LV for contractile energy assistance, considering the LV could provide prognostic and therapeutic targets for treating RV failure in PH.
View details for DOI 10.14814/phy2.14347
View details for PubMedID 32367677
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Modeling Secondary Iron Overload Cardiomyopathy with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Cell reports
2020; 32 (2): 107886
Abstract
Excessive iron accumulation in the heart causes iron overload cardiomyopathy (IOC), which initially presents as diastolic dysfunction and arrhythmia but progresses to systolic dysfunction and end-stage heart failure when left untreated. However, the mechanisms of iron-related cardiac injury and how iron accumulates in human cardiomyocytes are not well understood. Herein, using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we model IOC and screen for drugs to rescue the iron overload phenotypes. Human iPSC-CMs under excess iron exposure recapitulate early-stage IOC, including oxidative stress, arrhythmia, and contractile dysfunction. We find that iron-induced changes in calcium kinetics play a critical role in dysregulation of CM functions. We identify that ebselen, a selective divalent metal transporter 1 (DMT1) inhibitor and antioxidant, could prevent the observed iron overload phenotypes, supporting the role of DMT1 in iron uptake into the human myocardium. These results suggest that ebselen may be a potential preventive and therapeutic agent for treating patients with secondary iron overload.
View details for DOI 10.1016/j.celrep.2020.107886
View details for PubMedID 32668256
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Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates.
Developmental cell
2020
Abstract
Transposable elements (TEs) comprise nearly half of the human genome and are often transcribed or exhibit cis-regulatory properties with unknown function in specific processes such as heart development. In the case of endogenous retroviruses (ERVs), a TE subclass, experimental interrogation is constrained as many are primate-specific or human-specific. Here, we use primate pluripotent stem-cell-derived cardiomyocytes that mimic fetal cardiomyocytes in vitro to discover hundreds of ERV transcripts from the primate-specific MER41 family, some of which are regulated by the cardiogenic transcription factor TBX5. The most significant of these are located within BANCR, a long non-coding RNA (lncRNA) exclusively expressed in primate fetal cardiomyocytes. Functional studies reveal that BANCR promotes cardiomyocyte migration in vitro and ventricular enlargement in vivo. We conclude that recently evolved TE loci such as BANCR may represent potent de novo developmental regulatory elements that can be interrogated with species-matching pluripotent stem cell models.
View details for DOI 10.1016/j.devcel.2020.07.006
View details for PubMedID 32763147
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Molecular imaging of cardiac regenerative medicine
Current Opinion in Biomedical Engineering
2019; 9: 66-73
View details for DOI 10.1016/j.cobme.2019.04.006
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An in Vivo miRNA Delivery System for Restoring Infarcted Myocardium.
ACS nano
2019
Abstract
A major challenge in myocardial infarction (MI)-related heart failure treatment using microRNA is the efficient and sustainable delivery of miRNAs into myocardium to achieve functional improvement through stimulation of intrinsic myocardial restoration. In this study, we established an in vivo delivery system using polymeric nanoparticles to carry miRNA (miNPs) for localized delivery within a shear-thinning injectable hydrogel. The miNPs triggered proliferation of human embryonic stem cell-derived cardiomyocytes and endothelial cells (hESC-CMs and hESC-ECs) and promoted angiogenesis in hypoxic conditions, showing significantly lower cytotoxicity than Lipofectamine. Furthermore, one injected dose of hydrogel/miNP in MI rats demonstrated significantly improved cardiac functions: increased ejection fraction from 45% to 64%, reduced scar size from 20% to 10%, and doubled capillary density in the border zone compared to the control group at 4 weeks. As such, our results indicate that this injectable hydrogel/miNP composite can deliver miRNA to restore injured myocardium efficiently and safely.
View details for DOI 10.1021/acsnano.9b03343
View details for PubMedID 31149806
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Radiolabeled Duramycin Promising Translational Imaging of Myocardial Apoptosis
JACC-CARDIOVASCULAR IMAGING
2018; 11 (12): 1834-1836
View details for DOI 10.1016/j.jcmg.2017.12.009
View details for Web of Science ID 000451932700016
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Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix.
Nature biomedical engineering
2018; 2 (2): 104-113
Abstract
Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen-dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury. The biomaterial can serve as a generic delivery system to improve functional outcomes in cell-replacement therapy.
View details for DOI 10.1038/s41551-018-0191-4
View details for PubMedID 29721363
View details for PubMedCentralID PMC5927627
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Radiolabeled Duramycin: Promising Translational Imaging of Myocardial Apoptosis.
JACC. Cardiovascular imaging
2018
View details for PubMedID 29454760
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Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction.
Stem cell reports
2018; 10 (2): 422–35
Abstract
Non-human primates (NHPs) can serve as a human-like model to study cell therapy using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). However, whether the efficacy of NHP and human iPSC-CMs is mechanistically similar remains unknown. To examine this, RNU rats received intramyocardial injection of 1 × 107NHP or human iPSC-CMs or the same number of respective fibroblasts or PBS control (n = 9-14/group) at 4 days after 60-min coronary artery occlusion-reperfusion. Cardiac function and left ventricular remodeling were similarly improved in both iPSC-CM-treated groups. To mimic the ischemic environment in the infarcted heart, both cultured NHP and human iPSC-CMs underwent 24-hr hypoxia in vitro. Both cells and media were collected, and similarities in transcriptomic as well as metabolomic profiles were noted between both groups. In conclusion, both NHP and human iPSC-CMs confer similar cardioprotection in a rodent myocardial infarction model through relatively similar mechanisms via promotion of cell survival, angiogenesis, and inhibition of hypertrophy and fibrosis.
View details for PubMedID 29398480
View details for PubMedCentralID PMC5830958
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Tracking Human Pluripotent Stem Cell-Derived Cardiomyocytes in Post-Myocardial Infarction Heart with Photoacoustic Imaging
LIPPINCOTT WILLIAMS & WILKINS. 2017
View details for Web of Science ID 000520552700282
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Photoacoustic Imaging of Embryonic Stem Cell-Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles
Advanced Functional Materials
2017
View details for DOI 10.1002/adfm.201704939
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Imaging Cardiac Stem Cell Therapy
Cardiac Regeneration
Springer. 2017: 241–258
View details for DOI 10.1007/978-3-319-56106-6_11
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Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- Versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Stem cells (Dayton, Ohio)
2017
Abstract
Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome.Human ESCs and iPSCs were differentiated into cardiomyocytes using small molecule inhibitors. Fluorescence-activated cell sorting (FACS) analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable to the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective.We demonstrate for the first time that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future. This article is protected by copyright. All rights reserved.
View details for PubMedID 28710827
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Detection and delineation of squamous neoplasia with hyperspectral imaging in a mouse model of tongue carcinogenesis.
Journal of biophotonics
2017
Abstract
yperspectral imaging (HSI) holds the potential for the noninvasive detection of cancers. Oral cancers are often diagnosed at a late stage when treatment is less effective and the mortality and morbidity rates are high. Early detection of oral cancer is, therefore, crucial in order to improve the clinical outcomes. To investigate the potential of HSI as a non-invasive diagnostic tool, an animal study was designed to acquire hyperspectral images of in vivo and ex vivo mouse tongues from a chemically induced tongue carcinogenesis model. A variety of machine-learning algorithms, including discriminant analysis, ensemble learning, and support vector machines, were evaluated for tongue neoplasia detection using HSI and were validated by the reconstructed pathological gold-standard maps. The diagnostic performance of HSI, autofluorescence imaging, and fluorescence imaging were compared in this study. Color-coded prediction maps were generated to display the predicted location and distribution of premalignant and malignant lesions. This study suggests that hyperspectral imaging combined with machine-learning techniques can provide a non-invasive tool for the quantitative detection and delineation of squamous neoplasia. Detection and delineation of tongue neoplasia with hyperspectral imaging validated by the pathological gold standard.
View details for DOI 10.1002/jbio.201700078
View details for PubMedID 28921845
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Magnetic Resonance Imaging of Cardiac Strain Pattern Following Transplantation of Human Tissue Engineered Heart Muscles
CIRCULATION-CARDIOVASCULAR IMAGING
2016; 9 (11)
Abstract
The use of tissue engineering approaches in combination with exogenously produced cardiomyocytes offers the potential to restore contractile function after myocardial injury. However, current techniques assessing changes in global cardiac performance after such treatments are plagued by relatively low detection ability. Since the treatment is locally performed, this detection could be improved by myocardial strain imaging that measures regional contractility.Tissue engineered heart muscles (EHMs) were generated by casting human embryonic stem cell-derived cardiomyocytes with collagen in preformed molds. EHMs were transplanted (n=12) to cover infarct and border zones of recipient rat hearts 1 month after ischemia reperfusion injury. A control group (n=10) received only sham placement of sutures without EHMs. To assess the efficacy of EHMs, magnetic resonance imaging and ultrasound-based strain imaging were performed before and 4 weeks after transplantation. In addition to strain imaging, global cardiac performance was estimated from cardiac magnetic resonance imaging. Although no significant differences were found for global changes in left ventricular ejection fraction (control -9.6±1.3% versus EHM -6.2±1.9%; P=0.17), regional myocardial strain from tagged magnetic resonance imaging was able to detect preserved systolic function in EHM-treated animals compared with control (control 4.4±1.0% versus EHM 1.0±0.6%; P=0.04). However, ultrasound-based strain failed to detect any significant change (control 2.1±3.0% versus EHM 6.3±2.9%; P=0.46).This study highlights the feasibility of using cardiac strain from tagged magnetic resonance imaging to assess functional changes in rat models following localized regenerative therapies, which may not be detected by conventional measures of global systolic performance.
View details for DOI 10.1161/CIRCIMAGING.116.004731
View details for Web of Science ID 000388482500003
View details for PubMedID 27903535
View details for PubMedCentralID PMC5378466
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Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas
STEM CELL REPORTS
2016; 6 (2): 176-187
Abstract
The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking.
View details for DOI 10.1016/j.stemcr.2015.12.008
View details for PubMedID 26777057
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Framework for hyperspectral image processing and quantification for cancer detection during animal tumor surgery
JOURNAL OF BIOMEDICAL OPTICS
2015; 20 (12)
Abstract
Hyperspectral imaging (HSI) is an imaging modality that holds strong potential for rapid cancer detection during image-guided surgery. But the data from HSI often needs to be processed appropriately in order to extract the maximum useful information that differentiates cancer from normal tissue. We proposed a framework for hyperspectral image processing and quantification, which includes a set of steps including image preprocessing, glare removal, feature extraction, and ultimately image classification. The framework has been tested on images from mice with head and neck cancer, using spectra from 450- to 900-nm wavelength. The image analysis computed Fourier coefficients, normalized reflectance, mean, and spectral derivatives for improved accuracy. The experimental results demonstrated the feasibility of the hyperspectral image processing and quantification framework for cancer detection during animal tumor surgery, in a challenging setting where sensitivity can be low due to a modest number of features present, but potential for fast image classification can be high. This HSI approach may have potential application in tumor margin assessment during image-guided surgery, where speed of assessment may be the dominant factor.
View details for DOI 10.1117/1.JBO.20.12.126012
View details for Web of Science ID 000368440300037
View details for PubMedID 26720879
View details for PubMedCentralID PMC4691647
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Simulating cardiac ultrasound image based on MR diffusion tensor imaging
MEDICAL PHYSICS
2015; 42 (9): 5144-5156
Abstract
Cardiac ultrasound simulation can have important applications in the design of ultrasound systems, understanding the interaction effect between ultrasound and tissue and setting the ground truth for validating quantification methods. Current ultrasound simulation methods fail to simulate the myocardial intensity anisotropies. New simulation methods are needed in order to simulate realistic ultrasound images of the heart.The proposed cardiac ultrasound image simulation method is based on diffusion tensor imaging (DTI) data of the heart. The method utilizes both the cardiac geometry and the fiber orientation information to simulate the anisotropic intensities in B-mode ultrasound images. Before the simulation procedure, the geometry and fiber orientations of the heart are obtained from high-resolution structural MRI and DTI data, respectively. The simulation includes two important steps. First, the backscatter coefficients of the point scatterers inside the myocardium are processed according to the fiber orientations using an anisotropic model. Second, the cardiac ultrasound images are simulated with anisotropic myocardial intensities. The proposed method was also compared with two other nonanisotropic intensity methods using 50 B-mode ultrasound image volumes of five different rat hearts. The simulated images were also compared with the ultrasound images of a diseased rat heart in vivo. A new segmental evaluation method is proposed to validate the simulation results. The average relative errors (AREs) of five parameters, i.e., mean intensity, Rayleigh distribution parameter σ, and first, second, and third quartiles, were utilized as the evaluation metrics. The simulated images were quantitatively compared with real ultrasound images in both ex vivo and in vivo experiments.The proposed ultrasound image simulation method can realistically simulate cardiac ultrasound images of the heart using high-resolution MR-DTI data. The AREs of their proposed method are 19% for the mean intensity, 17.7% for the scale parameter of Rayleigh distribution, 36.8% for the first quartile of the image intensities, 25.2% for the second quartile, and 19.9% for the third quartile. In contrast, the errors of the other two methods are generally five times more than those of their proposed method.The proposed simulation method uses MR-DTI data and realistically generates cardiac ultrasound images with anisotropic intensities inside the myocardium. The ultrasound simulation method could provide a tool for many potential research and clinical applications in cardiac ultrasound imaging.
View details for DOI 10.1118/1.4927788
View details for Web of Science ID 000360645000017
View details for PubMedID 26328966
View details for PubMedCentralID PMC4537486
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DTI template-based estimation of cardiac fiber orientations from 3D ultrasound
MEDICAL PHYSICS
2015; 42 (6): 2915-2924
Abstract
Cardiac muscle fibers directly affect the mechanical, physiological, and pathological properties of the heart. Patient-specific quantification of cardiac fiber orientations is an important but difficult problem in cardiac imaging research. In this study, the authors proposed a cardiac fiber orientation estimation method based on three-dimensional (3D) ultrasound images and a cardiac fiber template that was obtained from magnetic resonance diffusion tensor imaging (DTI).A DTI template-based framework was developed to estimate cardiac fiber orientations from 3D ultrasound images using an animal model. It estimated the cardiac fiber orientations of the target heart by deforming the fiber orientations of the template heart, based on the deformation field of the registration between the ultrasound geometry of the target heart and the MRI geometry of the template heart. In the experiments, the animal hearts were imaged by high-frequency ultrasound, T1-weighted MRI, and high-resolution DTI.The proposed method was evaluated by four different parameters: Dice similarity coefficient (DSC), target errors, acute angle error (AAE), and inclination angle error (IAE). Its ability of estimating cardiac fiber orientations was first validated by a public database. Then, the performance of the proposed method on 3D ultrasound data was evaluated by an acquired database. Their average values were 95.4% ± 2.0% for the DSC of geometric registrations, 21.0° ± 0.76° for AAE, and 19.4° ± 1.2° for IAE of fiber orientation estimations. Furthermore, the feasibility of this framework was also performed on 3D ultrasound images of a beating heart.The proposed framework demonstrated the feasibility of using 3D ultrasound imaging to estimate cardiac fiber orientation of in vivo beating hearts and its further improvements could contribute to understanding the dynamic mechanism of the beating heart and has the potential to help diagnosis and therapy of heart disease.
View details for DOI 10.1118/1.4921121
View details for Web of Science ID 000356998300019
View details for PubMedID 26127045
View details for PubMedCentralID PMC4441706
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Spectral-spatial classification for noninvasive cancer detection using hyperspectral imaging
JOURNAL OF BIOMEDICAL OPTICS
2014; 19 (10)
Abstract
Early detection of malignant lesions could improve both survival and quality of life of cancer patients. Hyperspectral imaging (HSI) has emerged as a powerful tool for noninvasive cancer detection and diagnosis, with the advantage of avoiding tissue biopsy and providing diagnostic signatures without the need of a contrast agent in real time. We developed a spectral-spatial classification method to distinguish cancer from normal tissue on hyperspectral images. We acquire hyperspectral reflectance images from 450 to 900 nm with a 2-nm increment from tumor-bearing mice. In our animal experiments, the HSI and classification method achieved a sensitivity of 93.7% and a specificity of 91.3%. The preliminary study demonstrated that HSI has the potential to be applied in vivo for noninvasive detection of tumors.
View details for DOI 10.1117/1.JBO.19.10.106004
View details for Web of Science ID 000345837200021
View details for PubMedID 25277147
View details for PubMedCentralID PMC4183763
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Measuring myofiber orientations from high-frequency ultrasound images using multiscale decompositions
PHYSICS IN MEDICINE AND BIOLOGY
2014; 59 (14): 3907-3924
Abstract
High-frequency ultrasound (HFU) has the ability to image both skeletal and cardiac muscles. The quantitative assessment of these myofiber orientations has a number of applications in both research and clinical examinations; however, difficulties arise due to the severe speckle noise contained in the HFU images. Thus, for the purpose of automatically measuring myofiber orientations from two-dimensional HFU images, we propose a two-step multiscale image decomposition method. It combines a nonlinear anisotropic diffusion filter and a coherence enhancing diffusion filter to extract myofibers. This method has been verified by ultrasound data from simulated phantoms, excised fiber phantoms, specimens of porcine hearts, and human skeletal muscles in vivo. The quantitative evaluations of both phantoms indicated that the myofiber measurements of our proposed method were more accurate than other methods. The myofiber orientations extracted from different layers of the porcine hearts matched the prediction of an established cardiac mode and demonstrated the feasibility of extracting cardiac myofiber orientations from HFU images ex vivo. Moreover, HFU also demonstrated the ability to measure myofiber orientations in vivo.
View details for DOI 10.1088/0031-9155/59/14/3907
View details for Web of Science ID 000338771300016
View details for PubMedID 24957945
View details for PubMedCentralID PMC4137038
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Targeted Iron-Oxide Nanoparticle for Photodynamic Therapy and Imaging of Head and Neck Cancer
ACS NANO
2014; 8 (7): 6620-6632
Abstract
Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic.
View details for DOI 10.1021/nn501652j
View details for Web of Science ID 000339463100016
View details for PubMedID 24923902
View details for PubMedCentralID PMC4155749
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Automatic segmentation of right ventricular ultrasound images using sparse matrix transform and a level set
PHYSICS IN MEDICINE AND BIOLOGY
2013; 58 (21): 7609-7624
Abstract
An automatic segmentation framework is proposed to segment the right ventricle (RV) in echocardiographic images. The method can automatically segment both epicardial and endocardial boundaries from a continuous echocardiography series by combining sparse matrix transform, a training model, and a localized region-based level set. First, the sparse matrix transform extracts main motion regions of the myocardium as eigen-images by analyzing the statistical information of the images. Second, an RV training model is registered to the eigen-images in order to locate the position of the RV. Third, the training model is adjusted and then serves as an optimized initialization for the segmentation of each image. Finally, based on the initializations, a localized, region-based level set algorithm is applied to segment both epicardial and endocardial boundaries in each echocardiograph. Three evaluation methods were used to validate the performance of the segmentation framework. The Dice coefficient measures the overall agreement between the manual and automatic segmentation. The absolute distance and the Hausdorff distance between the boundaries from manual and automatic segmentation were used to measure the accuracy of the segmentation. Ultrasound images of human subjects were used for validation. For the epicardial and endocardial boundaries, the Dice coefficients were 90.8 ± 1.7% and 87.3 ± 1.9%, the absolute distances were 2.0 ± 0.42 mm and 1.79 ± 0.45 mm, and the Hausdorff distances were 6.86 ± 1.71 mm and 7.02 ± 1.17 mm, respectively. The automatic segmentation method based on a sparse matrix transform and level set can provide a useful tool for quantitative cardiac imaging.
View details for DOI 10.1088/0031-9155/58/21/7609
View details for Web of Science ID 000326377100012
View details for PubMedID 24107618
View details for PubMedCentralID PMC3925785
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Measuring body layer vibration of vocal folds by high-frame-rate ultrasound synchronized with a modified electroglottograph
JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
2013; 134 (1): 528-538
Abstract
The body-cover concept suggests that the vibration of body layer is an indispensable component of vocal fold vibration. To quantify this vibration, a synchronized system composed of a high-frame-rate ultrasound and a modified electroglottograph (EGG) was employed in this paper to simultaneously image the body layer vibration and record the vocal fold vibration phase information during natural phonations. After data acquisition, the displacements of in vivo body layer vibrations were measured from the ultrasonic radio frequency data, and the temporal reconstruction method was used to enhance the measurement accuracy. Results showed that the modified EGG, the waveform and characteristic points of which were identical to the conventional EGG, resolved the position conflict between the ultrasound transducer and EGG electrodes. The location and range of the vibrating body layer in the estimated displacement image were more clear and discernible than in the ultrasonic B-mode image. Quantitative analysis for vibration features of the body layer demonstrated that the body layer moved as a unit in the superior-inferior direction during the phonation of normal chest registers.
View details for DOI 10.1121/1.4807652
View details for Web of Science ID 000321908500071
View details for PubMedID 23862828
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Characterization of the homogeneous tissue mixture approximation in breast imaging dosimetry
MEDICAL PHYSICS
2012; 39 (8): 5050-5059
Abstract
To compare the estimate of normalized glandular dose in mammography and breast CT imaging obtained using the actual glandular tissue distribution in the breast to that obtained using the homogeneous tissue mixture approximation.Twenty volumetric images of patient breasts were acquired with a dedicated breast CT prototype system and the voxels in the breast CT images were automatically classified into skin, adipose, and glandular tissue. The breasts in the classified images underwent simulated mechanical compression to mimic the conditions present during mammographic acquisition. The compressed thickness for each breast was set to that achieved during each patient's last screening cranio-caudal (CC) acquisition. The volumetric glandular density of each breast was computed using both the compressed and uncompressed classified images, and additional images were created in which all voxels representing adipose and glandular tissue were replaced by a homogeneous mixture of these two tissues in a proportion corresponding to each breast's volumetric glandular density. All four breast images (compressed and uncompressed; heterogeneous and homogeneous tissue) were input into Monte Carlo simulations to estimate the normalized glandular dose during mammography (compressed breasts) and dedicated breast CT (uncompressed breasts). For the mammography simulations the x-ray spectra used was that used during each patient's last screening CC acquisition. For the breast CT simulations, two x-ray spectra were used, corresponding to the x-ray spectra with the lowest and highest energies currently being used in dedicated breast CT prototype systems under clinical investigation. The resulting normalized glandular dose for the heterogeneous and homogeneous versions of each breast for each modality was compared.For mammography, the normalized glandular dose based on the homogeneous tissue approximation was, on average, 27% higher than that estimated using the true heterogeneous glandular tissue distribution (Wilcoxon Signed Rank Test p = 0.00046). For dedicated breast CT, the overestimation of normalized glandular dose was, on average, 8% (49 kVp spectrum, p = 0.00045) and 4% (80 kVp spectrum, p = 0.000089). Only two cases in mammography and two cases in dedicated breast CT with a tube voltage of 49 kVp resulted in lower dose estimates for the homogeneous tissue approximation compared to the heterogeneous tissue distribution.The normalized glandular dose based on the homogeneous tissue mixture approximation results in a significant overestimation of dose to the imaged breast. This overestimation impacts the use of dose estimates in absolute terms, such as for risk estimates, and may impact some comparative studies, such as when modalities or techniques with different x-ray energies are used. The error introduced by the homogeneous tissue mixture approximation in higher energy x-ray modalities, such as dedicated breast CT, although statistically significant, may not be of clinical concern. Further work is required to better characterize this overestimation and potentially develop new metrics or correction factors to better estimate the true glandular dose to breasts undergoing imaging with ionizing radiation.
View details for DOI 10.1118/1.4737025
View details for Web of Science ID 000307917600043
View details for PubMedID 22894430
View details for PubMedCentralID PMC3416880
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Measuring Body-Cover Vibration of Vocal Folds Based on High-Frame-Rate Ultrasonic Imaging and High-Speed Video
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2011; 58 (8)
Abstract
Vibration of vocal folds is a body-cover layered vibration pattern due to the two-layer tissue structures of vocal folds. A method based on a synchronal imaging system is proposed in order to image and measure the body-cover vibration pattern of vocal folds. This imaging system contains two parts: high-frame-rate ultrasonic imaging part and high-speed video part, which can synchronously image the vibration of the body and cover layers a thigh speed. Then, image analysis methods are applied to measure the body-cover vibration of vocal folds from both recorded image sequences. We analyze characteristics of body-layer vibration based on the measurements from designed experiments. Moreover, these results meet simulations of a body-cover model.
View details for DOI 10.1109/TBME.2011.2157156
View details for Web of Science ID 000293700800029
View details for PubMedID 21606016
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Improving Reliability and Accuracy of Vibration Parameters of Vocal Folds Based on High-Speed Video and Electroglottography
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
2009; 56 (6): 1744-1754
Abstract
Quantified vibration parameters of vocal folds, including parameters directly extracted from high-speed video (HSV) and electroglottography (EGG), and inverse parameters based on models, can accurately describe the mechanism of phonation and also classify the abnormal in clinics. In order to improve the reliability and accuracy of these parameters, this paper provides a method based on an integrated recording system. This system includes two parts: HSV and EGG, which can record vibration information of vocal folds simultaneously. An image processing approach that bases on Zernike moments operator and an improved level set algorithm is proposed to detect glottal edges at subpixel-level aiming at image series recorded by HSV. An approach is also introduced for EGG data to extract three kinds of characteristic points for special vibration instants. Finally, inverse parameters of vocal folds can be optimized by a genetic algorithm based on the experimental vibration behaviors synthesized with these parameters and the simulations of a two-mass model. The results of a normal phonation experiment indicate that the parameters extracted by this method are more accurate and reliable than those extracted by general methods, which were only on the basis of HSV data and with pixel-level processing approaches in former studies.
View details for DOI 10.1109/TBME.2009.2015772
View details for Web of Science ID 000266990400018
View details for PubMedID 19272979