Publications by authors named "Chenggong Yan"

25 Publications

  • Page 1 of 1

Cycle-Consistent Generative Adversarial Network: Effect on Radiation Dose Reduction and Image Quality Improvement in Ultralow-Dose CT for Evaluation of Pulmonary Tuberculosis.

Korean J Radiol 2021 Mar 9. Epub 2021 Mar 9.

The D-Lab, Department of Precision Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The The Netherlands.

Objective: To investigate the image quality of ultralow-dose CT (ULDCT) of the chest reconstructed using a cycle-consistent generative adversarial network (CycleGAN)-based deep learning method in the evaluation of pulmonary tuberculosis.

Materials And Methods: Between June 2019 and November 2019, 103 patients (mean age, 40.8 ± 13.6 years; 61 men and 42 women) with pulmonary tuberculosis were prospectively enrolled to undergo standard-dose CT (120 kVp with automated exposure control), followed immediately by ULDCT (80 kVp and 10 mAs). The images of the two successive scans were used to train the CycleGAN framework for image-to-image translation. The denoising efficacy of the CycleGAN algorithm was compared with that of hybrid and model-based iterative reconstruction. Repeated-measures analysis of variance and Wilcoxon signed-rank test were performed to compare the objective measurements and the subjective image quality scores, respectively.

Results: With the optimized CycleGAN denoising model, using the ULDCT images as input, the peak signal-to-noise ratio and structural similarity index improved by 2.0 dB and 0.21, respectively. The CycleGAN-generated denoised ULDCT images typically provided satisfactory image quality for optimal visibility of anatomic structures and pathological findings, with a lower level of image noise (mean ± standard deviation [SD], 19.5 ± 3.0 Hounsfield unit [HU]) than that of the hybrid (66.3 ± 10.5 HU, < 0.001) and a similar noise level to model-based iterative reconstruction (19.6 ± 2.6 HU, > 0.908). The CycleGAN-generated images showed the highest contrast-to-noise ratios for the pulmonary lesions, followed by the model-based and hybrid iterative reconstruction. The mean effective radiation dose of ULDCT was 0.12 mSv with a mean 93.9% reduction compared to standard-dose CT.

Conclusion: The optimized CycleGAN technique may allow the synthesis of diagnostically acceptable images from ULDCT of the chest for the evaluation of pulmonary tuberculosis.
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http://dx.doi.org/10.3348/kjr.2020.0988DOI Listing
March 2021

Structural and functional radiomics for lung cancer.

Eur J Nucl Med Mol Imaging 2021 Mar 11. Epub 2021 Mar 11.

The D-Lab, Department of Precision Medicine, GROW-School for Oncology, Maastricht University Medical Centre+, 6229, Maastricht, The Netherlands.

Introduction: Lung cancer ranks second in new cancer cases and first in cancer-related deaths worldwide. Precision medicine is working on altering treatment approaches and improving outcomes in this patient population. Radiological images are a powerful non-invasive tool in the screening and diagnosis of early-stage lung cancer, treatment strategy support, prognosis assessment, and follow-up for advanced-stage lung cancer. Recently, radiological features have evolved from solely semantic to include (handcrafted and deep) radiomic features. Radiomics entails the extraction and analysis of quantitative features from medical images using mathematical and machine learning methods to explore possible ties with biology and clinical outcomes.

Methods: Here, we outline the latest applications of both structural and functional radiomics in detection, diagnosis, and prediction of pathology, gene mutation, treatment strategy, follow-up, treatment response evaluation, and prognosis in the field of lung cancer.

Conclusion: The major drawbacks of radiomics are the lack of large datasets with high-quality data, standardization of methodology, the black-box nature of deep learning, and reproducibility. The prerequisite for the clinical implementation of radiomics is that these limitations are addressed. Future directions include a safer and more efficient model-training mode, merge multi-modality images, and combined multi-discipline or multi-omics to form "Medomics."
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http://dx.doi.org/10.1007/s00259-021-05242-1DOI Listing
March 2021

Clinical significance of evaluation of collateral circulation in short-term prognosis of wake-up stroke patients.

Adv Clin Exp Med 2021 Feb;30(2):183-188

Department of Neurology, Pudong New Area People's Hospital, Shanghai, China.

Background: In recent years, the clinical significance of collateral circulation in vascular embolism has been gradually found.

Objectives: To investigate the relationship between collateral circulation and short-term prognosis of wake-up stroke patients.

Material And Methods: The present observational study enrolled 269 cases of wake-up ischemic stroke patients. All patients presented with mismatched low perfusion volume/main infraction volume and received thrombolytic therapy after admission. The hemorrhagic transformation rate was recorded. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grading was used for evaluation of collateral circulation. The stroke condition was determined using the National Institutes of Health Stroke Scale (NIHSS). The Barthel Index (BI) score was used for measurement of quality of life. The Modified Rankin Scale (mRS) was used for measurement of prognosis.

Results: The hypertension, diabetes and current smoker rates were significantly higher. The baseline NHISS scores and NIHSS scores after 24 h were remarkably lower. The NIHSS scores were markedly lower in ASITN/SIR grade 2-3 patients compared with ASITN/SIR grade 0-1 patients at 1 week, 2 weeks, 4 weeks, and 3 months after treatment. Patients with ASITN/SIR grade 2-3 had lower mRS score and higher BI scores. The ASITN/SIR grade was an independent risk factor for bad prognosis of wake-up ischemic stroke patients in 3 months.

Conclusions: Collateral circulation condition may be associated with short-term prognosis of wake-up stroke patients. Patients with worse collateral circulation may present higher risk for bad short-term prognosis.
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http://dx.doi.org/10.17219/acem/121927DOI Listing
February 2021

Ultrasmall Superparamagnetic Iron Oxide Labeled Silk Fibroin/Hydroxyapatite Multifunctional Scaffold Loaded With Bone Marrow-Derived Mesenchymal Stem Cells for Bone Regeneration.

Front Bioeng Biotechnol 2020 30;8:697. Epub 2020 Jun 30.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Numerous tissue-engineered constructs have been investigated as bone scaffolds in regenerative medicine. However, it remains challenging to non-invasively monitor the biodegradation and remodeling of bone grafts after implantation. Herein, silk fibroin/hydroxyapatite scaffolds incorporated with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were successfully synthesized, characterized, and implanted subcutaneously into the back of nude mice. The USPIO labeled scaffolds showed good three-dimensional porous structures and mechanical property, thermal stability for bone repair. After loaded with bone marrow-derived mesenchymal stem cells (BMSCs), the multifunctional scaffolds promoted cell adhesion and growth, and facilitated osteogenesis by showing increased levels of alkaline phosphatase activity and up-regulation of osteoblastic genes. Furthermore, quantitative magnetic resonance imaging (MRI) results provided valuable information on scaffolds degradation and bone formation simultaneously, which was further confirmed by computed tomography and histological examination. These findings demonstrated that the incorporation of USPIO into BMSCs-loaded multifunctional scaffold system could be feasible to noninvasively monitor bone regeneration by quantitative MRI. This tissue engineering strategy provides a promising tool for translational application of bone defect repair in clinical scenarios.
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http://dx.doi.org/10.3389/fbioe.2020.00697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338306PMC
June 2020

Recommendations for coronavirus disease 2019 (COVID-19) prevention and infection control in the radiology department: Chinese experience.

Clin Imaging 2021 Jan 1;69:33-36. Epub 2020 Jul 1.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, People's Republic of China; Quality Control Center of Radiology in Guangdong Province, No. 123 Huifu Road West, Guangzhou 510180, Guangdong, People's Republic of China. Electronic address:

The coronavirus disease 2019 (COVID-19) outbreak, first reported in Wuhan, China, is gradually spreading worldwide. For diagnosis, chest computed tomography is a conventional, noninvasive imaging modality that is very accurate for detection and evaluation of pneumonia and is an important adjunct to real-time reverse transcription polymerase chain reaction diagnosis of the virus. Previous studies have reported typical computed tomography imaging features indicative of COVID-19, such as multifocal ground-glass opacities with or without consolidation. With the sharply increasing demand for computed tomography examination during the outbreak, ensuring appropriate infection control in radiology departments is challenging. Thus, advanced training and education in standardized infection control and prevention practice are essential. The purpose of this brief review is to summarize such training and education for clinical management of this outbreak for radiology department personnel. We will describe standard transmission-based precautions, workflow for computed tomography examination of fever patients, and decontamination management of a radiology department.
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http://dx.doi.org/10.1016/j.clinimag.2020.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327467PMC
January 2021

Development of a clinical decision support system for severity risk prediction and triage of COVID-19 patients at hospital admission: an international multicentre study.

Eur Respir J 2020 08 20;56(2). Epub 2020 Aug 20.

The D-Lab, Dept of Precision Medicine, GROW - School for Oncology, Maastricht University Medical Center+, Maastricht, The Netherlands.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality.

Objective: To develop and validate a machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission.

Method: 725 patients were used to train and validate the model. This included a retrospective cohort from Wuhan, China of 299 hospitalised COVID-19 patients from 23 December 2019 to 13 February 2020, and five cohorts with 426 patients from eight centres in China, Italy and Belgium from 20 February 2020 to 21 March 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix.

Results: In the retrospective cohort, the median age was 50 years and 137 (45.8%) were male. In the five test cohorts, the median age was 62 years and 236 (55.4%) were male. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.93, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 55.0% to 88.0%, most of which performed better than the pneumonia severity index. The cut-off values of the low-, medium- and high-risk probabilities were 0.21 and 0.80. The online calculators can be found at www.covid19risk.ai.

Conclusion: The machine-learning model, nomogram and online calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission.
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http://dx.doi.org/10.1183/13993003.01104-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331655PMC
August 2020

Intravoxel incoherent motion diffusion-weighted MRI in patients with breast cancer: Correlation with tumor stroma characteristics.

Eur J Radiol 2019 Nov 20;120:108686. Epub 2019 Sep 20.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.

Purpose: To determine whether imaging parameters derived from intravoxel incoherent motion (IVIM) diffusion weighted imaging (DWI) vary according to tumor-stroma ratio(TSR) or dominant stroma type of breast cancer.

Methods: We prospectively enrolled 77 patients with breast cancer who underwent IVIM DWI on a 3.0 T MR scanner. The values of IVIM parameters (D, D* and f) were measured. After surgery, TSR or dominant stroma type was evaluated. The relationship between imaging parameters and tumor stroma characteristics was analyzed.

Results: The mean D and f values were lower in stroma-poor tumor than in stroma-rich tumor (P = 0.012, 0.015). The mean D value was lower in the collagen-dominant type than in fibroblast-dominant or lymphocyte-dominant type (P = 0.032, 0.043). According to multivariate linear regression analyses, tumor size (P = 0.007), TSR (P = 0.008), dominant stroma type (collagen dominant, P = 0.012), and histological grade (P = 0.031) were independently correlated with D value; and tumor size (P = 0.011), TSR (P = 0.021) and histological grade (P = 0.037) were independently correlated with f value.

Conclusion: In breast cancer, D and f values show significant differences according to TSR, and D value is lower in collagen dominant type than in fibroblast dominant or lymphocyte dominant types.
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http://dx.doi.org/10.1016/j.ejrad.2019.108686DOI Listing
November 2019

Mitochondria-targeted aggregation-induced emission active near infrared fluorescent probe for real-time imaging.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Jan 6;224:117456. Epub 2019 Aug 6.

Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

Mitochondria are essential organelles in eukaryotic cells and act as the energy powerhouse and biosynthetic compartment. Fluorescent dyes are widely used powerful molecular tools for analytical sensing and optical imaging. Low photostability, short excitation and emission wavelengths, and aggregation-induced quenching effects restrict the application of traditional commercial mitochondrial fluorescent probes for bioimaging. In this study, using rhodamine as the acceptor and phenothiazine as the donor, we synthesized a novel mitochondrial-targeted near infrared (NIR) fluorescent probe, MIT-PZR. Due to low cytotoxicity, great photostability and high specificity for mitochondria targeting, MIT-PZR has enormous potential for cell imaging. Furthermore, with a sizeable Stokes shift (emission peak at 705 nm), MIT-PZR penetrated tissues providing stable red fluorescence for imaging in vivo. The histological assessment of various tissues after treatment with MIT-PZR indicated that it has good biocompatibility. Thus, MIT-PZR is a promising mitochondrial NIR fluorescent probe for future application in clinical diagnosis and modern biological research.
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http://dx.doi.org/10.1016/j.saa.2019.117456DOI Listing
January 2020

Preparation and characterization of 3D porous conductive scaffolds with magnetic resonance enhancement in tissue engineering.

Biomed Mater 2019 05 28;14(4):045013. Epub 2019 May 28.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, People's Republic of China.

Magnetic resonance imaging (MRI), as a diagnostic tool in tissue engineering, has received widespread attention because of its ability to consistently provide degradation and absorption of implants in vivo. For some specific human tissues and organs, such as nerves, muscles and myocardium, their regeneration requires tissue engineering scaffolds have a good electrical conductivity. Graphene oxide (GO) has been extensively studied as a conductive biomaterial having mechanical reinforcement. Based on the above, we propose an MRI conductive scaffold containing gelatin (Gel)/gelatin-polycaprolactone (Gel-PCL)/ultra-small paramagnetic iron oxide (USPIO)/graphene oxide (GO) (Gel/Gel-PCL/USPIO/GO). Their physical and chemical properties as well as biocompatibility are measured in vitro. The purpose of doping USPIO was developed for non-invasive monitoring of tissue engineered implants and tissue reconstruction. Functional modification of GO to match electrophysiological requirement. Co-culture with bone marrow mesenchymal stem cells showed good biocompatibility. Blood experiments have also demonstrated the feasibility of scaffolds as tissue engineered implants. The USPIO-labeled conductive scaffold, as an effective image-guided and electrically stimulating implant, appears to be a reconstruction platform for specific tissues and organs.
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http://dx.doi.org/10.1088/1748-605X/ab1d9cDOI Listing
May 2019

Ultralow-dose CT with knowledge-based iterative model reconstruction (IMR) in evaluation of pulmonary tuberculosis: comparison of radiation dose and image quality.

Eur Radiol 2019 Oct 29;29(10):5358-5366. Epub 2019 Mar 29.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China.

Objectives: To evaluate the image quality of ultralow-dose computed tomography (ULDCT) reconstructed with knowledge-based iterative model reconstruction (IMR) in patients with pulmonary tuberculosis (TB).

Methods: This IRB-approved prospective study enrolled 59 consecutive patients (mean age, 43.9 ± 16.6 years; F:M 18:41) with known or suspected pulmonary TB. Patients underwent a low-dose CT (LDCT) using automatic tube current modulation followed by an ULDCT using fixed tube current. Raw image data were reconstructed with filtered-back projection (FBP), hybrid iterative reconstruction (iDose), and IMR. Objective measurements including CT attenuation, image noise, and contrast-to-noise ratio (CNR) were assessed and compared using repeated-measures analysis of variance. Overall image quality and visualization of normal and pathological findings were subjectively scored on a five-point scale. Radiation output and subjective scores were compared by the paired Student t test and Wilcoxon signed-rank test, respectively.

Results: Compared with FBP and iDose, IMR yielded significantly lower noise and higher CNR values at both dose levels (p < 0.01). Subjective ratings for pathological findings including centrilobular nodules, consolidation, tree-in-bud, and cavity were significantly better with ULDCT IMR images than those with LDCT iDose images (p < 0.01), but blurred edges were observed. With IMR implementation, a 59% reduction of the mean effective dose was achieved with ULDCT (0.28 ± 0.02 mSv) compared with LDCT (0.69 ± 0.15 mSv) without impairing image quality (p < 0.001).

Conclusions: IMR offers considerable noise reduction and improvement in image quality for patients with pulmonary TB undergoing chest ULDCT at an effective dose of 0.28 mSv.

Key Points: • Radiation dose is a major concern for tuberculosis patients requiring repeated follow-up CT. • IMR allows substantial radiation dose reduction in chest CT without compromising image quality. • ULDCT reconstructed with IMR allows accurate depiction of CT features of pulmonary tuberculosis.
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http://dx.doi.org/10.1007/s00330-019-06129-4DOI Listing
October 2019

Detecting GPC3-Expressing Hepatocellular Carcinoma with L5 Peptide-Guided Pretargeting Approach: In Vitro and In Vivo MR Imaging Experiments.

Contrast Media Mol Imaging 2018 10;2018:9169072. Epub 2018 Sep 10.

Department of Medical Imaging Centre, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Objective: To investigate the potential of L5 peptide-guided pretargeting approach to identify GPC3-expressing hepatocellular carcinoma (HCC) using ultrasmall superparamagnetic iron oxide (USPIO) as the MR probe.

Methods: Immunofluorescence with carboxyfluorescein- (FAM-) labeled L5 peptide was performed in HepG2 cells. Polyethylene glycol-modified USPIO (PEG-USPIO) and its conjugation with streptavidin (SA-PEG-USPIO) were synthesized, and their hydrodynamic diameters, zeta potential, T relaxivity, and cytotoxicity were measured. In vitro and in vivo two-step pretargeting MR imaging was performed on HepG2 cells and tumor-bearing mice after the administration of biotinylated L5 peptide (first step), followed by SA-PEG-USPIO (second step). Prussian blue staining was performed to assess iron deposition in tumors.

Results: The high specificity of L5 peptide for GPC3 was demonstrated. Generation of SA-PEG-USPIO nanoparticles with good biocompatibility (an average hydrodynamic diameter of 35.97 nm and a zeta potential of -7.91 mV), superparamagnetism ( = 0.1039 × 10 mMs), and low toxicity was achieved. The pretargeting group showed more enhancement than the nonpretargeting group both in vitro (60% vs 20%, < 0.05) and in vivo (32% vs 6%, < 0.001). Substantial iron deposition was only observed in HepG2 cells and tumors in the pretargeting group.

Conclusion: L5 peptide-guided, two-step pretargeting approach with USPIO as the MR imaging probe is a lucrative strategy to specifically identify GPC3-expressing HCC.
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http://dx.doi.org/10.1155/2018/9169072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151370PMC
January 2019

Multifunctional NIR-responsive poly(vinylpyrrolidone)-Cu-Sb-S nanotheranostic agent for photoacoustic imaging and photothermal/photodynamic therapy.

Acta Biomater 2018 07 9;74:334-343. Epub 2018 May 9.

Guangdong Provincial Key Laboratory of Cancer Immunotherapy, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

Ternary copper-based chalcogenide nanomaterials have become rather attractive due to the near-infrared (NIR) response in cancer theranostic fields. However, it is still challenging to further improve the theranostic efficiency of these nanomaterials. Herein, Cu-Sb-S nanoparticles (NPs) around 24 nm are synthesized facilely and functionalized with poly(vinylpyrrolidone) (PVP). Under the NIR irradiation, the resultant PVP-Cu-Sb-S NPs exhibit a relatively high photothermal conversion efficiency of 53.16% and a simultaneous reactive oxygen species (ROS) generation effect. Due to these outstanding photothermal/photodynamic effects, excellent tumor ablation results can be achieved by the combination of PVP-Cu-Sb-S NPs and 808 nm NIR laser treatments without obvious side effect. In addition, they show remarkable contrast enhancement according to in vitro and in vivo photoacoustic (PA) imaging. These PVP-Cu-Sb-S NPs could be served as a multifunctional nanotheranostic agent for PA imaging, photothermal/photodynamic cancer therapy.

Statement Of Significance: Highly theranostic efficiency ternary copper-based chalcogenide nanomaterials has not been fully developed yet. Herein we report the PVP-Cu-Sb-S nanoparticles (NPs) with relatively high photothermal efficiency, simultaneous reactive oxygen species generation effect and photoacoustic imaging capability. The photothermal conversion efficiency of PVP-Cu-Sb-S NPs is higher than most of copper-based chalcogenide nanomaterials reported before. These findings provide a new kind of ternary copper-based chalcogenide with an enhanced theranostic effect, which could be served as a promising multifunctional nanotheranostic agent in the field of biomedical application.
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http://dx.doi.org/10.1016/j.actbio.2018.05.011DOI Listing
July 2018

Radiation Dose Reduction by Using CT with Iterative Model Reconstruction in Patients with Pulmonary Invasive Fungal Infection.

Radiology 2018 07 10;288(1):285-292. Epub 2018 Apr 10.

From the Department of Medical Imaging Center (C.Y., C.L., Y.W., W.X., H.Z., Y.X.) and Department of Hematology (J.X., Q.W.), Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou 510515, Guangdong, People's Republic of China.

Purpose To compare the diagnostic quality of reduced radiation dose computed tomography (CT) with iterative model reconstruction (IMR) versus that of conventional low-dose CT in patients with pulmonary invasive fungal infection. Materials and Methods This prospective observational study included 48 patients (mean age ± standard deviation, 39.9 years ± 11.3) known to have or suspected of having pulmonary invasive fungal infection between October 2016 and July 2017. Patients underwent CT with IMR (at 80 kV with 20 mA) immediately after low-dose CT (at 80 kV with automatic exposure control). Images were reconstructed by using a hybrid iterative reconstruction (HIR) algorithm and IMR. Two radiologists independently assessed subjective image quality, noise, and visibility of normal and abnormal findings by using a five-point scale. Objective measurements, including image noise, contrast-to-noise ratio (CNR), and corresponding figure of merit (FOM), were compared by using repeated-measures analysis of variance with Bonferroni post hoc tests for multiple comparisons. Results The mean effective dose was 0.3 mSv ± 0.3 for CT with IMR and 0.7 mSv ± 0.2 for low-dose CT (P < .01). When the image noise and CNR were normalized to the effective dose, CT images obtained with IMR had significantly higher FOM than did other image series (P < .0001). Subjectively, visibility of CT features of invasive fungal infection on CT scans reconstructed with IMR was rated as noninferior to that on low-dose CT scans reconstructed with HIR, except for the halo sign. Conclusion CT with IMR had approximately 60% dose reduction compared with conventional low-dose CT, with reduced noise and improved depiction of abnormal findings, in patients with pulmonary invasive fungal infection.
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http://dx.doi.org/10.1148/radiol.2018172107DOI Listing
July 2018

Non-invasive monitoring of hydrogel degradation and cartilage regeneration by multiparametric MR imaging.

Theranostics 2018 13;8(4):1146-1158. Epub 2018 Jan 13.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.

Numerous biodegradable hydrogels for cartilage regeneration have been widely used in the field of tissue engineering. However, to non-invasively monitor hydrogel degradation and efficiently evaluate cartilage restoration in situ is still challenging. A ultrasmall superparamagnetic iron oxide (USPIO)-labeled cellulose nanocrystal (CNC)/silk fibroin (SF)-blended hydrogel system was developed to monitor hydrogel degradation during cartilage regeneration. The physicochemical characterization and biocompatibility of the hydrogel were evaluated . The hydrogel degradation and cartilage regeneration of different implants were assessed using multiparametric magnetic resonance imaging (MRI) and further confirmed by histological analysis in a rabbit cartilage defect model for 3 months. USPIO-labeled hydrogels showed sufficient MR contrast enhancement and retained stability without loss of the relaxation rate. Neither the mechanical properties of the hydrogels nor the proliferation of bone-marrow mesenchymal stem cells (BMSCs) were affected by USPIO labeling . CNC/SF hydrogels with BMSCs degraded more quickly than the acellular hydrogels as reflected by the MR relaxation rate trends . The morphology of neocartilage was noninvasively visualized by the three-dimensional water-selective cartilage MRI scan sequence, and the cartilage repair was further demonstrated by macroscopic and histological observations. This USPIO-labeled CNC/SF hydrogel system provides a new perspective on image-guided tissue engineering for cartilage regeneration.
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http://dx.doi.org/10.7150/thno.22514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817116PMC
January 2019

A photostable cationic fluorophore for long-term bioimaging.

J Mater Chem B 2017 Dec 17;5(46):9183-9188. Epub 2017 Nov 17.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, P. R. China.

Fluorophores for efficient long-term bioimaging are of great importance to fully understand the cellular and molecular processes of disease. In this study, a bright and photostable cationic fluorophore (PPB) was successfully developed as a long-term tracer. The PPB displayed advanced properties such as high fluorescence efficiency, large Stokes shift, low cytotoxicity, and good biocompatibility. Moreover, the PPB exhibited comparable photostability to the commercial cell tracker Qtracker 585. More importantly, the PPB can trace HeLa cells as long as 16 passages in vitro and monitor tumor growth for 27 days in vivo. These remarkable features endow the PPB as an ideal fluorescent probe for long-term bioimaging applications.
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http://dx.doi.org/10.1039/c7tb02668dDOI Listing
December 2017

Conjugated Polymer Containing Organic Radical for Optical/MR Dual-Modality Bioimaging.

ACS Appl Mater Interfaces 2017 Dec 12;9(51):44316-44323. Epub 2017 Dec 12.

Medical Imaging Center, Nanfang Hospital, ‡Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, and §School of Pharmaceutical Sciences, Southern Medical University , Guangzhou 510515, People's Republic of China.

Optical/MRI bimodal probes have attracted much attention due to palmary soft tissue resolution and high imaging sensitivity. In this study, poly[fluorene-co-alt-p-phenylene] containing organic radical (PFP-TEMPO+) is successfully developed for optical and MRI dual-modality bioimaging. PFP-TEMPO+ displays advanced properties such as fluorescence emission, high photostablilty, reasonable T relaxation effect, low cytotoxicity, and good biocompatibility. Moreover, the ability of PFP-TEMPO+ for tumor tissues imaging confirms that it could be used as an optical and MRI imaging probe for in vivo imaging. The results of the present work disclose the potential applications of PFP-TEMPO+ as an optical and MRI contrast agent.
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http://dx.doi.org/10.1021/acsami.7b15052DOI Listing
December 2017

Glucose functionalized carbon quantum dot containing organic radical for optical/MR dual-modality bioimaging.

Mater Sci Eng C Mater Biol Appl 2018 Jan 18;82:190-196. Epub 2017 Aug 18.

Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, PR China; School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

The organic paramagnetic compounds nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents. Herein, we report the synthesis and characterization of glucose modified carbon quantum dot containing 2,2,6,6-tetramethyl-piperidinooxy (TEMPO) for targeted bimodal MR/optical imaging of tumor cells. CQD-TEMPO-Glu shows the greatest potentials for bioimaging applications in view of low cytotoxicity, good biocompatibility, green fluorescence emission and high T1 relaxivities. The in vitro MR and optical imaging results confirm enhanced cellular internalization of CQD-TEMPO-Glu in cancer cells through GLUT mediated endocytosis. These results confirm that CQD-TEMPO-Glu is expected to be widely exploited as dual-modal contrast for cancer imaging.
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http://dx.doi.org/10.1016/j.msec.2017.08.074DOI Listing
January 2018

Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer.

Int J Nanomedicine 2017 12;12:6787-6797. Epub 2017 Sep 12.

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People's Republic of China.

Bombesin (BBN), an analog of gastrin-releasing peptide (GRP), specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC). Here, we synthesized a BBN-modified gadolinium oxide (GdO) nanoprobe containing fluorescein (GdO-5(6)-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN) for targeted magnetic resonance (MR)/optical dual-modality imaging of PC. The GdO-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy. The longitudinal relaxivity (r) of GdO-FI-PEG-BBN (r =4.23 mMs) is comparable to that of clinically used Magnevist (Gd-DTPA). Fluorescence microscopy and in vitro cellular MRI demonstrated GRP receptor-specific and enhanced cellular uptake of the GdO-FI-PEG-BBN in PC-3 tumor cells. Moreover, GdO-FI-PEG-BBN showed more remarkable contrast enhancement than the corresponding nontargeted GdO-FI-PEG according to in vivo MRI and fluorescent imaging. Tumor immunohistochemical analysis further demonstrated improved accumulation of the targeted nanoprobe in tumors. BBN-conjugated GdO may be a promising nanoplatform for simultaneous GRP receptor-targeted molecular cancer diagnosis and antitumor drug delivery in future clinical applications.
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http://dx.doi.org/10.2147/IJN.S139246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602459PMC
March 2018

Mitochondrial targeted fluorescent probe with AIE characteristics for bioimaging.

Mater Sci Eng C Mater Biol Appl 2017 Aug 18;77:129-135. Epub 2017 Mar 18.

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

In this work, a new benzothiazole based mitochondrial tracker, Bth-Mito, is synthesized by with 2-benzothiazoleacetonitrile and 4-(diethylamino)-benzaldehyde. Bth-Mito is weakly fluorescent when dissolved in the good solvent but becomes highly emissive in poor solvents, showing a phenomenon of aggregation-induced emission. Bth-Mito shows the greatest potentials for bioimaging applications in view of low cytotoxicity and high photostability. Bth-Mito could penetrate cells to give stable green fluorescence, even after continuous irradiation, making it suitable candidate for time-lapse and long-term bioimaging application. Moreover, Bth-Mito could specifically localize in mitochondrial. Furthermore, in vivo imaging studies on nude mice have revealed that Bth-Mito could be used as optical imaging probe for in vivo imaging. Histological assessment of tissues treated with Bth-Mito also further confirmed the low toxicity and good biocompatibility of Bth-Mito.
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http://dx.doi.org/10.1016/j.msec.2017.03.127DOI Listing
August 2017

A novel fluorescence probe based on triphenylamine Schiff base for bioimaging and responding to pH and Fe.

Mater Sci Eng C Mater Biol Appl 2017 Mar 5;72:551-557. Epub 2016 Dec 5.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, PR China. Electronic address:

A novel fluorescence probe 1 based on triphenylamine was synthesized and characterized by NMR, IR, high resolution mass spectrometry and elemental analysis. Its fluorescence was quenched when pH below 2. There was a linear relationship between the fluorescence intensity and pH value ranged from 2 to 7. And its fluorescence emission was reversibility in acidic and alkaline solution. Furthermore, it exhibited remarkable selectivity and high sensitivity to Fe and was able to detect Fe in aqueous solution with low detection limit of 0.511μM. Job plot showed that the binding stoichiometry of 1 with Fe was 1:1. Further observations of H NMR titration suggested that coordination interaction between Fe and nitrogen atom on CN bond promoted the intramolecular charge transfer (ICT) or energy transfer process causing fluorescence quenching. Additionally, 1 was also able to be applied for detecting Fe in living cell and bioimaging.
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http://dx.doi.org/10.1016/j.msec.2016.11.108DOI Listing
March 2017

Use of intravoxel incoherent motion diffusion-weighted MR imaging for assessment of treatment response to invasive fungal infection in the lung.

Eur Radiol 2017 Jan 14;27(1):212-221. Epub 2016 May 14.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, No.1838 Guangzhou Avenue North, Guangzhou, 510515, People's Republic of China.

Objectives: The purpose of this study was to determine whether intravoxel incoherent motion (IVIM) -derived parameters and apparent diffusion coefficient (ADC) could act as imaging biomarkers for predicting antifungal treatment response.

Methods: Forty-six consecutive patients (mean age, 33.9 ± 13.0 y) with newly diagnosed invasive fungal infection (IFI) in the lung according to EORTC/MSG criteria were prospectively enrolled. All patients underwent diffusion-weighted magnetic resonance (MR) imaging at 3.0 T using 11 b values (0-1000 sec/mm). ADC, pseudodiffusion coffiecient D*, perfusion fraction f, and the diffusion coefficient D were compared between patients with favourable (n=32) and unfavourable response (n=14).

Results: f values were significantly lower in the unfavourable response group (12.6%±4.4%) than in the favourable response group (30.2%±8.6%) (Z=4.989, P<0.001). However, the ADC, D, and D* were not significantly different between the two groups (P>0.05). Receiver operating characteristic curve analyses showed f to be a significant predictor for differentiation, with a sensitivity of 93.8% and a specificity of 92.9%.

Conclusions: IVIM-MRI is potentially useful in the prediction of antifungal treatment response to patients with IFI in the lung. Our results indicate that a low perfusion fraction f may be a noninvasive imaging biomarker for unfavourable response.

Key Points: • Recognition of IFI indicating clinical outcome is important for treatment decision-making. • IVIM can reflect diffusion and perfusion information of IFI lesions separately. • Perfusion characteristics of IFI lesions could help differentiate treatment response. • An initial low f may predict unfavourable response in IFI.
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http://dx.doi.org/10.1007/s00330-016-4380-9DOI Listing
January 2017

Organic Radical Contrast Agents Based on Polyacetylenes Containing 2,2,6,6-Tetramethylpiperidine 1-Oxyl (TEMPO): Targeted Magnetic Resonance (MR)/Optical Bimodal Imaging of Folate Receptor Expressing HeLa Tumors in Vitro and in Vivo(a).

Macromol Biosci 2015 Jun 13;15(6):788-98. Epub 2015 Feb 13.

School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.

Nitroxides have great potential as magnetic resonance imaging (MRI) contrast agents for tumor detection. Polyacetylenes(PAs) containing 2,2,6,6-tetramethyl-piperidine oxyl (TEMPO) and poly(ethylene glycol) were synthesized via metathesis polymerization of the corresponding substituted acetylenes to be used for targeted bimodal MRI /optical imaging of tumors. The poly(ethylene glycol) in the polyacetylenes enables covalent conjugation of carboxyl fluorescein and folic acid (FA) with hydroxyl groups to develop targeted multifunctional organic radical contrast agents (ORCAs). In vitro studies confirm the excellent binding specificity and subsequent enhanced cellular internalization of the targeted ORCAs (PA-TEMPO-FI-FA) without cytotoxicity. In vivo T1-weighted MRI demonstrates the active tumor targeting ability of PA-TEMPO-FI-FA to generate specific contrast enhancement in mice bearing HeLa tumors. Moreover, longitudinal optical imaging displays high tumor accumulation after 1 h post-injection of PA-TEMPO-FI-FA. These results indicate that multifunctional ORCAs may provide a tumor-targeted delivery platform for further molecular imaging guided cancer therapy.
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http://dx.doi.org/10.1002/mabi.201400403DOI Listing
June 2015

Lung MRI of invasive fungal infection at 3 Tesla: evaluation of five different pulse sequences and comparison with multidetector computed tomography (MDCT).

Eur Radiol 2015 Feb 18;25(2):550-7. Epub 2014 Sep 18.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, Guangdong, People's Republic of China.

Objectives: To evaluate the diagnostic performance of five MR sequences to detect pulmonary infectious lesions in patients with invasive fungal infection (IFI), using multidetector computed tomography (MDCT) as the reference standard.

Methods: Thirty-four immunocompromised patients with suspected IFI underwent MDCT and MRI. The MR studies were performed using five pulse sequences at 3.0 T: T2-weighted turbo spin echo (TSE), short-tau inversion recovery (STIR), spectrally selective attenuated inversion recovery (SPAIR), T1-weighted high resolution isotropic volume excitation (e-THRIVE) and T1-weighted fast field echo (T1-FFE). The size, lesion-to-lung contrast ratio and the detectability of pulmonary lesions on MR images were assessed. Image quality and artefacts on different sequences were also rated.

Results: A total of 84 lesions including nodules (n = 44) and consolidation (n = 40) were present in 75 lobes. SPAIR and e-THRIVE images achieved high overall lesion-related sensitivities for the detection of pulmonary abnormalities (90.5% and 86.9%, respectively). STIR showed the highest lesion-to-lung contrast ratio for nodules (21.8) and consolidation (17.0), whereas TSE had the fewest physiological artefacts.

Conclusions: MRI at 3.0 T can depict clinically significant pulmonary IFI abnormalities with high accuracy compared to MDCT. SPAIR and e-THRIVE are preferred sequences for the detection of infectious lesions of 5 mm and larger.

Key Points: • A radiation-free radiological method is desirable for assessing pulmonary infectious lesions • MRI at 3 T can depict lung infiltrates with good concordance to MDCT • SPAIR and e-THRIVE are favourable sequences for the detection of pulmonary lesions • The greatest benefit is for the diagnosis of lesions larger than 5 mm.
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http://dx.doi.org/10.1007/s00330-014-3432-2DOI Listing
February 2015

Choroid plexus tumours: classification, MR imaging findings and pathological correlation.

J Med Imaging Radiat Oncol 2013 Apr 28;57(2):176-83. Epub 2012 Dec 28.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangdong, China.

Introduction: Choroid plexus tumours (CPTs) are extremely rare intraventricular neoplasms and are prone to bleeding during surgery. The purpose of this study was to summarise the MR imaging characteristics of 13 CPT cases.

Methods: Magnetic resonance images of 13 patients (six men and seven women; mean age 21.1 years) with pathologically proved CPTs were retrospectively reviewed. MR findings of the tumours were evaluated, with emphasis on their location, size, shape, internal architecture, margin and pattern and degree of enhancement. Differences in signal intensity characteristics were also investigated on MR images and analysed according to histological subtypes.

Results: Lesions were in the lateral ventricles (n = 7), fourth ventricle (n = 5) and cisterna magna (n = 1), with a mean size of 5.0 cm (range 2.0-7.9 cm). The tumour parenchyma was a mixture of nodular or patchy areas of inhomogeneous isointense to slightly hyperintense signal on T2-weighted images. On postcontrast MR images, all lesions, except for one, had moderate to marked contrast enhancement. Multiple tortuous areas of 'flow void' signal extended through all the tumours except for two. A thin capsule could be seen in six cases.

Conclusion: Observation of large intraventricular tumours with inhomogeneity on T2-weighted images and flow void is suggestive of CPTs. Checking for signs of a thin capsule, extensive peritumoural oedema and necrosis may be useful when classifying CPTs.
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http://dx.doi.org/10.1111/1754-9485.12013DOI Listing
April 2013

Anti-αvβ3 antibody guided three-step pretargeting approach using magnetoliposomes for molecular magnetic resonance imaging of breast cancer angiogenesis.

Int J Nanomedicine 2013 11;8:245-55. Epub 2013 Jan 11.

Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Purpose: Pretargeting of biomarkers with nanoparticles in molecular imaging is promising to improve diagnostic specificity and realize signal amplification, but data regarding its targeting potential in magnetic resonance (MR) imaging are limited. The purpose of this study was to evaluate the tumor angiogenesis targeting efficacy of the anti-αvβ3 antibody guided three-step pretargeting approach with magnetoliposomes.

Methods: Polyethylene glycol-modified and superparamagnetic iron oxide-encapsulated magnetoliposomes with and without biotin were synthesized and characterized. The cytotoxicity of both probes was evaluated using the methyl thiazdyl tetrazolium assay, and their cellular uptake by mouse macrophage was visualized using Prussian blue staining. Three-step pretargeting MR imaging was performed on MDA-MB-435S breast cancer-bearing mice by intravenous administration of biotinylated anti-αvβ3 monoclonal antibodies (first step), followed by avidin and streptavidin (second step), and by biotinylated magnetoliposomes or magnetoliposomes in the targeted or nontargeted group, respectively (third step). The specificity of αvβ3 targeting was assessed by histologic examinations.

Results: The developed magnetoliposomes were superparamagnetic and biocompatible as confirmed by cell toxicity assay. The liposomal bilayer and polyethylene glycol modification protected Fe(3)O(4) cores from uptake by macrophage cells. MR imaging by three-step pretargeting resulted in a greater signal enhancement along the tumor periphery, occupying 7.0% of the tumor area, compared with 2.0% enhancement of the nontargeted group (P < 0.05). Histologic analysis demonstrated the targeted magnetoliposomes colocalized with neovasculature, which was responsible for the MR signal decrease.

Conclusion: These results indicate that our strategy for MR imaging of αvβ3-integrin is an effective means for sensitive detection of tumor angiogenesis, and may provide a targetable nanodelivery system for anticancer drugs.
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http://dx.doi.org/10.2147/IJN.S38678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548418PMC
September 2013