Articles

The effects of segmentation algorithms on the measurement of ¹⁸F-FDG PET texture parameters in non-small cell lung cancer

Measures of tumour heterogeneity derived from 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) scans are increasingly reported as potential biomarkers of non-small cell l...

Authors: Usman Bashir, Gurdip Azad, Muhammad Musib Siddique, Saana Dhillon, Nikheel Patel, Paul Bassett, David Landau, Vicky Goh and Gary Cook

Microglial depletion and activation: A [¹¹C]PBR28 PET study in nonhuman primates

The 18-kDa translocator protein (TSPO) is an important target for assessing neuroimmune function in brain with positron-emission tomography (PET) imaging. The goal of this work was to assess two [¹¹C]PBR28 imagin...

Authors: Ansel T. Hillmer, Daniel Holden, Krista Fowles, Nabeel Nabulsi, Brian L. West, Richard E. Carson and Kelly P. Cosgrove

Assessment of simplified ratio-based approaches for quantification of PET [¹¹C]PBR28 data

Kinetic modelling with metabolite-corrected arterial plasma is considered the gold standard for quantification of [¹¹C]PBR28 binding to the translocator protein (TSPO), since there is no brain region devoid of TS...

Authors: Granville J. Matheson, Pontus Plavén-Sigray, Anton Forsberg, Andrea Varrone, Lars Farde and Simon Cervenka

Pharmacokinetics, microscale distribution, and dosimetry of alpha-emitter-labeled anti-PD-L1 antibodies in an immune competent transgenic breast cancer model

Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted deli...

Authors: Jessie R. Nedrow, Anders Josefsson, Sunju Park, Tom Bäck, Robert F. Hobbs, Cory Brayton, Frank Bruchertseifer, Alfred Morgenstern and George Sgouros

FLT-PET for early response evaluation of colorectal cancer patients with liver metastases: a prospective study

Fluoro-L-thymidine (FLT) is a positron emission tomography/computed tomography (PET/CT) tracer which reflects proliferative activity in a cancer lesion. The main objective of this prospective explorative study...

Authors: Marie Benzon Mogensen, Annika Loft, Marianne Aznar, Thomas Axelsen, Ben Vainer, Kell Osterlind and Andreas Kjaer

Erratum to: Quantitative 18F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring

Authors: Joshua D. Schaefferkoetter, Ziting Wang, Mary C. Stephenson, Sharmili Roy, Maurizio Conti, Lars Eriksson, David W. Townsend, Thomas Thamboo and Edmund Chiong

Use of a digital phantom developed by QIBA for harmonizing SUVs obtained from the state-of-the-art SPECT/CT systems: a multicenter study

Although quantitative analysis using standardized uptake value (SUV) becomes realistic in clinical single-photon emission computed tomography/computed tomography (SPECT/CT) imaging, reconstruction parameter se...

Authors: Tadaki Nakahara, Hiromitsu Daisaki, Yasushi Yamamoto, Takashi Iimori, Kazuyuki Miyagawa, Tomoya Okamoto, Yoshiki Owaki, Nobuhiro Yada, Koichi Sawada, Ryotaro Tokorodani and Masahiro Jinzaki

Test-retest reproducibility of [¹¹C]-l-deprenyl-D₂ binding to MAO-B in the human brain

[¹¹C]-l-deprenyl-D₂ is a positron emission tomography (PET) radioligand for measurement of the monoamine oxidase B (MAO-B) activity in vivo brain. The estimation of the test-retest reproducibility is important fo...

Authors: Ryosuke Arakawa, Per Stenkrona, Akihiro Takano, Sangram Nag, Rafael S. Maior and Christer Halldin

PET/CT scanning with 3D acquisition is feasible for quantifying myocardial blood flow when diagnosing coronary artery disease

The quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR) are useful approaches for evaluating the functional severity of coronary artery disease (CAD). ¹⁵O-water positron emission tomogra...

Authors: Osamu Manabe, Masanao Naya, Tadao Aikawa, Masahiko Obara, Keiichi Magota, Markus Kroenke, Noriko Oyama-Manabe, Kenji Hirata, Daiki Shinyama, Chietsugu Katoh and Nagara Tamaki

Response assessment with the CXCR4-directed positron emission tomography tracer [⁶⁸Ga]Pentixafor in a patient with extranodal marginal zone lymphoma of the orbital cavities

CXCR4 belongs to the family of chemokine receptors. Together with its sole known ligand CXCL12 (SDF-1alpha), it has a pivotal role during organogenesis and for homing of hematopoietic stem cells. CXCR4 is over...

Authors: Peter Herhaus, Stefan Habringer, Tibor Vag, Katja Steiger, Julia Slotta-Huspenina, Carlos Gerngroß, Benedikt Wiestler, Hans-Jürgen Wester, Markus Schwaiger and Ulrich Keller

Clinical value of fluorine-18α-methyltyrosine PET in patients with gliomas: comparison with fluorine-18 fluorodeoxyglucose PET

We investigated the relationship between metabolic activity and histological features of gliomas using fluorine-18α-methyltyrosine (¹⁸F-FAMT) positron emission tomography (PET) compared with fluorine-18 fluorodeo...

Authors: Keishi Horiguchi, Masahiko Tosaka, Tetsuya Higuchi, Yukiko Arisaka, Kenichi Sugawara, Junko Hirato, Hideaki Yokoo, Yoshito Tsushima and Yuhei Yoshimoto

Monitoring response to anti-angiogenic mTOR inhibitor therapy in vivo using ¹¹¹In-bevacizumab

The ability to image vascular endothelial growth factor (VEGF) could enable prospective, non-invasive monitoring of patients receiving anti-angiogenic therapy. This study investigates the specificity and pharm...

Authors: Neel Patel, Sarah Able, Danny Allen, Emmanouil Fokas, Bart Cornelissen, Fergus V. Gleeson, Adrian L. Harris and Katherine A. Vallis

Towards standardization of ¹⁸F-FET PET imaging: do we need a consistent method of background activity assessment?

PET with O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-backg...

Authors: Marcus Unterrainer, Franziska Vettermann, Matthias Brendel, Adrien Holzgreve, Michael Lifschitz, Matthias Zähringer, Bogdana Suchorska, Vera Wenter, Ben M. Illigens, Peter Bartenstein and Nathalie L. Albert

Quantitative analysis of dynamic ¹⁸F-FDG PET/CT for measurement of lung inflammation

An inflammatory reaction in the airways and lung parenchyma, comprised mainly of neutrophils and alveolar macrophages, is present in some patients with chronic obstructive pulmonary disease (COPD). Thoracic fl...

Authors: Christopher Coello, Marie Fisk, Divya Mohan, Frederick J. Wilson, Andrew P. Brown, Michael I. Polkey, Ian Wilkinson, Ruth Tal-Singer, Philip S. Murphy, Joseph Cheriyan and Roger N. Gunn

Clinical and imaging-based prognostic factors in radioembolisation of liver metastases from colorectal cancer: a retrospective exploratory analysis

The aim of this study was to investigate the relationship between absorbed dose and response of colorectal cancer liver metastases treated with [⁹⁰Y]-resin microspheres and to explore possible clinical and imagin...

Authors: Kathy P. Willowson, Aimee R. Hayes, David L. H. Chan, Michael Tapner, Elizabeth J. Bernard, Richard Maher, Nick Pavlakis, Stephen J. Clarke and Dale L. Bailey

Optimization of diagnostic performance for differentiation of recurrence from radiation necrosis in patients with metastatic brain tumors using tumor volume-corrected ¹¹C-methionine uptake

Tumor to normal tissue ratio (T/N ratio) on ¹¹C-methionine (¹¹C-MET) positron emission tomography/computed tomography (PET/CT) is affected by variable factors. We investigated whether T/N ratio cutoff values corr...

Authors: Tae-Young Jung, In-Young Kim, Sa-Hoe Lim, Ki Seong Park, Dong-Yeon Kim, Shin Jung, Kyung-Sub Moon, Woo-Youl Jang, Sae-Ryung Kang, Sang-Geon Cho, Jung-Joon Min, Hee-Seung Bom and Seong Young Kwon

Cryogenic transmission electron microscopy: the technique of choice for the characterization of polymeric nanocarriers

This letter is meant to make scientists aware of the proper application of transmission electron microscopy (TEM) for the assessment of polymeric self-assemblies. Cryogenic (cryo)-TEM should be the method of c...

Authors: Adrianus C. Laan and Antonia G. Denkova

First in-human radiation dosimetry of ⁶⁸Ga-NODAGA-RGDyK

Integrin-targeting radiopharmaceuticals have potential broad applications, spanning from cancer theranostics to cardiovascular diseases. We have previously reported preclinical dosimetry results of ⁶⁸Ga-NODAGA-RG...

Authors: Silvano Gnesin, Periklis Mitsakis, Francesco Cicone, Emmanuel Deshayes, Vincent Dunet, Augusto F. Gallino, Marek Kosinski, Sébastien Baechler, Franz Buchegger, David Viertl and John O. Prior

Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases

18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone sci...

Authors: Cecilia Wassberg, Mark Lubberink, Jens Sörensen and Silvia Johansson

Analysis of progress and challenges for various patterns of c-MET-targeted molecular imaging: a systematic review

Mesenchymal–epithelial transition factor also named c-MET is a receptor tyrosine kinase for the hepatocyte growth factor that plays a pivotal role in tumorigenesis. c-MET-targeted therapies have been tested in...

Authors: Zhaoguo Han, Yongyi Wu, Kai Wang, Yadi Xiao, Zhen Cheng, Xilin Sun and Baozhong Shen

Targeting mannose receptor expression on macrophages in atherosclerotic plaques of apolipoprotein E-knockout mice using ¹¹¹In-tilmanocept

Atherosclerotic plaque phenotypes are classified based on the extent of macrophage infiltration into the lesions, and the presence of certain macrophage subsets might be a sign for plaque vulnerability. The ma...

Authors: Zohreh Varasteh, Fabien Hyafil, Nadège Anizan, Devy Diallo, Rachida Aid-Launais, Sarajo Mohanta, Yuanfang Li, Miriam Braeuer, Katja Steiger, Jonathan Vigne, Zhengtao Qin, Stephan G. Nekolla, Jean-Etienne Fabre, Yvonne Döring, Dominique Le Guludec, Andreas Habenicht…

Carotid atherosclerotic plaques standardised uptake values: software challenges and reproducibility

Positron emission tomography–computed tomography (PET-CT) carotid standardised uptake values (SUV) of ¹⁸F-fluorodeoxyglucose (¹⁸FDG) have been proposed as an inflammatory biomarker for determining cerebrovascular...

Authors: Nicola Giannotti, Martin J. O’Connell, Shane J. Foley, Peter J. Kelly and Jonathan P. McNulty

Effective dose estimation for oncological and neurological PET/CT procedures

The aim of this study was to retrospectively evaluate the patient effective dose (ED) for different PET/CT procedures performed with a variety of PET radiopharmaceutical compounds.

Authors: Josep M. Martí-Climent, Elena Prieto, Verónica Morán, Lidia Sancho, Macarena Rodríguez-Fraile, Javier Arbizu, María J. García-Velloso and José A. Richter

Therapeutic efficacy of α-radioimmunotherapy with different activity levels of the ²¹³Bi-labeled monoclonal antibody MX35 in an ovarian cancer model

The aim of this study was to compare the therapeutic efficacy of two different activity levels of the ²¹³Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inocu...

Authors: Anna Gustafsson-Lutz, Tom Bäck, Emma Aneheim, Ragnar Hultborn, Stig Palm, Lars Jacobsson, Alfred Morgenstern, Frank Bruchertseifer, Per Albertsson and Sture Lindegren

Partial volume correction of brain PET studies using iterative deconvolution in combination with HYPR denoising

Accurate quantification of PET studies depends on the spatial resolution of the PET data. The commonly limited PET resolution results in partial volume effects (PVE). Iterative deconvolution methods (IDM) have...

Authors: Sandeep S. V. Golla, Mark Lubberink, Bart N. M. van Berckel, Adriaan A. Lammertsma and Ronald Boellaard

The effect of post-injection ¹⁸F-FDG PET scanning time on texture analysis of peripheral nerve sheath tumours in neurofibromatosis-1

Texture features are being increasingly evaluated in ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) as adjunctive imaging biomarkers in a number of different cancers. Whilst studies have report...

Authors: Eitan Lovat, Musib Siddique, Vicky Goh, Rosalie E. Ferner, Gary J. R. Cook and Victoria S. Warbey

Characterization of indeterminate renal masses with molecular imaging: how do we turn potential into reality?

Authors: Steven P. Rowe, Mehrbod S. Javadi, Mohamad E. Allaf and Michael A. Gorin

High-throughput high-volume nuclear imaging for preclinical in vivo compound screening^§

Preclinical single-photon emission computed tomography (SPECT)/CT imaging studies are hampered by low throughput, hence are found typically within small volume feasibility studies. Here, imaging and image anal...

Authors: Sven Macholl, Ciara M. Finucane, Jacob Hesterman, Stephen J. Mather, Rachel Pauplis, Deirdre Scully, Jane K. Sosabowski and Erwan Jouannot

Design, synthesis and evaluation in an LPS rodent model of neuroinflammation of a novel ¹⁸F-labelled PET tracer targeting P2X7

The P2X7 receptor has been shown to play a fundamental role in the initiation and sustenance of the inflammatory cascade. The development of a novel fluorine-18 PET tracer superior and with a longer half-life ...

Authors: Enrico Raffaele Fantoni, Diego Dal Ben, Simonetta Falzoni, Francesco Di Virgilio, Simon Lovestone and Antony Gee

Tracking dendritic cell migration into lymph nodes by using a novel PET probe ¹⁸F-tetrafluoroborate for sodium/iodide symporter

Recently, ¹⁸F-tetrafluoroborate (TFB) was used as a substrate for the human sodium/iodide symporter (hNIS) reporter gene. This study evaluated the feasibility of performing molecular-genetic imaging by using the ...

Authors: Sang Bong Lee, Ho Won Lee, Hongje Lee, Yong Hyun Jeon, Sang-Woo Lee, Byeong-Cheol Ahn, Jaetae Lee and Shin Young Jeong

Impact of the EARL harmonization program on automatic delineation of metabolic active tumour volumes (MATVs)

The clinical validation of the EARL harmonization program for standardised uptake value (SUV) metrics is well documented; however, its potential for defining metabolic active tumour volume (MATV) has not yet b...

Authors: Charline Lasnon, Blandine Enilorac, Hosni Popotte and Nicolas Aide

Visual evaluation and differentiation of renal oncocytomas from renal cell carcinomas by means of ^99mTc-sestamibi SPECT/CT

Despite the progress in the quality of multiphasic CT and MRI scans, it is still difficult to fully characterize a solid kidney lesion. Approximately 10% of all solid renal tumours turn out to be oncocytomas. ...

Authors: Antonios Tzortzakakis, Ove Gustafsson, Mattias Karlsson, Linnea Ekström-Ehn, Rammin Ghaffarpour and Rimma Axelsson

Assessment of safety, efficacy, and dosimetry of a novel 18-kDa translocator protein ligand, [¹¹C]CB184, in healthy human volunteers

N,N-di-n-propyl-2-[2-(4-[¹¹C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([¹¹C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), ...

Authors: Muneyuki Sakata, Kenji Ishibashi, Masamichi Imai, Kei Wagatsuma, Kenji Ishii, Kentaro Hatano, Kiichi Ishiwata and Jun Toyohara

I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury

Traumatic brain injury (TBI) causes brain dysfunction in many patients. Using C-11 flumazenil (FMZ) positron emission tomography (PET), we have detected and reported the loss of neuronal integrity, leading to ...

Authors: Kagari Abiko, Katsunori Ikoma, Tohru Shiga, Chietsugu Katoh, Kenji Hirata, Yuji Kuge, Kentaro Kobayashi and Nagara Tamaki

Comparison of diagnostic performance of four software packages for phase dyssynchrony analysis in gated myocardial perfusion SPECT

Phase analysis of gated myocardial perfusion single-photon emission computed tomography (SPECT) for assessment of left ventricular (LV) dyssynchrony was investigated using the following dedicated software pack...

Authors: Koichi Okuda, Kenichi Nakajima, Shinro Matsuo, Soichiro Kashiwaya, Hiroto Yoneyama, Takayuki Shibutani, Masahisa Onoguchi, Mitsumasa Hashimoto and Seigo Kinuya

Quantitative ¹⁸F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring

The use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflictin...

Authors: Joshua D. Schaefferkoetter, Ziting Wang, Mary C. Stephenson, Sharmili Roy, Maurizio Conti, Lars Eriksson, David W. Townsend, Thomas Thamboo and Edmund Chiong

Beta-amyloid deposition in patients with major depressive disorder with differing levels of treatment resistance: a pilot study

Lack of treatment response in patients with late-life depression is common. The role of brain beta-amyloid (Aβ) deposition in treatment outcome in subjects with late-life depression remains unclear. The presen...

Authors: Peng Li, Ing-Tsung Hsiao, Chia-Yih Liu, Chia-Hsiang Chen, She-Yao Huang, Tzu-Chen Yen, Kuan-Yi Wu and Kun-Ju Lin

Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer; methodological issues to avoid mismanagement of the patients

Authors: Siamak Sabour

New approaches for the reliable in vitro assessment of binding affinity based on high-resolution real-time data acquisition of radioligand-receptor binding kinetics

Resolving the kinetic mechanisms of biomolecular interactions have become increasingly important in early-phase drug development. Since traditional in vitro methods belong to dose-dependent assessments, bindin...

Authors: Markus Zeilinger, Florian Pichler, Lukas Nics, Wolfgang Wadsak, Helmut Spreitzer, Marcus Hacker and Markus Mitterhauser

Voxel-based mapping of grey matter volume and glucose metabolism profiles in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disease of the nervous system involving both upper and lower motor neurons. The patterns of structural and metabolic brain alterations are still unc...

Authors: M-S. Buhour, F. Doidy, A. Mondou, A. Pélerin, L. Carluer, F. Eustache, F. Viader and B. Desgranges

Characteristics of immunoglobulin G4-related aortitis/periaortitis and periarteritis on fluorodeoxyglucose positron emission tomography/computed tomography co-registered with contrast-enhanced computed tomography

We aimed to assess the positivity, distribution, quantitative degree of vessel inflammation, and clinical characteristics of IgG4-related aortitis/periarteritis and periarteritis (IgG4-aortitis), and to examin...

Authors: Satoshi Yabusaki, Noriko Oyama-Manabe, Osamu Manabe, Kenji Hirata, Fumi Kato, Noriyuki Miyamoto, Yoshihiro Matsuno, Kohsuke Kudo, Nagara Tamaki and Hiroki Shirato

¹⁸F-FDG-labeled red blood cell PET for blood-pool imaging: preclinical evaluation in rats

Red blood cells (RBCs) labeled with single-photon emitters have been clinically used for blood-pool imaging. Although some PET tracers have been introduced for blood-pool imaging, they have not yet been widely...

Authors: Yohji Matsusaka, Tadaki Nakahara, Kazuhiro Takahashi, Yu Iwabuchi, Chiyoko Nishime, Mayumi Kajimura and Masahiro Jinzaki

SPECT image segmentation for estimation of tumour volume and activity concentration in ¹⁷⁷Lu-DOTATATE radionuclide therapy

Dosimetry in radionuclide therapy has the potential to allow for a treatment tailored to the individual patient. One therapeutic radiopharmaceutical where patient-specific dosimetry is feasible is ¹⁷⁷Lu-DOTATATE,...

Authors: Johan Gustafsson, Anna Sundlöv and Katarina Sjögreen Gleisner

Pharmacokinetic modeling of [¹¹C]flumazenil kinetics in the rat brain

Preferred models for the pharmacokinetic analysis of [¹¹C]flumazenil human studies have been previously established. However, direct translation of these models and settings to animal studies might be sub-optimal...

Authors: Isadora Lopes Alves, David Vállez García, Andrea Parente, Janine Doorduin, Rudi Dierckx, Ana Maria Marques da Silva, Michel Koole, Antoon Willemsen and Ronald Boellaard

Quantitative evaluation of oxygen metabolism in the intratumoral hypoxia: ¹⁸F-fluoromisonidazole and ¹⁵O-labelled gases inhalation PET

Intratumoral hypoxia is one of the resistant factors in radiotherapy and chemotherapy for cancer. Although it is detected by ¹⁸F-fluoromisonidazole (FMISO) PET, the relationship between intratumoral hypoxia and o...

Authors: Tadashi Watabe, Yasukazu Kanai, Hayato Ikeda, Genki Horitsugi, Keiko Matsunaga, Hiroki Kato, Kayako Isohashi, Kohji Abe, Eku Shimosegawa and Jun Hatazawa

3D skeletal uptake of ¹⁸F sodium fluoride in PET/CT images is associated with overall survival in patients with prostate cancer

Sodium fluoride (NaF) positron emission tomography combined with computer tomography (PET/CT) has shown to be more sensitive than the whole-body bone scan in the detection of skeletal uptake due to metastases ...

Authors: Sarah Lindgren Belal, May Sadik, Reza Kaboteh, Nezar Hasani, Olof Enqvist, Linus Svärm, Fredrik Kahl, Jane Simonsen, Mads H. Poulsen, Mattias Ohlsson, Poul F. Høilund-Carlsen, Lars Edenbrandt and Elin Trägårdh

Erratum to: Test-retest analysis of a non-invasive method of quantifying [(11)C]-PBR28 binding in Alzheimer's disease

Authors: Akshay Nair, Mattia Veronese, Xiaohui Xu, Charles Curtis, Federico Turkheimer, Robert Howard and Suzanne Reeves

The extent to which standardized uptake values reflect FDG phosphorylation in the liver and spleen as functions of time after injection of ¹⁸F-fluorodeoxyglucose

In FDG PET/CT, standardized uptake value (SUV) is used to measure metabolic activity but detects un-phosphorylated FDG as well as phosphorylated FDG (FDG6P). Our aim was to determine the proportions of intrahe...

Authors: Georgia Keramida, Constantinos D. Anagnostopoulos and A. Michael Peters

Impact of PET acquisition durations on image quality and lesion detectability in whole-body ⁶⁸Ga-PSMA PET-MRI

While ⁶⁸Ga-PSMA PET-MRI might be superior to PET-CT with regard to soft tissue assessment in prostate cancer evaluation, it is also known to potentially introduce additional PET image artefacts. Therefore, the im...

Authors: Benjamin Noto, Florian Büther, Katharina Auf der Springe, Nemanja Avramovic, Walter Heindel, Michael Schäfers, Thomas Allkemper and Lars Stegger

Comparison of machine learning methods for classifying mediastinal lymph node metastasis of non-small cell lung cancer from ¹⁸F-FDG PET/CT images

This study aimed to compare one state-of-the-art deep learning method and four classical machine learning methods for classifying mediastinal lymph node metastasis of non-small cell lung cancer (NSCLC) from ¹⁸F-F...

Authors: Hongkai Wang, Zongwei Zhou, Yingci Li, Zhonghua Chen, Peiou Lu, Wenzhi Wang, Wanyu Liu and Lijuan Yu