Recent advances in molecular imaging of atherosclerotic plaques and thrombosis.

As the complications of atherosclerosis such as myocardial infarction and stroke are still one of the leading causes of mortality worldwide, the development of new diagnostic tools for the early detection of plaque instability and thrombosis is urgently needed. Advanced molecular imaging probes based on functional nanomaterials in combination with cutting edge imaging techniques are now paving the way for novel and unique approaches to monitor the inflammatory progress in atherosclerosis. This review focuses on the development of various molecular probes for the diagnosis of plaques and thrombosis in atherosclerosis, along with perspectives of their diagnostic applications in cardiovascular diseases. Specifically, we summarize the biological targets that can be used for atherosclerosis and thrombosis imaging. Then we describe the emerging molecular imaging techniques based on the utilization of engineered nanoprobes together with their challenges in clinical translation.

[1]  Y. Magata,et al.  Macrophage-targeted, enzyme-triggered fluorescence switch-on system for detection of embolism-vulnerable atherosclerotic plaques. , 2019, Journal of controlled release : official journal of the Controlled Release Society.

[2]  P. Weissberg,et al.  Molecular and metabolic imaging of atherosclerosis. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  Qiwen Chen,et al.  Recent advances in different modal imaging-guided photothermal therapy. , 2016, Biomaterials.

[4]  E M Sevick-Muraca,et al.  A review of performance of near-infrared fluorescence imaging devices used in clinical studies. , 2015, The British journal of radiology.

[5]  Matthew Tirrell,et al.  Active targeting of early and mid-stage atherosclerotic plaques using self-assembled peptide amphiphile micelles. , 2014, Biomaterials.

[6]  Gareth Loy,et al.  7T MR of intracranial pathology: Preliminary observations and comparisons to 3T and 1.5T , 2016, NeuroImage.

[7]  D. Celermajer Noninvasive detection of atherosclerosis. , 1998, The New England journal of medicine.

[8]  J. Zwanenburg,et al.  MRI of the carotid artery at 7 Tesla: Quantitative comparison with 3 Tesla , 2015, Journal of magnetic resonance imaging : JMRI.

[9]  Hao Hong,et al.  Positron Emission Tomography Imaging of Atherosclerosis , 2013, Theranostics.

[10]  Hongki Yoo,et al.  Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors , 2016, Scientific Reports.

[11]  C. H. J. Choi,et al.  Recent Advances in Managing Atherosclerosis via Nanomedicine. , 2018, Small.

[12]  Zahi A. Fayad,et al.  Imaging of atherosclerotic cardiovascular disease , 2008, Nature.

[13]  Hamidreza Arandiyan,et al.  Lanthanide‐Doped Upconversion Nanoparticles: Emerging Intelligent Light‐Activated Drug Delivery Systems , 2016, Advanced science.

[14]  S. Wickline,et al.  Thrombin‐inhibiting perfluorocarbon nanoparticles provide a novel strategy for the treatment and magnetic resonance imaging of acute thrombosis , 2011, Journal of thrombosis and haemostasis : JTH.

[15]  J. Zamorano,et al.  Non-Invasive Detection of Extracellular Matrix Metalloproteinase Inducer EMMPRIN, a New Therapeutic Target against Atherosclerosis, Inhibited by Endothelial Nitric Oxide , 2018, International journal of molecular sciences.

[16]  S. Harris,et al.  OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice , 2012, Journal of Lipid Research.

[17]  J. Bulte,et al.  Fluorine (19F) MRS and MRI in biomedicine , 2011, NMR in biomedicine.

[18]  J. Gillard,et al.  Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque Macrophages , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[19]  Suresh Gadde,et al.  Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis. , 2016, ACS nano.

[20]  J. Michel,et al.  Functional imaging of atherosclerosis to advance vascular biology. , 2009, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[21]  Yu-Chen Chen,et al.  In vivo MRI detection of carotid atherosclerotic lesions and kidney inflammation in ApoE-deficient mice by using LOX-1 targeted iron nanoparticles. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[22]  Wei Feng,et al.  Biodistribution of sub-10 nm PEG-modified radioactive/upconversion nanoparticles. , 2013, Biomaterials.

[23]  S. Dhar,et al.  Biodegradable synthetic high-density lipoprotein nanoparticles for atherosclerosis , 2013, Proceedings of the National Academy of Sciences.

[24]  Y. Urano,et al.  Design and synthesis of fluorescent probes for selective detection of highly reactive oxygen species in mitochondria of living cells. , 2007, Journal of the American Chemical Society.

[25]  N. Hayashi,et al.  Enhancement of the intracranial arterial wall at MR imaging: relationship to cerebral atherosclerosis. , 1995, Radiology.

[26]  K König,et al.  Clinical two‐photon microendoscopy , 2007, Microscopy research and technique.

[27]  J. Frangioni In vivo near-infrared fluorescence imaging. , 2003, Current opinion in chemical biology.

[28]  Steven B. Feinstein,et al.  Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? , 2007, Vascular medicine.

[29]  Zhuang Liu,et al.  Carbon nanotubes for biomedical imaging: the recent advances. , 2013, Advanced drug delivery reviews.

[30]  G. Lippi,et al.  Arterial thrombus formation in cardiovascular disease , 2011, Nature Reviews Cardiology.

[31]  Kai Yang,et al.  Facile preparation of multifunctional upconversion nanoprobes for multimodal imaging and dual-targeted photothermal therapy. , 2011, Angewandte Chemie.

[32]  Qingsong Mei,et al.  Near-Infrared Excited Orthogonal Emissive Upconversion Nanoparticles for Imaging-Guided On-Demand Therapy. , 2019, ACS nano.

[33]  A. Algra,et al.  Intracranial Vessel Wall Lesions on 7T MRI (Magnetic Resonance Imaging): Occurrence and Vascular Risk Factors The SMART-MR Study , 2019, Stroke.

[34]  Anna Nowogrodzki,et al.  The world’s strongest MRI machines are pushing human imaging to new limits , 2018, Nature.

[35]  Hisataka Kobayashi,et al.  Dendrimer-based contrast agents for molecular imaging. , 2008, Current topics in medicinal chemistry.

[36]  19F molecular MR imaging for detection of brain tumor angiogenesis: in vivo validation using targeted PFOB nanoparticles , 2012, Angiogenesis.

[37]  Ralph Weissleder,et al.  Optical Visualization of Cathepsin K Activity in Atherosclerosis With a Novel, Protease-Activatable Fluorescence Sensor , 2007, Circulation.

[38]  R. Forsythe,et al.  Emerging techniques in atherosclerosis imaging , 2019, The British journal of radiology.

[39]  H. Kai Novel non‐invasive approach for visualizing inflamed atherosclerotic plaques using fluorodeoxyglucose‐positron emission tomography , 2010, Geriatrics & gerontology international.

[40]  E. V. van Beek,et al.  Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. , 2012, Journal of the American College of Cardiology.

[41]  Wei Li,et al.  In Vivo Targeting and Imaging of Atherosclerosis Using Multifunctional Virus-Like Particles of Simian Virus 40. , 2016, Nano letters.

[42]  Chun Yuan,et al.  MRI of carotid atherosclerosis: clinical implications and future directions , 2010, Nature Reviews Cardiology.

[43]  Jie Shen,et al.  Lanthanide-doped upconverting luminescent nanoparticle platforms for optical imaging-guided drug delivery and therapy. , 2013, Advanced drug delivery reviews.

[44]  Hyungwoo Kim,et al.  Recent Progress on Near-Infrared Photoacoustic Imaging: Imaging Modality and Organic Semiconducting Agents , 2019, Polymers.

[45]  Eric D. Pressly,et al.  Assessment of Targeted Nanoparticle Assemblies for Atherosclerosis Imaging with Positron Emission Tomography and Potential for Clinical Translation. , 2019, ACS applied materials & interfaces.

[46]  A. Nederveen,et al.  Emerging Magnetic Resonance Imaging Techniques for Atherosclerosis Imaging. , 2019, Arteriosclerosis, thrombosis, and vascular biology.

[47]  J. Bodle,et al.  High-Resolution Magnetic Resonance Imaging: An Emerging Tool for Evaluating Intracranial Arterial Disease , 2013, Stroke.

[48]  G. Hansson Immune and inflammatory mechanisms in the development of atherosclerosis. , 1993, British heart journal.

[49]  F. Cao,et al.  Optical/MRI dual-modality imaging of M1 macrophage polarization in atherosclerotic plaque with MARCO-targeted upconversion luminescence probe. , 2019, Biomaterials.

[50]  Chih-Ming Ho,et al.  Monocyte recruitment to endothelial cells in response to oscillatory shear stress , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[51]  Giorgio Russolillo,et al.  Partial least squares algorithms and methods , 2013 .

[52]  M. Mollenhauer,et al.  Neutrophil-derived myeloperoxidase promotes atherogenesis and neointima formation in mice. , 2016, International journal of cardiology.

[53]  Vasilis Ntziachristos,et al.  Looking and listening to light: the evolution of whole-body photonic imaging , 2005, Nature Biotechnology.

[54]  Z. Fayad,et al.  Fractionated feridex and positive contrast: In vivo MR imaging of atherosclerosis , 2008, Magnetic resonance in medicine.

[55]  B. Tang,et al.  A LRET-based luminescence nanoprobe for in situ imaging of CD36 activation and CD36-oxLDL binding in atherogenesis. , 2019, Analytical chemistry.

[56]  Xing-jie Liang,et al.  Biomedical nanomaterials for imaging-guided cancer therapy. , 2012, Nanoscale.

[57]  F. Caruso,et al.  Low-Fouling and Biodegradable Protein-Based Particles for Thrombus Imaging. , 2018, ACS nano.

[58]  M. Biran,et al.  Nanoparticles functionalised with an anti-platelet human antibody for in vivo detection of atherosclerotic plaque by magnetic resonance imaging. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[59]  R. Kanwar,et al.  Engineered atherosclerosis-specific zinc ferrite nanocomplex-based MRI contrast agents , 2016, Journal of Nanobiotechnology.

[60]  Christopher Poon,et al.  Gadolinium-Functionalized Peptide Amphiphile Micelles for Multimodal Imaging of Atherosclerotic Lesions , 2016, ACS omega.

[61]  Erkki Ruoslahti,et al.  Targeting atherosclerosis by using modular, multifunctional micelles , 2009, Proceedings of the National Academy of Sciences.

[62]  Z. Fayad,et al.  An ApoA-I mimetic peptide high-density-lipoprotein-based MRI contrast agent for atherosclerotic plaque composition detection. , 2008, Small.

[63]  P. Barthélémy,et al.  Iron oxide core oil-in-water nanoemulsion as tracer for atherosclerosis MPI and MRI imaging. , 2017, International journal of pharmaceutics.

[64]  M. Ladd,et al.  Wall Contrast Enhancement of Thrombosed Intracranial Aneurysms at 7T MRI , 2019, American Journal of Neuroradiology.

[65]  Sarah E Bohndiek,et al.  Contrast agents for molecular photoacoustic imaging , 2016, Nature Methods.

[66]  Rodolfo Miranda,et al.  Engineering Iron Oxide Nanoparticles for Clinical Settings , 2014, Nanobiomedicine.

[67]  J. Westra,et al.  Feasibility of [18F]-RGD for ex vivo imaging of atherosclerosis in detection of αvβ3 integrin expression , 2015, Journal of Nuclear Cardiology.

[68]  D. Berman,et al.  Coronary Atherosclerosis T1-Weighed Characterization With Integrated Anatomical Reference: Comparison With High-Risk Plaque Features Detected by Invasive Coronary Imaging. , 2017, JACC. Cardiovascular imaging.

[69]  S. Wickline,et al.  Molecular imaging of atherosclerosis with nanoparticle-based fluorinated MRI contrast agents. , 2015, Nanomedicine.

[70]  Mathias Hoehn,et al.  Labeling cells for in vivo tracking using (19)F MRI. , 2012, Biomaterials.

[71]  P. Doevendans,et al.  Recent developments and new perspectives on imaging of atherosclerotic plaque: role of anatomical, cellular and molecular MRI Part I and II , 2009, The International Journal of Cardiovascular Imaging.

[72]  L. Gutiérrez,et al.  Unambiguous detection of atherosclerosis using bioorthogonal nanomaterials. , 2019, Nanomedicine : nanotechnology, biology, and medicine.

[73]  Kai Jiang,et al.  Dual-Modal Magnetic Resonance and Fluorescence Imaging of Atherosclerotic Plaques in Vivo Using VCAM-1 Targeted Tobacco Mosaic Virus , 2014, Nano letters.

[74]  Patrick J. Gaffney,et al.  Quantitative “magnetic resonance immunohistochemistry” with ligand‐targeted 19F nanoparticles , 2004 .

[75]  R. Willette,et al.  Differential uptake of ferumoxtran‐10 and ferumoxytol, ultrasmall superparamagnetic iron oxide contrast agents in rabbit: Critical determinants of atherosclerotic plaque labeling , 2005, Journal of magnetic resonance imaging : JMRI.

[76]  Jie Tian,et al.  Molecular Imaging of Vulnerable Atherosclerotic Plaques in Vivo with Osteopontin-Specific Upconversion Nanoprobes. , 2017, ACS nano.

[77]  K. Moore,et al.  Macrophages in the Pathogenesis of Atherosclerosis , 2011, Cell.

[78]  Z. Fayad,et al.  Imaging and Nanomedicine in Inflammatory Atherosclerosis , 2014, Science Translational Medicine.

[79]  E. Bramucci,et al.  Thrombogenic potential of human coronary atherosclerotic plaques. , 2001, Blood.

[80]  René M. Botnar,et al.  Novel Approach for In Vivo Detection of Vulnerable Coronary Plaques Using Molecular 3-T CMR Imaging With an Albumin-Binding Probe. , 2018, JACC. Cardiovascular imaging.

[81]  Jinming Hu,et al.  Functionalization of NaGdF4 nanoparticles with a dibromomaleimide-terminated polymer for MR/optical imaging of thrombosis , 2020 .

[82]  H. Saji,et al.  Activatable fluorescence imaging of macrophages in atherosclerotic plaques using iron oxide nanoparticles conjugated with indocyanine green. , 2018, Atherosclerosis.

[83]  T. Hyeon,et al.  Nanostructured T1 MRI contrast agents , 2009 .

[84]  Po-Hsiang Tsui,et al.  Discrimination between Newly Formed and Aged Thrombi Using Empirical Mode Decomposition of Ultrasound B-Scan Image , 2015, BioMed research international.

[85]  S. Wickline,et al.  Molecular imaging by cardiovascular MR. , 2007, Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance.

[86]  Erling Falk,et al.  Update on acute coronary syndromes: the pathologists' view. , 2013, European heart journal.

[87]  Gerald Stübiger,et al.  Gold nanoparticle-conjugated anti-oxidized low-density lipoprotein antibodies for targeted lipidomics of oxidative stress biomarkers. , 2013, Analytical chemistry.

[88]  A. Malik,et al.  Signaling mechanisms regulating endothelial permeability. , 2006, Physiological reviews.

[89]  Konstantin Sokolov,et al.  Plasmonic intravascular photoacoustic imaging for detection of macrophages in atherosclerotic plaques. , 2009, Nano letters.

[90]  A. Speghini,et al.  Optical spectroscopy of nanocrystalline cubic Y2O3:Er3+ obtained by combustion synthesis , 2000 .

[91]  Shai Ashkenazi,et al.  Photoacoustic lifetime imaging of dissolved oxygen using methylene blue. , 2010, Journal of biomedical optics.

[92]  Tianfu Wang,et al.  Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications , 2016, Theranostics.

[93]  L. Ngo,et al.  The FLARE™ Intraoperative Near-Infrared Fluorescence Imaging System: A First-in-Human Clinical Trial in Breast Cancer Sentinel Lymph Node Mapping , 2009, Annals of Surgical Oncology.

[94]  Vasilis Ntziachristos,et al.  A macrophage uptaking near-infrared chemical probe CDnir7 for in vivo imaging of inflammation. , 2014, Chemical communications.

[95]  C. Bode,et al.  Targeting Ligand-Induced Binding Sites on GPIIb/IIIa via Single-Chain Antibody Allows Effective Anticoagulation Without Bleeding Time Prolongation , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[96]  K. Seung,et al.  Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. , 2002, Journal of the American College of Cardiology.

[97]  B. Zhang,et al.  Improved in vivo detection of atherosclerotic plaques with a tissue factor-targeting magnetic nanoprobe. , 2019, Acta biomaterialia.

[98]  Stanislav Emelianov,et al.  Methodical study on plaque characterization using integrated vascular ultrasound, strain and spectroscopic photoacoustic imaging , 2011, BiOS.

[99]  Shobha Ghosh,et al.  Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis , 2017, Translational research : the journal of laboratory and clinical medicine.

[100]  Megan C. Garland,et al.  A Bright Future for Precision Medicine: Advances in Fluorescent Chemical Probe Design and Their Clinical Application. , 2016, Cell chemical biology.

[101]  P. Choyke,et al.  New strategies for fluorescent probe design in medical diagnostic imaging. , 2010, Chemical reviews.

[102]  J. Leor,et al.  E‐selectin‐targeted copolymer reduces atherosclerotic lesions, adverse cardiac remodeling, and dysfunction , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[103]  Susan Hua,et al.  Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization , 2018, Front. Pharmacol..

[104]  Vasilis Ntziachristos,et al.  Optoacoustic Imaging of Naphthalocyanine: Potential for Contrast Enhancement and Therapy Monitoring , 2015, The Journal of Nuclear Medicine.

[105]  Wanwan Li,et al.  Gold nanoparticles for photoacoustic imaging. , 2015, Nanomedicine.

[106]  K. Kikuchi,et al.  Perfluorocarbon‐Based 19F MRI Nanoprobes for In Vivo Multicolor Imaging , 2018, Angewandte Chemie.

[107]  Hongcheng Shi,et al.  Detection of vulnerable atherosclerosis plaques with a dual-modal single-photon-emission computed tomography/magnetic resonance imaging probe targeting apoptotic macrophages. , 2015, ACS applied materials & interfaces.

[108]  H. Yang,et al.  Multifunctional and Redox-Responsive Self-Assembled Magnetic Nanovectors for Protein Delivery and Dual-Modal Imaging. , 2017, ACS applied materials & interfaces.

[109]  C. McNamara,et al.  Role of smooth muscle cells in the initiation and early progression of atherosclerosis. , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[110]  Hak Soo Choi,et al.  Cartilage-Specific Near-Infrared Fluorophores for Biomedical Imaging. , 2015, Angewandte Chemie.

[111]  Ralph Weissleder,et al.  Polymeric Nanoparticle PET/MR Imaging Allows Macrophage Detection in Atherosclerotic Plaques , 2013, Circulation research.

[112]  Ralph Weissleder,et al.  Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis , 2008, Circulation.

[113]  Da Xing,et al.  Fluorescence Quenching Nanoprobes Dedicated to In Vivo Photoacoustic Imaging and High-Efficient Tumor Therapy in Deep-Seated Tissue. , 2015, Small.

[114]  Wenpei Fan,et al.  On The Latest Three‐Stage Development of Nanomedicines based on Upconversion Nanoparticles , 2016, Advanced materials.

[115]  Kai Jiang,et al.  Shaping bio-inspired nanotechnologies to target thrombosis for dual optical-magnetic resonance imaging. , 2015, Journal of materials chemistry. B.

[116]  Kwangmeyung Kim,et al.  Comparison of in vivo targeting ability between cRGD and collagen‐targeting peptide conjugated nano‐carriers for atherosclerosis , 2018, Journal of controlled release : official journal of the Controlled Release Society.

[117]  S. Jackson Arterial thrombosis—insidious, unpredictable and deadly , 2011, Nature Medicine.

[118]  A. Bongers,et al.  Myeloperoxidase is a potential molecular imaging and therapeutic target for the identification and stabilization of high-risk atherosclerotic plaque , 2018, European heart journal.

[119]  Paul Schoenhagen,et al.  Emergence of targeted molecular imaging in atherosclerotic cardiovascular disease , 2009, Expert review of cardiovascular therapy.

[120]  C. Weber,et al.  Atherosclerosis: current pathogenesis and therapeutic options , 2011, Nature Medicine.

[121]  Jian Zhang,et al.  Inflammation-targeted gold nanorods for intravascular photoacoustic imaging detection of matrix metalloproteinase-2 (MMP2) in atherosclerotic plaques. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[122]  J. Egido,et al.  Targeted gold-coated iron oxide nanoparticles for CD163 detection in atherosclerosis by MRI , 2015, Scientific Reports.

[123]  J. Rudd,et al.  PET imaging of inflammation in atherosclerosis , 2014, Nature Reviews Cardiology.

[124]  D. Zhao,et al.  Lab on upconversion nanoparticles: optical properties and applications engineering via designed nanostructure. , 2015, Chemical Society reviews.

[125]  V. Fuster,et al.  Clinical Imaging of the High-Risk or Vulnerable Atherosclerotic Plaque , 2001, Circulation research.

[126]  Ping Gong,et al.  Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy. , 2014, ACS nano.

[127]  S. Caruthers,et al.  Molecular imaging and therapy of atherosclerosis with targeted nanoparticles , 2007, Journal of magnetic resonance imaging : JMRI.

[128]  J. G. Solé,et al.  1.3 μm emitting SrF2:Nd3+ nanoparticles for high contrast in vivo imaging in the second biological window , 2015, Nano Research.

[129]  E. Tremoli,et al.  Tissue factor in atherosclerosis. , 1999, Atherosclerosis.

[130]  B. Delman,et al.  Emerging Use of Ultra-High-Field 7T MRI in the Study of Intracranial Vascularity: State of the Field and Future Directions , 2019, American Journal of Neuroradiology.

[131]  M. Sung,et al.  Enhancement of the photostability and retention time of indocyanine green in sentinel lymph node mapping by anionic polyelectrolytes. , 2011, Biomaterials.

[132]  Yao Sun,et al.  Multimodality Molecular Imaging of Cardiovascular Disease Based on Nanoprobes , 2018, Cellular Physiology and Biochemistry.

[133]  Mark J Post,et al.  Nanoparticles for optical molecular imaging of atherosclerosis. , 2009, Small.

[134]  Paul C. Beard Photoacoustic imaging of blood vessel equivalent phantoms , 2002, SPIE BiOS.

[135]  E. Ratchford,et al.  Usefulness of coronary and carotid imaging rather than traditional atherosclerotic risk factors to identify firefighters at increased risk for cardiovascular disease. , 2014, The American journal of cardiology.

[136]  R. Schreiber,et al.  Programmable nanoparticle functionalization for in vivo targeting , 2013, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[137]  Matthew Tirrell,et al.  Monocyte‐Targeting Supramolecular Micellar Assemblies: A Molecular Diagnostic Tool for Atherosclerosis , 2015, Advanced healthcare materials.

[138]  Y. Lei,et al.  Nanoparticle targeting to diseased vasculature for imaging and therapy. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[139]  V. Fuster,et al.  Early identification of atherosclerotic disease by noninvasive imaging , 2010, Nature Reviews Cardiology.

[140]  P. Matthews,et al.  Near Infrared Fluorescence (NIRF) Molecular Imaging of Oxidized LDL with an Autoantibody in Experimental Atherosclerosis , 2016, Scientific Reports.

[141]  B. Ludewig,et al.  The in and out of monocytes in atherosclerotic plaques: Balancing inflammation through migration. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[142]  Paulino Vacas-Jacques,et al.  Clinical Characterization of Coronary Atherosclerosis With Dual-Modality OCT and Near-Infrared Autofluorescence Imaging. , 2016, JACC. Cardiovascular imaging.

[143]  J. Fujimoto Optical coherence tomography for ultrahigh resolution in vivo imaging , 2003, Nature Biotechnology.

[144]  J. Zwanenburg,et al.  Clinical applications of 7 T MRI in the brain. , 2013, European journal of radiology.

[145]  Wei Wang,et al.  Recent developments in multimodality fluorescence imaging probes , 2018, Acta pharmaceutica Sinica. B.

[146]  R. Krams,et al.  Molecular MR imaging of collagen in mouse atherosclerosis by using paramagnetic CNA35 micelles , 2012 .

[147]  Hsiao-Ying Wey,et al.  Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease , 2017, Nature Communications.

[148]  Feng Cao,et al.  In vivo MR and Fluorescence Dual-modality Imaging of Atherosclerosis Characteristics in Mice Using Profilin-1 Targeted Magnetic Nanoparticles , 2016, Theranostics.

[149]  R. Kruger,et al.  Photoacoustic ultrasound (PAUS)--reconstruction tomography. , 1995, Medical physics.

[150]  E. Warburton,et al.  Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography , 2015, Nature Communications.

[151]  V. Bulmus,et al.  The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications , 2010 .

[152]  K. Ley,et al.  Immune and inflammatory mechanisms of atherosclerosis (*). , 2009, Annual review of immunology.

[153]  Joseph J. Richardson,et al.  Ligand-Functionalized Poly(ethylene glycol) Particles for Tumor Targeting and Intracellular Uptake. , 2019, Biomacromolecules.

[154]  R. Virmani,et al.  Mechanisms of Plaque Formation and Rupture , 2014 .

[155]  Ralph Weissleder,et al.  Enzyme-Sensitive Magnetic Resonance Imaging Targeting Myeloperoxidase Identifies Active Inflammation in Experimental Rabbit Atherosclerotic Plaques , 2009, Circulation.

[156]  M. E. Kooi,et al.  Accumulation of Ultrasmall Superparamagnetic Particles of Iron Oxide in Human Atherosclerotic Plaques Can Be Detected by In Vivo Magnetic Resonance Imaging , 2003, Circulation.

[157]  Lihong V. Wang,et al.  In vivo photoacoustic tomography of chemicals: high-resolution functional and molecular optical imaging at new depths. , 2010, Chemical reviews.

[158]  T. Villines,et al.  Cardiovascular Imaging for the Primary Prevention of Atherosclerotic Cardiovascular Disease Events , 2015, Current Cardiovascular Imaging Reports.

[159]  T. Beyer,et al.  Quantitative assessment of atherosclerotic plaques on 18F-FDG PET/MRI: comparison with a PET/CT hybrid system , 2016, European Journal of Nuclear Medicine and Molecular Imaging.

[160]  Liangping Zhou,et al.  Ultrasmall NaGdF4 Nanodots for Efficient MR Angiography and Atherosclerotic Plaque Imaging , 2014, Advanced materials.

[161]  L. Boussel,et al.  Clinical and Histological Significance of Gadolinium Enhancement in Carotid Atherosclerotic Plaque , 2012, Stroke.

[162]  Gijs van Soest,et al.  Photoacoustic imaging of human coronary atherosclerosis in two spectral bands , 2013, Photoacoustics.

[163]  Chun Yuan,et al.  In Vivo Quantitative Measurement of Intact Fibrous Cap and Lipid-Rich Necrotic Core Size in Atherosclerotic Carotid Plaque: Comparison of High-Resolution, Contrast-Enhanced Magnetic Resonance Imaging and Histology , 2005, Circulation.

[164]  B. Tang,et al.  Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis , 2018, Nature Communications.

[165]  Lynne McCormick,et al.  Whole body cardiovascular magnetic resonance imaging to stratify symptomatic and asymptomatic atherosclerotic burden in patients with isolated cardiovascular disease , 2016, BMC Medical Imaging.

[166]  S A Wickline,et al.  Novel MRI Contrast Agent for Molecular Imaging of Fibrin: Implications for Detecting Vulnerable Plaques , 2001, Circulation.

[167]  A. Nederveen,et al.  Evaluation of ultrasmall superparamagnetic iron-oxide (USPIO) enhanced MRI with ferumoxytol to quantify arterial wall inflammation. , 2017, Atherosclerosis.

[168]  Zhuxian Zhou,et al.  Gadolinium-based contrast agents for magnetic resonance cancer imaging. , 2013, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[169]  N. Tamaki,et al.  FDG uptake and glucose transporter subtype expressions in experimental tumor and inflammation models. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[170]  Martin J Graves,et al.  In Vivo Detection of Macrophages in Human Carotid Atheroma: Temporal Dependence of Ultrasmall Superparamagnetic Particles of Iron Oxide–Enhanced MRI , 2004, Stroke.

[171]  A. Loewy,et al.  Osteopontin Transcription in Aortic Vascular Smooth Muscle Cells Is Controlled by Glucose-regulated Upstream Stimulatory Factor and Activator Protein-1 Activities* , 2002, The Journal of Biological Chemistry.

[172]  T. Derlin,et al.  Anti-MYC-associated zinc finger protein antibodies are associated with inflammatory atherosclerotic lesions on 18F-fluorodeoxyglucose positron emission tomography. , 2017, Atherosclerosis.

[173]  R. Weissleder,et al.  Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. , 1990, Radiology.

[174]  Jie Tian,et al.  MRI/optical dual-modality imaging of vulnerable atherosclerotic plaque with an osteopontin-targeted probe based on Fe3O4 nanoparticles. , 2017, Biomaterials.

[175]  Juan Li,et al.  Plant Polyphenol-Assisted Green Synthesis of Hollow CoPt Alloy Nanoparticles for Dual-Modality Imaging Guided Photothermal Therapy. , 2016, Small.

[176]  V. Fuster,et al.  MRI and Characterization of Atherosclerotic Plaque: Emerging Applications and Molecular Imaging , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[177]  R. Gropler,et al.  Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography–Based Imaging—Brief Report , 2018, Arteriosclerosis, thrombosis, and vascular biology.

[178]  E. Berg,et al.  Humanization and pharmacokinetics of a monoclonal antibody with specificity for both E- and P-selectin. , 1998, Journal of immunology.

[179]  Huang-Hao Yang,et al.  Co9Se8 Nanoplates as a New Theranostic Platform for Photoacoustic/Magnetic Resonance Dual‐Modal‐Imaging‐Guided Chemo‐Photothermal Combination Therapy , 2015, Advanced materials.

[180]  David Saloner,et al.  High resolution imaging of the intracranial vessel wall at 3 and 7 T using 3D fast spin echo MRI , 2016, Magnetic Resonance Materials in Physics, Biology and Medicine.

[181]  P. Beard Biomedical photoacoustic imaging , 2011, Interface Focus.

[182]  H. Jo,et al.  Multifunctional Nanoparticles Facilitate Molecular Targeting and miRNA Delivery to Inhibit Atherosclerosis in ApoE–/– Mice , 2015, ACS nano.

[183]  Peng Chen,et al.  Organic Dye Based Nanoparticles for Cancer Phototheranostics. , 2018, Small.

[184]  Z. Fayad,et al.  Annexin A5-functionalized bimodal nanoparticles for MRI and fluorescence imaging of atherosclerotic plaques. , 2010, Bioconjugate chemistry.

[185]  Zahi A Fayad,et al.  Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography , 2007, Nature Medicine.

[186]  J. Hamilton,et al.  In vivo Detection of Vulnerable Atherosclerotic Plaque by MRI in a Rabbit Model , 2010, Circulation. Cardiovascular imaging.

[187]  J. Ruíz-Cabello,et al.  Surface-Functionalized Nanoparticles by Olefin Metathesis: A Chemoselective Approach for In Vivo Characterization of Atherosclerosis Plaque. , 2015, Chemistry.

[188]  Fabien Hyafil,et al.  Ferumoxtran-10–Enhanced MRI of the Hypercholesterolemic Rabbit Aorta: Relationship Between Signal Loss and Macrophage Infiltration , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[189]  Ming Wu,et al.  Lipid micelles packaged with semiconducting polymer dots as simultaneous MRI/photoacoustic imaging and photodynamic/photothermal dual-modal therapeutic agents for liver cancer. , 2016, Journal of materials chemistry. B.

[190]  M. Olschewski,et al.  Magnetic Resonance Imaging Contrast Agent Targeted Toward Activated Platelets Allows In Vivo Detection of Thrombosis and Monitoring of Thrombolysis , 2008, Circulation.

[191]  P. Serruys,et al.  Invasive or non-invasive imaging for detecting high-risk coronary lesions? , 2017, Expert review of cardiovascular therapy.

[192]  R. Weissleder,et al.  An azulene dimer as a near-infrared quencher. , 2002, Angewandte Chemie.

[193]  Megan C. Garland,et al.  Dual-Modality Activity-Based Probes as Molecular Imaging Agents for Vascular Inflammation , 2016, The Journal of Nuclear Medicine.

[194]  P. Libby,et al.  Atheroma Susceptible to Thrombosis Exhibit Impaired Endothelial Permeability In Vivo as Assessed by Nanoparticle-Based Fluorescence Molecular Imaging , 2017, Circulation. Cardiovascular imaging.

[195]  Guillermo J Tearney,et al.  Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green. , 2016, JACC. Cardiovascular imaging.

[196]  Samir Mitragotri,et al.  Platelet-like Nanoparticles: Mimicking Shape, Flexibility, and Surface Biology of Platelets To Target Vascular Injuries , 2014, ACS nano.

[197]  Vasilis Ntziachristos,et al.  Cardiovascular optoacoustics: From mice to men – A review , 2019, Photoacoustics.

[198]  Ralph Weissleder,et al.  Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis , 2006, Circulation.

[199]  Qiangbin Wang,et al.  A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo. , 2016, Nanoscale.

[200]  P. Little,et al.  Non-invasive imaging techniques for the differentiation of acute and chronic thrombosis. , 2019, Thrombosis research.

[201]  H. Lee,et al.  Use of contrast enhancement and high-resolution 3D black-blood MRI to identify inflammation in atherosclerosis. , 2010, JACC. Cardiovascular imaging.

[202]  Jianhua Hao,et al.  Simultaneous synthesis and functionalization of water-soluble up-conversion nanoparticles for in-vitro cell and nude mouse imaging. , 2011, Nanoscale.

[203]  Z. Fayad,et al.  Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis , 2017, ACS nano.

[204]  R. Dixon,et al.  Magnetic Resonance Imaging of Atherosclerotic Plaque at Clinically Relevant Field Strengths (1T) by Targeting the Integrin α4β1 , 2018, Scientific Reports.

[205]  S. Emelianov,et al.  Intravascular photoacoustic imaging using an IVUS imaging catheter , 2007, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.

[206]  S. Emelianov,et al.  Detection of lipid in atherosclerotic vessels using ultrasound-guided spectroscopic intravascular photoacoustic imaging , 2010, Optics express.

[207]  J. Cheon,et al.  Iron Oxide Based Nanoparticles for Multimodal Imaging and Magnetoresponsive Therapy. , 2015, Chemical reviews.

[208]  J. Debatin,et al.  Magnetic Resonance Imaging of Atherosclerotic Plaque With Ultrasmall Superparamagnetic Particles of Iron Oxide in Hyperlipidemic Rabbits , 2001, Circulation.

[209]  S. Gambhir,et al.  Light in and sound out: emerging translational strategies for photoacoustic imaging. , 2014, Cancer research.

[210]  Mark J. Miller,et al.  Quantifying progression and regression of thrombotic risk in experimental atherosclerosis , 2015, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[211]  Sébastien Lecommandoux,et al.  Photo‐triggered polymer nanomedicines: From molecular mechanisms to therapeutic applications , 2019, Advanced drug delivery reviews.

[212]  W. Ouwehand,et al.  Detection of Atherosclerotic Inflammation by 68Ga-DOTATATE PET Compared to [18F]FDG PET Imaging , 2017, Journal of the American College of Cardiology.

[213]  Philippe Robert,et al.  Comparison of Different Types of Blood Pool Agents (P792, MS325, USPIO) in a Rabbit MR Angiography-like Protocol , 2003, Investigative radiology.

[214]  Da Xing,et al.  Gadolinium(III)-gold nanorods for MRI and photoacoustic imaging dual-modality detection of macrophages in atherosclerotic inflammation. , 2013, Nanomedicine.

[215]  Stanislav Y. Emelianov,et al.  Biomedical Applications of Photoacoustic Imaging with Exogenous Contrast Agents , 2011, Annals of Biomedical Engineering.

[216]  Xiaolong Liu,et al.  Magnetite nanocluster@poly(dopamine)-PEG@ indocyanine green nanobead with magnetic field-targeting enhanced MR imaging and photothermal therapy in vivo. , 2016, Colloids and surfaces. B, Biointerfaces.

[217]  L. Velázquez-Villegas,et al.  Nutrition and Atherosclerosis. , 2015, Archives of medical research.

[218]  Valentin Fuster,et al.  Imaging of atherosclerosis: magnetic resonance imaging. , 2011, European heart journal.

[219]  Wei Feng,et al.  Polyphosphoric acid capping radioactive/upconverting NaLuF4:Yb,Tm,153Sm nanoparticles for blood pool imaging in vivo. , 2013, Biomaterials.

[220]  Jiwon Kim,et al.  Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging. , 2018, Biomaterials.

[221]  B. Wall,et al.  Rare-earth-doped biological composites as in vivo shortwave infrared reporters , 2013, Nature Communications.

[222]  Michael Scott,et al.  Quantifying the Evolution of Vascular Barrier Disruption in Advanced Atherosclerosis with Semipermeant Nanoparticle Contrast Agents , 2011, PloS one.

[223]  Rolf Schubert,et al.  Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction, biological half‐lives and sensitivity , 2014, NMR in biomedicine.

[224]  Guosong Hong,et al.  Multifunctional in vivo vascular imaging using near-infrared II fluorescence , 2012, Nature Medicine.

[225]  Kai Chen,et al.  PET/NIRF/MRI triple functional iron oxide nanoparticles. , 2010, Biomaterials.

[226]  M. Stuber,et al.  Fluorine MR Imaging of Inflammation in Atherosclerotic Plaque in Vivo. , 2015, Radiology.

[227]  W. Mulder,et al.  Targeting myeloperoxidase in inflammatory atherosclerosis. , 2018, European heart journal.