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Tufaro V, Jaffer FA, Serruys PW, Onuma Y, van der Steen AFW, Stone GW, Muller JE, Marcu L, Van Soest G, Courtney BK, Tearney GJ, Bourantas CV. Emerging Hybrid Intracoronary Imaging Technologies and Their Applications in Clinical Practice and Research. JACC Cardiovasc Interv 2024; 17:1963-1979. [PMID: 39260958 DOI: 10.1016/j.jcin.2024.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 06/24/2024] [Accepted: 07/02/2024] [Indexed: 09/13/2024]
Abstract
Intravascular ultrasound and optical coherence tomography are used with increasing frequency for the care of coronary patients and in research studies. These imaging tools can identify culprit lesions in acute coronary syndromes, assess coronary stenosis severity, guide percutaneous coronary intervention (PCI), and detect vulnerable plaques and patients. However, they have significant limitations that have stimulated the development of multimodality intracoronary imaging catheters, which provide improvements in assessing vessel wall pathology and guiding PCI. Prototypes combining 2 or even 3 imaging probes with complementary attributes have been developed, and several multimodality systems have already been used in patients, with near-infrared spectroscopy intravascular ultrasound-based studies showing promising results for the identification of high-risk plaques. Moreover, postmortem histology studies have documented that hybrid imaging catheters can enable more accurate characterization of plaque morphology than standalone imaging. This review describes the evolution in the field of hybrid intracoronary imaging; presents the available multimodality catheters; and discusses their potential role in PCI guidance, vulnerable plaque detection, and the assessment of endovascular devices and emerging pharmacotherapies targeting atherosclerosis.
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Affiliation(s)
- Vincenzo Tufaro
- Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom; Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy
| | - Farouc A Jaffer
- Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Yoshinobu Onuma
- Department of Cardiology, University of Galway, Galway, Ireland
| | | | - Gregg W Stone
- Department of Cardiology, The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai, New York, New York, USA
| | - James E Muller
- Brigham and Women's Hospital, Division of Cardiovascular Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Laura Marcu
- Department of Biomedical Engineering, University of California, Davis, California, USA
| | - Gijs Van Soest
- Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Brian K Courtney
- Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada; Conavi Medical Inc, Toronto, Ontario, Canada
| | - Guillermo J Tearney
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Harvard-MIT Health Sciences and Technology, Cambridge, Massachusetts, USA
| | - Christos V Bourantas
- Department of Cardiology, Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom; Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; Institute of Cardiovascular Sciences, University College London, London, United Kingdom.
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Tesoro L, Hernandez I, Saura M, Badimón L, Zaragoza C. Novel cutting edge nano-strategies to address old long-standing complications in cardiovascular diseases. A comprehensive review. Eur J Clin Invest 2024; 54:e14208. [PMID: 38622800 DOI: 10.1111/eci.14208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 03/21/2024] [Accepted: 03/23/2024] [Indexed: 04/17/2024]
Abstract
BACKGROUND Cardiovascular diseases (CVD) impact a substantial portion of the global population and represent a significant threat to experiencing life-threatening outcomes, such as atherosclerosis, myocardial infarction, stroke and heart failure. Despite remarkable progress in pharmacology and medical interventions, CVD persists as a major public health concern, and now ranks as the primary global cause of death and the highest consumer of global budgets. Ongoing research endeavours persist in seeking novel therapeutic avenues and interventions to deepen our understanding of CVD, enhance prevention measures, and refine treatment strategies. METHODS Nanotechnology applied to the development of new molecular probes with diagnostic and theranostic properties represents one of the greatest technological challenges in preclinical and clinical research. RESULTS The application of nanotechnology in cardiovascular medicine holds great promise for advancing our understanding of CVDs and revolutionizing their diagnosis and treatment strategies, ultimately improving patient care and outcomes. In addition, the capacity of drug encapsulation in nanoparticles has significantly bolstered their biological safety, bioavailability and solubility. In combination with imaging technologies, molecular imaging has emerged as a pivotal therapeutic tool, offering insight into the molecular events underlying disease and facilitating targeted treatment approaches. CONCLUSION Here, we present a comprehensive overview of the recent advancements in targeted nanoparticle approaches for diagnosing CVDs, encompassing molecular imaging techniques, underscoring the significant progress in theranostic, as a novel and promising therapeutic strategy.
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Affiliation(s)
- Laura Tesoro
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
| | - Ignacio Hernandez
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
| | - Marta Saura
- Unidad de Fisiología, Departamento de Biología de Sistemas, Universidad de Alcalá (IRYCIS), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Lina Badimón
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Cardiovascular-Program ICCC, Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Barcelona, Spain
- Cardiovascular Research Chair, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Carlos Zaragoza
- Unidad Mixta de Investigación Cardiovascular, Departamento de Cardiología, Universidad Francisco de Vitoria, Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Samridhi, Setia A, Mehata AK, Priya V, Pradhan A, Prasanna P, Mohan S, Muthu MS. Nanoparticles for Thrombus Diagnosis and Therapy: Emerging Trends in Thrombus-theranostics. Nanotheranostics 2024; 8:127-149. [PMID: 38328614 PMCID: PMC10845253 DOI: 10.7150/ntno.92184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 12/09/2023] [Indexed: 02/09/2024] Open
Abstract
Cardiovascular disease is one of the chief factors that cause ischemic stroke, myocardial infarction, and venous thromboembolism. The elements that speed up thrombosis include nutritional consumption, physical activity, and oxidative stress. Even though the precise etiology and pathophysiology remain difficult topics that primarily rely on traditional medicine. The diagnosis and management of thrombosis are being developed using discrete non-invasive and non-surgical approaches. One of the emerging promising approach is ultrasound and photoacoustic imaging. The advancement of nanomedicines offers concentrated therapy and diagnosis, imparting efficacy and fewer side effects which is more significant than conventional medicine. This study addresses the potential of nanomedicines as theranostic agents for the treatment of thrombosis. In this article, we describe the factors that lead to thrombosis and its consequences, as well as summarize the findings of studies on thrombus formation in preclinical and clinical models and also provide insights on nanoparticles for thrombus imaging and therapy.
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Affiliation(s)
- Samridhi
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
| | - Aseem Setia
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
| | - Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
| | - Vishnu Priya
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
| | - Aditi Pradhan
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
| | - Pragya Prasanna
- National Institute of Pharmaceutical Education and Research, Hajipur, Bihar, India
| | - Syam Mohan
- Substance Abuse and Toxicology Research Centre, Jazan University, Jazan 45142, Saudi Arabia
- School of Health Sciences, University of Petroleum and Energy Studies, Dehradun 248007, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi-221005, India
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Merkes JM, Hasenbach A, Kiessling F, Hermann S, Banala S. Sensing Reactive Oxygen Species with Photoacoustic Imaging Using Conjugation-Extended BODIPYs. ACS Sens 2021; 6:4379-4388. [PMID: 34898171 DOI: 10.1021/acssensors.1c01674] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Short-lived reactive intermediates such as reactive oxygen species (ROS) regulate many physiological processes, but overproduction can also lead to severe tissue dysfunction. Thus, there is a high demand for noninvasive detection of reactive molecules, which, however, is challenging. Herein, we report photoacoustic detection of ROS using conjugated BODIPY probes (ROS-BODIPYs). The ROS reaction with conjugated BODIPYs induced a redshift in absorption by ∼100 nm into the near infrared (from ∼700 to ∼800 nm), quenched fluorescence, and generated strong photoacoustic (PA) signals. Thus, the ROS-activated and ROS-nonactivated states of ROS-BODIPYs can be detected in vivo by PA and fluorescence imaging. Interestingly, ROS activation is reversible, in the presence of excess reducing agents, e.g., citric acid, converted back to its original state, suggesting that ROS-BODIPYs can be useful for the detection of over production of ROS but not physiological amounts. This makes the imaging independent of accumulation of the activated probe with the physiological ROS amounts and thus strongly improves applicability and highlights the translational potential of ROS-BODIPYs for detecting overexpression of ROS in vivo by optical and photoacoustic imaging methods.
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Affiliation(s)
- Jean Michél Merkes
- Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
- Institute for Experimental Molecular Imaging University Clinic, RWTH Aachen University, Forckenbeckstra. 55, 52074 Aachen, Germany
- Fraunhofer Institute for Digital Medicine MEVIS, Max-von-Laue-Str. 2, 28359 Bremen, Germany
| | - Alexa Hasenbach
- European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, 48149 Münster, Germany
| | - Fabian Kiessling
- Institute for Experimental Molecular Imaging University Clinic, RWTH Aachen University, Forckenbeckstra. 55, 52074 Aachen, Germany
- Fraunhofer Institute for Digital Medicine MEVIS, Max-von-Laue-Str. 2, 28359 Bremen, Germany
| | - Sven Hermann
- European Institute for Molecular Imaging, University of Münster, Waldeyerstr. 15, 48149 Münster, Germany
| | - Srinivas Banala
- Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
- Institute for Experimental Molecular Imaging University Clinic, RWTH Aachen University, Forckenbeckstra. 55, 52074 Aachen, Germany
- Fraunhofer Institute for Digital Medicine MEVIS, Max-von-Laue-Str. 2, 28359 Bremen, Germany
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Tian H, Lin L, Ba Z, Xue F, Li Y, Zeng W. Nanotechnology combining photoacoustic kinetics and chemical kinetics for thrombosis diagnosis and treatment. CHINESE CHEM LETT 2021. [DOI: 10.1016/j.cclet.2021.05.070] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Abstract
Fuelled by innovation, optical microscopy plays a critical role in the life sciences and medicine, from basic discovery to clinical diagnostics. However, optical microscopy is limited by typical penetration depths of a few hundred micrometres for in vivo interrogations in the visible spectrum. Optoacoustic microscopy complements optical microscopy by imaging the absorption of light, but it is similarly limited by penetration depth. In this Review, we summarize progress in the development and applicability of optoacoustic mesoscopy (OPAM); that is, optoacoustic imaging with acoustic resolution and wide-bandwidth ultrasound detection. OPAM extends the capabilities of optical imaging beyond the depths accessible to optical and optoacoustic microscopy, and thus enables new applications. We explain the operational principles of OPAM, its placement as a bridge between optoacoustic microscopy and optoacoustic macroscopy, and its performance in the label-free visualization of tissue pathophysiology, such as inflammation, oxygenation, vascularization and angiogenesis. We also review emerging applications of OPAM in clinical and biological imaging.
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Yu J, Pin S, Lin X, Su M, Bai M, Kim K. Photostable, hydrophilic, and near infrared quaterrylene-based dyes for photoacoustic imaging. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2018; 93:1012-1019. [PMID: 30274031 PMCID: PMC6172961 DOI: 10.1016/j.msec.2018.09.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2017] [Revised: 05/14/2018] [Accepted: 09/04/2018] [Indexed: 01/22/2023]
Abstract
Novel near-infrared contrast agents based on the quaterrylene structure were strategically developed and tested for high photo-stability. Both a dendrimeric quaterrylene molecule, QR-G2-COOH, and a small molecule cationic quaterrylene dye, QR-4PyC4, remain optically stable and continue to generate a competitive photoacoustic response when irradiated by short near-infrared laser pulses for a relatively long time in an in-vitro cell study, unlike indocyanine green that rapidly decreases photoacoustic signal amplitude. The small molecule dye, QR-4PyC4 exhibits not only significantly higher cellular uptake rate than QR-G2-COOH and indocyanine green, but also low toxicity at a concentration of up to 10 μM. The dendrimeric dye, QR-G2-COOH that has surface functional groups available for conjugation with targeting and therapeutic agents shows the highest photoacoustic amplitude with high optical stability. Therefore, QR-4PyC4 can be a promising universal, sensitive and reliable photoacoustic contrast agent and QR-G2-COOH has great potential as a nano-platform with stable photoacoustic imaging capability.
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Affiliation(s)
- Jaesok Yu
- Center for Ultrasound Molecular Imaging and Therapeutics, Department of Medicine & Heart and Vascular Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA
| | - Shao Pin
- Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA
| | - Xiangwei Lin
- Center for Ultrasound Molecular Imaging and Therapeutics, Department of Medicine & Heart and Vascular Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA
| | - Meng Su
- Vanderbilt University Institute of Imaging Sciences, Nashville, TN 37232, USA
| | - Mingfeng Bai
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
| | - Kang Kim
- Center for Ultrasound Molecular Imaging and Therapeutics, Department of Medicine & Heart and Vascular Institute, University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA 15213, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh and UPMC, Pittsburgh, PA 15219, USA.
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Sowers T, Emelianov S. Exogenous imaging contrast and therapeutic agents for intravascular photoacoustic imaging and image-guided therapy. Phys Med Biol 2018; 63:22TR01. [PMID: 30403195 DOI: 10.1088/1361-6560/aae62b] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Intravascular photoacoustic (IVPA) imaging has been developed in recent years as a viable imaging modality for the assessment of atherosclerotic plaques. Exogenous imaging contrast and therapeutic agents further enhance this imaging modality and provide significant benefits. Imaging contrast agents can significantly increase photoacoustic signal, resulting in enhanced plaque detection and characterization. The ability to use these particles to molecularly target markers of disease progression makes it possible to determine patient-specific levels of risk and plan treatments accordingly. With improved diagnosis, clinicians will be able to use therapeutic agents that are synergistic with IVPA imaging to treat atherosclerotic patients. Pre-clinical and clinical studies with relevance to IVPA imaging have shown promise in the area of diagnosis and therapeutics. In this review, we present a variety of imaging contrast agents that are either designed for or are compatible with IVPA imaging, cover uses of therapeutic agents that compliment this imaging modality, and discuss future directions of research in the field.
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Affiliation(s)
- Timothy Sowers
- Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, United States of America. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, United States of America
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Harris-Birtill D, Singh M, Zhou Y, Shah A, Ruenraroengsak P, Gallina ME, Hanna GB, Cass AEG, Porter AE, Bamber J, Elson DS. Gold nanorod reshaping in vitro and in vivo using a continuous wave laser. PLoS One 2017; 12:e0185990. [PMID: 29045438 PMCID: PMC5646757 DOI: 10.1371/journal.pone.0185990] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 09/23/2017] [Indexed: 11/19/2022] Open
Abstract
Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics as they possess features which lend themselves in equal measures as contrast agents and catalysts for photothermal therapy. Their optical absorption spectral peak wavelength is determined by their size and shape. Photothermal therapy using GNRs is typically established using near infrared light as this allows sufficient penetration into the tumour matrix. Continuous wave (CW) lasers are the most commonly applied source of near infrared irradiation on GNRs for tumour photothermal therapy. It is perceived that large tumours may require fractionated or prolonged irradiation. However the true efficacy of repeated or protracted CW irradiation on tumour sites using the original sample of GNRs remains unclear. In this study spectroscopy and transmission electron microscopy are used to demonstrate that GNRs reshape both in vitro and in vivo after CW irradiation, which reduces their absorption efficiency. These changes were sustained throughout and beyond the initial period of irradiation, resulting from a spectral blue-shift and a considerable diminution in the absorption peak of GNRs. Solid subcutaneous tumours in immunodeficient BALB/c mice were subjected to GNRs and analysed with electron microscopy pre- and post-CW laser irradiation. This phenomenon of thermally induced GNR reshaping can occur at relatively low bulk temperatures, well below the bulk melting point of gold. Photoacoustic monitoring of GNR reshaping is also evaluated as a potential clinical aid to determine GNR absorption and reshaping during photothermal therapy. Aggregation of particles was coincidentally observed following CW irradiation, which would further diminish the subsequent optical absorption capacity of irradiated GNRs. It is thus established that sequential or prolonged applications of CW laser will not confer any additional photothermal effect on tumours due to significant attenuations in the peak optical absorption properties of GNRs following primary laser irradiation.
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Affiliation(s)
- David Harris-Birtill
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Mohan Singh
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Yu Zhou
- Department of Chemistry, Imperial College London, London, United Kingdom
| | - Anant Shah
- Joint Department of Physics and CRUK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, London, United Kingdom
| | - Pakatip Ruenraroengsak
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Materials and London Centre for Nanotechnology, Imperial College London, London, United Kingdom
| | - Maria Elena Gallina
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - George B. Hanna
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Anthony E. G. Cass
- Department of Chemistry, Imperial College London, London, United Kingdom
| | - Alexandra E. Porter
- Department of Materials and London Centre for Nanotechnology, Imperial College London, London, United Kingdom
| | - Jeffrey Bamber
- Joint Department of Physics and CRUK Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, London, United Kingdom
| | - Daniel S. Elson
- Hamlyn Centre for Robotic Surgery, Imperial College London, London, United Kingdom
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
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Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models. Int J Mol Sci 2016; 17:ijms17091511. [PMID: 27618031 PMCID: PMC5037788 DOI: 10.3390/ijms17091511] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 08/24/2016] [Accepted: 08/31/2016] [Indexed: 12/13/2022] Open
Abstract
Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies.
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Abstract
Molecular imaging offers great potential for noninvasive visualization and quantitation of the cellular and molecular components involved in atherosclerotic plaque stability. In this chapter, we review emerging molecular imaging modalities and approaches for quantitative, noninvasive detection of early biological processes in atherogenesis, including vascular endothelial permeability, endothelial adhesion molecule up-regulation, and macrophage accumulation, with special emphasis on mouse models. We also highlight a number of targeted imaging nanomaterials for assessment of advanced atherosclerotic plaques, including extracellular matrix degradation, proteolytic enzyme activity, and activated platelets using mouse models of atherosclerosis. The potential for clinical translation of molecular imaging nanomaterials for assessment of atherosclerotic plaque biology, together with multimodal approaches is also discussed.
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12
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Abstract
Photoacoustic (PA) imaging is a biomedical imaging modality that provides functional information regarding the cellular and molecular signatures of tissue by using endogenous and exogenous contrast agents. There has been tremendous effort devoted to the development of PA imaging agents, and gold nanoparticles as exogenous contrast agents have great potential for PA imaging due to their inherent and geometrically induced optical properties. The gold-based nanoparticles that are most commonly employed for PA imaging include spheres, rods, shells, prisms, cages, stars and vesicles. This article provides an overview of the current state of research in utilizing these gold nanomaterials for PA imaging of cancer, atherosclerotic plaques, brain function and image-guided therapy.
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Affiliation(s)
- Wanwan Li
- State Key Lab of Metal Matrix Composites, School of Materials Science & Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
| | - Xiaoyuan Chen
- Laboratory of Molecular Imaging & Nanomedicine (LOMIN), National Institute of Biomedical Imaging & Bioengineering (NIBIB), NIH, Bethesda, MD 20892, USA
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Di Paola M, Chiriacò F, Soloperto G, Conversano F, Casciaro S. Echographic imaging of tumoral cells through novel nanosystems for image diagnosis. World J Radiol 2014; 6:459-470. [PMID: 25071886 PMCID: PMC4109097 DOI: 10.4329/wjr.v6.i7.459] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 04/25/2014] [Accepted: 05/19/2014] [Indexed: 02/06/2023] Open
Abstract
Since the recognition of disease molecular basis, it has become clear that the keystone moments of medical practice, namely early diagnosis, appropriate therapeutic treatment and patient follow-up, must be approached at a molecular level. These objectives will be in the near future more effectively achievable thanks to the impressive developments in nanotechnologies and their applications to the biomedical field, starting-up the nanomedicine era. The continuous advances in the development of biocompatible smart nanomaterials, in particular, will be crucial in several aspects of medicine. In fact, the possibility of manufacturing nanoparticle contrast agents that can be selectively targeted to specific pathological cells has extended molecular imaging applications to non-ionizing techniques and, at the same time, has made reachable the perspective of combining highly accurate diagnoses and personalized therapies in a single theranostic intervention. Main developing applications of nanosized theranostic agents include targeted molecular imaging, controlled drug release, therapeutic monitoring, guidance of radiation-based treatments and surgical interventions. Here we will review the most recent findings in nanoparticles contrast agents and their applications in the field of cancer molecular imaging employing non-ionizing techniques and disease-specific contrast agents, with special focus on recent findings on those nanomaterials particularly promising for ultrasound molecular imaging and simultaneous treatment of cancer.
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Combination-targeting to multiple endothelial cell adhesion molecules modulates binding, endocytosis, and in vivo biodistribution of drug nanocarriers and their therapeutic cargoes. J Control Release 2014; 188:87-98. [PMID: 24933603 DOI: 10.1016/j.jconrel.2014.06.008] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2014] [Revised: 05/24/2014] [Accepted: 06/07/2014] [Indexed: 01/11/2023]
Abstract
Designing of drug nanocarriers to aid delivery of therapeutics is an expanding field that can improve medical treatments. Nanocarriers are often functionalized with elements that recognize cell-surface molecules involved in subcellular transport to improve targeting and endocytosis of therapeutics. Combination-targeting using several affinity elements further modulates this outcome. The most studied example is endothelial targeting via multiple cell adhesion molecules (CAMs), which mimics the strategy of leukocytes to adhere and traverse the vascular endothelium. Yet, the implications of this strategy on intracellular transport and in vivo biodistribution remain uncharacterized. We examined this using nanocarriers functionalized for dual- or triple-targeting to intercellular, platelet-endothelial, and/or vascular CAMs (ICAM-1, PECAM-1, VCAM-1). These molecules differ in expression level, location, pathological stimulation, and/or endocytic pathway. In endothelial cells, binding of PECAM-1/VCAM-1-targeted nanocarriers was intermediate to single-targeted counterparts and enhanced in disease-like conditions. ICAM-1/PECAM-1-targeted nanocarriers surpassed PECAM-1/VCAM-1 in control, but showed lower selectivity toward disease-like conditions. Triple-targeting resulted in binding similar to ICAM-1/PECAM-1 combination and displayed the highest selectivity in disease-like conditions. All combinations were effectively internalized by the cells, with slightly better performance when targeting receptors of different endocytic pathways. In vivo, ICAM-1/PECAM-1-targeted nanocarriers outperformed PECAM-1/VCAM-1 in control and disease-like conditions, and triple-targeted counterparts slightly enhanced this outcome in some organs. As a result, delivery of a model therapeutic cargo (acid sphingomyelinase, deficient in Niemann-Pick disease A-B) was enhanced to all affected organs by triple-targeted nanocarriers, particularly in disease-like conditions. Therefore, multi-CAM targeting may aid the optimization of some therapeutic nanocarriers, where the combination and multiplicity of the affinity moieties utilized allow modulation of targeting performance.
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Johnson JL, van Wijk K, Sabick M. Characterizing phantom arteries with multi-channel laser ultrasonics and photo-acoustics. ULTRASOUND IN MEDICINE & BIOLOGY 2014; 40:513-520. [PMID: 24412169 DOI: 10.1016/j.ultrasmedbio.2013.10.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2013] [Revised: 09/07/2013] [Accepted: 10/08/2013] [Indexed: 06/03/2023]
Abstract
Multi-channel photo-acoustic and laser ultrasonic waves are used to sense the characteristics of proxies for healthy and diseased vessels. The acquisition system is non-contacting and non-invasive with a pulsed laser source and a laser vibrometer detector. As the wave signatures of our targets are typically low in amplitude, we exploit multi-channel acquisition and processing techniques. These are commonly used in seismology to improve the signal-to-noise ratio of data. We identify vessel proxies with a diameter on the order of 1 mm, at a depth of 18 mm. Variations in scattered and photo-acoustic signatures are related to differences in vessel wall properties and content. The methods described have the potential to improve imaging and better inform interventions for atherosclerotic vessels, such as the carotid artery.
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Affiliation(s)
- Jami L Johnson
- Mechanical and Biomedical Engineering Department, Boise State University, Boise, Idaho, USA; Department of Physics, University of Auckland, Auckland, New Zealand.
| | - Kasper van Wijk
- Department of Physics, University of Auckland, Auckland, New Zealand
| | - Michelle Sabick
- Mechanical and Biomedical Engineering Department, Boise State University, Boise, Idaho, USA
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Lan SM, Wu YN, Wu PC, Sun CK, Shieh DB, Lin RM. Advances in noninvasive functional imaging of bone. Acad Radiol 2014; 21:281-301. [PMID: 24439341 DOI: 10.1016/j.acra.2013.11.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Revised: 11/20/2013] [Accepted: 11/26/2013] [Indexed: 02/03/2023]
Abstract
The demand for functional imaging in clinical medicine is comprehensive. Although the gold standard for the functional imaging of human bones in clinical settings is still radionuclide-based imaging modalities, nonionizing noninvasive imaging technology in small animals has greatly advanced in recent decades, especially the diffuse optical imaging to which Britton Chance made tremendous contributions. The evolution of imaging probes, instruments, and computation has facilitated exploration in the complicated biomedical research field by allowing longitudinal observation of molecular events in live cells and animals. These research-imaging tools are being used for clinical applications in various specialties, such as oncology, neuroscience, and dermatology. The Bone, a deeply located mineralized tissue, presents a challenge for noninvasive functional imaging in humans. Using nanoparticles (NP) with multiple favorable properties as bioimaging probes has provided orthopedics an opportunity to benefit from these noninvasive bone-imaging techniques. This review highlights the historical evolution of radionuclide-based imaging, computed tomography, positron emission tomography, and magnetic resonance imaging, diffuse optics-enabled in vivo technologies, vibrational spectroscopic imaging, and a greater potential for using NPs for biomedical imaging.
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17
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Ramos J, Rege K. Poly(aminoether)-gold nanorod assemblies for shRNA plasmid-induced gene silencing. Mol Pharm 2013; 10:4107-19. [PMID: 24066795 DOI: 10.1021/mp400080f] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal hyperthermia treatments, and therapeutic delivery for several diseases. We generated poly(aminoether)-GNR nanoassemblies using a layer-by-layer deposition approach based on the 1,4C-1,4Bis polymer from a library recently synthesized in our laboratory. Subtoxic concentrations of 1,4C-1,4Bis-GNR nanoassemblies were employed to deliver expression vectors that express shRNA ("shRNA plasmid") against firefly luciferase gene to knock down expression of the protein constitutively expressed in prostate cancer cells. The role of hydrodynamic size and zeta potential in determining nanoassembly mediated luciferase silencing was investigated. Finally, the theranostic potential of 1,4C-1,4Bis-GNR nanoassemblies was demonstrated using live cell two-photon induced luminescence bioimaging. Our results indicate that poly(aminoether)-GNR nanoassemblies are a promising theranostic platform for delivery of therapeutic payloads capable of simultaneous gene silencing and bioimaging.
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Affiliation(s)
- James Ramos
- Biomedical Engineering, School of Biological and Health Systems Engineering and ‡Chemical Engineering, School for Engineering of Matter, Transport, and Energy, Arizona State University , 501 E. Tyler Mall, ECG 303, Tempe, Arizona 85287-6106, United States
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18
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López de Pablo CS, Ramos Ávila JA, Fernández Cabada T, del Pozo Guerrero F, Serrano Olmedo JJ. Photoacoustic effect measurement in aqueous suspensions of gold nanorods caused by low-frequency and low-power near-infrared pulsing laser irradiation. APPLIED OPTICS 2013; 52:4698-4705. [PMID: 23842268 DOI: 10.1364/ao.52.004698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Accepted: 06/01/2013] [Indexed: 06/02/2023]
Abstract
When aqueous suspensions of gold nanorods are irradiated with a pulsing laser (808 nm), pressure waves appear even at low frequencies (pulse repetition rate of 25 kHz). We found that the pressure wave amplitude depends on the dynamics of the phenomenon. For fixed concentration and average laser current intensity, the amplitude of the pressure waves shows a trend of increasing with the pulse slope and the pulse maximum amplitude. We postulate that the detected ultrasonic pressure waves are a sort of shock waves that would be generated at the beginning of each pulse, because the pressure wave amplitude would be the result of the positive interference of all the individual shock waves.
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Affiliation(s)
- Cristina Sánchez López de Pablo
- Centre for Biomedical Technology (CTB), Universidad Politécnica de Madrid (UPM), Campus de Montegancedo, 28223, Pozuelo de Alarcón, Madrid, Spain.
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19
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Mehrmohammadi M, Yoon SJ, Yeager D, Emelianov SY. Photoacoustic Imaging for Cancer Detection and Staging. CURRENT MOLECULAR IMAGING 2013; 2:89-105. [PMID: 24032095 PMCID: PMC3769095 DOI: 10.2174/2211555211302010010] [Citation(s) in RCA: 135] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Cancer is one of the leading causes of death in the world. Diagnosing a cancer at its early stages of development can decrease the mortality rate significantly and reduce healthcare costs. Over the past two decades, photoacoustic imaging has seen steady growth and has demonstrated notable capabilities to detect cancerous cells and stage cancer. Furthermore, photoacoustic imaging combined with ultrasound imaging and augmented with molecular targeted contrast agents is capable of imaging cancer at the cellular and molecular level, thus opening diverse opportunities to improve diagnosis of tumors, detect circulating tumor cells and identify metastatic lymph nodes. In this paper we introduce the principles of photoacoustic imaging, and review recent developments in photoacoustic imagingas an emerging imaging modality for cancer diagnosis and staging.
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Affiliation(s)
- Mohammad Mehrmohammadi
- Department of Biomedical Engineering, University of Texas at Austin, Austin TX 78712, USA
- Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota 55901, USA
| | - Soon Joon Yoon
- Department of Biomedical Engineering, University of Texas at Austin, Austin TX 78712, USA
| | - Douglas Yeager
- Department of Biomedical Engineering, University of Texas at Austin, Austin TX 78712, USA
| | - Stanislav Y. Emelianov
- Department of Biomedical Engineering, University of Texas at Austin, Austin TX 78712, USA
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Ramos J, Huang HC, Rege K. Delivery of plasmid DNA to mammalian cells using polymer-gold nanorod assemblies. Methods Mol Biol 2013; 991:81-91. [PMID: 23546661 DOI: 10.1007/978-1-62703-336-7_9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Functionalized and surface-modified gold nanorods (GNRs) have emerged as promising vehicles for the delivery of several therapeutic agents. Ease of functionalization, increased stability, biocompatibility, and size-dependent plasmonic properties make gold nanorods attractive in sensing, imaging, and delivery to different cellular types. Here, we demonstrate the use of polyelectrolyte-coated GNRs (PE-GNRs) for delivering plasmid DNA to mammalian cells for transgene expression.
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Affiliation(s)
- James Ramos
- School of Biological and Health Systems & Chemical Engineering, Center for the Convergence of Physical Science and Cancer Biology, Arizona State University, Tempe, AZ, USA
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21
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McAteer MA, Choudhury RP. Targeted molecular imaging of vascular inflammation in cardiovascular disease using nano- and micro-sized agents. Vascul Pharmacol 2013; 58:31-8. [DOI: 10.1016/j.vph.2012.10.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2012] [Accepted: 10/19/2012] [Indexed: 01/15/2023]
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Ha SH, Carson AR, Kim K. Ferritin as a novel reporter gene for photoacoustic molecular imaging. Cytometry A 2012; 81:910-5. [PMID: 22949299 DOI: 10.1002/cyto.a.22160] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Revised: 07/27/2012] [Accepted: 07/29/2012] [Indexed: 11/10/2022]
Abstract
Reporter genes may serve as endogenous contrast agents in the field of photoacoustic (PA) molecular imaging (PMI), enabling greater characterization of detailed cellular processes and disease progression. To demonstrate the feasibility of using ferritin as a reporter gene, human melanoma SK-24 (SK-MEL-24) cells were co-transfected with plasmid expressing human heavy chain ferritin (H-FT) and plasmid expressing enhanced green fluorescent protein (pEGFP-C1) using lipofectamine™ 2000. Nontransfected SK-MEL-24 cells served as a negative control. Fluorescent imaging of GFP confirmed transfection and transgene expression in co-transfected cells. To detect iron accumulation due to ferritin overexpression in SK-MEL-24 cells, a focused high-frequency ultrasonic transducer (60 MHz, f/1.5), synchronized to a pulsed laser (fluence < 5 mJ/cm(2)) was used to scan the PA signal at a wide range NIR wavelengths (850-950 nm). PA signal intensity from H-FT transfected SK-MEL-24 cells was about 5-9 dB higher than nontransfected SK-MEL-24 cells at 850-950 nm. Immunofluorescence and RT-PCR analysis both indicate high levels of ferritin expression in H-FT transfected SK-MEL24 cells, with little ferritin expression in nontransfected SK-MEL-24 cells. In this study, the feasibility of using ferritin as a reporter gene for PMI has been demonstrated in vitro. The use of ferritin as a reporter gene represents a novel concept for PMI using an endogenous contrast agent and may provide various opportunities for molecular imaging and basic science research.
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Affiliation(s)
- Seung Han Ha
- Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA
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23
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Conversano F, Soloperto G, Greco A, Ragusa A, Casciaro E, Chiriacò F, Demitri C, Gigli G, Maffezzoli A, Casciaro S. Echographic detectability of optoacoustic signals from low-concentration PEG-coated gold nanorods. Int J Nanomedicine 2012; 7:4373-89. [PMID: 22927756 PMCID: PMC3420597 DOI: 10.2147/ijn.s33908] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2012] [Indexed: 01/12/2023] Open
Abstract
Purpose: To evaluate the diagnostic performance of gold nanorod (GNR)-enhanced optoacoustic imaging employing a conventional echographic device and to determine the most effective operative configuration in order to assure optoacoustic effectiveness, nanoparticle stability, and imaging procedure safety. Methods: The most suitable laser parameters were experimentally determined in order to assure nanoparticle stability during the optoacoustic imaging procedures. The selected configuration was then applied to a novel tissue-mimicking phantom, in which GNR solutions covering a wide range of low concentrations (25–200 pM) and different sample volumes (50–200 μL) were exposed to pulsed laser irradiation. GNR-emitted optoacoustic signals were acquired either by a couple of single-element ultrasound probes or by an echographic transducer. Off-line analysis included: (a) quantitative evaluation of the relationships between GNR concentration, sample volume, phantom geometry, and amplitude of optoacoustic signals propagating along different directions; (b) echographic detection of “optoacoustic spots,” analyzing their intensity, spatial distribution, and clinical exploitability. MTT measurements performed on two different cell lines were also used to quantify biocompatibility of the synthesized GNRs in the adopted doses. Results: Laser irradiation at 30 mJ/cm2 for 20 seconds resulted in the best compromise among the requirements of effectiveness, safety, and nanoparticle stability. Amplitude of GNR-emitted optoacoustic pulses was proportional to both sample volume and concentration along each considered propagation direction for all the tested boundary conditions, providing an experimental confirmation of isotropic optoacoustic emission. Average intensity of echographically detected spots showed similar behavior, emphasizing the presence of an “ideal” GNR concentration (100 pM) that optimized optoacoustic effectiveness. The tested GNRs also exhibited high biocompatibility over the entire considered concentration range. Conclusion: An optimal configuration for GNR-enhanced optoacoustic imaging was experimentally determined, demonstrating in particular its feasibility with a conventional echographic device. The proposed approach can be easily extended to quantitative performance evaluation of different contrast agents for optoacoustic imaging.
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Dorward DA, Lucas CD, Rossi AG, Haslett C, Dhaliwal K. Imaging inflammation: molecular strategies to visualize key components of the inflammatory cascade, from initiation to resolution. Pharmacol Ther 2012; 135:182-99. [PMID: 22627270 DOI: 10.1016/j.pharmthera.2012.05.006] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2012] [Accepted: 05/07/2012] [Indexed: 12/19/2022]
Abstract
Dysregulation of inflammation is central to the pathogenesis of innumerable human diseases. Understanding and tracking the critical events in inflammation are crucial for disease monitoring and pharmacological drug discovery and development. Recent progress in molecular imaging has provided novel insights into spatial associations, molecular events and temporal sequelae in the inflammatory process. While remaining a burgeoning field in pre-clinical research, increasing application in man affords researchers the opportunity to study disease pathogenesis in humans in situ thereby revolutionizing conventional understanding of pathophysiology and potential therapeutic targets. This review provides a description of commonly used molecular imaging modalities, including optical, radionuclide and magnetic resonance imaging, and details key advances and translational opportunities in imaging inflammation from initiation to resolution.
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Affiliation(s)
- D A Dorward
- MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
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25
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Jacobs AH, Tavitian B. Noninvasive molecular imaging of neuroinflammation. J Cereb Blood Flow Metab 2012; 32:1393-415. [PMID: 22549622 PMCID: PMC3390799 DOI: 10.1038/jcbfm.2012.53] [Citation(s) in RCA: 180] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2011] [Revised: 03/05/2012] [Accepted: 03/23/2012] [Indexed: 12/23/2022]
Abstract
Inflammation is a highly dynamic and complex adaptive process to preserve and restore tissue homeostasis. Originally viewed as an immune-privileged organ, the central nervous system (CNS) is now recognized to have a constant interplay with the innate and the adaptive immune systems, where resident microglia and infiltrating immune cells from the periphery have important roles. Common diseases of the CNS, such as stroke, multiple sclerosis (MS), and neurodegeneration, elicit a neuroinflammatory response with the goal to limit the extent of the disease and to support repair and regeneration. However, various disease mechanisms lead to neuroinflammation (NI) contributing to the disease process itself. Molecular imaging is the method of choice to try to decipher key aspects of the dynamic interplay of various inducers, sensors, transducers, and effectors of the orchestrated inflammatory response in vivo in animal models and patients. Here, we review the basic principles of NI with emphasis on microglia and common neurologic disease mechanisms, the molecular targets which are being used and explored for imaging, and molecular imaging of NI in frequent neurologic diseases, such as stroke, MS, neurodegeneration, epilepsy, encephalitis, and gliomas.
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Affiliation(s)
- Andreas H Jacobs
- European Institute for Molecular Imaging (EIMI) at the Westfalian Wilhelms-University of Münster (WWU), Münster, Germany.
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Ramos J, Rege K. Transgene delivery using poly(amino ether)-gold nanorod assemblies. Biotechnol Bioeng 2012; 109:1336-46. [PMID: 22170455 DOI: 10.1002/bit.24408] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Revised: 10/31/2011] [Accepted: 11/28/2011] [Indexed: 01/19/2023]
Abstract
Gold nanorods (GNRs) have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment, and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach; polymers from a poly(amino ether) library recently synthesized in our laboratory were employed to generate the PAE-GNR assemblies. PAE-GNR assemblies demonstrate long-term colloidal stability as well as the capacity to bind plasmid DNA by means of electrostatic interactions. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs generated using 1,4C-1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k-GNRs), a current standard for polymer-mediated gene delivery. The roles of polyelectrolyte chemistry and zeta-potential in determining transgene expression efficacies of PAE-GNR assemblies were investigated. Our results indicate that stable and effective PAE-GNR assemblies are a promising engineered platform for transgene delivery. PAE-GNRs also have the potential to be used simultaneously for photothermal ablation, photothermally enhanced drug and gene delivery, and biological imaging, thus making them a powerful theranostic platform.
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Affiliation(s)
- James Ramos
- School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-6106, USA
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Luke GP, Yeager D, Emelianov SY. Biomedical applications of photoacoustic imaging with exogenous contrast agents. Ann Biomed Eng 2011; 40:422-37. [PMID: 22048668 DOI: 10.1007/s10439-011-0449-4] [Citation(s) in RCA: 257] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2011] [Accepted: 10/19/2011] [Indexed: 02/07/2023]
Abstract
Photoacoustic imaging is a biomedical imaging modality that provides functional information, and, with the help of exogenous contrast agents, cellular and molecular signatures of tissue. In this article, we review the biomedical applications of photoacoustic imaging assisted with exogenous contrast agents. Dyes, noble metal nanoparticles, and other constructs are contrast agents which absorb strongly in the near-infrared band of the optical spectrum and generate strong photoacoustic response. These contrast agents, which can be specifically targeted to molecules or cells, have been coupled with photoacoustic imaging for preclinical and clinical applications ranging from detection of cancer cells, sentinel lymph nodes, and micrometastasis to angiogenesis to characterization of atherosclerotic plaques. Multi-functional agents have also been developed, which can carry drugs or simultaneously provide contrast in multiple imaging modalities. Furthermore, contrast agents were used to guide and monitor the therapeutic procedures. Overall, photoacoustic imaging shows significant promise in its ability to assist in diagnosis, therapy planning, and monitoring of treatment outcome for cancer, cardiovascular disease, and other pathologies.
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