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Zhou C, Jiang J, Huang S, Wang J, Cui X, Wang W, Chen M, Peng J, Shi N, Wang B, Zhang A, Zhang Q, Li Q, Cui S, Xue S, Wang W, Tang N, Cui D. An ingestible near-infrared fluorescence capsule endoscopy for specific gastrointestinal diagnoses. Biosens Bioelectron 2024; 257:116209. [PMID: 38640795 DOI: 10.1016/j.bios.2024.116209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 02/29/2024] [Accepted: 03/11/2024] [Indexed: 04/21/2024]
Abstract
Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.
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Affiliation(s)
- Cheng Zhou
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Jinlei Jiang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Songwei Huang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Junhao Wang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Xinyuan Cui
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China
| | - Weicheng Wang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Mingrui Chen
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Jiawei Peng
- National Engineering Center for Nanotechnology, Shanghai, 200240, PR China
| | - Nanqing Shi
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Bensong Wang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Amin Zhang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Qian Zhang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Qichao Li
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Shengsheng Cui
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Shenghao Xue
- Department of Prothodontics, Shanghai Stomatological Hospital & School of Stomatology, Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, PR China
| | - Wei Wang
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
| | - Ning Tang
- Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, PR China.
| | - Daxiang Cui
- School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, PR China; National Engineering Center for Nanotechnology, Shanghai, 200240, PR China.
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2
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Setia A, Mehata AK, Priya V, Pawde DM, Jain D, Mahto SK, Muthu MS. Current Advances in Nanotheranostics for Molecular Imaging and Therapy of Cardiovascular Disorders. Mol Pharm 2023; 20:4922-4941. [PMID: 37699355 DOI: 10.1021/acs.molpharmaceut.3c00582] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/14/2023]
Abstract
Cardiovascular diseases (CVDs) refer to a collection of conditions characterized by abnormalities in the cardiovascular system. They are a global problem and one of the leading causes of mortality and disability. Nanotheranostics implies to the combination of diagnostic and therapeutic capabilities inside a single nanoscale platform that has allowed for significant advancement in cardiovascular diagnosis and therapy. These advancements are being developed to improve imaging capabilities, introduce personalized therapies, and boost cardiovascular disease patient treatment outcomes. Significant progress has been achieved in the integration of imaging and therapeutic capabilities within nanocarriers. In the case of cardiovascular disease, nanoparticles provide targeted delivery of therapeutics, genetic material, photothermal, and imaging agents. Directing and monitoring the movement of these therapeutic nanoparticles may be done with pinpoint accuracy by using imaging modalities such as cardiovascular magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), photoacoustic/ultrasound, and fluorescence imaging. Recently, there has been an increasing demand of noninvasive for multimodal nanotheranostic platforms. In these platforms, various imaging technologies such as optical and magnetic resonance are integrated into a single nanoparticle. This platform helps in acquiring more accurate descriptions of cardiovascular diseases and provides clues for accurate diagnosis. Advances in surface functionalization methods have strengthened the potential application of nanotheranostics in cardiovascular diagnosis and therapy. In this Review, we have covered the potential impact of nanomedicine on CVDs. Additionally, we have discussed the recently developed various nanoparticles for CVDs imaging. Moreover, advancements in the CMR, CT, PET, ultrasound, and photoacoustic imaging for the CVDs have been discussed. We have limited our discussion to nanomaterials based clinical trials for CVDs and their patents.
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Affiliation(s)
- Aseem Setia
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Abhishesh Kumar Mehata
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Vishnu Priya
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Datta Maroti Pawde
- School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed-to-be University, Shirpur, Dhule, Maharashtra 425405, India
| | - Dharmendra Jain
- Department of Cardiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Sanjeev Kumar Mahto
- School of Biomedical Engineering, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
| | - Madaswamy S Muthu
- Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, Uttar Pradesh 221005, India
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3
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Lin YY, Christiansen BA. Non-Invasive Compression-Induced Anterior Cruciate Ligament (ACL) Injury and In Vivo Imaging of Protease Activity in Mice. J Vis Exp 2023:10.3791/65249. [PMID: 37843296 PMCID: PMC10680551 DOI: 10.3791/65249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2023] Open
Abstract
Traumatic joint injuries such as anterior cruciate ligament (ACL) rupture or meniscus tears commonly lead to post-traumatic osteoarthritis (PTOA) within 10-20 years following injury. Understanding the early biological processes initiated by joint injuries (e.g., inflammation, matrix metalloproteinases (MMPs), cathepsin proteases, bone resorption) is crucial for understanding the etiology of PTOA. However, there are few options for in vivo measurement of these biological processes, and the early biological responses may be confounded if invasive surgical techniques or injections are used to initiate OA. In our studies of PTOA, we have used commercially available near-infrared protease activatable probes combined with fluorescence reflectance imaging (FRI) to quantify protease activity in vivo following non-invasive compression-induced ACL injury in mice. This non-invasive ACL injury method closely recapitulates clinically relevant injury conditions and is completely aseptic since it does not involve disrupting the skin or the joint capsule. The combination of these injury and imaging methods allows us to study the time course of protease activity at multiple time points following a traumatic joint injury.
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Affiliation(s)
- Yu-Yang Lin
- Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis Health
| | - Blaine A Christiansen
- Lawrence J. Ellison Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of California Davis Health;
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4
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Hanscom M, Cave DR. Endoscopic capsule robot-based diagnosis, navigation and localization in the gastrointestinal tract. Front Robot AI 2022; 9:896028. [PMID: 36119725 PMCID: PMC9479458 DOI: 10.3389/frobt.2022.896028] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 08/08/2022] [Indexed: 01/10/2023] Open
Abstract
The proliferation of video capsule endoscopy (VCE) would not have been possible without continued technological improvements in imaging and locomotion. Advancements in imaging include both software and hardware improvements but perhaps the greatest software advancement in imaging comes in the form of artificial intelligence (AI). Current research into AI in VCE includes the diagnosis of tumors, gastrointestinal bleeding, Crohn’s disease, and celiac disease. Other advancements have focused on the improvement of both camera technologies and alternative forms of imaging. Comparatively, advancements in locomotion have just started to approach clinical use and include onboard controlled locomotion, which involves miniaturizing a motor to incorporate into the video capsule, and externally controlled locomotion, which involves using an outside power source to maneuver the capsule itself. Advancements in locomotion hold promise to remove one of the major disadvantages of VCE, namely, its inability to obtain targeted diagnoses. Active capsule control could in turn unlock additional diagnostic and therapeutic potential, such as the ability to obtain targeted tissue biopsies or drug delivery. With both advancements in imaging and locomotion has come a corresponding need to be better able to process generated images and localize the capsule’s position within the gastrointestinal tract. Technological advancements in computation performance have led to improvements in image compression and transfer, as well as advancements in sensor detection and alternative methods of capsule localization. Together, these advancements have led to the expansion of VCE across a number of indications, including the evaluation of esophageal and colon pathologies including esophagitis, esophageal varices, Crohn’s disease, and polyps after incomplete colonoscopy. Current research has also suggested a role for VCE in acute gastrointestinal bleeding throughout the gastrointestinal tract, as well as in urgent settings such as the emergency department, and in resource-constrained settings, such as during the COVID-19 pandemic. VCE has solidified its role in the evaluation of small bowel bleeding and earned an important place in the practicing gastroenterologist’s armamentarium. In the next few decades, further improvements in imaging and locomotion promise to open up even more clinical roles for the video capsule as a tool for non-invasive diagnosis of lumenal gastrointestinal pathologies.
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Hanscom M, Stead C, Feldman H, Marya NB, Cave D. Video Capsule Endoscopy and Device-Assisted Enteroscopy. Dig Dis Sci 2022; 67:1539-1552. [PMID: 34383197 PMCID: PMC8358900 DOI: 10.1007/s10620-021-07085-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/20/2021] [Indexed: 12/09/2022]
Abstract
Mark Hanscom Courtney Stead Harris Feldman Neil B. Marya David Cave.
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Affiliation(s)
- Mark Hanscom
- grid.168645.80000 0001 0742 0364Division of Gastroenterology, University of Massachusetts Medical School, Worcester, MA 01655 USA
| | - Courtney Stead
- grid.168645.80000 0001 0742 0364Department of Medicine, University of Massachusetts Medical School, Worcester, MA USA
| | - Harris Feldman
- grid.168645.80000 0001 0742 0364Department of Medicine, University of Massachusetts Medical School, Worcester, MA USA
| | - Neil B. Marya
- grid.168645.80000 0001 0742 0364Division of Gastroenterology, University of Massachusetts Medical School, Worcester, MA 01655 USA
| | - David Cave
- grid.168645.80000 0001 0742 0364Division of Gastroenterology, University of Massachusetts Medical School, Worcester, MA 01655 USA
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6
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Wartak A, Kelada AK, Leon Alarcon PA, Bablouzian AL, Ahsen OO, Gregg AL, Wei Y, Bollavaram K, Sheil CJ, Farewell E, VanTol S, Smith R, Grahmann P, Baillargeon AR, Gardecki JA, Tearney GJ. Dual-modality optical coherence tomography and fluorescence tethered capsule endomicroscopy. BIOMEDICAL OPTICS EXPRESS 2021; 12:4308-4323. [PMID: 34457416 PMCID: PMC8367220 DOI: 10.1364/boe.422453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 06/02/2021] [Accepted: 06/02/2021] [Indexed: 06/13/2023]
Abstract
OCT tethered capsule endomicroscopy (TCE) is an emerging noninvasive diagnostic imaging technology for gastrointestinal (GI) tract disorders. OCT measures tissue reflectivity that provides morphologic image contrast, and thus is incapable of ascertaining molecular information that can be useful for improving diagnostic accuracy. Here, we introduce an extension to OCT TCE that includes a fluorescence (FL) imaging channel for attaining complementary, co-registered molecular contrast. We present the development of an OCT-FL TCE capsule and a portable, plug-and-play OCT-FL imaging system. The technology is validated in phantom experiments and feasibility is demonstrated in a methylene blue (MB)-stained swine esophageal injury model, ex vivo and in vivo.
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Affiliation(s)
- Andreas Wartak
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Dermatology, Harvard Medical School, Harvard University, Boston, MA 02115, USA
| | - Alfred K. Kelada
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Paola A. Leon Alarcon
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Ara L. Bablouzian
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Osman O. Ahsen
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Dermatology, Harvard Medical School, Harvard University, Boston, MA 02115, USA
| | - Abigail L. Gregg
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Yuxiao Wei
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA
| | - Keval Bollavaram
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
| | - Conor J. Sheil
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Dermatology, Harvard Medical School, Harvard University, Boston, MA 02115, USA
| | - Edward Farewell
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Schuyler VanTol
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Rachel Smith
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Patricia Grahmann
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Aaron R. Baillargeon
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
| | - Joseph A. Gardecki
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Department of Dermatology, Harvard Medical School, Harvard University, Boston, MA 02115, USA
| | - Guillermo J. Tearney
- Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
- Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
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7
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Novel Clinical Applications and Technical Developments in Video Capsule Endoscopy. Gastrointest Endosc Clin N Am 2021; 31:399-412. [PMID: 33743934 DOI: 10.1016/j.giec.2020.12.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Video capsule endoscopy is entering its third decade. After slow acceptance, it has become the gold standard in diagnosing small intestinal disorders. This article summarizes new practical applications for capsule endoscopy outside the small intestine. From 2 randomized controlled trials, it is becoming clear that it has a role in the management of patients with hematemesis and nonhematemesis bleeding. Under active investigation are novel applications of capsule technology, including the potential ability to sample luminal contents or tissue, self-propelled capsules, incorporation of other imaging techniques beyond white light, such as ultrasound and fluorescents, and the possibility of drug delivery.
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8
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Ottobrini L, Martelli C, Lucignani G. Optical Imaging Agents. Mol Imaging 2021. [DOI: 10.1016/b978-0-12-816386-3.00035-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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9
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Cummins G, Cox BF, Ciuti G, Anbarasan T, Desmulliez MPY, Cochran S, Steele R, Plevris JN, Koulaouzidis A. Gastrointestinal diagnosis using non-white light imaging capsule endoscopy. Nat Rev Gastroenterol Hepatol 2019; 16:429-447. [PMID: 30988520 DOI: 10.1038/s41575-019-0140-z] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Capsule endoscopy (CE) has proved to be a powerful tool in the diagnosis and management of small bowel disorders since its introduction in 2001. However, white light imaging (WLI) is the principal technology used in clinical CE at present, and therefore, CE is limited to mucosal inspection, with diagnosis remaining reliant on visible manifestations of disease. The introduction of WLI CE has motivated a wide range of research to improve its diagnostic capabilities through integration with other sensing modalities. These developments have the potential to overcome the limitations of WLI through enhanced detection of subtle mucosal microlesions and submucosal and/or transmural pathology, providing novel diagnostic avenues. Other research aims to utilize a range of sensors to measure physiological parameters or to discover new biomarkers to improve the sensitivity, specificity and thus the clinical utility of CE. This multidisciplinary Review summarizes research into non-WLI CE devices by organizing them into a taxonomic structure on the basis of their sensing modality. The potential of these capsules to realize clinically useful virtual biopsy and computer-aided diagnosis (CADx) is also reported.
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Affiliation(s)
- Gerard Cummins
- School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK.
| | | | - Gastone Ciuti
- The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy
| | | | - Marc P Y Desmulliez
- School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK
| | - Sandy Cochran
- School of Engineering, University of Glasgow, Glasgow, UK
| | - Robert Steele
- School of Medicine, University of Dundee, Dundee, UK
| | - John N Plevris
- Centre for Liver and Digestive Disorders, The Royal Infirmary of Edinburgh, Edinburgh, UK
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10
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Ding S, Blue RE, Moorefield E, Yuan H, Lund PK. Ex Vivo and In Vivo Noninvasive Imaging of Epidermal Growth Factor Receptor Inhibition on Colon Tumorigenesis Using Activatable Near-Infrared Fluorescent Probes. Mol Imaging 2018; 16:1536012117729044. [PMID: 28884622 PMCID: PMC5595252 DOI: 10.1177/1536012117729044] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background: Near-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection. Objective: To test whether 3-dimensional (3-D) noninvasive in vivo NIRF imaging can detect effects of epidermal growth factor receptor (EGFR) inhibitor on both polypoid and flat tumor load in azoxymethane (AOM)-induced colon tumors or tumors in ApcMin/+ mice. Methods: The AOM-injected KK-HIJ mice received EGFR inhibitor diet or chow diet. These and ApcMin/+ mice were given cathepsin-activatable probes (ProSense 680) before imaging. In vivo imaging was performed using quantitative tomographic NIRF imaging. Ex vivo imaging and histologic examination were performed. Dual imaging by micro computed tomography (CT) and 3D NIRF imaging was used to verify tumor location. Results: Tumor load reduction by EGFR inhibition was detected ex vivo using cathepsin B probes. In vivo imaging revealed intense activation of probes only in large tumors. Dual imaging with microCT and 3D NIRF imaging improved tumor detection in vivo. Conclusions: The 3-D NIRF imaging with ProSense 680 can detect and quantify drug effects on colon tumors ex vivo. The NIRF imaging with ProSense 680 probe has limitations as a valid nonendoscopic method for intestinal tumor detection. Combing with other imaging modalities will improve the specificity and sensitivity of intestinal tumor detection in vivo.
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Affiliation(s)
- Shengli Ding
- 1 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Randall E Blue
- 1 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Emily Moorefield
- 1 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Hong Yuan
- 2 Department of Radiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Pauline K Lund
- 1 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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11
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Bhutani MS, Uthamanthil R, Suzuki R, Shetty A, Klumpp SA, Nau W, Stafford RJ. Endoscopic ultrasound-guided inoculation of transmissible venereal tumor in the colon: A large animal model for colon neoplasia. Endosc Ultrasound 2016; 5:85-93. [PMID: 27080606 PMCID: PMC4850800 DOI: 10.4103/2303-9027.180471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background: To develop and evaluate the feasibility of emerging interventions, animal models with accurate anatomical environment are required. Objectives: We aimed to establish a clinically relevant colorectal tumor model with canine transmissible venereal tumor (CTVT) utilizing endoscopic ultrasound (EUS) imaging guidance. Design: Survival study using a canine model. Setting: Endoscopic animal research laboratory at a tertiary cancer center. Materials and Methods: This study involved five canines. Interventions: A colorectal tumor model was established and evaluated in five canines under cyclosporine immune suppression. Under endoscopic imaging guidance, saline was injected into the submucosal layer forming a bleb. Subsequently, CTVT was inoculated into the bleb under EUS guidance. Endoscopy was the primary method of assessing tumor growth. Tumors developed in 60-130 days. Upon detection of lesions >1 cm, the animals were euthanized and the tumors were harvested for histopathological characterization. Main outcome measurements: Success rate of tumor growth. The presence or absence of vasculature inside tumors. Results: Colorectal tumor successfully developed in three out of the five animals (60%). Among the ones with tumor growth, average inoculated CTVT volume, incubation time, and tumor size was 1.8 cc, 65.7 days, and 2.0 cm, respectively. The two animals without tumor growth were observed for >100 days. In all the tumors, vascular structure was characterized with CD31 imunohistochemical stain. Limitations: Small number of animals. Conclusion: We succeeded in creating a new colorectal tumor canine model with CTVT utilizing EUS.
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Affiliation(s)
- Manoop S Bhutani
- Department of Gastroenterology, Hepatology and Nutrition, UT MD Anderson Cancer Center, Houston,Texas, USA
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12
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Singeap AM, Stanciu C, Trifan A. Capsule endoscopy: The road ahead. World J Gastroenterol 2016; 22:369-378. [PMID: 26755883 PMCID: PMC4698499 DOI: 10.3748/wjg.v22.i1.369] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Revised: 08/04/2015] [Accepted: 09/30/2015] [Indexed: 02/07/2023] Open
Abstract
Since its introduction into clinical practice 15 years ago, capsule endoscopy (CE) has become the first-line investigation procedure in some small bowel pathologies, and more recently, dedicated esophageal and colon CE have expanded the fields of application to include the upper and lower gastrointestinal disorders. During this time, CE has become increasingly popular among gastroenterologists, with more than 2 million capsule examinations performed worldwide, and nearly 3000 PubMed-listed studies on its different aspects published. This huge interest in CE may be explained by its non-invasive nature, patient comfort, safety, and access to anatomical regions unattainable via conventional endoscopy. However, CE has several limitations which impede its wider clinical applications, including the lack of therapeutic capabilities, inability to obtain biopsies and control its locomotion. Several research groups are currently working to overcome these limitations, while novel devices able to control capsule movement, obtain high quality images, insufflate the gut lumen, perform chromoendoscopy, biopsy of suspect lesions, or even deliver targeted drugs directly to specific sites are under development. Overlooking current limitations, especially as some of them have already been successfully surmounted, and based on the tremendous progress in technology, it is expected that, by the end of next 15 years, CE able to perform both diagnostic and therapeutic procedures will remain the major form of digestive endoscopy. This review summarizes the literature that prognosticates about the future developments of CE.
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13
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Keuchel M, Kurniawan N, Baltes P, Bandorski D, Koulaouzidis A. Quantitative measurements in capsule endoscopy. Comput Biol Med 2015; 65:333-47. [PMID: 26299419 DOI: 10.1016/j.compbiomed.2015.07.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 07/16/2015] [Accepted: 07/17/2015] [Indexed: 12/14/2022]
Abstract
This review summarizes several approaches for quantitative measurement in capsule endoscopy. Video capsule endoscopy (VCE) typically provides wireless imaging of small bowel. Currently, a variety of quantitative measurements are implemented in commercially available hardware/software. The majority is proprietary and hence undisclosed algorithms. Measurement of amount of luminal contamination allows calculating scores from whole VCE studies. Other scores express the severity of small bowel lesions in Crohn׳s disease or the degree of villous atrophy in celiac disease. Image processing with numerous algorithms of textural and color feature extraction is further in the research focuses for automated image analysis. These tools aim to select single images with relevant lesions as blood, ulcers, polyps and tumors or to omit images showing only luminal contamination. Analysis of motility pattern, size measurement and determination of capsule localization are additional topics. Non-visual wireless capsules transmitting data acquired with specific sensors from the gastrointestinal (GI) tract are available for clinical routine. This includes pH measurement in the esophagus for the diagnosis of acid gastro-esophageal reflux. A wireless motility capsule provides GI motility analysis on the basis of pH, pressure, and temperature measurement. Electromagnetically tracking of another motility capsule allows visualization of motility. However, measurement of substances by GI capsules is of great interest but still at an early stage of development.
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Affiliation(s)
- M Keuchel
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany.
| | - N Kurniawan
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany
| | - P Baltes
- Clinic for Internal Medicine, Bethesda Krankenhaus Bergedorf, Glindersweg 80, 21029 Hamburg, Germany
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Near-Infrared Confocal Laser Endomicroscopy Detects Colorectal Cancer via an Integrin αvβ3 Optical Probe. Mol Imaging Biol 2015; 17:450-60. [DOI: 10.1007/s11307-015-0825-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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15
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Satkunananthan PB, Anderson MJ, De Jesus NM, Haudenschild DR, Ripplinger CM, Christiansen BA. In vivo fluorescence reflectance imaging of protease activity in a mouse model of post-traumatic osteoarthritis. Osteoarthritis Cartilage 2014; 22:1461-9. [PMID: 25278057 PMCID: PMC4185155 DOI: 10.1016/j.joca.2014.07.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Accepted: 07/10/2014] [Indexed: 02/02/2023]
Abstract
OBJECTIVE Joint injuries initiate a surge of inflammatory cytokines and proteases that contribute to cartilage and subchondral bone degeneration. Detecting these early processes in animal models of post-traumatic osteoarthritis (PTOA) typically involves ex vivo analysis of blood serum or synovial fluid biomarkers, or histological analysis of the joint. In this study, we used in vivo fluorescence reflectance imaging (FRI) to quantify protease, matrix metalloproteinase (MMP), and Cathepsin K activity in mice following anterior cruciate ligament (ACL) rupture. We hypothesized that these processes would be elevated at early time points following joint injury, but would return to control levels at later time points. DESIGN Mice were injured via tibial compression overload, and FRI was performed at time points from 1 to 56 days after injury using commercially available activatable fluorescent tracers to quantify protease, MMP, and cathepsin K activity in injured vs uninjured knees. PTOA was assessed at 56 days post-injury using micro-computed tomography and whole-joint histology. RESULTS Protease activity, MMP activity, and cathepsin K activity were all significantly increased in injured knees relative to uninjured knees at all time points, peaking at 1-7 days post-injury, then decreasing at later time points while still remaining elevated relative to controls. CONCLUSIONS This study establishes FRI as a reliable method for in vivo quantification of early biological processes in a translatable mouse model of PTOA, and provides crucial information about the time course of inflammation and biological activity following joint injury. These data may inform future studies aimed at targeting these early processes to inhibit PTOA development.
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Affiliation(s)
- Patrick B. Satkunananthan
- University of California-Davis Medical Center, Department of Orthopaedic Surgery,University of California-Davis, Biomedical Engineering Graduate Group
| | - Matthew J. Anderson
- University of California-Davis Medical Center, Department of Orthopaedic Surgery
| | - Nicole M. De Jesus
- University of California-Davis, Biomedical Engineering Graduate Group,University of California-Davis Medical Center, Department of Pharmacology
| | - Dominik R. Haudenschild
- University of California-Davis Medical Center, Department of Orthopaedic Surgery,University of California-Davis, Biomedical Engineering Graduate Group
| | - Crystal M. Ripplinger
- University of California-Davis, Biomedical Engineering Graduate Group,University of California-Davis Medical Center, Department of Pharmacology
| | - Blaine A. Christiansen
- University of California-Davis Medical Center, Department of Orthopaedic Surgery,University of California-Davis, Biomedical Engineering Graduate Group
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16
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Ma W, Ma L, Zhe H, Bao C, Wang N, Yang S, Wang K, Cao F, Cheng Y, Cheng Y. Detection of esophageal squamous cell carcinoma by cathepsin B activity in nude mice. PLoS One 2014; 9:e92351. [PMID: 24618814 PMCID: PMC3950293 DOI: 10.1371/journal.pone.0092351] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 02/21/2014] [Indexed: 02/05/2023] Open
Abstract
Background and Objective Despite great progress in treatment, the prognosis for patients with esophageal squamous cell carcinoma (ESCC) remains poor, highlighting the importance of early detection. Although upper endoscopy can be used for the screening of esophagus, it has limited sensitivity for early stage disease. Thus, development of new diagnosis approach to improve diagnostic capabilities for early detection of ESCC is an important need. The aim of this study was to assess the feasibility of using cathepsin B (CB) as a novel imaging target for the detection of human ESCC by near-infrared optical imaging in nude mice. Methods Initially, we examined specimens from normal human esophageal tissue, intraepithelial neoplasia lesions, tumor in situ, ESCC and two cell lines including one human ESCC cell line (Eca-109) and one normal human esophageal epithelial cell line (HET-1A) for CB expression by immunohistochemistry and western blot, respectively. Next, the ability of a novel CB activatable near-infrared fluorescence (NIRF) probe detecting CB activity presented in Eca-109 cells was confirmed by immunocytochemistry. We also performed in vivo imaging of tumor bearing mice injected with the CB probe and ex vivo imaging of resected tumor xenografts and visceral organs using a living imaging system. Finally, the sources of fluorescence signals in tumor tissue and CB expression in visceral organs were identified by histology. Results CB was absent in normal human esophageal mucosa, but it was overexpressed in ESCC and its precursor lesions. The novel probe for CB activity specifically detected ESCC xenografts in vivo and in vitro. Conclusions CB was highly upregulated in human ESCC and its precursor lesions. The elevated CB expression in ESCC allowed in vivo and in vitro detection of ESCC xenografts in nude mice. Our results support the usefulness of CB activity as a potential imaging target for the detection of human ESCC.
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Affiliation(s)
- Wei Ma
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China
- Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Lie Ma
- Department of Cardiology, Cardiovascular and Cerebrovascular Disease Hospital, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Hong Zhe
- Department of Radiation Oncology, Cancer Hospital, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Cihang Bao
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China
| | - Nana Wang
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China
| | - Shaoqi Yang
- Digestive System Department, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Kai Wang
- Department of Oncology, Wendeng Center Hospital, Weihai, China
| | - Fangli Cao
- Department of Oncology, Liaocheng People's Hospital, Liaocheng, China
| | - Yanna Cheng
- School of Pharmaceutical Sciences, Shandong University, Jinan, China
| | - Yufeng Cheng
- Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, China
- * E-mail:
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17
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Comparison of multiple enzyme activatable near-infrared fluorescent molecular probes for detection and quantification of inflammation in murine colitis models. Inflamm Bowel Dis 2014; 20:363-77. [PMID: 24374874 PMCID: PMC4618379 DOI: 10.1097/01.mib.0000440612.98950.79] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Activatable near-infrared fluorescent (NIRF) probes have been used for ex vivo and in vivo detection of intestinal tumors in animal models. We hypothesized that NIRF probes activatable by cathepsins or metalloproteinases will detect and quantify dextran sulphate sodium (DSS)-induced acute colonic inflammation in wild type mice or chronic colitis in interleukin-10 (IL-10)-null mice ex vivo or in vivo. METHODS Wild type mice given DSS, water controls, and IL-10-null mice with chronic colitis were administered probes by retro-orbital injection. FMT2500 LX system imaged fresh and fixed intestine ex vivo and mice in vivo. Inflammation detected by probes was verified by histology and colitis scoring. NIRF signal intensity was quantified using 2-dimensional region of interest ex vivo or 3-dimensional region of interest analysis in vivo. RESULTS Ex vivo, 7 probes tested yielded significant higher NIRF signals in colon of DSS-treated mice versus controls. A subset of probes was tested in IL-10-null mice and yielded strong ex vivo signals. Ex vivo fluorescence signal with 680 series probes was preserved after formalin fixation. In DSS and IL-10-null models, ex vivo NIRF signal strongly and significantly correlated with colitis scores. In vivo, ProSense680, CatK680FAST, and MMPsense680 yielded significantly higher NIRF signals in DSS-treated mice than controls, but background was high in controls. CONCLUSIONS Both cathepsin or metalloproteinase-activated NIRF probes can detect and quantify colonic inflammation ex vivo. ProSense680 yielded the strongest signals in DSS colitis ex vivo and in vivo, but background remains a problem for in vivo quantification of colitis.
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Abstract
Molecular imaging is a novel field in gastroenterology that uses fluorescently labelled probes to specifically highlight neoplastic lesions on the basis of their molecular signature. The development of molecular imaging has been driven by the need to improve endoscopic diagnosis and by progress in targeted therapies in gastrointestinal oncology to provide individualized treatment, which coincides with progress in endoscopy techniques and further miniaturization of detection devices. Different exogenous molecular probes for imaging include labelled antibodies, oligopeptides, affibodies(™) (Affibody AB, Bromma, Sweden), aptamers and activatable probes. Molecular imaging has been evaluated in two major indications: many trials have studied molecular imaging as a red flag technique to improve detection of lesions in wide-field imaging; on the other hand, microscopic analysis has been investigated for in vivo characterization of the molecular fingerprint of tumours with the ultimate goal of assessing the likelihood of response to targeted therapy. This Review focusses on the applications of molecular imaging that have immediate potential for translational science or imminent transition into clinical practice of gastrointestinal endoscopy.
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Soga K, Handa O, Yamada M, Sakagami J, Yagi N, Naito Y, Yoshikawa T, Itoh Y, Arizono N. In vivo imaging of intestinal helminths by capsule endoscopy. Parasitol Int 2013; 63:221-8. [PMID: 24050882 DOI: 10.1016/j.parint.2013.09.006] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2012] [Revised: 08/29/2013] [Accepted: 09/10/2013] [Indexed: 12/18/2022]
Abstract
This review examines the use of digestive endoscopy to visualize intestinal helminths. The infections caused by these parasites are responsible for high levels of morbidity and mortality. These helminths can be visualized using gastroduodenal endoscopy, endoscopic retrograde cholangiopancreatography, and colonoscopy. Endoscopic examination of the small bowel is limited by its considerable length and its distance from the mouth and anus. Since capsule endoscopy (CE) was first reported in 2000, it has been established as a noninvasive modality for the investigation of the gastrointestinal tract. CE is used as a first-line tool for imaging various small-bowel diseases, mainly obscure gastrointestinal bleeding and Crohn's disease. Since the Food and Drug Administration (FDA) approved CE in 2001, the indications for its use have expanded widely. For example, CE can be used to visualize the in vivo kinetics of intestinal helminths. If the current trends in technological development continue, CE will become more widely used to facilitate the diagnosis and treatment of helminth infections in the near future.
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Affiliation(s)
- Koichi Soga
- Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan; Department of Gastroenterology, Nishijin Hospital, Kyoto 602-8319, Japan.
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20
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In vivo molecular imaging of epidermal growth factor receptor in patients with colorectal neoplasia using confocal laser endomicroscopy. Cancer Lett 2012; 330:200-7. [PMID: 23220286 DOI: 10.1016/j.canlet.2012.11.044] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Revised: 11/25/2012] [Accepted: 11/27/2012] [Indexed: 01/12/2023]
Abstract
Epidermal growth factor receptor (EGFR) plays an important role in tumorigenesis of colorectal cancer (CRC), and its in vivo molecular imaging in rodent models has become the subject of an increased number of studies using novel imaging techniques for gastrointestinal endoscopy. Current study aimed to evaluate the use of confocal endomicroscopy (CLE) for in vivo molecular imaging of EGFR in patients with colorectal neoplasia. Molecular imaging of colorectal neoplasia in patients was performed by CLE after topical application of a fluorescent-labeled molecular probe against EGFR. Representative images of CLE were chosen to calculate EGFR-specific fluorescence intensity. Targeted biopsy specimens were taken from each examined site during in vivo imaging for histology and immunohistochemistry (IHC). During in vivo molecular imaging in 37 patients, an EGFR-specific fluorescence signal was present in 18/19 CRC, and 12/18 colorectal adenomas. No or only weak fluorescence signal was observed in vivo in 10 cases of normal mucosa. CLE is a novel tool that could be used in molecular imaging with specific targeting of EGFR in patients with colorectal neoplasia. This technique demonstrates a promising imaging approach for targeted therapies of colorectal neoplasia.
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21
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Ding S, Blue RE, Chen Y, Scull B, Lund PK, Morgan D. Molecular Imaging of Gastric Neoplasia with Near-Infrared Fluorescent Activatable Probes. Mol Imaging 2012. [DOI: 10.2310/7290.2012.00014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- Shengli Ding
- From the Department of Cell and Molecular Physiology and Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biological Sciences, Kent State University, Kent, OH; and Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN
| | - Randall Eric Blue
- From the Department of Cell and Molecular Physiology and Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biological Sciences, Kent State University, Kent, OH; and Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN
| | - Yijing Chen
- From the Department of Cell and Molecular Physiology and Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biological Sciences, Kent State University, Kent, OH; and Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN
| | - Brooks Scull
- From the Department of Cell and Molecular Physiology and Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biological Sciences, Kent State University, Kent, OH; and Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN
| | - Pauline Kay Lund
- From the Department of Cell and Molecular Physiology and Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biological Sciences, Kent State University, Kent, OH; and Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN
| | - Douglas Morgan
- From the Department of Cell and Molecular Physiology and Division of Gastroenterology, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Biological Sciences, Kent State University, Kent, OH; and Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN
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22
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Ding S, Blue RE, Chen Y, Scull B, Lund PK, Morgan D. Molecular imaging of gastric neoplasia with near-infrared fluorescent activatable probes. Mol Imaging 2012; 11:507-515. [PMID: 23084251 PMCID: PMC3689298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2023] Open
Abstract
Gastric cancer is the second leading cause of cancer mortality worldwide and is projected to rise to tenth in all-cause mortality in the near term. Early detection requires improved sensitivity and specificity of endoscopic imaging with novel methods. The objective of this study was to evaluate the utility of activatable molecular probes for the detection of gastric cancer both in vivo and ex vivo in a preclinical model. Smad4⁺/⁻ mice, which develop spontaneous gastric neoplasia, were compared to normal wild-type controls. Cathepsin-activatable and matrix metalloproteinase (MMP)-activatable molecular probes were injected 24 hours and 6 hours before imaging, respectively. In vivo imaging was performed using quantitative tomographic near-infrared fluorescence (NIRF) imaging. For validation, ex vivo imaging and histologic examination were performed. Molecular imaging in vivo of Smad4⁺/⁻ gastric cancer murine models revealed intense activation of both cathepsin B and MMP probes. Ex vivo imaging and histology confirmed that the detected neoplasms were adenocarcinomas and hyperplastic lesions. This study provides proof of principle that the cathepsin- and MMP-activatable molecular probes are activated in the Smad4⁺/⁻ murine model of spontaneous gastric adenocarcinoma and can be imaged by both in vivo and ex vivo NIRF methods. The cathepsin probe also detects hyperplastic lesions.
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Affiliation(s)
- Shengli Ding
- Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Randall Eric Blue
- Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Yijing Chen
- Department of Biological Sciences, Kent State University, Kent, OH
| | - Brooks Scull
- Department of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN
| | - Pauline Kay Lund
- Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Douglas Morgan
- Division of Gastroenterology, University of North Carolina, Chapel Hill, NC
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Abstract
Now, more than 10 years after the approval of video capsule endoscopy (VCE), the technology has become an essential component in the management of several clinical conditions. Currently, two capsules are approved in the USA for visualizing the small bowel mucosa, one capsule is authorized for oesophageal assessment and several others are in use or under evaluation worldwide. New investigations have focused on optical improvements, advances in intestinal cleansing and risk reduction strategies to optimize VCE methodologies in clinical care. Established indications diagnosed using VCE include unexplained gastrointestinal bleeding, small bowel Crohn's disease (in adults and children >10 years old), localization of small bowel tumours and a broad range of miscellaneous abnormalities. Investigations are ongoing to determine the utility of VCE in colon cancer screening, assessment of oesophageal disorders and diagnosis of coeliac disease. Active research is in progress into ways to improve the efficacy of VCE recording interpretation, prolong imaging time and further enhance optics and imaging methods. To expand the potential utility of VCE, novel devices that can manoeuvre within or insufflate the gut lumen, tag or biopsy suspect lesions, or target drug delivery to specific sites are in development. To facilitate these advances, consortia have been organized to promote innovative VCE technologies.
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24
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Kwon YS, Cho YS, Yoon TJ, Kim HS, Choi MG. Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms. World J Gastrointest Endosc 2012; 4:57-64. [PMID: 22442742 PMCID: PMC3309894 DOI: 10.4253/wjge.v4.i3.57] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2011] [Revised: 01/22/2012] [Accepted: 03/02/2012] [Indexed: 02/05/2023] Open
Abstract
Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.
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Affiliation(s)
- Yong-Soo Kwon
- Yong-Soo Kwon, Tae-Jong Yoon, Department of Applied Bioscience, CHA University, Seoul 135081, South Korea
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25
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Penna FJ, Freilich DA, Alvarenga C, Nguyen HT. Improving Lymph Node Yield in Retroperitoneal Lymph Node Dissection Using Fluorescent Molecular Imaging: A Novel Method of Localizing Lymph Nodes in Guinea Pig Model. Urology 2011; 78:232.e15-8. [DOI: 10.1016/j.urology.2011.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2010] [Revised: 02/23/2011] [Accepted: 03/07/2011] [Indexed: 02/01/2023]
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Atreya R, Waldner MJ, Neurath MF. Molecular imaging: interaction between basic and clinical science. Gastroenterol Clin North Am 2010; 39:911-22. [PMID: 21093763 DOI: 10.1016/j.gtc.2010.08.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
One of the major proceedings in the field of gastrointestinal endoscopy has been the advent of molecular imaging, which possesses the potential to have a significant effect on the existing diagnostic and therapeutic paradigms. Molecular imaging encompasses different methods that enable the visualization of disease-specific morphologic or functional alterations of the mucosa based on the molecular signature of individual cells. This development has been made possible by advancements in basic science coupled with technological innovations in endoscopy, both facilitating the identification and characterization of mucosal lesions in vivo based on the lesions' molecular composition rather than their morphologic structure alone. Novel studies based on fluorescent antibody imaging pave the road toward clinical translation and give hope for improved diagnosis and targeted therapies in gastrointestinal diseases.
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Affiliation(s)
- Raja Atreya
- Medical Clinic I, University of Erlangen-Nuremberg, Ulmenweg 18, 91056 Erlangen, Germany
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27
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Sheth RA, Mahmood U. Optical molecular imaging and its emerging role in colorectal cancer. Am J Physiol Gastrointest Liver Physiol 2010; 299:G807-20. [PMID: 20595618 PMCID: PMC3774281 DOI: 10.1152/ajpgi.00195.2010] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2010] [Accepted: 06/30/2010] [Indexed: 01/31/2023]
Abstract
Colorectal cancer remains a major cause of morbidity and mortality in the United States. The advent of molecular therapies targeted against specific, stereotyped cellular mutations that occur in this disease has ushered in new hope for treatment options. However, key questions regarding optimal dosing schedules, dosing duration, and patient selection remain unanswered. In this review, we describe how recent advances in molecular imaging, specifically optical molecular imaging with fluorescent probes, offer potential solutions to these questions. We begin with an overview of optical molecular imaging, including discussions on the various methods of design for fluorescent probes and the clinically relevant imaging systems that have been built to image them. We then focus on the relevance of optical molecular imaging to colorectal cancer. We review the most recent data on how this imaging modality has been applied to the measurement of treatment efficacy for currently available as well as developmental molecularly targeted therapies. We then conclude with a discussion on how this imaging approach has already begun to be translated clinically for human use.
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Affiliation(s)
- Rahul A Sheth
- Massachusetts General Hospital, Harvard Medical School, Boston, USA
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28
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Goetz M, Fottner C, Kiesslich R. [Molecular imaging of the small intestine]. Internist (Berl) 2010; 51:702-10. [PMID: 20424814 DOI: 10.1007/s00108-009-2567-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Molecular imaging uses the molecular signature of cells for targeted minimally-invasive detection and characterization of gastrointestinal pathologies. Exogenous fluorescent agents serve as molecular beacons for visualization of specific surface markers or metabolic activity in the target tissue. Molecular imaging with radioactively labeled substances is well established in nuclear medicine for wide-field detection of lesions in the small intestine. In gastrointestinal endoscopy, both macroscopic detection by endogenous or exogenous fluorescence and microscopic visualization by endomicroscopy have been investigated in clinical trials, however have not yet been evaluated in larger patient cohorts. Still, molecular imaging has the potential to greatly enhance our understanding of gastrointestinal pathology and to impact on future clinical algorithms and science in gastroenterology.
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Affiliation(s)
- M Goetz
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Langenbeckstrasse 1, Mainz, Germany.
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29
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Dufort S, Sancey L, Wenk C, Josserand V, Coll JL. Optical small animal imaging in the drug discovery process. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2010; 1798:2266-73. [PMID: 20346346 DOI: 10.1016/j.bbamem.2010.03.016] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/17/2009] [Revised: 03/15/2010] [Accepted: 03/17/2010] [Indexed: 02/07/2023]
Abstract
Molecular imaging of tumors in preclinical models is of the utmost importance for developing innovative cancer treatments. This field is moving extremely rapidly, with recent advances in optical imaging technologies and sophisticated molecular probes for in vivo imaging. The aim of this review is to provide a succinct overview of the imaging modalities available for rodents and with focus on describing optical probes for cancer imaging.
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Affiliation(s)
- S Dufort
- Institut Albert Bonniot, BP 170, 38 042 Grenoble cedex 9, France
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30
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Abstract
Molecular imaging is a rapidly growing new discipline in gastrointestinal endoscopy. It uses the molecular signature of cells for minimally-invasive, targeted imaging of gastrointestinal pathologies. Molecular imaging comprises wide field techniques for the detection of lesions and microscopic techniques for in vivo characterization. Exogenous fluorescent agents serve as molecular beacons and include labeled peptides and antibodies, and probes with tumor-specific activation. Most applications have aimed at improving the detection of gastrointestinal neoplasia with either prototype fluorescence endoscopy or confocal endomicroscopy, and first studies have translated encouraging results from rodent and tissue models to endoscopy in humans. Even with the limitations of the currently used approaches, molecular imaging has the potential to greatly impact on future endoscopy in gastroenterology.
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Affiliation(s)
- Martin Goetz
- I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Langenbeckstr. 1, D-55131 Mainz, Germany.
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Levin G, Shirvan A, Grimberg H, Reshef A, Yogev-Falach M, Cohen A, Ziv I. Novel fluorescence molecular imaging of chemotherapy-induced intestinal apoptosis. JOURNAL OF BIOMEDICAL OPTICS 2009; 14:054019. [PMID: 19895121 DOI: 10.1117/1.3253303] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Chemotherapy-induced enteropathy (CIE) is one of the most serious complications of anticancer therapy, and tools for its early detection and monitoring are highly needed. We report on a novel fluorescence method for detection of CIE, based on molecular imaging of the related apoptotic process. The method comprises systemic intravenous administration of the ApoSense fluorescent biomarker (N,N(')-didansyl-L-cystine DDC) in vivo and subsequent fluorescence imaging of the intestinal mucosa. In the reported proof-of-concept studies, mice were treated with either taxol+cyclophosphamide or doxil. DDC was administered in vivo at various time points after drug administration, and tracer uptake by ileum tissue was subsequently evaluated by ex vivo fluorescent microscopy. Chemotherapy caused marked and selective uptake of DDC in ileal epithelial cells, in correlation with other hallmarks of apoptosis (i.e., DNA fragmentation and Annexin-V binding). Induction of DDC uptake occurred early after chemotherapy, and its temporal profile was parallel to that of the apoptotic process, as assessed histologically. DDC may therefore serve as a useful tool for detection of CIE. Future potential integration of this method with fluorescent endoscopic techniques, or development of radio-labeled derivatives of DDC for emission tomography, may advance early diagnosis and monitoring of this severe adverse effect of chemotherapy.
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Affiliation(s)
- Galit Levin
- Aposense Ltd., 5 Ha'Odem Street, P.O. Box 7119, Petach-Tiqva 49170, Israel
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32
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Gastrointestinal endoscopy nears "the molecular era". Gastrointest Endosc 2008; 68:528-30. [PMID: 18760179 DOI: 10.1016/j.gie.2008.03.1075] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2008] [Accepted: 03/17/2008] [Indexed: 02/08/2023]
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