Molecular Magnetic Resonance Imaging of Acute Vascular Cell Adhesion Molecule-1 Expression in a Mouse Model of Cerebral Ischemia

Hoyte, Lisa; Brooks, Keith J.; Nagel, Simon; Akhtar, Asim M.; Chen, Ruoli; Mardiguian, Sylvie; McAteer, Martina A.; Anthony, Daniel C.; Choudhury, Robin P.; Buchan, Alastair M.; Sibson, Nicola R.

doi:10.1038/jcbfm.2009.287

Cited by 72 publications

(57 citation statements)

References 38 publications

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“…Alternatively to P- or E-selectin targeting, Hoyte et al [43] used an iron oxide-based contrast agent to detect vascular cell adhesion molecule 1 (VCAM-1) upregulation after stroke. In this study, micron-sized particles of iron oxide (MPIO, Dynabeads®) were functionalized with VCAM-1 antibodies (αVCAM-1), and intravenously injected 3 h after transient MCAO in mice.…”

Section: Molecular Mri Of Inflammatory Markersmentioning

confidence: 99%

“…MPIO, which contain very high amounts of iron oxide, are an important example of such particles, with sizes in the micrometer range. Commercially available polystyrene/divinylbenzene MPIO such as employed by Hoyte et al [43] are adequate for preclinical investigations. But these particles are inert, which excludes their application in humans.…”

Section: Future Directionsmentioning

confidence: 99%

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Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies

et al. 2012

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Cellular and molecular magnetic resonance imaging (MRI) strategies for studying the spatiotemporal profile of neuroinflammatory processes after stroke are increasingly being explored since the first reports appeared about a decade ago. These strategies most often employ (super)paramagnetic contrast agents, such as (ultra)small particles of iron oxide and gadolinium chelates, for MRI-based detection of specific leukocyte populations or molecular inflammatory markers that are involved in the pathophysiology of stroke or plasticity. In this review we describe achievements, limitations and prospects in the field of cellular and molecular MRI of neuroinflammation in preclinical and clinical stroke. Several studies in rodent stroke models have demonstrated the application of MRI contrast agents for imaging of monocyte infiltration, which served as the foundation for pilot (small-scale proof-of-concept) cellular MRI studies in stroke patients. This may be achieved with isolated cells that are loaded with contrast agent through in vitro incubation prior to systemic administration. Alternatively, superparamagnetic iron oxide particles may be directly injected into the circulation to allow in vivo uptake by phagocytic cells. Both strategies have been successfully employed to measure the spatiotemporal profile of invasion of monocytes in and around cerebral ischemic lesions in experimental stroke models. Molecular MRI studies with target-specific contrast agents have shown the capability for in vivo detection of molecular markers after experimental stroke. For example, (super)paramagnetic micro- or nanoparticles that are functionalized with a ligand (e.g. an antibody) for specific cell adhesion molecules, such as E-selectin and vascular cell adhesion molecule 1 (VCAM-1), can target inflamed, activated endothelium, whose presence can subsequently be detected with MRI. Present applications remain limited as most of the currently available contrast agents provide relatively poor contrast enhancement, which is not easily discriminated from endogenous sources of tissue contrast. Nevertheless, current developments of more efficient particles, such as biocompatible liposomes, micelles and nanoemulsions that can contain high payloads of (super)paramagnetic material as well as other substances, such as dyes and drugs, may open a window of opportunities for promising translational multimodal imaging strategies that enable in vivo assessment of (neuroinflammatory) disease markers, therapeutic targets as well as drug delivery after stroke.

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Section: Molecular Mri Of Inflammatory Markersmentioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies

et al. 2012

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“…This property has previously been used to track MPIO-labeled tumor cells in mouse models, thus enabling visualization of early metastasis distribution in the brain with sensitivity down to a single metastatic cell loaded with ∼50 pg iron at an imaging field strength of 1.5 T (17). Alternatively, conjugation of MPIO with targeting ligands enables their accumulation at sites where specific molecules are expressed (18)(19)(20)(21)(22)(23)(24)(25). Importantly, the targeted MPIO are not taken up by endothelial cells and do not enter the brain, thus providing an endovascular biomarker for pathology within the brain.…”

mentioning

confidence: 99%

Molecular MRI enables early and sensitive detection of brain metastases

Serres

Soto

Hamilton

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

129

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Metastasis to the brain is a leading cause of cancer mortality. The current diagnostic method of gadolinium-enhanced MRI is sensitive only to larger tumors, when therapeutic options are limited. Earlier detection of brain metastases is critical for improved treatment. We have developed a targeted MRI contrast agent based on microparticles of iron oxide that enables imaging of endothelial vascular cell adhesion molecule-1 (VCAM-1). Our objectives here were to determine whether VCAM-1 is up-regulated on vessels associated with brain metastases, and if so, whether VCAM-1-targeted MRI enables early detection of these tumors. Early up-regulation of cerebrovascular VCAM-1 expression was evident on tumor-associated vessels in two separate murine models of brain metastasis. Metastases were detectable in vivo using VCAM-1-targeted MRI 5 d after induction (<1,000 cells). At clinical imaging resolutions, this finding is likely to translate to detection at tumor volumes two to three orders of magnitude smaller (0.3-3 × 10 5 cells) than those volumes detectable clinically (10 7 -10 8 cells). VCAM-1 expression detected by MRI increased significantly (P < 0.0001) with tumor progression, and tumors showed no gadolinium enhancement. Importantly, expression of VCAM-1 was shown in human brain tissue containing both established metastases and micrometastases. Translation of this approach to the clinic could increase therapeutic options and change clinical management in a substantial number of cancer patients.

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“…A more targeted approach has been the use of magnetization-susceptible labeling of vascular cell adhesion molecule-1, which has been effective in detecting the inflammatory changes in both core and penumbral regions in the brain after middle cerebral artery occlusion in a mouse model of stroke. 144 Molecular imaging of the expressed genome is still very early in its development. In contrast to high-throughput techniques now available for transcriptomics, epigenomics, proteomics, and metabolomics, molecular imaging labeling to date delineates only 1 or very few selected targets at a time.…”

Section: Molecular Imagingmentioning

confidence: 99%

The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association

Musunuru¹,

Ingelsson²,

Fornage³

et al. 2017

Circ Cardiovasc Genet

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Abstract-There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigenetic modifications, RNA transcripts, proteins, and metabolites, which together can be considered the "expressed genome." The emergence of high-throughput technologies, including epigenomics, transcriptomics, proteomics, and metabolomics, is now making it possible to address the contributions of the expressed genome to cardiovascular disorders. This statement describes how the expressed genome can currently and, in the future, potentially be used to diagnose diseases and to predict who will develop diseases such as coronary artery disease, stroke, heart failure, and arrhythmias. (Circ Cardiovasc Genet. 2017;10:e000037. DOI: 10.1161/HCG.0000000000000037.)Key Words: AHA Scientific Statements ◼ cardiovascular diseases ◼ DNA ◼ epigenomics ◼ genome ◼ metabolomics ◼ proteomics ◼ strokeThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on March 13, 2017, and the American Heart Association Executive Committee on April 17, 2017. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The American Heart Association requests that this document be cited as follows: Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://professional.heart.org/statements. Select the "Guidelines & Statements" drop-down menu, then click "Publication Development."Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/CopyrightPermission-Guidelines_UCM_300404_Article.jsp. A link to the "Copyright Permissions Request Form" appears on the right side of the page. I n no small part as a result of the completion of the Human Genome Project, considerable effort has been invested over the past few decades in understanding the contribution of genetics to the risk of cardiovascular diseases and stroke. Genomewide association studies, candidate gene sequencing studies, a...

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Molecular Magnetic Resonance Imaging of Acute Vascular Cell Adhesion Molecule-1 Expression in a Mouse Model of Cerebral Ischemia

Cited by 72 publications

References 38 publications

Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies

Imaging Neuroinflammation after Stroke: Current Status of Cellular and Molecular MRI Strategies

Molecular MRI enables early and sensitive detection of brain metastases

The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association

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