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Contrast-Enhanced, Molecular Imaging of Vascular Inflammation in the Mouse Model by Simultaneous PET/MRI

Du, Siyi and Ng, Thomas S. C. and House, Adrian and Tang, Tang and Zheng, Lin and Tu, Chuqiao and Peake, Janice and Espiritu, Imelda E. and Ma, Kwan-Liu and Pinkerton, Kent and Jacobs, Russell E. and Louie, Angelique Y. (2019) Contrast-Enhanced, Molecular Imaging of Vascular Inflammation in the Mouse Model by Simultaneous PET/MRI. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20191219-112734829

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Abstract

Despite advances in diagnosis and management, cardiovascular diseases (CVDs) remain the leading cause of death in the US. Atherosclerosis is the most common form of CVD and the vulnerability of atherosclerotic plaques to rupture is a primary determinant for risk of catastrophic ischemic events. Current imaging of atherosclerotic disease focuses on assessing plaque size and the degree of luminal stenosis, which are not good predictors of plaque stability. Functional methods to identify biomarkers of inflammation in plaques could facilitate assessment of plaque instability to allow early intervention. In this study, we validate the use of a purpose-built, magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) insert for multimodal, molecular imaging of vulnerable plaques in mice. We illustrate the application of PET to screen for inflamed regions to guide the application of MRI. Molecular MRI visualizes regions of vascular inflammation and is coupled with anatomical MRI to generate detailed maps of the inflammatory marker within the context of an individual vessel. As a testbed for this imaging methodology, we developed a multimodal, iron oxide nanoparticle (NP) targeting vascular cell adhesion molecule-1 (VCAM-1) for simultaneous PET/MRI of vascular inflammation performed on a mouse carotid ligation model. In vitro cell studies confirmed that the NPs are not cytotoxic to liver cells. In vivo simultaneous PET/MRI imaging identified regions of inflammation. Three-dimensional rendering of the MRI data facilitated high-resolution visualization of patterns of inflammation along the injured vessel. Histology validated the co-localization of the NPs with VCAM-1 expression at sites of induced inflammation. The results of this work validate the utility of the simultaneous PET/MR insert as a research tool for small animals and lays groundwork to further advance the potential clinical utility of integrated imaging systems.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2019.12.16.878652DOIDiscussion Paper
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Louie, Angelique Y.0000-0001-6610-5356
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Dec. 17, 2019. The authors wish to thank F. Hayes and P. Kysar for their help with TEM and P. Hrvatin for help with AA spectroscopy. We thank Andre Jefferson and Haick Issian of the Caltech Radiation Safety office for help with the radiation studies and Naomi Santa-Maria for technical assistance in imaging. We thank Simon Cherry and his group for technical assistance with the hybrid imaging insert. The authors wish to acknowledge the National Institutes of Health (EB008576-01 and EB000993), the Center for Molecular and Genomic Imaging at the University of California, Davis (U24 CA 110804), and the NMR award of the University of California, Davis for support of this work. Author Contributions: AYL conceived and designed experiments; SD, TN, AH, TT, CT contributed to experiment design, performed experiments and contributed to data analysis; LZ prepared computer programs to render the imaging data; JP, IE performed and provided training for histology; REJ, KP contributed to experimental design and data analysis. The authors declare no conflict of interest.
Funders:
Funding AgencyGrant Number
NIHEB008576-01
NIHEB000993
NIHU24 CA 110804
University of California, DavisUNSPECIFIED
Subject Keywords:Multimodality imaging; MRI/PET; dual-mode imaging; nanoparticle; atherosclerosis; vulnerable plaque; cardiovascular imaging; vessel wall; VCAM
Record Number:CaltechAUTHORS:20191219-112734829
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191219-112734829
Official Citation:Contrast-Enhanced, Molecular Imaging of Vascular Inflammation in the Mouse Model by Simultaneous PET/MRI Siyi Du, Thomas S.C. Ng, Adrian House, Tang Tang, Lin Zheng, Chuqiao Tu, Janice Peake, Imelda E. Espiritu, Kwan-Liu Ma, Kent Pinkerton, Russell E. Jacobs, Angelique Y. Louie bioRxiv 2019.12.16.878652; doi: https://doi.org/10.1101/2019.12.16.878652
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:100374
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:20 Dec 2019 15:28
Last Modified:20 Dec 2019 15:28

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