CC BY-NC-ND 4.0 · Thromb Haemost 2023; 123(05): 545-554
DOI: 10.1055/a-2005-8784
Atherosclerosis and Ischaemic Disease

Longitudinal In Vivo Monitoring of Atheroprogression in Hypercholesterolemic Mice Using Photoacoustic Imaging

Bartolo Ferraro
1   Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
2   DZHK, Partner Site Munich Heart Alliance, Munich, Germany
3   Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig- Maximilians-University Munich, Planegg-Martinsried, Germany
,
Pierangela Giustetto
4   Fujifilm VisualSonics Consultant, Amsterdam, The Netherlands
5   Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
,
Olga Schengel
6   Institute for Experimental Pathology (ExPat), Centre for Molecular Biology of Inflammation (ZMBE), University of Münster, Münster, Germany
,
Ludwig T. Weckbach
2   DZHK, Partner Site Munich Heart Alliance, Munich, Germany
3   Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig- Maximilians-University Munich, Planegg-Martinsried, Germany
7   Medizinische Klinik und Poliklinik I, Klinikum der Universität, Ludwig-Maximilians-University Munich, Munich, Germany
8   Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University Munich, University Hospital, Planegg-Martinsried, Germany
,
Lars Maegdefessel
2   DZHK, Partner Site Munich Heart Alliance, Munich, Germany
9   Department of Vascular and Endovascular Surgery, Technical University Munich, Munich, Germany
10   Department of Medicine, Karolinska Institutet, Stockholm, Sweden
,
Oliver Soehnlein
1   Institute for Cardiovascular Prevention (IPEK), LMU Munich, Munich, Germany
2   DZHK, Partner Site Munich Heart Alliance, Munich, Germany
6   Institute for Experimental Pathology (ExPat), Centre for Molecular Biology of Inflammation (ZMBE), University of Münster, Münster, Germany
11   Department of Physiology and Pharmacology (FyFa), Karolinska Institutet, Stockholm, Sweden
› Author Affiliations
Funding The authors' research is supported by the Deutsche Forschungsgemeinschaft (SFB914 TP B08, SFB1123 A6 and B5, SFB1009 A13, CRC TRR332 A2 and Z1), the Leducq Foundation, the 448 Else Kröner Fresenius Stiftung, and FUJIFILM VisualSonics, Inc.


Abstract

Background and Aim The ability to recognize and monitor atherosclerotic lesion development using noninvasive imaging is crucial in preventive cardiology. The aim of the present study was to establish a protocol for longitudinal monitoring of plaque lipid, collagen, and macrophage burden as well as of endothelial permeability.

Methods and Results Photoacoustic signals derived from endogenous or exogenous dyes assessed in vivo, in plaques of albino Apoe −/− mice, correlated with lesion characteristics obtained after histomorphometric and immunofluorescence analyses, thus supporting the validity of our protocol. Using models of atheroprogression and regression, we could apply our imaging protocol to the longitudinal observation of atherosclerotic lesion characteristics in mice.

Conclusions The present study shows an innovative approach to assess arterial inflammation in a non-invasive fashion, applicable to longitudinal analyses of changes of atherosclerotic lesion composition. Such approach could prove important in the preclinical testing of therapeutic interventions in mice carrying pre-established lesions.

Authors' Contribution

B.F. acquired and analyzed all data and wrote the manuscript; P.G. and O.Sch. contributed to data acquisition; L.T.W. and L.M. provided intellectual input; O.S. conceived and supervised the study, provided funding, and wrote the manuscript.


Supplementary Material



Publication History

Received: 08 February 2022

Accepted: 27 October 2022

Accepted Manuscript online:
03 January 2023

Article published online:
30 January 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The Mediterranean diet, its components, and cardiovascular disease. Am J Med 2015; 128 (03) 229-238
  • 2 Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol 2011; 12 (03) 204-212
  • 3 Phinikaridou A, Andia ME, Lavin B, Smith A, Saha P, Botnar RM. Increased vascular permeability measured with an albumin-binding magnetic resonance contrast agent is a surrogate marker of rupture-prone atherosclerotic plaque. Circ Cardiovasc Imaging 2016; 9 (12) e004910
  • 4 Yeager D, Chen YS, Litovsky S, Emelianov S. Intravascular photoacoustics for image-guidance and temperature monitoring during plasmonic photothermal therapy of atherosclerotic plaques: a feasibility study. Theranostics 2013; 4 (01) 36-46
  • 5 Lemaster JE, Jokerst JV. What is new in nanoparticle-based photoacoustic imaging?. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2017; 9 (01)
  • 6 Wang LV, Hu S. Photoacoustic tomography: in vivo imaging from organelles to organs. Science 2012; 335 (6075): 1458-1462
  • 7 Zackrisson S, van de Ven SMWY, Gambhir SS. Light in and sound out: emerging translational strategies for photoacoustic imaging. Cancer Res 2014; 74 (04) 979-1004
  • 8 Wu D, Huang L, Jiang MS, Jiang H. Contrast agents for photoacoustic and thermoacoustic imaging: a review. Int J Mol Sci 2014; 15 (12) 23616-23639
  • 9 Karlas A, Fasoula NA, Paul-Yuan K. et al. Cardiovascular optoacoustics: from mice to men - a review. Photoacoustics 2019; 14: 19-30
  • 10 Hui J, Cao Y, Zhang Y. et al. Real-time intravascular photoacoustic-ultrasound imaging of lipid-laden plaque in human coronary artery at 16 frames per second. Sci Rep 2017; 7 (01) 1417
  • 11 Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957; 226 (01) 497-509
  • 12 Kang NY, Park SJ, Ang XW. et al. A macrophage uptaking near-infrared chemical probe CDnir7 for in vivo imaging of inflammation. Chem Commun (Camb) 2014; 50 (50) 6589-6591
  • 13 Lundeberg E, Van Der Does AM, Kenne E, Soehnlein O, Lindbom L. Assessing large-vessel endothelial permeability using near-infrared fluorescence imaging–brief report. Arterioscler Thromb Vasc Biol 2015; 35 (04) 783-786
  • 14 Razansky D, Harlaar NJ, Hillebrands JL. et al. Multispectral optoacoustic tomography of matrix metalloproteinase activity in vulnerable human carotid plaques. Mol Imaging Biol 2012; 14 (03) 277-285
  • 15 Cui JZ, Lee L, Sheng X. et al. In vivo characterization of doxycycline-mediated protection of aortic function and structure in a mouse model of Marfan syndrome-associated aortic aneurysm. Sci Rep 2019; 9 (01) 2071
  • 16 Park S, Jung U, Lee S, Lee D, Kim C. Contrast-enhanced dual mode imaging: photoacoustic imaging plus more. Biomed Eng Lett 2017; 7 (02) 121-133
  • 17 Weber J, Beard PC, Bohndiek SE. Contrast agents for molecular photoacoustic imaging. Nat Methods 2016; 13 (08) 639-650
  • 18 Gujrati V, Mishra A, Ntziachristos V. Molecular imaging probes for multi-spectral optoacoustic tomography. Chem Commun (Camb) 2017; 53 (34) 4653-4672
  • 19 Zhang J, Yang S, Ji X, Zhou Q, Xing D. Characterization of lipid-rich aortic plaques by intravascular photoacoustic tomography: ex vivo and in vivo validation in a rabbit atherosclerosis model with histologic correlation. J Am Coll Cardiol 2014; 64 (04) 385-390
  • 20 Jansen K, Wu M, van der Steen AF, van Soest G. Photoacoustic imaging of human coronary atherosclerosis in two spectral bands. Photoacoustics 2013; 2 (01) 12-20
  • 21 Sekar SK, Bargigia I, Mora AD. et al. Diffuse optical characterization of collagen absorption from 500 to 1700 nm. J Biomed Opt 2017; 22 (01) 15006
  • 22 Park E, Lee YJ, Lee C, Eom TJ. Effective photoacoustic absorption spectrum for collagen-based tissue imaging. J Biomed Opt 2020; 25 (05) 1-8
  • 23 Park SJ, Kim B, Choi S. et al. Imaging inflammation using an activated macrophage probe with Slc18b1 as the activation-selective gating target. Nat Commun 2019; 10 (01) 1111
  • 24 Alam SR, Stirrat C, Richards J. et al. Vascular and plaque imaging with ultrasmall superparamagnetic particles of iron oxide. J Cardiovasc Magn Reson 2015; 17 (01) 83
  • 25 Tsang VTC, Li X, Wong TTW. A review of endogenous and exogenous contrast agents used in photoacoustic tomography with different sensing configurations. Sensors (Basel) 2020; 20 (19) 5595
  • 26 Karlas A, Kallmayer M, Bariotakis M. et al. Multispectral optoacoustic tomography of lipid and hemoglobin contrast in human carotid atherosclerosis. Photoacoustics 2021; 23: 100283