Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice

Claudia Calcagno; John A David; Abdallah G Motaal; Bram F Coolen; Thijs Beldman; Alexandra Corbin; Arnav Kak; Sarayu Ramachandran; Alison Pruzan; Arthi Sridhar; Raphael Soler; Christopher M Faries; Zahi A Fayad; Willem J M Mulder; Gustav J Strijkers

doi:10.1002/nbm.4823

Self-gated, dynamic contrast-enhanced magnetic resonance imaging with compressed-sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice

NMR Biomed. 2023 Jan;36(1):e4823. doi: 10.1002/nbm.4823. Epub 2022 Sep 23.

Authors

Claudia Calcagno^{1

2}, John A David³, Abdallah G Motaal⁴, Bram F Coolen⁵, Thijs Beldman^{6

7}, Alexandra Corbin^{1

2}, Arnav Kak⁸, Sarayu Ramachandran^{1

2}, Alison Pruzan^{1

2}, Arthi Sridhar⁹, Raphael Soler^{10

11}, Christopher M Faries^{1

2}, Zahi A Fayad^{1

2}, Willem J M Mulder^{1

2

6

7}, Gustav J Strijkers^{1

5}

Affiliations

¹ Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, USA.
² Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, USA.
³ Amsterdam University Medical Centers, Department of Medical Biochemistry, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Siemens Healthineers, Cardiovascular Care Group, Advanced Therapies Business, Erlangen, Germany.
⁵ Amsterdam University Medical Centers, Department of Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands.
⁶ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
⁷ Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
⁸ University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹ Department of Hematology/Oncology, UTHealth McGovern Medical School, Houston, TX, USA.
¹⁰ CNRS, CRMBM, Marseille, France.
¹¹ Department of Vascular and Endovascular Surgery, Hôpital Universitaire de la Timone, APHM, Marseille, France.

Abstract

High-risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self-gated, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe^-/- atherosclerotic mice during natural disease progression. Twenty-four, 8-week-old, female Apoe^-/- mice were divided into four groups (n = 6 each) and imaged with self-gated DCE-MRI at 4, 8, 12, and 16 weeks after high-fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high-fat diet and imaged longitudinally at the same time points. Aortic-root pseudo-concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash-in and washout slopes (b₁ and b₂ ) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b₂ , indicating contrast agent washout, was significantly higher in mice kept on an high-fat diet for longer periods of time (p = 0.03). Group comparison revealed significant differences between mice on a high-fat diet for 4 versus 16 weeks (p = 0.03). Macrophage density also significantly increased with diet duration (p = 0.009). Spearman correlation between b₂ from DCE-MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p = 0.20). Validated piecewise linear modeling of the DCE-MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single-slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.

Keywords: DCE-MRI; atherosclerosis; inflammation; microvascularization; mouse; self-gated.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Aorta, Thoracic*
Contrast Media*
Disease Progression
Female
Magnetic Resonance Imaging
Mice

Substances

Contrast Media

Abstract

Publication types

MeSH terms

Substances

Grants and funding