Non-Invasive Photoacoustic Imaging of In Vivo Mice with Erythrocyte Derived Optical Nanoparticles to Detect CAD/MI

Yonggang Liu; Taylor Hanley; Hao Chen; Steven R Long; Sanjiv S Gambhir; Zhen Cheng; Joseph C Wu; Georges El Fakhri; Bahman Anvari; Raiyan T Zaman

doi:10.1038/s41598-020-62868-1

Non-Invasive Photoacoustic Imaging of In Vivo Mice with Erythrocyte Derived Optical Nanoparticles to Detect CAD/MI

Sci Rep. 2020 Apr 6;10(1):5983. doi: 10.1038/s41598-020-62868-1.

Authors

Yonggang Liu¹, Taylor Hanley², Hao Chen³, Steven R Long⁴, Sanjiv S Gambhir^{3

5

6}, Zhen Cheng³, Joseph C Wu^{1

3

7}, Georges El Fakhri^{8

9}, Bahman Anvari¹⁰, Raiyan T Zaman^{11

12}

Affiliations

¹ Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA, USA.
² Department of Bioengineering, University of California, Riverside, CA, USA.
³ Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Pathology, University of California, San Francisco, CA, United States.
⁵ Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Bioengineering, Stanford University School of Medicine, Stanford, CA, USA.
⁷ Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁸ Department of Radiology, Harvard Medical School, Boston, MA, USA.
⁹ Gordon Center for Medical Imaging, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Department of Bioengineering, University of California, Riverside, CA, USA. anvarib@ucr.edu.
¹¹ Molecular Imaging Program at Stanford, Stanford University School of Medicine, Stanford, CA, USA. rzaman@mgh.harvard.edu.
¹² Department of Bioengineering, Stanford University School of Medicine, Stanford, CA, USA. rzaman@mgh.harvard.edu.

Abstract

Coronary artery disease (CAD) causes mortality and morbidity worldwide. We used near-infrared erythrocyte-derived transducers (NETs), a contrast agent, in combination with a photoacoustic imaging system to identify the locations of atherosclerotic lesions and occlusion due to myocardial-infarction (MI). NETs (≈90 nm diameter) were fabricated from hemoglobin-depleted mice erythrocyte-ghosts and doped with Indocyanine Green (ICG). Ten weeks old male C57BL/6 mice (n = 9) underwent left anterior descending (LAD) coronary artery ligation to mimic vulnerable atherosclerotic plaques and their rupture leading to MI. 150 µL of NETs (20 µM ICG,) was IV injected via tail vein 1-hour prior to photoacoustic (PA) and fluorescence in vivo imaging by exciting NETs at 800 nm and 650 nm, respectively. These results were verified with histochemical analysis. We observed ≈256-fold higher PA signal from the accumulated NETs in the coronary artery above the ligation. Fluorescence signals were detected in LAD coronary, thymus, and liver. Similar signals were observed when the chest was cut open. Atherosclerotic lesions exhibited inflammatory cells. Liver demonstrated normal portal tract, with no parenchymal necrosis, inflammation, fibrosis, or other pathologic changes, suggesting biocompatibility of NETs. Non-invasively detecting atherosclerotic plaques and stenosis using NETs may lay a groundwork for future clinical detection and improving CAD risk assessment.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Coronary Artery Disease / diagnostic imaging*
Coronary Vessels / diagnostic imaging*
Disease Models, Animal
Erythrocytes*
Mice
Myocardial Infarction / diagnostic imaging*
Nanoparticles*
Optical Imaging / methods*
Photoacoustic Techniques / methods*