Biomaterial Database

In Vivo Molecular K-Edge Imaging of Atherosclerotic Plaque Using Photon-counting CT. 2021

Salim A Si-Mohamed, and Monica Sigovan, and Jessica C Hsu, and Valérie Tatard-Leitman, and Lara Chalabreysse, and Pratap C Naha, and Thibaut Garrivier, and Riham Dessouky, and Miruna Carnaru, and Loic Boussel, and David P Cormode, and Philippe C Douek

From the University of Lyon, National Institute of Applied Sciences of Lyon, University Claude Bernard Lyon 1, Jean Monnet University-Saint Etienne, French National Centre for Scientific Research, Institut national de la santé et de la recherche médicale, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé Unité mixte de recherche 5220, U1206, F-69621, Lyon, France (S.A.S.M., M.S., V.T.L., R.D., L.B., P.C.D.); Departments of Radiology (S.A.S.M., T.G., L.B., P.C.D.) and Pathology (L.C.), Hospices Civils de Lyon, Lyon, France; Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (J.C.H., P.C.N., D.P.C.); Department of Radiology, Faculty of Medicine, Zagazig University, Egypt (R.D.); and Department of Rheumatology, Allergy, and Immunology, Yale University, New Haven, Conn (M.C.).

Background Macrophage burden is a major factor in the risk of atherosclerotic plaque rupture, and its evaluation remains challenging with molecular noninvasive imaging approaches. Photon-counting CT (PCCT) with k-edge imaging aims to allow for the specific detection of macrophages using gold nanoparticles. Purpose To perform k-edge imaging in combination with gold nanoparticles to detect and quantify the macrophage burden within the atherosclerotic aortas of rabbits. Materials and Methods Atherosclerotic and control New Zealand white rabbits were imaged before and at several time points up to 2 days after intravenous injection of gold nanoparticles (3.5 mL/kg, 65 mg gold per milliliter). Aortic CT angiography was performed at the end of the follow-up using an intravenous injection of an iodinated contrast material. Gold k-edge and conventional CT images were reconstructed for qualitative and quantitative assessment of the macrophage burden. PCCT imaging results were compared with findings at histologic examination, quantitative histomorphometry, transmission electron microscopy, and quantitative inductively coupled plasma optical emission spectrometry. Pearson correlations between the macrophage area measured in immunostained sections and the concentration of gold and attenuation measured in the corresponding PCCT sections were calculated. Results Seven rabbits with atherosclerosis and four control rabbits without atherosclerosis were analyzed. In atherosclerotic rabbits, calcifications were observed along the aortic wall before injection. At 2 days after injection of gold nanoparticles, only gold k-edge images allowed for the distinction of plaque enhancement within calcifications and for lumen enhancement during angiography. A good correlation was observed between the gold concentration measured within the wall and the macrophage area in 35 plaques (five per rabbit) (r = 0.82; 95% CI: 0.67, 0.91; P < .001), which was higher than that observed on conventional CT images (r = 0.41; 95% CI: 0.09, 0.65; P = .01). Transmission electron microscopy and inductively coupled plasma optical emission spectrometry analyses confirmed the gold k-edge imaging findings. Conclusion Photon-counting CT with gold nanoparticles allowed for the noninvasive evaluation of both molecular and anatomic information in vivo in rabbits with atherosclerotic plaques. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Leiner in this issue.

UI	MeSH Term	Description	Entries
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006046	Gold	A yellow metallic element with the atomic symbol Au, atomic number 79, and atomic weight 197. It is used in jewelry, goldplating of other metals, as currency, and in dental restoration. Many of its clinical applications, such as ANTIRHEUMATIC AGENTS, are in the form of its salts.
D000072226	Computed Tomography Angiography	A non-invasive method that uses a CT scanner for capturing images of blood vessels and tissues. A CONTRAST MATERIAL is injected, which helps produce detailed images that aid in diagnosing VASCULAR DISEASES.	Angiography, CT,Angiography, Computed Tomography,CT Angiography,Angiographies, CT,Angiographies, Computed Tomography,CT Angiographies,Computed Tomography Angiographies,Tomography Angiographies, Computed,Tomography Angiography, Computed
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001011	Aorta	The main trunk of the systemic arteries.	Aortas
D001018	Aortic Diseases	Pathological processes involving any part of the AORTA.	Aortic Disease,Disease, Aortic,Diseases, Aortic
D017023	Coronary Angiography	Radiography of the vascular system of the heart muscle after injection of a contrast medium.	Angiography, Coronary,Angiographies, Coronary,Coronary Angiographies
D017785	Photons	Discrete concentrations of energy, apparently massless elementary particles, that move at the speed of light. They are the unit or quantum of electromagnetic radiation. Photons are emitted when electrons move from one energy state to another. (From Hawley's Condensed Chemical Dictionary, 11th ed)