Dual-energy computed tomography imaging of atherosclerotic plaques in a mouse model using a liposomal-iodine nanoparticle contrast agent.
BACKGROUND
The accumulation of macrophages in inflamed atherosclerotic plaques has long been recognized. In an attempt to develop an imaging agent for detection of vulnerable plaques, we evaluated the feasibility of a liposomal-iodine nanoparticle contrast agent for computed tomography imaging of macrophage-rich atherosclerotic plaques in a mouse model.


RESULTS
Liposomal-iodine formulations varying in particle size and polyethylene glycol coating were fabricated and shown to stably encapsulate the iodine compound. In vitro uptake studies using optical and computed tomography imaging in the RAW 264.7 macrophage cell line identified the formulation that promoted maximal uptake. Dual-energy computed tomography imaging using this formulation in apolipoprotein E-deficient (ApoE(-/-)) mice (n=8) and control C57BL/6 mice (n=6) followed by spectral decomposition of the dual-energy images enabled imaging of the liposomes localized in the plaque. Imaging cytometry confirmed the presence of liposomes in the plaque and their colocalization with a small fraction (≈2%) of the macrophages in the plaque.


CONCLUSIONS
The results demonstrate the feasibility of imaging macrophage-rich atherosclerotic plaques using a liposomal-iodine nanoparticle contrast agent and dual-energy computed tomography.
Singleton Department of Pediatric Radiology, Texas Children's Hospital, Houston, TX 77030, USA.
Rohan
R
Bhavane
Cristian
C
Badea
Ketan B
KB
Ghaghada
Darin
D
Clark
Deborah
D
Vela
Anoosha
A
Moturu
Akshaya
A
Annapragada
G Allan
GA
Johnson
James T
JT
Willerson
Ananth
A
Annapragada
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001027:Aortography / Q000379:methods*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D003287:Contrast Media / Q000008:administration & dosage / Q000378:metabolism; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005434:Flow Cytometry; D008081:Liposomes; D008264:Macrophages / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000008:administration & dosage / Q000378:metabolism
D001057:Apolipoproteins E; D003287:Contrast Media; D008081:Liposomes; D014283:Triiodobenzoic Acids; C044834:iodixanol