Multimodal CARS microscopy determination of the impact of diet on macrophage
infiltration and lipid accumulation on plaque formation in ApoE-deficient mice.
Authors Lim RS, Kratzer A, Barry NP, Miyazaki-Anzai S, Miyazaki M, Mantulin WW, Levi M,
Potma EO, Tromberg BJ
Submitted By Moshe Levi on 8/1/2012
Status Published
Journal Journal of lipid research
Year 2010
Date Published 7/1/2010
Volume : Pages 51 : 1729 - 1737
PubMed Reference 20208058
Abstract We characterized several cellular and structural features of early stage Type
II/III atherosclerotic plaques in an established model of atherosclerosis-the
ApoE-deficient mouse-by using a multimodal, coregistered imaging system that
integrates three nonlinear optical microscopy (NLOM) contrast mechanisms:
coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG),
and two-photon excitation fluorescence (TPEF). Specifically, the infiltration of
lipid-rich macrophages and the structural organization of collagen and elastin
fibers were visualized by CARS, SHG, and TPEF, respectively, in thick tissue
specimens without the use of exogenous labels or dyes. Label-free CARS imaging
of macrophage accumulation was confirmed by histopathology using CD68 staining.
A high-fat, high-cholesterol Western diet resulted in an approximate 2-fold
increase in intimal plaque area, defined by CARS signals of lipid-rich
macrophages. Additionally, analysis of collagen distribution within lipid-rich
plaque regions revealed nearly a 4-fold decrease in the Western diet-fed mice,
suggesting NLOM sensitivity to increased matrix metalloproteinase (MMP) activity
and decreased smooth muscle cell (SMC) accumulation. These imaging results
provide significant insight into the structure and composition of early stage
Type II/III plaque during formation and allow for quantitative measurements of
the impact of diet and other factors on critical plaque and arterial wall

Investigators with authorship
Moshe LeviGeorgetown University