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Increased microvascularization and vessel permeability associate with active inflammation in human atheromata.

Research paper by Viviany R VR Taqueti, Marcelo F MF Di Carli, Michael M Jerosch-Herold, Galina K GK Sukhova, Venkatesh L VL Murthy, Eduardo J EJ Folco, Raymond Y RY Kwong, C Keith CK Ozaki, Michael M Belkin, Matthias M Nahrendorf, Ralph R Weissleder, Peter P Libby

Indexed on: 30 Aug '14Published on: 30 Aug '14Published in: Circulation. Cardiovascular imaging



Abstract

Studies have shown the feasibility of imaging plaques with 2-deoxy-2-[(18)F]fluoroglucose (FDG) positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging with inconsistent results. We sought to investigate the relationship between markers of inflammatory activation, plaque microvascularization, and vessel wall permeability in subjects with carotid plaques using a multimodality approach combining FDG positron emission tomography, dynamic contrast-enhanced magnetic resonance imaging, and histopathology.Thirty-two subjects with carotid stenoses underwent noninvasive imaging with FDG positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging, 46.9% (n=15) before carotid endarterectomy. We measured FDG uptake (target:background ratio [TBR]) by positron emission tomography and K(trans) (reflecting microvascular permeability and perfusion) by magnetic resonance imaging and correlated imaging with immunohistochemical markers of macrophage content (CD68), activated inflammatory cells (major histocompatibility complex class II), and microvessels (CD31) in plaque and control regions. TBR and K(trans) correlated significantly with tertiles of CD68(+) (P=0.009 and P=0.008, respectively), major histocompatibility complex class II(+) (P=0.003 and P<0.001, respectively), and CD31(+) (P=0.004 and P=0.008, respectively). Regions of plaques were associated with increased CD68(+) (P=0.002), major histocompatibility complex class II(+) (P=0.002), CD31(+) (P=0.02), TBR (P<0.0001), and K(trans) (P<0.0001), as compared with those without plaques. Microvascularization correlated with macrophage content (rs=0.52; P=0.007) and inflammatory activity (rs=0.68; P=0.0001) and TBR correlated with K(trans) (rs=0.53; P<0.0001). In multivariable mixed linear regression modeling, TBR remained independently associated with K(trans) (β[SE], 2.68[0.47]; P<0.0001).Plaque regions with active inflammation, as determined by macrophage content and major histocompatibility complex class II expression, showed increased FDG uptake, which correlated with increased K(trans) and microvascularization. The correlation between K(trans) and TBR was moderate, direct, highly significant, and independent of clinical symptoms and plaque luminal severity.

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