Viviany R Taqueti1, Marcelo F Di Carli1, Michael Jerosch-Herold1, Galina K Sukhova1, Venkatesh L Murthy1, Eduardo J Folco1, Raymond Y Kwong1, C Keith Ozaki1, Michael Belkin1, Matthias Nahrendorf1, Ralph Weissleder1, Peter Libby2. 1. From the Heart and Vascular Institute (V.R.T., M.F.D.C., G.K.S., E.J.F., R.Y.K., C.K.O., M.B., P.L.), Noninvasive Cardiovascular Imaging Program, Nuclear Medicine and Molecular Imaging Division, Department of Radiology (V.R.T., M.F.D.C., M.J.-H., R.Y.K.), Brigham and Women's Hospital, and Center for Systems Biology, Massachusetts General Hospital (M.N., R.W.), Harvard Medical School, Boston, MA; and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.). 2. From the Heart and Vascular Institute (V.R.T., M.F.D.C., G.K.S., E.J.F., R.Y.K., C.K.O., M.B., P.L.), Noninvasive Cardiovascular Imaging Program, Nuclear Medicine and Molecular Imaging Division, Department of Radiology (V.R.T., M.F.D.C., M.J.-H., R.Y.K.), Brigham and Women's Hospital, and Center for Systems Biology, Massachusetts General Hospital (M.N., R.W.), Harvard Medical School, Boston, MA; and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.). plibby@rics.bwh.harvard.edu.
Abstract
BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.
BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.
Authors: Martine T B Truijman; Robert M Kwee; Raf H M van Hoof; Evelien Hermeling; Robert J van Oostenbrugge; Werner H Mess; Walter H Backes; Mat J Daemen; Jan Bucerius; Joachim E Wildberger; Marianne Eline Kooi Journal: Stroke Date: 2013-10-10 Impact factor: 7.914
Authors: William Kerwin; Andrew Hooker; Mary Spilker; Paolo Vicini; Marina Ferguson; Thomas Hatsukami; Chun Yuan Journal: Circulation Date: 2003-02-18 Impact factor: 29.690
Authors: Frank D Kolodgie; Herman K Gold; Allen P Burke; David R Fowler; Howard S Kruth; Deena K Weber; Andrew Farb; L J Guerrero; Motoya Hayase; Robert Kutys; Jagat Narula; Aloke V Finn; Renu Virmani Journal: N Engl J Med Date: 2003-12-11 Impact factor: 91.245
Authors: Clare M Dollery; Caroline A Owen; Galina K Sukhova; Alexandra Krettek; Steven D Shapiro; Peter Libby Journal: Circulation Date: 2003-05-27 Impact factor: 29.690
Authors: Philip Joseph; Amorina Ishai; Venkatesh Mani; David Kallend; James H F Rudd; Zahi A Fayad; Ahmed Tawakol Journal: Eur J Nucl Med Mol Imaging Date: 2016-10-13 Impact factor: 9.236
Authors: Heather L Teague; Mark A Ahlman; Abass Alavi; Denisa D Wagner; Andrew H Lichtman; Matthias Nahrendorf; Filip K Swirski; Frank Nestle; Joel M Gelfand; Mariana J Kaplan; Steven Grinspoon; Paul M Ridker; David E Newby; Ahmed Tawakol; Zahi A Fayad; Nehal N Mehta Journal: J Am Coll Cardiol Date: 2017-09-12 Impact factor: 24.094