This Article Abstract Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (31) Citing Articles via Google Scholar Google Scholar Articles by Tawakol, A. Articles by Fischman, A. J. Search for Related Content PubMed PubMed Citation Articles by Tawakol, A. Articles by Fischman, A. J. Related Collections Related Article

In Vivo ¹⁸ F-Fluorodeoxyglucose Positron Emission Tomography Imaging Provides a Noninvasive Measure of Carotid Plaque Inflammation in Patients

Ahmed Tawakol, MD^_*,_*, Raymond Q. Migrino, MD, Gregory G. Bashian, MD^_*, Shahinaz Bedri, MBBS, David Vermylen, BA^_*, Ricardo C. Cury, MD, Denise Yates, PhD, Glenn M. LaMuraglia, MD^||, Karen Furie, MD, Stuart Houser, MD, Henry Gewirtz, MD^_*, James E. Muller, MD^_*, Thomas J. Brady, MD and Alan J. Fischman, MD, PhD

^_* Department of Medicine (Cardiac Unit), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Department of Radiology and Nuclear Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
^|| Division of Vascular and Endovascular Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 1 Axial positron emission tomographic (PET) images and the co-registered computed tomographic (CT) images from 2 patients, 1 (patient A) who manifested low 18 F-fluorodeoxyglucose (FDG) uptake in the region of the carotid plaque and 1 (patient B) with high FDG uptake in the region of the carotid plaque. The region of the excised carotid plaque is noted with arrows . (A) Carotid plaque specimen taken from the patient with low FDG uptake (patient A). The corresponding trichrome-stained histologic specimen demonstrates a collagen-rich plaque with low lipid content, and CD68 staining on the high-powered images demonstrates limited macrophage infiltration. These histologic features are consistent with a metabolically stable and potentially clinically stable plaque. (B) Carotid plaque specimen taken from the patient with high FDG uptake (patient B). The corresponding trichrome-stained histologic specimen demonstrates a complex plaque with a necrotic core, and the CD68 staining demonstrates intense macrophage infiltration. These histologic features are consistent with a metabolically unstable plaque which is vulnerable to rupture.

View larger version (84K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Trichrome- (10x magnification) and CD68-stained (200x magnification) carotid specimens that correspond to the images in Figure 1 . The boxes in the trichrome-stained images indicate the regions corresponding to the high-powered CD68 stains. (A and B) As described in Figure 1 .

View larger version (9K): [in this window] [in a new window] [Download PPT slide]   Figure 3 Noninvasive positron emission tomography (PET) measurement of 18 F-fluorodeoxyglucose (FDG) uptake versus macrophage staining. The PET measurement of carotid plaque FDG uptake (target-to-background ratio [T/B]) in patients was compared with histologic assessment of inflammation in the corresponding sections taken during carotid endarterectomy. There was a significant correlation between T/B and macrophage density.

View larger version (7K): [in this window] [in a new window] [Download PPT slide]   Figure 4 Mean within-patient 18 F-fluorodeoxyglucose (FDG) uptake versus inflammation in carotid endarterectomy patients. For each of the 17 subjects, all histologic sections were averaged to generate a mean per-patient value for percentage macrophage staining. Likewise, the corresponding imaging data were combined to generate a mean target-to-background ratio (T/B) for each patient. There was a significant correlation between mean T/B and mean inflammation (r = 0.85; p < 0.001). The correlation remained significant (r = 0.82; p < 0.001) even after the outlier with the highest plaque inflammation was removed from the analysis.

View larger version (12K): [in this window] [in a new window] [Download PPT slide]   Figure 5 Positron emission tomography (PET) measurement of 18 F-fluorodeoxyglucose (FDG) uptake versus smooth muscle cell staining. The PET measurement of FDG uptake (target-to-background ratio [T/B]) in patients was compared with histologic assessment of smooth muscle cell staining (anti-SMA stain) in the corresponding sections taken during carotid endarterectomy. There was no correlation between FDG uptake and smooth muscle cell staining (r = 0.15; p = 0.54).

View larger version (15K): [in this window] [in a new window] [Download PPT slide]   Figure 6 Distribution of 18 F-fluorodeoxyglucose (FDG) uptake in patients grouped by average plaque inflammation. Patients were grouped according to the average amount of inflammation in their carotid specimens and the average FDG uptake determined for each group. The ranges assigned to these groups reflect the levels of inflammation shown to be important in previous histologic studies (14,20,21 ). The box plot shows mean values (thick lines) and 25th and 75 percentile values (upper and lower box boundaries) . The length of the whiskers from the box boundaries represents standard error of the mean. The mean FDG uptake value for each group was significantly different. T/B = target-to-background ratio.