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Focal and multi-focal plaque macrophage distributions in patients with acute and stable presentations of coronary artery disease

Briain D. MacNeill, MB, MSC^*,, Ik-Kyung Jang, MD, PHD^*, Brett E. Bouma, PHD, Nicusor Iftimia, PHD, Masamichi Takano, MD, PHD^*,, Hiroshi Yabushita, MD, PHD^*,,||, Milen Shishkov, PHD, Christopher R. Kauffman, BS, Stuart L. Houser, MD^,, H.Thomas Aretz, MD, Denise DeJoseph, ACNP^*, Elkan F. Halpern, PHD and Guillermo J. Tearney, MD, PHD^,,*

^* Cardiology Division
Wellman Center for Photomedicine
Department of Pathology
Department of Radiology, Harvard Medical School, Boston, MassachusettsUSA
^|| Department of Cardiology, Kinki University School of Medicine, Kinki, Japan

View larger version (159K): [in a new window]   Figure 1 Fibrous cap segmentation and macrophage density images for lipid-rich plaques. (a) A normalized standard deviation (NSD) image demonstrating high macrophage density (blue red) at a site of disruption (arrow) within a lipid-rich plaque (LP). The * represents guide wire shadow artifact. (b) Optical coherence tomography (OCT) image of an LP. The * represents guide wire shadow artifact. A 500 µm scale bar is shown in the top right-hand corner. (c) Outline (red) of the segmented fibrous cap of the OCT image depicted in panel b. (d) Normalized standard deviation image superimposed over a standard intensity image shows locations (blue red) corresponding to increased macrophage density. The color scale bar represents the color mapping of the NSD parameter.

View larger version (21K): [in a new window]   Figure 2 Multi-focal macrophage density results. (a) Bar graph showing macrophage density at culprit and remote sites for each clinical syndrome. Standard error bars are represented. Within each clinical syndrome no significant difference was found between the macrophage content at culprit and remote lesions. (b) Scatter plot of macrophage density in culprit lesions relative to that at remote sites within the same patient. Linear regression equation, Pearson's correlation coefficient (r), and p value are depicted in the insert. ACS = acute coronary syndrome; SAP = stable angina pectoris; STEMI = ST-segment elevation myocardial infarction.

View larger version (77K): [in a new window]   Figure 3 Focal macrophage density results. (a) Optical coherence tomography (OCT) image of a rupture site (outlined in red) overlying a lipid-rich plaque (LP). The * represents guide wire shadow. A 500 µm scale bar is seen in the top right-hand corner. (b) Bar graph representing mean macrophage density at sites of rupture, corresponding to outlined segment in panel a, compared with the rest of the plaque. Standard error bars are represented. (c and d) Receiver operating characteristic curves for surface and subsurface macrophage density for prediction of an acute coronary event at culprit sites (panel c) and remote sites (panel d). Areas under curve (AUC) for surface and subsurface macrophage density and the p value are noted in the insert.