Use of OCT to Localize Macrophages Ik-Kyung Jang, MD, PhD Professor of Medicine Harvard Medical School

Disclosure Research grant: LLI/St Disclosure Research grant: LLI/St. Jude medical, Medtronic, Abbott Vascular, JNJ Consultant: LLI/St. Jude medical

Macrophages by OCT Stable Angina Post-MI T LP LP Lumen

Ex Vivo Macrophage Study Low Mf High Mf 250 µm OCT CD68

Linear NSD vs. CD68 CD68 % area > 10 % - NSD cutoff 6.2% SENS 100% (70-100%) SPEC 100% (60 -100%) Tearney. Circulation, 2003

Macrophage Analysis (119 plaques) Cap segmentation- Entire fibrous cap Rupture Surface: < 50 µm from lumen Subsurface: > 50 µm from lumen NSD computation- Definition: Macrophage Density ~ Mean NSD within Segmented Region 0% 10%

Tissue Property Analysis

Tissue Property Analysis

Evaluation of Macrophage in Patients Macrophage density ~ clinical syndrome Rupture vs. non-rupture site density Surface vs. subsurface density

Macrophage Density Clinical Presentations * *P < 0.001

Macrophage Density Culprit vs. Remote Sites

Macrophage Density Rupture Sites

Macrophage Density Surface versus Subsurface Culprit Remote Surface AUC = 0.79 Subsurface AUC = 0.69 P = 0.035 Surface AUC = 0.73 Subsurface AUC = 0.72 P = 0.80 Surface cap macrophage density is more predictive of clinical syndrome than subsurface macrophage density at culprit, but not remote sites

Aim of the study Evaluate the relationships between local plaque fibrous cap macrophage density, the peripheral WBC count, and the plaque characteristics

Correlation of WBC count with Macrophage Density and Fibrous Cap Thickness 16.0 14.0 12.0 10.0 8.0 6.0 4.0 WBC count 2.0 0.0 Macrophage Density (%) 5.5 5.0 4.5 3.5 3.0 2.5 Fibrous Cap Thickness (Ln) r = 0.483, p < 0.001 r = - 0.423, p < 0.013

Association Between Macrophage Density and Fibrous Cap Thickness 10.0 8.0 6.0 4.0 2.0 5.5 5.0 4.5 3.5 3.0 2.5 Ln of Fibrous Cap Thickness

Macrophage Density Non TCFA vs TCFA 9.0 A p < 0.001 8.0 7.0 6.0 5.0 4.0 3.0 5.0 (1.9) 7.4 (1.8) Non TCFA TCFA Values are median (interquartile range)

Aim of the study remodeling assessed by IVUS and underlying Evaluate the association between coronary artery remodeling assessed by IVUS and underlying macrophage density identified by OCT

Association Between Remodeling and Underlying Plaque Macrophage Density 7.0 6.9 6.0 5.8 Mean Macrophage Density (NSD %) 5.0 4.0 3.9 3.0 Positive Absent Negative

Summary Macrophage can be detected and localized in vivo. Increased Macrophage density in ACS. Correlation between macrophage density and plaque characteristics (TCFA) and systemic inflammation (WBC). Correlation between macrophage density and positive remodeling.

Limitations The difference in macrophage density is marginal.

Limitations The difference in macrophage density is marginal. Enzymatic activity of macrophage is not known. Measuring NSD, not macrophage. 4. Prognostic utility is unknown.