for the Integrated Biomarker and Imaging Study-2 InvestigatorsBackground-Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is expressed abundantly in the necrotic core of coronary lesions, and products of its enzymatic activity may contribute to inflammation and cell death, rendering plaque vulnerable to rupture. Methods and Results-This study compared the effects of 12 months of treatment with darapladib (an oral Lp-PLA 2 inhibitor, 160 mg daily) or placebo on coronary atheroma deformability (intravascular ultrasound palpography) and plasma high-sensitivity C-reactive protein in 330 patients with angiographically documented coronary disease. Secondary end points included changes in necrotic core size (intravascular ultrasound radiofrequency), atheroma size (intravascular ultrasound gray scale), and blood biomarkers. Background therapy was comparable between groups, with no difference in low-density lipoprotein cholesterol at 12 months (placebo, 88Ϯ34 mg/dL; darapladib, 84Ϯ31 mg/dL; Pϭ0.37). In contrast, Lp-PLA 2 activity was inhibited by 59% with darapladib (PϽ0.001 versus placebo). After 12 months, there were no significant differences between groups in plaque deformability (Pϭ0.22) or plasma highsensitivity C-reactive protein (Pϭ0.35). In the placebo-treated group, however, necrotic core volume increased significantly (4.5Ϯ17.9 mm 3 ; Pϭ0.009), whereas darapladib halted this increase (Ϫ0.5Ϯ13.9 mm 3 ; Pϭ0.71), resulting in a significant treatment difference of Ϫ5.2 mm 3 (Pϭ0.012). These intraplaque compositional changes occurred without a significant treatment difference in total atheroma volume (Pϭ0.95). Conclusions-Despite adherence to a high level of standard-of-care treatment, the necrotic core continued to expand among patients receiving placebo. In contrast, Lp-PLA 2 inhibition with darapladib prevented necrotic core expansion, a key determinant of plaque vulnerability. These findings suggest that Lp-PLA 2 inhibition may represent a novel therapeutic approach.

Background-In vivo detection of vulnerable plaques is presently limited by a lack of diagnostic tools. Intravascular ultrasound elastography is a new technique based on intravascular ultrasound and has the potential to differentiate between different plaques phenotypes. However, the predictive value of intravascular elastography to detect vulnerable plaques had not been studied. Methods and Results-Postmortem coronary arteries were investigated with intravascular elastography and subsequently processed for histology. In histology, a vulnerable plaque was defined as a plaque consisting of a thin cap (Ͻ250 m) with moderate to heavy macrophage infiltration and at least 40% of atheroma. In elastography, a vulnerable plaque was defined as a plaque with a high strain region at the surface with adjacent low strain regions. In 24 diseased coronary arteries, we studied 54 cross sections. In histology, 26 vulnerable plaques and 28 nonvulnerable plaques were found. Receiver operator characteristic analysis revealed a maximum predictive power for a strain value threshold of 1.26%. The area under the receiver operator characteristic curve was 0.85. The sensitivity was 88%, and the specificity was 89% to detect vulnerable plaques. Linear regression showed high correlation between the strain in caps and the amount of macrophages (PϽ0.006) and an inverse relation between the amount of smooth muscle cells and strain (PϽ0.0001). Plaques, which are declared vulnerable in elastography, have a thinner cap than nonvulnerable plaques (PϽ0.0001). Conclusions-Intravascular elastography has a high sensitivity and specificity to detect vulnerable plaques in vitro.

We describe a route toward contactless imaging of arterial oxygen saturation (SpO2) distribution within tissue, based upon detection of a two-dimensional matrix of spatially resolved optical plethysmographic signals at different wavelengths. As a first step toward SpO2-imaging we built a monochrome CMOS-camera with apochromatic lens and 3lambda-LED-ringlight (lambda1 = 660 nm, lambda2 = 810 nm, lambda3 = 940 nm; 100 LEDs lambda(-1)). We acquired movies at three wavelengths while simultaneously recording ECG and respiration for seven volunteers. We repeated this experiment for one volunteer at increased frame rate, additionally recording the pulse wave of a pulse oximeter. Movies were processed by dividing each image frame into discrete Regions of Interest (ROIs), averaging 10 x 10 raw pixels each. For each ROI, pulsatile variation over time was assigned to a matrix of ROI-pixel time traces with individual Fourier spectra. Photoplethysmograms correlated well with respiration reference traces at three wavelengths. Increased frame rates revealed weaker pulsations (main frequency components 0.95 and 1.9 Hz) superimposed upon respiration-correlated photoplethysmograms, which were heartbeat-related at three wavelengths. We acquired spatially resolved heartbeat-related photoplethysmograms at multiple wavelengths using a remote camera. This feasibility study shows potential for non-contact 2-D imaging reflection-mode pulse oximetry. Clinical devices, however, require further development.