As my comments in Nature Cardiology Reviews show, I strongly disagree with many aspects of the article Otsuka et al. (Nature Reviews Cardiology (2014) ) and their response article above "Matching human pathology...". Virmani et. al. These types of misconceptions I feel have contributed to holding back the field for over a decade.

Several comments on cardiovascular OCT
1. Current OCT approaches do not reliable measure necrotic cores. With OCT, to identify TCFA, in addition to cap thickness you need to identify if it has a necrotic core. There are several problems with this. First the OCT literature has looked at the presence of lipid but histopathology studies have focused on necrotic cores. They are not the same thing. So no one actually has studied the imaging characteristics of necrotic cores, whose characteristic are often distorted by multiple scattering. Second, we have previously published it is unlikely that the current ‘diffuse borders’ criteria is actually measuring lipid or necrotic cores (based both on the data and theoretical reasons). This seems to be the opinion of the 2012 consensus study but you have to search to find it (J Am Coll Cardiol 2012;59:1058–72). For reasons we have discussed here and in other work, it is more likely the diffuse borders are lipid collections in the intima rather than anything specific to the core. It is just more likely that necrotic plaques have lipid in their intima (multiple scattering). We have previous published this can be removed with parallel ultrasound.
2. Current OCT approaches unlikely measure macrophages. It is unlikely current OCT techniques measure macrophages. We have stated in previous work are concerns over the one publication that suggests it does and in the current paper we discuss some of the reasons. That groups work used an algorithm and speckle variation. So the claim in the Otsuka et al that they actually caused shadowing is extremely unlikely and more likely do to other elements seen in the histopathology. Macrophages are a low scatterer in a high scattering environment (lipid and calcium). Recently Phillips JE et. al. have come to similar conclusions. We do not believe the approach in Tearney, G. J. et al. Circ. 107, 113–119 (2003) reliably measures macrophages. Again it seems to be the opinion of the consensus study but was an important point not emphasized.


3. As we presented in the TCT and should be published shortly, we believe that the TCFA that trigger ACS are in close proximity to longitudinal core we term shafts. In Virmani et. al. (Nature Reviews Cardiology (2014) doi:10.1038/nrcardio.2014.62-c2) there is a misunderstanding where I am quoted as believing these (shafts, intrapalque cavities, or whatever term) are due potentially to flushes during the procedures. I do not believe that so it is a misunderstanding. I believe they may be key in understanding which TCFAs lead to ACSs.
4. The TCFA that trigger ACS are likely in close proximity to necrotic longitudinal shafts (or intraplaque cavities or necrotic core whatever name you choose). We have a paper coming out in the next two weeks on this.
5. Inflammation causes atherosclerosis and is present after rupture (which is a highly thrombogenic environment ) but there is no evidence a aware of inflammation leads to rupture.