Correspondence Letter by Stone and Mintz Regarding Article, “Unreliable Assessment of Necrotic Core by Virtual Histology Intravascular Ultrasound in Porcine Coronary Artery Disease” To the Editor:

We read with interest the article by Thim et al1 in which no correlation was found between the size of necrotic core determined by virtual histology intravascular ultrasound (VH IVUS) and actual histology in adult atherosclerosis-prone minipigs. The authors’ implication that caution is therefore warranted “in the interpretation of [human] studies relying on VH IVUS for monitoring of treatment effects, event prediction, and validation of other imaging modalities” would appear to exceed what may reliably be concluded from this study on several grounds. First, although the authors acknowledge that coregistration of VH IVUS frames and histological sections may be problematic, IVUS images are sampled every 0.5 mm on average, compared to every 4 mm for pathological sections in the study by Thim et al, introducing even greater error in matching (which cannot be over-come by use of fiduciary branch points or use of balloon angioplasty footprints). Moreover, tissue sections usually are 4 to 5 m in thickness compared to VH images, which are produced from IVUS beams typically 200 to 300 m in thickness. Therefore, given the marked longitudinal pathological variability that can be present every few micrometers,2 it is inappropriate to align a given histo-logical section to an IVUS frame and expect high correlation in quantification of individual tissue components. Second, despite this limitation, the lack of correlation between VH IVUS and histology, necrotic core area in the present report was driven primarily by 1 point in the upper left quadrant of Figure 1A.1 Using the data in this graph, if this outlier is removed, one can calculate that r0.79 (P0.0003), indicating very good correlation. Third (and not commonly appreciated), there often is major disagreement between pathologists when assessing histology.3,4 Pertinent to the present report, from a study in which 4 highly experienced cardiac pathologists assessed 30 Movat pentachrome coronary histology slides, in only 7 (23%) cases was there agreement about histological classification among all, with the greatest source of variability being in the location and quantity of necrotic cor