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3-D Analysis of Fibrous Caps Suggests Need to Rethink Atherosclerotic Plaque Vulnerability

Key findings

  • Non-culprit atherosclerotic plaques with very thin fibrous caps, called thin-cap fibroatheroma (TCFAs), are vulnerable to rupture and may be associated with greater risk of major cardiovascular events in the future
  • Currently, fibrous cap thickness is measured at an arbitrary point with 2-D optical coherence tomography
  • 3-D computer-assisted volumetric analysis showed that in patients presenting with either ST-elevation myocardial infarction (STEMI) or stable angina (SA), TCFAs were dispersed throughout non-culprit plaques, rather than being concentrated in one area creating a single weak point
  • Compared with SA patients, STEMI patients had a greater median number of TCFAs, greater median largest single TCFA area and greater median total sum TCFA area, but in both groups there was marked diversity in number and size of TCFAs
  • These results may redefine the concept of plaque vulnerability

The fibrous caps covering the lipid cores of atherosclerotic lesions vary in thickness, a key determinant of plaque stability. In the PROSPECT trial TCFA in non-culprit areas predicted major cardiovascular events. However, a more recent study from Massachusetts General Hospital showed that TCFA led to major cardiovascular events in only 1% of patients followed for two years.

The definition of TCFA might partly explain these contradictory findings. Currently, fibrous cap thickness (FCT) is measured at an arbitrary point determined by visually assessing 2-D optical coherence tomography (OCT) images. That method is poorly reproducible. Also, even though two lesions may have TCFA with the same FCT, the distribution and total area of the fibrous cap may differ.

Ik-Kyung Jang, MD, PhD, director of the Cardiology Laboratory for Integrative Physiology and Imaging in the Cardiology Division at Mass General, and colleagues are using a computer algorithm that allows 3-D volumetric analysis of fibrous caps. As they report in Circulation Journal, their observations have prompted them to reconsider the mechanisms of plaque rupture and which patients are at high risk of acute coronary syndromes.

Study Methodology

The researchers selected 23 patients with STEMI caused by plaque rupture from the Mass General OCT Registry, a data set of patients who have undergone OCT of the coronary arteries at 20 sites across six countries, and identified 27 non-culprit lesions in the culprit vessels. Non-culprit lesions were defined as plaques seen on coronary angiogram that had not been treated, with a diameter stenosis of >30% on OCT examination.

An additional 23 SA patients with 27 non-culprit plaques were matched to the STEMI patients by age and gender. With the aid of the computer algorithm, the researchers segmented FC boundaries in each frame of the OCT images. Next, the FCT at every point of the cap boundary was determined, and the FCT area per plaque was summed and classified using one of three categories: <80 μm (defined as TCFA), 80–200 μm or >200 μm.

Patterns of TCFA

The 3-D analysis showed that TCFAs were dispersed throughout the plaques, creating multiple weak areas. This pattern was especially notable in STEMI patients, who had an almost three-fold greater number of TCFAs, as well as a three-fold larger surface area in individual TCFA as compared to SA patients. Significantly, patients with STEMI had a larger area of FCT <200 μm and a smaller area of FCT >200 μm, as compared to SA patients. Moreover, the researchers showed that even in patients with STEMI, there is great variability in both the number of TCFAs as well as the size of the largest single TCFA.

Research Implications

The researchers suggest that plaque vulnerability may not depend on the single-point thickness of FC, as measured in current practice, but rather on the largest area of thin FC or even the sum of several TCFAs located near each other.

The data also suggest, the research team says, that changes in the whole FC pattern may be a better indicator of response to treatment and risk of future cardiovascular events than FCT measured at a single location.

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