Imaging and analysis of microcalcifications and lipid/necrotic core calcification in fibrous cap atheroma

The presence of microcalcifications (µCalcs) >5 µm within the cap of human fibroatheroma has been shown to produce a 200-700% increase in peak circumferential stress, which can transform a stable plaque into a vulnerable one, whereas µCalcs < 5 µm do not appear to increase risk. We quantitatively examine the possibility to distinguish caps with µCalcs > 5 µm based on the gross morphological features of fibroatheromas, and the correlation between the size and distribution of µCalcs in the cap and the calcification in the lipid/necrotic core beneath it. Atherosclerotic lesions (N = 72) were imaged using HR-μCT at 2.1-μm resolution for detailed analysis of atheroma morphology and composition, and validated using non-decalcified histology. At 2.1-μm resolution one observes four different patterns of calcification within the lipid/necrotic core, and is able to elucidate the 3D spatial progression of the calcification process using these four patterns. Of the gross morphological features identified, only minimum cap thickness positively correlated with the existence of µCalcs > 5 µm in the cap. We also show that µCalcs in the cap accumulate in the vicinity of the lipid/necrotic core boundary with few on the lumen side of the cap. HR-μCT enables three-dimensional assessment of soft tissue composition, lipid content, calcification patterns within lipid/necrotic cores and analysis of the axial progression of calcification within individual atheroma. The distribution of µCalcs within the cap is highly non-uniform and decreases sharply as one proceeds from the lipid pool/necrotic core boundary to the lumen.