Quantification of serial changes in plaque burden using multi-detector computed tomography in experimental atherosclerosis

Assessment of changes in plaque volume is increasingly used as a surrogate-endpoint in clinical trials testing the efficacy of anti-atherosclerotic interventions. Multi-detector computed tomography (MDCT) can detect and quantify non-calcified atherosclerotic plaques, but its ability to monitor changes in plaque volume has not yet been tested. We sought to test the ability of MDCT to detect and quantify serial changes in atheroma burden in comparison with magnetic resonance imaging (MRI).

Rabbits (n=12) with experimentally induced abdominal atherosclerosis were randomized to receive a plaque-regressing agent (recombinant apoA-I(Milano), n=8) or placebo (n=4). All animals underwent two 64-slice MDCT angiography and MRI studies (pre- and post-treatment). The primary endpoint was the change in plaque burden (defined as vessel wall volume in the 5cm distal to the left renal artery) between pre- and post-treatment MDCT in comparison with MRI.

MDCT detected a significant decrease in plaque burden caused by recombinant apoA-I(Milano) (464 [423-535] to 405 [363-435]mm(3), p=0.03) that was confirmed by MRI (324 [286-412] to 298 [282-399]mm(3), p=0.03). No significant effect was noted in the placebo group either by MDCT or MRI. There were strong correlations between both modalities for the quantification of plaque burden (r=0.750, p<0.001) and change in plaque burden (r=0.657, p=0.020). MDCT overestimated plaque burden compared to MRI. On MDCT, the mean interobserver variability for plaque burden was 2.5+/-0.4%.

In an animal model of atherosclerosis, MDCT accurately documented serial changes in aortic plaque burden, demonstrating good correlation and agreement with MRI-derived measurements and low interobserver variability.