Introduction

Atherosclerosis of the carotid artery accounts for about a fifth of ischemic strokes (1). Rupture of a vulnerable atherosclerotic plaque can lead to thrombus formation and, subsequently, to ischemic events (1, 2). During recent years, identification of patients with an increased stroke risk has turned from plaque stenosis severity to identifying plaque composition (3, 4). Intraplaque microvessels are thought to play an important role in atherogenesis, since they may facilitate entrance of red blood cells and inflammatory cells into the plaque tissue due to increased endothelial permeability (5). Several studies demonstrated the pharmacokinetic parameter Ktrans obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to quantify plaque neovasculature noninvasively (6). It was recently demonstrated that patients with cardiovascular events demonstrated a larger adventitial Ktrans, but the same study also showed that there was no significant difference in adventitial Ktrans in the ipsilateral symptomatic plaque versus the contralateral asymptomatic plaque in patients with documented cerebrovascular ischemic events (n=20) (6,7). The objective of our study is to investigate whether there is a difference between Ktrans between the symptomatic (ipsilateral) and asymptomatic (contralateral) carotid plaque in a relatively large study.

Materials & Methods

88 symptomatic patients with >2mm ipsilateral carotid plaque underwent 3T MRI (Achieva; Philips Healthcare, Best, the Netherlands; or Discovery MR 750; GE Healthcare, Milwaukee, Wisconsin) using a dedicated 8-channel carotid RF coil (Shanghai Chenguan Medical Technologies Co., Shanghai, China). DCE-MRI was used to assess plaque microvasculature. A contrast medium (CM), Gadobutrol (Gadovist, Bayer Healthcare, Berlin, Germany) using a dose of 0.1 mmol/kg body weight, was injected with a power injector (Spectris Solaris, Medrad, Warrendale, PA, USA) with a rate of 0.5ml/second followed by a 20 ml saline bolus at that same rate. The DCE-MRI acquisition was continued for six minutes after contrast injection.Ktrans the contrast medium transfer rate from the microvasculature to the extracellular space, was calculated for the entire symptomatic and contralateral asymptomatic plaque, using a pharmacokinetic model (Patlak) (8). A multisequence MRI protocol including pre-and post-contrast T1 weighted (T1w) quadruple inversion recovery (QIR) turbo spin echo (TSE) MR imaging was used to identify the presence of a lipid-rich-necrotic-core (LRNC). The inner and outer vessel wall contours of the ipsilateral symptomatic and the contralateral carotid plaque on all slice positions were delineated. The total vessel wall area was divided by the sum of the luminal and vessel wall area, resulting in the normalized wall index (NWI), an indicator of plaque burden. A lipid-rich necrotic core (LRNC) was identified as a region within the bulk of the plaque that did not show contrast enhancement on the post-contrast T1W quadruple inversion recovery (QIR) images. Differences in Ktrans between the symptomatic and asymptomatic side were assessed using a paired samples T-test. Independent samples T-test was used to compare means between plaques with and without LRNC.

Results

A significantly lower vessel wall Ktrans was found in the symptomatic carotid plaque compared to the asymptomatic side (0.062±0.0017 min-1 versus 0.057±0.0020 min-1, p=0.033). Mean Ktrans of the adventitia showed no significant difference between the two sides (symptomatic 0.058±0.0020 min-1 versus asymptomatic 0.061±0.0028 min-1, p=0.29). Furthermore, there was a significant lower Ktrans in plaques with a LRNC (0.061±0.017 min-1 versus 0.054±0.014 min-1, p=0.041).

Discussion

This study confirms earlier results by Wang et al that there is no difference in advential Ktrans of ipsilateral symptomatic versus contralateral asymptomatic plaque in patients with cerebrovascular ischemic events. In addition, we found a significant lower Ktrans of the entire vessel wall on the symptomatic side compared to the asymptomatic side in symptomatic stroke individuals. Furthermore, there was a significant lower mean Ktrans in plaques with a LRNC. Our finding of lower values of plaque microvasculature in symptomatic plaques are unexpected, since microvasculature has been proposed as a vulnerable plaque characteristic. The decrease in vasa vasorum in the symptomatic plaques might be due to a higher amount of necrotic tissue on this side.

Conclusion

The symptomatic carotid plaque shows a significantly lower Ktrans, indicative for a decrease of leaky plaque microvasculature in symptomatic plaques. This may be related to a larger amount of necrotic tissue in symptomatic plaques.

Acknowledgements

No acknowledgement found.

References

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