Radiology: Contrast-enhanced US can assess carotid plaque inflammation

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By quantifying microbubble retention within carotid plaque, late-phase contrast-enhanced ultrasound (US) depicts clear differences between groups of subjects with plaque ipsilaterial to symptoms and asymptomatic plaques, according to a study in the May issue of Radiology.

According to David Owen, MBBS, from the department of experimental medicine and toxicology at Imperial College London, Hammersmith Hospital in London, and colleagues, a consensus has emerged that carotid plaques that are most vulnerable to rupture are those with an abundance of macrophages and a large inflammatory infiltrate. Usually, imaging of these plaque components is achieved with FDG-PET or MRI imaging enhanced with either iron oxide or gadolinium particles. But, according to the authors, these techniques are too costly to be used in routine clinical practice.

On the other hand, late-phase contrast material-enhanced ultrasonography could, the authors said, represent a low-cost modality that could be used to detect plaque inflammation.

The authors studied 37 subjects (27 men, mean age 69.7 years; 10 women, mean age 70.3 years) between December 2008 and May 2009 with late phase contrast material-enhanced ultrasound by using flash imaging, with a nonlinear mode at an intermediate mechanical index of 0.34, six minutes after bolus contrast agent injection.

The researchers defined the plaques as symptomatic if symptoms consistent with stroke, transient ischemic attack or amaurosis fugax had occurred in the neurovascular territory of the plaque studied within 12 months prior to entry into the study. Plaques were defined as asymptomatic if no such events had ever occurred within the neurovascular territory. Raw linear data were used to quantify echogenicity of the plaque, which was normalized to lumen echogenicity.

The authors were able to obtain evaluable data for all 37 subjects in the study, and none reported an adverse event during the study. Forty-three percent had symptomatic plaques and 57 percent had asymptomatic plaques. Normalized LP plaque echogenicity was greater in the symptomatic group (0.39) than in the asymptomatic group (0.69). There was a moderate inverse correlation between normalized LP plaque echogenicity and gray-scale median score.

According to the authors, the results show that the late-phase contrast-enhanced US echogenicity of carotid plaques is greater in symptomatic plaques (those within the neurovascular territory of a recent cerebrovascular event) than in asymptomatic plaques. This suggests that plaques responsible for cerebrovascular events are those that tend to have late US enhancement.

“The fact that the late-phase echogenicities of plaque and lumen are of similar magnitude implies that microbubbles have accumulated within the plaque,” the authors wrote. “Therefore, we suggest that by depicting retained untargeted microbubbles, LP contrast-enhanced US has the potential to depict inflammation, endothelial activation, or both within carotid plaque in vivo.”

According to the authors, this is the first study showing that microbubbles “passively target atherosclerotic carotid plaque in humans.” Consequently, the authors added, “this finding may have important clinical consequences for patients at high risk of plaque rupture and consequent stroke because ex vivo analysis of atherosclerotic plaques has shown that plaques that cause rupture are characterized by an abundance of macrophages and an inflammatory infiltrate.”

Late-phase contrast-enhanced US, the authors concluded, is a “technique that may be useful in the identification of asymptomatic patients who might benefit from intensive medical or surgical therapy or as a biomarker with which to investigate pharmacodynamic effects of experimental molecules."