Non-invasive in Vivo Characterization of Human Carotid Plaques with Acoustic Radiation Force Impulse Ultrasound: Comparison with Histology after Endarterectomy

Abstract

Ischemic stroke from thromboembolic sources is linked to carotid artery atherosclerotic disease with a trend toward medical management in asymptomatic patients. Extent of disease is currently diagnosed by noninvasive imaging techniques that measure luminal stenosis, but it has been suggested that a better biomarker for determining risk of future thromboembolic events is plaque morphology and composition. Specifically, plaques that are composed of mechanically-soft lipid/necrotic regions covered by thin fibrous caps are the most vulnerable to rupture. An ultrasound technique that noninvasively interrogates the mechanical properties of soft tissue, called acoustic radiation force impulse (ARFI) imaging, has been developed as a new modality for atherosclerotic plaque characterization using phantoms and atherosclerotic pigs, but the technique has yet to be validated in vivo in humans. In this preliminary study, in vivo ARFI imaging is presented in a case-study format from four patients undergoing clinically-indicated carotid endarterectomy and compared to histology. In two type Va plaques, characterized by lipid/necrotic cores covered by fibrous caps, mean ARFI displacements in focal regions were high relative to the surrounding plaque material, suggesting soft features covered by stiffer layers within the plaques. In two type Vb plaques, characterized by heavy calcification, mean ARFI peak displacements were low relative to the surrounding plaque and arterial wall, suggesting stiff tissue. This pilot study demonstrates the feasibility and challenges of transcutaneous ARFI for characterizing the material and structural composition of carotid atherosclerotic plaques via mechanical properties, in humans, in vivo.

On the Feasibility of Quantifying Fibrous Cap Thickness With Acoustic Radiation Force Impulse (ARFI) Ultrasound

“…To validate simulation results, data were compared against two in vivo examples of carotid plaque with histologically-verified fibrous caps [26]. As was done in the simulation study, in vivo data were motion tracked with eight kernel sizes whose length was determined with respect to the center frequency of the tracking pulses (6.15 MHz).…”

“…These studies suggest that ARFI can discriminate necrotic/lipid from fibrous/calcified regions, which appear as areas of relatively-high displacement and relatively-low displacement, respectively. Anecdotally, some of these studies have shown that ARFI can visualize a FC in vivo as an area of low-displacement covering an area of high-displacement [26], however, the capability to quantify FC thickness has yet to be rigorously explored.…”

“…Additionally, we hypothesize that mechanical interaction between the FC and NC and ARFI displacement underestimation may influence FC measurement performance. These hypotheses are first tested in silico and then demonstrated clinically for two fibroatheromatous carotid plaques with validation by spatially-matched histology [26]. Overall, this study serves as a first evaluation of transcutaneous ARFI’s ability to quantify FC thickness.…”

Performance of acoustic radiation force impulse ultrasound imaging for carotid plaque characterization with histologic validation

“…Following a previously described protocol 16 , a total of 25 patients undergoing clinically indicated CEA were recruited from UNC Hospitals. Inclusion criteria included asymptomatic carotid artery disease with >60% Doppler-indicated stenosis and unresponsive to medical management (i.e patients with known disease who are being managed with antihypertensive medication, cholesterol medication and smoking cessation, who have progression of stenosis implied unresolved naive to medical management) or symptomatic carotid artery disease with a stenosis suspected to be the source of emboli.…”

“…ARFI imaging was performed with the carotid artery in longitudinal orientation using a Siemens Acuson Antares (Siemens Medical Solutions USA Inc., Ultrasound Division) and a VF7-3 linear array 16 . Data acquisition, processing, and image rendering methods are described in the online-only Data Supplement.…”