Detection of Unstable Carotid Plaque by Tissue Doppler Imaging and Contrast-Enhanced Ultrasound in a Patient with Recurrent Amaurosis Fugax

Ultrasound (US) is one of the most important diagnostic tools available for the detection and evaluation of carotid stenosis. The case of a 70-year-old woman with recurrent right-sided amaurosis fugax presented here highlights the way in which tissue Doppler imaging (TDI) and contrast-enhanced US (CEUS) may aid in the diagnosis of carotid plaque vulnerability. Furthermore, the novel inverse fly-through technique was used for the three-dimensional visualization of the carotid stenosis.


Introduction
Stroke risk in patients with carotid stenosis may vary widely. e risk of ipsilateral ischemic stroke is increased in patients with a previous stroke. Furthermore, stroke risk increases progressively with the severity of carotid stenosis. e risk of a recurrent stroke or transient ischemic attack (TIA) is the greatest immediately aer the initial ischemic event and decreases over time, as does the potential bene�t which may be derived from carotid endarterectomy (CEA) [1]. e case presented here highlights the capabilities of modern vascular ultrasound techniques in the diagnosis and characterization of carotid artery stenosis.

Case Presentation
A 70-year-old woman was admitted aer transient right monocular visual loss on the day of presentation and on the previous day. e medical history revealed that, eight years before, the patient had undergone right CEA for symptomatic stenosis of the internal carotid artery (ICA). Preceding that operation, the patient had suffered two TIAs with reversible paresis of the le arm. US examination on admission revealed a 60 percent right-sided ICA stenosis (Figure 1(a)). e prosthetic patch used to close the longitudinal arteriotomy could be clearly visualized (Figure 1(b)). Cranial MRI showed an old small subcortical infarct located in the right precentral gyrus as well as a very small area of restricted diffusion in the territory of the right middle cerebral artery (MCA). Cardiac workup, including electrocardiography, 24-hour Holter monitoring, and transthoracic echocardiography, did not reveal any abnormalities suggesting cardioembolic etiology.
An extended US examination including CEUS (Aplio 500, Toshiba, Otawa, Japan, in combination with the echo enhancer SonoVue, Bracco, Constance, Germany) demonstrated neovascularization of the carotid plaque (arrows in Figure 2(a)). Tissue Doppler imaging (TDI) revealed increased elastic deformability of the ICA in the vicinity of the area of plaque neovascularization indicating enhanced plaque elasticity (Figure 3(a)). e novel inverse �y-through  US technique was used for three-dimensional imaging of the carotid stenosis and planning of potential surgery ( Figure  3(b)).
In summary, the most likely explanation of the recurrent transient monocular visual loss of our patient was amaurosis fugax secondary to right-sided 60 percent ICA stenosis. A�er weighing all risks and bene�ts, a recommendation for CEA was made. e procedure was performed promptly and went without complication. A good correlation was found between US �ndings and the microscopic examination of the CEA specimen (Figures 2(b), 4(a)-4(c)). In particular, histological analysis of the culprit lesion showed plaque neovascularization in the area previously identi�ed by US (Figures 2(a) and 2(b)). In line with the US �nding of increased plaque deformability (Figure 3(a)), histological examination revealed plaque neovascularization and invasion of in�ammatory cells with acute intraplaque hemorrhage and intraplaque thrombus formation (Figures 4(a)-4(c)), most likely due to previous intraplaque bleeding. Meanwhile, the patient has been symptom free for over three months. She takes 100 mg q. d. acetylsalicylic acid for secondary prevention of stroke. Regular US follow-up examinations of the carotid and vertebral arteries have been scheduled.

Discussion
e recent advances in noninvasive carotid imaging promise the identi�cation of new carotid plaque vulnerability markers. It is to be hoped that this will further improve the assessment of stroke risk associated with carotid stenosis.
Symptomatic carotid artery disease is associated with plaque neovascularization, intraplaque hemorrhage, and invasion of in�ammatory cells. CEUS increasingly provides the means to quantify the degree of neovascularization of an atherosclerotic plaque. Since neovascularization is associated with an in�ammatory in�ltrate, CEUS may also indicate increased invasion of in�ammatory cells [2][3][4].
Hypoechogenicity is already well established as a marker of high-risk carotid lesions [5]. TDI offers the additional opportunity to evaluate plaque characteristics such as tissue elasticity and the velocity at which tissue deformation occurs. e elastic properties of the tissue are shown as color-coded two-dimensional TDI images. Although more experience and data are necessary, the combination of several high-end US techniques will likely also facilitate the visualization of the transitional zone between an intraplaque thrombus and the less elastic �brous tissue surrounding it. Finally, the threedimensional inverse �y-through US technique allows video reconstruction of the contrast-enhanced blood vessel [6]. Importantly, by changing the vectors, the stenotic segment can be visualized from any direction (Figure 3(b)).
While there is already good data showing the value of CEUS in the diagnosis of carotid plaque neovascularisation, more work will be required to delineate the speci�c value of novel US techniques such as TDI and the three-dimensional �y-through technique.