Michelle Christina Johansen, MD
Saito K, Nagatsuka K, Ishibashi-Ueda H, Watanabe A, Kannki H, and Iihara K. Contrast-Enhanced Ultrasound for the Evaluation of Neovascularization in Atherosclerotic Carotid Artery Plaques. Stroke. 2014
In 1948, Dr. George Ludwig, a Navy physician first used ultrasound technology to diagnose gallstones in the United States. Six years previously, Dr. Karl Dussik, Neurologist and Psychiatrist at the University of Vienna, described the use of ultrasound in diagnosis of brain tumors. In the ensuing decades, the use of ultrasound for medical diagnosis dramatically escalated, and this modality that relies upon high frequency sound waves to produce dynamic images of internal structures, is still heavily relied upon in some specialties. The advent of CT and MRI however directed the neurologist away from ultrasound, particularly in regard to blood vessel imaging.
Saito et al. postulate that the use of contrast-enhanced ultrasound (CEUS) in patients with known carotid stenosis to quantitatively evaluate neo-vessels would aid in the identification of vulnerable plaques. The foundation for the study centers on the idea that proliferation of blood vessels in plaque predicts vulnerability for rupture. It is known that plaque disruption tends to occur at points where the plaque surface is weakest and most vulnerable. This coincides with points where stresses (biomechanical or hemodynamic) acting on plaques are concentrated. The authors therefore utilized CEUS on the plaque shoulder. Fifty consecutive patients who underwent carotid endarterectomy (CEA) were enrolled. Carotid ultrasound was performed and the plaques were classified as echolucent or echogenic. CEUS was then performed and the investigators calculated enhanced intensity (EI) in the core, plaque shoulder and vessel lumen. Plaque specimens from these patients status post CEA were obtained and the histopathology was reviewed.
The authors found that the contrast (EI) of plaque shoulders was greater than that of plaque cores. This correlated with histopathology that revealed fewer neo-vessels in the cores. The authors also found EIs associated with density of neo-vessels in the plaque shoulders. EIs were significantly higher in ruptured plaques as well as in symptomatic plaques. The conclusion of the investigators is that CEUS can predict and stratify plaque vulnerability thereby enhancing evaluation and treatment of atherosclerotic disease.
In the era of increasing medical costs, the study makes an appealing argument. Ultrasound is less invasive, easily transportable and takes relatively less time than the average diagnostic brain MRI. So should all accredited stroke centers invest in more ultrasound machines? There are many questions that the practicing vascular neurologist should contemplate before relying upon this tool for clinical decision making. While ultrasound is a dynamic imaging modality, it is also highly dependent on the operator and thus the reproducibility of results is an important issue to consider. This study also revolves around contrastenhanced ultrasound which over the preceding years, has been an object of contention for the FDA. In 2007, they issued a black box warningand mandated a 30-minute monitoring period after use in all patients. This has since been removed but the administration of contrast still remains a consideration. CEUS also remains relatively inaccessible. This study was also conducted in an Asian population which represents an isolated cohort. Literature has demonstrated that the risk factors and pathophysiology of strokes in this demographic is different than those with other ethnic backgrounds. How accurate then are these results when applied to other patient populations?
While catching the wave of contrast enhanced ultrasound is a thrilling prospect, more research is certainly needed before this modality is ready for primetime.
Great post, Dr. Johansen.
With hope, this, in concert with other carotid plaque morphological features, as well as "downstream" transcranial Doppler findings (spontaneous microemboli, ipsilateral exhausted vasomotor reactivity), help to select that ever-elusive subset of patients with asymptomatic carotid stenosis who benefit from more intervention, medical or surgical. It seems no one biomarker will do (although I'll be happy to be wrong about that!) but a battery of these neurosonological findings may inform best practice.