Japanese Congress of Neurological Surgeons Presidential Address—Treatment of Carotid Artery Stenosis Based on Plaque Imaging

3-D: 3-dimensional BMI: brain–machine interface CAS: carotid artery stenting CEA: carotid endarterectomy CT: computed tomography EPD: embolic protection device HIS: high-intensity signals IVUS: intravascular ultrasonography JCNS: Japanese Congress of Neurological Surgeons MRA: magnetic resonance angiography MRI: magnetic resonance imaging OCT: optical coherence tomography RCT: randomized controlled trial TOF: time-of-flight The theme of the 36th Japanese Congress of Neurological Surgeons (JCNS) was “Art and science of neurosurgery” (Figure 1). In the neurosurgical field, there are 2 important directions: one is the “State of the Art,” namely, to hone our surgical skills and evolve our application of technology. The other is the “State of the Science,” to continue research to improve our fundamental understanding and develop new therapies. In the meeting, application of a new navigation system to reach surgically difficult lesions such as posterior fossa tumors was shown.1,2 Another example of “State of the Art” shown in the meeting was the performance of clinical studies such as a randomized controlled trials (RCTs) such as the Japan Adult Moyamoya Trial to elucidate the efficacy of extracranial-intracranial bypass to reduce rebleeding in patients with moyamoya disease.3 On the other hand, regarding “State of the Science,” a brain–machine interface (BMI) was introduced, representing a new technology that decodes cortical activity to allow physical control of a robotic arm.4 In the meeting, clinical application of this BMI to a patient suffering from amyotrophic lateral sclerosis was introduced. In the future, BMI may be able to compensate for neurological deficits caused by intractable diseases.FIGURE 1: Congress preview poster for the 36th JCNS.In this report, carotid artery stenosis treatment according to plaque imaging is introduced as an example of “State of the Science.” Carotid artery stenosis is one of the major causes of cerebral infarction, and medical therapy with antiplatelet agents, carotid endarterectomy (CEA), and carotid artery stenting (CAS) have been performed. CEA is known to be superior to medical treatment in terms of stroke prevention from 4 different RCTs.5-8 On the other hand, some patients have risks during surgical treatment due to systemic diseases or anatomic reasons. CAS has also been performed as a less invasive treatment. Three RCTs have compared CEA and CAS, but the noninferiority of CAS was not demonstrated.9-11 On the other hand, another trial for patients at high risk of CEA showed the noninferiority of CAS.12 In addition, the other 2 RCTs for normal risk patients for CEA showed the noninferiority of this method.13,14 In Japan, CAS was approved in 2008 for high-risk patients for CEA. Actually, CAS was already being performed more frequently than CEA before its approval. The number of CAS was increasing annually, and is now performed at almost double the rate of CEA. However, CAS has weak points, such as a risk of distal embolism, which may lead to permanent neurological deficits. Reducing ischemic events during and after the procedure is therefore important. Recently, performing plaque imaging before interventions for carotid artery stenosis has been gaining popularity, because plaque characteristics are known to be related to the frequency of ischemic stroke after CAS (Figure 2). We reported that ischemic events were more frequent when patients showed soft plaque on preoperative magnetic resonance imaging (MRI).15-21FIGURE 2: Schematic of the cause of distal embolism after filter-protected CAS.In this manuscript, we introduce the concept of treatment selection based on plaque imaging to reduce periprocedural ischemic events. PLAQUE IMAGING Carotid duplex scan, MRI or MR angiography (MRA), computed tomography (CT), and intravascular ultrasonography (IVUS) are major methods for imaging plaque. Also, we reported the usefulness of optical coherence tomography (OCT) based on our clinical trial. Carotid Duplex Scan Ultrasonography is noninvasive and easy to use even at the bedside. This is thus one of the major modalities for plaque imaging all over the world. Low echoic plaque has been known to be unstable (soft plaque).22,23 Although the accuracy for detecting recent intraplaque hemorrhage is reportedly relatively high (specificity, 79%; sensitivity, 75%).24,25 However, ultrasonography sometimes provides poor-quality images, particularly in cases with calcification or a high-positioned bifurcation. Magnetic Resonance Imaging Plaque characterization has recently become possible on MRI, such as the black blood method reported by Yuan C et al.26 With this method, vessel wall identification is possible because intravascular signals can be removed. Plaque is regarded as soft when the plaque/muscle ratio is more than 1.25 (Figure 3). This finding is useful, but requires the use of high-resolution MRI systems such as 3-T MRI.27 As a result, this modality is not available in all institutes.FIGURE 3: MR carotid plaque imaging—measurement of signal intensity ratio on a T1-weighted image of black blood MRI. A region of interest was set in the carotid plaque (blue) and sternocleidomastoid muscle (red).Magnetic Resonance Angiography We have previously reported that plaque contained hemorrhage when high-intensity signals (HIS) were demonstrated on time-of-flight (TOF)-MRA.16 In this report, we pathologically investigated the plaque specimen obtained by CEA to verify this finding. Subsequently, intraplaque hemorrhage was confirmed when HIS was demonstrated on TOF-MRA (Figure 4). Furthermore, we retrospectively analyzed rates of ischemic events (transient ischemic attack or stroke) during and after CAS in our institute. We observed ischemic events in 8 patients (7.2%), all of whom had a history of stroke. New ischemic lesions after CAS were detected on diffusion-weighted imaging at a higher rate in HIS-positive groups (5.8%) compared to HIS-negative groups (35.1%; P = .002). Also, ischemic symptoms after CAS were more frequently observed in HIS-positive groups (18.4%) than in HIS-negative groups (1/74, 1.4%; P = .003). Multivariate analysis showed that the independent predictor of ischemic symptoms after CAS was intraplaque HIS on TOF-MRA. This represents a simple method to identify intraplaque hemorrhage on images of routine TOF-MRA, with no requirement for special sequences.FIGURE 4: Hyperintensity signal in the plaque on TOF-MRA and its pathology. A, A high-intensity lesion is seen in the plaque on TOF-MRA (arrow). B, Macroscopic view of the surgical specimen of carotid plaque reveals massive intraplaque hemorrhageComputed Tomography CT is usually performed to detect calcification of the arterial wall, although some trials have evaluated plaque characteristics using CT attenuation values.28 Severely calcified lesions are known to be difficult to dilate by balloon angioplasty or stenting. Calcification is hard to evaluate by duplex scan or MRI. On CTA, the relationship between vessel wall and calcification has been extensively demonstrated, so entirely circumferential calcifications that are known to represent difficult lesions for stenting can be discriminated. Intravascular Ultrasonography The efficacy of IVUS has been reported to predict embolization and cerebral complications during CAS. Virtual histology IVUS is also useful to know intraplaque components.29,30 A color-coded map of the plaque provides detailed morphological information, and seems to represent a useful addition to conventional IVUS. This method is reimbursed under the Japanese healthcare system, and is therefore routinely used in our regular treatment. We have reported its usefulness in terms of stroke prediction after CAS.17 Optical Coherence Tomography OCT is a light-based imaging method with a new fiber-optic technology. The resolution of OCT is approximately 10-folds higher than that of IVUS. For example, by using IVUS, intraluminal thrombus is hard to demonstrate during CAS, but it was clearly visualized by OCT.31-33 More recently, 3-dimensional (3-D) images have become available, and can clearly show plaque prolapse through stent struts. TOOLS TO IMPROVE CLINICAL RESULTS OF CAS Cerebral Protection Cerebral protection using a filter or balloons has recently been performed to prevent distal embolism resulting from migration of debris into the cerebral circulation. The efficacy of these embolic protection devices (EPDs) was shown by an RCT.34 So, recent RCTs have requested the use of EPDs where possible. Three kinds of EPDs are currently in use: distal filter, distal balloon, and proximal balloon protection devices. Among these, filter devices are most frequently used as the simplest approach, and can maintain antegrade blood flow during protection. We therefore do not have to worry about the duration of protection. However, proximal protection devices have recently been reported as superior to filter devices in terms of protecting against distal embolism in an RCT.35 New-Generation Stent Double-layered micromesh stents are now being used in Europe. We tested one of these devices, CASPER, with approval of our institutional review board and patients’ consent for the study. Here, we show examples of reconstructed 3-D OFDI images of the stenotic region covered by the stents. In a patient with a large amount of soft plaque, plaque protrusion was observed just after regular stent deployment. In contrast, plaque protrusion was prevented by a double-layer micromesh stent (Figure 5).FIGURE 5: Comparison of findings from OCT immediately after deployment of a regular stent A and a double-layer micromesh stent B. Plaque protrusion through stent struts can be seen with the regular stent (arrow), but not with the micromesh stent.Although the incidences of adverse events such as thrombosis or restenosis during mid- to long-term follow-up are unknown, use of these stents is expected to reduce periprocedural ischemic events. Actually, favorable preliminary results have been reported from Europe,36,37 and a clinical trial is ongoing in Japan. FUTURE PROSPECTS CAS is basically less invasive and expected to be performed more frequently due to the aging of the population. Indications are widening based on the development of new devices. Obtaining better clinical results will involve the selection of appropriate treatments and devices according to the plaque characteristics identified preoperatively. CONCLUSION CAS is a simpler, less-invasive therapy than CEA, and the key to better results is selecting better treatment and more appropriate devices based on preoperative imaging of the plaque. Disclosures The author was provided with a research fund from Terumo Corporation in 2015. The author has no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.