Clinical Utility of Intravascular Ultrasound (IVUS) in Carotid Artery Interventions: A Systematic Review and Meta-analysis.

BACKGROUND: Carotid plaque morphology plays an important role in determining outcome of carotid artery stenting (CAS). Intravascular ultrasound (IVUS) and its extension VH (Virtual Histology)-IVUS evaluate plaque characteristics in real time and guide decision making during stenting. To date, there is no consensus about indications of IVUS and its validated methods. This systematic review and meta-analysis aims to evaluate the clinical utility of IVUS in carotid artery interventions (CAS) and develop a future consensus for research and practice parameters. METHODS: A systematic review and meta-analysis was performed of the English literature articles published till February 2021. Studies reporting on IVUS parameters and findings and also its performance compared with other imaging modalities were included in review. Pooled prevalence with 95% confidence intervals (CI) was calculated. The statistical analysis was conducted in R version 3.6.2. RESULTS: A total of 2015 patients from 29 studies were included. Proportional meta-analysis was performed on 1566 patients from 11 studies. In 9 studies, stroke/transient ischemic attack (TIA) had a pooled prevalence of 4% (95% CI 3%-5%) while asymptomatic stroke had a pooled prevalence of 46% (95% CI 31%-62%) in 4 studies following IVUS. Two studies reported that IVUS detected more plaque protrusion compared with angiography (n=33/396 vs 11/396). IVUS led to stent type or size change in 8 of 48 cases which were missed on angiography in 3 other studies. Concordance between VH-IVUS and true histology was good at 80% to 85% reported in 2 studies. CONCLUSIONS: This systematic review and meta-analysis showed, though IVUS fared better to computed tomography (CT)/magnetic resonance (MR) angiography for better stent selection during CAS, with low to moderate risk of bias in the studies included. However, large scale, preferably randomized controlled studies are needed to predict its role in determining clinical outcome.

A mechanical coil insertion system for endovascular coil embolization of intracranial aneurysms.

Like other fields of medicine, robotics and mechanization might be introduced into endovascular coil embolization of intracranial aneurysms for effective treatment. We have already reported that coil insertion force could be smaller and more stable when the coil delivery wire is driven mechanically at a constant speed. Another background is the difficulty in synchronizing operators' minds and hands when two operators control the microcatheter and the coil respectively. We have therefore developed a mechanical coil insertion system enabling a single operator to insert coils at a fixed speed while controlling the microcatheter. Using our new system, the operator manipulated the microcatheter with both hands and drove the coil using foot switches simultaneously. A delivery wire force sensor previously reported was used concurrently, allowing the operator to detect excessive stress on the wire. In vitro coil embolization was performed using three methods: simple mechanical advance of the coil; simple mechanical advance of the coil with microcatheter control; and driving (forward and backward) of the coil using foot switches in addition to microcatheter control. The system worked without any problems, and did not interfere with any procedures. In experimental coil embolization, delivery wire control using the foot switches as well as microcatheter manipulation helped to achieve successful insertion of coils. This system could offer the possibility of developing safer and more efficient coil embolization. Although we aim at total mechanization and automation of procedures in the future, microcatheter manipulation and synchronized delivery wire control are still indispensable using this system.

Subcutaneous hematoma associated with manual cervical massage during carotid artery stenting. A case report.

We describe a patient with subcutaneous hematoma associated with manual cervical massage during carotid artery stenting.A 73-year-old man with left cervical carotid artery stenosis presented with left amaurosis fugax. We performed carotid artery stenting using distal embolic protection with balloon occlusion. Dual antiplatelet therapy was maintained in the periprocedural period and an anticoagulant agent was administered during the procedure. Because the aspiration catheter became entrapped by the stent, it did not reach the distal side of the stenotic lesion, and manual compression of the cervical region was therefore performed. Immediately afterwards, a subcutaneous hemorrhage occurred in the cervical region. There was no postoperative dyspnea due to enlargement of the hematoma, which was absorbed spontaneously.Cervical subcutaneous hematoma can occur in the cervical region due to cervical massage in patients who are receiving adjuvant antiplatelet therapy and anticoagulation therapy.

The mechanism of catheter kickback in the final stage of coil embolization for aneurysms: the straightening phenomenon.

The catheter kickback phenomenon often occurs in the last stage of coil packing for cerebral aneurysms. This behavior is considered the result of either a lack of space in the sac or a stiff detaching zone. In order to clarify its mechanism, focused stretch-resistance (SR) coil simulation models were tested. Various commercially available SR coils were inserted into a cylinder or an aneurismal sac made from a silicone tube with a smaller than prescribed diameter. A magnified SR coil model (straight type) of fishing line was created for simulation. Numerical analysis for the changes in coil behavior were verified. All SR coils showed hardening and straightening at the last few millimeters, resulting in catheter kickback. In a magnified coil experiment, straightening was also realized when folding into a narrow cylinder. The SR line coursed in the canal of the first loops and shifted to the outside in the middle portion. Gaps among first coil pitches were enlarged on after insertion into the narrower space. Shortage of the SR line was calculated to reach a maximum of 32%. The straightening phenomenon is due to SR line shortening and subsequent condensation of pitches of the first loops at the coil end. Coil tail flexibility was lost, and the coil behaved as a stiff wire. Straightening is an important factor in the kickback phenomenon. Shorter final SR coils should be selected, and coil designs should be improved.

Can periprocedural hypotension in carotid artery stenting be predicted? A carotid morphologic autonomic pathologic scoring model using virtual histology to anticipate hypotension.

SUMMARY: Periprocedural hypotension, which frequently occurs during carotid artery stenting (CAS), is an important risk factor for complications such as stroke or death after CAS. To determine if a scoring model can be established to predict periprocedural hypotension (systolic blood pressure < or = 90 mm Hg) and prolonged periprocedural hypotension (requiring vasopressor for > 3 hours) in CAS, we conducted a prospective cohort study of patients undergoing interventional treatment of cervical carotid artery stenosis in an urban tertiary referral hospital from April 2006 to April 2007. Forty-eight stenotic lesions in 45 consecutive patients treated with CAS were included in the study. Multivariate analysis showed three independent risk factors of periprocedural hypotension; "fibrous plaque on Virtual Histology" (P = 0.029), "stenotic lesion involving both the common carotid artery and internal carotid artery on angiogram" (P = 0.004), and "patients without history of diabetes mellitus" (P = 0.020). Further, "distance between carotid bifurcation and point of minimum lumen size < or = 10 mm on angiogram" (P = 0.003) was an independent risk factor of prolonged periprocedural hypotension. Carotid morphologic autonomic pathologic score (carotid MAPS), determined by adding one point for each of those risk factors (total 0 to 4), had good discrimination for both periprocedural hypotension (area under receiver operating characteristic curve: ROC AUC = 0.876; SE 0.053) and prolonged periprocedural hypotension (ROC AUC = 0.811; SE 0.066). Carotid MAPS is useful for predicting periprocedural hypotension and prolonged periprocedural hypotension during CAS.

Morphological study of aneurysms at the junction of the superior cerebellar artery.

SUMMARY: Superior cerebellar artery (SCA) aneurysms sometimes involve the origin of the SCA making treatment difficult. We focused on the morphological characteristics of SCA aneurysms and adjacent vascular structures to apply clinical decision-making for the treatment strategy. Sixty-nine SCA aneurysms, including 34 ruptured and 35 unruptured ones, had been treated for over 12 years. Multiple aneurysms were associated in 30 patients. The pattern of the neck position of aneurysms was classified into three types: Type A: no SCA-involved type; Type B: half involved type with SCA originating from the aneurysmal neck; Type C: pure SCA aneurysm with all the neck mounting on SCA. Morphological and clinical analysis was done between ruptured and unruptured aneurysms and among the three types. There was no difference in patient profile between ruptured and unruptured aneurysms. The angle formed by the posterior cerebral artery and SCA on the aneurysm side was obtuse in 62 (90%) patients. From the morphological point of view the SCA-involved type (types B + C) was significantly more prevalent in ruptured aneurysms (77%). Bleb formation was particular in ruptured aneurysms. As for the treatment, the risk of SCA occlusion and incomplete and attempted operation was particularly high in cases with SCA-involved type. Although SCA aneurysms may grow due to the hemodynamic stress at the opened bifurcation between the PCA and SCA, the neck shifting to the origin of SCA, particularly in ruptured lesions,may suggest some other etiological mechanism. SCA-involved type aneurysms had a high treatment risk of SCA occlusion and tended to incomplete treatment to avoid such ischemic complications.

Dural arteriovenous fistula at the anterior condylar confluence.

SUMMARY: We reviewed the records of eight patients with a dural arteriovenous fistula (DAVF) close to the hypoglossal canal and determined the angioarchitecture of the clinical entity at the anterior condylar confluence. Eight patients with DAVF received endovascular treatment at our institute over the past five years. Imaging with selective three-dimensional angiography and thin-slice computed tomography were used to identify the fistula and evaluate the drainage pattern. Based on the angiographic findings, the ascending pharyngeal artery was the main feeder in all cases, and the occipital, middle meningeal, posterior auricular, and posterior meningeal arteries also supplied the DAVF to varying degrees. Contralateral contribution was found in five patients. The main drainage route was the external vertebral plexus via the lateral condylar veins in four patients, the inferior petrosal sinus in three patients, and the internal jugular vein via the connecting emissary veins in one patient. Selective angiography identified the shunt point at the anterior condylar confluence close to the anterior condylar vein. Shunt occlusion with transvenous coil packing was performed in all cases; transarterial feeder embolization was also used in three patients. Two patients treated with tight packing of the anterior condylar vein developed temporary or prolonged hypoglossal palsy. Based on our results, the main confluence of the shunt is located at the anterior condylar confluence connecting the anterior condylar vein and multiple channels leading to the extracranial venous systems. To avoid postoperative nerve palsy, the side of the anterior condylar vein in the hypoglossal canal should not be densely packed with coils. Evaluating the angioarchitecture using the selective three-dimensional angiography and tomographic imaging greatly helps to determine the target and strategy of endovascular treatment for these DAVF.

Neuronal specificity of alpha-synuclein toxicity and effect of Parkin co-expression in primates.

Recombinant adeno-associated viral (rAAV) vector-mediated overexpression of alpha-synuclein (alphaSyn) protein has been shown to cause neurodegeneration of the nigrostriatal dopaminergic pathway in rodents and primates. Using serotype-2 rAAV vectors, we recently reported the protective effect of Parkin on alphaSyn-induced nigral dopaminergic neurodegeneration in a rat model. Here we investigated the neuronal specificity of alphaSyn toxicity and the effect of Parkin co-expression in a primate model. We used another serotype (type-1) of AAV vector that was confirmed to deliver genes of interest anterogradely and retrogradely to neurons in rats. The serotype-1 rAAV (rAAV1) carrying alphaSyn cDNA (rAAV1-alphaSyn), and a cocktail of rAAV1-alphaSyn and rAAV1 carrying parkin cDNA (rAAV1-parkin) were unilaterally injected into the striatum of macaque monkeys, resulting in protein expression in striatonigral GABAergic and nigrostriatal dopaminergic neurons. Injection of rAAV1-alphaSyn alone decreased tyrosine hydroxylase immunoreactivity in the striatum compared with the contralateral side injected with a cocktail of rAAV1-alphaSyn and rAAV1-parkin. Immunostaining of striatonigral GABAergic neurons was similar on both sides. Overexpression of Parkin in GABAergic neurons was associated with less accumulation of alphaSyn protein and/or phosphorylation at Ser129 residue. Our results suggest that the toxicity of accumulated alphaSyn is not induced in non-dopaminergic neurons and that the alphaSyn-ablating effect of Parkin is exerted in virtually all neurons in primates.

The current status of treatment strategies for cerebral aneurysms in nagoya university and affiliated hospitals based on a questionnaire survey.

SUMMARY: We investigated differences in the treatment strategies for ruptured aneurysms among 26 hospitals affiliated with Nagoya University and any changes in those strategies based on responses to a questionnaire.We also surveyed the data concerning patients with a ruptured aneurysm collected from our affiliated hospitals between 2001 and 2002. In half of the institutes, angiography is performed immediately after an urgent medical examination, there are only five hospitals (20%) which have a basic policy of terminating the angiography within three to six hours after onset. In half of the institutes, the timing of the treatment also depends on the location of the aneurysm. In particular, the treatment for vertebro-basilar aneurysms tends to be done the next day or later. Low-grade subarachnoid hemorrhage (SAH) patients with mild symptoms tended not to be given any sedative drugs (46%), while patients with SAH in some institutes were sedated without informed consent regardless of the severity. The main treatment method for most anterior circulation aneurysms was clipping. Concerning aneurysms located in the posterior circulation and the origin of the ophthalmic artery, clipping and coiling were equally selected. Almost all the hospitals (92%) responded that their treatment strategy had not changed even after the report of the International Subarachnoid Aneurysm Trial (ISAT). There is a great deal of difference in treatment strategies and indications among institutions. In particular, institutions without neuroendovascular interventionists (NETists) frequently persist in the conventional policy, making it urgently necessary to bring NETists up-to-date on the latest advance in endovascular treatment.

Coincident stimulation of convergent cortical inputs enhances immediate early gene induction in the striatum.

The effect of coincident stimulation of convergent corticostriatal inputs was analyzed by the induction of immediate early genes in striatal neurons. Cortical motor areas were stimulated through implanted electrodes in awake, behaving rats, and the induction of the mRNAs encoding the immediate early genes (IEGs) c-fos and arc was analyzed in the striatum with in situ hybridization histochemistry. In the first experiment, unilateral stimulation of the medial agranular cortex, orofacial region of the lateral agranular cortex or the forelimb region of the lateral agranular cortex resulted in IEG induction in the striatum, which was restricted to the topographically related area receiving input from the stimulated cortical area. In a second experiment, stimulation parameters were altered, including frequency, number of pulses/train, and number of trains/s. These parameters did not have a significant effect on IEG induction. Notably, in some cases, in which there was IEG induction not only in the stimulated cortical region, but also in the homologous area in the contralateral hemisphere, very robust IEG induction was observed in the striatum. In a third experiment, the orofacial regions of the lateral agranular cortex of both hemispheres were stimulated coincidently. All of these animals showed robust striatal IEG induction. This IEG induction was attenuated by pretreatment with an NMDA antagonist MK-801. In a fourth experiment, we tested whether the coincidence of bilateral cortical stimulation contributed to the efficacy of striatal IEG induction. Either alternating stimulation or coincident stimulation of non-homologous cortical regions produced significantly lower striatal IEG induction than obtained with coincident stimulation of homologous cortical areas. Enhanced striatal IEG induction occurred in indirect striatal neurons, labeled with enkephalin, but was also present in a large number of enkephalin-negative neurons, most of which are likely direct pathway neurons. These results suggest that regional and temporal convergence of cortical inputs enhances striatal IEG induction.

Animal models of cervical artery dissection.

We developed a canine model of arterial dissection and serially observed morphological changes angiographically and histopathologically to clarify the causes and mechanisms resulting in dissecting aneurysm formation or arterial occlusion. Intimal defects of various sizes and shapes were made on the arterial walls to provide an entry zone for dissection, so as to simulate the extent of arterial wall injury. Our experimental model showed angiographic and histopathological changes similar to those in clinical cases. As for our initial findings immediately after lesioning, either a double shadow (pseudolumen) or stenosis of the affected artery, due to compression from the subadventitial hematoma, was observed in the angiograms of all lesions. In some lesions with a pseudolumen, a dissecting aneurysm developed subsequently. Some arteries showing focal occlusion recanalized, and stenosis spontaneously improved. Very small dissections resulted in spontaneous healing, while a large intimal entry zone caused stenotic lesions. However, a medium-sized entry zone (4-6 mm) may induce aneurysm formation. The different features of dissection may be caused by the characteristics of flow into the subadventitial cavity and by thrombogenesis. Morphological changes after arterial dissection were closely related to the extent of intimal injury, suggesting that the size of the intimal entry zone may determine whether or not a dissecting aneurysm is formed.

Computer simulation of flow dynamics in paraclinoidal aneurysms.

SUMMARY: Endovascular treatment, which is very useful method especially for paraclinoidal aneurysms, has the limitations of coil compaction and recanalization, which are difficult to predict. We tried to understand flow dynamic features, one of the important factors of such problems, using computer flow dynamics (CFD) simulations. CFD simulations were made in paraclinoidal aneurysm model of different size and protruded directions. Flow patterns, flow velocities and pressure are analyzed. Although the pressure on the aneurismal orifice is highest in the aneurysm protruding vertically - upward, the flow velocity is highest in the superior-medial protruding one. Significant difference is not observed in either flow patterns, flow velocities or pressures on the aneurismal orifices between the sizes of aneurismal sac. Among paraclinoidal aneurysms, an aneurysm protruding to superior-medially receives the most severe haemodynamic stresses at the orifice and the aneurysm size does not cause significant differences in the aspect of flow dynamics. It should be considered in the treatment of such aneurysms.

Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys.

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor-related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor-related areas, we investigated the pattern of projections involving the higher-order motor-related areas, such as the presupplementary motor area (pre-SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor-related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract-tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre-SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre-SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre-SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre-SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre-SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.

Local hyperthermia enhances thrombosis in aneurysms containing platinum coils.

SUMMARY: Despite recent technical advances in embolization of cerebral aneurysms with platinum coils, some aneurysms eventually resulted in incomplete packing with remnant neck or dome filling. Such a situation with a remaining inflow zone may pose a risk of rupture and subsequent regrowth. Metals characteristically generate heat under high-frequency alternating magnetic fields (AMF). We used this property to induce local hyperthermia and promote thrombogenesis in incompletely packed aneurysms. Glass model aneurysms packed with coils were subjected to AMF to investigate the correlation between weight of platinum and temperature elevation and the correlation between flow rates of water through the model and temperature elevation. Next, activated coagulation time (ACT) of blood obtained from dogs was studied at various temperatures. Finally, side-wall aneurysms created in the canine carotid artery using a venous patch were packed with platinum coils. Change in temperature and angiographic changes were investigated after AMF application. In the glass model, the weight of platinum was correlated with elevation of temperature, and a negative logarithmic correlation was evident between flow rate and elevation of temperature. Elevation of blood sample temperature tended to shorten ACT. In canine carotid aneurysms, elevation of intra-aneurysmal temperature was confirmed and sufficient elevation of temperature was found to promote angiographically evident thrombogenesis of the remnant space after AMF application. Local hyperthermia may be useful in completing luminal obliteration of aneurysms after coil embolization. It may particularly useful for ruptured aneurysms to prevent the early rerupture.

Feasibility of photocrosslinkable chitosan as an embolization material for aneurysms. Biological reaction after aneurysm embolization.

SUMMARY: The purpose of this study was to evaluate the feasibility of photocrosslinkable chitosan as an embolization material for aneurysms. Three experimental aneurysms were created in three Japanese white rabbits. All of the aneurysms were packed with chitosan hydrogel. Histopathologic data were analyzed on two, seven, and 30 days after embolization. Unorganized clots and minimal inflammation around the applied chitosan hydrogel were observed two days after implantation. After seven days, the chitosan was reduced and inflammatory response appeared. At 30 days, most of the aneurysm lumen was replaced with inflammatory cells, and the remaining chitosan was not observed. Severe complications such as anaphylaxis did not occur after the embolization with the chitosan. These results suggest that photocrosslinkable chitosan might be a candidate for an embolization material for endovascular treatment of cerebral aneurysms.

Nagoya university training system for neuroendovascular therapists.

SUMMARY: It is very important to train more neuroendovascular therapists (NETists) in response to Japan's growing social needs. Since the supply of qualified NETists is still insufficient to cover Japanese institutions, therefore some emergency cases with indications for endovascular therapy may be overlooked, untreated or treated by other methods resulting in unfavorable outcomes. Thus, neuroendovascular therapies are situated as one of the important tratment modalities for neurosurgical diseases (1,2). We studied our present states of the endovascular neurosurgery and introduce our training system.

Computer simulation of flow dynamics in an intracranial aneurysm. Effects of vessel wall pulsation on a case of ophthalmic aneurysm.

SUMMARY: Using a supercomputer, the authors studied the effect of vessel wall pulsation on flow dynamics with a three-dimensional model simulating both a rigid and pulsatile style. The design of the aneurysm models was set with a 5 mm dome diameter and a 1 or 3 mm orifice size to simulate a carotid-ophthalmic aneurysm. Flow dynamics were analyzed according to flow pattern, wall pressure and wall shear stress. The flow pattern in the aneurysm sac showed the great difference between rigid and pulsatile models particularly in the small-neck aneurysm model. The arterial wall tended to be exposed to a higher pressure peak in the pulsatile model than in the rigid one, especially at its bifurcation and curved regions. Sites of shear stress peak were found on the aneurysmal dome as well as at the distal end of the orifice in both rigid and pulsatile models. The effects of vessel-wall pulsation should be considered whenever evaluating conditions in and around an aneurysm.

Treatment Strategy for Cerebral Aneurysms Based on the Evidence of the Efficacy of GDC Embolization.

SUMMARY: The authors reviewed 531 patients with cerebral aneurysms treated with Guglielmi detachable coils (GDCs) over 5 years to clarify both the advantages and disadvantages of embolization based on the evidence of complications by aneurysm profile. There were 52 technical complications, 25 of which resulted in unfavorable patient outcomes. Intraoperative rupture, the most serious complication exacerbating the patient's condition, occurred in 19 patients, 4 of whom expired. All of these aneurysms were very small and were mostly located in the AcomA and PICA portions. Thirteen patients encountered thromboembolic complications, 6 of whom were elderly with acute ruptured aneurysms at MCA and the tip of BA. For large or giant aneurysms manifesting the mass effect, particularly those in the ICA-C2 portion compressing the optic nerve, the saccular packing did little to ameliorate the symptoms, and subsequent surgical or endovascular trapping was needed. Therefore, saccular embolization of endovascularly difficult, very small AcomA aneurysms and large C2 aneurysm with visual symptoms should be used sparingly based on a risk-benefit assessment.

Treatment strategy for aneurysms of the posterior cerebral artery.

SUMMARY: The authors carried out a retrospective review of the records of 12 patients with aneurysms of the posterior cerebral artery (PCA). Four were asymptomatic, 1 presented with a mass effect, and 7 with a subarachnoid haemorrhage (SAH). Of the 7 ruptured aneurysms, 3 were embolized and 2 were clipped. However, 2 patients died from rebleeding before any treatment. Of the 5 unruptured aneurysms, 1 was embolized with coils but the remaining 4 have been conservatively observed. No aneurysms have ruptured during the follow-up period, and 3 have thrombosed spontaneously. According to our results, the PCA aneurysms should be treated aggressively in the early phase. Although the preservation of the anatomical integrity of the PCA should naturally be one of the prime objectives, PCA occlusion may sometimes be inevitable when treating large or fusiform aneurysms. On the other hand, conservative therapy is one of the options for the treatment of incidentally encountered unruptured ones, because these have the possibility of spontaneous thrombosis.