Usefulness of "AcT ratio" in diagnosis of internal carotid artery stenosis: a multicenter, retrospective, observational study.

PURPOSE: The ratio of the internal carotid artery (ICA) to the common carotid artery (CCA), especially the "AcT ratio," which is a modified measurement method of acceleration time, is useful for diagnosing ICA-origin stenosis. However, previous studies were single-center studies. Therefore, this multicenter, retrospective, cross-sectional study aimed to determine whether a method using the AcT ratio is useful for estimating stenosis rates. METHODS: This study included 461 vessels subjected to carotid artery ultrasonography and evaluation for ICA-origin stenosis via NASCET at four hospitals. The duration from the steep rise point to the inflection point or the first peak was defined as AcT on pulsed wave Doppler. The AcT ratio was calculated as AcT of ICA/AcT of ipsilateral CCA. The AcT ratio and rate of ICA-origin stenosis were analyzed using Pearson's correlation coefficient, simple regression analysis, and ROC curve. RESULTS: A significant positive correlation was observed between the AcT ratio and NASCET stenosis. NASCET stenosis of ≥ 50% had a sensitivity, specificity, and negative predictive value (NPV) of 70.2%, 71.6%, and 91.5%, respectively, when the cut-off value of the AcT ratio was 1.17. NASCET stenosis of ≥ 70% had a sensitivity, specificity, and NPV of 70.5%, 72.1%, and 95.9%, respectively, when the cut-off value of the AcT ratio was 1.22. CONCLUSIONS: The findings of this multicenter, retrospective, cross-sectional study suggest that the AcT ratio is useful for diagnosing ICA-origin stenosis, especially for diagnosis by exclusion. NASCET stenosis of ≥ 50% was considered unlikely if the Act ratio was ≤ 1.17, whereas NASCET stenosis of ≥ 70% was considered unlikely if it was ≤ 1.22.

Neovascularization From the Carotid Artery Lumen Into the Carotid Plaque Confirmed by Contrast-Enhanced Ultrasound and Histology.

OBJECTIVE: This study was aimed at assessing intraplaque neovessels, focusing on neovascularization from the vascular luminal side using contrast-enhanced ultrasound (CEUS) and determining that this contrast effect indicates that the neovessel is connected to the vessel lumen histopathologically. Whether plaque vulnerability can be assessed more accurately was also investigated. METHODS: We enrolled consecutive patients with internal carotid artery stenosis who underwent carotid endarterectomy (CEA) and pre-operative CEUS with perflubutane of the carotid arteries. We graded the contrast effect semi-quantitatively from the vascular luminal and adventitial sides. We compared the contrast effect with the pathological findings, especially the neovascularization of the CEA specimens. RESULTS: In total, 68 carotid arterial atheromatous plaques (47 symptomatic) were analyzed. Symptomatic plaques were significantly correlated with stronger contrast effects from the luminal side than from the adventitial side (p = 0.0095). Microbubbles from the luminal side appeared to flow mainly into the plaque shoulder. The contrast effect value for the plaque shoulder and neovessel density were significantly correlated (ρ = 0.35, p = 0.031). Neovessel density was significantly higher in symptomatic than in asymptomatic plaques (56.2 ± 43.7/mm2 and 18.1 ± 15.2/mm2, respectively, p < 0.0001). Serial histological sections of CEA specimens in a symptomatic plaque with a strong contrast effect from the luminal side revealed multiple neovessels fenestrated to the vessel lumen with endothelial cells, consistent with the CEUS findings. CONCLUSION: Contrast-enhanced ultrasound can be used to evaluate neovessels originating from the luminal side, histopathologically confirmed in serial sections. Symptomatic vulnerable plaque is correlated more significantly with intraplaque neovascularization from the luminal side than with neovascularization from the adventitia.

Development of evaluation system for cerebral artery occlusion in emergency medical services: noninvasive measurement and utilization of pulse waves.

Rapid reperfusion therapy can reduce disability and death in patients with large vessel occlusion strokes (LVOS). It is crucial for emergency medical services to identify LVOS and transport patients directly to a comprehensive stroke center. Our ultimate goal is to develop a non-invasive, accurate, portable, inexpensive, and legally employable in vivo screening system for cerebral artery occlusion. As a first step towards this goal, we propose a method for detecting carotid artery occlusion using pulse wave measurements at the left and right carotid arteries, feature extraction from the pulse waves, and occlusion inference using these features. To meet all of these requirements, we use a piezoelectric sensor. We hypothesize that the difference in the left and right pulse waves caused by reflection is informative, as LVOS is typically caused by unilateral artery occlusion. Therefore, we extracted three features that only represented the physical effects of occlusion based on the difference. For inference, we considered that the logistic regression, a machine learning technique with no complex feature conversion, is a reasonable method for clarifying the contribution of each feature. We tested our hypothesis and conducted an experiment to evaluate the effectiveness and performance of the proposed method. The method achieved a diagnostic accuracy of 0.65, which is higher than the chance level of 0.43. The results indicate that the proposed method has potential for identifying carotid artery occlusions.

An Ultrasonographic Evaluation for the Early Detection of Nerve Root Changes in Herpes Zoster-associated Motor Paresis.

We herein report a case of herpes zoster complicated by right-arm paralysis, wherein cervical nerve root ultrasonography enabled the early diagnosis and a therapeutic efficacy evaluation. A 71-year-old man developed progressive weakness in the muscles innervated by the right C5-6 nerve root following the appearance of a painful rash. Cervical nerve root ultrasonography revealed C5-6 nerve root inflammatory swelling. Methylprednisolone pulse therapy and subsequent oral prednisolone therapy gradually improved the muscle weakness. At three weeks following admission, ultrasonography revealed C5-6 nerve root inflammatory swelling improvement. Ultrasonography may aid in the early detection of nerve root inflammatory swelling and help monitor treatment efficacy.

Embolic stroke induced by rotational persistent 1st intersegmental artery compression.

A 45-year-old man suffered multiple cerebral infarctions in the vertebrobasilar artery territory, followed by second stroke against conservative treatment. Radiological examinations revealed intra-arterial defect in left persistent 1st intersegmental artery (PFIA) at C1 level, suggesting mural thrombus, and mechanical compression of left PFIA at the level with head rotation to the right clearly revealed by reconstructed 3-dimensional radiological images, but no findings of atlantoaxial instability. One month after the second stroke, posterior fixation was performed. Postoperative course was uneventful without subsequent stroke for 24 months. This unique case demonstrated that PFIA might associate with cerebral stroke as a clinical condition of bow hunter's stroke even in middle age. Reconstructed 3-dimensional radiological images might be useful for clear demonstration of the pathophysiology in this complex clinical entity.

Two-Dimensional Wavenumber Analysis Implemented in Ultrasonic Vector Doppler Method with Focused Transmit Beams.

The multi-angle Doppler method was introduced for the estimation of velocity vectors by measuring axial velocities from multiple directions. We have recently reported that the autocorrelation-based velocity vector estimation could be ameliorated significantly by estimating the wavenumbers in two dimensions. Since two-dimensional wavenumber estimation requires a snapshot of an ultrasonic field, the method was first implemented in plane wave imaging. Although plane wave imaging is predominantly useful for examining blood flows at an extremely high temporal resolution, it was reported that the contrast in a B-mode image obtained with a few plane wave emissions was lower than that obtained with focused beams. In this study, the two-dimensional wavenumber analysis was first implemented in a framework with focused transmit beams. The simulations showed that the proposed method achieved an accuracy in velocity estimation comparable to that of the method with plane wave imaging. Furthermore, the performances of the methods implemented in focused beam and plane wave imaging were compared by measuring human common carotid arteries in vivo. Image contrasts were analyzed in normal and clutter-filtered B-mode images. The method with focused beam imaging achieved a better contrast in normal B-mode imaging, and similar velocity magnitudes and angles were obtained by both the methods with focused beam and plane wave imaging. In contrast, the method with plane wave imaging gave a better contrast in a clutter-filtered B-mode image and smaller variances in velocity magnitudes than those with focused beams.

Age and composition of the thrombus retrieved by mechanical thrombectomy from patients with acute ischemic stroke are associated with revascularization and clinical outcomes.

INTRODUCTION: Understanding the composition of stroke thrombi retrieved by mechanical thrombectomy is essential to clarify the pathogenesis of stroke. However, it is difficult to evaluate thrombus composition precisely and objectively. Immunohistochemical staining was used to evaluate thrombus composition and age. MATERIALS AND METHODS: Consecutive thrombi (n = 108) retrieved from patients who underwent mechanical thrombectomy for acute large-vessel ischemic stroke were retrospectively analyzed. Lytic features of granulocytes and CD163 were estimated as indicators of the age of the cardioembolic (CE) thrombus. RESULTS: The stroke subtypes were as follows: CE, 74 cases; large artery atherosclerosis, 11; undetermined etiology, 12; and other determined etiology, 11. There were no statistical differences in thrombi composition according to stroke subtypes. The fibrin area was positively correlated with the red blood cell (RBC) and platelet areas. The following analysis was performed using CE only. Regarding age, the thrombus was judged as fresh in 30.0 % and older in 70.0 % based on the lytic features. The RBC areas of older thrombi were smaller than those of fresh thrombi. The puncture-to-reperfusion time of older thrombi was longer than that of fresh thrombi. Platelet-rich thrombi were associated with a greater number of maneuvers, a smaller prevalence of TICI 3, and unfavorable functional outcomes compared to platelet-poor thrombi. The number of CD163 positive cells in thrombi with anticoagulants was higher than in those without anticoagulants. CONCLUSION: Thrombus composition correlated with revascularization and clinical outcomes. The composition of an acute ischemic thrombus may reflect the pathophysiology of stroke and influence treatment efficacy.

Ultrasound-guided computed tomography angiography for the diagnosis of rotational vertebral artery occlusion: 2 case reports and technical notes.

Rotational vertebral artery occlusion is a rare cause of ischemic stroke in the vertebrobasilar arteries. While computed tomography angiography (CTA) is less invasive for the diagnosis of rational vertebral artery occlusion than digital subtraction angiography and more useful for elucidating the correlation between vertebrobasilar arteries and the surrounding structure, carotid ultrasound is noninvasive and more beneficial for the real-time evaluation of the hemodynamic change with neck rotation compared to CTA. Here, we reported 2 cases of rotational vertebral artery occlusion in patients aged 81 and 38 years and proposed a novel technique for its diagnosis using ultrasound-guided CTA. We suggest that the combination of ultrasound and CTA is useful for diagnosing rotational vertebral artery occlusion, which would compensate for the disadvantages of CTA alone.

Simulation study on the effects of cancellous bone structure in the skull on ultrasonic wave propagation.

The transcranial Doppler method (TCD) enables the measurement of cerebral blood flow velocity and detection of emboli by applying an ultrasound probe to the temporal bone window, or the orbital or greater occipital foramina. TCD is widely used for evaluation of cerebral vasospasm after subarachnoid hemorrhage, early detection of patients with arterial stenosis, and the assessment of brain death. However, measurements often become difficult in older women. Among various factors contributing to this problem, we focused on the effect of the diploe in the skull bone on the penetration of ultrasound into the brain. In particular, the effect of the cancellous bone structure in the diploe was investigated. Using a 2D digital bone model, wave propagation through the skull bone was investigated using the finite-difference time-domain (FDTD) method. We fabricated digital bone models with similar structure but different BV/TV (bone volume/total volume) values in the diploe. At a BV/TV of approximately 50-60% (similar to that of older women), the minimum ultrasound amplitude was observed as a result of scattering and multiple reflections in the cancellous diploe. These results suggest that structural changes such as osteoporosis may be one factor hampering TCD measurements.

Measurement of flow velocity vectors in carotid artery using plane wave imaging with repeated transmit sequence.

PURPOSE: Doppler-based methods are widely used for blood flow imaging in clinical settings. However, they inherently estimate the velocity component only in the axial direction. Therefore, various studies of angle-independent methods have been conducted. The multi-angle Doppler method is one such angle-independent method, in which the velocity vector is estimated using axial velocities obtained from multiple directions by steering an ultrasonic beam. Recently, plane wave imaging, which realizes a very high frame rate of several thousand frames per second, was applied to the multi-angle Doppler method. However, the maximum detectable velocity, i.e., the aliasing limit, was reduced depending on the number of steering angles. In the present study, the feasibility of a specific transmit sequence, namely, the repeated transmit sequence, was examined using the plane-wave multi-angle Doppler method. METHOD: In the repeated transmit sequence, plane waves were emitted to the same direction twice, after which the steering angle was changed. By repeating the same procedure, a pair of beamformed radio-frequency (RF) signals could be obtained under each beam steering angle. By applying the autocorrelation method to each pair of RF signals, the time interval between the RF signals could be kept as the pulse repetition interval (PRI). The feasibility of such a transmit sequence was examined by numerical simulation and in vivo measurement of a human carotid artery. RESULTS: The simulation results showed that the maximum steering angles of over 10 degrees were not feasible with the linear array used in the present study. The feasible maximum steering angle would depend on the element pitch of the probe relative to the ultrasonic wavelength. By limiting the maximum steering angles to 5 and 10 degrees, bias errors were 9.2% and 11.3%, respectively, and root mean squared errors were 21.5% and 16.9%, respectively. Also, flow velocity vectors in a human carotid artery could be visualized with the proposed method. CONCLUSION: The multi-angle Doppler method was implemented in plane wave imaging with the repeated transmit sequence, and the proposed method was shown to be feasible through numerical simulation and in vivo measurement of a carotid artery.

Gene Expression Profiles of Human Cerebral Organoids Identify PPAR Pathway and PKM2 as Key Markers for Oxygen-Glucose Deprivation and Reoxygenation.

Ischemic stroke is one of the most common neurological diseases. However, the impact of ischemic stroke on human cerebral tissue remains largely unknown due to a lack of ischemic human brain samples. In this study, we applied cerebral organoids derived from human induced pluripotent stem cells to evaluate the effect of oxygen-glucose deprivation/reoxygenation (OGD/R). Pathway analysis showed the relationships between vitamin digestion and absorption, fat digestion and absorption, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and complement and coagulation cascades. Combinational verification with transcriptome and gene expression analysis of different cell types revealed fatty acids-related PPAR signaling pathway and pyruvate kinase isoform M2 (PKM2) as key markers of neuronal cells in response to OGD/R. These findings suggest that, although there remain some limitations to be improved, our ischemic stroke model using human cerebral organoids would be a potentially useful tool when combined with other conventional two-dimensional (2D) mono-culture systems.

Investigation of feasibility of singular value decomposition clutter filter in plane wave imaging with packet transmission sequence.

PURPOSE: Assessment of blood flow is an important function in diagnostic ultrasound imaging. Color flow imaging is one such method widely used in the clinical setting. Since autocorrelation suffers from aliasing, the time interval between successive transmissions of ultrasonic pulses should be as short as possible. For this purpose, a specific transmit-receive sequence, namely, packet transmission, is widely used in color flow imaging. Also, plane wave imaging recently introduced to ultrasound imaging significantly contributes to improvement of the temporal resolution. Furthermore, a singular value decomposition (SVD) clutter filter reportedly outperforms a conventional clutter filter. In the present study, the feasibility of the SVD clutter filter in plane wave imaging with the packet transmission sequence was investigated. METHOD: In the present study, the packet transmission sequence was implemented in plane wave imaging by sending plane waves multiple times in the same direction before changing the steering angle. In the first strategy, like conventional color flow imaging with line-by-line acquisition using a focused transmit beam, a clutter filter was applied to ultrasonic radio-frequency (RF) signals in each packet. In the second strategy, the number of transmissions per packet was set at two, and a clutter filter was applied to RF signals obtained from the first or second transmission in different packets. RESULTS: The in vivo experimental results on a human carotid artery showed that the second strategy with an SVD filter realized significantly better performance than the first strategy with a polynomial regression filter used as a conventional filter. CONCLUSION: An SVD clutter filter was feasible in plane wave imaging with the packet transmission sequence, and the performance was improved by limiting the number of transmissions per packet to two.

Blood Flow Visualization and Wall Shear Stress Measurement of Carotid Arteries Using Vascular Vector Flow Mapping.

Carotid artery ultrasound is extensively used to assess early- and late-stage atherosclerosis via the intima-media thickness and increased blood flow velocity caused by stenosis, respectively. However, the effect of wall shear stress (WSS) has not been considered to date. This study aimed to visualize the blood flow of carotid arteries and measured WSS using vector flow mapping (VFM) developed specifically for vascular use. Patients with cerebrovascular diseases were prospectively enrolled and examined with carotid ultrasound using VFM Vascular. WSS was calculated in the common carotid artery and internal carotid artery. Blood flow in 82 common carotid arteries was visualized with VFM Vascular. The maximum and mean WSSs were negatively correlated with age and intima-media thickness. The WSS in 16 internal carotid artery plaques was significantly higher upstream of the plaque than downstream. Therefore, VFM Vascular is a promising method that provides a novel indicator of atherosclerosis.

Bilateral carotid artery dissection due to Eagle syndrome in a patient with vascular Ehlers-Danlos syndrome: a case report.

BACKGROUND: Patients with vascular Ehlers-Danlos syndrome (EDS) occasionally suffer from arterial dissection. Eagle syndrome, which is caused by an elongated styloid process and also causes arterial dissection, is difficult to diagnose and could sometimes be overlooked. Little is known of the coexistence of these two diseases, and treatment strategy is not established. Here, we present a case of bilateral internal carotid artery (ICA) dissection due to Eagle syndrome in a patient with vascular EDS. CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of sudden onset of mild sensory disturbance in his left limbs. He had a history of Ehlers-Danlos syndrome (EDS) and also had left cervical internal carotid artery (ICA) dissection 3 years before. Diffusion-weighted imaging showed acute cerebral infarcts in the right hemisphere. Cervical computed tomography angiography (CTA) revealed the right ICA narrowing at the cervical portion in addition to the previous left cervical ICA dissection. Cervical magnetic resonance imaging (MRI) revealed double-lumen and intramural hematoma at the narrowing portion of the right cervical ICA, which indicates arterial dissection. CT also revealed bilateral elongated styloid processes which are close to each side of cervical ICA. We diagnosed him as bilateral ICA dissection due to bilateral Eagle syndrome. Considering vascular complications due to vascular EDS, we performed closer follow-up with transoral carotid ultrasonography (TOCU). In 4 months, his right ICA dissection gradually improved without stroke recurrence or deterioration of dissection. CONCLUSIONS: Since patients with vascular EDS easily develop arterial dissection, Eagle syndrome may be overlooked. Clinicians should consider Eagle syndrome in the case of vascular EDS with extracranial ICA dissection and close follow-up should be prioritized in cases of Eagle syndrome with vascular EDS.

GlycoBIST: A System for Automatic Glycan Profiling of a Target Protein Using Milli-Bead Array in a Tip.

Lectin is a biomolecule that recognizes a specific part of glycans and, thus, has been used widely as a probe for glycoprotein analysis. Owing to the wide repertoire in nature combined with the recent two decades of advances in microarray technology, the multiplexed use of lectins has been widely used for glycan profiling of endogenous proteins. Because protein glycosylation is recognized as being biologically important and is expected to be a reliable disease marker, lectin microarray analysis with highly sensitive detection has been used to discover disease-relevant glycosylation alterations. However, the conventional system is limited to research purposes; thus, its implementation in clinical settings is warranted. Here, we provide an automatic glycan profiling method using GlycoBIST. A unique array format is used for 10-plexed lectin-glycoprotein interaction analysis on 1-mm-sized beads, which are arranged vertically in a capillary-shaped plastic tip. Using a one-boxed autopipetting machine, the whole process (including interaction, washing, and detection) is performed automatically and serially, resulting in reproducible measurements. In this article, a typical method for glycan profiling of a purified glycoprotein and the fabrication of GlycoBIST tips is explained. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Fabrication of a GlycoBIST tip Basic Protocol 2: Automatic profiling of a target glycoprotein using GlycoBIST.

Lectin Bead Array in a Single Tip Facilitates Fully Automatic Glycoprotein Profiling.

A quantitative description of glyco-alteration/differences in diseases can lead to the development of a diagnostic agent for use in vitro to monitor the degree of change in target glycoproteins. Analytical systems have been developed along with the progress of omics-oriented technologies. For clinical implementation, their full automation is required with an apparatus that is simple to operate. Here, we report an automatic analysis system for quantitative characterization of glyco-alteration/differences that depends on the unique strategy of "bead arrays in a single tip." The alternative lectin array can obtain a minimum characterization of the glycan profile for nanogram quantities of an endogenous glycoprotein. A simple autopipetting robot produces the precise chemiluminescence detection of glycan-lectin interactions with a wide dynamic range that is superior to fluorescence-based lectin arrays. The tip-based array format enables automatic glycan profiling from sample pretreatment to detection with low variation and linear detection, which may facilitate the use of this lectin array in clinical practice.

Appropriate Flow Reduction for Unilateral Ruptured Vertebral Artery Dissection by Proximal Clipping to Prevent Rebleeding and Medullary Infarction.

BACKGROUND: Medullary infarction (MI) occasionally occurs after treatment of ruptured vertebral artery dissection (VAD). The aim of this study was to validate whether flow reduction for ruptured unilateral VAD by proximal clipping prevents rebleeding and MI in comparison with trapping. METHODS: Thirty-one patients who underwent direct surgery or endovascular procedures for unilateral ruptured VAD and postoperative magnetic resonance imaging (MRI), including 9 patients treated with trapping and 22 patients treated with proximal clipping, were enrolled. For posterior inferior cerebellar artery (PICA)-involved type VAD, occipital artery to PICA anastomosis was added as needed to isolate the rupture point. The rate of rebleeding and the occurrence of MI on MRI were compared between the 2 groups. RESULTS: There was no rebleeding after treatment in all 31 patients. However, 5 patients had MI on postoperative MRI (16.1%, κ = 0.903). In 5 of the 9 patients treated with trapping, MI was seen on MRI after treatment (55.6%). On the other hand, 0 of the 22 patients treated with proximal clipping developed MI (P < 0.01). CONCLUSIONS: Appropriate flow reduction for ruptured unilateral VAD by proximal clipping is thought to be effective for preventing rebleeding and avoiding MI.

Utility of Complementary Magnetic Resonance Plaque Imaging and Contrast-Enhanced Ultrasound to Detect Carotid Vulnerable Plaques.

Background We aimed to improve the assessment quality of plaque vulnerability with combined use of magnetic resonance imaging and contrast-enhanced ultrasound ( CEUS ). Methods and Results We prospectively enrolled 71 patients with internal carotid artery stenosis who underwent carotid endarterectomy and performed preoperative CEUS and magnetic resonance plaque imaging. We distinguished high-signal-intensity plaques ( HIP s) and non- HIP s based on magnetization-prepared rapid acquisition with gradient echo images. We graded them according to the CEUS contrast effect and compared the CEUS images with the carotid endarterectomy specimens. Among the 70 plaques, except 1 carotid endarterectomy tissue sample failure, 59 were classified as HIP s (43 symptomatic) and 11 were classified as non- HIP s (5 symptomatic). Although the magnetization-prepared rapid acquisition with gradient echo findings alone had no significant correlation with symptoms ( P=0.07), concomitant use of magnetization-prepared rapid acquisition with gradient echo and CEUS findings did show a significant correlation ( P<0.0001). CEUS showed that all 5 symptomatic non- HIP s had a high-contrast effect. These 5 plaques were histopathologically confirmed as vulnerable, with extensive neovascularization but only a small amount of intraplaque hemorrhage. Conclusions Complementary use of magnetic resonance imaging and CEUS to detect intraplaque hemorrhage and neovascularization in plaques can be useful for evaluating plaque vulnerability, consistent with the destabilization process associated with neovessel formation and subsequent intraplaque hemorrhage.