Diagnostic performance of intraoperative cone beam computed tomography compared with postoperative magnetic resonance imaging for detecting hemorrhagic transformation after endovascular treatment following large vessel occlusion.

OBJECTIVES: Early detection of hemorrhagic transformation (HT) in patients with large vessel occlusion (LVO) after endovascular treatment is important for postoperative patient management. We investigated the diagnostic performance of intraoperative cone beam computed tomography (CBCT) with reference standard magnetic resonance imaging (MRI) for detecting HT. MATERIALS AND METHODS: Consecutive patients with LVO treated by endovascular treatment who underwent intraoperative CBCT and postoperative MRI were included. Two observers evaluated all images for the presence of HT. Sensitivity and specificity for detecting HT were calculated with MRI as reference standard. The observers classified HT according to the European Cooperative Acute Stroke Study (ECASS). Inter-method and inter-rater agreement for the detection of HT and for the ECASS classification were assessed using kappa or weighted Brennan-Prediger (wBP) statistics. RESULTS: Images of 106 procedures (94 for anterior circulation) were analyzed. The sensitivity and specificity for detecting HT on CBCT were 0.77 and 0.83, respectively, for all procedures and 0.83 and 0.8, respectively, for anterior circulation. The inter-method agreement for HT detection (κ = 0.63 overall, κ = 0.69 anterior circulation) and ECASS classification (wBP = 0.67 overall, wBP = 0.77 anterior circulation) were substantial. The inter-rater agreement for HT detection (κ = 0.87 overall, κ = 0.85 anterior circulation) and for ECASS classification (wBP = 0.95 overall, wBP = 0.92 anterior circulation) were almost perfect. CONCLUSIONS: The diagnostic performance of CBCT for the detection of HT in stroke patients treated for LVO was acceptable with excellent inter-rater agreement. Intraoperative CBCT may be useful to trigger early interventions if HT is detected, although detailed classifications of HT may be difficult.

4D Digital Subtraction Angiography for the Temporal Flow Visualization of Intracranial Aneurysms and Vascular Malformations.

PURPOSE: To assess the benefit and radiation dose of four-dimensional (4D) digital subtraction angiography (DSA) - a time resolved three-dimensional (3D) DSA application - to evaluate the flow and architecture of aneurysms and vascular malformations. METHODS: All patients with cerebrovascular disease were considered who underwent 4D-DSA at our institution between January 2015 and February 2016. For the aneurysm patients, we evaluated the image quality in terms of the visualization of contrast flow in the aneurysm on a 3-point scale (excellent, fair and poor). Interrater agreement between two raters was estimated using Cohen's Kappa statistics. For the shunt disease patients, the additional information obtained from the 4D-DSA was described for each disease. The median radiation dose and volume of contrast medium required for the acquisitions were estimated. RESULTS: A total of 173 patients underwent 4D-DSA; 126 intracranial aneurysms, 10 arteriovenous malformations (AVM), 15 dural arteriovenous fistula (dAVF) and 22 other diseases. For aneurysm patients, excellent and fair visualization of the intra-aneurysmal flow was observed in 27.7%, 72.3%, and excellent (κ = 0.9) agreement between the raters was found. For AVM and dAVF patients, 4D-DSA clarified the complex vasculature by viewing the discrete time phase of contrast filling. Median radiation dose for intracranial lesions was 79.6 mGy for 6s 4D-DSA, and 175 mGy for 12s 4D-DSA. The median amount of contrast medium used was 18.0 ml for 6s 4D-DSA and 21.0 ml for 12s 4D-DSA. CONCLUSIONS: 4D-DSA provided additional information regarding intra-aneurysmal flow and contributed to detect different component of nidus or shunt points.

Modified colored three-dimensional posterior and temporal cranial fossa model with mobility of the joint between C1 and occipital condyle.

BACKGROUND: Skull base surgery requires anatomical knowledge and appropriate surgical technique in bone drilling. We developed a newly modified three-dimensional (3D) model of the posterior cranial fossa as a learning tool that improves knowledge of skull base anatomy and surgical approaches, including skull base drilling techniques. METHODS: This bone model of the posterior cranial fossa was created based on computed tomography data using a 3D printer, and incorporates artificial cranial nerves, cerebral vessels, bony structures, dura mater, and cerebellar tentorial dura. These anatomical components are differentiated with various colors. In addition, the atlanto-occipital junction can be mobilized to fully expose the surface of the cartilage between the C1 condyle and occipital condyle to allow drilling to open the hypoglossal canal under a wide surgical field. The usefulness of the model for practicing skull base surgical approaches was evaluated. RESULTS: Experience of bone drilling, dural dissection, and 3D positioning of important structures, including cranial nerves and blood vessels, was identical to that in actual surgery. CONCLUSIONS: This model is designed to facilitate teaching anatomical knowledge and essential epidural procedure-related skills, and is useful for teaching the essential elements of posterior skull base surgery.

A Novel Braided Stent With Customized Simulation Software for Treatment of Intracranial Aneurysms: Multicenter Prospective Trial Before Unrestricted Clinical Application.

BACKGROUND AND OBJECTIVES: Planning/guidance software became important tools for physicians' presurgical optimal decision-making. However, there are no intracranial stent products with specifically associated simulation software. We report the "premarket" clinical trial of a new braided stent with a customized simulation software. METHODS: A stent system with 3 mesh density types (16, 24, and 32 wire mesh) was designed based on computational flow dynamics technology, and a simulation software (virtual stent planner [VSP]) was developed for the optimal stent deployment planning. Stents were selected after simulation on preoperative 3D-processed angioimages, and accuracy of the VSP was evaluated. RESULTS: Thirty-three unruptured intracranial aneurysms were successfully treated with VSP guidance. Twenty aneurysms (61%) were anterior circulation aneurysms, and 13 (39%) were posterior circulation aneurysms. The average aneurysm size was 7.1 mm, and the mean follow-up period was 19.2 months (11-39.0). There was no major recurrence or retreatment during follow-up, 2 morbidity cases, and no mortality. VSP planning presented slightly smaller stent dimensions compared with postdeployment: 24.2 vs 25.5 mm average, error -1.3 mm, and difference rate-5.46%. CONCLUSION: Based on this result, the new stents and software guidance system were approved by the Ministry of Health and Welfare as a combined medical device. VSP provided precise deployment with minimal error compared with actual stent and can contribute to better stent deployment even for less experienced physicians.

Dual-phase Au-Pt alloys free from magnetic susceptibility artifacts in magnetic resonance imaging.

PURPOSE: Magnetic resonance imaging (MRI) devices are frequently used in image-based diagnosis. In the case of large artifacts, which are generated in magnetic resonance (MR) images when magnetic materials, such as metals, are present in the body, these devices are less useful. This study aimed to develop a dual-phase Au-Pt alloy that does not generate artifacts in MR images and has high workability to prepare medical devices. MATERIALS AND METHODS: A processing method to produce a dual-phase Au-Pt alloy was established, and the magnetic susceptibility and artifacts of different alloy compositions were determined using a SQUID (superconducting quantum interference device) flux meter and a 1.5 T-MRI system. The crystallographic phases of the prepared alloy samples were identified using X-ray diffraction. Sample cross-sections were observed using a metallurgical microscope. Furthermore, a thinning test was conducted to examine alloy workability. RESULTS: Dual-phase Au-Pt alloys Au70Pt30 and Au67Pt33-the former heat-treated at 800 and 850 °C and the latter heat-treated at 900 °C-generated minimal artifacts when imaged in a 1.5 T-MRI system. Their volume magnetic susceptibility increased as the heat-treatment temperature decreased. The alloy surfaces were observed to be uniform. Moreover, the workability of the dual-phase alloy was considerably better than that of the single-phase alloy. CONCLUSION: Volume magnetic susceptibility could be controlled by changing the composition and processing temperature of the Au-Pt alloys. Dual-phase Au-Pt alloys those do not generate magnetic susceptibility artifacts in MRI images and have good workability could be prepared. The alloys are expected to be used in the preparation of various implantable medical devices.

Direct carotid exposure approach in the treatment of anterior circulation unruptured intracranial aneurysms for elderly patients.

BACKGROUND AND PURPOSE: The direct carotid exposure approach (DCEA) is a technical option for elderly patients with severe vessel tortuosity due to arteriosclerosis. We evaluated complications related to antiplatelet/anticoagulant management and compared the DCEA to standard transfemoral/transbrachial approaches (TFBA) in the treatment of unruptured intracranial aneurysms for elderly patients. METHODS: From August 2017 to August 2020, 52 patients (53 procedures) aged over 75 years with unruptured aneurysms in the anterior circulation were treated at our institution. All patients received dual antiplatelet drugs before the procedure. Eleven patients (21.2%) (12 procedures) were treated with the DCEA. The rest were treated with TFBA. The main indication of the DCEA was an unfavorable aortic arch or vessel tortuosity. Complications and the duration of the procedure were compared between the two groups. RESULTS: There were no significant differences between the two groups in age, aneurysm location, preoperative antiplatelet use, heparin use, or maximum activated clotting time (ACT) values. All endovascular treatments were successfully performed by DCEA. Among all parameters, the DCEA group had only bigger average aneurysm diameter (14 mm) and higher number of pipeline embolic device (PED) placement (58%). Time to the guiding-catheter placement was not significantly different between the groups (DCEA vs TFBA = 31.0 min vs 24.7 min, p = 0.178).　No significant complications of DCEA, such as subcutaneous hematomas, were observed.　. CONCLUSION: Even with the use of antiplatelet and anticoagulation therapy, the DCEA can be performed safely for unruptured aneurysms in elderly patients.

Clinical outcomes of procedures combining endovascular embolization with a direct surgical approach in a hybrid operating room for the treatment of refractory dural arteriovenous fistulas.

BACKGROUND: We reviewed the clinical outcomes of a procedure that combines endovascular embolization and a direct surgical approach in a hybrid operating room (OR) for the treatment of refractory dural arteriovenous fistulas (dAVFs). METHODS: All patients with intracranial dAVFs who underwent a procedure combining endovascular embolization and direct surgical approach with biplane angiography or a robotic C-arm system in a hybrid OR between February 2004 and June 2020 were considered. Borden grading, occlusion rate, pre-and post-operative modified Rankin Scale (mRS) scores, and complications were retrospectively investigated. The pre-and postoperative mRS scores were compared using the Wilcoxon signed-ranks test. RESULTS: We evaluated 14 arteriovenous fistulas (AVFs) in consecutive 13 patients. Of these, ten AVFs were previously treated with endovascular embolization, ten were located in the transverse-sigmoid sinus, and four in the cortical vein. The Borden grade was II in two AVFs and III in 12 AVFs. Immediate occlusion of the AVF was achieved in 13 AVFs, and gradual occlusion was observed in one case. The median preoperative mRS was 1 (0-3), whereas the median postoperative mRS was 0 (0-1) which indicated marked improvement (P = 0.006). Complications including postoperative transient visual disturbance and intraprocedural extravasation were observed in only two cases. CONCLUSION: The combination of endovascular embolization and direct surgical approach in a hybrid OR could achieve sufficient occlusion of refractory AVFs with acceptable complication rates and improved symptoms.

Visualization of extracranial-intracranial bypass in moyamoya patients using intraoperative three-dimensional digital subtraction angiography with intravenous contrast injection and robotic C-arm: patient series.

BACKGROUND: The authors describe a noninvasive intraoperative imaging strategy of three-dimensional (3D) digital subtraction angiography (DSA) with intravenous (IV) contrast injection, using indocyanine green (ICG) as a test bolus, during extracranial-intracranial (EC-IC) bypass surgery for moyamoya disease. OBSERVATIONS: Four patients underwent EC-IC bypass surgery in a hybrid operating room. During the surgery, bypass patency was verified using ICG videoangiography and Doppler ultrasonography. After skin closure, the patients under anesthesia underwent IV 3D-DSA with a robotic C-arm in which the scan delay time for the 3D-DSA scan was estimated from the arrival time of ICG during the ICG videoangiography. One day after the surgery, the patients underwent magnetic resonance angiography (MRA). The IV 3D-DSA images were retrospectively compared with those obtained with other modalities. Good bypass patency was confirmed on IV 3D-DSA, ICG videoangiography, Doppler ultrasonography, and postoperative MRA in all cases. The delay time determined using ICG videoangiography as a test bolus resulted in IV 3D-DSA with adequate image quality, allowing assessment of the spatial relationships between the vessels and anastomoses from all directions. LESSONS: To evaluate bypass patency and anatomical relationships immediately after EC-IC bypass surgery, IV 3D-DSA may be a useful modality. ICG videoangiography can be used to determine the scan delay time.

Visual complications after coil embolization of internal carotid artery aneurysms at the ophthalmic segment.

BACKGROUND: Coil embolization of aneurysms of the ophthalmic segment of the internal carotid artery (ICA-OphA ANs) has potential risks of visual complications. We analyzed this risk and focused on the relationship of the ophthalmic artery (OphA) origin with the aneurysm neck. METHODS: From January 2003 to April 2018, 179 unruptured ICA-OphA ANs were treated with endovascular surgery in our institution. Two ruptured and four aneurysms with missing data were excluded. Finally, 173 unruptured aneurysms were included in this study. The aneurysms were classified into three groups according to the location of the OphA origin: Separate, Shared, and Dome type. We retrospectively assessed visual complications based on the relationship between types of aneurysm and postoperative angiographic findings for the OphA. RESULTS: Visual deficits remained permanent in eleven cases (6.4%). In the Dome type, visual complications were significantly more frequent compared to the Separate type. Change in the OphA flow was significantly associated with a higher complication rate of 2.9%, but patients with changed OphA flow had a significant rate of 7.5% (p = 0.020). We found no significant difference in the incidence of visual complications concerning the use of perioperative antithrombotic therapy. CONCLUSIONS: The location of OphA origin regarding the aneurysmal neck and postoperative OphA flow were significantly correlated with the visual outcome after coil embolization for ICA-OphA ANs. Post-procedural flow in the OphA was an important factor affecting the rate of ischemic retinal complications. Retinal embolic events occurred with preserved flow in the OphA, albeit at a lower rate.

Flow Diverter Apposition in Patients with Large or Giant Intracranial Aneurysms Evaluated on Three-Dimensional Fusion Images Acquired by High-Resolution Cone-Beam Computed Tomography and Digital Subtraction Angiography.

OBJECTIVE: To investigate flow diverter (FD) apposition on fused images acquired by high-resolution cone-beam computed tomography (CBCT) and 3-dimensional (3D) digital subtraction angiography. METHODS: Patients with large or giant internal carotid artery aneurysms treated with Pipeline FDs who underwent CBCT imaging at our institution between October 2016 and May 2019 were included. Two neurosurgeons measured the maximum malapposition between FDs and vessel walls on 3D fusion images of high-resolution CBCT images displaying the FD and 3D digital subtraction angiography images displaying the vessels. Associations between the relative malapposition, FD diameter, vessel diameter, proximal and distal vessel diameter discrepancy, and siphon angle were evaluated by linear regression analysis. Inter-rater and intermethod (3D and 2D image) agreements of the malapposition measurements were assessed by Bland-Altman analysis and by interclass correlation coefficients. RESULTS: Images of 2 patients were excluded because of image artifacts or fusion errors, and 3D fusion images were acquired in the remaining 26 patients. Our results did not suggest that relative malapposition was associated with vessel diameter (P = 0.12), vessel diameter discrepancy (P = 0.60), or syphon angle (P = 0.34), but relative malapposition increased by an estimated 13% (95% confidence interval: 4%-23%, P = 0.006) for each 1 mm increase in FD diameter. Inter-rater and intermethod agreements for apposition measurements were excellent and good, respectively. CONCLUSIONS: Three-dimensional fusion images provided clear visualization of structures of both the stent and parent artery with excellent diagnostic reliability. Careful deployment may be needed for FDs with larger diameters, as they tended to have larger relative malapposition.

Comparison of Clinical Outcomes After Stent-Assisted Coiling with 3 Types of Self-Expanding Laser-Cut Stents in Patients with Wide-Necked Intracranial Aneurysms.

OBJECTIVE: We report the clinical outcomes of stent-assisted coiling for wide-necked intracranial aneurysms using 3 low-profile laser-cut stents and compare the results according to stent type. METHODS: All patients treated with stent-assisted coiling for their intracranial aneurysms at our hospital between July 2010 and September 2019 were reviewed. We selected patients with Enterprise, Neuroform EZ, or Neuroform Atlas stents who underwent imaging follow-up and investigated aneurysm and stent features, stent-related complications, recanalization, and retreatment rates. We compared the retreatment risk among the patients treated with the 3 stent types using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: We evaluated 364 consecutive cases (103 Enterprise, 105 Neuroform EZ, and 156 Neuroform Atlas stents). Neuroform Atlas was more frequently used in distal vessels: 8 (7.8%) Enterprise, 2 (1.9%) Neuroform EZ, and 41 (26.3%) Neuroform Atlas cases, respectively. The median follow-up durations were 6.49, 4.91, and 1.24 years for the Enterprise, Neuroform EZ, and Neuroform Atlas cases, respectively, and retreatment was performed in 11 (10.1%), 9 (8.6%), and 6 (3.8%) cases. In the first 2 years of follow-up, the estimated retreatment risk ratios for Neuroform EZ and Neuroform Atlas with Enterprise as reference were 0.63 (95% confidence interval, 0.24-1.65; P = 0.35) and 0.54 (95% confidence interval, 0.18-1.59; P = 0.26), respectively. CONCLUSIONS: Neuroform Atlas stents were more frequently deployed in small-caliber vessels compared with the other 2 types of stents. The complication rate and retreatment risk until at least 1 year after the aneurysm treatment appeared to be similar for the 3 stent types.

Fragmentation of calcified plaque after carotid artery stenting in heavily calcified circumferential stenosis.

INTRODUCTION: We assessed the morphological change of calcified plaque after carotid artery stenting (CAS) in vessels with heavily calcified circumferential lesions and discuss the possible mechanisms of stent expansion in these lesions. METHODS: We performed 18 CAS procedures in 16 patients with severe carotid artery stenosis accompanied by plaque calcification involving more than 75% of the vessel circumference. All patients underwent multidetector-row computed tomography (MDCT) to evaluate lesion calcification before and within 3 months after intervention. The angiographic outcome immediately after CAS and follow-up angiographs obtained 6 months post-CAS were examined. RESULTS: The preoperative mean arc of the calcifications was 320.1 +/- 24.5 degrees (range 278-360 degrees ). In all lesions, CAS procedures were successfully carried out; excellent dilation with residual stenosis

Preoperative Light Transmission Aggregometry Values Predict for Thromboembolic Complications After Stent-Assisted Coil Embolization.

OBJECTIVE: Risk control of thromboembolic complications (TECs) during stent-assisted coil embolization (SACE) for unruptured intracranial aneurysms (UIAs) is crucial for satisfactory treatment outcomes. We retrospectively evaluated the data from our cohort of SACE for UIAs to analyze the role of anatomical, clinical, and stent type-related factors to determine the optimal preoperative values of light transmission aggregometry (LTA) for TEC prevention. METHODS: From July 2015 to May 2018, we retrospectively analyzed the data from 132 patients with SACE-treated UIAs at our hospital. Data regarding the aneurysm location, maximum diameter, stent type used, preoperative LTA value, and ischemic and hemorrhagic complications were collected. Aspirin 100 mg and clopidogrel 75 mg were started 7 days before surgery, with a "boost" dose (an additional 75 mg of clopidogrel for an LTA value >60%) added after August 2016 to address clopidogrel resistance. After multivariate analysis, we developed our original combined parameter termed the thromboembolic predictor (TEP). Receiver operating characteristic (ROC) analysis for TEP and each significant variable was performed. RESULTS: TECs were confirmed in 5 of the 132 patients (3.8%) and hemorrhagic complications in 9 of the 132 patients (6.8%). From the multivariate analysis results, the LTA value and maximum diameter were chosen as significant variables and included in the TEP. ROC analysis of the LTA value revealed a sensitivity and specificity of 0.866 and 0.600, respectively (area under the curve, 0.747), with a cutoff of 62%. TEP permitted the establishment of an optimal LTA value according to the aneurysm maximum diameter to predict for TECs. The complication rate for the Neuroform EZ, Enterprise, Neuroform Atlas, and LVIS stents was 2.9%, 10.5%, 1.4%, and 14.3%, respectively. CONCLUSIONS: The preoperative LTA value contributes to the prediction of TECs after SACE for UIAs. The TEP (relating the LTA cutoff to aneurysm size) allows for improved antiplatelet therapy adjustment before SACE to reduce TECs.

Identification of Metal-Binding Peptides and Their Conjugation onto Nanoparticles of Superparamagnetic Iron Oxides and Liposomes.

Metallic materials are used for clinical medical devices such as vascular stents and coils to treat both ischemic and hemorrhagic vascular diseases. An antiplatelet drug is required to avoid thromboembolic complication until metallic surface is covered with a neo-endothelial cell layer. It is important to identify endothelial cell coverage on the metallic surface. However, it is difficult since there are no selective ligands. Here, we used the phage display method to identify peptide ligands that had high affinity for the metallic surface of Ni-Ti stents, Pt-W coils, and Co-Cr stents. The binding assay using fluorescence labeling revealed that several synthetic peptides could bind onto those surfaces. We also chose some oligopeptides for the conjugation onto superparamagnetic iron oxide (SPIO) nanoparticles and liposome-encapsulating SPIO nanoparticles and studied their ability to bind to the stent and coils. By SEM and fluorophotometry, we found that those modified SPIOs and liposomes were selectively bound onto those surfaces. In addition, both treated stents and coils could be detected by magnetic resonance imaging due to the magnetic artifact through the SPIOs and liposomes that were immobilized onto the surface. Thus, we identified metal-binding peptides which may enable to stop antiplatelet therapy after vascular stenting or coiling.

Visualization of stent apposition after stent-assisted coiling of intracranial aneurysms using high resolution 3D fusion images acquired by C-arm CT.

PURPOSE: We used an imaging technique based on 3-dimensional (3D) C-arm CT to assess the apposition of three types of stents after coiling of intracranial aneurysms. METHODS: All patients with intracranial aneurysms were considered who received stent-assisted coiling with Enterprise2, Neuroform EZ, or Neuroform Atlas stents confirmed by C-arm CT imaging at our institution between June 2015 and November 2017. A 3D digital subtraction angiography (DSA) scan for vessel imaging followed by a high-resolution cone beam CT (HR-CBCT) scan for coil and stent imaging was performed. The images were fused to obtain dual volume 3D fusion images. We investigated malapposition of the stent trunk (crescent sign) and of the stent edges (edge malapposition) and used the χ2 statistic to test for an association with stent types. Inter-rater agreement between two raters was estimated using Cohen's kappa statistics. RESULTS: We evaluated 75 consecutive cases. Enterprise2 stents were used in 22 cases, Neuroform EZ in 26, and Neuroform Atlas in 27 cases. By stent type, crescent sign was detected in 27% of Enterprise2, 8% of Neuroform EZ, and none of Neuroform Atlas stents (p=0.007), while edge malapposition was detected in 27% of Enterprise2, 58% of Neuroform EZ, and 30% of Neuroform Atlas stents (p=0.05). Excellent (κ=0.81) and good (κ=0.78) agreement between the raters was found for the detection of edge apposition and crescent sign, respectively. CONCLUSION: Stent malapposition was clearly visualized by dual volume 3D imaging. The Neuroform Atlas stents showed good apposition even in vessels with strong curvature.

Combination of high-resolution cone beam computed tomography and metal artefact reduction software: a new image fusion technique for evaluating intracranial stent apposition after aneurysm treatment.

We introduce a new imaging technique to improve visualisation of stent apposition after endovascular treatment of brain aneurysms employing high-resolution cone beam CT and three-dimensional digital subtraction angiography. After performing a stent-assisted coil embolisation of brain aneurysm, the image datasets were processed with a metal artefact reduction software followed by the automated image fusion programmes. Two patients who underwent aneurysm coiling using a Neuroform stent were evaluated. The reconstructed 3D images showed a detailed structure of the stent struts and identified malappositions of the deployed stents. Case 1 showed good apposition on the outer curvature side of the carotid siphon, while the inner curvature side showed prominent malapposition. Case 2, with multiple aneurysms, showed good apposition on both outer and inner curvature sides, although inward prolapse of the struts was observed. This new imaging technique may help evaluate stent apposition after the endovascular aneurysm treatment.

Modification of human MSC surface with oligopeptide-PEG-lipids for selective binding to activated endothelium.

Promising cell therapies using mesenchymal stem cells (MSCs) is proposed for stroke patients. Therefore, we aimed to efficiently accumulate human MSC (hMSC) to damaged brain area to improve the therapeutic effect using poly(ethylene glycol) (PEG)-conjugated phospholipid (PEG-lipid) carrying an oligopeptide as a ligand, specific for E-selectin which is upregulated on activated endothelial cells under hypoxia-like stroke. Here we synthesized E-selectin-binding oligopeptide (ES-bp) conjugated with PEG spacer having different molecular weights from 1 to 40 kDa. We found that ES-bp can be immobilized onto the hMSC surface through PEG-lipid without influence on cell growth and differentiation into adipocytes and osteocytes, respectively. It is also possible to control the immobilization of ES-bp on hMSC surface (<108 ES-bp per cell). Immobilized ES-bp can be continuously immobilized at the outside of cell membrane when PEG-lipids with PEG 5 and 40 kDa were used. In addition, the modified hMSC can specifically attach onto E-selectin-immobilized surface as a model surface of activated endothelium in human blood, indicating the sufficient number of immobilized ES-bp onto hMSC. Thus, this technique is one of the candidates for hMSC accumulation to cerebral infarction area. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1779-1792, 2019.

Intraprocedural plaque protrusion resulting in cerebral embolism during carotid angioplasty with stenting.

An 82-year-old man with an asymptomatic left high-grade carotid stenosis was treated with carotid artery stenting (CAS) under distal protection. The procedure consisted with predilation with a 5 x 40 mm percutaneous transluminal angioplasty (PTA) balloon, deployment of a 10 x 20 mm self-expandable stent, post-dilation with a 7 x 20 mm PTA balloon, and aspiration of debris with 60 ml of blood. The cervical carotid angiogram immediately after deflation of the distal blocking balloon demonstrated a small in-stent filling defect of the contrast medium that protruded from the anterior wall of the carotid artery. The following cranial carotid angiogram showed abrupt occlusion of the left middle cerebral artery (MCA). Because the in-stent lesion had vanished in the repeat study after recognition of this embolic event, it was suggested that an embolus had been liberated from the in-stent lesion, reaching the left MCA and obliterating it. In this case, the embolus was speculated to originate in the ruptured plaque, which protruded into the stent through the cells of the device and became liberated into the bloodstream. Attention should be paid so as not to overlook any plaque protrusion, which may be seen subsequently as a cerebral embolism on the angiogram obtained immediately after CAS.

Ischemic Stroke Detection by Analyzing Heart Rate Variability in Rat Middle Cerebral Artery Occlusion Model.

Although early reperfusion therapy is effective for acute ischemic stroke, limited therapeutic time-window resulted in only 10% of patients receiving reperfusion therapy. A fast and reliable stroke detection method is desired so that patients can receive early reperfusion therapy. It has been reported that ischemic stroke affects heart rate variability (HRV), which reflects activities of the autonomic nervous function. Thus, ischemic stroke may be detected at an acute stage through monitoring HRV. This paper proposes an HRV-based ischemic stroke detection algorithm by using multivariate statistical process control (MSPC), which is a well-known anomaly detection algorithm. As a feasibility study before collecting a large amount of clinical data from human patients, this paper used the middle cerebral artery occlusion (MCAO) model in rats for collecting HRV data shortly after ischemic stroke onsets. The 11 MCAO-operated rats and 11 sham-operated rats were prepared, and HRV data of three sham-operated rats were used for model construction. The data on the other 19 rats were used for its validation. The experimental result showed that sensitivity and specificity of the proposed algorithm were 82% and 75%, respectively. Thus, the present work shows the possibility of realizing an HRV-based ischemic stroke detection system for human patients.

Spasm induced by protection balloon during carotid artery stenting.

PURPOSE: The PercuSurge system is a distal balloon embolic protection device used for carotid artery stenting (CAS). We performed a retrospective study on the prognosis and clinical effects of spasms induced by the PercuSurge GuardWire system (PercuSurge-induced spasm). MATERIALS AND METHODS: We performed CAS in 118 carotid stenoses using the PercuSurge system. Of the 118 procedures, 31 (26.3%) of the patients experienced PercuSurge-induced spasm, and all underwent postoperative follow-up studies by cerebral angiography and antiplatelet treatment. RESULTS: On follow-up angiograms obtained a mean of 5.2 months (range 3-10 months) after CAS, all 31 PercuSurge-induced spasms had disappeared, and no delayed stenosis was found at the sites where the spasms had occurred. No ischemic events due to the spasms occurred during a mean follow-up of 13 months (range 3-32 months). CONCLUSION: In the hands of physicians experienced in endovascular surgery, CAS using the PercuSurge system is a safe method with which to treat patients with carotid stenosis. Our study demonstrated that PercuSurge-induced spasms had no morphological or clinical adverse effects.