Kazuhide Hamada

Development of Nanofiber-Covered Stents Using Electrospinning: In Vitro and Acute Phase In Vivo Experiments

There are some technical difficulties in treating for a broad necked aneurysm and a higher incidence of recurrence. Because of these drawbacks, more innovative techniques for superior endovascular reconstructive treatment are required. We developed a novel covered stent employing electrospinning to deposit fine polyurethane (PU) fibers onto stents. An in vitro water leak test was designed and applied prior to animal testing to estimate the performance of covered stents and to determine the appropriate amount of PU fibers on a stent. Two tenths of a milligram of PU fibers proved to be sufficient to prevent water leakage. Then, the efficacy of the covered stents to that of bare stents was compared using 10 rabbits in which model aneurysms had been formed at the right common carotid artery by the elastase method. Angiographic evaluation on day 1 posttreatment (acute phase) revealed complete occlusion of the aneurysms and the patency of the parent arteries in animals treated with covered stents. At 10 days poststenting (subacute phase), the aneurysm neck was completely covered with neointimal layer as shown by scanning electron microscopic examination. The PU-covered stent holds promise as a device for treating cerebral aneurysms.

Inflammatory Biomarkers in Atherosclerosis: Pentraxin 3 Can Become a Novel Marker of Plaque Vulnerability

Inflammation is crucially involved in the development of carotid plaques. We examined the relationship between plaque vulnerability and inflammatory biomarkers using intraoperative blood and tissue specimens. We examined 58 patients with carotid stenosis. Following carotid plaque magnetic resonance imaging, 41 patients underwent carotid artery stenting (CAS) and 17 underwent carotid endarterectomy (CEA). Blood samples were obtained from the femoral artery (systemic) and common carotid artery immediately before and after CAS (local). Seventeen resected CEA tissue samples were embedded in paraffin, and histopathological and immunohistochemical analyses for IL-6, IL-10, E-selectin, adiponectin, and pentraxin 3 (PTX3) were performed. Serum levels of IL-6, IL-1β, IL-10, TNFα, E-selectin, VCAM-1, adiponectin, hs-CRP, and PTX3 were measured by multiplex bead array system and ELISA. CAS-treated patients were classified as stable plaques (n = 21) and vulnerable plaques (n = 20). The vulnerable group showed upregulation of the proinflammatory cytokines (IL-6 and TNFα), endothelial activation markers (E-selectin and VCAM-1), and inflammation markers (hs-CRP and PTX3) and downregulation of the anti-inflammatory markers (adiponectin and IL-10). PTX3 levels in both systemic and intracarotid samples before and after CAS were higher in the vulnerable group than in the stable group. Immunohistochemical analysis demonstrated that IL-6 was localized to inflammatory cells in the vulnerable plaques, and PTX3 was observed in the endothelial and perivascular cells. Our findings reveal that carotid plaque vulnerability is modulated by the upregulation and downregulation of proinflammatory and anti-inflammatory factors, respectively. PTX3 may thus be a potential predictive marker of plaque vulnerability.

Usefulness of arterial spin-labeling images in periictal state diagnosis of epilepsy

PURPOSE Arterial spin-labeling (ASL) perfusion MRI, a noninvasive method of assessing cerebral blood flow, is becoming a diagnostic tool of epilepsy. This study was undertaken to evaluate the diagnostic validity of ASL in patients with status epilepticus (SE) in a periictal state. METHOD Twenty cases with SE were studied. Patients were imaged at a 3T MRI including ASL and diffusion-weighted imaging (DWI), and were also examined using electroencephalography (EEG). The abnormal findings of ASL were compared with those obtained from DWI and EEG. RESULT Focal hyperperfusion was found in the cortical territory of 13 cases (65%). In 10 of those 13 cases, the ASL hyperperfusion region corresponded to DWI high intensity and EEG abnormality. Two cases showed hyperperfusion corresponding to EEG abnormalities in ASL despite the absence of high intensity in DWI. The remaining single case showed hyperperfusion in ASL despite the absence of high intensity in DWI and EEG abnormalities. Hyperperfusion in the subcortical territory was observed in the ipsilateral thalamus in three cases and in the contralateral cerebellum in one case. CONCLUSION Our results suggest that ASL is a useful tool to diagnose status epilepticus and localization of the epilepsy focus.

Novel Dynamic Four-Dimensional CT Angiography Revealing 2-Type Motions of Cerebral Arteries

Background and Purpose— We developed a novel dynamic 4-dimensional CT angiography to accurately evaluate dynamics in cerebral aneurysm. Methods— Dynamic 4-dimensional CT angiography achieved high-resolution 3-dimensional imaging with temporal resolution in a beating heart using dynamic scanning data sets reconstructed with a retrospective simulated R-R interval reconstruction algorithm. Results— Movie artifacts disappeared on dynamic 4-dimensional CT angiography movies of 2 kinds of stationary phantoms (titanium clips and dry bone). In the virtual pulsating aneurysm model, pulsation on the dynamic 4-dimensional CT angiography movie resembled actual movement in terms of pulsation size. In a clinical study, dynamic 4-dimensional CT angiography showed 2-type motions: pulsation and anatomic positional changes of the cerebral artery. Conclusions— This newly developed 4-dimensional visualizing technique may deliver some clues to clarify the pathophysiology of cerebral aneurysms.

STA-MCA Bypass for the Treatment of Ischemic Stroke

It is considered controversial whether superficial temporal artery (STA)-middle cerebral artery (MCA) bypass affects the outcome of patients with ischemic stroke. This prospective study was undertaken to demonstrate the effect of STA-MCA bypass on the cerebral blood flow and neurological status of the patients with ischemic stroke. Seventy-five patients underwent unilateral or bilateral STA-MCA bypass surgery. The selection of the patients closely adhered to the criteria of the Japan EC-IC Bypass Trial (JET). Cerebral blood flow (CBF) before and after Diamox administration was measured by single photon emission computed tomography (SPECT) using iodine-123-N-isopropyl-p-iodoamphetamine (IMP). MRI, contrast-enhanced 3D CT scans, and angiography were performed on each patient pre- and postoperatively. Bypass surgery was successfully done in all patients. CBF was significantly increased after STA-MCA bypass (P < 0.05). In addition, reservation of CBF was significantly improved after STA-MCA bypass (P < 0.05). Patients with transient ischemic attack (TIA) did not experience recurrence of such episodes after STA-MCA bypass. The neurological deficit was unchanged in patients with complete stroke after bypass surgery. However, the NIH stroke scale was significantly improved after bypass surgery (P < 0.01). In addition, the satisfaction rate of treatment as assessed by the patients themselves was very high after STA-MCA bypass (>90%) compared to the conservative treatment group (<50%). STA-MCA bypass still plays a limited role in the treatment of ischemic stroke, but may become a bright hope in depressed patients after cerebral ischemia.

Aneurysm Organization Effects of Gellan Sulfate Core Platinum Coil with Tenascin-C in a Simulated Clinical Setting and the Possible Mechanism

BACKGROUND This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting. METHODS Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm-occlusion status was evaluated angiographically and histologically at 2 weeks post coiling. As each rabbit coiled aneurysm provided only 2-3 tissue slices due to technical limitations and prevented immunohistochemical evaluations, a PC, GSCC, or GSCC-TNC was randomly implanted in a rat blind-ended model (n = 3, respectively) and the organization effects were immunohistochemically evaluated for expressions of tenascin-C (TNC), transforming growth factor-beta (TGF-β), and matrix metalloproteinase-9 (MMP-9) 2 weeks later. RESULTS Coil handling was similar among the 3 kinds of coils. GSCCs showed a significantly higher ratio of organized area to the aneurysmal cavity than PCs, but GSCC-TNCs had the greatest organization-promoting effects on aneurysms (the ratio of organized area/aneurysmal luminal area: PC, 17.9 ± 7.1%; GSCC, 54.2 ± 18.3%; GSCC-TNC, 82.5 ± 5.8%). GSCC-TNCs had intense immunoreactivities for TNC, TGF-β, and MMP-9 in the organized thrombosis and tunica media. GSCCs also showed intense immunoreactivities for TNC, TGF-β, and MMP-9, although the extent was less than GSCC-TNCs. The immunoreactivities were hardly found in unorganized thrombus and the tunica media of aneurysm wall in the PC group. CONCLUSIONS This study first showed that GSCC-TNCs promote intra-aneurysmal clot organization in simulated clinical settings using rabbits possibly through the TGF-β and MMP-9 upregulation.

Simultaneous Spinal and Intracranial Chronic Subdural Hematoma Cured by Craniotomy and Laminectomy: A Video Case Report

Simultaneous spinal and intracranial chronic subdural hematoma (CSDH) is a rare entity. A 67-year-old man visited our hospital due to headache after diving into a river 2 weeks before. Non-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) revealed bilateral intracranial CSDH. The bilateral CSDH was evacuated and his symptoms improved. Three days after craniotomy, he complained of sensory disturbance on his buttocks. Lumbar MRI showed a space-occupying lesion behind the thecal sac at L5. CT with myelography showed a subdural mass lesion; there was no communication with the subarachnoid space. Fourteen days after craniotomy, L5 laminectomy was performed and the dura mater was incised carefully. The video shows that a liquid hematoma similar to the intracranial CSDH flowed out, followed by cerebrospinal fluid. His symptoms improved after the operation and the hematoma did not recur. This is a rare condition of spinal CSDH demonstrated by neuroimaging and intraoperative video.

Simple immersion of filter devices into an urokinase solution prevents fibrin net formation during carotid artery stenting

Slow-flow phenomenon is frequently observed during carotid artery stenting (CAS) with a filter embolic protection device. It results in technical difficulties and can lead to adverse neurological events. Flow impairment is thought to be caused by plaque entrapped by the filter and/or blood coagulation on the filter. Characteristics of heparin- or urokinase-treated polyurethanes were analyzed by surface plasmon resonance, and the fibrinolytic activity of the urokinase-treated filter of Angioguard XP was estimated by the fibrin plate assay. A filter membrane of Angioguard XP protection device was treated with a heparin or urokinase solution. In clinical studies, six and nine patients were treated by CAS using Angioguard XP modified with heparin and urokinase, respectively. Filter membranes were examined by scanning electron microscopy (SEM). From in vitro studies, it appeared that urokinase adsorbed and remained on the Angioguard XP filter, and its fibrinolytic activity was demonstrated even after washing with saline; heparin, however, was easily washed out from the surface. From clinical study, some filter pores were obstructed in all six patients in the heparin group and in three patients in the urokinase group. Fibrin net was found on the filter in five of six patients in the heparin group and in one of nine patients in the urokinase group. Treatment of an Angioguard XP filter with a urokinase solution is effective in preventing pore occlusion and may reduce occurrence of the slow-flow phenomenon.