Yasuyuki Umeda

Low Wall Shear Stress Is Independently Associated With the Rupture Status of Middle Cerebral Artery Aneurysms

Background and Purpose— We determined which hemodynamic parameter independently characterizes the rupture status of middle cerebral artery (MCA) aneurysms using computational fluid dynamics analysis. Methods— In 106 patient-specific geometries of MCA aneurysms (43 ruptured, 63 unruptured), morphological and hemodynamic parameters were compared between the ruptured and unruptured groups. Multivariate logistic regression analysis was performed to determine parameters that independently characterized the rupture status of MCA aneurysms. Results— Univariate analyses showed that the aspect ratio, wall shear stress (WSS), normalized WSS, oscillatory shear index, WSS gradient, and aneurysm-formation index were significant parameters. The size of the aneurysmal dome and the gradient oscillatory number were not significantly different between the 2 groups. With multivariate analyses, only lower WSS was significantly associated with the rupture status of MCA aneurysms. Conclusions— WSS may be the most reliable parameter characterizing the rupture status of MCA aneurysms.

Using computational fluid dynamics analysis to characterize local hemodynamic features of middle cerebral artery aneurysm rupture points.

OBJECTIVE Although rupture of cerebral aneurysms typically occurs at the fragile wall at the apex or pole, some aneurysms rupture through the body or the neck. The purpose of this study was to clarify the association between aneurysm rupture points and hemodynamic features through the use of computational fluid dynamics (CFD) analysis. METHODS Twelve ruptured middle cerebral artery bifurcation aneurysms were analyzed by 3-dimensional computed tomographic angiography and CFD. Rupture points were evaluated on intraoperative videos by 3 independent neurosurgeons. Wall shear stress (WSS) was calculated at the rupture point, aneurysm dome, and parent artery. Intra-aneurysmal flow patterns were evaluated with cross-sectional velocity vector planes that included the rupture points. RESULTS The mean WSS at the rupture point (0.29 Pa) was significantly lower than that at the dome (2.27 Pa) and the parent artery (8.19 Pa) (P < .01). All rupture points were located within the area of WSS ≤ 11.2% of the WSS at the parent artery. WSS at the rupture point was correlated with the minimum WSS at the dome (r = 0.64, P < .05), but not with aneurysm size (r = 0.26) or the aspect ratio (r = 0.16). Flow patterns revealed that all rupture points were located in lower-velocity area, which was associated with complex flow patterns and/or deviating necks. CONCLUSIONS This study highlights the relationship between the local hemodynamic features and the rupture points observed during the microsurgical clipping. CFD may determine a rupture point of aneurysms using the feature of markedly low WSS.

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.

Midline Lumbar Fusion with Cortical Bone Trajectory Screw

A novel cortical bone trajectory (CBT) screw technique provides an alternative fixation technique for lumbar spine. Trajectory of CBT screw creates a caudo-cephalad path in sagittal plane and a medio-lateral path in axial plane, and engages cortical bone in the pedicle. The theoretical advantage is that it provides enhanced screw grip and interface strength. Midline lumbar fusion (MIDLF) is composed of posterior mid-line approach, microsurgical laminectomy, and CBT screw fixation. We adopted the MIDLF technique for lumbar spondylolisthesis. Advantages of this technique include that decompression and fusion are available in the same field, and it minimizes approach-related damages. To determine whether MIDLF with CBT screw is as effective as traditional approach and it is minimum invasive technique, we studied the clinical and radiological outcomes of MIDLF. Our results indicate that MIDLF is effective and minimum invasive technique. Evidence of effectiveness of MIDLF is that patients had good recovery score, and that CBT screw technique was safety in clinical and stable in radiological. MIDLF with CBT screw provides the surgeon with additional options for fixation. This technique is most likely to be useful for treating lumbar spondylolisthesis in combination with midline decompression and insertion of an interbody graft, such as the transforaminal lumbar interbody fusion or posterior lumbar interbody fusion techniques.

High-Risk Plaque for Carotid Artery Stenting Evaluated With 3-Dimensional T1-Weighted Gradient Echo Sequence

Background and Purpose— Preventing cerebral embolisms is a major concern with carotid artery stenting (CAS). This study evaluated 3-dimensional T1-weighted gradient echo (3D T1GRE) sequence to predict cerebral embolism related to CAS. Methods— We performed quantitative analyses of the characteristics of 47 carotid plaques before CAS by measuring the signal intensity ratio (SIR) and plaque volume using 3D T1GRE images. We used T1-weighted turbo field echo sequence to obtain 3D T1GRE images. We also evaluated diffusion-weighted images (DWI) of the brain before and after CAS to detect ischemic lesions (DWI lesions) from cerebral emboli. Results— SIR (2.17 [interquartile range 1.50–3.07] versus 1.35 [interquartile range 1.08–1.97]; P=0.010) and plaque volume (456 mm3 [interquartile range 256–696] versus 301 mm3 [interquartile range 126–433]; P=0.008) were significantly higher in the group of patients positive for DWI lesions (P-group: n=26) than DWI lesion-negative patients (N-group: n=21). In multivariate logistic regression analysis, SIR (P=0.007) and plaque volume (P=0.042) were independent predictors of DWI lesions with CAS. Furthermore, SIR (rs=0.42, P=0.005) and plaque volume (rs=0.36, P=0.012) were positively correlated with the number of DWI lesions. From analysis of a receiver-operating characteristic curve, the most reliable cutoff values of SIR and plaque volume to predict DWI lesions related to CAS were 1.80 and 373 mm3, respectively. Conclusions— Quantitative evaluation of carotid plaques using 3D T1GRE images may be useful in predicting cerebral embolism related to CAS.

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.

Stagnation and complex flow in ruptured cerebral aneurysms: a possible association with hemostatic pattern.

OBJECT Histopathological examination has revealed that ruptured cerebral aneurysms have different hemostatic patterns depending on the location of the clot formation. In this study, the authors investigated whether the hemostatic patterns had specific hemodynamic features using computational fluid dynamics (CFD) analysis. METHODS Twenty-six ruptured middle cerebral artery aneurysms were evaluated by 3D CT angiography and harvested at the time of clipping. The hemostatic patterns at the rupture points were assessed by means of histopathological examination, and morphological parameters were obtained. Transient analysis was performed, and wall shear stress-related hemodynamic parameters and invariant Q (vortex core region) were calculated. The morphological and hemodynamic parameters were compared among the hemostatic patterns. RESULTS Hematoxylin and eosin staining of the aneurysm wall showed 13 inside-pattern, 9 outside-pattern, and 4 other-pattern aneurysms. Three of the 26 aneurysms were excluded from further analysis, because their geometry models could not be generated due to low vascular CT values. Mann-Whitney U-tests showed that lower dome volume (0.04 cm3 vs 0.12 cm3, p = 0.014), gradient oscillatory number (0.0234 vs 0.0289, p = 0.023), invariant Q (-0.801 10-2/sec2 vs -0.124 10-2/sec2, p = 0.045) and higher aneurysm formation indicator (0.986 vs 0.963, p = 0.041) were significantly related to inside-pattern aneurysms when compared with outside-pattern aneurysms. CONCLUSIONS Inside-pattern aneurysms may have simpler flow patterns and less flow stagnation than outside-pattern aneurysms. CFD may be useful to characterize the hemostatic pattern of ruptured cerebral aneurysms.

Preventive effects of cilostazol against the development of shunt-dependent hydrocephalus after subarachnoid hemorrhage

OBJECTIVE Chronic hydrocephalus develops in association with the induction of tenascin-C (TNC), a matricellular protein, after aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to examine if cilostazol, a selective inhibitor of phosphodiesterase Type III, suppresses the development of chronic hydrocephalus by inhibiting TNC induction in aneurysmal SAH patients. METHODS The authors retrospectively reviewed the factors influencing the development of chronic shunt-dependent hydrocephalus in 87 patients with Fisher Grade 3 SAH using multivariate logistic regression analyses. Cilostazol (50 or 100 mg administered 2 or 3 times per day) was administered from the day following aneurysmal obliteration according to the preference of the attending neurosurgeon. As a separate study, the effects of different dosages of cilostazol on the serum TNC levels were chronologically examined from Days 1 to 12 in 38 SAH patients with Fisher Grade 3 SAH. RESULTS Chronic hydrocephalus occurred in 12 of 36 (33.3%), 5 of 39 (12.8%), and 1 of 12 (8.3%) patients in the 0 mg/day, 100 to 200 mg/day, and 300 mg/day cilostazol groups, respectively. The multivariate analyses showed that older age (OR 1.10, 95% CI 1.13-1.24; p = 0.012), acute hydrocephalus (OR 23.28, 95% CI 1.75-729.83; p = 0.016), and cilostazol (OR 0.23, 95% CI 0.05-0.93; p = 0.038) independently affected the development of chronic hydrocephalus. Higher dosages of cilostazol more effectively suppressed the serum TNC levels through Days 1 to 12 post-SAH. CONCLUSIONS Cilostazol may prevent the development of chronic hydrocephalus and reduce shunt surgery, possibly by the inhibition of TNC induction after SAH.

A Case of Moyamoya Disease with a Transient Neurologic Deterioration Associated with Subcortical Low Intensity on Fluid-Attenuated Inversion Recovery Magnetic Resonance Images After Bypass Surgery

BACKGROUND Moyamoya disease often is treated by revascularization surgery. In this report, we are the first to describe a case of moyamoya disease that repeatedly showed a transient subcortical low intensity (SCLI) on fluid-attenuated inversion recovery (FLAIR) magnetic resonance images postoperatively. CASE DESCRIPTION A 59-year-old woman presenting with repeated transient ischemia underwent right superficial temporal artery to middle cerebral artery anastomosis with encephalo-duro-myo-synangiosis. After the operation, the patient had a transient neurologic deterioration. Findings on magnetic resonance imaging were not particular apart from SCLI and sulcal hyperintensity on FLAIR images, but no abnormalities in cerebral blood flow on single-photon emission computed tomography with N-isopropyl [123I]-p-iodoamphetamine and no abnormalities on electroencephalogram were found. Symptoms improved in a few days, and SCLI on FLAIR images disappeared in a few months. Thereafter, when the left-sided bypass surgery was performed, similar findings occurred in the left cerebral hemisphere. CONCLUSIONS The mechanisms of transient SCLI on FLAIR images remain unclear, but this finding appears to be associated with a postoperative transient neurologic deterioration.

Hemodynamic characteristics of hyperplastic remodeling lesions in cerebral aneurysms

Background & purpose Hyperplastic remodeling (HR) lesions are sometimes found on cerebral aneurysm walls. Atherosclerosis is the results of HR, which may cause an adverse effect on surgical treatment for cerebral aneurysms. Previous studies have demonstrated that atherosclerotic changes had a correlation with certain hemodynamic characteristics. Therefore, we investigated local hemodynamic characteristics of HR lesions of cerebral aneurysms using computational fluid dynamics (CFD). Methods Twenty-four cerebral aneurysms were investigated using CFD and intraoperative video recordings. HR lesions and red walls were confirmed on the intraoperative images, and the qualification points were determined on the center of the HR lesions and the red walls. The qualification points were set on the virtual operative images for evaluation of wall shear stress (WSS), normalized WSS (NWSS), oscillatory shear index (OSI), relative residence time (RRT), and aneurysm formation indicator (AFI). These hemodynamic parameters at the qualification points were compared between HR lesions and red walls. Results HR lesions had lower NWSS, lower AFI, higher OSI and prolonged RRT compared with red walls. From analysis of the receiver-operating characteristic curve for hemodynamic parameters, OSI was the most optimal hemodynamic parameter to predict HR lesions (area under the curve, 0.745; 95% confidence interval, 0.603–0.887; cutoff value, 0.00917; sensitivity, 0.643; specificity, 0.893; P<0.01). With multivariate logistic regression analyses using stepwise method, NWSS was significantly associated with the HR lesions. Conclusions Although low NWSS was independently associated with HR lesions, OSI is the most valuable hemodynamic parameter to distinguish HR lesions from red walls.