Tetsuya Hashimoto

BACKGROUND: The potential heterogeneity in occlusive thrombi caused by in situ propagation by secondary thrombosis after embolic occlusion could obscure the characteristics of original thrombi, preventing the clarification of a specific thrombus signature for the etiology of ischemic stroke. We aimed to investigate the heterogeneity of occlusive thrombi by pretreatment imaging. METHODS: Among consecutive stroke patients with acute embolic anterior circulation large vessel occlusion treated with thrombectomy, we retrospectively reviewed 104 patients with visible occlusive thrombi on pretreatment non-contrast computed tomography admitted from January 2015 to December 2018. A region of interest was set on the whole thrombus on non-contrast computed tomography under the guidance of computed tomography angiography. The region of interest was divided equally into the proximal and distal segments and the difference in Hounsfield unit densities between the two segments was calculated. RESULTS: Hounsfield unit density in the proximal segment was higher than that in the distal segment (mean difference 4.45; p < 0.001), regardless of stroke subtypes. On multivariate analysis, thrombus length was positively correlated (β = 0.25; p < 0.001) and time from last-known-well to imaging was inversely correlated (β = -0.0041; p = 0.002) with the difference in Hounsfield unit densities between the proximal and distal segments. CONCLUSIONS: The difference in density between the proximal and distal segments increased as thrombi became longer and decreased as thrombi became older after embolic occlusion. This time/length-dependent thrombus heterogeneity between the two segments is suggestive of secondary thrombosis initially occurring on the proximal side of the occlusion.

BACKGROUND AND PURPOSE: Acute leptomeningeal collateral flow is vital for maintaining perfusion to penumbral tissue in acute ischemic stroke caused by large-vessel occlusion. In this study, we aimed to investigate the clinically available indicators of leptomeningeal collateral variability in embolic large-vessel occlusion. MATERIALS AND METHODS: Among prospectively registered consecutive patients with acute embolic anterior circulation large-vessel occlusion treated with thrombectomy, we analyzed 108 patients admitted from January 2015 to December 2019 who underwent evaluation of leptomeningeal collateral status on pretreatment CTA. Clinical characteristics, extent of leukoaraiosis on MR imaging, embolic stroke subtype, time of imaging, occlusive thrombus characteristics, presenting stroke severity, and clinical outcome were collected. The clinical indicators of good collateral status (>50% collateral filling of the occluded territory) were analyzed using multivariate logistic regression analysis. RESULTS: Good collateral status was present in 67 patients (62%) and associated with independent functional outcomes at 3 months. Reduced leukoaraiosis (total Fazekas score, 0-2) was positively related to good collateral status (OR, 9.57; 95% CI, 2.49-47.75), while the cardioembolic stroke mechanism was inversely related to good collateral status (OR, 0.17; 95% CI, 0.02-0.87). In 82 patients with cardioembolic stroke, shorter thrombus length (OR, 0.91 per millimeter increase; 95% CI, 0.82-0.99) and reduced leukoaraiosis (OR, 5.79; 95% CI, 1.40-29.61) were independently related to good collateral status. CONCLUSIONS: Among patients with embolic large-vessel occlusion, reduced leukoaraiosis, noncardiac embolism mechanisms including embolisms of arterial or undetermined origin, and shorter thrombus length in cardioembolism are indicators of good collateral flow.

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>BACKGROUND</jats:title> <jats:p>Appropriate thrombus-device interaction is critical for recanalization. Histology can serve as a proxy for mechanical properties, and thus inform technique selection.</jats:p> </jats:sec> <jats:sec> <jats:title>OBJECTIVE</jats:title> <jats:p>To investigate the value of histologic characterization, we conducted a systematic review and meta-analysis on the relationship between thrombus histology and recanalization, technique, etiology, procedural efficiency, and imaging findings.</jats:p> </jats:sec> <jats:sec> <jats:title>METHODS</jats:title> <jats:p>In this meta-analysis, we identified studies published between March 2010 and March 2020 reporting findings related to the histologic composition of thrombi in large vessel occlusion stroke. Studies with at least 10 patients who underwent mechanical thrombectomy using stent retriever or aspiration were considered. Only studies in which retrieved thrombi were histologically processed were included. Patient-level data were requested when data could not be directly extracted. The primary outcome assessed was the relationship between thrombus histology and angiographic outcome.</jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>A total of 22 studies encompassing 1623 patients met inclusion criteria. Clots associated with good angiographic outcome had higher red blood cell (RBC) content (mean difference [MD] 9.60%, 95% CI 3.85-15.34, P = .008). Thrombi retrieved by aspiration had less fibrin (MD −11.39, 95% CI −22.50 to −0.27, P = .046) than stent-retrieved thrombi. Fibrin/platelet-rich clots were associated with longer procedure times (MD 13.20, 95% CI 1.30-25.10, P = .037). Hyperdense artery sign was associated with higher RBC content (MD 14.17%, 95% CI 3.07-25.27, P = .027). No relationship was found between composition and etiology.</jats:p> </jats:sec> <jats:sec> <jats:title>CONCLUSION</jats:title> <jats:p>RBC-rich thrombi were associated with better recanalization outcomes and shorter procedure times, suggesting that preinterventional compositional characterization may yield important prognostic and therapeutic guidance.</jats:p> </jats:sec>

BACKGROUND: Experimental evidence that stent retriever thrombectomy (SRT) may cause arterial wall damage is increasing, although histopathologic findings focused on vessel wall injury after SRT have not fully been reported in humans. CASE DESCRIPTION: We describe an autopsy case of an 82-year-old woman who presented with acute left intracranial internal carotid artery occlusion and received SRT. When we attempted to catheterize the M1 segment of the normal middle cerebral artery (MCA), we were not aware of a duplicated MCA and advanced the microcatheter into the main MCA trunk with a smaller caliber than that of the normal M1 segment. A 6-mm Trevo thrombectomy device was deployed from the main MCA trunk but was insufficiently expanded in the MCA segment. Two passes with a Trevo resulted in failed recanalization. The patient died on postoperative day 4 because of extensive infarction. Autopsy revealed a duplicated MCA and subintimal arterial dissection in the proximal segment of the main MCA trunk. The supraclinoid internal carotid artery also revealed endothelial denudation and mural thrombus. CONCLUSIONS: We provide a histopathologic report of vessel wall injury after SRT that caused failed recanalization. Anatomic variations of the MCA should be considered when selecting suitable thrombectomy devices in order to avoid vessel wall injury.

<jats:sec><jats:title>Background and purpose</jats:title><jats:p>Vascular wall components (VWCs) are sometimes identified as collagen fibers in specimens retrieved by thrombectomy from acute stroke patients. However, their clinical significance and associated factors remain unclear. The purpose of this study was to clarify the factors associated with VWCs in retrieved thrombi.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Consecutive acute stroke patients treated endovascularly using the Penumbra aspiration catheter or stent retrievers (SRs) at our institute from November 2013 to April 2016 were retrospectively reviewed, and the retrieved thrombi were evaluated histopathologically. VWCs were defined as banded collagen fibers with a distinct boundary observed at the rim or outside of the retrieved thrombi. Factors associated with the presence of VWCs were studied.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 150 specimens (76 specimens retrieved by the Penumbra, 74 by SRs) from 101 patients (47 women, age 74.9±11.1 years) were investigated. Applied thrombectomy devices were aspiration catheters in 42 patients, SRs in 21 patients, and both in 38 patients. VWCs were observed in 24 specimens (16%) from 22 patients. A low proportion of erythrocyte components (41.7±24.8% vs 55.0±26.3%, P=0.01), a high frequency of the devices reaching the M2/P2 (75% vs 50%, P=0.02), and a high number of device passages (P for trend=0.02) were associated with VWC positive thrombi. Successful recanalization (Treatment in Cerebral Ischemia ≥2b) tended to be less frequent in patients with VWC positive thrombi than in those without (73% vs 89%, P=0.06).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The histopathology of occlusive thrombi, arterial sites where devices reached, and number of device passages, might affect the presence of VWCs in retrieved thrombi.</jats:p></jats:sec>

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is known to be a rare but devastating complication of carotid artery revascularization. Because patients with acute ischemic stroke due to acute major cerebral and/or cervical artery occlusion treated with endovascular reperfusion therapy may have impaired autoregulation in the cerebral vasculature, these patients may also develop CHS. Despite the growing number of endovascular reperfusion procedures for acute ischemic stroke, this complication has only rarely been reported. CASE DESCRIPTION: A 77-year-old man developed acute cerebral infarction as the result of occlusions of the right internal carotid artery and right middle cerebral artery. After systemic intravenous injection of recombinant tissue-type plasminogen activator, endovascular reperfusion therapy was initiated. The occluded arteries were successfully recanalized with thrombectomy by using a stent retriever for the middle cerebral artery and stent placement for the origin of the internal carotid artery. However, head computed tomography obtained 12 hours after treatment showed acute intracranial hemorrhage that did not involve the ischemic lesions. Under evaluation with transcranial near-infrared spectroscopy and single-photon emission computed tomography, the hemorrhage was considered to have been caused by CHS after reperfusion therapy. CONCLUSIONS: CHS may lead to unfavorable outcomes after reperfusion therapy for acute ischemic stroke. Recognizing clinical deterioration caused by CHS can be challenging in patients with neurologic disorders of acute ischemic stroke. Therefore, it is important to perform routine monitoring of regional cerebral oxygen saturation by using near-infrared spectroscopy, perform single-photon emission computed tomography promptly to evaluate cerebral blood flow, and maintain strict antihypertensive therapy to prevent CHS after reperfusion therapy.

OBJECTIVE: 11C-Pittsburgh compound-B (11C-PIB) positron emission tomography (PET) is used to visualize and quantify amyloid deposition in the brain cortex in pathological conditions such as Alzheimer's disease (AD). Intense 11C-PIB retention is also observed in the white matter (WM) of both healthy individuals and AD patients. However, the clinical implications of this retention in brain WM have not been clarified. We investigated the relationship between the extent of white matter lesions (WMLs) and the binding potential of 11C-PIB (BPND) in the WM in patients with hypertensive small vessel disease. We further examined the relationship between the extent of WMLs and BPND in WML and in normal-appearing white matter (NAWM). METHODS: Twenty-one hypertensive vasculopathy patients, without AD and major cerebral arterial stenosis and/or occlusion, were enrolled (9 women, 68 ± 7 years). Regions of WML and NAWM were extracted using magnetization-prepared rapid gradient-echo and fluid-attenuated inversion recovery of magnetic resonance images. Volumes of interest (VOIs) were set in the cortex-subcortex, basal ganglia, and centrum semiovale (CS). BPND in the cortex-subcortex, basal ganglia, CS, WML, and NAWM were estimated on 11C-PIB PET using Logan graphical analysis with cerebellar regions as references. The relationships between WML volume and BPND in each region were examined by linear regression analysis. RESULTS: BPND was higher in the CS and basal ganglia than in the cortex-subcortex regions. WML volume had a significant inverse correlation with BPND in the CS (Slope = -0.0042, R 2  = 0.44, P < 0.01). For intra WM comparison, BPND in NAWM was significantly higher than that in WML. In addition, although there were no correlations between WML volume and BPND in WML, WML volume was significantly correlated inversely with BPND in NAWM (Slope = -0.0017, R 2  = 0.26, P = 0.02). CONCLUSIONS: 11C-PIB could be a marker of not only cortical amyloid-β deposition but also WM injury accompanying the development of WMLs in hypertensive small vessel disease.

<jats:sec> <jats:title>Background and Purpose—</jats:title> <jats:p>Histopathologic evaluation of occlusive thrombi retrieved from cerebral arteries using endovascular therapy is possible. We investigated the relationship between successful reperfusion after thrombectomy and histopathologic characteristics of retrieved thrombi.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods—</jats:title> <jats:p>Among consecutive patients with acute ischemic stroke treated with endovascular therapy at our institute from December 2010 to July 2015, we retrospectively reviewed those with acute major arterial occlusion from which retrieved thrombi were evaluated histopathologically. Obtained thrombi were assessed for the existence of atheromatous gruel, organization, and the ratios of erythrocyte and fibrin/platelet components. Successful reperfusion was defined as the modified Treatment in Cerebral Ischemia grade of 2b to 3.</jats:p> </jats:sec> <jats:sec> <jats:title>Results—</jats:title> <jats:p> Of 83 patients studied, 58 (70%) underwent successful reperfusion. Atheromatous gruel was less frequently identified (3% versus 20%; <jats:italic>P</jats:italic> =0.024), and the proportion of erythrocyte components was higher (57±23% versus 47±24%; <jats:italic>P</jats:italic> =0.042) in thrombi retrieved from the reperfused than the unreperfused group. On multivariate logistic regression analysis, atheromatous gruel was inversely related (odds ratio, 0.062; 95% confidence interval, 0.002–0.864), and &gt;64% erythrocyte components (cutoff obtained from receiver operating characteristic curve) were positively related (odds ratio, 4.352; 95% confidence interval, 1.185–19.363) to successful reperfusion. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions—</jats:title> <jats:p>Successful reperfusion could be associated with the histopathology of occlusive thrombi, including the existence of atheromatous gruel and proportion of erythrocyte components.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial Registration—</jats:title> <jats:p> URL: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">http://www.clinicaltrials.gov</jats:ext-link> . Unique identifier: NCT02251665. </jats:p> </jats:sec>

OBJECTIVE: Cerebral microbleeds (CMBs), probably reflecting microangiopathy, have not yet sufficiently been examined in association with cerebral blood flow (CBF) and metabolism. We investigated the relationships between CMBs, and CBF and metabolism in symptomatic small vessel disease. METHODS: We enrolled 22 patients with symptomatic small vessel disease without severe stenosis (>50 %) in major cerebral arteries. Volumes of white matter lesions (WMLs) and number of CMBs were assessed on images of fluid-attenuated inversion recovery and gradient-echo T2*-weighted magnetic resonance imaging, respectively. Patients were divided into two groups according to the median number of CMBs (group I <5, n = 10; group II ≥5, n = 12). Parametric images of CBF, cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction and cerebral blood volume were estimated using positron emission tomography and (15)O-labeled gases. The functional values in the cortex-subcortex, basal ganglia, and centrum semiovale were compared between the two groups. RESULTS: Volumes of WMLs of group II were larger than those of group I (median: 38.4; range: 25.1-91.5 mL vs. median: 11.3; range: 4.2-73.4 mL, p = 0.01). In the centrum semiovale, the mean CBF of group II was significantly lower than that of group I (12.6 ± 2.6 vs. 15.6 ± 3.3 mL/100 g/min, p = 0.04). In the other regions, there were no significant differences in either CBF or CMRO2 between the two groups. CONCLUSIONS: Our study indicated that increases in the number of CMBs with larger volumes of WMLs were associated with cerebral ischemia in the deep white matter in patients with symptomatic small vessel disease.