Inflammatory Biomarkers and Intracranial Hemorrhage after Endovascular Thrombectomy.

BACKGROUND: Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage - more specifically, inflammatory biomarkers present in baseline serology. METHODS: We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor. RESULTS: Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage). CONCLUSION: Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.

Arteries of the Lower Limb-Embryology, Variations, and Clinical Significance.

OBJECTIVES: The purpose of this article is to review the embryology of the lower limb arterial anatomy along with common variants and their clinical relevance. DESIGN: Embryologic variations of the lower limb arterial system may be explained by i.) persistence of primordial arterial segments, ii.) abnormal fusion, iii.) segmental hypoplasia/absence, or a combination of both. Persistent sciatic artery, corona mortis, and popliteal entrapment syndrome will also be discussed with associated symptoms, and potential complications. CONCLUSION: Knowledge of these variations is essential for surgical and endovascular management as failure to recognize them can result in complications.

Conservative management of type 1A endoleaks at completion angiogram in endovascular repair of infra-renal abdominal aortic aneurysms with current generation stent grafts.

PURPOSE: Proximal type 1A endoleaks on completion intra-operative angiography are not infrequently seen following endovascular abdominal aneurysm repair (EVAR). The natural course of these leaks is not well established. We sought to determine the rate of spontaneous resolution and a conservative treatment approach to these endoleaks. METHODS: All cases involving endovascular repairs of infra-renal abdominal aortic aneurysms resulting in proximal type 1A endoleak on final intra-operative completion angiography were retrospectively reviewed from 1 April 2010 and 30 March 2015. Demographic, pre and post-procedural imaging, and clinical outcomes were reviewed. Summarizing descriptive statistics are reported. RESULTS: Of the 337 patients who underwent an EVAR, 24 patients (7.1%) had a proximal type 1A endoleak on final intra-operative angiography. Twenty-two of 24 patients (92%) with proximal type 1A endoleaks had spontaneous resolution on follow-up imaging without any intervention, while two (8%) patients had a persistent endoleak. One of these patients required intervention. The median follow-up for patients with resolved endoleaks was 2.5 years vs. 4 and 6 years, respectively, for patients that did not resolve spontaneously. CONCLUSION: A conservative approach may be used in the management of patients with proximal type 1A endoleaks on completion angiography once maximum proximal seal was achieved intra-operatively as the vast majority of these leaks spontaneously seal.

Collateral Scoring on CT Angiogram Must Evaluate Phase and Regional Pattern.

PURPOSE: We measured anterior cerebral artery (ACA)-middle cerebral artery (MCA) and posterior cerebral artery (PCA)-MCA pial filling on single-phase computed tomography angiograms (sCTAs) in acute ischemic stroke and correlate with the CTA-based Massachusetts General Hospital (MGH) and digital subtraction angiography (DSA)-based American Society of Interventional and Therapeutic Neuroradiology (ASITN) score. METHODS: Patients with acute stroke and M1 MCA±intracranial internal carotid artery occlusion on baseline CTA were included. Baseline sCTA was assessed for phase of image acquisition. An evaluator assessed collaterals using the Calgary Collateral (CC) Score (measures pial arterial filling in ACA-MCA and PCA-MCA regions separately), the CTA-based MGH score, and on DSA using the ASITN score. Infarct volumes were measured on 24- to 48-hour magnetic resonance imaging/ computed tomography. RESULTS: Of 106 patients, baseline sCTA was acquired in early arterial phase in 9.9%, peak arterial in 50.7%, equilibrium in 32.4%, early venous in 5.6%, and late venous in 1.4%. Variance in ACA-MCA collaterals explained only 32% of variance in PCA-MCA collaterals on the CC score (Spearman's correlation coefficient rho [rho]=0.56). Correlation between ACA-MCA collaterals and the MGH score was strong (rho=0.8); correlation between PCA-MCA collaterals and this score was modest (rho=0.54). Correlation between ACA-MCA collaterals and the ASITN score was modest (n=53, rho=0.43); and correlation between PCA-MCA collaterals and ASITN score was poor (rho=0.33). Of the CTA-based scores, the CC Score (Akaike [AIC] 1022) was better at predicting follow-up infarct volumes than was the MGH score (AIC 1029). CONCLUSION: Collateral assessments in acute ischemic stroke are best done using CTA with temporal resolution and by assessing regional variability. ACA-MCA and MCA-PCA collaterals should be evaluated separately.

Association Between CT Angiogram Collaterals and CT Perfusion in the Interventional Management of Stroke III Trial.

BACKGROUND AND PURPOSE: Collateral flow can determine ischemic core and tissue at risk. Using the Interventional Management of Stroke (IMS) III trial data, we explored the relationship between computed tomography angiogram (CTA) collateral status and CT perfusion (CTP) parameters. METHODS: Baseline CTA collaterals were trichotomized as good, intermediate, and poor, and CTP studies were analyzed to quantify ischemic core, tissue at risk, and mismatch ratios. Kruskal-Wallis and Spearman tests were used to measure the strength of association and correlation between CTA collaterals and CTP parameters. RESULTS: A total of 95 patients had diagnostic CTP studies in the IMS III trial. Of these, 53 patients had M1/M2 middle cerebral artery±intracranial internal carotid artery occlusion, where baseline CTA collateral grading was performed. CTA collaterals were associated with smaller CTP measured ischemic core volume (P=0.0078) and higher mismatch (P=0.0004). There was moderate negative correlation between collaterals and core (rs=-0.45; 95% confidence interval, -0.64 to -0.20) and moderate positive correlation between collaterals and mismatch (rs=0.53; 95% confidence interval, 0.29-0.71). CONCLUSION: Better collaterals were associated with smaller ischemic core and higher mismatch in the IMS III trial. Collateral assessment and perfusion imaging identify the same biological construct about ischemic tissue sustenance.

The Role of Vascular Imaging in the Initial Assessment of Patients with Acute Ischemic Stroke.

Over the last few years, improvement in radiological imaging and treatment has changed the management of acute ischemic stroke. We have made significant advances in not only the imaging modalities themselves but also in identifying imaging parameters that can help us predict patient outcomes with both intravascular thrombolysis and endovascular thrombectomy. In this review, we describe the added utility of baseline vascular imaging including computed tomography angiography and magnetic resonance angiography in the diagnosis and management of patients with acute ischemic stroke. We focus on information these imaging modalities provide on clot characteristics, tissue state, collateral status, and endovascular planning. We also highlight the benefits of newer imaging modalities like dynamic computed tomography angiography (CTA) and multi-phase CTA. Lastly, we also describe some of the disadvantages of vascular imaging in ischemic stroke.

Occult anterograde flow is an under-recognized but crucial predictor of early recanalization with intravenous tissue-type plasminogen activator.

BACKGROUND AND PURPOSE: Thrombolysis depends on the ability of blood and thrombolytic agents to permeate thrombus. We devised a novel technique to quantify blood permeating through thrombi and determine whether this parameter predicts early recanalization with intravenous tissue-type plasminogen activator. METHODS: Intravenous tissue-type plasminogen activator-treated patients with stroke and complete occlusion on computed tomographic angiography were analyzed using perfusion computed tomography and a delay insensitive algorithm. We generated maps that measure delay in arrival time of contrast within the intracranial arterial tree (T0 maps). A positive sloped regression line of T0 values measured along artery silhouette distal to thrombus was defined as marker of permeable thrombus (occult anterograde flow). Median T0 values at proximal and distal thrombus interface were measured. Early recanalization was assessed on first angiography of subsequent intra-arterial procedure or on a 4-hour computed tomographic angiography. RESULTS: Of 66 patients, occult anterograde flow was detected in 17 (25.8%). Early recanalization was more in patients with occult anterograde flow versus not (66.7 versus 29.7%; P=0.031). Median T0 value (in s) at distal thrombus interface (1.5 versus 3.8; P=0.006) and difference in median T0 value between proximal and distal thrombus interface (1.3 versus 3.7; P=0.014) were less in early recanalizers versus in nonrecanalizers. In multivariable analysis, patients with occult anterograde flow and T0 value difference between proximal and distal thrombus interface ≤2 s recanalized most (71.4%; odds ratio, 12.15; 95% confidence interval, 2.05-71.91), whereas patients with retrograde flow and T0 value difference >2 s recanalized least (25.9%; odds ratio, 1). CONCLUSIONS: Occult anterograde flow through thrombus can be assessed by perfusion computed tomography T0 maps and predicts early recanalization with intravenous tissue-type plasminogen activator robustly.

Differential Effect of Baseline Computed Tomographic Angiography Collaterals on Clinical Outcome in Patients Enrolled in the Interventional Management of Stroke III Trial.

BACKGROUND AND PURPOSE: In the Interventional Management of Stroke (IMS) III trial, we sought to demonstrate evidence of a differential treatment effect of endovascular treatment of acute ischemic stroke compared with intravenous tissue-type plasminogen activator, according to baseline collateral status measured using computed tomographic angiography. METHODS: Of 656 patients enrolled in Interventional Management of Stroke III trial, 306 had baseline computed tomographic angiography. Of these, 185 patients had M1 middle cerebral artery ± intracranial internal carotid artery occlusion, where baseline collateral status could be measured. Collateral status was assessed by consensus using 3 different ordinal scales and categorized as good, intermediate, and poor. Multivariable modeling was used to assess the effect of collateral status and treatment type on clinical outcome by modified Rankin Scale (mRS 0-2, mRS 0-1, and the ordinal mRS). RESULTS: Of 185 patients, 126 randomized to endovascular therapy (87.6% recanalized, 41.3% 90-day mRS 0-2) and 59 to intravenous tissue-type plasminogen activator only (60.5% recanalized, 30.5% 90-day mRS 0-2). In multivariable modeling, collateral status was a significant predictor of all clinical outcomes (P<0.05). Maximal benefit with endovascular treatment across all clinical outcomes was seen in patients with intermediate collaterals, some benefit in patients with good collaterals, and none in patients with poor collaterals, although small sample size limited the power of the analysis to show a statistically significant interaction between collateral status and treatment type (P>0.05). CONCLUSION: Using data from a large randomized controlled trial (IMS III), we show that baseline computed tomographic angiography collaterals are a robust determinant of final clinical outcome and could be used to select patients for endovascular therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov/ct2/show/. Unique identifier: 0020NCT00359424.

Multiphase CT Angiography: A New Tool for the Imaging Triage of Patients with Acute Ischemic Stroke.

PURPOSE: To describe the use of an imaging selection tool, multiphase computed tomographic (CT) angiography, in patients with acute ischemic stroke (AIS) and to demonstrate its interrater reliability and ability to help determine clinical outcome. MATERIALS AND METHODS: The local ethics board approved this study. Data are from the pilot phase of PRoveIT, a prospective observational study analyzing utility of multimodal imaging in the triage of patients with AIS. Patients underwent baseline unenhanced CT, single-phase CT angiography of the head and neck, multiphase CT angiography, and perfusion CT. Multiphase CT angiography generates time-resolved images of pial arteries. Pial arterial filling was scored on a six-point ordinal scale, and interrater reliability was tested. Clinical outcomes included a 50% or greater decrease in National Institutes of Health Stroke Scale (NIHSS) over 24 hours and 90-day modified Rankin Scale (mRS) score of 0-2. The ability to predict clinical outcomes was compared between single-phase CT angiography, multiphase CT angiography, and perfusion CT by using receiver operating curve analysis, Akaike information criterion (AIC), and Bayesian information criterion (BIC). RESULTS: A total of 147 patients were included. Interrater reliability for multiphase CT angiography is excellent (n = 30, κ = 0.81, P < .001). At receiver operating characteristic curve analysis, the ability to predict clinical outcome is modest (C statistic = 0.56, 95% confidence interval [CI]: 0.52, 0.63 for ≥50% decrease in NIHSS over 24 hours; C statistic = 0.6, 95% CI: 0.53, 0.68 for 90-day mRS score of 0-2) but better than that of models using single-phase CT angiography and perfusion CT (P < .05 overall). With AIC and BIC, models that use multiphase CT angiography are better than models that use single-phase CT angiography and perfusion CT for a decrease of 50% or more in NIHSS over 24 hours (AIC = 166, BIC = 171.7; values were lowest for multiphase CT angiography) and a 90-day mRS score of 0-2 (AIC = 132.1, BIC = 137.4; values were lowest for multiphase CT angiography). CONCLUSION: Multiphase CT angiography is a reliable tool for imaging selection in patients with AIS.

Thrombus Characteristics Are Related to Collaterals and Angioarchitecture in Acute Stroke.

BACKGROUND: We have theorized that clots with stasis are longer. We therefore explored the relationship between thrombus imaging characteristics on noncontrast computed tomography (NCCT) and magnetic resonance imaging (MRI) with clot length and pial collaterals on baseline computed tomography angiography (CTA). METHODS: Prospective study of acute ischemic stroke patients (2005-2009) from Keimyung University. Patients with known stroke symptom onset time, baseline CTA, MRI, and with M1-Middle Cerebral Artery (MCA)±intracranial internal carotid artery (ICA) occlusions were included. Clot length and pial collaterals were measured on baseline CTA. RESULTS: A total of 104 patients (mean age 65.1±12.28 years, 56.7% male, median baseline National Institutes of Health Stroke Scale 13) with intracranial ICA + MCA (n=50) or isolated M1-MCA (n=54) occlusions were included. Hyperdense sign on NCCT had a median clot length of 42.3 mm versus 29.5 mm when hyperdense negative (p=0.02). Clots showing blooming artifact on gradient recall echo MRI had a median length of 39.1 mm versus 24.5 mm without blooming (p=0.005). Patients with poor baseline collaterals on CTA had longer clots than those with intermediate/good collaterals (median clot length 49.4 mm vs 34.9 mm vs 20.5 mm respectively, p<0.001). In censored logistic regression modeling, clot length was an independent predictor of hyperdense sign (p=0.05) and of the presence of blooming artifact (p=0.006). CONCLUSIONS: Clot length and baseline collateral status are independent predictors of clot hyperdensity on NCCT and blooming artifact on gradient recall echo. Longer clots are more likely to be hyperdense and to bloom more, probably because portions of these clots are freshly formed locally due to of stasis of blood around the original clot. This stasis could be because of poor collaterals and inefficient angio-architecture within the cerebral arterial tree.

Recanalization and clinical outcome of occlusion sites at baseline CT angiography in the Interventional Management of Stroke III trial.

PURPOSE: To use baseline computed tomographic (CT) angiography to analyze imaging and clinical end points in an Interventional Management of Stroke III cohort to identify patients who would benefit from endovascular stroke therapy. MATERIALS AND METHODS: The primary clinical end point was 90-day dichotomized modified Rankin Scale (mRS) score. Secondary end points were 90-day mRS score distribution and 24-hour recanalization. Prespecified subgroup was baseline proximal occlusions (internal carotid, M1, or basilar arteries). Exploratory analyses were subsets with any occlusion and specific sites of occlusion (two-sided α = .01). RESULTS: Of 656 subjects, 306 (47%) underwent baseline CT angiography or magnetic resonance angiography. Of 306, 282 (92%) had arterial occlusions. At baseline CT angiography, proximal occlusions (n = 220) demonstrated no difference in primary outcome (41.3% [62 of 150] endovascular vs 38% [27 of 70] intravenous [IV] tissue-plasminogen activator [tPA]; relative risk, 1.07 [99% confidence interval: 0.67, 1.70]; P = .70); however, 24-hour recanalization rate was higher for endovascular treatment (n = 167; 84.3% [97 of 115] endovascular vs 56% [29 of 52] IV tPA; P < .001). Exploratory subgroup analysis for any occlusion at baseline CT angiography did not demonstrate significant differences between endovascular and IV tPA arms for primary outcome (44.7% [85 of 190] vs 38% [35 of 92], P = .29), although ordinal shift analysis of full mRS distribution demonstrated a trend toward more favorable outcome (P = .011). Carotid T- or L-type occlusion (terminal internal carotid artery [ICA] with M1 middle cerebral artery and/or A1 anterior cerebral artery involvement) or tandem (extracranial or intracranial) ICA and M1 occlusion subgroup also showed a trend favoring endovascular treatment over IV tPA alone for primary outcome (26% [12 of 46] vs 4% [one of 23], P = .047). CONCLUSION: Significant differences were identified between treatment arms for 24-hour recanalization in proximal occlusions; carotid T- or L-type and tandem ICA and M1 occlusions showed greater recanalization and a trend toward better outcome with endovascular treatment. Vascular imaging should be mandated in future endovascular trials to identify such occlusions. Online supplemental material is available for this article.

Operator Intracranial Dose Protection During Fluoroscopic-Guided Interventions.

PURPOSE: We utilized an anthropomorphic model made with a human skull to determine how different personal protective equipment influence operator intracranial radiation absorbed dose. MATERIALS AND METHODS: A custom anthropomorphic phantom made with a human skull coated with polyurethane rubber, mimicking superficial tissues, and was mounted onto a plastic thorax. To simulate scatter, an acrylic plastic scatter phantom was placed onto the fluoroscopic table with a 1.5 mm lead apron on top. Two Radcal radiation detectors were utilized; one inside of the skull and a second outside. Fluoroscopic exposures were performed with and without radiation protective equipment in AP, 45-degree RAO, and 45-degree LAO projections. RESULTS: The skull and soft tissues reduce intracranial radiation by 76% when compared to radiation outside the skull. LAO (308.95 µSv/min) and RAO projections (96.47µSv/min) result in significantly higher radiation exposure to the primary operator when compared to an AP projection (54 µSv/min). All tested radiation protection equipment demonstrated various reduction in intracranial radiation when compared to no protection. The hood (68% reduction in AP, 91% LAO, and 43% in RAO), full cover (53% reduction in AP, 76% in LAO, and 54% in RAO), and open top with ear coverage (43% reduction in AP, 77% reduction in LAO, and 22% in RAO) demonstrated the most reduction in intracranial radiation when compared to the control. CONCLUSION: All tested equipment provided various degrees of additional intracranial protection. The skull and soft tissues attenuate a portion of intracranial radiation.

The proximal balloon occlusion together with direct thrombus aspiration (protect plus) technique: Experience at a tertiary comprehensive stroke center.

BACKGROUND: Timely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver for salvaging penumbra. We re-evaluated the previously described PROTECT (PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy) Plus technique at a tertiary comprehensive stroke center. METHODS: We retrospectively analyzed all patients who underwent mechanical thrombectomy with stentrievers between May 2011 and April 2020. Patients were divided between those who underwent PROTECT Plus and those who did not (proximal balloon occlusion with stent retriever only). We compared the groups in terms of reperfusion, groin to reperfusion time, symptomatic intracranial hemorrhage (sICH), modified Rankin Scale (mRS) score at discharge. RESULTS: Within the study period, 167 (71.4%) PROTECT Plus and 67 (28.6%) non-PROTECT patients which met our inclusion criteria. There was no statistically significant difference in the number of patients with successful reperfusion (mTICI >2b) between the techniques (85.0% vs 82.1%; p = 0.58). The PROTECT Plus group had lower rates of mRS ≤2 at discharge (40.1% vs 57.6%; p = 0.016). The rate of sICH was comparable (p = 0.35) between the PROTECT Plus group (7.2%) and the non-PROTECT group (3.0%). CONCLUSION: The PROTECT Plus technique using a BGC, a distal reperfusion catheter and stent retriever is feasible for recanalization of large vessel occlusions. Successful recanalization, first-pass recanalization and complication rates are similar between PROTECT Plus and non-PROTECT stent retriever techniques. This study adds to an existing body of literature detailing techniques that use both a stent retriever and a distal reperfusion catheter to maximize recanalization for patients with large vessel occlusions.

Identifying Thrombus on Non-Contrast CT in Patients with Acute Ischemic Stroke.

The hyperdense sign is a marker of thrombus in non-contrast computed tomography (NCCT) datasets. The aim of this work was to determine optimal Hounsfield unit (HU) thresholds for thrombus segmentation in thin-slice non-contrast CT (NCCT) and use these thresholds to generate 3D thrombus models. Patients with thin-slice baseline NCCT (≤2.5 mm) and MCA-M1 occlusions were included. CTA was registered to NCCT, and three regions of interest (ROIs) were placed in the NCCT, including: the thrombus, contralateral brain tissue, and contralateral patent MCA-M1 artery. Optimal HU thresholds differentiating the thrombus from non-thrombus tissue voxels were calculated using receiver operating characteristic analysis. Linear regression analysis was used to predict the optimal HU threshold for discriminating the clot only based on the average contralateral vessel HU or contralateral parenchyma HU. Three-dimensional models from 70 participants using standard (45 HU) and patient-specific thresholds were generated and compared to CTA clot characteristics. The optimal HU threshold discriminating thrombus in NCCT from other structures varied with a median of 51 (IQR: 49-55). Experts chose 3D models derived using patient-specific HU models as corresponding better to the thrombus seen in CTA in 83.8% (31/37) of cases. Patient-specific HU thresholds for segmenting the thrombus in NCCT can be derived using normal parenchyma. Thrombus segmentation using patient-specific HU thresholds is superior to conventional 45 HU thresholds.

What constitutes the M1 segment of the middle cerebral artery?

Intravenous tissue plasminogen activator has limited efficacy in fibrinolysis of large proximal intracranial thrombi. Thus, recent endovascular acute stroke trials restricted their selection criteria to patients with proximal occlusions in the anterior circulation. Although the terminal internal carotid artery occlusion is relatively easy to identify, there is often a debate as to what constitutes a proximal (involving the M1 segment) versus a distal (involving the M2 segment and beyond) middle cerebral artery occlusion. In light of overwhelming evidence demonstrating superiority of endovascular treatment in patients with proximal occlusion, this distinction has significant practical implications in patient selection. Here we present a brief review of the proximal (M1) segment of the middle cerebral artery anatomy and provide practical methods to recognize and separate the M1 and M2 segments. In keeping with the belief that CT angiography (CTA) (preferably multiphase CTA) is the ideal screening test for patients with emergent large vessel occlusion, we have provided tips for expeditious and accurate vascular imaging interpretation.