Performance of CT ASPECTS and Collateral Score in Risk Stratification: Can Target Perfusion Profiles Be Predicted without Perfusion Imaging?

BACKGROUND AND PURPOSE:Endovascular trials suggest that revascularization benefits a subset of acute ischemic stroke patients with large-artery occlusion and small-core infarct volumes. The objective of our study was to identify thresholds of noncontrast CT–ASPECTS and collateral scores on CT angiography that best predict ischemic core volume thresholds quantified by CT perfusion among patients with acute ischemic stroke.MATERIALS AND METHODS:Fifty-four patients with acute ischemic stroke (<12 hours) and MCA/intracranial ICA occlusion underwent NCCT/CTP during their initial evaluation. CTP analysis was performed on a user-independent platform (RApid processing of PerfusIon and Diffusion), computing core infarct (defined as CBF of <30% normal). A target mismatch profile consisting of infarction core of ≤50 mL was selected to define candidates with acute ischemic stroke likely to benefit from revascularization.RESULTS:NCCT-ASPECTS of ≥9 with a CTA collateral score of 3 had 100% specificity for identifying patients with a CBF core volume of ≤50 mL. NCCT-ASPECTS of ≤6 had 100% specificity for identifying patients with a CBF core volume of >50 mL. In our cohort, 44 (81%) patients had an NCCT-ASPECTS of ≥9, a CTA collateral score of 3, or an NCCT-ASPECTS of ≤6.CONCLUSIONS:Using an NCCT-ASPECTS of ≥9 or a CTA collateral score of 3 best predicts CBF core volume infarct of ≤50 mL, while an NCCT-ASPECTS of ≤6 best predicts a CBF core volume infarct of >50 mL. Together these thresholds suggest that a specific population of patients with acute ischemic stroke not meeting such profiles may benefit most from CTP imaging to determine candidacy for revascularization.

Revascularization aims to prevent progression of ischemic injury in acute ischemic stroke (AIS).^1–4 Recent success in trials of endovascular AIS therapy, while restoring motivation for acute stroke intervention, has left the subject of an optimal patient-selection paradigm largely unaddressed.^5–8 While the primary goals in this setting include timely revascularization, the relative merits of expedited triage versus identification of target imaging profiles remain the subject of ongoing inquiry. Contemporary guidelines on AIS management, therefore, remain inconclusive as to the role of multimodal imaging selection.⁹We recently reported the benefits of a high-speed computing tool for CT perfusion analysis over qualitative approaches to imaging triage for prognostication among patients with anterior circulation AIS.¹⁰ The findings therein suggested that a user- and vendor-independent computational tool may outperform purely qualitative approaches in outcome prediction. Similar implementations of this tool in recent, prospective endovascular trials suggested strong results as an approach to patient selection; however, the relative contribution of CTP-based selection criteria, among other trial-specific features, remains uncertain in light of the overall favorable outcomes reported across disparate trial designs.^5–8The objective of our study was to identify thresholds of NCCT-ASPECTS and collateral score on CT angiography that best predict ischemic core volume thresholds quantified by CTP among patients with AIS.     

Prediction of Infarction and Reperfusion in Stroke by Flow- and Volume-Weighted Collateral Signal in MR Angiography

BACKGROUND AND PURPOSE:In proximal anterior circulation occlusive strokes, collateral flow is essential for good outcome. Collateralized vessel intensity in TOF- and contrast-enhanced MRA is variable due to different acquisition methods. Our purpose was to quantify collateral supply by using flow-weighted signal in TOF-MRA and blood volume–weighted signal in contrast-enhanced MRA to determine each predictive contribution to tissue infarction and reperfusion.MATERIALS AND METHODS:Consecutively (2009–2013), 44 stroke patients with acute proximal anterior circulation occlusion met the inclusion criteria with TOF- and contrast-enhanced MRA and penumbral imaging. Collateralized vessels in the ischemic hemisphere were assessed by TOF- and contrast-enhanced MRA using 2 methods: 1) visual 3-point collateral scoring, and 2) collateral signal quantification by an arterial atlas-based collateral index. Collateral measures were tested by receiver operating characteristic curve and logistic regression against 2 imaging end points of tissue-outcome: final infarct volume and percentage of penumbra saved.RESULTS:Visual collateral scores on contrast-enhanced MRA but not TOF were significantly higher in patients with good outcome. Visual collateral scoring on contrast-enhanced MRA was the best rater-based discriminator for final infarct volume < 90 mL (area under the curve, 0.81; P < .01) and percentage of penumbra saved >50% (area under the curve, 0.67; P = .04). Atlas-based collateral index of contrast-enhanced MRA was the overall best independent discriminator for final infarct volume of <90 mL (area under the curve, 0.94; P < .01). Atlas-based collateral index combining the signal of TOF- and contrast-enhanced MRA was the overall best discriminator for effective reperfusion (percentage of penumbra saved >50%; area under the curve, 0.89; P < .001).CONCLUSIONS:Visual scoring of contrast-enhanced but not TOF-MRA is a reliable predictor of infarct outcome in stroke patients with proximal arterial occlusion. By atlas-based collateral assessment, TOF- and contrast-enhanced MRA both contain predictive signal information for penumbral reperfusion. This could improve risk stratification in further studies.

In stroke patients with acute proximal artery occlusion, collateral blood supply is pivotal for functional outcome.¹ Collateral perfusion limits ischemic core expansion by maintaining oligemic tissue-at-risk until reperfusion takes place and is an independent predictor of final infarct volume and clinical outcome.^1–3 Collaterals enhance recanalization and avert hemorrhagic transformation by minimizing severe local perfusion impairment.^4,5 For rapidly applicable and reproducible collateral assessment in the triage of acute stroke, several angiographic scoring methods have been introduced.^2,6–8 Contrary to DSA, direct visualization of time-resolved collateral flow in the leptomeningeal arteries is not possible with conventional CTA or MRA. Instead, the visual abundance of contrasted, collateralized vessels distal to the occlusion has been used as a surrogate scoring system for leptomeningeal collateral supply in high-resolution CTA.^1,7,9 In particular, a malignant CTA collateral profile is highly specific for poor outcome.⁹Collateral assessment using TOF- or contrast-enhanced (CE)-MRA is less straightforward. Visualization of collateralized vessels distal to mainstem occlusion is problematic in TOF-MRA, which is highly sensitive to low flow due to spin saturation.^10,11 In CE-MRA, T1-shortening by gadolinium induces a vessel signal nearly independent of blood flow (for a sufficiently broad bolus) and primarily depends on blood volume (ie, intravascular volume). The different signal of collateralized vessels in both modalities may contain independent information; however, the efficacy of collateral assessment for outcome prediction attributed to each MRA technique has not been investigated in detail.^11–14 Our purpose was to differentially quantify collateralized vessels in proximal anterior circulation occlusive strokes, including both flow-weighted signal in TOF-MRA and volume-weighted signal in CE-MRA, and to determine each predictive contribution to tissue outcome.     

DWI Reversal Is Associated with Small Infarct Volume in Patients with TIA and Minor Stroke

BACKGROUND AND PURPOSE:More than half of patients with TIA/minor stroke have ischemic lesions on early DWI, which represent irreversibly damaged tissue. The presence and volume of DWI lesions predict early deterioration in this population. We aimed to study the rate and implications of DWI reversal in patients with TIA/minor stroke.MATERIALS AND METHODS:Patients with TIA/minor stroke were prospectively enrolled and imaged within 24 hours of onset. Patients were followed for 3 months with repeat MR imaging either at day 30 or 90. Baseline DWI/PWI and follow-up FLAIR final infarct volumes were measured.RESULTS:Of 418 patients included, 55.5% had DWI and 37% had PWI (time-to-peak of the impulse response ≥2 seconds'' delay) lesions at baseline. The median time from symptom onset to baseline and follow-up imaging was 13.4 (interquartile range, 12.7) and 78.73 hours (interquartile range, 60.2), respectively. DWI reversal occurred in 5.7% of patients. The median DWI lesion volume was significantly smaller in those with reversal (0.26 mL, interquartile range = 0.58 mL) compared with those without (1.29 mL, interquartile range = 3.6 mL, P = .002); 72.7% of DWI reversal occurred in cortically based lesions. Concurrent tissue hypoperfusion (time-to-peak of the impulse response ≥2 seconds) was seen in 36.4% of those with DWI reversal versus 62.4% without (P = .08). DWI reversal occurred in 3.3% of patients with penumbral patterns (time-to-peak of the impulse response ≥6 seconds − DWI) > 0 and in 6.8% of those without penumbral patterns (P = .3). The severity of hypoperfusion, defined as greater prolongation of time-to-peak of the impulse response (≥2, ≥4, ≥6, ≥8 seconds), did not affect the likelihood of DWI reversal (linear trend, P = .147). No patient with DWI reversal had an mRS score of ≥2 at 90 days versus 18.2% of those without reversal (P = .02).CONCLUSIONS:DWI reversal is uncommon in patients with TIA/minor stroke and is more likely to occur in those with smaller baseline lesions. DWI reversal should not have a significant effect on the accuracy of penumbra definition.

Multiple studies have shown that more than half of patients with TIA/minor stroke have evidence of acute ischemic tissue injury on early DWI.^1–3 The presence and the volume of DWI lesions carry a negative prognostic value in this population.^4–6 The DWI-restricted lesions are thought to represent the irreversibly damaged ischemic core.⁷ This premise was recently brought into question by studies suggesting a high rate of DWI lesion reversal in patients with stroke who had undergone thrombolytic therapy.^8,9 A recent systematic review of the published literature on DWI hyperintense tissue outcome reported variable rates of DWI reversal (0%–83%), with a mean reversal rate of 24% in patients with ischemic stroke.¹⁰ In most patients, the size of the acute infarct correlated with both the final infarct volume on follow-up T2/FLAIR imaging and the clinical outcome.^11,12 Most previous work on DWI reversal has been undertaken in patients with moderate-to-severe strokes. Patients with TIA or minor stroke have smaller volumes of ischemia and potentially may have a higher likelihood of reversal. Previous imaging studies have reported reversal of the DWI signal in patients with TIA, but these were relatively small series, without scheduled follow-up imaging and DWI reversal was not studied systematically.^13–15Potentially salvageable tissue known as the “ischemic penumbra” represents viable tissue at risk of infarct that has not yet infarcted.¹⁶ Various methods are used to define the ischemic penumbra on MR imaging, including the mismatch between perfusion and diffusion¹⁷ or clinical-diffusion mismatch.¹⁸ All of these definitions rely on DWI lesions representing irreversibly damaged ischemic core.DWI reversibility, therefore, has implications in both accurate assessment of ischemic core and penumbra and outcome prediction.We, therefore, aimed to determine the rate and characteristics of DWI reversal in 2 large prospective imaging cohorts of patients with TIA/minor stroke. We studied the correlation among the DWI lesion volume, lesion location, concurrent baseline hypoperfusion on perfusion-weighted imaging, the severity of the perfusion deficit, and the reversal of DWI signal on follow-up FLAIR/T2 imaging in this population.     

Pretreatment Advanced Imaging in Patients with Stroke Treated with IV Thrombolysis: Evaluation of a Multihospital Data Base

BACKGROUND AND PURPOSE:CT angiography, CT perfusion, and MR imaging have all been advocated as potentially useful in treatment planning for patients with acute ischemic stroke. We evaluated a large multihospital data base to determine how the use of advanced imaging is evolving in patients treated with intravenous thrombolysis.MATERIALS AND METHODS:Patients with acute ischemic stroke receiving IV thrombolytic therapy from 2008 to 2011 were identified by using the Premier Perspective data base. Mortality and discharge to long-term care rates were compared following multivariate logistic regression between patients who received head CT only versus those who received CTA without CT perfusion, CT perfusion, or MR imaging.RESULTS:Of 12,429 included patients, 7305 (59%) were in the CT group, 2359 (19%) were in the CTA group, 848 (7%) were in the CTP group, and 1917 (15%) were in the MR group. From 2008 to 2011, the percentage of patients receiving head CT only decreased from 64% to 55%, while the percentage who received cerebral CT perfusion increased from 3% to 8%. The use of CT angiography and MR imaging marginally increased (1%–2%). Outcomes were similar between CT only and advanced imaging patients, except discharge to long-term care was slightly more frequent in the CTP group (OR = 1.17 [95% CI, 0.96–1.43]; P = .0412) and MR group (OR = 1.14 [95% CI, 1.01–1.28]; P = .0177) and mortality was lower in the MR group (OR = 0.64 [95% CI, 0.52–0.79]; P < .0001).CONCLUSIONS:Use of advanced imaging is increasing in patients treated with IV thrombolysis. While there were differences in outcomes among imaging groups, the clinical effect of advanced imaging remains unclear.

The potential benefit of intravenous thrombolytic therapy for acute ischemic stroke decreases rapidly with time. Because of wide variability in collateral circulation, time elapsed since onset is a crude indicator of the potential benefit of treatment in each patient. Advanced imaging might provide a means to refine selection of patients who could potentially benefit from revascularization therapy. The advanced imaging techniques that might add clinically useful information in the setting of acute ischemic stroke include CT angiography, CT perfusion, and MR imaging. CT angiography can be used to identify patients with large-artery occlusions potentially amenable to intra-arterial therapy,^1–3 and CT angiography source images have been proposed as a means of evaluating collateral circulation.^4–6 CT perfusion may potentially allow discrimination between salvageable brain (“penumbra”) and brain already doomed to infarction (“ischemic core”)^2,7–10 and thus may be useful in helping to refine selection of patients for IV thrombolysis^11,12 or intra-arterial thrombectomy.^13–15 MR perfusion and diffusion imaging have also been reported to be useful in screening patients for intravenous therapy.^16–22While advanced imaging techniques hold promise for the evaluation of patients with acute ischemic stroke, there is variation in techniques and definitions of parameters that limit wide application and acceptance of these techniques.^4,23–25 There is currently no consensus on a standard imaging approach for acute ischemic stroke. We studied a large data base of hospitals in the United States to assess the recent use of advanced imaging in patients with acute ischemic stroke treated with intravenous thrombolysis, including an evaluation of the use of advanced imaging, with respect to patient outcome.     

Hyperattenuated Intracerebral Lesions after Mechanical Recanalization in Acute Stroke

BACKGROUND AND PURPOSE:Following mechanical recanalization of an acute intracranial vessel occlusion, hyperattenuated lesions are frequently found on postinterventional cranial CT. They represent either blood or—more frequently—enhancement of contrast agent. Here, we aimed to evaluate the prognostic value of these hyperattenuated intracerebral lesions.MATERIALS AND METHODS:One hundred one consecutive patients with acute stroke in the anterior circulation who underwent mechanical recanalization were included. Risk factors for hyperattenuated intracerebral lesions were assessed, and lesion volume was compared with the volume of final infarction. Clinical outcome and relative risk of secondary hemorrhage were determined in patients with and without any hyperattenuated lesions and compared.RESULTS:The frequency of hyperattenuated lesions was 84.2%. Risk factors for hyperattenuated lesions were female sex, higher NIHSS score on admission, and higher amount of contrast agent applied. On follow-up, 3 patients showed no infarction; 53 patients, an ischemic infarction; and 45 patients, a hemorrhagic infarction. In all except 1 case, final volume of infarction (median = 92.4 mL) exceeded the volume of hyperattenuated intracerebral lesions (median = 5.6 mL). Patients with hyperattenuated lesions were at a 4 times higher relative risk for hemorrhagic transformation but had no significantly worse clinical outcome.CONCLUSIONS:Our data show that the extent of postinterventional hyperattenuated intracerebral lesions underestimates the volume of final infarction. Although hyperattenuated lesions indicate a higher risk of secondary hemorrhagic transformation, their presence seems not to be of any prognostic value regarding clinical outcome.

Hyperattenuated intracerebral lesions are a frequent finding on postinterventional cranial CT following intra-arterial reperfusion therapy in acute ischemic stroke.^1–5 These hyperattenuated lesions have been documented and described since the 1990s. It has been suggested that hyperattenuated lesions persisting longer than 24 hours correlate with hemorrhagic lesions, whereas hyperattenuated intracerebral lesions that are no longer discernible on the 24-hour follow-up examination correspond to contrast enhancement.^6,7 The presence of hyperattenuated intracerebral lesions was considered a risk factor for secondary hemorrhage accompanied by deterioration of neurologic symptoms.^3–5 However, hyperattenuated lesions do not always indicate hemorrhage, and rapid clearance of the contrast medium on postinterventional cranial CT (CCT) has been reported to be a good prognostic sign.^1,6 A recent small study found no increased risk of symptomatic hemorrhage or negative clinical prognosis in patients with hyperattenuated intracerebral lesions compared with those without.⁸ On the other hand, Costalat et al⁹ recently reported that hyperattenuated intracerebral lesions on postinterventional CCT were significantly associated with poorer clinical outcome. To our knowledge, larger studies on the prognostic value of hyperattenuated intracerebral lesions are lacking to date.Thus, the aim of this study was to further evaluate the prevalence of hyperattenuated lesions following mechanical recanalization of acute vessel occlusions in the anterior circulation, to identify risk factors for their occurrence, and to assess their prognostic value.     

Patient Outcomes and Cerebral Infarction after Ruptured Anterior Communicating Artery Aneurysm Treatment

BACKGROUND AND PURPOSE:Anterior communicating artery aneurysm rupture and treatment is associated with high rates of dependency, which are more severe after clipping compared with coiling. To determine whether ischemic injury might account for these differences, we characterized cerebral infarction burden, infarction patterns, and patient outcomes after surgical or endovascular treatment of ruptured anterior communicating artery aneurysms.MATERIALS AND METHODS:We performed a retrospective cohort study of consecutive patients with ruptured anterior communicating artery aneurysms. Patient data and neuroimaging studies were reviewed. A propensity score for outcome measures was calculated to account for the nonrandom assignment to treatment. Primary outcome was the frequency of frontal lobe and striatum ischemic injury. Secondary outcomes were patient mortality and clinical outcome at discharge and at 3 months.RESULTS:Coiled patients were older (median, 55 versus 50 years; P = .03), presented with a worse clinical status (60% with Hunt and Hess Score >2 versus 34% in clipped patients; P = .02), had a higher modified Fisher grade (P = .01), and were more likely to present with intraventricular hemorrhage (78% versus 56%; P = .03). Ischemic frontal lobe infarction (OR, 2.9; 95% CI, 1.1–8.4; P = .03) and recurrent artery of Heubner infarction (OR, 20.9; 95% CI, 3.5–403.7; P < .001) were more common in clipped patients. Clipped patients were more likely to be functionally dependent at discharge (OR, 3.2; P = .05) compared with coiled patients. Mortality and clinical outcome at 3 months were similar between coiled and clipped patients.CONCLUSIONS:Frontal lobe and recurrent artery of Heubner infarctions are more common after surgical clipping of ruptured anterior communicating artery aneurysms, and are associated with poorer clinical outcomes at discharge.

Subarachnoid hemorrhage secondary to rupture of a cerebral aneurysm affects 30,000 people in the United States every year and results in significant morbidity and mortality.¹ Clinical outcomes after aneurysm rupture and treatment are influenced by cumulative cerebral infarction burden.^2,3 Furthermore, patients who recover from aneurysm rupture are often left with disabling cognitive deficits that may result in the patient''s dependency on others, which is reflect by higher mRS scores.^4,5 The severity of these cognitive deficits has been correlated to the Hunt and Hess Scale (HHS) grade on admission, older age, aneurysm location, and treatment-related brain injury.^6–8Anterior communicating artery aneurysms (AcomAs) are among the most commonly identified ruptured aneurysms,^9,10 and AcomA rupture and treatment are more strongly associated with cognitive and behavioral deficits relative to other aneurysm locations.^5,11–14 The cause of these neuropsychiatric deficits remains uncertain, but prior studies have suggested ischemic injury to the frontal cortex, ventromedial prefrontal (orbitofrontal) cortex, or striatum as a possible etiology.^15–17Ruptured aneurysms may be successfully treated by microsurgical clipping or endovascular coil embolization.^5,9,18 However, surgical clipping of AcomAs has been associated with more severe cognitive and behavioral deficits and higher rates of patient dependency compared with endovascular coil embolization, which may be caused by retraction injury to the frontal lobe or other causes of cerebral infarction.^{2,5,11,13,14,17,19}Our primary aim was to determine whether there is an increase in frontal lobe or striatum ischemic injury after treatment with surgical clipping compared with coil embolization in patients with ruptured AcomA. Our secondary outcomes were patient mortality and clinical outcome at discharge and at 3 months of follow-up. We therefore characterized patterns of cerebral ischemic injury and patient outcomes after treatment of ruptured AcomA at our neurovascular referral center.     

Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts

BACKGROUND AND PURPOSE:Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst.MATERIALS AND METHODS:Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%–80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated.RESULTS:The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8–49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0–3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%–100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic (P < .001) and cosmetic (P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient.CONCLUSIONS:Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation.

Branchial cleft cyst (BCC) is a congenital epithelial cyst, which may arise in the lateral neck. The lesions are thought to represent failed obliteration of one of the brachial clefts during embryonic development.¹ Although BCC is benign, some patients have pain, swelling, neck discomfort, and cosmetic problems. Surgery is curative in patients with BCC, but in addition to the need for general anesthesia, its drawbacks include scarring and postoperative morbidity. Therefore, minimally invasive treatment such as ultrasonography (US)-guided chemical ablation has been suggested as an alternative treatment for BCC.^2–7Both chemical ablation with picibanil (OK-432) and ethanol ablation (EA) are widely used to treat cystic lesions of the neck and oral cavity, such as thyroid cyst, ranula, and lymphatic malformation,^8–13 but only a few studies have focused on the use of either treatment in BCCs. Since Fukumoto et al² initially used EA on 3 BCCs in 1994, several studies have reported success rates of roughly 60% in patients with BCC treated with OK-432.^3–7 However, OK-432 is not widely accepted as an alternative to an operation because of its limited efficacy and adverse effects such as fever and local pain after the procedure.^3–7 In patients with thyroid cysts, EA has been recommended as a first-line treatment technique, rather than OK-432, due to its higher efficacy and safety.^14–17 However, except for a case report by Fukumoto et al, there have been no studies on the efficacy and safety of EA in BCC, to our knowledge. Therefore, in this retrospective study, we evaluated the efficacy and safety of EA for the treatment of BCC in patients from 2 hospitals (Ajou Univeristy Medical Center, Sharing and Happiness Hospital).     

Effect of Collaterals on Clinical Presentation,Baseline Imaging,Complications, and Outcome in Acute Stroke

BACKGROUND AND PURPOSE:Good CTA collaterals independently predict good outcome in acute ischemic stroke. Our aim was to evaluate the role of collateral circulation and its added benefit over CTP-derived total ischemic volume as a predictor of baseline NIHSS score, total ischemic volume, hemorrhagic transformation, final infarct size, and a modified Rankin Scale score >2.MATERIALS AND METHODS:This was a retrospective study of 395 patients with stroke dichotomized by recanalization (recanalization positive/recanalization negative) and collateral status. Clot burden score was quantified on baseline CTA. Total ischemic volumes were derived from thresholded CTP maps. Final infarct size was assessed on follow-up CT/MRI. We performed uni-/multivariate analyses for each outcome, adjusting for rtPA status, using general linear (continuous variables) and logistic (binary variables) regression. Model comparison with collateral score and total ischemic volume was performed using the F or likelihood ratio test.RESULTS:Collateral presence independently and inversely predicted all outcomes except hemorrhagic transformation in patients who were recanalization negative and mRS >2 in patients who were recanalization positive. The greatest collateral benefit occurred in patients who were recanalization negative, contributing 16.5% and 19.2% of the variability for final infarct size and mRS >2. The collateral score model is superior to the total ischemic volume for mRS >2 prediction, but a combination of total ischemic volume and collateral score is superior for mRS >2 and final infarct prediction (24% and 28% variability, respectively). In patients who were recanalization positive, a model including collateral score and total ischemic volume was superior to that of total ischemic volume for hemorrhagic transformation and final infarct prediction but was muted compared with patients who were recanalization negative (11.3% and 16.9% variability).CONCLUSIONS:Collateral circulation is an independent predictor of all outcomes, but the magnitude of significance varies, greater in patients who were recanalization negative versus recanalization positive. Total ischemic volume assessment is complementary to collateral score in many cases.

In the setting of acute ischemic stroke, revascularization therapies are administered with the intent of salvaging ischemic penumbra by restoring antegrade flow.¹ Even though conventional angiography is considered the gold standard for collateral circulation assessment, CT angiography is increasingly used in triaging patients with acute stroke.²Growing evidence underscores the importance of the collateral circulation in maintaining the penumbra and predicting radiological and clinical response to revascularization.^3,4 Good CTA collaterals independently predict good outcome in acute ischemic stroke^1,2 and correlate with smaller admission infarct size.⁵ CTA collateral scoring demonstrates good interrater reliability^2,6–8; is widely available, including after-hours; and has the advantage of not requiring advanced postprocessing, which is subject to a host of technical differences.⁹ The best means of accurate collateral assessment is debated^1,10–13; however, irrespective of the method of assessment, collateral status significantly predicts clinical outcome and risk of infarct.^2,14,15 Limitations of collateral evaluation are that vessel opacification is time- and acquisition speed–dependent, indicating the need for time-invariant CTA imaging.^10,11 Additionally, the tissue perfusion status is not directly imaged in contradistinction to CT perfusion, in which penumbral prediction is well-studied.¹⁶A recent study suggested that a good clinical outcome could only be achieved in the presence of recanalization and good-to-intermediate collateral status. No effect was seen in patients without recanalization. Furthermore, the effect of other comorbid clinical (blood pressure, glycemic status, presence of vascular risk factors, and so forth) or radiological features (clot burden score [CBS], clot location, hemorrhagic transformation [HT]) was not considered in outcome determination.¹³ The relationship of collateral status and these other imaging and clinical stroke predictors, independent of recanalization status, for major outcomes is also not well-established in large acute stroke populations. Emphasis on collateral status has increased due to its recent inclusion in patient selection for endovascular treatment¹⁷; however, the added predictive value of collateral score (CS) over perfusion imaging assessment of total ischemia is not well-studied. We hypothesized that for a given recanalization status in the absence of perfusion availability, collateral determination significantly predicts baseline stroke severity (quantified by the baseline National Institutes of Health Stroke Scale score [bNIHSS]) and clinical (hemorrhagic transformation, 90-day modified Rankin Scale score of > 2) and radiological outcomes (final infarct volume). In the present study, we also sought to quantify the added value of a CS over CTP-estimated total ischemic volume (TIV). The added contribution was assessed independent of recanalization status and accounted for additional important clinical and imaging covariates in multivariate models.     

The Impact of Arterial Collateralization on Outcome after Intra-Arterial Therapy for Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Although intra-arterial therapy for acute ischemic stroke is associated with superior recanalization rates, improved clinical outcomes are inconsistently observed following successful recanalization. There is emerging concern that unfavorable arterial collateralization, though unproven, predetermines poor outcome. We hypothesized that poor leptomeningeal collateralization, assessed by preprocedural CTA, is associated with poor outcome in patients with acute ischemic stroke undergoing intra-arterial therapy.MATERIALS AND METHODS:We retrospectively analyzed patients with acute ischemic stroke with intracranial ICA and/or MCA occlusions who received intra-arterial therapy. The collaterals were graded on CTA. Univariate and multivariate analyses were used to investigate the association between the dichotomized leptomeningeal collateral score and functional outcomes at 3-months mRS ≤2, mortality, and intracranial hemorrhages.RESULTS:Eighty-seven patients were included. The median age was 66 years (interquartile range, 54–76 years) and the median NIHSS score at admission was 18 (interquartile range, 14–20). The leptomeningeal collateral score 3 was found to have significant association with the good functional outcome at 3 months: OR = 3.13; 95% CI, 1.25–7.825; P = .016. This association remained significant when adjusted for the use of IV tissue plasminogen activator: alone, OR = 2.998; 95% CI, 1.154–7.786; P = .024; and for IV tissue plasminogen activator and other confounders (age, baseline NIHSS score, and Thrombolysis in Cerebral Infarction grades), OR = 2.985; 95% CI, 1.027–8.673; P = .045.CONCLUSIONS:We found that poor arterial collateralization, defined as a collateral score of <3, was associated with poor outcome, after adjustment for recanalization success. We recommend that future studies include collateral scores as one of the predictors of functional outcome.

Intravenous tissue plasminogen activator is the only proved reperfusion therapy for acute ischemic stroke. However, a narrow therapeutic time window (<4.5 hours) limits its use because the clinical effectiveness is critically time-dependent.^1–3 In addition, recanalization rates with IV-tPA are low in the setting of large-artery occlusion, (eg, ICA occlusion <10%).^4–6 Intra-arterial therapy (IAT) has higher recanalization rates than intravenous thrombolysis, but this result has not been matched by concordant improvement in clinical outcomes.^7–9 Two recent randomized trials comparing IAT with IV-tPA, the Interventional Management of Stroke III trial and the Local versus Systemic Thrombolysis for Acute Ischemic Stroke trial, did not demonstrate superiority.^10,11Inadequate arterial collateralization is a possible mechanism to explain the mismatch between recanalization success and clinical outcome, apart from the presence of an already infarcted ischemic core and an incomplete microcirculatory reperfusion after focal cerebral ischemia.^12,13 A favorable arterial collateralization as determined by a robust leptomeningeal anastomoses profile may enhance recanalization, improve downstream reperfusion, reduce the extent of infarct core and ischemic lesion growth, decrease hemorrhagic transformation, and improve outcome postrevascularization.^14–16The leptomeningeal collateral scoring system based on CTA correlates with clinical outcome.^17–21 However, its role in IAT is unclear. We hypothesized that a poor leptomeningeal CTA score predicts clinical futility in patients undergoing IAT independent of recanalization status.     

Hypoperfusion Intensity Ratio Correlates with CTA Collateral Status in Large-Vessel Occlusion Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Collateral blood supply is a key determinant of outcome in large-vessel occlusion acute ischemic stroke. Single- and multiphase CTA collateral scoring systems have been described but are subjective and require training. We aimed to test whether the CTP-derived hypoperfusion intensity ratio is associated with CTA collateral status and whether a threshold hypoperfusion intensity ratio exists that predicts poor CTA collaterals.MATERIALS AND METHODS:Imaging and clinical data of consecutive patients with large-vessel occlusion acute ischemic stroke were retrospectively reviewed. Single-phase CTA and multiphase CTA scoring were performed by 2 blinded neuroradiologists using the Tan, Maas, and Calgary/Menon methods. CTP was processed using RApid processing of PerfusIon and Diffusion software (RAPID). Hypoperfusion intensity ratio = ratio of brain volume with time-to-maximum >10 seconds over time-to-maximum >6-second volume. Correlation between the hypoperfusion intensity ratio and CTA collateral scores was calculated using the Pearson correlation. The optimal threshold of the hypoperfusion intensity ratio for predicting poor collaterals was determined using receiver operating characteristic curve analysis.RESULTS:Fifty-two patients with large-vessel occlusion acute ischemic stroke were included. Multiphase CTA collateral scoring showed better interrater agreement (κ = 0.813) than single-phase CTA (Tan, κ = 0.587; Maas, κ = 0.273). The hypoperfusion intensity ratio correlated with CTA collateral scores (multiphase CTA: r = −0.55; 95% CI, −0.67 to −0.40; P ≤ .001). The optimal threshold for predicting poor multiphase CTA collateral status was a hypoperfusion intensity ratio of >0.45 (sensitivity = 78%; specificity = 76%; area under the curve = 0.86). Patients with high hypoperfusion intensity ratio/poor collateral status had lower ASPECTS/larger infarcts, higher NIHSS scores, and larger hypoperfused volumes.CONCLUSIONS:The hypoperfusion intensity ratio is associated with CTA collateral status in patients with large-vessel occlusion acute ischemic stroke. The hypoperfusion intensity ratio is an automated and quantitative alternative to CTA collateral scoring methods for both clinical and future stroke trial settings.

Endovascular thrombectomy (EVT) is the standard of care for eligible patients with large-vessel occlusion (LVO) acute ischemic stroke (AIS) up to 24 hours from symptom onset.^1-4 During LVO AIS, brain tissue in the territory of an acute LVO progresses with time through varying states of ischemia (penumbra) to infarction if untreated, with retrograde leptomeningeal collateral flow supplying the ischemic brain tissue (penumbra) beyond the LVO. The quality of collateral blood supply to the affected hemisphere in LVO AIS is a significant predictor of infarct size and growth, patient functional outcome,^5,6 and the rate of hemorrhagic transformation.^7-9 As a result, collateral status may impact eligibility for EVT as well as appropriateness for patient transfer to an EVT-capable hospital.^10,11Currently, imaging triage of collateral status is most commonly performed using CTA, and several CTA scoring systems have been devised. The Tan and Maas scoring systems were designed to evaluate collaterals on single-phase CTA (sCTA).^12-14 Multiphase CTA (mCTA), which includes additional late arterial and late venous phase CTAs, is the most widely studied and validated.¹⁵ The Calgary/Menon mCTA scoring system takes into account delayed filling of the MCA territory, which may be seen only in the late arterial or late venous phases. A limitation of these visual scoring systems, however, is their reliance on qualitative assessment, resulting in the need for additional training, susceptibility to reader bias, and interrater variability.¹⁶CTP is a widely used neuroimaging technique in the work-up of LVO AIS. Maps derived from CTP can be used to estimate the size of established infarct core relative to the volume of hypoperfused brain at risk of infarction (commonly referred to as penumbra).^17,18 Measuring infarct core volume and penumbra from sCTA or mCTA techniques is limited by temporal resolution. CTP acquisitions track the contrast density–bolus time curve for 45–60 seconds versus only 1–3 acquisition time points of sCTA or mCTA.The time for brain tissue to progress from ischemic penumbra to irreversibly infarcted core varies. Collateral status is the main determinant of how quickly the penumbral tissue will progress to irreversible infarct core. This progression can happen within an hour in some patients and in others it can take >24 hours because collateral status varies from patient to patient, as well as with changes in cerebral perfusion pressure during work-up, transfer, and treatment (eg, induction/intubation) of the patient. Obtaining a quantitative measure of collateral status from the CTP acquisition may obviate the need to measure it from a CTA (single-phase or multiphase) and help prognosticate the rate of progression of the penumbral volume to irreversible infarction.The hypoperfusion intensity ratio (HIR), defined as the ratio of the volume of tissue with a time-to-maximum (Tmax) of >10 seconds divided by the volume of tissue with a Tmax of >6 seconds,¹⁹ can be quantitatively derived from CT perfusion datasets. The HIR is a potential objective measure of collateral status¹⁹ and may be a surrogate for CTA scoring methods. This has been supported in post hoc analyses of small subcohorts of large randomized controlled trials primarily aimed at assessment of the effectiveness of EVT.^20,21 Recently, for M1 segment MCA occlusions, the HIR was found to correlate well with collateral scoring using the criterion standard diagnostic cerebral angiography (DCA) scoring (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology method) at the time of EVT.^22,23The purpose of this study was to assess whether the HIR correlates with sCTA and mCTA collateral status in patients presenting acutely with anterior circulation LVO AIS. We also aimed to determine whether a threshold HIR exists to indicate good-versus-poor mCTA collateral status.     

Computer-Assisted Volumetric Measurement of Core Infarct Volume in Pediatric Patients: Feasibility for Clinical Use and Development of Quantitative Metrics for Outcome Prediction

BACKGROUND AND PURPOSE:Infarct volume may predict clinical outcome in acute stroke, but manual segmentation techniques limit its routine use. We hypothesized that computer-assisted volumetric analysis to quantify acute infarct volume will show no difference compared with manual segmentation but will show increased speed of performance and will correlate with outcome.MATERIALS AND METHODS:Patients with acute stroke younger than 18 years were included. Infarct volume on diffusion-weighted imaging was quantified by using computer-assisted volumetric and manual techniques. The Pediatric Stroke Outcome Measure scored clinical outcome. Computer-assisted volumetric and manual techniques were compared with correlation coefficients. Linear regression analysis compared Pediatric Stroke Outcome Measure with core infarct volume and percentage volume of brain infarction.RESULTS:Twenty-three patients were analyzed (mean age, 4.6 years). Mean infarct volume from computer-assisted volumetric and manual approaches was 65.6 and 63.7 mL, respectively (P = .56). Concordance correlation between methods was 0.980, and between users, 0.968. The mean times for segmentation between computer-assisted volumetric and manual techniques were <1 minute and 7.3 minutes (P < .001). The mean infarct volumes for good and poor outcome groups were 7.4 and 75.7 mL (P < .007). The mean percentages of infarcted brain parenchyma for good and poor outcome groups were 0.6% and 10.4% (P < .006). Volumes of 32 mL and 3% for infarcted brain were associated with poor outcome in all patients.CONCLUSIONS:Computer-assisted volumetric quantification of infarct volume is reproducible, is significantly faster than manual techniques, and may have important applications for future clinical workflow. Core infarct volumes and infarct percentage correlated with outcome severity.

Stroke in the pediatric population is occurring at increasingly younger ages with an increasing incidence estimated at 3–5 per 100,000 according to the US Nationwide Inpatient Sample (http://www.healthdata.gov/data/dataset/hcup-nationwide-inpatient-sample-nis), which showed annual increases in acute ischemic stroke admissions from 1995 to 2008.^1–6 However, pediatric stroke remains under-recognized among health care providers; a lack of evidence-based treatment and management guidelines specific to the pediatric population further complicates this problem.^7,8 This represents a critical health care problem, given the potential cost to society in terms of life-years of disability and life-years lost in the face of increasing incidence of acute ischemic arterial infarction of children.^6,7,9,10Recent studies support infarct volume quantification as a potential tool in the pediatric population for predicting clinical outcome.^11–13 For example, Ganesan et al¹⁴ observed that infarcts of >10% parenchymal volume on T2-weighted imaging were associated with poor outcomes. Additionally, Domi et al¹⁵ reported that reduced diffusion in the corticospinal tract was a predictor of motor outcomes. Furthermore, investigations in adults have suggested that core infarct volume quantification correlates best with long-term outcome; this finding lends credibility to a similar approach in pediatric stroke.^16–19Currently, the criterion standard for volumetric assessment involves manual segmentation, which can be time-consuming and technically challenging. These impediments may limit its use in the emergency setting, where time is critical for management. For these reasons, computer-assisted volumetry (CAV) applied to diffusion-weighted imaging may represent a potential tool to aid in the detection of core infarct volume in the pediatric population. With regard to neuroimaging, CAV has recently been used in the examination of recurrent glioblastoma with high reproducibility and speed compared with conventional manual approaches.The purpose of this study was to describe a novel CAV technique for assessment of core infarct volume within the pediatric population. Specifically, we describe the reliability and feasibility of this technique compared with traditional manual approaches in patients with acute stroke. Additionally, the relationship between infarct volume and clinical outcomes by using the Pediatric Stroke Outcome Measure (PSOM) scale will be obtained.^20,21     

Middle Cerebral Artery Stenosis in Patients with Acute Ischemic Stroke and TIA in Israel

BACKGROUND AND PURPOSE:Middle cerebral artery stenosis is not frequent but a well-established cause of first and recurrent ischemic stroke. Our aim was to investigate middle cerebral artery stenosis in the biethnic (Jewish and Arab) population of patients with acute ischemic stroke and transient ischemic attack in northern Israel.MATERIALS AND METHODS:The study population included 1344 patients from the stroke data registry who had been hospitalized in the neurologic department because of acute ischemic stroke (1041) or TIA (303) and had undergone transcranial Doppler sonographic examination during the hospitalization.RESULTS:Of the 1344 patients, 120 (8.9%) were found to have MCA stenosis. The patients with intracranial stenosis were older and had more vascular risk factors (hypertension, diabetes, and hyperlipidemia) and vascular diseases (ischemic heart and peripheral vascular disease) than those without intracranial stenosis. Logistic regression analysis revealed that diabetes (P = .002) and peripheral vascular disease (P = .01), but not ethnicity, were independent and significant predictors for the presence of MCA stenosis.CONCLUSIONS:An independent and significant correlation was found between MCA stenosis and vascular risk factors (diabetes mellitus) and vascular diseases, thus emphasizing the similarity of intracranial MCA stenosis and other vascular diseases originating from atherosclerosis. There was no influence of ethnicity on intracranial stenosis in our population.

Intracranial stenosis is most commonly due to an atherosclerotic lesion of the intracranial vessels, leading to subsequent narrowing or occlusion of these vessels.^1,2 This condition is being increasingly recognized as an important and underestimated etiology in acute ischemic stroke.^3–5 Differences in the prevalence of intracranial stenosis in various populations have been reported, with the most vulnerable patients seeming to be Asians, Hispanics, and African Americans.^6–10 Because intracranial stenosis usually represents an atherosclerotic lesion, it is not surprising that there is a clear correlation between intracranial stenosis and vascular diseases and vascular risk factors.^11–15The aim of the present study was to search for possible determinants of potentially symptomatic middle cerebral artery stenosis in patients with stroke and transient ischemic attack in a biethnic (Jewish and Arab) population of northern Israel.Many studies in the literature suggest different transcranial Doppler sonography (TCD) parameters (peak systolic velocity, mean velocity) and different values as cutoffs for the diagnosis of intracranial stenosis. There are also many different definitions in the literature of intracranial stenosis (eg, “mild, moderate, and severe,” “less and more than 50%,” “50%–69% and more than 70%,” and so forth). There are still no generally accepted criteria for moderate intracranial stenosis. In this study, potentially symptomatic intracranial stenosis was defined as cases in which TCD examination showed a peak velocity in the middle cerebral artery, either left or right, of ≥140 cm/s. This value was used by some researchers as a criterion correlating with MCA stenosis of ≥50%.^3,16     

Emergent Endovascular Management of Long-Segment and Flow-Limiting Carotid Artery Dissections in Acute Ischemic Stroke Intervention with Multiple Tandem Stents

BACKGROUND AND PURPOSE:Although most cervical dissections are managed medically, emergent endovascular treatment may become necessary in the presence of intracranial large-vessel occlusions, flow-limiting and long-segment dissections with impending occlusion, and/or hypoperfusion-related ischemia at risk of infarction. We investigated the role of emergent endovascular stenting of long-segment carotid dissections in the acute ischemic stroke setting.MATERIALS AND METHODS:We retrospectively studied long-segment carotid dissections requiring stent reconstruction with multiple tandem stents (≥3 stents) and presenting with acute (<12 hours) ischemic stroke symptoms (NIHSS score, ≥4). We analyzed patient demographics, vascular risk factors, clinical presentations, imaging/angiographic findings, technical procedures/complications, and clinical outcomes.RESULTS:Fifteen patients (mean age, 51.5 years) with acute ischemic stroke (mean NIHSS score, 15) underwent endovascular stent reconstruction for vessel and/or ischemic tissue salvage. All carotid dissections presented with >70% flow limiting stenosis and involved the distal cervical ICA with a minimum length of 3.5 cm. Carotid stent reconstruction was successful in all patients with no residual stenosis or flow limitation. Nine patients (60%) harbored intracranial occlusions, and 6 patients (40%) required intra-arterial thrombolysis/thrombectomy, achieving 100% TICI 2b–3 reperfusion. Two procedural complications were limited to thromboembolic infarcts from in-stent thrombus and asymptomatic hemorrhagic infarct transformation (7% morbidity, 0% mortality). Angiographic and ultrasound follow-up confirmed normal carotid caliber and stent patency, with 2 cases of <20% in-stent stenosis. Early clinical improvement resulted in a mean discharge NIHSS score of 6, and 9/15 (60%) patients achieved a 90-day mRS of ≤2.CONCLUSIONS:Emergent stent reconstruction of long-segment and flow-limiting carotid dissections in acute ischemic stroke intervention is safe and effective, with favorable clinical outcomes, allowing successful thrombectomy, vessel salvage, restoration of cerebral perfusion, and/or prevention of recurrent thromboembolic stroke.

Cervical carotid or vertebral artery dissections are a common cause of acute ischemic stroke (AIS) in middle-aged and young adults.^1–3 The prognosis of cervical dissections is favorable, with the standard of care being medical management as the majority of patients respond to anticoagulation/antiplatelet therapy.^4,5 Delayed endovascular stenting of cervical dissections is reserved for patients presenting with recurrent ischemic symptoms and/or thromboembolic strokes refractory to medical management, progression of dissection-related stenosis, or symptomatic/enlarging dissecting pseudoaneurysms. Emergent endovascular treatment may also be required for cervical dissections presenting with concomitant intracranial thromboemboli/emergent large-vessel occlusion (ELVO), flow-limiting and long-segment lesions with impending occlusion, and/or hypoperfusion-related ischemia at risk of cerebral infarction.Multiple randomized controlled trials have proved endovascular thrombectomy the standard of care in the treatment of ELVO.^6–8 Since superimposed extracranial carotid or intracranial atherosclerotic disease and dissections are often an etiology of ELVO, recent studies have evaluated endovascular angioplasty/stenting techniques combined with intracranial thrombectomy. Adjunctive angioplasty/stenting techniques may be valuable in tandem carotid-intracranial occlusions secondary to acutely ruptured carotid atherosclerotic plaques, underlying intracranial atherosclerotic disease at risk for rethrombosis, or severe flow-limiting cervical/intracranial dissections. Furthermore, extracranial carotid stent placement may be necessary in emergent settings to provide distal access for intracranial thrombectomy, vessel salvage, or revascularization in hypoperfusion ischemic syndromes without sufficient intracranial collaterals. Several investigators have demonstrated the feasibility of emergency ICA stenting combined with intracranial thrombectomy for tandem ICA–MCA occlusions with acceptable rates of successful recanalization, complications, and clinical outcomes.^9–14 In two of the recent multicenter trials that demonstrated a benefit of endovascular thrombectomy for AIS, carotid artery stent placement was necessary in 8.6%–12.9% of patients.^6,7Few studies have focused on the endovascular management of spontaneous cervical dissections with or without tandem intracranial ELVOs in the AIS setting, often limited to small sample sizes because most dissections can be managed medically postthrombectomy.^15–17 We report on a unique cohort presenting for AIS intervention secondary to long-segment and flow-limiting carotid dissections requiring multiple tandem stents for endovascular reconstruction, irrespective of intracranial ELVO or successful thrombolysis/thrombectomy.     

Automatic Quantification of Subarachnoid Hemorrhage on Noncontrast CT

BACKGROUND AND PURPOSE:Quantification of blood after SAH on initial NCCT is an important radiologic measure to predict patient outcome and guide treatment decisions. In current scales, hemorrhage volume and density are not accounted for. The purpose of this study was to develop and validate a fully automatic method for SAH volume and density quantification.MATERIALS AND METHODS:The automatic method is based on a relative density increase due to the presence of blood from different brain structures in NCCT. The method incorporates density variation due to partial volume effect, beam-hardening, and patient-specific characteristics. For validation, automatic volume and density measurements were compared with manual delineation on NCCT images of 30 patients by 2 radiologists. The agreement with the manual reference was compared with interobserver agreement by using the intraclass correlation coefficient and Bland-Altman analysis for volume and density.RESULTS:The automatic measurement successfully segmented the hemorrhage of all 30 patients and showed high correlation with the manual reference standard for hemorrhage volume (intraclass correlation coefficient = 0.98 [95% CI, 0.96–0.99]) and hemorrhage density (intraclass correlation coefficient = 0.80 [95% CI, 0.62–0.90]) compared with intraclass correlation coefficient = 0.97 (95% CI, 0.77–0.99) and 0.98 (95% CI, 0.89–0.99) for manual interobserver agreement. Mean SAH volume and density were, respectively, 39.3 ± 31.5 mL and 62.2 ± 5.9 Hounsfield units for automatic measurement versus 39.7 ± 32.8 mL and 61.4 ± 7.3 Hounsfield units for manual measurement. The accuracy of the automatic method was excellent, with limits of agreement of −12.9–12.1 mL and −7.6–9.2 Hounsfield units.CONCLUSIONS:The automatic volume and density quantification is very accurate compared with manual assessment. As such, it has the potential to provide important determinants in clinical practice and research.

Despite improvements, the treatment of SAH is associated with high fatality rates and affects fairly young adults: up to half of all cases of SAH are fatal within 30 days, and the mean age of presentation is 55 years.^1–5 There is strong agreement among studies that the amount of subarachnoid blood on initial NCCT has a highly predictive value regarding patient outcome and the incidence of vasospasm and concomitant delayed cerebral ischemia.^3,4,6–9 Hemorrhagic density may be of equal importance in predicting patient outcome, but this has not been validated properly.^3,10–12 Currently several grading systems are used to assess the initial clinical and radiologic features of SAH.^7,8,13–15 However, there is still an ongoing discussion about the optimal method of grading SAH on NCCT.^3,7,16–18 The 2 most commonly used scales of Fisher et al⁷ and Hijdra et al⁸ have come under criticism; authors referred to these scales as rather gross estimators, difficult to apply, lacking quantification, and cumbersome in the clinical setting.^3,17,19–22 Moreover, hemorrhage density is not considered in these scales. A quantitative volume and density measurement may reduce interobserver variability in comparison with current scales and would provide physicians with a potentially valuable tool for outcome prediction and treatment guidance.²³ As such, the aim of this study was to design and validate a reliable and easy-to-apply automatic measurement for subarachnoid hemorrhage quantification.     

Safety and Efficacy of Endovascular Sonolysis Using the EkoSonic Endovascular System in Patients with Acute Stroke

BACKGROUND AND PURPOSE:Sonolysis is a new therapeutic procedure for arterial recanalization. The aim of this study was to confirm the safety and efficacy of endovascular sonolysis by using the EkoSonic Endovascular System in subjects with acute ischemic stroke.MATERIALS AND METHODS:Patients with acute ischemic stroke with occlusion of the middle cerebral artery or basilar artery were enrolled consecutively in this prospective study. The control group (44 MCA and 12 BA occlusions) was selected from historical controls. EkoSonic Endovascular System was started within 8 hours after stroke onset. The NIHSS score at hospital admission, after 24 hours, and at 7 days; arterial recanalization; early neurologic improvement; symptomatic intracerebral hemorrhage; and favorable 3-month clinical outcome defined as a modified Rankin Scale score of 0–2 were evaluated by statistical means.RESULTS:Fourteen patients (10 men; mean age, 65.1 ± 11.2 years; median NIHSS score, 16.5) underwent EkoSonic endovascular sonolysis. Arterial recanalization after endovascular treatment was achieved in 6 of 7 (85.7%) patients with MCA occlusion (4 complete recanalizations) and in all 7 (100%) patients with BA occlusion (6 complete recanalizations). No (0%) symptomatic intracerebral hemorrhage or periprocedural complications occurred. Seven (50%) patients were independent at 3 months (median mRS score, 2). Early neurologic improvement and favorable clinical outcome were significantly more frequent in patients with MCA occlusion undergoing EkoSonic endovascular sonolysis than in controls (100% and 71.4% versus 4.6% and 13.6% of patients; P = .0001 and P = .003, respectively). Three-month mortality was significantly lower in patients with BA occlusion undergoing EkoSonic endovascular sonolysis than in controls (0% versus 66.7% patients, P = .013).CONCLUSIONS:In this small study, EkoSonic endovascular sonolysis allowed safe and potentially effective revascularization in patients experiencing acute ischemic stroke.

Acute occlusion of cervical or intracranial arteries is the most common cause of ischemic stroke. Detection of arterial occlusion during the first 6 hours after the onset of ischemic stroke is possible in ≤70% of patients.^1–4 Clinical studies have shown that the prognosis of patients with occlusion of the intracranial arteries in the acute phase of ischemic stroke is worse compared with patients without occlusion of a major intracranial artery.⁵ One of the most important prognostic factors in patients with occlusion of the intracranial arteries is the time to recanalization.^6–9Data from a meta-analysis of 53 clinical trials (2066 patients) suggest that early recanalization is present in only 24.1% of patients without specific treatment (spontaneous recanalization), 46.2% of patients treated with intravenous thrombolysis, 63.2% of patients treated with intra-arterial thrombolysis, 67.5% of patients treated with combined IV thrombolysis–IAT, and in ≤83.6% of patients treated by mechanical methods.⁵The options for acceleration of recanalization of intracranial artery occlusion are the following: IV thrombolysis, IAT, or combined thrombolysis; mechanical recanalization by using several mechanical devices for thrombectomy and/or stent placement; and remote or local sonolysis.^10–24 Endovascular sonolysis can be used to accelerate and achieve recanalization of intracranial arterial occlusion.^22–24The aim of the present study was to confirm the safety and efficacy of endovascular sonolysis by using the EkoSonic Endovascular System (EKOS, Bothell, Washington) in patients with acute ischemic stroke with occlusion of the middle cerebral artery or basilar artery within 8 hours after stroke onset.     

Predictors of Reperfusion in Patients with Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Ischemic stroke studies emphasize a difference between reperfusion and recanalization, but predictors of reperfusion have not been elucidated. The aim of this study was to evaluate the relationship between reperfusion and recanalization and identify predictors of reperfusion.MATERIALS AND METHODS:From the Dutch Acute Stroke Study, 178 patients were selected with an MCA territory deficit on admission CTP and day 3 follow-up CTP and CTA. Reperfusion was evaluated on CTP, and recanalization on CTA, follow-up imaging. Reperfusion percentages were calculated in patients with and without recanalization. Patient admission and treatment characteristics and admission CT imaging parameters were collected. Their association with complete reperfusion was analyzed by using univariate and multivariate logistic regression.RESULTS:Sixty percent of patients with complete recanalization showed complete reperfusion (relative risk, 2.60; 95% CI, 1.63–4.13). Approximately one-third of patients showed some discrepancy between recanalization and reperfusion status. Lower NIHSS score (OR, 1.06; 95% CI, 1.01–1.11), smaller infarct core size (OR, 3.11; 95% CI, 1.46–6.66; and OR, 2.40; 95% CI, 1.14–5.02), smaller total ischemic area (OR, 4.20; 95% CI, 1.91–9.22; and OR, 2.35; 95% CI, 1.12–4.91), lower clot burden (OR, 1.35; 95% CI, 1.14–1.58), distal thrombus location (OR, 3.02; 95% CI, 1.76–5.20), and good collateral score (OR, 2.84; 95% CI, 1.34–6.02) significantly increased the odds of complete reperfusion. In multivariate analysis, only total ischemic area (OR, 6.12; 95% CI, 2.69–13.93; and OR, 1.91; 95% CI, 0.91–4.02) was an independent predictor of complete reperfusion.CONCLUSIONS:Recanalization and reperfusion are strongly associated but not always equivalent in ischemic stroke. A smaller total ischemic area is the only independent predictor of complete reperfusion.

Patients with acute ischemic stroke presenting within 4.5 hours are treated with IV-rtPA to dissolve the thrombus and achieve revascularization.¹ A recent consensus meeting on stroke imaging research (Acute Stroke Imaging Research Roadmap II) suggests that revascularization is a combination of 3 different mechanisms: 1) recanalization, referring to arterial patency; 2) reperfusion, which refers to antegrade microvascular perfusion; and 3) collateralization, which refers to microvascular perfusion via pial arteries or other anastomotic arterial channels that bypass the primary site of vessel occlusion.² Recanalization, reperfusion, and collateralization can be evaluated by CTA and CTP, which are frequently used in dedicated stroke imaging protocols. An important reason to look at the revascularization mechanisms separately is the concept that recanalization of an arterial occlusion, as visualized on CTA, does not necessarily lead to complete reperfusion and improved clinical outcome.^3,4 Furthermore, reperfusion can also occur without afferent vessel recanalization through collateralization of the ischemic area by collateral flow.^5,6Many previous studies, including those investigating intra-arterial therapy, consider recanalization to be synonymous with reperfusion.^7–10 Other articles suggest that this assumption is not justified and found reperfusion to be a better predictor of follow-up infarct volume and clinical outcome than recanalization.^{5,8,9,11–15}Although recanalization correlates well with improved reperfusion rates, it is unclear which other clinical and imaging factors influence reperfusion.^5,6,11,12,16 Knowing which factors, available before treatment decisions, predict complete reperfusion could aid in decision-making. Treatment with IV-rtPA, good collateral scores and lesion geography (location of the infarct relative to penumbra), and structure (solitary or multiple infarct areas) have been related to reperfusion status assessed with CT or MR imaging.^5,15,17–19The aim of this study was to evaluate the relationship between reperfusion and recanalization and to investigate which clinical and CT imaging parameters, available on admission, can help predict complete reperfusion in patients with acute ischemic stroke.     

Autosomal Dominant Polycystic Kidney Disease and Intracranial Aneurysms: Is There an Increased Risk of Treatment?

BACKGROUND AND PURPOSE:Autosomal dominant polycystic kidney disease is associated with an increased risk of intracranial aneurysms. Our purpose was to assess whether there is an increased risk during aneurysm coiling and clipping.MATERIALS AND METHODS:Data were obtained from the National Inpatient Sample (2000–2011). All subjects had an unruptured aneurysm clipped or coiled and were divided into polycystic kidney (n = 189) and control (n = 3555) groups. Primary end points included in-hospital mortality, length of stay, and total hospital charges. Secondary end points included the International Classification of Diseases, Ninth Revision codes for iatrogenic hemorrhage or infarction; intracranial hemorrhage; embolic infarction; and carotid and vertebral artery dissections.RESULTS:There was a significantly greater incidence of iatrogenic hemorrhage or infarction, embolic infarction, and carotid artery dissection in the patients with polycystic kidney disease compared with the control group after endovascular coiling. There was also a significantly greater incidence of iatrogenic hemorrhage or infarction in the polycystic kidney group after surgical clipping. However, the hospital stay was not longer in the polycystic kidney group, and the total hospital charges were not higher. Additional analysis within the polycystic kidney group revealed a significantly shorter length of stay but similar in-hospital costs when subjects underwent coiling versus clipping.CONCLUSIONS:Patients with polycystic kidney disease face an increased risk during intracranial aneurysm treatment, whether by coiling or clipping. This risk, however, does not translate into longer hospital stays or increased hospital costs. Despite the additional catheterization-related risks of dissection and embolization, coiling results in shorter hospital stays and similar mortality compared with clipping.

Autosomal dominant polycystic kidney disease (ADPCKD) is a genetic disorder affecting 1 in 1000 individuals worldwide and is associated with an increased risk of intracranial aneurysms, ranging from 4% to 23%^1–6 compared with the general population risk of 2%–3%.^7–10 Patients with ADPCKD are also at increased risk for aneurysm rupture earlier in life (mean age, 35–45 years),^1,11–13 compared with the general population (mean age, 50–54 years).^14,15There is evidence that the associated vascular defects in ADPCKD may be due to mutations in the PKD1 and PKD2 genes, located on the short arm of chromosomes 16 and 4.^16,17 Abnormalities of these genes in mouse models correspond with increased rates of arterial dissection, arterial rupture, and intracranial vascular abnormalities.¹⁸ To our knowledge, only 1 study to date has investigated whether these issues engender an increased risk when treating intracranial aneurysms (whether by endovascular coiling or surgical clipping).² The purpose of this investigation was to assess whether ADPCKD confers an increased peri- and immediate postprocedural risk of aneurysm coiling and clipping.     

Strategies of Collateral Blood Flow Assessment in Ischemic Stroke: Prediction of the Follow-Up Infarct Volume in Conventional and Dynamic CTA

BACKGROUND AND PURPOSE:Collateral blood flow is an important prognostic marker in the acute stroke situation but approaches for assessment vary widely. Our aim was to compare strategies of collateral blood flow assessment in dynamic and conventional CTA in their ability to predict the follow-up infarction volume.MATERIALS AND METHODS:We retrospectively included all patients with an M1 occlusion from an existing cohort of 1912 consecutive patients who underwent initial multimodal stroke CT and follow-up MR imaging or nonenhanced CT. Collateralization was assessed in both conventional CT angiography and dynamic CT angiography by using 3 different collateral grading scores and segmentation of the volume of hypoattenuation. Arterial, arteriovenous, and venous phases were reconstructed for dynamic CT angiography, and all collateral scores and the volume of hypoattenuation were individually assessed for all phases. Different grading systems were compared by using the Bayesian information criterion calculated for multivariate regression analyses (Bayesian information criterion difference = 2–6, “positive”; Bayesian information criterion difference = 6–10, “strong”; Bayesian information criterion difference = >10, “very strong”).RESULTS:One hundred thirty-six patients (mean age, 70.4 years; male sex, 41.2%) were included. In the multivariate analysis, models containing the volume of hypoattenuation showed a significantly better model fit than models containing any of the 3 collateral grading scores in conventional CT angiography (Bayesian information criterion difference = >10) and dynamic CT angiography (Bayesian information criterion difference = >10). All grading systems showed the best model fit in the arteriovenous phase. For the volume of hypoattenuation, model fit was significantly higher for models containing the volume of hypoattenuation as assessed in the arteriovenous phase of dynamic CT angiography compared with the venous phase (Bayesian information criterion difference = 6.2) and the arterial phase of dynamic CT angiography (Bayesian information criterion difference = >10) and in comparison with conventional CT angiography (Bayesian information criterion difference = >10).CONCLUSIONS:The use of dynamic CT angiography within the arteriovenous phase by using quantification of the volume of hypoattenuation is the superior technique for assessment of collateralization among the tested approaches.

In acute ischemic stroke, leptomeningeal collateral vessels provide blood flow to the ischemic bed of the occluded artery.^1,2 The extent of collateralization is an independent predictor of a small-lesion volume on follow-up imaging³ and a favorable clinical outcome.⁴ It has been further shown to predict response to intravenous thrombolysis⁵ and to determine penumbral tissue loss.⁶ Noninvasive imaging of collaterals can be performed by using CT angiography^7,8 or MR angiography.⁹ CTA offers the advantages of a wide availability and short scanning times.One strategy to assess collateral blood flow in CTA is through grading of collateral vessels in the territory of the occluded artery.^4,7,8 Currently, several different grading scores have been published,¹⁰ which differ not only in the number of categories of each score but also in the type of assessment (ie, an assessment relative to the contralateral hemisphere or absolute quantification). The 3 most commonly used scores in the literature include the following: 1) an absolute score assessing the percentage of the ischemic bed in which collateral filling is seen,³ 2) a relative score comparing collateral vessel enhancement within the ischemic bed with similar contralateral vessels,⁸ and 3) a detailed relative score comparing collateral vessel enhancement with similar contralateral vessels within each ASPECTS region.¹¹Another strategy to assess collateral blood flow is through quantification of hypoattenuated brain tissue in CTA source images.^12–15 Whereas hypoattenuation in nonenhanced CT (NECT) images represents the brain tissue net water uptake,¹⁶ hypoattenuation in CT angiography suggests an area receiving limited blood flow, which has been shown to correlate with initial diffusion-weighted images¹⁵ and follow-up lesion size.¹⁴ However, this correlation might be heavily influenced by the time point of image acquisition.¹³Recently, Smit et al¹⁷ demonstrated that conventional CTA can fail to capture delayed collateral enhancement. Delay-insensitive CT angiography with acquisition of multiple timeframes can help overcome this limitation. Its value in assessing the maximal extent of collateralization has been shown in several studies.^5,17,18 However, the time point of image analysis might play an important role in correctly assessing the prognostic value of the collateralization.The aim of our study was the following: 1) to determine the optimal time-phase for reconstruction of the dynamic CTA images to best predict follow-up lesion volume, and 2) to compare the predictive value of the volume of hypoattenuation with different collateral vessel grading scores.     

Outcomes Are Not Different between Patients with Intermediate and High DWI-ASPECTS after Stent-Retriever Embolectomy for Acute Anterior Circulation Stroke

BACKGROUND AND PURPOSE:Questions remain as to what benefits embolectomy provides to patients presented with considerable early ischemic changes on baseline imaging studies. This study aimed to investigate the impact of the Alberta Stroke Program Early CT Score applied to DWI on treatment outcomes in patients with acute stroke undergoing stent-retriever embolectomy.MATERIALS AND METHODS:We retrospectively analyzed the clinical and DWI data from 171 patients with acute anterior circulation stroke who were treated with stent-retriever embolectomy within 6 hours of symptom onset. DWI-ASPECTS scores were analyzed with the full scale or were dichotomized (4–6 versus 7–10). Patients with DWI-ASPECTS ≤3 were excluded from the study. Associations between outcome and clinical and radiologic factors were determined with a multivariate logistic regression analysis. A good outcome was defined as a modified Rankin Scale score of 0–2 at 3 months.RESULTS:The median DWI-ASPECTS was 7 (interquartile range, 6–8). The rates of good outcome, symptomatic hemorrhage, and mortality were not different between high DWI-ASPECTS (scores of 7–10) and intermediate DWI-ASPECTS (scores of 4–6) groups. In patients with an intermediate DWI-ASPECTS, good outcome was achieved in 46.5% (20/43) of patients with successful revascularization, whereas no patients without successful revascularization had a good outcome (P = .016). In multivariate logistic regression analysis, independent predictors of good outcome were age and successful revascularization.CONCLUSIONS:Our study suggested that there were no differences in outcomes between patients with a high DWI-ASPECTS and those with an intermediate DWI-ASPECTS who underwent stent-retriever embolectomy for acute anterior circulation stroke. Thus, patients with an intermediate DWI-ASPECTS otherwise eligible for endovascular therapy may not be excluded from stent-retriever embolectomy or stroke trials.

Recent randomized controlled trials have shown that stent-retriever embolectomy in addition to standard care was associated with improved functional outcome in patients with acute anterior circulation stroke due to large-vessel occlusion within 6–8 hours of symptom onset.^1–5 For further advancement in treating acute anterior circulation stroke, it is becoming important to more clearly refine the selection criteria for stent-retriever embolectomy. Several clinical and imaging factors are known to be associated with functional outcomes after endovascular treatment for acute anterior circulation stroke.^6–9 However, questions remain as to what benefits embolectomy provides to patients who present at extended time periods or those with considerable early ischemic changes on baseline imaging studies. Furthermore, the imaging technique that best determines candidacy for embolectomy in these patients remains unknown.ASPECTS is a 10-point semiquantitative scoring system, which was developed to offer the simplicity and reliability of CT to assess early ischemic changes in patients with acute ischemic stroke in the anterior circulation.¹⁰ ASPECTS has recently been applied to DWI, which is much more sensitive and accurate in the detection of acute infarction than noncontrast CT.^11–14 A recent study showed that interrater agreement for DWI-ASPECTS was superior to that for CT-ASPECTS and that DWI-ASPECTS outperformed CT-ASPECTS in predicting functional outcome at 90 days.⁹ The DWI-ASPECTS can also provide similar risk assessment far more rapidly than measurement of the infarct volume on DWI, an independent predictable marker of the clinical outcome, in patients with anterior circulation stroke.^9,15–17 However, few studies have investigated the association between pretreatment DWI-ASPECTS and functional outcome after stent-retriever embolectomy in patients with acute anterior circulation stroke.^9,14,18Although several studies showed that a DWI-ASPECTS of 7 was the optimal cutoff value for predicting clinical outcomes in patients undergoing intra-arterial or IV pharmacologic thrombolysis,^19–21 results of recent studies have suggested that some patients with a DWI-ASPECTS of <7 may still benefit from complete recanalization.¹⁴ Successful revascularization can be achieved more frequently by using stent-based embolectomy than by using pharmacologic thrombolysis or other mechanical devices.^1–5 In this context, patients with acute stroke and a DWI-ASPECTS of <7 might have a similar chance of a good outcome compared with those with a higher DWI-ASPECTS if they are treated with stent-retriever embolectomy in a short time window. However, this hypothesis has not been tested. Thus, this study aimed to investigate the impact of DWI-ASPECTS on functional outcome in patients with acute anterior circulation stroke who underwent stent-retriever embolectomy.     

Mechanical Thrombectomy of Distal Occlusions in the Anterior Cerebral Artery: Recanalization Rates,Periprocedural Complications,and Clinical Outcome

BACKGROUND AND PURPOSE:Patients with acute ischemic stroke in the anterior circulation are at risk for either primary or, following mechanical thrombectomy, secondary occlusion of the anterior cerebral artery. Because previous studies had only a limited informative value, we report our data concerning the frequency and location of distal anterior cerebral artery occlusions, recanalization rates, periprocedural complications, and clinical outcome.MATERIALS AND METHODS:We performed a retrospective analysis of prospectively collected data of patients with acute ischemic stroke undergoing mechanical thrombectomy in the anterior circulation between June 2010 and April 2015.RESULTS:Of 368 patients included in this analysis, we identified 30 (8.1%) with either primary (n = 17, 4.6%) or secondary (n = 13, 3.5%) embolic occlusion of the distal anterior cerebral artery. The recanalization rate after placement of a stent retriever was 88%. Periprocedural complications were rare and included vasospasms (n = 3, 10%) and dissection (n = 1, 3.3%). However, 16 (53.5%) patients sustained an (at least partial) infarction of the anterior cerebral artery territory. Ninety days after the ictus, clinical outcome according to the modified Rankin Scale score was the following: 0–2, n = 11 (36.6%); 3–4, n = 9 (30%); 5–6, n = 10 (33.3%).CONCLUSIONS:Occlusions of the distal anterior cerebral artery affect approximately 8% of patients with acute ischemic stroke in the anterior circulation receiving mechanical thrombectomy. Despite a high recanalization rate and a low complication rate, subsequent (partial) infarction in the anterior cerebral artery territory occurs in approximately half of patients. Fortunately, clinical outcome appears not to be predominately unfavorable.

Mechanical thrombectomy (MT) is an effective treatment in acute ischemic stroke secondary to a large-vessel occlusion.^1–4 Patients with acute ischemic stroke secondary to an occlusion of the internal carotid artery–T, middle cerebral artery trunk (M1), or MCA secondary division (M2) have relatively high rates of revascularization and favorable clinical outcomes after MT.^5,6 Unfortunately, for patients with ICA-T occlusions and MCA occlusions, there is a risk of approximately 8.6%–11.4% for secondary emboli into the anterior cerebral artery (ACA), especially the distal branches such as the pericallosal artery, during MT.^2,7,8 Although various technical possibilities, such as proximal flow control or combined aspiration, have been recommended to reduce the risk of secondary emboli^9–13, occlusions of the distal ACA occur.Regardless of the cause of the occlusion (primary occlusion or secondary emboli during MT), cerebral infarctions in the ACA territory may cause relevant clinical deficits by affecting the primary or supplementary motor areas.¹⁴ In a previous, relatively small patient cohort (n = 6), treatment of secondary ACA occlusions was technically successful in 80% of the cases and uneventful in all instances.⁷We present data on the frequency and location of distal ACA occlusions, recanalization rates, periprocedural complications, and clinical outcome.