Livia T. Morais

Clot Length Distribution and Predictors in Anterior Circulation Stroke Implications for Intra-Arterial Therapy

Background and Purpose— Thin-section noncontrast computed tomography images can be used to measure hyperdense clot length in acute ischemic stroke. Clots ≥8 mm have a very low probability of intravenous tissue-type plasminogen activator recanalization and hence may benefit from a bridging intra-arterial approach. To understand the prevalence of such clots, we sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. Methods— Of 623 consecutive patients with acute ischemic stroke, 53 met inclusion criteria: presentation <8 hours from onset; intracranial internal carotid artery-terminus or proximal-middle cerebral artery occlusion; admission thin-slice noncontrast computed tomography (⩽2.5 mm); and no intravenous tissue-type plasminogen activator pretreatment. For each patient, hyperdense clot length was measured and recorded along with additional relevant imaging and clinical data. Results— Mean age was 70 years, and mean time to computed tomography was 213 minutes. Median baseline National Institutes of Health Stroke Scale was 16.5. Occlusions were located in the internal carotid artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean and median clot lengths (mm) of 18.5 (±14.2) and 16.1 (7.6–25.2), respectively. Occlusion location was the strongest predictor of clot length (multivariate, P=0.02). Clot length was ≥8 mm in 94%, 73%, and 22% of internal carotid artery-terminus, M1, and M2 occlusions, respectively. Conclusions— The majority of anterior circulation proximal occlusions are ≥8 mm long, helping to explain the low published rates of intravenous tissue-type plasminogen activator recanalization. Internal carotid artery-terminus occlusion is an excellent marker for clot length ≥8 mm; vessel-imaging status alone may be sufficient. Thin-section noncontrast computed tomography seems useful for patients with middle cerebral artery occlusion because of the wide variability of clot lengths.

In Acute Stroke, Can CT Perfusion-Derived Cerebral Blood Volume Maps Substitute for Diffusion-Weighted Imaging in Identifying the Ischemic Core?

Background and Purpose In the treatment of patients with suspected acute ischemic stroke, increasing evidence suggests the importance of measuring the volume of the irreversibly injured “ischemic core.” The gold standard method for doing this in the clinical setting is diffusion-weighted magnetic resonance imaging (DWI), but many authors suggest that maps of regional cerebral blood volume (CBV) derived from computed tomography perfusion imaging (CTP) can substitute for DWI. We sought to determine whether DWI and CTP-derived CBV maps are equivalent in measuring core volume. Methods 58 patients with suspected stroke underwent CTP and DWI within 6 hours of symptom onset. We measured low-CBV lesion volumes using three methods: “objective absolute,” i.e. the volume of tissue with CBV below each of six published absolute thresholds (0.9–2.5 mL/100 g), “objective relative,” whose six thresholds (51%-60%) were fractions of mean contralateral CBV, and “subjective,” in which two radiologists (R1, R2) outlined lesions subjectively. We assessed the sensitivity and specificity of each method, threshold, and radiologist in detecting infarction, and the degree to which each over- or underestimated the DWI core volume. Additionally, in the subset of 32 patients for whom follow-up CT or MRI was available, we measured the proportion of CBV- or DWI-defined core lesions that exceeded the follow-up infarct volume, and the maximum amount by which this occurred. Results DWI was positive in 72% (42/58) of patients. CBV maps’ sensitivity/specificity in identifying DWI-positive patients were 100%/0% for both objective methods with all thresholds, 43%/94% for R1, and 83%/44% for R2. Mean core overestimation was 156–699 mL for objective absolute thresholds, and 127–200 mL for objective relative thresholds. For R1 and R2, respectively, mean±SD subjective overestimation were -11±26 mL and -11±23 mL, but subjective volumes differed from DWI volumes by up to 117 and 124 mL in individual patients. Inter-rater agreement regarding the presence of infarction on CBV maps was poor (kappa = 0.21). Core lesions defined by the six objective absolute CBV thresholds exceeded follow-up infarct volumes for 81%-100% of patients, by up to 430–1002 mL. Core estimates produced by objective relative thresholds exceeded follow-up volumes in 91% of patients, by up to 210-280 mL. Subjective lesions defined by R1 and R2 exceeded follow-up volumes in 18% and 26% of cases, by up to 71 and 15 mL, respectively. Only 1 of 23 DWI lesions (4%) exceeded final infarct volume, by 3 mL. Conclusion CTP-derived CBV maps cannot reliably substitute for DWI in measuring core volume, or even establish which patients have DWI lesions.

Admission Insular Infarction >25% Is the Strongest Predictor of Large Mismatch Loss in Proximal Middle Cerebral Artery Stroke

Background and Purpose— Previous univariate analyses have suggested that proximal middle cerebral artery infarcts with insular involvement have greater severity and are more likely to progress into surrounding penumbral tissue at risk. We hypothesized that a practical, simple scoring method to assess percent insular ribbon infarction (PIRI score) would improve prediction of penumbral loss over other common imaging biomarkers. Methods— Of consecutive acute stroke patients from 2003 to 2008, 45 with proximal middle cerebral artery–only occlusion met inclusion criteria, including available penumbral imaging. Infarct (diffusion-weighted imaging), tissue at risk (magnetic resonance mean transit time), and final infarct volume (magnetic resonance/computed tomography) were manually segmented. Diffusion-weighted imaging images were rated according to the 5-point PIRI score (0, normal; 1, <25%; 2, 25%–49%; 3, 50%–74%; 4, ≥75% insula involvement). Percent mismatch loss was calculated as an outcome measure of infarct progression. Receiver operating characteristic curve and multivariate analyses were performed. Results— Mean admission diffusion-weighted imaging infarct volume was 30.9 (±38.8) mL and median (interquartile range) PIRI score was 3 (0.75–4). PIRI score was significantly correlated with percent mismatch loss (P<0.0001). When percent mismatch loss was dichotomized based on its median value (30.0%), receiver operating characteristic curve area under curve was 0.89 (P=0.0001) with a 25% insula infarction optimal threshold. After adjusting for time to imaging and treatment, binary logistic regression, including dichotomized PIRI (25% threshold), age, National Institutes of Health Stroke Scale score, diffusion-weighted imaging infarct volume, and computed tomography angiography collateral score as covariates, revealed that only dichotomized insula score (P=0.03) and age (P=0.02) were independent predictors of large (68.2%) versus small (8.1%) mismatch loss. There was excellent interobserver agreement for dichotomized PIRI scoring (&kgr;=0.91). Conclusions— Admission insular infarction >25% is the strongest predictor of large mismatch loss in this cohort of proximal middle cerebral artery occlusive stroke. This outcome marker may help to identify treatment-eligible patients who are in greatest need of rapid reperfusion therapy.

Imaging-based selection for intra-arterial stroke therapies

Reperfusion therapy is the only proven treatment for acute ischemic stroke.1 ,2 For proximal arterial occlusions, intra-arterial treatment (IAT) yields substantially higher rates of early revascularization than FDA-approved treatment with intravenous tissue plasminogen activator (tPA).3 However, recent randomized controlled trials (RCTs) show no added clinical benefit of IAT compared with standard medical management.4–6 Although there are clear limitations to these trials,7 a major lesson is that the signal of benefit favoring IAT is much smaller than expected. In this context, improving patient selection for IAT remains essential, with neuroimaging playing a central role. This article begins with a pathophysiologic argument for the importance of imaging, discusses the available neuroimaging tools and their reliability and reviews the evidence supporting the use of imaging to predict the response to IAT. Current guidelines recommend a time window of 6 h for intra-arterial thrombolysis.8 Mechanical therapies are cleared for use up to 8 h. Although the time window for IAT efficacy remains unclear,9 treatment efficacy erodes with time,10 placing a clear emphasis on rapid treatment delivery. However, this has come at the expense of potentially valuable neuroimaging as well as a rigorous approach to imaging interpretation. In both the SYNTHESIS Expansion and Interventional Management of Stroke (IMS) III trials (table 1), only a non-contrast CT (NCCT) scan was required prior to enrollment.5 ,6 The primary imaging exclusion criterion for the SYNTHESIS Expansion trial (in addition to hemorrhage) was the presence of well-established infarction (as a marker of potentially longer stroke duration). For IMS III, it was the presence of clear hypodensity involving more than one-third of the middle cerebral artery (MCA) territory. As will be discussed, these findings are of limited value in excluding patients who are unlikely to respond to treatment. The major limitation of …

In patients with suspected acute stroke, CT perfusion-based cerebral blood flow maps cannot substitute for DWI in measuring the ischemic core

Background Neuroimaging may guide acute stroke treatment by measuring the volume of brain tissue in the irreversibly injured “ischemic core.” The most widely accepted core volume measurement technique is diffusion-weighted MRI (DWI). However, some claim that measuring regional cerebral blood flow (CBF) with CT perfusion imaging (CTP), and labeling tissue below some threshold as the core, provides equivalent estimates. We tested whether any threshold allows reliable substitution of CBF for DWI. Methods 58 patients with suspected stroke underwent DWI and CTP within six hours of symptom onset. A neuroradiologist outlined DWI lesions. In CBF maps, core pixels were defined by thresholds ranging from 0%-100% of normal, in 1% increments. Replicating prior studies, we used receiver operating characteristic (ROC) curves to select thresholds that optimized sensitivity and specificity in predicting DWI-positive pixels, first using only pixels on the side of the brain where infarction was clinically suspected (“unilateral” method), then including both sides (“bilateral”). We quantified each method and threshold’s accuracy in estimating DWI volumes, using sums of squared errors (SSE). For the 23 patients with follow-up studies, we assessed whether CBF-derived volumes inaccurately exceeded follow-up infarct volumes. Results The areas under the ROC curves were 0.89 (unilateral) and 0.90 (bilateral). Various metrics selected optimum CBF thresholds ranging from 29%-32%, with sensitivities of 0.79–0.81, and specificities of 0.83–0.85. However, for the unilateral and bilateral methods respectively, volume estimates derived from all CBF thresholds above 28% and 22% were less accurate than disregarding imaging and presuming every patient’s core volume to be zero. The unilateral method with a 30% threshold, which recent clinical trials have employed, produced a mean core overestimation of 65 mL (range: –82–191), and exceeded follow-up volumes for 83% of patients, by up to 191 mL. Conclusion CTP-derived CBF maps cannot substitute for DWI in measuring the ischemic core.

Response to Letter Regarding Article, “Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-Arterial Therapy”

We thank Wanklyn et al1 for their comments. We agree wholeheartedly that even in the setting of long clots (eg, ≥8 mm), intravenous recombinant tissue-type plasminogen activator (tPA) should be administered rapidly to eligible acute ischemic stroke patients. Although the probability of early intravenous tPA recanalization of such clots is low, it is not zero, as demonstrated by the cases provided. Indeed, in a nonrandomized Virtual International Stroke Trials Archive (VISTA) study, intravenous tPA benefit extended to patients with severe neurological deficits, up to National Institutes of Health Stroke Scale score of 24.2 We know that many of these patients with severe stroke harbor proximal occlusions and long clots. One argument against intravenous tPA use for long …

Clot Length Distribution and Predictors in Anterior Circulation Stroke

Background and Purpose— Thin-section noncontrast computed tomography images can be used to measure hyperdense clot length in acute ischemic stroke. Clots ≥8 mm have a very low probability of intravenous tissue-type plasminogen activator recanalization and hence may benefit from a bridging intra-arterial approach. To understand the prevalence of such clots, we sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. Methods— Of 623 consecutive patients with acute ischemic stroke, 53 met inclusion criteria: presentation <8 hours from onset; intracranial internal carotid artery-terminus or proximal-middle cerebral artery occlusion; admission thin-slice noncontrast computed tomography (⩽2.5 mm); and no intravenous tissue-type plasminogen activator pretreatment. For each patient, hyperdense clot length was measured and recorded along with additional relevant imaging and clinical data. Results— Mean age was 70 years, and mean time to computed tomography was 213 minutes. Median baseline National Institutes of Health Stroke Scale was 16.5. Occlusions were located in the internal carotid artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean and median clot lengths (mm) of 18.5 (±14.2) and 16.1 (7.6–25.2), respectively. Occlusion location was the strongest predictor of clot length (multivariate, P=0.02). Clot length was ≥8 mm in 94%, 73%, and 22% of internal carotid artery-terminus, M1, and M2 occlusions, respectively. Conclusions— The majority of anterior circulation proximal occlusions are ≥8 mm long, helping to explain the low published rates of intravenous tissue-type plasminogen activator recanalization. Internal carotid artery-terminus occlusion is an excellent marker for clot length ≥8 mm; vessel-imaging status alone may be sufficient. Thin-section noncontrast computed tomography seems useful for patients with middle cerebral artery occlusion because of the wide variability of clot lengths.

Clot length Distribution and Predictors in Anterior Circulation Stroke: Implications for IA Therapy

Background and Purpose— Thin-section noncontrast computed tomography images can be used to measure hyperdense clot length in acute ischemic stroke. Clots ≥8 mm have a very low probability of intravenous tissue-type plasminogen activator recanalization and hence may benefit from a bridging intra-arterial approach. To understand the prevalence of such clots, we sought to determine the distribution and predictors of clot lengths in consecutive anterior circulation proximal artery occlusions. Methods— Of 623 consecutive patients with acute ischemic stroke, 53 met inclusion criteria: presentation <8 hours from onset; intracranial internal carotid artery-terminus or proximal-middle cerebral artery occlusion; admission thin-slice noncontrast computed tomography (⩽2.5 mm); and no intravenous tissue-type plasminogen activator pretreatment. For each patient, hyperdense clot length was measured and recorded along with additional relevant imaging and clinical data. Results— Mean age was 70 years, and mean time to computed tomography was 213 minutes. Median baseline National Institutes of Health Stroke Scale was 16.5. Occlusions were located in the internal carotid artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean and median clot lengths (mm) of 18.5 (±14.2) and 16.1 (7.6–25.2), respectively. Occlusion location was the strongest predictor of clot length (multivariate, P=0.02). Clot length was ≥8 mm in 94%, 73%, and 22% of internal carotid artery-terminus, M1, and M2 occlusions, respectively. Conclusions— The majority of anterior circulation proximal occlusions are ≥8 mm long, helping to explain the low published rates of intravenous tissue-type plasminogen activator recanalization. Internal carotid artery-terminus occlusion is an excellent marker for clot length ≥8 mm; vessel-imaging status alone may be sufficient. Thin-section noncontrast computed tomography seems useful for patients with middle cerebral artery occlusion because of the wide variability of clot lengths.