Percent Insular Ribbon Infarction for Predicting Infarct Growth Rate and 90-Day Outcomes in Large-Vessel Occlusive Stroke: Secondary Analysis of Prospective Clinical Trial Data.

BACKGROUND. Insight into the natural history of infarct growth could help identify patients with slowly progressing stroke who may benefit from delayed endovascular thrombectomy (EVT). OBJECTIVE. The purpose of this article is to evaluate associations of percent insular ribbon infarction (PIRI) with infarct growth rate (IGR) and 90-day outcomes in patients with large-vessel occlusive stroke. METHODS. This retrospective study was a secondary analysis of a prior clinical trial that enrolled patients with acute stroke not treated with reperfusion therapies from January 2007 to June 2009. The present analysis evaluated 31 trial patients (median age, 71 years; 12 women, 19 men) with anterior-circulation large-vessel occlusion who underwent serial MRI examinations. Two neuroradiologists independently scored PIRI on presentation MRI examinations on the basis of the ratio of the length of the portion of the insula showing restricted diffusion to the insula's total length using a previously described 0-4 scale; scores were categorized (mild [0-1], moderate [2], or severe [3-4]), and discrepancies were resolved by consensus. The 90-day modified Rankin Scale (mRS) was obtained. As part of earlier clinical trial analyses, collateral pattern on CTA was classified as symmetric, malignant, or other, and infarct volumes were measured on DWI during the initial 48 hours after presentation and on FLAIR at 90 days. RESULTS. Interrater agreement for PIRI category was strong (κ = 0.89). PIRI was mild in 10, moderate in four, and severe in 17 patients. For mild, moderate, and severe PIRI, median IGR from onset to presentation was 1.6 cm3/h, 8.5 cm3/h, and 17.5 cm3/h (p < .001); median IGR from presentation to 48 hours was 0.3 cm3/h, 0.2 cm3/h, and 1.2 cm3/h (p = .005); median 90-day infarct volume was 9.4 cm3, 39.8 cm3, and 108.6 cm3 (p = .01); and 90-day mRS of 2 or less occurred in 78%, 67%, and 6% of patients (p = .001). In multivariable models controlling for age, internal carotid artery occlusion, and collateral pattern, PIRI category independently predicted onset-to-presentation IGR (ß = 1.5), presentation-to-48-hour IGR (ß = 1.3), and 90-day mRS of 2 or less (OR = 0.2). For predicting 90-day mRS of 2 or less, mild-to-moderate PIRI had sensitivity of 90.0% and specificity of 84.2%; symmetric collateral pattern had sensitivity of 70.0% and specificity of 73.7%. CONCLUSION. PIRI was independently associated with IGR and 90-day outcome. CLINICAL IMPACT. PIRI may help identify patients who could benefit from late-window EVT when requiring transfer to EVT-capable centers.

Symmetric CTA Collaterals Identify Patients with Slow-progressing Stroke Likely to Benefit from Late Thrombectomy.

Background Understanding ischemic core growth rate (IGR) is key in identifying patients with slow-progressing large vessel occlusion (LVO) stroke who may benefit from delayed endovascular thrombectomy (EVT). Purpose To evaluate whether symmetric collateral pattern at CT angiography (CTA) can help to identify patients with low IGR and small 24-hour diffusion-weighted MRI ischemic core volume in patients with LVO not treated with reperfusion therapies. Materials and Methods In this secondary analysis of clinical trial data from before EVT became standard of care from January 2007 to June 2009, patients with anterior proximal LVO not treated with reperfusion therapies were evaluated. All patients underwent admission CTA and at least three MRI examinations at four time points over 48 hours. Arterial phase CTA collaterals at presentation were categorized as symmetric, malignant, or other. Diffusion-weighted MRI ischemic core volume and IGR at multiple time points were determined. The IGR at presentation was defined as follows: (ischemic core volume in cubic centimeters)/(time since stroke symptom onset in hours). Multivariable analyses and receiver operator characteristic analyses were used. Results This study evaluated 31 patients (median age, 71 years; interquartile range, 61-81 years; 19 men) with median National Institutes of Health Stroke Scale (NIHSS) score of 13. Collaterals were symmetric (45%; 14 of 31), malignant (13%; four of 31), or other (42%; 13 of 31). Median ischemic core volume was different between collateral patterns at all time points. Presentation was as follows: symmetric, 16 cm3; other, 69 cm3; and malignant, 104 cm3 (P < .001). At 24 hours, median ischemic core volumes were as follows: symmetric, 28 cm3; other, 156 cm3; and malignant, 176 cm3 (P < .001). Median IGR was also different, and most pronounced at presentation: symmetric, 4 cm3 per hour; other, 17 cm3 per hour; and malignant, 20 cm3 per hour (P < .001). After multivariable adjustment, independent determinants of higher presentation IGR included only higher NIHSS (parameter estimate [ß = 0.20; 95% CI: 0.05, 0.36; P = .008) and worse collaterals (ß = -2.90; 95% CI: -4.31, -1.50; P < .001). The only independent determinant of 24-hour IGR was worse collaterals (ß = -2.03; 95% CI: -3.28, -0.78; P = .001). Symmetric collaterals had sensitivity of 87% (13 of 15) and specificity of 94% (15 of 16) for 24-hour ischemic core volume less than 50 cm3 (area under the receiver operating characteristic curve, 0.92; 95% CI: 0.81, 1.00; P < .001). Conclusion In patients with large vessel occlusion not treated with reperfusion therapies, symmetric collateral pattern at CT angiography was common and highly specific for low ischemic core growth rate and small 24-hour ischemic core volume as assessed at diffusion-weighted MRI. After further outcome studies, collateral status at presentation may prove useful in triage for endovascular thrombectomy, especially when MRI and CT perfusion are unavailable. Clinical trial registration no. NCT00414726. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Messina in this issue.

Myo-Inositol Levels Measured with MR Spectroscopy Can Help Predict Failure of Antiangiogenic Treatment in Recurrent Glioblastoma.

Background Patients with recurrent glioblastoma (GBM) are often treated with antiangiogenic agents, such as bevacizumab (BEV). Despite therapeutic promise, conventional MRI methods fail to help determine which patients may not benefit from this treatment. Purpose To use MR spectroscopic imaging (MRSI) with intermediate and short echo time to measure corrected myo-inositol (mI)normalized by contralateral creatine (hereafter, mI/c-Cr) in participants with recurrent GBM treated with BEV and to investigate whether such measurements can help predict survivorship before BEV initiation (baseline) and at 1 day, 4 weeks, and 8 weeks thereafter. Materials and Methods In this prospective longitudinal study (2016-2020), spectroscopic data on mI-a glial marker and osmoregulator within the brain-normalized by contralateral creatine in the intratumoral, contralateral, and peritumoral volumes of patients with recurrent GBM were evaluated. Area under the receiver operating characteristic curve (AUC) was calculated for all volumes at baseline and 1 day, 4 weeks, and 8 weeks after treatment to determine the ability of mI/c-Cr to help predict survivorship. Results Twenty-one participants (median age ± standard deviation, 62 years ± 12; 15 men) were evaluated. Lower mI/c-Cr in the tumor before and during BEV treatment was predictive of poor survivorship, with receiver operating characteristic analyses showing an AUC of 0.75 at baseline, 0.87 at 1 day after treatment, and 1 at 8 weeks after. A similar result was observed in contralateral normal-appearing tissue and the peritumoral volume, with shorter-term survivors having lower levels of mI/c-Cr. In the contralateral volume, a lower ratio of mI to creatine (hereafter, mI/Cr) predicted shorter-term survival at baseline and all other time points. Within the peritumoral volume, lower mI/c-Cr levels were predictive of shorter-term survival at baseline (AUC, 0.80), at 1 day after treatment (AUC, 0.93), and at 4 weeks after treatment (AUC, 0.68). Conclusion Lower levels of myo-inositol normalized by contralateral creatine within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and antiangiogenic treatment failure as early as before bevacizumab treatment. Adapting MR spectroscopic imaging alongside conventional MRI modalities conveys critical information regarding the biologic characteristics of tumors to help better treat individuals with recurrent glioblastoma. Clinical trial registration no. NCT02843230 © RSNA, 2021 Online supplemental material is available for this article.

Cardiovascular Risk Factors Affect Specific Segments of the Intracranial Vasculature in High-Resolution (HR) Vessel Wall Imaging (VWI).

OBJECTIVES: Luminal-based imaging have identified different risk factors for extracranial and intracranial atherosclerosis (ICAS), but these techniques are known to underestimate the true extent of the disease. High-resolution (HR) vessel wall imaging (VWI) has recently gained recognition as a valuable tool in the assessment of ICAS. The aim of this study is to determine the association between cardiovascular risk factors and specific intracranial vessel segment involvement using HR-VWI. MATERIALS AND METHODS: From January 2017 to January 2020, consecutive patients ≥ 18 years-old undergoing HR-VWI of the brain were identified. Patients with history of primary or secondary vasculitis, reversible cerebral vasoconstriction syndrome, or moya-moya were excluded. The presence of vessel wall thickening and enhancement were assessed in the perpendicular plane for each vessel segment by two neuroradiologists. Univariate and multivariate analyses were performed to assess associations between imaging findings and cardiovascular risk factors. Interrater reliability was calculated. RESULTS: Seventy-one patients (39 men; mean age: 55.9 years) were included. Vessel wall enhancement was seen in 39/71 (55%). A total number of 105 vessel segments demonstrated abnormal enhancement and 79/105 (75%) had an eccentric pattern. Eccentric vessel wall enhancement was independently associated with age >65 years-old in the ICA (OR 9.0, CI 2.1 - 38.2, p < 0.01) and proximal MCA (OR 4.0, CI 1.2 - 13.2, p = 0.02), and with hyperlipidemia in the posterior circulation (OR 44.0, CI2.9-661.0, p<0.01). CONCLUSION: There is a significant association between eccentric vessel wall enhancement of the ICA and proximal MCA in patients with age > 65; and of the proximal posterior circulation (basilar - PCA1) with hyperlipidemia.

Multivariable analysis on factors associated with aneurysm rupture in patients with multiple intracranial aneurysms.

PURPOSE: Multiple intracranial aneurysms (MIA) occur in one-third of patients with intracranial aneurysms (IA), and have been previously associated with an overall worse prognosis. Risk factors for IA formation and rupture in patients with a single IA are well-known. However, risk factors associated with rupture in patients with MIA have been less studied. METHODS: We performed a retrospective search of patients with MIA identified by computed tomography angiography (CTA) within a 10-year period. Patients with > 1 saccular aneurysm with size ≥ 2.0 mm were included. The location, size, number, and rupture status of the aneurysms were recorded. Patient demographics and cerebrovascular risk factors were obtained from electronic medical records. The primary endpoint of this study was to determine the association of these factors with aneurysmal rupture. The case-fatality rate was evaluated as a secondary outcome. RESULTS: Of the 2957 patients with IA in our CTA database, 425 patients were diagnosed with MIA and were therefore included in our study. A total of 1082 aneurysms were identified. Predictors of increased risk of aneurysmal rupture were age (OR 0.98, 95% CI, 0.96-0.99), size ≥ 5 mm (OR 4.4, 95% CI 2.76-7.0); and location in the anterior communicating artery complex (AcomC) (OR 2.62, 95% CI, 1.46-4.72) or posterior communicating artery (PCOM) (OR 2.66, 95% CI, 1.45-4.87). CONCLUSIONS: Younger age, aneurysm size ≥ 5 mm, and location in the AcomC and PCOM were independently associated with aneurysmal rupture in patients with MIA. Identifying these features could help recognize patients who might benefit from early intervention.

Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

Limited reliability of computed tomographic perfusion acute infarct volume measurements compared with diffusion-weighted imaging in anterior circulation stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) can reliably identify critically ischemic tissue shortly after stroke onset. We tested whether thresholded computed tomographic cerebral blood flow (CT-CBF) and CT-cerebral blood volume (CT-CBV) maps are sufficiently accurate to substitute for DWI for estimating the critically ischemic tissue volume. METHODS: Ischemic volumes of 55 patients with acute anterior circulation stroke were assessed on DWI by visual segmentation and on CT-CBF and CT-CBV with segmentation using 15% and 30% thresholds, respectively. The contrast:noise ratios of ischemic regions on the DWI and CT perfusion (CTP) images were measured. Correlation and Bland-Altman analyses were used to assess the reliability of CTP. RESULTS: Mean contrast:noise ratios for DWI, CT-CBF, and CT-CBV were 4.3, 0.9, and 0.4, respectively. CTP and DWI lesion volumes were highly correlated (R(2)=0.87 for CT-CBF; R(2)=0.83 for CT-CBV; P<0.001). Bland-Altman analyses revealed little systemic bias (-2.6 mL) but high measurement variability (95% confidence interval, ±56.7 mL) between mean CT-CBF and DWI lesion volumes, and systemic bias (-26 mL) and high measurement variability (95% confidence interval, ±64.0 mL) between mean CT-CBV and DWI lesion volumes. A simulated treatment study demonstrated that using CTP-CBF instead of DWI for detecting a statistically significant effect would require at least twice as many patients. CONCLUSIONS: The poor contrast:noise ratios of CT-CBV and CT-CBF compared with those of DWI result in large measurement error, making it problematic to substitute CTP for DWI in selecting individual acute stroke patients for treatment. CTP could be used for treatment studies of patient groups, but the number of patients needed to identify a significant effect is much higher than the number needed if DWI is used.

Rate of Contrast Extravasation on Computed Tomographic Angiography Predicts Hematoma Expansion and Mortality in Primary Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: In primary intracerebral hemorrhage, the presence of contrast extravasation after computed tomographic angiography (CTA), termed the spot sign, predicts hematoma expansion and mortality. Because the biological underpinnings of the spot sign are not fully understood, we investigated whether the rate of contrast extravasation, which may reflect the rate of bleeding, predicts expansion and mortality beyond the simple presence of the spot sign. METHODS: Consecutive intracerebral hemorrhage patients with first-pass CTA followed by a 90-second delayed postcontrast CT (delayed CTA) were included. CTAs were reviewed for spot sign presence by 2 blinded readers. Spot sign volumes on first-pass and delayed CTA and intracerebral hemorrhage volumes were measured using semiautomated software. Extravasation rates were calculated and tested for association with hematoma expansion and mortality using uni- and multivariable logistic regressions. RESULTS: One hundred and sixty-two patients were included, 48 (30%) of whom had ≥1 spot sign. Median spot sign volume was 0.04 mL on first-pass CTA and 0.4 mL on delayed CTA. Median extravasation rate was 0.23 mL/min overall and 0.30 mL/min among expanders versus 0.07 mL/min in nonexpanders. Extravasation rates were also significantly higher in patients who died in hospital: 0.27 mL/min versus 0.04 mL/min. In multivariable analysis, the extravasation rate was independently associated with in-hospital mortality (odds ratio, 1.09 [95% confidence interval, 1.04-1.18], P=0.004), 90-day mortality (odds ratio, 1.15 [95% confidence interval, 1.08-1.27]; P=0.0004), and hematoma expansion (odds ratio, 1.03 [95% confidence interval, 1.01-1.08]; P=0.047). CONCLUSIONS: Contrast extravasation rate, or spot sign growth, further refines the ability to predict hematoma expansion and mortality. Our results support the hypothesis that the spot sign directly measures active bleeding in acute intracerebral hemorrhage.