Is the optimal Tmax threshold identifying perfusion deficit volumes variable across MR perfusion software packages? A pilot study.

PURPOSE: Accurate quantification of ischemic core and ischemic penumbra is mandatory for late-presenting acute ischemic stroke. Substantial differences between MR perfusion software packages have been reported, suggesting that the optimal Time-to-Maximum (Tmax) threshold may be variable. We performed a pilot study to assess the optimal Tmax threshold of two MR perfusion software packages (A: RAPID®; B: OleaSphere®) by comparing perfusion deficit volumes to final infarct volumes as ground truth. METHODS: The HIBISCUS-STROKE cohort includes acute ischemic stroke patients treated by mechanical thrombectomy after MRI triage. Mechanical thrombectomy failure was defined as a modified thrombolysis in cerebral infarction score of 0. Admission MR perfusion were post-processed using two packages with increasing Tmax thresholds (≥ 6 s, ≥ 8 s and ≥ 10 s) and compared to final infarct volume evaluated with day-6 MRI. RESULTS: Eighteen patients were included. Lengthening the threshold from ≥ 6 s to ≥ 10 s led to significantly smaller perfusion deficit volumes for both packages. For package A, Tmax ≥ 6 s and ≥ 8 s moderately overestimated final infarct volume (median absolute difference: - 9.5 mL, interquartile range (IQR) [- 17.5; 0.9] and 0.2 mL, IQR [- 8.1; 4.8], respectively). Bland-Altman analysis indicated that they were closer to final infarct volume and had narrower ranges of agreement compared with Tmax ≥ 10 s. For package B, Tmax ≥ 10 s was closer to final infarct volume (median absolute difference: - 10.1 mL, IQR: [- 17.7; - 2.9]) versus - 21.8 mL (IQR: [- 36.7; - 9.5]) for Tmax ≥ 6 s. Bland-Altman plots confirmed these findings (mean absolute difference: 2.2 mL versus 31.5 mL, respectively). CONCLUSIONS: The optimal Tmax threshold for defining the ischemic penumbra appeared to be most accurate at ≥ 6 s for package A and ≥ 10 s for package B. This implies that the widely recommended Tmax threshold ≥ 6 s may not be optimal for all available MRP software package. Future validation studies are required to define the optimal Tmax threshold to use for each package.

Etiologies of spontaneous acute intracerebral hemorrhage: A pictorial review.

Spontaneous acute intracerebral hemorrhage (SAIH) is a common and life-threatening condition that affects more than three million patients each year. Of these, one in three patients die within one month of onset and the remaining two in three patients have varying degrees of disability and neurological impairment. The role of radiology is paramount in optimizing patient outcomes by diagnosing SAIH, its potential complications, and the most likely etiology. While the positive diagnosis of SAIH is straightforward, the etiologic diagnosis is broad, covering primary SAIH (hypertension, cerebral amyloid angiopathy) and secondary SAIH (vascular malformations, nonatheromatous vasculopathies, neoplasia, coagulation disorders, toxicants). This pictorial review illustrates the imaging of spontaneous SAIH with an emphasis on etiologic workup.

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial.

BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.

Association of Blood Biomarkers of Inflammation With Penumbra Consumption After Mechanical Thrombectomy in Patients With Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: The objective of this study was to assess the relationship between blood biomarkers of inflammation and lesion growth within the penumbra in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). METHODS: The HIBISCUS-STROKE cohort enrolled patients admitted in the Lyon Stroke Center for an anterior circulation AIS treated with MT after brain MRI assessment. Lesion growth within the penumbra was assessed on day 6 MRI using a voxel-based nonlinear coregistration method and dichotomized into low and high according to the median value. C-reactive protein, interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, soluble tumor necrosis factor receptor I, soluble form suppression of tumorigenicity 2 (sST2), soluble P-selectin, vascular cellular adhesion molecule-1, and matrix metalloproteinase-9 were measured in sera at 4 time points within the first 48 hours. Reperfusion was considered as successful if Thrombolysis in Cerebral Infarction score was 2b/2c/3. A multiple logistic regression model was performed to detect any association between area under the curve (AUC) of these biomarkers within the first 48 hours and a high lesion growth within the penumbra. RESULTS: Ninety patients were included. The median lesion growth within the penumbra was 2.3 (0.7-6.2) mL. On multivariable analysis, a high sST2 AUC (OR 3.77, 95% CI 1.36-10.46), a high baseline DWI volume (OR 3.65, 95% CI 1.32-10.12), and a lack of successful reperfusion (OR 0.19, 95% CI 0.04-0.92) were associated with a high lesion growth within the penumbra. When restricting analyses to patients with successful reperfusion (n = 76), a high sST2 AUC (OR 5.03, 95% CI 1.64-15.40), a high baseline DWI volume (OR 3.74, 95% CI 1.22-11.53), and a high penumbra volume (OR 3.25, 95% CI 1.10-9.57) remained associated with a high lesion growth within the penumbra. DISCUSSION: High sST2 levels within the first 48 hours are associated with a high lesion growth within the penumbra.

Large vessel cardioembolic stroke and embolic stroke of undetermined source share a common profile of matrix metalloproteinase-9 level and susceptibility vessel sign length.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for up to 25% of ischemic strokes. Identification of biomarkers that could improve the prediction of stroke subtype and subsequently of stroke prevention still remains a major issue. METHODS: The HIBISCUS-STROKE cohort includes ischemic stroke patients with large vessel occlusion treated with mechanical thrombectomy following admission magnetic resonance imaging. Presence and length of susceptibility vessel sign (SVS) were assessed by gradient-recalled echo T2*-weighted imaging. Matrix metalloproteinase-9 (MMP-9) was measured on sera collected at admission. A multiple logistic regression model was performed to detect independent markers distinguishing cardioembolic (CE) from large-artery atherosclerosis (LAA) subtype. RESULTS: A total of 147 patients were included, of them the etiology was distributed as follows: 86 (58.5%) CE, 26 (17.7%) LAA, and 35 (23.8%) ESUS. The optimal cutoff for differentiating CE from LAA subtype was 14.5 mm for SVS length (sensitivity, 79.7%; specificity, 72.7%) and 1110 ng/ml for admission MMP-9 level (sensitivity, 85.3%; specificity, 52.2%). Multivariate analysis revealed that current smoking (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.01-0.93), tandem occlusion (OR 0.01, 95% CI 0.01-0.21), SVS length (OR 0.78, 95% CI 0.63-0.97), and admission MMP-9 level (OR 0.99, 95% CI 0.99-1.00) were inversely associated with CE subtype. SVS length and MMP-9 level did not differ between ESUS and CE subtypes. CONCLUSION: SVS length and admission MMP-9 level may improve the prediction of CE subtype whose profile is close to ESUS, thus suggesting a common cardiac embolic source.

Association of Interleukin-6 Levels and Futile Reperfusion After Mechanical Thrombectomy.

OBJECTIVE: To assess whether interleukin-6 (IL-6) level is a marker of futile reperfusion in patients with acute ischemic stroke (AIS) with large vessel occlusion treated with mechanical thrombectomy (MT). METHODS: The Cohort of Patients to Identify Biological and Imaging Markers of Cardiovascular Outcomes in Stroke (HIBISCUS-STROKE) includes patients with AIS treated with MT after MRI. We performed a sequential assessment of IL-6 (admission, 6 hours, 24 hours, 48 hours and 3 months from admission). Among patients with successful reperfusion (Thrombolysis in Cerebral Infarction scale 2b/3), reperfusion was considered effective if 3-month modified Rankin Scale (mRS) score was 0 to 2 and futile if 3-month mRS score was 3 to 6. Our model was adjusted for the main confounding variables. RESULTS: One hundred sixty-four patients represent the study population. One hundred thirty-three patients had successful reperfusion (81.1%), while in 46 (34.6%), reperfusion was classified as futile. In single-variable analyses, high IL-6 levels at 6, 24, and 48 hours in combination with a higher age, a prestroke mRS score >2, a history of hypertension or diabetes, lack of current smoking, a higher baseline NIH Stroke Scale score, the absence of associated intravenous thrombolysis, an intracranial internal carotid artery or a tandem occlusion, and an increased infarct growth were associated with futile reperfusion. After multivariable analyses, a high IL-6 level at 24 hours (odds ratio 6.15, 95% confidence interval 1.71-22.10) remained associated with futile reperfusion. CONCLUSIONS: IL-6 is a marker of futile reperfusion in the setting of MT.

Conventional MRI radiomics in patients with suspected early- or pseudo-progression.

BACKGROUND: After radiochemotherapy, 30% of patients with early worsening MRI experience pseudoprogression (Psp) which is not distinguishable from early progression (EP). We aimed to assess the diagnostic value of radiomics in patients with suspected EP or Psp. METHODS: Radiomics features (RF) of 76 patients (53 EP and 23 Psp) retrospectively identified were extracted from conventional MRI based on four volumes-of-interest. Subjects were randomly assigned into training and validation groups. Classification model (EP versus Psp) consisted of a random forest algorithm after univariate filtering. Overall (OS) and progression-free survivals (PFS) were predicted using a semi-supervised principal component analysis, and forecasts were evaluated using C-index and integrated Brier scores (IBS). RESULTS: Using 11 RFs, radiomics classified patients with 75.0% and 76.0% accuracy, 81.6% and 94.1% sensitivity, 50.0% and 37.5% specificity, respectively, in training and validation phases. Addition of MGMT promoter status improved accuracy to 83% and 79.2%, and specificity to 63.6% and 75%. OS model included 14 RFs and stratified low- and high-risk patients both in the training (hazard ratio [HR], 3.63; P = .002) and the validation (HR, 3.76; P = .001) phases. Similarly, PFS model stratified patients during training (HR, 2.58; P = .005) and validation (HR, 3.58; P = .004) phases using 5 RF. OS and PFS forecasts had C-index of 0.65 and 0.69, and IBS of 0.122 and 0.147, respectively. CONCLUSIONS: Conventional MRI radiomics has promising diagnostic value, especially when combined with MGMT promoter status, but with moderate specificity. In addition, our results suggest a potential for predicting OS and PFS.

Favorable revascularization therapy in patients with ASPECTS ≤ 5 on DWI in anterior circulation stroke.

BACKGROUND: A low baseline Alberta Stroke Programme Early CT Score (ASPECTS) is strongly associated with low rates of favorable outcome in patients with acute stroke. OBJECTIVE: To evaluate the efficacy and safety of revascularization therapy in patient with ASPECTS ≤5 in anterior circulation infarct. METHODS: We retrospectively analyzed 108 consecutive patients presenting low ASPECTS on diffusion-weighted imaging. Sixty patients were treated by mechanical thrombectomy, including 34 patients who received simultaneously intravenous thrombolysis. A control group of 48 patients not eligible for reperfusion therapy gave us a perspective on the natural history. Clinical outcome was evaluated at 90 days using the modified Rankin Scale (mRS) score. Hemicraniectomy after malignant infarction, mortality, and symptomatic intracranial haemorrhage (sICH) were also reported. RESULTS: Thrombolysis in Cerebral Infarction 2b-3 was assessed in 75% of treated patients. Reperfusion therapy led to significantly reduced disability (mRS score 0-2) at 90 days compared with the control group (30% vs 2.1%, p<0.001), hemicraniectomy (3.3% vs 22.9%, p=0.002), and death at 90 days (25% vs 47.9%, p=0.01). The sICH level was similar in treated patients and in the control group (p=0.78). Patients aged ≤70 years in the thrombectomy group had a significantly better clinical outcome than older patients (37.5% vs 10%, p=0.02), regardless of baseline characteristics or recanalization rate. CONCLUSIONS: In patients with acute stroke in the anterior circulation and ASPECTS ≤5 revascularization therapy contributes to a favorable clinical outcome at 90 days, especially in patients younger than 70 years.

Determination of a shear rate threshold for thrombus formation in intracranial aneurysms.

BACKGROUND: Particular intra-aneurysmal blood flow conditions, created naturally by the growth of an aneurysm or induced artificially by implantation of a flow diverter stent (FDS), can potentiate intra-aneurysmal thrombosis. The aim of this study was to identify hemodynamic indicators, relevant to this process, which could be used as a prediction of the success of a preventive endovascular treatment. METHOD: A cross sectional study on 21 patients was carried out to investigate the possible association between intra-aneurysmal spontaneous thrombus volume and the dome to neck aspect ratio (AR) of the aneurysm. The mechanistic link between these two parameters was further investigated through a Fourier analysis of the intra-aneurysmal shear rate (SR) obtained by computational fluid dynamics (CFD). This analysis was first applied to 10 additional patients (4 with and 6 without spontaneous thrombosis) and later to 3 patients whose intracranial aneurysms only thrombosed after FDS implantation. RESULTS: The cross sectional study revealed an association between intra-aneurysmal spontaneous thrombus volume and the AR of the aneurysm (R(2)=0.67, p<0.001). Fourier analysis revealed that in cases where thrombosis occurred, the SR harmonics 0, 1, and 2 were always less than 25/s, 10/s, and 5/s, respectively, and always greater than these values where spontaneous thrombosis was not observed. CONCLUSIONS: Our study suggests the existence of an SR threshold below which thrombosis will occur. Therefore, by analyzing the SR on patient specific data with CFD techniques, it may be potentially possible to predict whether or the intra-aneurysmal flow conditions, after FDS implantation, will become prothrombotic.

The pCONus device for the endovascular treatment of wide neck bifurcation aneurysms.

BACKGROUND AND PURPOSE: The pCONus is a new stent featuring a distal end that opens like a blossoming flower with four petals. The device is implanted in the aneurysm sac at the level of the neck. We report our initial experience in a series of patients treated with this device. METHODS: This retrospective study was approved by the authors' ethics committees. 18 patients with 19 unruptured wide neck bifurcation intracranial aneurysms (IA) were treated by pCONus placement and coiling. Technical issues, immediate post treatment angiographic findings, and clinical and imaging follow-up were assessed. RESULTS: Embolization was successful in all patients. There were 11 women and 7 men with a mean age of 60 years. Median aneurysm size was 9 mm (range 5.5-25 mm). The device was precisely placed and detached in all cases, allowing for subsequent coiling. Two patients experienced a symptomatic complication, one of which, a thromboembolism, was related to the use of the pCONus. This patient had a slight hand paresis. 16 patients had a normal neurological examination at discharge. Immediate anatomical results were 13 complete occlusions, 2 neck remnants, and 4 incomplete occlusions. Imaging follow-up was obtained in 12 patients (mean 9.5 months, range 2-24 months) and showed 9 stable occlusions and 3 recanalizations, of which 2 were retreated. CONCLUSIONS: In this initial series of patients, endovascular treatment of wide neck bifurcation IAs with the pCONus was feasible, with acceptable clinical and anatomical outcomes. Further studies are needed to evaluate the indications, safety, and efficacy of this new device.