Jayme C. Kosior

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study

BACKGROUND In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. METHODS PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. FINDINGS We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47–73) for the positive predictive value and 78% (71–84) for the negative predictive value, with 51% (39–63) sensitivity and 85% (78–90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). INTERPRETATION These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. FUNDING Canadian Stroke Consortium and NovoNordisk Canada.

Recurrent events in transient ischemic attack and minor stroke: what events are happening and to which patients?

Background and Purpose— The risk of a recurrent stroke after transient ischemic attack (TIA) or minor stroke is high. Clinical trials are needed to assess acute treatment options in these patients. We sought to evaluate the type of recurrent events and to identify which subsets of patients are at risk for recurrent events. Methods— One hundred and eighty patients with TIA or minor stroke were examined within 12 hours and underwent brain MRI within 24 hours. Any neurological deterioration was recorded, and a combination of clinical and MRI factors were used to create a combined event classification. Subgroups of patients analyzed included classical TIA, patients with NIHSS=0, and patients with NIHSS >0 in ED. Results— Overall there were 38 events in 36 patients (20% event rate); 20 were symptomatic and 18 were silent (only evident because of the follow up MRI). 18/20 (90%) symptomatic events were associated with progression of presenting symptoms, compared to 2/20 (10%) with a clear recurrent stroke distinct from the original event. We found a low risk of recurrent stroke among classical definition TIA patients (1.1%). Patients with an NIHSS=0 in the ED, had an intermediate event rate (6.6%) between TIA (classical – 1.1%) and NIHSS >0 (14.4%; &khgr;2 test for trend, P=0.02). All clinical categories of patient (TIA, stroke, NIHSS=0) accumulated silent lesions on MRI. Conclusions— Most events were classified as stroke progression or infarct growth rather than a recurrent stroke. A low risk of recurrence was found in patients with classical TIA and those with no neurological deficits on initial assessment.

Quantomo: validation of a computer-assisted methodology for the volumetric analysis of intracerebral haemorrhage.

Background Volume measurements of intracerebral haemorrhage are prognostically important and are increasingly used in clinical trials to measure the effects of potential interventions. The purpose of this work is to establish the reliability of haematoma volume measurements obtained using a computer-assisted method called Quantomo (for quantitative tomography) and the ABC/2 method. Hypothesis Quantomo reliably detects smaller changes in intracerebral haemorrhage volume as compared with the ABC/2 method because computer-assisted volume measurements are tailored to measure the geometry of individual haematoma volumes whereas the ABC/2 method approximates all haematoma volumes as ellipsoids. Methods Thirty randomly selected computed tomography scans with intracerebral haemorrhage were measured by four raters a total of four times each (two sessions using Quantomo and two using the ABC/2 method). Interrater and intrarater reliability for both techniques were calculated simultaneously using a two-way random-effects analysis of variance model. The precision of intracerebral haemorrhage volume measurement was quantified as the minimum detectable difference with 95% confidence intervals. Results The median (first quartile and third quartile) intracerebral haemorrhage volume measurements of all rater and sessions for Quantomo were 32·7 ml (6·2 and 54·4 ml) and for ABC/2 40·7 ml (8·6 and 76·0 ml). Quantomo intracerebral haemorrhage volume measurements were more precise, having an inter- and intrarater minimum detectable difference of 8·1 and 5·3 ml, while the inter- and intrarater minimum detectable difference for ABC/2 were 37·0 and 15·7 ml. Conclusions Quantomo is a computer-assisted methodology that is more reliable for quantifying intracerebral haemorrhage volume as compared with the ABC/2 method.

Normal Magnetic Resonance Perfusion-Weighted Imaging in Lacunar Infarcts Predicts a Low Risk of Early Deterioration

Background: Current clinical tools to identify lacunar infarct patients at risk of deterioration are inadequate, and imaging techniques to predict fluctuation and deterioration would be of value. We sought to determine the occurrence of MRI perfusion-weighted imaging (PWI) abnormalities in lacunes, and whether they help predict clinical and radiological outcome. Methods: Patients with lacunar stroke or TIA were selected from a prospective MR imaging study. MRI was performed within 24 h of the event and follow-up imaging completed at 30 or 90 days. Baseline perfusion maps were qualitatively assessed and infarct volumes measured. Early clinical deterioration (NIHSS worsening of ≥3 points within 72 h of event) and 90-day modified Rankin Scale score (mRS) were recorded. Results: Twenty-two patients were included. Fifteen (68.2%) had abnormal PWI at the site of the diffusion-weighted imaging lesion. Patients with abnormal PWI were more likely to have stroke than TIA as their index event (RR 2.2, 95% CI 0.9–5.2, p = 0.02). Early clinical deterioration occurred in 4 patients (18.2%), all of whom had abnormal PWI. PWI lesions were not associated with a higher 90-day NIHSS or mRS score, nor did they predict infarct volume growth. Conclusions: MR-PWI abnormalities are seen in two thirds of lacunar infarcts, and are associated with stroke rather than TIA. Normal PWI identifies patients at low risk of early clinical deterioration.

Measurement of length of hyperdense MCA sign in acute ischemic stroke predicts disappearance after IV tPA.

We sought to assess the hypothesis that length and volumes of middle cerebral artery (MCA) thrombus were associated with disappearance of the hyperdense middle cerebral artery sign (HMCAS) in acute ischemic stroke.

3-Tesla versus 1.5-Tesla magnetic resonance diffusion and perfusion imaging in hyperacute ischemic stroke.

Background: Clinical 3-tesla magnetic resonance imaging systems are becoming widespread. No studies have examined differences between 1.5-tesla and 3-tesla imaging for the assessment of hyperacute ischemic stroke (<6 h from symptom onset). Our objective was to compare 1.5-tesla and 3-tesla diffusion and perfusion imaging for hyperacute stroke using optimized protocols. Methods: Three patients or their surrogate provided informed consent. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) was performed sequentially at 1.5 T and 3 T. DWI, apparent diffusion coefficient (ADC) maps and relative time-to-peak (TTP) maps were registered and assessed. DWI contrast-to-noise ratio (CNR) and ADC contrast were measured and compared. The infarct lesion volume (ILV) and thresholded ischemic volume (TIV) were estimated on the ADC and TTP maps, respectively, with the penumbral volume being defined as the difference between these volumes. Results: Qualitatively, the 3-tesla TTP images exhibited greater feature detail. Quantitatively, the DWI CNR and ILV were similar at both field strengths, the ADC contrast was greater at 3 T and the TIV and penumbral volumes were much smaller at 3 T. Conclusions: Overall, the 3-tesla diffusion and perfusion images were at least as good and in some ways superior to the 1.5-tesla images for assessing hyperacute stroke. The TTP maps showed greater feature detail at 3 T. The ischemic and penumbra volumes were much greater at 1.5 T, indicating a potential difference in the diagnostic utility of the PWI-DWI mismatch between field strengths.

PerfTool: A software platform for investigating bolus-tracking perfusion imaging quantification strategies†

To develop a software platform, PerfTool (for perfusion tool), for the comprehensive evaluation of bolus‐tracking quantitative perfusion imaging methods and algorithms, along with a method to rapidly visualize and evaluate the performance of algorithms.

Robust dynamic susceptibility contrast MR perfusion using 4D nonlinear noise filters

To investigate if 4D (simultaneous space and time) nonlinear filtering techniques can produce more robust cerebral blood flow (CBF) estimates by reducing noise in acquired dynamic susceptibility contrast (DSC) MR perfusion data.

Atlas-Based Topographical Scoring for Magnetic Resonance Imaging of Acute Stroke

Background and Purpose— The Alberta Stroke Program Early CT Score (ASPECTS), a 10-point scale, is a clinical tool for assessment of early ischemic changes after stroke based on the location and extent of a visible stroke lesion. It has been extended for use with MR diffusion-weighted imaging. The purpose of this work was to automate a MR topographical score (MR-TS) using a digital atlas to develop an objective tool for large-scale analyses and possibly reduce interrater variability and slice orientation differences. Methods— We assessed 30 patients with acute ischemic stroke with a diffusion lesion who provided informed consent. Patients were imaged by CT and MRI within 24 hours of symptom onset. An MR-TS digital atlas was generated using the ASPECTS scoring sheet and anatomic MR data sets. Automated MR topographical scores (auto-MR-TS) were obtained based on the overlap of lesions on apparent diffusion coefficient maps with MR-TS atlas regions. Auto-MR-TS scores were then compared with scores derived manually (man-MR-TS) and with conventional CT ASPECTS scores. Results— Of the 30 patients, 29 were assessed with auto-MR-TS. Auto-MR-TS was significantly lower than CT ASPECTS (P<0.001), but with a median difference of only 1 point. There was no significant difference between the auto-MR-TS and the man-MR-TS with a median difference of 0 points; 86% of patient scores differed by ≤1 point. Conclusion— Auto-MR-TS provides a measure of stroke severity in an automated fashion and facilitates more objective, sensitive, and potentially more complex ASPECTS-based scoring.

Improved dynamic susceptibility contrast (DSC)-MR perfusion estimates by motion correction

To investigate the effect of patient motion on quantitative cerebral blood flow (CBF) maps in ischemic stroke patients and to evaluate the efficacy of a motion‐correction scheme.