Exploring Reperfusion Following Endovascular Thrombectomy.

Background and Purpose- Cerebral perfusion in acute ischemic stroke patients is often assessed before endovascular thrombectomy (EVT), but rarely after. Perfusion data obtained following EVT may provide additional prognostic information. We developed a tool to quantitatively derive perfusion measurements from digital subtraction angiography (DSA) data and examined perfusion in patients following EVT. Methods- Source DSA images from acute anterior circulation stroke patients undergoing EVT were retrospectively assessed. Following deconvolution, maps of mean transit time (MTT) were generated from post-EVT DSA source data. Thrombolysis in Cerebral Infarction grades and MTT in patients with and without hemorrhagic transformation (HT) at 24 hours were compared. Receiver operating characteristic modeling was used to classify the presence/absence of HT at 24 hours by MTT. Results- Perfusion maps were generated in 50 patients using DSA acquisitions that were a median (interquartile range) of 9 (8-10) seconds in duration. The median post-EVT MTT within the affected territory was 2.6 (2.2-3.3) seconds. HT was observed on follow-up computed tomography in 16 (32%) patients. Thrombolysis in Cerebral Infarction grades did not differ in patients with HT from those without (P=0.575). Post-EVT MTT maps demonstrated focal areas of hyperperfusion (n=8) or persisting hypoperfusion (n=3) corresponding to the regions where HT later developed. The relationship between MTT and HT was U-shaped; HT occurred in patients at both the lowest and highest extremes of MTT. An MTT threshold <2 or >4 seconds was 81% sensitive and 94% specific for classifying the presence of HT at follow-up. Conclusions- Perfusion measurements can be obtained using DSA perfusion with minimal changes to current stroke protocols. Perfusion imaging post-recanalization may have additional clinical utility beyond visual assessment of source angiographic images alone.

Lower Blood Pressure Is Not Associated With Decreased Arterial Spin Labeling Estimates of Perfusion in Intracerebral Hemorrhage.

Background Subacute ischemic lesions in intracerebral hemorrhage ( ICH ) have been hypothesized to result from hypoperfusion. Although studies of cerebral blood flow ( CBF ) indicate modest hypoperfusion in ICH , these investigations have been limited to early time points. Arterial spin labeling ( ASL ), a magnetic resonance imaging technique, can be used to measure CBF without a contrast agent. We assessed CBF in patients with ICH using ASL and tested the hypothesis that CBF is related to systolic blood pressure ( SBP ). Methods and Results In this cross-sectional study, patients with ICH were assessed with ASL at 48 hours, 7 days, and/or 30 days after onset. Relative CBF ( rCBF ; ratio of ipsilateral/contralateral perfusion) was measured in the perihematomal regions, hemispheres, border zones, and the perilesional area in patients with diffusion-weighted imaging hyperintensities. Twenty-patients (65% men; mean± SD age, 68.5±12.7 years) underwent imaging with ASL at 48 hours (N=12), day 7 (N=6), and day 30 (N=11). Median (interquartile range) hematoma volume was 13.1 (6.3-19.3) mL. Mean± SD baseline SBP was 185.4±25.5 mm Hg. Mean perihematomal rCBF was 0.9±0.2 at 48 hours at all time points. Baseline SBP and other SBP measurements were not associated with a decrease in rCBF in any of the regions of interest ( P≥0.111). r CBF did not differ among time points in any of the regions of interest ( P≥0.097). Mean perilesional rCBF was 1.04±0.65 and was unrelated to baseline SBP ( P=0.105). Conclusions ASL can be used to measure rCBF in patients with acute and subacute ICH . Perihematomal CBF was not associated with SBP changes at any time point. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00963976.

Aggressive blood pressure reduction is not associated with decreased perfusion in leukoaraiosis regions in acute intracerebral hemorrhage patients.

Leukoaraiosis regions may be more vulnerable to decreases in cerebral perfusion. We aimed to assess perfusion in leukoaraiosis regions in acute intracerebral hemorrhage (ICH) patients. We tested the hypothesis that aggressive acute BP reduction in ICH patients is associated with hypoperfusion in areas of leukoaraiosis. In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), patients with ICH <24 hours duration were randomized to two systolic BP (SBP) target groups (<150 mmHg vs. <180 mmHg). Computed tomography perfusion (CTP) imaging was performed 2h post-randomization. Leukoaraiosis tissue volumes were planimetrically measured using semi-automated threshold techniques on the acute non-contrast CT. CTP source leukoaraiosis region-of-interest object maps were co-registered with CTP post-processed maps to assess cerebral perfusion in these areas. Seventy-one patients were included with a mean age of 69±11.4 years, 52 of whom had leukoaraiosis. The mean relative Tmax (rTmax) of leukoaraiotic tissue (2.3±2s) was prolonged compared to that of normal appearing white matter in patients without leukoaraiosis (1.1±1.2s, p = 0.04). In the 52 patients with leukoaraiosis, SBP in the aggressive treatment group (145±20.4 mmHg, n = 27) was significantly lower than that in the conservative group (159.9±13.1 mmHg, n = 25, p = 0.001) at the time of CTP. Despite this SBP difference, mean leukoaraiosis rTmax was similar in the two treatment groups (2.6±2.3 vs. 1.8±1.6 seconds, p = 0.3). Cerebral perfusion in tissue affected by leukoaraiosis is hypoperfused in acute ICH patients. Aggressive BP reduction does not appear to acutely aggravate cerebral hypoperfusion.

Early hematoma retraction in intracerebral hemorrhage is uncommon and does not predict outcome.

BACKGROUND: Clot retraction in intracerebral hemorrhage (ICH) has been described and postulated to be related to effective hemostasis and perihematoma edema (PHE) formation. The incidence and quantitative extent of hematoma retraction (HR) is unknown. Our aim was to determine the incidence of HR between baseline and time of admission. We also tested the hypothesis that patients with HR had higher PHE volume and good prognosis. METHODS: This was a retrospective single-centre study in which serial planimetric volume measurements of the total hematoma volume (parenchymal (IPH) and intraventricular (IVH)) and PHE were performed in ICH patients with baseline non-contrast computed tomography (CT) completed within 6 hours of onset and follow-up CT 24 (±12) hours from symptom onset. HR was defined as a decrease in volume of >3ml or >15%, and hematoma expansion (HE) as an increase of >6ml or >30%. All other patients were categorized as stable hematoma (HS). Good outcome was defined as modified Rankin Scale (mRS) 0-2 at 90 days. RESULTS: A total of 136 patients (mean age = 69.3±13.39 years, 58.1% male) were included. Median (interquartile range) baseline total hematoma volume was 14.96 (7.80, 31.88) ml. HR >3ml and >15% occurred in 6 (4.4%) and 8 (5.9%) patients, respectively. Neither definition of HR was associated with follow-up PHE (p>0.297) or good outcome (p>0.249). IVH was the only independent predictor of HR (p<0.0241). CONCLUSIONS: Early HR is rare and associated with IVH, but not with PHE or clinical outcome. There was no relationship between HR, PHE, and patient prognosis. Therefore, HR is unlikely to be a useful endpoint in clinical ICH studies.

Magnitude of Hematoma Volume Measurement Error in Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Limiting intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) expansion is a common target for acute ICH studies and, therefore, accurate measurement of hematoma volumes is required. We investigated the amount of hematoma volume difference between computed tomography scans that can be considered as measurement error. METHODS: Five raters performed baseline (<6 hours) and 24-hour total hematoma (ICH+IVH) computer-assisted volumetric analysis from 40 selected ICH patients from the Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) study cohort twice. Estimates of intrarater and interrater reliability are expressed as intraclass correlation coefficients and minimum detectable difference (MDD). RESULTS: Total hematoma volumetric analyses had excellent intra- and interrater agreements (intraclass correlation coefficients 0.994 and 0.992, respectively). MDD for intra- and interrater volumes was 6.68 and 7.72 mL, respectively, and were higher the larger total hematoma volume was and in patients with subarachnoid hemorrhage or IVH. MDD for total hematoma volume measurement of 10.4 mL was found in patients with largest hematoma volumes. In patients with subarachnoid hemorrhage or IVH, MDD for total hematoma volume was 10.3 and 10.4 mL, respectively. In patients without IVH, MDD for intra- and interrater pure ICH volumes were 3.82 and 5.83 mL, respectively. CONCLUSIONS: A threshold higher than 10.4 mL seems to be reliable to avoid error of total hematoma volume measurement in a broad range of patients. An absolute ICH volume increase of >6 mL, commonly used as outcome in ICH studies, seems well above MDD and, therefore, could be used to reliably detect ICH expansion.

Perihematomal Edema Is Greater in the Presence of a Spot Sign but Does Not Predict Intracerebral Hematoma Expansion.

BACKGROUND AND PURPOSE: Perihematomal edema volume may be related to intracerebral hemorrhage (ICH) volume at baseline and, consequently, with hematoma expansion. However, the relationship between perihematomal edema and hematoma expansion has not been well established. We aimed to investigate the relationship among baseline perihematomal edema, the computed tomographic angiography spot sign, hematoma expansion, and clinical outcome in patients with acute ICH. METHODS: Predicting Hematoma Growth and Outcome in Intracerebral Hemorrhage Using Contrast Bolus CT (PREDICT) was a prospective observational cohort study of ICH patients presenting within 6 hours from onset. Patients underwent computed tomography and computed tomographic angiography scans at baseline and 24-hour computed tomography scan. A post hoc analysis of absolute perihematomal edema and relative perihematomal edema (absolute perihematomal edema divided by ICH) volumes was performed on baseline computed tomography scans (n=353). Primary outcome was significant hematoma expansion (>6 mL or >33%). Secondary outcomes were early neurological deterioration, 90-day mortality, and poor outcome. RESULTS: Absolute perihematomal edema volume was higher in spot sign patients (24.5 [11.5-41.8] versus 12.6 [6.9-22] mL; P<0.001), but it was strongly correlated with ICH volume (ρ=0.905; P<0.001). Patients who experienced significant hematoma expansion had higher absolute perihematomal edema volume (18.4 [10-34.6] versus 11.8 [6.5-22] mL; P<0.001) but similar relative perihematomal edema volume (1.09 [0.89-1.37] versus 1.12 [0.88-1.54]; P=0.400). Absolute perihematomal edema volume and poorer outcomes were higher by tertiles of ICH volume, and perihematomal edema volume did not independently predict significant hematoma expansion. CONCLUSIONS: Perihematomal edema volume is greater at baseline in the presence of a spot sign. However, it is strongly correlated with ICH volume and does not independently predict hematoma expansion.

Ischemia in intracerebral hemorrhage is associated with leukoaraiosis and hematoma volume, not blood pressure reduction.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) lesions have been identified both inside and outside the perihematoma region. We tested the hypotheses that larger hematoma volumes and blood pressure reduction are associated with DWI lesions. METHODS: Hematoma and perihematoma edema volumes were measured using planimetric techniques in 117 intracerebral hemorrhage (ICH) patients who underwent DWI. Perihematoma and remote DWI lesion volumes were measured using apparent diffusion coefficient thresholds for moderate (<730×10(-6) mm/s) and severe (<550×10(-6) mm/s) ischemia. Acute blood pressure change over the first 24 hours was calculated. RESULTS: The median (interquartile range) time to magnetic resonance imaging was 2 (1-5) days. Median hematoma volume was 9.8 (2.6-23.0) mL, and median perihematoma edema volume was 7.0 (2.9-18.6) mL. A small portion of the perihematoma region contained tissue below the thresholds for moderate (8.0 [2.9-14.5]%) and severe ischemia (1.1 [0.3-3.5]%). Ischemic perihematoma tissue volumes were correlated with hematoma volumes (R=0.52, P<0.001), but not maximal systolic blood pressure drop at 24 hours (R=-0.09, P=0.38). Remote DWI lesions were found in 17 (14.5%) patients (mean volume=0.44±0.3 mL). Patients with remote DWI lesions had higher rates of antiplatelet use (P=0.01), prior ICH (P=0.03), lobar ICH (0.04), and larger leukoaraiosis volumes (P=0.02). Maximal systolic blood pressure drop at 24 hours was similar in patients with (-20.5 [-55, -10] mm Hg) and without remote DWI lesions (-27 [-46, -13] mm Hg, P=0.96). CONCLUSIONS: Small DWI lesions within and outside the perihematoma region are common in primary ICH. Perihematoma DWI lesions were independently associated with larger hematoma volumes. Remote DWI lesions may be an epiphenomenon associated with the underlying microvascular pathogenesis. These data do not support a hemodynamic mechanism of ischemic injury after primary ICH.

National Institutes of Health Stroke Scale score is an unreliable predictor of perfusion deficits in acute stroke.

BACKGROUND: Perfusion-weighted magnetic resonance imaging is not routinely used to investigate stroke/transient ischemic attack. Many clinicians use perfusion-weighted magnetic resonance imaging selectively in patients with more severe neurological deficits, but optimal selection criteria have never been identified. AIMS AND/OR HYPOTHESIS: We tested the hypothesis that a National Institutes of Health Stroke Scale score threshold can be used to predict the presence of perfusion-weighted magnetic resonance imaging deficits in patients with acute ischemic stroke/transient ischemic attack. METHODS: National Institutes of Health Stroke Scale scores were prospectively assessed in 131 acute stroke/transient ischemic attack patients followed by magnetic resonance imaging, including perfusion-weighted magnetic resonance imaging within 72 h of symptom onset. Patients were dichotomized based on the presence or absence of perfusion deficits using a threshold of Tmax (time to peak maps after the impulse response) delay ≥four-seconds and a hypoperfused tissue volume of ≥1 ml. RESULTS: Patients with perfusion deficits (77/131, 59%) had higher median (interquartile range) National Institutes of Health Stroke Scale scores (8 [12]) than those without perfusion deficits (3 [4], P < 0.001). A receiver operator characteristic analysis indicated poor to moderate sensitivity of National Institutes of Health Stroke Scale scores for predicting perfusion deficits (area under the curve = 0.787). A National Institutes of Health Stroke Scale score of ≥6 was associated with specificity of 85%, but sensitivity of only 69%. No National Institutes of Health Stroke Scale score threshold identified all cases of perfusion-weighted magnetic resonance imaging deficits with sensitivity >94%. CONCLUSIONS: Although higher National Institutes of Health Stroke Scale scores are predictive of perfusion deficits, many patients with no clinically detectable signs have persisting cerebral blood flow changes. A National Institutes of Health Stroke Scale score threshold should therefore not be used to select patients for perfusion-weighted magnetic resonance imaging. Perfusion-weighted magnetic resonance imaging should be considered in all patients presenting with acute focal neurological deficits, even if these deficits are transient.

Blood-brain barrier compromise does not predict perihematoma edema growth in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: There are limited data on the extent of blood-brain barrier (BBB) compromise in acute intracerebral hemorrhage patients. We tested the hypotheses that BBB compromise measured with permeability-surface area product (PS) is increased in the perihematoma region and predicts perihematoma edema growth in acute intracerebral hemorrhage patients. METHODS: Patients were randomized within 24 hours of symptom onset to a systolic blood pressure (SBP) treatment of <150 (n=26) or <180 mm Hg (n=27). Permeability maps were generated using computed tomographic perfusion source data acquired 2 hours after randomization, and mean PS was measured in the hematoma, perihematoma, and hemispheric regions. Hematoma and edema volumes were measured on noncontrast computed tomographic scans obtained at baseline, 2 hours and 24 hours after randomization. RESULTS: Patients were randomized at a median (interquartile range) time of 9.3 hours (14.1) from symptom onset. Treatment groups were balanced with respect to baseline SBP and hematoma volume. Perihematoma PS (5.1±2.4 mL/100 mL per minute) was higher than PS in contralateral regions (3.6±1.7 mL/100 mL per minute; P<0.001). Relative edema growth (0-24 hours) was not predicted by perihematoma PS (ß=-0.192 [-0.06 to 0.01]) or SBP change (ß=-0.092 [-0.002 to 0.001]). SBP was lower in the <150 target group (139.2±22.1 mm Hg) than in the <180 group (159.7±12.3 mm Hg; P<0.0001). Perihematoma PS was not different between groups (4.9±2.4 mL/100 mL per minute for the <150 group, 5.3±2.4 mL/100 mL per minute for the <180 group; P=0.51). CONCLUSIONS: BBB permeability is focally increased in the hematoma and perihematoma regions of acute intracerebral hemorrhage patients. BBB compromise does not predict acute perihematoma edema volume or edema growth. SBP reduction does not affect BBB permeability. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00963976.

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

BACKGROUND: 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. METHODS: This is a retrospective cohort study of acute ischemic stroke patients with MCA occlusion admitted to the University Hospital in Canada. The length and volumes of the HMCAS was measured on the plain CT by placing CTA images (CTA source images or MIP images) side-by-side. RESULTS: Seventy-six patients with acute stroke having HMCAS on noncontrast CT (NCCT) with M1 MCA occlusion confirmed by CT angiography or digital subtraction angiography and received tPA. The treatments received were: IV tPA 41(53.9%) and endovascular treatment ± IV tPA 35 (46.1%). In the IV tPA group, the rate of disappearance varied depending on the baseline HMCAS length. Short length HMCAS (<10 mm) disappeared in 6/7 (85.7%) (P < .001). Medium length HMCAS (10-20 mm) disappeared in 9/24 (37.5%). No cases of long length HMCAS (>20 mm) disappeared (0/10) (P = .05). Rate of disappearance of HMCAS was found to be volume dependent (P < .002). CONCLUSION: HMCAS length >10 mm infrequently disappears with IV tPA suggesting a potential need for ancillary therapy in this group.

Planimetric hematoma measurement in patients with intraventricular hemorrhage: is total volume a preferred target for reliable analysis?

BACKGROUND AND PURPOSE: Reliable quantification of both intracerebral hemorrhage and intraventricular hemorrhage (IVH) volume is important for hemostatic trials. We evaluated the reliability of computer-assisted planimetric volume measurements of IVH. METHODS: Computer-assisted planimetry was used to quantify IVH volume. Five raters measured IVH volumes, total (intracerebral hemorrhage+IVH) volumes, and Graeb scores from 20 randomly selected computed tomography scans twice. Estimates of interrater and intrarater reliability were calculated and expressed as an intrarater correlation coefficient and an absolute minimum detectable difference. RESULTS: Planimetric IVH volume analysis had excellent intra- and interrater agreement (intrarater correlation coefficient, 0.96 and 0.92, respectively), which was superior to the Graeb score (intrarater correlation coefficient, 0.88 and 0.83). Minimum detectable differences for intra- and interrater volumes were 12.1 mL and 17.3 mL, and were dependent on the total size of the hematoma; hematomas smaller than the median 43.8 mL had lower minimum detectable differences, whereas those larger than the median had higher minimum detectable differences. Planimetric total hemorrhage volume analysis had the best intra- and interrater agreement (intrarater correlation coefficient, 0.99 and 0.97, respectively). CONCLUSIONS: Computer-assisted planimetric techniques provide a reliable measurement of ventricular hematoma volume, but are susceptible to higher absolute error when assessing larger hematomas.

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 47­73) for the positive predictive value and 78% (71­84) for the negative predictive value, with 51% (39­63) sensitivity and 85% (78­90) 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.

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.

Perfusion parameters derived from bolus-tracking perfusion imaging are immune to tracer recirculation.

PURPOSE: To investigate the impact of tracer recirculation on estimates of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). MATERIALS AND METHODS: The theoretical model used to derive CBF, CBV, and MTT was examined. CBF and CBV estimates with and without tracer recirculation were compared in computer simulations to examine the effects of tracer recirculation. RESULTS: The equations used to derive CBF, CBV, and MTT assume that the arterial input function and tissue tracer signals define the input and output signals, respectively, of a linear time-invariant system. As a result of the principle of superposition, these perfusion parameters are immune to tracer recirculation, which was confirmed by computer simulation. However, limited acquisition durations can lead to CBV and CBF errors of up to 50%. CONCLUSION: Tracer recirculation does not impact estimation of CBF, CBV, or MTT. However, previous approaches used to remove recirculation effects may be beneficial when used to compensate for limited acquisition durations in which the passage of the bolus is not adequately captured.

Reliability of measuring lesion volumes in transient ischemic attack and minor stroke.

BACKGROUND AND PURPOSE: Lesion volume measurements in disabling ischemic stroke have excellent reliability, but it is not clear whether this is also true for small lesions. We assessed the reliability of measuring baseline and follow-up lesion volumes in transient ischemic attack and minor stroke. METHODS: Patients who presented with a transient ischemic attack or minor stroke (NIHSS < or = 3) who had brain MRI within 24 hours from symptom onset and at 30-day follow-up and had an acute lesion on baseline MRI were included. Using semiautomated software, 4 stroke fellows independently assessed ischemic lesions twice on acute diffusion-weighted imaging and follow-up fluid-attenuated inversion recovery. RESULTS: Eighty patients were included, with a median baseline NIHSS of 1. Mean baseline diffusion-weighted imaging lesion volume was 3.4+/-7.4 mL (87.5% had <5 mL). There was excellent inter-rater/intrarater reliability, with intraclass correlation coefficients of 0.94/0.96 for acute diffusion-weighted imaging, 0.74/0.92 for follow-up fluid-attenuated inversion recovery, and 0.81/0.93 for growth. CONCLUSIONS: We found excellent concordance between and within raters for acute diffusion-weighted imaging and 30-day follow-up fluid-attenuated inversion recovery lesion volume measurements in patients with transient ischemic attack and minor stroke.

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

Defining the CT angiography 'spot sign' in primary intracerebral hemorrhage.

PURPOSE: The computed tomogram angiography (CTA) 'spot sign' describes foci of intralesional enhancement associated with hematoma expansion in primary intracerebral hemorrhage patients. A consistent radiological definition is required for two proposed recombinant Factor VIIa trials planning patient dichotomization according to 'spot sign' presence or absence. We propose radiological criteria for diagnosis of the CTA 'spot sign' and describe different morphological patterns. MATERIAL AND METHODS: A prospective cohort of 36 consecutive patients presenting with primary intracerebral hemorrhage (ICH) were enrolled in a multicenter collaborative study, and have been included for the present analysis. Three reviewers analyzed the CTA studies in a blinded protocol. Analysis of specific ICH and 'spot sign' features was performed including prevalence, number, size, location, morphology and Hounsfield unit density. RESULTS: Twelve of thirty-six patients (33%) demonstrated a total of 19 enhancing foci consistent with the CTA 'spot sign'. Mean maximal axial 'spot sign' dimension was 3.7 +/- 2.2 mm and mean density was 216 +/- 57.7 HU. No significant differences in age or blood pressure (p = 0.7), glucose (p = 0.9), INR/PTT (p = 0.3 and 0.4) or hematoma location (p = 0.3) were demonstrated between patients with or without the 'spot sign'. Consensus definition and classification criteria for the CTA 'spot sign' are proposed. CONCLUSION: The 'spot sign' is defined as spot-like and/or serpiginous foci of enhancement, within the margin of a parenchymal hematoma without connection to outside vessels. The 'spot sign' is greater than 1.5 mm in maximal dimension and has a Hounsfield unit density at least double that of background hematoma density.

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 > or = 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.

Cerebral blood flow estimation in vivo using local tissue reference functions.

PURPOSE: To evaluate the use of bolus signals obtained from tissue as reference functions (or local reference functions [LRFs]) rather than arterial input functions (AIFs) when deriving cross-calibrated cerebral blood flow (CBF(CC)) estimates via deconvolution. MATERIALS AND METHODS: AIF and white matter (WM) LRF CBF(CC) maps (cross-calibrated so that normal WM was 23.7 mL/minute/100 g) derived using singular value decomposition (SVD) were examined in 28 ischemic stroke patients. Median CBF(CC) estimates from normal gray matter (GM) and ischemic tissue were obtained. RESULTS: AIF and LRF median CBF(CC) estimates resembled one another for all 28 patients (average paired CBF(CC) difference 0.4 +/- 1.7 mL/minute/100 g and -0.4 +/- 1.4 mL/minute/100 g in GM and ischemic tissue, respectively). Wilcoxon signed-rank comparisons of patient median CBF(CC) measurements revealed no statistically significant differences between using AIFs and LRFs (P > 0.05). CONCLUSION: If CBF is quantified using a patient-specific cross-calibration factor, then LRF CBF estimates are at least as accurate as those from AIFs. Therefore, until AIF quantification is achievable in vivo, perfusion protocols tailored for LRFs would simplify the methodology and provide more reliable perfusion information.