Acute stroke imaging selection for mechanical thrombectomy in the extended time window: is it time to go back to basics? A review of current evidence.

Treatment with endovascular therapy in the extended time window for acute ischaemic stroke with large vessel occlusion involves stringent selection criteria based on the two landmark studies DAWN and DEFUSE3. Current protocols typically include the requirement of advanced perfusion imaging which may exclude a substantial proportion of patients from receiving a potentially effective therapy. Efforts to offer endovascular reperfusion therapies to all appropriate candidates may be facilitated by the use of simplified imaging selection paradigms with widely available basic imaging techniques, such as non-contrast CT and CT angiography. Currently available evidence from our literature review suggests that patients meeting simplified imaging selection criteria may benefit as much as those patients selected using advanced imaging techniques (CT perfusion or MRI) from endovascular therapy in the extended time window. A comprehensive understanding of the role of imaging in patient selection is critical to optimising access to endovascular therapy in the extended time window and improving outcomes in acute stroke. This article provides an overview on current developments and future directions in this emerging area.

A longitudinal magnetic resonance imaging study of neurodegenerative and small vessel disease, and clinical cognitive trajectories in non demented patients with transient ischemic attack: the PREVENT study.

BACKGROUND: Late-life cognitive decline, caused by progressive neuronal loss leading to brain atrophy years before symptoms are detected, is expected to double in Canada over the next two decades. Cognitive impairment in late life is attributed to vascular and lifestyle related risk factors in mid-life in a substantial proportion of cases (50%), thereby providing an opportunity for effective prevention of cognitive decline if incipient disease is detected earlier. Patients presenting with transient ischemic attack (TIA) commonly display some degree of cognitive impairment and are at a 4-fold increased risk of dementia. In the Predementia Neuroimaging of Transient Ischemic Attack (PREVENT) study, we will address what disease processes (i.e., Alzheimer's vs. vascular disease) lead to neurodegeneration, brain atrophy, and cognitive decline, and whether imaging measurements of brain iron accumulation using quantitative susceptibility mapping predicts subsequent brain atrophy and cognitive decline. METHODS: A total of 440 subjects will be recruited for this study with 220 healthy subjects and 220 TIA patients. Early Alzheimer's pathology will be determined by cerebrospinal fluid samples (including tau, a marker of neuronal injury, and amyloid ß1-42) and by MR measurements of iron accumulation, a marker for Alzheimer's-related neurodegeneration. Small vessel disease will be identified by changes in white matter lesion volume. Predictors of advanced rates of cerebral and hippocampal atrophy at 1 and 3 years will include in vivo Alzheimer's disease pathology markers, and MRI measurements of brain iron accumulation and small vessel disease. Clinical and cognitive function will be assessed annually post-baseline for a period of 5-years using a clinical questionnaire and a battery of neuropsychological tests, respectively. DISCUSSION: The PREVENT study expects to demonstrate that TIA patients have increased early progressive rates of cerebral brain atrophy after TIA, before cognitive decline can be clinically detected. By developing and optimizing high-level machine learning models based on clinical data, image-based (quantitative susceptibility mapping, regional brain, and white matter lesion volumes) features, and cerebrospinal fluid biomarkers, PREVENT will provide a timely opportunity to identify individuals at greatest risk of late-life cognitive decline early in the course of disease, supporting future therapeutic strategies for the promotion of healthy aging.

Use of Noncontrast Computed Tomography and Computed Tomographic Perfusion in Predicting Intracerebral Hemorrhage After Intravenous Alteplase Therapy.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is a feared complication of intravenous alteplase therapy in patients with acute ischemic stroke. We explore the use of multimodal computed tomography in predicting this complication. METHODS: All patients were administered intravenous alteplase with/without intra-arterial therapy. An age- and sex-matched case-control design with classic and conditional logistic regression techniques was chosen for analyses. Outcome was parenchymal hemorrhage on 24- to 48-hour imaging. Exposure variables were imaging (noncontrast computed tomography hypoattenuation degree, relative volume of very low cerebral blood volume, relative volume of cerebral blood flow ≤7 mL/min·per 100 g, relative volume of Tmax ≥16 s with all volumes standardized to z axis coverage, mean permeability surface area product values within Tmax ≥8 s volume, and mean permeability surface area product values within ipsilesional hemisphere) and clinical variables (NIHSS [National Institutes of Health Stroke Scale], onset to imaging time, baseline systolic blood pressure, blood glucose, serum creatinine, treatment type, and reperfusion status). RESULTS: One-hundred eighteen subjects (22 patients with parenchymal hemorrhage versus 96 without, median baseline NIHSS score of 15) were included in the final analysis. In multivariable regression, noncontrast computed tomography hypoattenuation grade (P<0.006) and computerized tomography perfusion white matter relative volume of very low cerebral blood volume (P=0.04) were the only significant variables associated with parenchymal hemorrhage on follow-up imaging (area under the curve, 0.73; 95% confidence interval, 0.63-0.83). Interrater reliability for noncontrast computed tomography hypoattenuation grade was moderate (κ=0.6). CONCLUSIONS: Baseline hypoattenuation on noncontrast computed tomography and very low cerebral blood volume on computerized tomography perfusion are associated with development of parenchymal hemorrhage in patients with acute ischemic stroke receiving intravenous alteplase.

Regional Comparison of Multiphase Computed Tomographic Angiography and Computed Tomographic Perfusion for Prediction of Tissue Fate in Ischemic Stroke.

BACKGROUND AND PURPOSE: Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction. METHODS: Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models. RESULTS: Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models (P<0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models (P>0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score (P<0.01) and each delay score category (P<0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category (P<0.05). CONCLUSIONS: Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients.

Occult anterograde flow is an under-recognized but crucial predictor of early recanalization with intravenous tissue-type plasminogen activator.

BACKGROUND AND PURPOSE: Thrombolysis depends on the ability of blood and thrombolytic agents to permeate thrombus. We devised a novel technique to quantify blood permeating through thrombi and determine whether this parameter predicts early recanalization with intravenous tissue-type plasminogen activator. METHODS: Intravenous tissue-type plasminogen activator-treated patients with stroke and complete occlusion on computed tomographic angiography were analyzed using perfusion computed tomography and a delay insensitive algorithm. We generated maps that measure delay in arrival time of contrast within the intracranial arterial tree (T0 maps). A positive sloped regression line of T0 values measured along artery silhouette distal to thrombus was defined as marker of permeable thrombus (occult anterograde flow). Median T0 values at proximal and distal thrombus interface were measured. Early recanalization was assessed on first angiography of subsequent intra-arterial procedure or on a 4-hour computed tomographic angiography. RESULTS: Of 66 patients, occult anterograde flow was detected in 17 (25.8%). Early recanalization was more in patients with occult anterograde flow versus not (66.7 versus 29.7%; P=0.031). Median T0 value (in s) at distal thrombus interface (1.5 versus 3.8; P=0.006) and difference in median T0 value between proximal and distal thrombus interface (1.3 versus 3.7; P=0.014) were less in early recanalizers versus in nonrecanalizers. In multivariable analysis, patients with occult anterograde flow and T0 value difference between proximal and distal thrombus interface ≤2 s recanalized most (71.4%; odds ratio, 12.15; 95% confidence interval, 2.05-71.91), whereas patients with retrograde flow and T0 value difference >2 s recanalized least (25.9%; odds ratio, 1). CONCLUSIONS: Occult anterograde flow through thrombus can be assessed by perfusion computed tomography T0 maps and predicts early recanalization with intravenous tissue-type plasminogen activator robustly.

Time-Dependent Computed Tomographic Perfusion Thresholds for Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Among patients with acute ischemic stroke, we determine computed tomographic perfusion (CTP) thresholds associated with follow-up infarction at different stroke onset-to-CTP and CTP-to-reperfusion times. METHODS: Acute ischemic stroke patients with occlusion on computed tomographic angiography were acutely imaged with CTP. Noncontrast computed tomography and magnectic resonance diffusion-weighted imaging between 24 and 48 hours were used to delineate follow-up infarction. Reperfusion was assessed on conventional angiogram or 4-hour repeat computed tomographic angiography. Tmax, cerebral blood flow, and cerebral blood volume derived from delay-insensitive CTP postprocessing were analyzed using receiver-operator characteristic curves to derive optimal thresholds for combined patient data (pooled analysis) and individual patients (patient-level analysis) based on time from stroke onset-to-CTP and CTP-to-reperfusion. One-way ANOVA and locally weighted scatterplot smoothing regression was used to test whether the derived optimal CTP thresholds were different by time. RESULTS: One hundred and thirty-two patients were included. Tmax thresholds of >16.2 and >15.8 s and absolute cerebral blood flow thresholds of <8.9 and <7.4 mL·min(-1)·100 g(-1) were associated with infarct if reperfused <90 min from CTP with onset <180 min. The discriminative ability of cerebral blood volume was modest. No statistically significant relationship was noted between stroke onset-to-CTP time and the optimal CTP thresholds for all parameters based on discrete or continuous time analysis (P>0.05). A statistically significant relationship existed between CTP-to-reperfusion time and the optimal thresholds for cerebral blood flow (P<0.001; r=0.59 and 0.77 for gray and white matter, respectively) and Tmax (P<0.001; r=-0.68 and -0.60 for gray and white matter, respectively) parameters. CONCLUSIONS: Optimal CTP thresholds associated with follow-up infarction depend on time from imaging to reperfusion.

Multiphase CT Angiography: A New Tool for the Imaging Triage of Patients with Acute Ischemic Stroke.

PURPOSE: To describe the use of an imaging selection tool, multiphase computed tomographic (CT) angiography, in patients with acute ischemic stroke (AIS) and to demonstrate its interrater reliability and ability to help determine clinical outcome. MATERIALS AND METHODS: The local ethics board approved this study. Data are from the pilot phase of PRoveIT, a prospective observational study analyzing utility of multimodal imaging in the triage of patients with AIS. Patients underwent baseline unenhanced CT, single-phase CT angiography of the head and neck, multiphase CT angiography, and perfusion CT. Multiphase CT angiography generates time-resolved images of pial arteries. Pial arterial filling was scored on a six-point ordinal scale, and interrater reliability was tested. Clinical outcomes included a 50% or greater decrease in National Institutes of Health Stroke Scale (NIHSS) over 24 hours and 90-day modified Rankin Scale (mRS) score of 0-2. The ability to predict clinical outcomes was compared between single-phase CT angiography, multiphase CT angiography, and perfusion CT by using receiver operating curve analysis, Akaike information criterion (AIC), and Bayesian information criterion (BIC). RESULTS: A total of 147 patients were included. Interrater reliability for multiphase CT angiography is excellent (n = 30, κ = 0.81, P < .001). At receiver operating characteristic curve analysis, the ability to predict clinical outcome is modest (C statistic = 0.56, 95% confidence interval [CI]: 0.52, 0.63 for ≥50% decrease in NIHSS over 24 hours; C statistic = 0.6, 95% CI: 0.53, 0.68 for 90-day mRS score of 0-2) but better than that of models using single-phase CT angiography and perfusion CT (P < .05 overall). With AIC and BIC, models that use multiphase CT angiography are better than models that use single-phase CT angiography and perfusion CT for a decrease of 50% or more in NIHSS over 24 hours (AIC = 166, BIC = 171.7; values were lowest for multiphase CT angiography) and a 90-day mRS score of 0-2 (AIC = 132.1, BIC = 137.4; values were lowest for multiphase CT angiography). CONCLUSION: Multiphase CT angiography is a reliable tool for imaging selection in patients with AIS.

Thrombus Characteristics Are Related to Collaterals and Angioarchitecture in Acute Stroke.

BACKGROUND: We have theorized that clots with stasis are longer. We therefore explored the relationship between thrombus imaging characteristics on noncontrast computed tomography (NCCT) and magnetic resonance imaging (MRI) with clot length and pial collaterals on baseline computed tomography angiography (CTA). METHODS: Prospective study of acute ischemic stroke patients (2005-2009) from Keimyung University. Patients with known stroke symptom onset time, baseline CTA, MRI, and with M1-Middle Cerebral Artery (MCA)±intracranial internal carotid artery (ICA) occlusions were included. Clot length and pial collaterals were measured on baseline CTA. RESULTS: A total of 104 patients (mean age 65.1±12.28 years, 56.7% male, median baseline National Institutes of Health Stroke Scale 13) with intracranial ICA + MCA (n=50) or isolated M1-MCA (n=54) occlusions were included. Hyperdense sign on NCCT had a median clot length of 42.3 mm versus 29.5 mm when hyperdense negative (p=0.02). Clots showing blooming artifact on gradient recall echo MRI had a median length of 39.1 mm versus 24.5 mm without blooming (p=0.005). Patients with poor baseline collaterals on CTA had longer clots than those with intermediate/good collaterals (median clot length 49.4 mm vs 34.9 mm vs 20.5 mm respectively, p<0.001). In censored logistic regression modeling, clot length was an independent predictor of hyperdense sign (p=0.05) and of the presence of blooming artifact (p=0.006). CONCLUSIONS: Clot length and baseline collateral status are independent predictors of clot hyperdensity on NCCT and blooming artifact on gradient recall echo. Longer clots are more likely to be hyperdense and to bloom more, probably because portions of these clots are freshly formed locally due to of stasis of blood around the original clot. This stasis could be because of poor collaterals and inefficient angio-architecture within the cerebral arterial tree.

CT perfusion cerebral blood volume does not always predict infarct core in acute ischemic stroke.

We investigated the practical clinical utility of the CT perfusion (CTP) cerebral blood volume (CBV) parameter for differentiating salvageable from non-salvageable tissue in acute ischemic stroke (AIS). Fifty-five patients with AIS were imaged within 6 h from onset using CTP. Admission CBV defect (CBVD) volume was outlined using previously established gray and white matter CBV thresholds for infarct core. Admission cerebral blood flow (CBF) hypoperfusion and CBF/CBV mismatch were visually evaluated. Truncation of the ischemic time-density curve (ITDC) and hypervolemia status at admission, recanalization at 24-h CT angiography, hemorrhagic transformation (HT) at 24 h and/or 7-day non-contrast CT (NCCT), final infarct volume as indicated by 3-month NCCT defect (NCCTD) and 3-month modified Rankin Score were determined. Patients with recanalization and no truncation had the highest correlation (R = 0.81) and regression slope (0.80) between CBVD and NCCTD. Regression slopes were close to zero for patients with admission hypervolemia with/without recanalization. Hypervolemia underestimated (p = 0.02), while recanalization and ITDC truncation overestimated (p = 0.03) the NCCTD. Among patients with confirmed recanalization at 24 h, 38 % patients had an admission CBF/CBV mismatch within normal appearing areas on respective NCCT. 83 % of these patients developed infarction in admission hypervolemic CBF/CBV mismatch tissue. A reduction in CBV is a valuable predictor of infarct core when the acquisition of ITDC data is complete and hypervolemia is absent within the tissue destined to infarct. Raised or normal CBV is not always indicative of salvageable tissue, contrary to the current definition of penumbra.

Quantifying cerebral blood flow in an adult pig ischemia model by a depth-resolved dynamic contrast-enhanced optical method.

Dynamic contrast-enhanced (DCE) near-infrared (NIR) methods have been proposed for bedside monitoring of cerebral blood flow (CBF). These methods have primarily focused on qualitative approaches since scalp contamination hinders quantification. In this study, we demonstrate that accurate CBF measurements can be obtained by analyzing multi-distance time-resolved DCE data with a combined kinetic deconvolution optical reconstruction (KDOR) method. Multi-distance time-resolved DCE-NIR measurements were made in adult pigs (n=8) during normocapnia, hypocapnia and ischemia. The KDOR method was used to calculate CBF from the DCE-NIR measurements. For validation, CBF was measured independently by CT under each condition. The mean CBF difference between the techniques was -1.7 mL/100 g/min with 95% confidence intervals of -16.3 and 12.9 mL/100 g/min; group regression analysis revealed a strong agreement between the two techniques (slope=1.06±0.08, y-intercept=-4.37±4.33 mL/100 g/min, p<0.001). The results of an error analysis suggest that little a priori information is needed to recover CBF, due to the robustness of the analytical method and the ability of time-resolved NIR to directly characterize the optical properties of the extracerebral tissue (where model mismatch is deleterious). The findings of this study suggest that the DCE-NIR approach presented is a minimally invasive and portable means of determining absolute hemodynamics in neurocritical care patients.

Arterial spin labelling reveals multi-regional cerebral hypoperfusion in patients with transient ischemic attack that are unrelated to ischemia location: A proof-of-concept study.

Background and Aims: Patients with transient ischemic attack (TIA) have a substantially increased risk of early dementia. In this exploratory study, we aim to determine whether patients with TIA have 1) measurable regional cerebral hypoperfusion unrelated to the location of ischemia, and 2) determine the relationship of regional cerebral blood flow (rCBF) with their cognitive profiles. Methods: Patients with TIA (N = 49) and seventy-nine (N = 79) age and sex matched controls underwent formal neuropsychological testing and MRI. Quantitative arterial spin labelling rCBF maps (mL/min/100 g) were registered to the corresponding high resolution T1-weighted image. Linear regression was used to determine the association between demographic, clinical and cognitive variables and rCBF. Results: Patients with TIA had significantly (p < 0.05) lower cognitive scores in the MMSE, MOCA, ACE-R, WAIS-IV DS Coding and Trail Making Tests A and B compared to controls. TIA patients had significantly lower rCBF in the left entorhinal cortex (p = 0.03), right posterior cingulate (p = 0.04), and right precuneus (p = 0.05), after adjusting for age and sex, that were unrelated to the regional anatomical volume and DWI positivity. Regional hypoperfusion in the right posterior cingulate and right precuneus was associated with impaired visual memory (BVMT total, p = 0.05 for both regions) and slower processing speed (TMT A, p = 0.04 and p = 0.01), respectively after adjusting for age and sex. Conclusions: TIA patients have patterns of regional hypoperfusion in multiple cortical regions unrelated to the parcellated regional anatomical volume or the presence of a DWI lesion. Regional hypoperfusion in patients with TIA may be an early marker conferring risk of future cognitive decline that needs to be confirmed by future studies.

The evolution of the cerebral blood volume abnormality in patients with ischemic stroke: a CT perfusion study.

BACKGROUND: Accurate identification of the acute infarct core abnormality is important for guiding acute stroke treatment. Abnormality volumes from diffusion-weighted MRI (DWI) and CT perfusion (CTP)-cerebral blood volume (CBV) are highly correlated. DWI lesions have been shown to be reversible at 24 h. PURPOSE: To examine the temporal profile of the CT perfusion (CTP)-derived CBV abnormality out to 7 days post ischemic stroke. MATERIAL AND METHODS: Twenty-six patients were included. Group A (n = 13) underwent a non-contrast CT (NCCT), CTP/CT angiography (CTA) within 6 h of stroke onset, CTP/CTA at 24 h, and CTP/NCCT at 5-7 days post stroke. Group B (n = 13) underwent a NCCT, CTP/CTA within 6 h of stroke onset, and NCCT at 5-7 days. Recanalization status was established in all patients. For both groups, infarct volumes were traced on 5-7 day NCCT images and superimposed onto all CTP-CBV functional maps to determine CBV. Group B (n = 13) admission images were used to define CBV infarct thresholds for gray and white matter. CBV-lesion over-estimation was determined for Group A using the thresholds from Group B. RESULTS: CBV (mL·100g(- 1); mean ± stdev) for gray/white matter, within confirmed infarcted regions (CBV(I)) at admission, 24 h, and 5-7 days were 1.82 ± 0.56, 1.56 ± 0.42, 1.75 ± 0.31, and 1.38 ± 0.65, 1.13 ± 0.31, 1.32 ± 0.44, respectively, when averaged over all patients (P > 0.05). Four patients had tissue time-density curves from ischemic lesions (TDC(i)) with an incomplete contrast medium wash-out phase (truncation) at admission and/or 24 h. Compared to admission, gray matter CBV(I) was higher at 5-7 days for patients with TDC(i) truncation (P < 0.05). There were no significant CBV(I) increases for the eight patients without truncation (P > 0.05). Over-estimation of acute CBV lesion was present in 3/4 (75%) and 1/9 (11%) of patients with/without TDC(i) truncation, respectively. CONCLUSION: CTP-derived CBV lesion reversal is associated with TDC(i) truncation during the acute stroke phase.

Automatic arterial input function selection in CT and MR perfusion datasets using deep convolutional neural networks.

PURPOSE: The computation of perfusion parameter images requires knowledge of the arterial blood flow in the form of an arterial input function (AIF). This work proposes a novel method to automatically identify AIFs in computed tomography perfusion (CTP) and dynamic susceptibility contrast perfusion-weighted MRI (PWI) datasets using a deep convolutional neural network (CNN). METHODS: One-hundred CTP and 100 PWI datasets of acute ischemic stroke patients were available for model development and evaluation. For each modality, 50 datasets were used for CNN training and 20 for validation using manually selected AIFs and non-arterial tissue concentration time curves. Model evaluation was performed using the remaining 30 independent validation datasets from each modality with manual AIF selections provided by two experts as ground truth. Additionally, AIFs were also extracted using an established automatic shape-based algorithm for comparison purposes. The extracted AIFs were compared using normalized cross-correlation and shape features as well as using the Dice similarity metric and volume of the corresponding hypoperfusion (Tmax > 6 s) lesions. RESULTS: The cross-correlation values comparing the manual AIFs and those extracted by the proposed CNN method were significantly greater than those comparing the manual AIFs to the shape-based comparison method. Likewise, hypoperfusion lesions generated using the manually selected AIFs and CNN-based AIFs showed higher Dice values compared to hypoperfusion lesions generated using the comparison AIF extraction method. Shape features for AIFs generated by the proposed method did not differ significantly from the manual AIFs, with the exception that the CNN-derived AIFs for the PWI datasets showed marginally greater peak heights. CONCLUSION: Deep convolutional neural network models are viable for the automatic extraction of the AIF from CTP and PWI datasets.

White matter tract microstructure and cognitive performance after transient ischemic attack.

BACKGROUND AND PURPOSE: Patients with transient ischemic attack (TIA) show evidence of cognitive impairment but the reason is not clear. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. We report WM changes using DTI and the relationship with neuropsychological performance in a cohort of transient ischemic attack (TIA) and non-TIA subjects. METHODS: Ninety-five TIA subjects and 51 non-TIA subjects were assessed using DTI and neuropsychological batteries. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated and measurements were collected from WM tracts. Adjusted mixed effects regression modelled the relationship between groups and DTI metrics. RESULTS: Transient ischemic attack subjects had a mean age of 67.9 ± 9.4 years, and non-TIA subjects had a mean age 64.9 ± 9.9 years. The TIA group exhibited higher MD values in the fornix (0.36 units, P < 0.001) and lower FA in the superior longitudinal fasciculus (SLF) (-0.29 units, P = 0.001), genu (-0.22 units, P = 0.016), and uncinate fasciculus (UF) (-0.26 units, P = 0.004). Compared to non-TIA subjects, subjects with TIA scored lower on the Addenbrooke's Cognitive Assessment-Revised (median score 95 vs 91, P = 0.01) but showed no differences in scores on the Montreal Cognitive Assessment (median 27 vs 26) or the Mini-Mental State Examination (median 30). TIA subjects had lower scores in memory (median 44 vs 52, P < 0.01) and processing speed (median 45 vs 62, P < 0.01) but not executive function, when compared to non-TIA subjects. Lower FA and higher MD in the fornix, SLF, and UF were associated with poorer performance on tests of visual memory and executive function but not verbal memory. Lower FA in the UF and fornix were related to higher timed scores on the TMT-B (P < 0.01), and higher SLF MD was related to higher scores on TMT-B (P < 0.01), confirming worse executive performance in the TIA group. CONCLUSIONS: DTI scans may be useful for detecting microstructural disease in TIA subjects before cognitive symptoms develop. DTI parameters, white matter hyperintensities, and vascular risk factors underly some of the altered neuropsychological measures in TIA subjects.

Defining reperfusion post endovascular therapy in ischemic stroke using MR-dynamic contrast enhanced perfusion.

OBJECTIVES: Cerebral blood flow (CBF) measurements after endovascular therapy (EVT) for acute ischemic stroke are important to distinguish early secondary injury related to persisting ischemia from that related to reperfusion when considering clinical response and infarct growth. METHODS: We compare reperfusion quantified by the modified Thrombolysis in Cerebral Infarction Score (mTICI) with perfusion measured by MRI dynamic contrast-enhanced perfusion within 5 h of EVT anterior circulation stroke. MR perfusion (rCBF, rCBV, rTmax, rT0) and mTICI scores were included in a predictive model for change in NIHSS at 24 h and diffusion-weighted imaging (DWI) lesion growth (acute to 24 h MRI) using a machine learning RRELIEFF feature selection coupled with a support vector regression. RESULTS: For all perfusion parameters, mean values within the acute infarct for the TICI-2b group (considered clinically good reperfusion) were not significantly different from those in the mTICI <2b (clinically poor reperfusion). However, there was a statistically significant difference in perfusion values within the acute infarct region of interest between the mTICI-3 group versus both mTICI-2b and <2b (p = 0.02). The features that made up the best predictive model for change in NIHSS and absolute DWI lesion volume change was rT0 within acute infarct ROI and admission CTA collaterals respectively. No other variables, including mTICI scores, were selected for these best models. The correlation coefficients (Root mean squared error) for the cross-validation were 0.47 (13.7) and 0.51 (5.7) for change in NIHSS and absolute DWI lesion volume change. CONCLUSION: MR perfusion following EVT provides accurate physiological approach to understanding the relationship of CBF, clinical outcome, and DWI growth. ADVANCES IN KNOWLEDGE: MR perfusion CBF acquired is a robust, objective reperfusion measurement providing following recanalization of the target occlusion which is critical to distinguish potential therapeutic harm from the failed technical success of EVT as well as improve the responsiveness of clinical trial outcomes to disease modification.

Temporal evolution and spatial distribution of quantitative T2 MRI following acute ischemia reperfusion injury.

BACKGROUND: Determining mechanisms of secondary stroke injury related to cerebral blood flow and the severity of microvascular injury contributing to edema and blood-brain barrier breakdown will be critical for the development of adjuvant therapies for revascularization treatment. AIM: To characterize the heterogeneity of the ischemic lesion using quantitative T2 imaging along with diffusion-weighted magnetic resonance imaging (DWI) within five hours of treatment. METHODS: Quantitative T2 magnetic resonance imaging was acquired within 5 h (baseline) and at 24 h (follow-up) of stroke treatment in 29 patients. Dynamic contrast enhanced permeability imaging was performed at baseline in a subgroup of patients. Absolute volume change and lesion percent change was determined for the quantitative T2, DWI, and absolute volume change sequences. A Gaussian process with RRELIEFF feature selection algorithm was used for prediction of relative quantitative T2 and DWI lesion growth, baseline and follow-up quantitative T2/DWI lesion ratios, and also NIHSS at 24 h and change in NIHSS from admission to 24 h. RESULTS: In n = 27 patients, median (interquartile range) lesion percent change was 114.8% (48.9%, 259.1%) for quantitative T2, 48.2% (-12.6%, 179.6%) for absolute volume change, and 62.7% (26.3%, 230.9%) for DWI, respectively. Our model, consisting of baseline NIHSS, CT ASPECTS, and systolic blood pressure, showed a strong correlation with quantitative T2 percent change (cross correlation R2 = 0.80). There was a strong predictive ability for quantitative T2/DWI lesion ratio at 24 h using baseline NIHSS and last seen normal to 24 h magnetic resonance imaging time (cross correlation R2 = 0.93). Baseline dynamic contrast enhanced permeability was moderately correlated to the baseline quantitative T2 values (rho = 0.38). CONCLUSION: Quantitative T2 imaging provides critical information for development of therapeutic approaches that could ameliorate microvascular damage during ischemia reperfusion.

Recanalization following Endovascular treatment and imaging of PErfusion, Regional inFarction and atrophy to Understand Stroke Evolution-NA1 (REPERFUSE-NA1).

RATIONALE: Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. AIM: The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume-Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. METHODS AND DESIGN: REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will be recruited (including 20% attrition) that have been randomized to either NA1 or placebo in the ESCAPE-NA1 trial. STUDY OUTCOMES: Primary-Early infarct growth measured using diffusion-weighted imaging will be at least 30% smaller in patients receiving NA1 compared to placebo. Secondary-Delayed secondary stroke injury at 90 days will be significantly reduced in patients receiving NA1 compared to placebo, as well as delayed secondary growth at 90 days. CONCLUSION: REPERFUSE-NA1 will demonstrate the effect of NA1 neuroprotection on reducing the early and delayed stroke injury after reperfusion treatment.

Hemorrhagic transformation of ischemic stroke: prediction with CT perfusion.

PURPOSE: To determine whether admission computed tomography (CT) perfusion-derived permeability-surface area product (PS) maps differ between patients with hemorrhagic acute stroke and those with nonhemorrhagic acute stroke. MATERIALS AND METHODS: This prospective study was institutional review board approved, and all participants gave written informed consent. Forty-one patients who presented with acute stroke within 3 hours after stroke symptom onset underwent two-phase CT perfusion imaging, which enabled PS measurement. Patients were assigned to groups according to whether they had hemorrhage transformation (HT) at follow-up magnetic resonance (MR) imaging and CT and/or whether they received tissue plasminogen activator (TPA) treatment. Clinical, demographic, and CT perfusion variables were compared between the HT and non-HT patient groups. Associations between PS and HT were tested at univariate and multivariate logistic regression analyses and receiver operating characteristic (ROC) analysis. RESULTS: HT developed in 23 (56%) patients. Patients with HT had higher National Institutes of Health Stroke Scale (NIHSS) scores (P = .005), poorer outcomes (P = .001), and a higher likelihood of having received TPA (P = .005) compared with patients without HT. Baseline blood flow (P = .17) and blood volume (P = .11) defects and extent of flow reduction (P = .27) were comparable between the two groups. The mean PS for the HT group, 0.49 mL x min(-1) x (100 g)(-1), was significantly higher than that for the non-HT group, 0.09 mL x min(-1) x (100 g)(-1) (P < .0001). PS (odds ratio, 3.5; 95% confidence interval [CI]: 1.69, 7.06; P = .0007) and size of hypoattenuating area at nonenhanced admission CT (odds ratio, 0.4; 95% CI: 0.2, 0.7; P = .002) were the only independent variables associated with HT at stepwise multivariate analysis. The mean area under the ROC curve was 0.918 (95% CI: 0.828, 1.00). The PS threshold of 0.23 mL x min(-1) x (100 g)(-1) had 77% sensitivity and 94% specificity for detection of HT. CONCLUSION: Admission PS measurement appears promising for distinguishing patients with acute stroke who are likely from those who are not likely to develop HT. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/250/3/867/DC1.

Diffusion-Weighted MRI Stroke Volume Following Recanalization Treatment is Threshold-Dependent.

PURPOSE: Infarct lesion segmentation has been problematic as there are a wide range of relative and absolute diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) thresholds that have been used for this purpose. We examined differences of stroke lesion volume and evolution evaluated by magnetic resonance imaging (MRI) during the immediate post-treatment phase (<5 h) and at 24 h. METHODS: In this study 33 acute ischemic stroke patients were imaged with MRI <5 h and 24 h post-reperfusion treatment. Lesion volumes were segmented on ADC maps and average DWI using literature cited absolute ADC and relative DWI thresholds. The segmented lesion volumes within both time points were compared and the absolute change in lesion volume (infarct growth) between the two time points was calculated and compared using Bland-Altman analysis. RESULTS: Lesion volumes differed significantly when different relative DWI or absolute ADC thresholds were used (p < 0.05), which held true for baseline as well as follow-up lesions. The median absolute changes in lesion volume from baseline to follow-up for ADC thresholds of 550 × 10-6 mm2/s, 600 × 10-6 mm2/s, 630 × 10-6 mm2/s and 650 × 10-6 mm2/s were 3.5 ml, 4.2 ml, 4.5 ml, and 6.5 ml, respectively (p < 0.05). Likewise, the median absolute changes in lesion volume from baseline to follow-up for DWI thresholds, k = 0.85, 1.28, 1.64, 1.96, and 2.7 were 10.1 ml, 7.3 ml, 5.7 ml, 5.4 ml and 4.2 ml, respectively (p < 0.05). CONCLUSION: Absolute lesion volumes and changes in lesion volumes (infarct growth) measured after recanalization treatment were dependent on absolute ADC and relative DWI thresholds, which may have clinical significance. Standardization of techniques for measuring DWI lesion volumes requires immediate attention.