Diffusion-weighted Imaging Lesion Growth Research Articles

Rapid Apparent Diffusion Coefficient Evolution After Early Revascularization.

Background and Purpose- In this era of endovascular therapy (EVT) with early, complete recanalization and reperfusion, we have observed an even more rapid apparent diffusion coefficient (ADC) normalization within the acute ischemic lesion compared with the natural history or IV-tPA-treated patient. In this study, we aimed to evaluate the effect of revascularization on ADC evolution within the core lesion in the first 24 hours in acute ischemic stroke patients. Methods- This retrospective study included anterior circulation acute ischemic stroke patients treated with EVT with or without intravenous tPA (IVT) from 2015 to 2017 compared with a consecutive cohort of IVT-only patients treated before 2015. Diffusion-weighted imaging and ADC maps were used to quantify baseline core lesions. Median ADC value change and core reversal were determined at 24 hours. Diffusion-weighted imaging lesion growth was measured at 24 hours and 5 days. Good clinical outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Results- Twenty-five patients (50%) received IVT while the other 25 patients received EVT (50%) with or without IVT. Between these patient groups, there were no differences in age, sex, baseline National Institutes of Health Stroke Scale, interhospital transfer, or IVT rates. Thirty-two patients (64%) revascularized with 69% receiving EVT. There was a significant increase in median ADC value of the core lesion at 24 hours in patients who revascularized compared with further ADC reduction in nonrevascularization patients. Revascularization patients had a significantly higher rate of good clinical outcome at 90 days, 63% versus 9% (P=0.003). Core reversal at 24 hours was significantly higher in revascularization patients, 69% versus 22% (P=0.002). Conclusions- ADC evolution in acute ischemic stroke patients with early, complete revascularization, now more commonly seen with EVT, is strikingly different from our historical understanding. The early ADC normalization we have observed in this setting may include a component of secondary injury and serve as a potential imaging biomarker for the development of future adjunctive therapies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.

Diffusion-weighted imaging lesion growth occurs despite recanalization in acute ischemic stroke: Implications for future treatment trials.

A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment. Infarct growth may occur even after successful recanalization and could represent an appropriate endpoint for future stroke therapy trials. Magnetic resonance diffusion-weighted imaging lesion volumes were obtained at 5 h (initial posttreatment) and 24 h (follow-up) after acute stroke treatment for n = 33 in ischemic stroke patients. Sample sizes per arm (90% power, 30% effect size) for diffusion-weighted imaging lesion growth between initial and 24 h, early change in the National Institutes of Health Stroke Scale between pre- and 24 h, National Institutes of Health Stroke Scale at 24 h, and diffusion-weighted imaging lesion volume at 24 h were estimated to power a placebo-controlled stroke therapy trial. For patients with poor recanalization (modified thrombolysis in cerebral infarction <2 a; modified arterial occlusion lesion = 0-2) (n = 11), the median diffusion-weighted imaging lesion growth was 8.1 (interquartile range: 4.5, 22.4) ml and with good recanalization (modified thrombolysis in cerebral infarction =2 b or 3; modified arterial occlusion lesion = 3) (n = 22), the median diffusion-weighted imaging lesion growth was 10.0 (interquartile range: 6.0, 28.2) ml ( P = 0.749). When considering a 30% effect size, the sample size required per arm to achieve significance in an acute stroke study would be: (1) N = 49 for the diffusion-weighted imaging lesion growth between initial posttreatment and follow-up time points, (2) N = 65 for the change in the National Institutes of Health Stroke Scale between admission and 24 h, (3) N = 259 for the National Institutes of Health Stroke Scale at 24 h, and (4) N = 256 for diffusion-weighted imaging volume at 24 h. Despite best efforts to recanalize the ischemic brain, early diffusion-weighted imaging lesion growth still occurs. Treatment trials in stroke should consider early diffusion-weighted imaging lesion growth as a surrogate outcome measure to significantly reduce sample sizes.

Impact of Initial Diffusion-Weighted Imaging Lesion Growth Rate on the Success of Endovascular Reperfusion Therapy.

Initial diffusion-weighted imaging lesion growth rate (IGR) assessed by diffusion-weighted imaging lesion volume divided by the delay from onset to magnetic resonance imaging offers an estimate of early brain infarction progression. We investigated the impact of IGR on the rate of favorable outcome according to the occurrence of a successful endovascular revascularization within 6 hours after onset in patients experiencing an acute brain infarction complicating internal carotid artery terminus/middle cerebral artery M1 occlusion. The primary study end point was a favorable outcome defined by a modified Rankin Scale score of ≤2, 90 days after onset. A Thrombolysis in Cerebral Infarction score 2b/3 defined a successful recanalization. A total of 166 patients were included. Median IGR was 7 mL/h (interquartile range, 2-26). Sixty-eight patients (41%) experienced a favorable outcome. After adjustment on age, systolic blood pressure, vessel site occlusion, National Institutes of Health Stroke Scale, and antithrombotic medication, increase in IGR was associated with a decreased occurrence of favorable outcome with an odds ratio per SD increase of 0.60 (95% confidence interval, 0.38-0.94; P=0.03). A successful recanalization was achieved among 56% of the patients after a median delay of 251 minutes (interquartile range, 211-291 minutes). Increasing IGR was associated with a decreased favorable outcome only when a successful recanalization was not achieved (adjusted odds ratio, 0.32; 95% confidence interval, 0.12-0.85; P=0.02). Proximal internal carotid artery/M1 occlusion did result into a wide range of IGR within 6 hours after onset. Increasing IGR was associated with a lower rate of favorable outcome after endovascular treatment overall and when a successful recanalization was not achieved.

Comparison between voxel-based and subtraction methods for measuring diffusion-weighted imaging lesion growth after thrombolysis

Infarct growth (IG) is used as surrogate end-point in therapeutic trials. For practical reasons, infarct growth is commonly assessed using simple subtraction of acute from follow-up diffusion-weighted imaging (DWI) lesion volumes. However, the volume subtraction method will underestimate true infarct growth in case of diffusion-weighted imaging lesion reversal. To measure the size of the difference between true infarct growth on voxel-based coregistration and infarct growth approximated with simple volume subtraction. We retrospectively analyzed 322 consecutive stroke patients (median (IQR) age: 70 years (57-80), National Institute of Health Stroke Score at admission 14 (8-19)), who underwent a magnetic resonance imaging before (DWI1) and ≈24 h (DWI2) after i.v.-thrombolysis. IGvoxel-based was defined as the volume of signal changes on DWI2 that did not overlap with that on coregistered DWI1. This was compared with simply subtracting DWI1 from DWI2 lesion volume (IGsubtracted). We also compared these two metrics for the prediction of three-month unfavorable outcome (mRS ≥ 2) using c-statistics of multivariable models, adjusted for age, and National Institute of Health Stroke Score. Infarct growth volume metrics were strongly correlated (ρ = 0.94), but IGsubtracted substantially underestimated IGvoxel-based (median (IQR): 9.52 (0.23-38.9) vs. 16.98 (4.4-45.4) mL). Of the 75 patients with shrinking or stable diffusion-weighted imaging lesion using volume subtraction, IGvoxel-based was ≥5 mL in 20 (27% of the subset, 6.2% of the whole population). Moreover, IGvoxel-based better predicted unfavorable outcome than IGsubtracted (c-statistics = 0.86 (95% CI, 0.82-0.90) vs. 0.82 (0.78-0.87), P = 0.003). At early post-thrombolysis time points, the simple subtraction of lesion volumes masked substantial diffusion-weighted imaging lesion growth in 6.2% of patients. Although more time-consuming, the voxel-based method may impact results of trials that use infarct growth attenuation as an end-point.

Normobaric hyperoxia markedly reduces brain damage and sensorimotor deficits following brief focal ischaemia.

'True' transient ischaemic attacks are characterized not only clinically, but also radiologically by a lack of corresponding changes on magnetic resonance imaging. During a transient ischaemic attack it is assumed that the affected tissue is penumbral but rescued by early spontaneous reperfusion. There is, however, evidence from rodent studies that even brief focal ischaemia not resulting in tissue infarction can cause extensive selective neuronal loss associated with long-lasting sensorimotor impairment but normal magnetic resonance imaging. Selective neuronal loss might therefore contribute to the increasingly recognized cognitive impairment occurring in patients with transient ischaemic attacks. It is therefore relevant to consider treatments to reduce brain damage occurring with transient ischaemic attacks. As penumbral neurons are threatened by markedly constrained oxygen delivery, improving the latter by increasing arterial O2 content would seem logical. Despite only small increases in arterial O2 content, normobaric oxygen therapy experimentally induces significant increases in penumbral O2 pressure and by such may maintain the penumbra alive until reperfusion. Nevertheless, the effects of normobaric oxygen therapy on infarct volume in rodent models have been conflicting, although duration of occlusion appeared an important factor. Likewise, in the single randomized trial published to date, early-administered normobaric oxygen therapy had no significant effect on clinical outcome despite reduced diffusion-weighted imaging lesion growth during therapy. Here we tested the hypothesis that normobaric oxygen therapy prevents both selective neuronal loss and sensorimotor deficits in a rodent model mimicking true transient ischaemic attack. Normobaric oxygen therapy was applied from the onset and until completion of 15 min distal middle cerebral artery occlusion in spontaneously hypertensive rats, a strain representative of the transient ischaemic attack-prone population. Whereas normoxic controls showed normal magnetic resonance imaging but extensive cortical selective neuronal loss associated with microglial activation (present both at Day 14 in vivo and at Day 28 post-mortem) and marked and long-lasting sensorimotor deficits, normobaric oxygen therapy completely prevented sensorimotor deficit (P < 0.02) and near-completely Day 28 selective neuronal loss (P < 0.005). Microglial activation was substantially reduced at Day 14 and completely prevented at Day 28 (P = 0.002). Our findings document that normobaric oxygen therapy administered during ischaemia nearly completely prevents the neuronal death, microglial inflammation and sensorimotor impairment that characterize this rodent true transient ischaemic attack model. Taken together with the available literature, normobaric oxygen therapy appears a promising therapy for short-lasting ischaemia, and is attractive clinically as it could be started at home in at-risk patients or in the ambulance in subjects suspected of transient ischaemic attack/early stroke. It may also be a straightforward adjunct to reperfusion therapies, and help prevent subtle brain damage potentially contributing to long-term cognitive and sensorimotor impairment in at-risk populations.

Abstract 182: Time is Brain on the Collateral Clock! Collaterals and Reperfusion Determine Tissue Injury

Background: The pace of ischemic injury due to stroke may vary due to collaterals and degree of reperfusion. Previous linear models that estimate time is brain have not incorporated individual patient data from advanced imaging such as diffusion-weighted imaging (DWI) and angiographic assessment of collateral grade or reperfusion. We developed a realistic model of ischemic injury using detailed imaging data in a homogenous cohort of isolated M1 middle cerebral artery occlusions. Methods: Retrospective analysis of a consecutive series of isolated M1 occlusions was conducted at an expert core lab. ASITN collateral grade was assessed at baseline and extent of reperfusion after endovascular therapy (EVT) was scored with 3 distinct versions of TICI. A separate imaging expert measured DWI lesion volumes on serial MRI acquired from admission to discharge. Graphical analyses illustrated curves demarcating extent of injury over time, based on both collateral grade and extent of reperfusion. Results: 126 patients (median age 73; 88 women; median NIHSS 17; median time to 1 st DWI, 4h08min) with acute stroke due to M1 occlusion (61 proximal, 65 distal) underwent EVT during a 6-year period. Median collateral grade was 2 (range 0-4) and median TICI, 2B (range 0-3). mTICI scores were 0 (n=18), 1 (6), 2A (25), 2B (73), and 3 (4) with 24 TICI 2C scores when evaluated in detail. Total number of DWI scans was 323, with mean 2.5 per patient. Collateral grade strongly influenced pace of development of initial tissue injury (ASITN 0, 0.445 cc/min; 1, 0.276 cc/min; 2, 0.178 cc/min; 3, 0.106 cc/min; 4, 0.031 cc/min). The relationship between time and DWI lesion growth was not linear, but best fit logarithmically (R 2 = 0.985, RMSE 2.1 for log fit; R 2 = 0.757, RMSE 8.1 for linear fit). Individual lesion growth varied markedly with both collateral grade (ANOVA p&lt;0.001) and the degree (TICI 2B/3 vs. 0,1,2A) of reperfusion (ANOVA p=0.013). Conclusions: Collateral grade and the degree of reperfusion strongly dictate the timecourse of ischemic injury in the brain after stroke onset. Advanced imaging and angiographic assessment of collaterals and reperfusion confirm a logarithmic, not linear, model that can be used to differentiate stroke patients and streamline therapeutic strategies.

Mechanisms of Unexplained Neurological Deterioration After Intravenous Thrombolysis

Unstable clinical course characterizes the first 24 hours after thrombolysis for anterior circulation stroke, including early neurological deterioration (END), a secondary complication consistently predictive of poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END remains unclear in the majority of cases (ENDunexplained). Based on the core/penumbra model, we tested the hypothesis that ENDunexplained is caused by infarct growth beyond the initial penumbra and assessed the associated vascular patterns. From our database of consecutive thrombolyzed patients (n=309), we identified 10 ENDunexplained cases who had undergone both admission and 24-hour MRI. Diffusion-weighted imaging lesion growth both within and beyond the acute penumbra (Tmax>6 seconds) was mapped voxelwise. These 10 cases were compared with 30 no-END controls extracted from the database blinded to 24-hour diffusion-weighted imaging to individually match cases (3/case) according to 4 previously identified clinical and imaging variables. As predicted, lesion growth beyond initial penumbra was present in 9 of 10 ENDunexplained patients (substantial in 8) and its volume was significantly larger in cases than controls (2P=0.047). All ENDunexplained cases had proximal arterial occlusion initially, of which only 2 had recanalized at 24 hours. In this exploratory study, most instances of ENDunexplained were related to diffusion-weighted imaging growth beyond acute penumbra. Consistent presence of proximal occlusion at admission and lack of recanalization at 24 hours in most cases suggest that hemodynamic factors played a key role, via for instance systemic instability/collateral failure or secondary thromboembolic processes. Preventing END after tissue-type plasminogen activator using, eg, early antithrombotics may therefore be feasible.

Early infarct growth predicts long-term clinical outcome after thrombolysis

BackgroundIschemic lesion growth may be a surrogate marker of clinical outcome, but no such interrelationship after thrombolysis has yet been determined. We evaluated the association between early infarct growth on diffusion-weighted imaging (DWI) and long-term clinical outcome after thrombolysis. MethodsWe retrospectively reviewed outcomes in patients with acute middle cerebral artery territory stroke who had been treated with intravenous tissue plasminogen activator or intra-arterial urokinase. DWI lesion volumes were measured at baseline and within 7days, and the difference was calculated. Clinical outcome was evaluated using the modified Rankin Scale (mRS) at 3months. Good and poor clinical outcomes were defined as: a) mRS 0–1 vs. mRS 2–6, b) mRS 0–2 vs. mRS 3–6, and c) responder analysis which was influenced by the baseline National Institutes of Health Stroke Scale (NIHSS) scores: good and poor outcomes were defined as mRS 0 vs. mRS 1–6 if the baseline NIHSS score was <8, mRS 0–1 vs. mRS 2–6 if the NIHSS score was 8–14, and mRS 0–2 vs. mRS 3–6 if the NIHSS score was >14. The relationship between the ischemic lesion volume change and clinical outcome was explored. The cut-off value of infarct growth predicting long-term outcome was estimated using receiver operating characteristic analysis. ResultsOf the 81 patients included, 67 (82.7%) showed lesion growth, and absolute growth was significantly related to poor outcomes (P<0.001 all for mRS 2–6, mRS 3–6, and responder analysis). Multivariate analysis showed that absolute lesion growth was an independent predictor of poor outcome, defined as mRS 2–6 (P=0.002; odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.10), mRS 3–6 (P=0.001; OR, 1.06; 95% CI, 1.02–1.10), and poor outcome by responder analysis (P=0.001; OR, 1.06; 95% CI, 1.03–1.10). The cut-off values of lesion growth that discriminated between good and poor outcomes were 14.11cm3 for mRS 2–6; 15.87cm3 for mRS 3–6; and 14.11cm3 in responder analysis. ConclusionsEarly DWI lesion growth is an independent predictor of poor outcome after thrombolysis and may serve a potential surrogate marker of clinical outcome in acute stroke trials.

Neuroprotection by Freezing Ischemic Penumbra Evolution Without Cerebral Blood Flow Augmentation With a Postsynaptic Density-95 Protein Inhibitor

The purpose of this study was to determine whether neuroprotection is feasible without cerebral blood flow augmentation in experimental permanent middle cerebral artery occlusion. Rats were subjected to permanent middle cerebral artery occlusion by the suture occlusion method and were treated 1 hour thereafter with a single 5-minute intravenous infusion of the postsynaptic density-95 protein inhibitor Tat-NR2B9c (7.5 mg/kg) or saline (n=8/group). Arterial spin-labeled perfusion-weighted MRI and diffusion weighted MRI were obtained with a 4.7-T Bruker system at 30, 45, 70, 90, 120, 150, and 180 minutes postmiddle cerebral artery occlusion to determine cerebral blood flow and apparent diffusion coefficient maps, respectively. At 24 hours, animals were neurologically scored (0 to 5), euthanized, and the brains stained with 2-3-5-triphenyl tetrazolium chloride to ascertain infarct volumes corrected for edema. Additionally, the effects of Tat-NR2B9c on adenosine 5'-triphosphate levels were measured in vitro in neurons subjected to oxygen-glucose deprivation. Final infarct volume was decreased by 30.3% in the Tat-NR2B9c-treated animals compared with controls (P=0.028). There was a significant improvement in 24 hours neurological scores in the Tat-NR2B9c group compared with controls, 1.8±0.5 and 2.8±1.0, respectively (P=0.021). Relative to controls, Tat-NR2B9c significantly attenuated diffusion-weighted imaging lesion growth and preserved the diffusion-weighted imaging/perfusion-weighted imaging mismatch (ischemic penumbra) without affecting cerebral blood flow in the ischemic core or penumbra. Tat-NR2B9c treatment of primary neuronal cultures resulted in 26% increase in cell viability and 34% greater adenosine 5'-triphosphate levels after oxygen-glucose deprivation. Preservation of adenosine 5'-triphosphate levels in vitro and neuroprotection in permanent middle cerebral artery occlusion in rats is achievable without cerebral blood flow augmentation using a postsynaptic density-95 protein inhibitor.

PROGNOSTIC SIGNIFICANCE OF BLOOD PRESSURE VARIABILITY AFTER THROMBOLYSIS IN ACUTE STROKE

Objective: To evaluate the impact of early blood pressure (BP) changes on diffusion-weighted imaging (DWI) lesion evolution and clinical outcome in patients with stroke treated with IV tissue plasminogen activator (tPA). Methods: We prospectively evaluated 80 patients with stroke with a documented middle cerebral artery occlusion treated with IV tPA. Multiple repeated systolic (SBP) and diastolic (DBP) BP measurements were obtained during 24 hours after admission. All patients underwent DWI, perfusion-weighted imaging, and magnetic resonance angiography before and 36–48 hours after thrombolysis. Recanalization was assessed on transcranial Doppler at 6 hours of stroke onset. NIH Stroke Scale scores were recorded at baseline and 24 hours. Modified Rankin Scale was used to assess 3-month outcome. Results: Recanalization occurred in 44 (55%) patients. BP variability, estimated as the SD of the mean, was associated with DWI lesion growth (r = 0.46, p = 0.0003 for SBP and r = 0.26, p = 0.02 for DBP), early clinical course (p = 0.06 for SBP and p = 0.01 for DBP), and 3-month outcome (p = 0.002 for SBP and 0.07 for DBP). However, the prognostic significance of BP changes differed depending on the presence of recanalization. SBP variability emerged as an independent predictor of DWI lesion growth (β: 6.9; 95% CI, 3.2 to 10.7, p = 0.003) and worse stroke outcome (OR: 11; 95% CI: 2.2 to 56.1; p = 0.004) in patients without recanalization, but not in recanalized patients. Conclusion: Blood pressure variability is associated with greater diffusion-weighted imaging lesion growth and worse clinical course in patients with stroke treated with IV tissue plasminogen activator. However, its impact varies depending on the occurrence of early recanalization after thrombolysis.

Prognostic significance of blood pressure variability after thrombolysis in acute stroke

To evaluate the impact of early blood pressure (BP) changes on diffusion-weighted imaging (DWI) lesion evolution and clinical outcome in patients with stroke treated with IV tissue plasminogen activator (tPA). We prospectively evaluated 80 patients with stroke with a documented middle cerebral artery occlusion treated with IV tPA. Multiple repeated systolic (SBP) and diastolic (DBP) BP measurements were obtained during 24 hours after admission. All patients underwent DWI, perfusion-weighted imaging, and magnetic resonance angiography before and 36-48 hours after thrombolysis. Recanalization was assessed on transcranial Doppler at 6 hours of stroke onset. NIH Stroke Scale scores were recorded at baseline and 24 hours. Modified Rankin Scale was used to assess 3-month outcome. Recanalization occurred in 44 (55%) patients. BP variability, estimated as the SD of the mean, was associated with DWI lesion growth (r = 0.46, p = 0.0003 for SBP and r = 0.26, p = 0.02 for DBP), early clinical course (p = 0.06 for SBP and p = 0.01 for DBP), and 3-month outcome (p = 0.002 for SBP and 0.07 for DBP). However, the prognostic significance of BP changes differed depending on the presence of recanalization. SBP variability emerged as an independent predictor of DWI lesion growth (beta: 6.9; 95% CI, 3.2 to 10.7, p = 0.003) and worse stroke outcome (OR: 11; 95% CI: 2.2 to 56.1; p = 0.004) in patients without recanalization, but not in recanalized patients. Blood pressure variability is associated with greater diffusion-weighted imaging lesion growth and worse clinical course in patients with stroke treated with IV tissue plasminogen activator. However, its impact varies depending on the occurrence of early recanalization after thrombolysis.

Speed of tPA-Induced Clot Lysis Predicts DWI Lesion Evolution in Acute Stroke

We sought to evaluate the impact of the speed of recanalization on the evolution of diffusion- weighted imaging (DWI) lesions and outcome in stroke patients treated with tissue-type plasminogen activator (tPA). We evaluated 113 consecutive stroke patients with a middle cerebral artery occlusion who were treated with intravenous tPA. All patients underwent multiparametric magnetic resonance imaging studies, including DWI and perfusion-weighted imaging before and 36 to 48 hours after administration of a tPA bolus. Patients were continuously monitored with transcranial Doppler during the first 2 hours after tPA administration. The pattern of recanalization on transcranial Doppler was defined as sudden (<1 minute), stepwise (1 to 29 minutes), or slow (>30 minutes). During transcranial Doppler monitoring, 13 (12.3%) patients recanalized suddenly, 32 (30.2%) recanalized in a stepwise manner, and 18 (17%) recanalized slowly. Baseline clinical and imaging parameters were similar among recanalization subgroups. At 36 to 48 hours, DWI lesion growth was significantly (P=0.001) smaller after sudden (3.23+/-10.5 cm(3)) compared with stepwise (24.9+/-37 cm(3)), slow (46.3+/-38 cm(3)), and no (51.7+/-34 cm(3)) recanalization. The slow pattern was associated with greater DWI growth (P=0.003), lesser degree of clinical improvement (P=0.021), worse 3-month outcome (P=0.032), and higher mortality (P=0.003). The speed of tPA-induced clot lysis predicts DWI lesion evolution and clinical outcome. Unlike sudden and stepwise patterns, slow recanalization is associated with greater DWI lesion growth and poorer short- and long-term outcomes.

Cooling for Acute Ischemic Brain Damage (COOL AID)

To report results of a randomized pilot clinical feasibility trial of endovascular cooling in patients with ischemic stroke. Forty patients with ischemic stroke presenting within 12 hours of symptom onset were enrolled in the study. An endovascular cooling device was inserted into the inferior vena cava of those randomized to hypothermia. A core body temperature of 33 degrees C was targeted for 24 hours. All patients underwent clinical assessment and MRI initially, at days 3 to 5 and days 30 to 37. Eighteen patients were randomized to hypothermia and 22 to receive standard medical management. Thirteen patients reached target temperature in a mean of 77 +/- 44 minutes. Most tolerated hypothermia well. Clinical outcomes were similar in both groups. Mean diffusion-weighted imaging (DWI) lesion growth in the hypothermia group (n = 12) was 90.0 +/- 83.5% compared with 108.4 +/- 142.4% in the control group (n = 11) (NS). Mean DWI lesion growth in patients who cooled well (n = 8) was 72.9 +/- 95.2% (NS). Induced moderate hypothermia is feasible using an endovascular cooling device in most patients with acute ischemic stroke. Further studies are needed to determine if hypothermia improves outcome.

Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection.

Effective therapy was not available for treatment of acute stroke until 1995, when tissue plasminogen activator (tPA) was shown to improve neurological and functional outcome in stroke patients who were treated within 3 hours of symptom onset. Currently, many patients do not qualify for tPA therapy because they present for evaluation beyond 3 hours after stroke onset. Attempts to expand the treatment window to 6 hours, using CT to select patients, have failed. Use of early MR imaging may provide significant advantages over CT for identification of patients who are likely to benefit from thrombolytic therapy because (1) the early perfusion-weighted imaging (PWI) lesion estimates the region of acute dysfunctional brain tissue, whereas the acute diffusion-weighted imaging (DWI) lesion appears to correspond to the core of the early infarction; (2) the mismatch between the acute PWI lesion and the smaller DWI lesion represents potentially salvageable brain tissue (an estimate of the ischemic penumbra); and (3) in patients with a PWI/DWI mismatch, early reperfusion is often associated with substantial clinical improvement and reversal or reduction of DWI lesion growth. Clinical trials that use new MRI techniques to screen patients may be able to identify a subset of acute stroke patients who are ideal candidates for thrombolytic therapy even beyond 3 hours after stroke onset.