Xenon-enhanced Computed Tomography Research Articles

Comparison of Cerebral Blood Flow Between Perfusion Computed Tomography and Xenon-Enhanced Computed Tomography for Normal Subjects

The purpose of this study was to clarify the difference between cerebral blood flow (CBF) by perfusion computed tomography (CT) and that by xenon-enhanced CT (Xe-CT) through simultaneous measurement. Xenon-enhanced CT and perfusion CT were continually performed on 7 normal subjects. Ratios of CBF by perfusion CT (P-CBF) to CBF by Xe-CT (Xe-CBF) were measured for 5 arterial territories; 3 were territories of 3 major arteries (the anterior [ACA], middle [MCA], and posterior [PCA] cerebral arteries), and the other 2 were areas of the thalamus and putamen. The ratios were 1.30 +/- 0.10, 1.26 +/- 0.15, 1.61 +/- 0.15, 0.801 +/- 0.087, and 0.798 +/- 0.080 for the ACA, MCA, PCA, thalamus, and putamen, respectively. Although a good correlation was observed between P-CBF and Xe-CBF for each territory, the ratios were significantly different (P < 0.0001) between 3 territory groups (group 1: ACA and MCA, group 2: PCA, and group 3: thalamus and putamen). The difference in the ratio of P-CBF to Xe-CBF between the 3 territory groups was considered to result principally from the features of P-CBF. To evaluate P-CBF properly, its territorial characteristics should be taken into account.

Cerebral Vasoreactivity: A Comparison of Color Velocity Imaging Quantification and Stable Xenon-Enhanced CT

Compromised cerebral vasoreactivity increases the risk of stroke. In this study, we sought to determine whether extracranial arterial blood flow volume measured on color velocity imaging quantification could be predictive of cerebral vasoreactivity after the administration of acetazolamide. Cerebral blood flow and extracranial arterial blood flow volume of 35 patients with symptomatic carotid occlusive disease were measured before and after the administration of acetazolamide on stable xenon CT and color velocity imaging quantification, respectively. The changes in unilateral extracranial arterial blood flow volume and respective hemispheric cerebral blood flow were compared. The mean difference in the percentage of change in flow volume, the 95% limit of agreement, and Cohen's kappa coefficient were calculated. A total of 64 unilateral extracranial arterial blood flow volume changes were successfully compared with the changes in the ipsilateral hemispheric cerebral blood flow. The mean difference in percentage of change in flow volume between the two techniques was 4.7%, with the 95% limit of agreement ranging from -90.2% to 99.7%. Cohen's kappa coefficient was 0.41 (95% confidence interval, 0.13-0.68; p = 0.001). The performance of color velocity imaging quantification for evaluating cerebral vasoreactivity is comparable to that of transcranial Doppler sonography. Because color velocity imaging quantification is not as limited as transcranial Doppler sonography, it could be an ideal complementary tool to transcranial Doppler sonography. More studies are required to define its clinical value.

CT Perfusion Imaging in Cerebral Ischemia

To the Editor: We read with interest the Guidelines and Recommendations for Perfusion Imaging in Cerebral Ischemia by the Writing Group on Perfusion Imaging, from the Council on Cardiovascular Radiology of the American Heart Association.1 The authors have succeeded admirably in summarizing the important recent developments of perfusion imaging and their relevance to clinical investigations of cerebral ischemia. We have been involved in the development of the First-Pass Bolus Tracking Methodology of CT Perfusion for over a decade and would like to comment on a few issues raised by the authors concerning this particular methodology. The Table is a comparison of the effective dose equivalent2 (HE) of each of the three perfusion imaging methods discussed in the Guidelines that involve the use of ionizing radiation. The effective dose equivalents for the 2 computed tomography (CT) techniques are estimated using the methodology published by Huda et al 3 based on the CT dose index values published for LightSpeed QXi scanners (General Electric Medical Systems). For CT scanners of other models or from other manufacturers, the values in the Table can be scaled proportionally according to the computed tomography dose index value of the scanner relative to the LightSpeed QXi scanner. View this table: The Table shows that CT perfusion (CTP) imaging does not necessarily give a higher radiation dose to the subject than XeCT and SPECT perfusion imaging. In comparison, a screening head CT scan has an effective dose equivalent of 1.5 mSv.3 With the recent interest in using a saline chaser to shorten the duration of the first transit of the contrast bolus through the brain, the scan duration for CTP can be reduced to around 25 to 30 s resulting in an even lower dose of 1.8 to 2.2 mSv. While xenon-enhanced computed tomography (XeCT) and single photon …

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The effect of maxillary sinus antrostomy size on xenon ventilation in the sheep model

A major goal of maxillary antrostomy is to increase sinus ventilation. Limited data exist regarding the effect of maxillary antrostomy size on sinus ventilation. We sought to quantify the effect of uncinectomy, small antrostomy, and large antrostomy on maxillary sinus ventilation using xenon-enhanced CT in the sheep model. MATERIALS, STUDY DESIGN, AND METHODS: A xenon-oxygen-air mixture was delivered to 8 fresh cadaveric sheep heads while repeated CT scans were performed through the maxillary sinuses. Baseline and postoperative studies were performed after an endoscopic uncinectomy, small antrostomy, or large antrostomy was created. Images were analyzed to measure the density of the xenon gas in the maxillary sinus as a function of time, generating a time constant. The time constants for both small antrostomy and large antrostomy were significantly different compared to baseline ( P = 0.003 for both). The time constant comparison between small antrostomy and large antrostomy was not significant ( P = 0.948). A small antrostomy produces a statistically significant increase in maxillary sinus ventilation over baseline. No significant further ventilation increase is obtained by creating a large antrostomy in the sheep model. This lends credence to the use of small antrostomies to improve maxillary sinus ventilation in human sinus surgery.

Centrifugal distribution of regional cerebral blood flow and its time course in traumatic intracerebral hematomas.

Cerebral blood flow (CBF) alterations following post-traumatic contusions have been demonstrated in recent papers. We evaluated regional CBF (rCBF) by means of Xenon-enhanced computerized tomography (Xe-CT) in 29 traumatic intracerebral hematomas, from 22 patients with severe head injury (GCS < or = 8). Fifty traumatic hematoma/Xe-CT CBF measurements were obtained from 39 Xe-CT studies performed during the acute phase (corresponding to the first 20 days post-injury). The rCBF was measured in three different regions of interest: the hemorrhagic core, the perihematoma edematous low-density area, and a 1-cm rim of perihematoma normal-appearing brain tissue, surrounding the edematous low-density area. We found a centrifugal improvement of rCBF as well as a decrease in the rates of CBF levels below 18 mL/100 g/min from the core to the periphery (p < 0.0001), which persisted over time. Ischemic rCBF values were detected in the perihematoma low-density area only in 24% of the traumatic hematomas. The time course of rCBF levels showed a reduced flow in the first 24 h, with a recovery of flow from day 2 to day 4, followed by another reduced flow (p < or = 0.0001) both in the perihematoma edematous low-density area and in the non-lesioned tissue. Our findings suggest that the only area with persistent ischemic values was the hemorrhagic core. Low rCBF levels seen in the perihematoma low-density area may only be ascribed partially to ischemia and can possibly recover over time. These results could encourage a surgical approach based on an early evacuation of the hemorrhagic core associated to a preservation of the surrounding edematous tissue.

Significance of a Reduced Cerebral Blood Flow During the First 12 Hours After Traumatic Brain Injury

It is controversial whether a low cerebral blood flow (CBF) simply reflects the severity of injury or whether ischemia contributes to the brain's injury. It is also not clear whether posttraumatic cerebral hypoperfusion results from intracranial hypertension or from pathologic changes of the cerebral vasculature. The answers to these questions have important implications for whether and how to treat a low CBF. We performed a retrospective analysis of 77 patients with severe traumatic brain injury who had measurement of CBF within 12 hours of injury. CBF was measured using xenon-enhanced computed tomography (XeCT). Global CBF, physiological parameters at the time of XeCT, and outcome measures were analyzed. Average global CBF for the 77 patients was 36+/-16 mL/100 g/minutes. Nine patients had an average global CBF<18 (average 12+/-5). The remaining 68 patients had a global CBF of 39+/-15. The initial ICP was >20 mmHg in 90% and >30 mmHg in 80% of patients in the group with CBF<18, compared to 33% and 16%, respectively, in the patients with CBF>or=18. Mortality was 90% at 6 months postinjury in patients with CBF<18. Mortality in the patients with CBF>18 was 19% at 6 months after injury. In patients with CBF<18 mL/100 g/minutes, intracranial hypertension plays a major causative role in the reduction in CBF. Treatment would most likely be directed at controlling intracranial pressure, but the early, severe intracranial hypertension also probably indicates a severe brain injury. For levels of CBF between 18 and 40 mL/100 g/minutes, the presence of regional hypoperfusion was a more important factor in reducing the average CBF.

Screening for Autonomic Temporal Lobe Epilepsy with Xenon-Enhanced Computed Tomography and Heart Rate Variability

Screening for Autonomic Temporal Lobe Epilepsy with Xenon-Enhanced Computed Tomography and Heart Rate Variability

The cortical ischemic core and not the consistently present penumbra is a determinant of clinical outcome in acute middle cerebral artery occlusion.

Patient selection for acute stroke therapy based on physiology rather than on time may lead to expansion of the therapeutic window, improved outcomes, and fewer side effects than currently achieved. This approach requires early determination of both irreversible (core) and reversible (penumbra) ischemia in acute stroke. Using established perfusion thresholds, we characterized the relationship among core, penumbra, and brain tissue perfused above penumbral thresholds (non-core/non-penumbra [NC/NP]) in 36 patients with middle cerebral artery (MCA) stem occlusion who underwent quantitative cerebral blood flow (CBF) assessment with xenon-enhanced CT within 6 hours of symptom onset. While great variability in the mean+/-SD percentage of core (37.6+/-18.7) and NC/NP (30.3+/-16.6) was observed, the percentage of penumbra was relatively constant from individual to individual, constituting approximately one third of the cortical MCA territory (32.1+/-7). In univariable and multivariable analyses, percent core and not percent penumbra was significantly associated with outcome. In acute MCA occlusion, penumbra is consistently present within a relatively narrow range, despite great variability in the size of core. This may explain why the core and not the penumbra is the main determinant of outcome in our group of patients. Recanalization therapy in acute MCA occlusion should ideally be guided by diagnostic methods capable of rapidly and reliably identifying irreversible ischemia.

Differences in acetazolamide vasoreactivity in patients with acute and chronic occlusion of the internal carotid artery

Using a xenon-enhanced computed tomography (Xe-CT) system, we measured cerebral blood flow (CBF) and acetazolamide vasoreactivity in 3 major vascular territories, the thalamus and putamen on both sides in 3 groups of patients undergoing the balloon occlusion test (BOT), with internal carotid occlusion (ICO) and with open carotids. In the ICO group, although the CBFs on the occluded side were similar to those in the BOT group, the vasoreactivity was significantly higher. The CBFs on the contralateral side were lower than those in the BOT group, but the vasoreactivity was similar. The vasoreactivity of the MCA on the occluded side mostly correlated with that in the other areas, similar to the results obtained in the open carotid group, although it was poorly correlated with other areas in the BOT group. Carotid artery occlusion may reduce CBF in a large area with restoration of vasoreactivity in the chronic stage.

Comparison of cerebral blood flow in computed tomographic hypodense areas of the brain in head-injured patients.

Hypodense lesions identified on computed tomographic (CT) scans are often assumed to indicate ischemia. The purpose of this study was to investigate regional cerebral blood flow (rCBF) in hypodense areas of the brain after severe traumatic brain injury. CBF was measured by stable xenon-enhanced CT scans. Hypodense areas were identified, and rCBF values as well as CT density were averaged for the region. Thirty (60%) of the 50 patients had a total of 45 hypodense regions, which were associated with either contusion (n = 30) or areas of infarction (n = 15). rCBF in the hypodense regions was variable, ranging from a low of 3.3 to a high of 72.5 ml/100 g/min. The cause of the lesion was the major factor associated with the level of rCBF. Although the average decrease in CT density was similar for the two types of lesions, the average rCBF was significantly lower and the difference in rCBF between the lesion and the contralateral side was greater when the hypodense lesion was associated with a contusion. A critical reduction in rCBF (<20 ml/100 g/min) was found in 19 (63%) of the hypodense regions associated with contusions but in only 4 (27%) of those from areas of infarction. Hypodensity on plain CT scans does not always indicate reduction in CBF. This association was found more commonly when the low-density area was associated with a contusion. In hypodense areas associated with infarction, rCBF was variable and not commonly in the ischemic range at the time the CBF measurement was obtained.

２．脳梗塞超急性期の脳血流画像の有用性

Purpose: Thrombolytic therapy has emerged as a new treatment option in the hyperacute stage of ischemic stroke. Although a 15% increase in meaningful rccovery has been observed at three months, it can also trigger devastating hemorrhagic transformations. Therefore, it is important to select suitable patients to undergo this treatment. The purpose of the present study was to evaluate the feasibility of cerebral blood flow (CBF) measurement by xenon-enhanced CT (Xe-CT) in patients with acute ischemic stroke as well as its potential in identifying the occluded artery and the stroke subtype. In effect, this study examines the potential for Xe-CT to select the appropriate candidates for thrombolytic therapy.Methods : In 36 sequential patients (average age: 64.1 ± 13.1) with sudden-onset of ischemic stroke (except for lacunar stroke) who had presented to our hospital within two hours after the onset, we performed Xe-CT and MRI diffusion-weighted imaging (DWI). A selective cerebral angiography was also done if further evaluation was warranted. We examined the sensitivity of Xe-CT in demonstrating the ischemic area compared with that of DWI, its potential to identify the stroke subtype, its ability to determine infarction and hemorrhage based on CBF thresholds, and its contribution to selection of thrombolysis candidates.Results: Xe-CT was completed safely in 31 out of 34 patients (91%). Within three hours after symptom onset, Xe-CT detected the ischemic area in most of the patients (94%), whereas DWI failed to do so in 24%. Of 14 patients who underwent both Xe-CT and angiography, the diagnosis of the stroke subtype determined by Xe-CT was confirmed to be correct by angiography in 11 patients (79%). The CBF threshold of nonhemorrhagic infarction in the gray matter became constant (19ml/100g/min) at 3-5 hours after the onset. In hemorrhagic infarction, however, the threshold was initially found to be lower (9ml/100g/min) at 3-5 hours and reaching comparable levels with non-hemorrhagic subtypes (17ml/100g/min) at 5-6 hours. Fourteen patients (39%) were excluded from participation in angiography or subsequent thrombolysis because of their Xe-CT findings.Conclusion: This study found that Xe-CT was feasible in patients with hyperacute ischemic stroke and more sensitive than DWI in detecting the ischemic area. Moreover, Xe-CT provided crucial information including the stroke subtype and residual CBF in the ischemic territory. Therefore, CBF measurement by Xe-CT may be useful in the patient selection criteria for thrombolytic therapy in the hyperacute phase.

Mixed dishomogeneous hemorrhagic brain contusions. Mapping of cerebral blood flow.

The aim of the study was to verify whether regional cerebral blood flow (rCBF) was distributed centrifugally in traumatic hemorrhagic contusions with multiple cores within an oedematous area. Seventeen traumatic brain contusions, from 14 patients with severe head injury (GCS < 9), were analyzed during 39 Xenon-enhanced computerized tomography (Xe-CT) studies. The CBF was measured in 3 concentric regions of interest (ROls): the hemorrhagic core, the intracontusional oedematous low density area and a 1 cm rim of pericontusional normal-appearing brain tissue surrounding the contusion. Differences between rCBFs in the three ROIs were found (p < 0.0001). rCBF in both the hemorrhagic core (21.4 +/- 19.4 ml/ 100gr/min) and the intracontusional low density area (28.4 +/- 19 ml/100gr/min) were lower than rCBF in pericontusional normal-appearing area (41.9 +/- 16 ml/100gr/min) (p < 0.0001). No significant differences were found between rCBF measured in the hemorrhagic core and intracontusional low density area (p = 0.184). Our study suggests that in the mixed density contusions with multiple hemorrhagic cores, the CBF is concentrically distributed, improving from the core to the periphery.

Noninvasive quantitative measurement of tissue blood flow in hepatocellular carcinoma using xenon-enhanced computed tomography.

The aim of this study was to quantitatively measure tissue blood flow (TBF) in hepatocellular carcinoma (HCC) by a noninvasive method using xenon (Xe) inhalation/CT scans and to correlate the measured TBF with histological features. TBF was measured in HCC with xenon-enhanced CT (xenon/CT) in 20 patients. In 15 patients with HCC diagnosed as hypervascular tumors by conventional CT, TBF of the tumors was significantly higher than that of noncancerous liver tissue (151.1 +/- 20 vs 42.6 +/- 20 ml/min/100 g). Histologically, these tumors were diagnosed as moderately-to-poorly differentiated HCC. In contrast, in five patients with hypovascular HCC, TBF of HCC was almost comparable to that of the noncancerous regions (45.3 +/- 6 vs 48.3 +/- 6 ml/min/100 g). All these tumors were well-differentiated HCC. In conclusions, the measured values of TBF correlate with the clinicopathologic features of liver tumors and nontumorous liver tissue in patients with HCC.

Induced acute arterial hypertension and regional cerebral flow in intracontusional low density area.

Traumatic brain contusions have been associated with regional ischemia. We aimed to measure the effect of induced supra-normal values of cerebral perfusion pressure (CPP) on regional cerebral blood flow (rCBF) in the intracontusional low density area surrounding the contusional hemorrhagic core. In 7 severely head injured patients (GCS < or = 8) harbouring a contusion larger than 2 cm, the rCBF levels were measured, by means of Xenon-enhanced CT, in: 1) the intracontusional low density area: 2) contralaterally, in a normal brain symmetric area. CBF studies were performed at a baseline CPP of 65.3 mmHg +/- 7 and after 20 minutes of norepinephrine-induced CPP supernormal values (88.3 mmHg +/- 10.5) (p = 0.0013). A "paradoxical" reduction of rCBF levels was observed in both the intracontusional low density area (p = 0.07) and the contralateral "normal" area (p = 0.08). In particular, this decrease of rCBF in the intracontusional low density area (-25.7 + 10 ml/100gr/min) (p = 0.0009) was present in only 4 cases, having a mean rCBF at baseline of 25 +/- 16 ml/100gr/min. In the remaining 3 cases in which rCBF at baseline was abnormally low (12 +/- 7 ml/ 100gr/min), rCBF values improved slightly (3.6 +/- 2 ml/100gr/min) (p = 0.61). An acute increase of CPP seems to marginally affect rCBF in the intracontusional low density area having critically reduced initial values, but may greatly reduce rCBF in subjects starting from non-critical baseline values.

CT Angiography and Xenon-Enhanced CT May Aid Acute-Stroke Evaluation

Advances in acute-stroke brain imaging, including MRI and CT, have demonstrated great variability in spontaneous recanalization of occluded vessels,

Changes of cerebral blood flow following dexamethasone treatment in brain tumour patients. A Xe/CT study.

It is not exactly known how dexamethasone improves the function of brain that is affected by tumour. Whether and in what sense dexamethasone influences cerebral blood flow has rarely been addressed and previous investigations have yielded inconsistent results. Stable xenon-enhanced computed tomography (Xe/CT) was used to assess the regional cerebral blood flow (rCBF) in 67 patients with supratentorial primary and secondary brain tumours. rCBF studies were done at least once prior to resection or stereotactic biopsy of the tumours. In nine patients repeated studies before surgery and in 15 patients additional studies after resective surgery were obtained. Dexamethasone was administered according to the clinical needs before surgery and systematically after surgery. Of the preoperative studies 30 were obtained before and 47 during dexamethasone treatment. The rCBF data were analysed upon correlations with daily dose, cumulative dose, and duration of dexamethasone treatment. Moreover, individual courses before and after surgery were examined. Mainly inverse correlations were found between the treatment parameters, particularly the daily dose of dexamethasone, and rCBF. Only in the subgroup of glioblastoma patients, a positive correlation was found of both duration and cumulative dose of dexamethasone with rCBF in oedema. Serial observations of individual patients confirmed the above findings, yet with possible exceptions. After tumour resection a clear improvement of rCBF was regularly observed. The beneficial effect of dexamethasone is not attributed to an increase of cerebral blood flow, because rather decreases of rCBF are mostly observed.

Lack of agreement between transcranial Doppler and Xe/CT cerebral blood flow in the detection of cerebrovascular reserves in patients with carotid occlusive disease

P41 Introduction: Transcranial Doppler ultrasonography (TCD) has been used to identify patients with compromised cerebrovascular reserve(CVR). Patients with compromised CVR have been shown to have an increased risk for stroke. Transcranial Doppler, however, has not been compared to the high resolution quantitative cerebral blood flow (CBF) method of stable xenon enhanced computed tomography (Xe/CT). Methods: Cerebrovascular reserves before and after acetazolamide administration (1 gram, i.v.) were measured by TCD insonation of the middle cerebral artery (MCA) and Xe/CT CBF. Thirty-one patients with carotid occlusive disease were studied. Calculations were based on two methods; for the first method Xe/CT CBF values were averaged over 4 levels of the MCA, the second method used the value for the MCA level with the lowest percent change. The threshold for identifying compromised CVR versus non-compromised CVR was 0% change(two standard deviations below normal)for both the TCD and the Xe/CT CBF analyses. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results: For the average MCA territory analyses TCD compared to Xe/CT CBF had a 42% sensitivity, a 90% specificity, a 50% positive predictive value and a 86% negative predictive value. The comparison of TCD to Xe/CT using the lowest MCA territory analysis for the Xe/CT CBF values also gave a sensitivity of 42%. The specificity and positive predictive value were both 100% and the negative predictive value was 72%. Discussion/ Conclusion: The sensitivity of TCD compared to Xe/CT CBF indicates a significant lack of agreement in identifing those patients with compromised CVR. The negative predictive value indicates that the number of patients identified with positive CVR (i.e. negative for compromised reserves)is not the same as with Xe/CT CBF. Physicians should consider this lack of correlation when using TCD to identify patients with compromised CVR. A direct prospective comparison to PET or a clinical prediction of stroke by Xe/CT needs to be done in order to determine the best technology.

Investigation of blood flow in meningothelial and fibrous meningiomas by xenon-enhanced CT scanning

We investigated whether xenon-enhanced computed tomography was able to separate meningothelial meningioma from fibrous meningioma. Cerebral blood flow was studied by xenon-enhanced computed tomography in six patients with incidentally detected intracranial meningiomas. All of the tumors were small (<32mm) and there was little or no péritumoral edema. Three patients had meningothelial meningioma and three patients had fibrous meningioma. The tumor blood flow and the contralateral tissue blood flow were determined. The ratio of these parameters was 7.753 ± 0.467 for meningothelial meningiomas and 0.809±0.105 for fibrous meningiomas, with a significant difference between the two tumor subtypes (p = 0.0185). There was no correlation between the signal intensity on magnetic resonance imaging and tumor subtype, and the findings on cerebral angiography also did not indicate the subtype. In conclusion, xenon-enhanced computed tomography showed a difference between smaller meningothelial and fibrous meningiomas in patients with normal surrounding brain tissue. We could not confirm that xenon-enhanced computed tomography was able to distinguish the subtype of meningioma because of the small number of subjects in this study, but our findings might expand interest in the clinical use of this method. [Neurol Res 2000; 22: 615-619]

Relationship between Cerebral Blood Flow and Clinical Outcome in Acute Stroke

Objective: The purpose of this study was to determine the relationship between cerebral blood flow (CBF) measurements in acute stroke and early clinical outcome. Material and Methods: The xenon-enhanced computed tomography (XeCT) CBF studies performed in 50 patients in the acute stage (within 8 h) of a hemispheric stroke were retrospectively analyzed. The mean CBF of the symptomatic vascular territory was compared to the corresponding territory in the contralateral hemisphere. Clinical assessment on admission and discharge was performed using the National Institutes of Health stroke scale (NIHSS). Results: Three groups were defined according to the degree of CBF asymmetry between the symptomatic and the contralateral asymptomatic vascular region. The CBF asymmetry was mild in group A (≤20%), moderate in group B (>20% and <60%) and severe in group C (≥60%). Patients in group A (n = 18) had a good outcome with a mean NIHSS score of 2 ± 2 at discharge. In group B, the patients (n = 22) had intermediate but variable outcomes: 2 patients died and the mean NIHSS score for the survivors was variable (mean NIHSS score: 9 ± 6). The patients in group C (n = 10) had a very poor outcome: 4 patients died and the survivors had a mean NIHSS score of 15 ± 1. Conclusions: Quantitative XeCT CBF measurements may be useful for selecting subgroups of stroke patients with different clinical outcomes. The possibility of predicting patient prognosis as early as in the first hours after the ischemic event may help to identify the appropriate target population that will benefit from aggressive stroke therapy.