Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Stroke. Author manuscript; available in PMC 2010 June 1.
Published in final edited form as:
PMCID: PMC2709767

MRI-based Selection for Intra-arterial Stroke Therapy: Value of Pre-treatment DWI Lesion Volume in Selecting Acute Stroke Patients Who Will Benefit from Early Recanalization


Background and Purpose

Recent studies demonstrate that an acute diffusion weighted imaging(DWI) lesion volume >70cm3 predicts poor outcome in stroke patients. We sought to determine if this threshold could identify patients treated with intra-arterial therapy(IAT) who would do poorly despite reperfusion. In patients with initial infarcts <70cm3, we sought to determine what effect recanalization and time to recanalization had on infarct growth and functional outcome.


We retrospectively studied 34 consecutive anterior circulation stroke patients who underwent pre-treatment DWI and perfusion weighted imaging(PWI) and subsequent IAT. Recanalization success and time to recanalization were recorded. Initial DWI and MTT lesion and final infarct volumes were determined. Patients were stratified based on initial infarct volume, recanalization status and time to recanalization. Statistical tests were performed to assess differences in clinical and imaging outcomes. Good clinical outcome was defined as a 3-month mRS≤2.


Among patients with initial infarcts >70cm3, all had poor outcomes despite a 50% recanalization rate, with mean infarct growth of 114cm3. These patients also had the largest MTT volumes(p<0.04). Patients with initial infarct volumes <70cm3 who recanalized early had the best clinical outcomes(p<0.008) with a 64% rate of mRS≤2 and the least infarct growth(p<0.03), with mean growth of 18cm3.


This study supports the use of an acute DWI lesion volume threshold as an imaging selection criterion for IAT. It also confirms the importance of early reperfusion in selected patients.

Keywords: Cerebral Infarction, Cerebral Revascularization, Magnetic Resonance Imaging


With the advent of advanced MR imaging such as diffusion-(DWI) and perfusion-weighted imaging(PWI), the concept of using imaging criteria as opposed to strict time limits to identify patients likely to benefit from thrombolysis has demonstrated growing promise. Multiple studies have demonstrated that intravenous thrombolysis can be safely and effectively given beyond the 3-hour window when patients are selected based on a perfusion-diffusion mismatch on MRI13.

The purpose of this study is to explore the use of advanced MR imaging in the setting of anterior circulation large vessel occlusion(LVO) treated with intra-arterial therapy(IAT). Using the imaging selection criterion employed in the DIAS(Desmoteplase in Acute Ischemic Stroke) trial of a PWI-DWI mismatch of at least 20% appears to have little discriminatory power for these patients with LVO, as the vast majority will satisfy this requirement4.

The use of a DWI lesion volume threshold appears to hold more promise. It has been demonstrated in recent studies that in anterior circulation strokes an acute DWI lesion volume greater than 70cm3 has a high specificity for poor outcomes, with or without therapy57. We sought to determine whether this DWI threshold could be applied to the pre-treatment MRI to identify patients who would do poorly despite recanalization. Furthermore, in those patients with an acute DWI lesion volume of less than 70cm3 at the time of intervention, we sought to evaluate whether recanalization status and time to recanalization predicted infarct growth and long-term functional outcome.


Patient Selection

We reviewed our acute stroke database for patients who presented to Massachusetts General Hospital(MGH) between February 2005-July 2007, and underwent IAT or a combination of IV tPA and IAT. Inclusion criteria for analysis were: (1)acute occlusion of the intracranial internal carotid artery(ICA) and/or proximal middle cerebral artery(MCA), including stem(M1) and proximal branch lesions(M2), on CT angiography(CTA); (2)pre-thrombolysis MR imaging; (3)follow-up CT or MR imaging performed within one week of stroke onset; and (4)available neurological follow-up at approximately three months after the stroke. Medical records were reviewed for clinical data. Our institutional review board approved the study.



The noncontrast head CT scan(NCCT) was acquired with contiguous 5-mm thick axial sections(140 kV, 300 mAs). The CTA was performed from the vertex to the aortic arch using 1.25-mm slice thickness, 0.625-mm reconstruction interval, 140kV, 300–500mAs. Isovue 370(Bracco Diagnostics) was injected through an 18-gauge intravenous line using a power injector(Medrad) at a rate of 3.5cc/s for a total volume of 100cc, followed by a saline “chaser” (4cc/s for 40cc). SmartPrep(GE Medical Systems, Waukesha) was used with a region-of-interest( ROI) centered over the aortic arch. Scanning was triggered once the ROI reached Δ50HU, with a ten-second scan delay.

In our emergency department stroke imaging protocol, CTA is performed to document the level and extent of intracranial vessel occlusion. If an occlusion is identified, the neurointerventional and stroke services consult on possible endovascular intervention. Because the CTA includes the aortic arch and neck, valuable information regarding the cervical vasculature (e.g., occlusion or severe stenosis) is provided prior to the procedure.


The DWI sequence was a balanced spin-echo echo-planar sequence acquired in the axial plane with the following parameters: TR 5000ms; TE 80–110ms; b-value 1000s/mm2; field of view 22cm; matrix size 128×128, zero-filled to 256×256; and slice thickness 5mm, with 1mm interslice gap. Five images per slice were acquired with the diffusion gradients turned off, followed by thirty images with the diffusion gradients applied in six different directions, for a total imaging time of three minutes, five seconds. Isotropic DWI images, ADC maps, and echo planar T2-weighted images were generated on the scanner console at the time of imaging.

For the PWI sequence, serial gradient echo echo-planar images were acquired, with TR/TE of 1500/40ms. Slice thickness and spacing were as specified above; 14–16 slices were acquired for each patient. Images were acquired at each of 46 or 80 time points. After a ten-second pre-injection delay during which baseline images were obtained, 20cc gadopentetate dimeglumine 0.5mol/L(Magnevist, Bayer HealthCare Pharmaceuticals) were injected at 5cc/s, followed by 20cc normal saline bolus . PWI images were converted to DR2 maps, and for each pixel, the area under each DR2 versus time curve was calculated as a measure of relative cerebral blood volume(CBV). Relative cerebral blood flow(CBF) was calculated using singular value decomposition deconvolution,8 with the arterial input function derived from the middle cerebral artery ipsilateral to the infarct. Mean transit time(MTT) was calculated by dividing CBV by CBF for each pixel.

Fluid Attenuated Inversion Recovery(FLAIR) imaging was performed using the following parameters: TR 10000ms, TE 140ms, FOV 22cm, matrix size 256×192, slice thickness 5mm, interslice gap 1mm.

Acute stroke therapies

Intravenous thrombolysis(IV tPA)

Patients meeting standard IV tPA criteria were given 0.9mg/kg of IV-tPA(10% bolus, 90% continuous infusion during 1 hour, up to a maximum of 90mg)9.

Intra-arterial reperfusion therapy

Inclusion criteria for IAT are: (1)large vessel occlusion(ICA, MCA M1 or M2 branches) on CTA; (2)NCCT without hemorrhage; (3)NCCT with parenchymal hypodensity less than one-third of the MCA territory, or a PWI-DWI mismatch greater than 20% with a DWI abnormality less than one-third of the MCA territory; (4)and ability to navigate a microcatheter to the level of the thrombus. Exclusion criteria are comparable to IV tPA criteria10.

Cerebral angiography is performed under general anesthesia to document the occlusion level. Mechanical means of clot retrieval/dissolution include the MERCI Retrieval System11, microwire maceration, balloon angioplasty and stent placement. For chemical thrombolysis, urokinase(Abbott Laboratories) is mixed to a dose of 5000U/cc, and is administered through the microcatheter into the clot. Typical doses are 250,000–750,000U. Of the above-mentioned stroke treatment tools, only the MERCI retrieval device is an FDA-approved treatment. The remainder of the mechanical tools and the use of urokinase represent off-label uses in the treatment of stroke.

Reperfusion was graded with the Mori scale: grade 0—complete occlusion; 1—distal movement of thrombus without reperfusion; 2—partial recanalization with reperfusion in <50% of the ischemic area; 3—partial recanalization with >50% reperfusion; 4—complete recanalization/reperfusion12, 13. This scale has been validated in the setting of large vessel occlusions treated with IAT, and has been shown to be more refined in its prognostic utility than the modified TIMI (Thrombolysis in Myocardial Infarction) scale, especially when reperfusion is partial13. The TICI (Thrombolysis in Cerebral Infarction) scale has been recently modified and is now equivalent to the Mori scale, with both scales dividing partial reperfusion into less than and more than 50% of the occluded territory.14 We defined recanalization as a Mori score≥2, as it has been shown that even partial reperfusion improves clinical outcome for patients undergoing IAT13, 15.

Imaging Analysis

Volume measurements of the lesion on admission DWI and MTT maps and follow-up MRI or noncontrast CT images were performed with a semi-automated commercially available image analysis program(Analyze, Biomedical Imaging Resource at the Mayo Foundation). A research assistant (L.V.) first outlined the regions of abnormality. Subsequently, the contours were edited by an experienced neuroradiologist (A.Y.) blinded to treatment and clinical outcome, and volume calculations were performed.

Clinical and Imaging Scoring

The National Institutes of Health Stroke Scale(NIHSS) score was used to assess the neurologic status of acute stroke patients on presentation to the emergency department. A modified Rankin scale(mRS) score at three months after the stroke was the primary clinical endpoint, and was obtained via retrospective review of the three-month clinic visit with the stroke neurologist, or via phone interview by a non-blinded interventional neuroradiologist. A mRS≤2 was considered a good outcome. The rate of parenchymal hematoma type 2(PH2, hemorrhage in >30% of the infarction with substantial mass effect) was assessed as a safety endpoint on follow-up CT or MR imaging. PH2 has been used as an imaging surrogate for symptomatic hemorrhage16. Among the 34 patients, an ECASS score could not be obtained for three. The mean time from ictus to follow-up imaging used for ECASS scoring was 2.4±2.1 days.

Statistical Analysis

Patients with an initial DWI lesion volume >70cm3 were termed the “Futile group,” comprising those patients who were likely to have a poor outcome regardless of successful recanalization. Patients with initial DWI volumes <70cm3 were divided by recanalization status, and then by time to recanalization where the mean time between pre-treatment MR imaging and vessel opening was used as a cutoff to separate the recanalizers into early and late groups. This yielded three additional groups: “Early recanalizers,” “Late recanalizers,” and “Non-recanalizers.” The four groups were compared for several variables. Categorical variables were analyzed using the two-tailed Fischer’s Exact test(VassarStats:, and continuous variables were analyzed using one-way ANOVA analysis(Statistics to Use, Kirkman T.W., Normality was tested with the Kolmogorov-Smirnov test(MedCalc Software, version Statistical significance was considered at p<0.05.


Thirty-four patients met our study criteria. Table 1 outlines the characteristics of the study group. Seventeen(50%) were male, and 21(62%) involved the left hemisphere. The mean patient age was 68.8±17.1 years. The median NIHSS score was 18(IQR 14–21). Occlusions were in the following vessels: 16 ICA, 15 M1 segment, and 3 M2 segment. All of the ICA occlusions extended into the MCA, of which 11 also extended into the proximal ACA. Nine(26%) patients had a good outcome at 3 months, two of whom had ICA occlusions. Nine patients died, five of whom had ICA occlusions. Full-dose IV tPA was administered in 12(35%) patients, two of whom had a good outcome.

Table 1
Baseline clinical and demographic variables, imaging characteristics, and outcomes

The average time from stroke onset to MR imaging was 4.1±2.3hours. The median admission DWI lesion volume was 21.4cm3(IQR,11.9–41.2), and the mean admission MTT lesion volume was 212.5±81.9cm3. A total of 26/34 patients(76%) demonstrated partial to complete recanalization(Mori grade 2–4) after IAT. For these patients, the average time from stroke onset to recanalization was 7.4±3.1hours, and from imaging to recanalization was 3.4±1.4hours. Time from stroke onset to follow-up imaging averaged 54.2±50.2hours, and CT was the follow-up imaging modality in 18(53%) patients. The median follow-up infarct size was 60.8cm3(IQR, 31.6–180.9). Mean infarct growth(final lesion minus initial lesion volume) was 63.0±71.5cm3.

When the 34 patients were dichotomized by 3-month outcome(Table 2), patients with good outcome(mRS≤2) had significantly lower NIHSS scores(15 [IQR 9–17] vs 19 [IQR 16–21], p<0.02), smaller follow-up lesion volumes(39.9±35.2cm3 vs 127.6±103.0cm3, p<0.02), and less infarct growth(16.4±19.7cm3 vs 79.8±76.1cm3, p<0.02). They were also more likely to have more M1 and M2 occlusions than ICA occlusions (p<0.01), and more likely to have diabetes mellitus(DM) type II (44% vs 8%, p<0.03). There was a trend for higher recanalization rates in patients with good outcome(100% vs 68%, p<0.08). There were no statistical differences in the remainder of the variables compared. Multiple logistic regression could not be performed due to the small number of patients in the study.

Table 2
Comparison of good (mRS ≤2) versus poor outcome in the entire study population (34 patients)

Only one patient had a PH2 hemorrhage. This was a 74yo female with a right terminal ICA occlusion extending into the MCA. Her admission NIHSS was 16. Her initial DWI lesion volume was 12.2cm3. She underwent mechanical embolectomy using the MERCI device with Mori 2 reperfusion at 5hrs,26min after imaging. She did not receive IV or IA thrombolytic. Her final infarct volume was 17.0cm3. This patient had a good outcome with 3-month mRS of zero.

Stratification based on initial DWI lesion volume and time to recanalization

Six patients had admission DWI volumes >70cm3, termed the “Futile group.” The mean admission DWI and MTT lesion volumes in this group were 140.7±54.7cm3 and 293.5±51.3cm3, respectively. 3/6 patients underwent successful recanalization(Mori grades 2–4), but all six had a poor outcome, including three deaths.

There were 28 patients with initial DWI lesion volumes <70cm3. Mean admission DWI and MTT lesion volumes were 20.0±12.8cm3 and 197.1±78.5cm3, respectively. Twenty-three of the 28 patients(82%) had partial or complete recanalization(Mori≥2). Nine of the 23 recanalizers had a good outcome. All five patients without recanalization had a poor outcome. Six patients died. The mean time from imaging to vessel opening was 3.3 hours. There were eleven “Early recanalizers”(< 3.3 hrs), twelve “Late recanalizers”(>3.3 hrs) and five “Non-recanalizers.”

Table 3 compares the baseline variables between the four groups. There was a significant difference in the distribution of the levels of occlusion(p<0.001). All patients in the Futile group had ICA occlusions. More ICA occlusions were also seen in the Late versus Early recanalizers(p<0.008). The remainder of the baseline variables were not statistically different among the four groups.

Table 3
Comparison of the baseline clinical and demographic variables between the four study groups

There was a significant difference in three-month outcome among the four groups. Seven out of eleven(64%) Early recanalizers, 2/12(17%) Late recanalizers, 0/5 Non-recanalizers and 0/6 Futile group patients achieved a good outcome(p<0.008, Figure 1). Pairwise comparisons demonstrated that the Early recanalizers had significantly better outcomes than the other groups. Furthermore, there was a difference in mortality among the four groups: 0/11 Early recanalizers, 4/12(33%) Late recanalizers, 2/5(40%) Non-recanalizers and 3/6(50%) Futile group patients died(p<0.04). The one PH2 hemorrhage was seen in the Late recanalizer group, and as previously mentioned this patient had a good outcome.

Figure 1
Clinical Outcome by Imaging selection and Time to Recanalization

Interestingly, the Futile group had the largest initial MTT lesion volumes(p<0.044, Figure 2). There was no statistical difference in mean admission DWI(p<0.88) and MTT(p<0.53) lesion volumes between Early, Late and Non-recanalizers.

Figure 2
Comparison of Mean Admission DWI and MTT Lesion Volumes in the Four Study Groups

There was a significant difference in infarct growth between the four groups(p<0.03, Figure 3). The greatest infarct growth was seen in the Futile group, which had a mean infarct growth of 114±30cm3. Infarct growth for Early-, Late-, and Non-recanalizers were 18±16cm3, 67±76cm3, and 93±90cm3, respectively. The difference in infarct growth between Early and Late recanalizers was statistically significant(p<0.05).

Figure 3
Infarct Growth in the Four Study Groups

The 23 recanalized patients with initial DWI lesion volumes <70cm3 were similarly divided into Early and Late recanalizers by mean time from stroke symptom onset to vessel opening(7.5±3.1 hours). There was no statistically significant difference in clinical outcome among the four groups when divided by this method(p<0.13). In fact, there was no time point cutoff from symptom onset to vessel opening that was associated with a significantly better outcome for Early recanalizers.


Patients with large vessel occlusion of the anterior circulation represent a relatively homogeneous population which accounts for the majority of the morbidity and mortality related to stroke17. Intra-arterial therapy appears to be more favorable than IV tPA for these proximal occlusions. A major advantage in studying patients undergoing IAT is that the degree and timing of recanalization are known. This data is largely lacking in stroke patients treated with IV tPA, where time to treatment is used as a surrogate variable.

This study demonstrates that in acute anterior circulation stroke patients undergoing IAT, those with initial infarct volumes less than 70cm3 who undergo early recanalization have the best clinical outcomes and the least infarct growth. These findings are consistent with the data from a number of prior IV tPA studies. In the DEFUSE trial, the best clinical outcomes were seen in those patients who had a PWI-DWI mismatch >20%, an initial DWI lesion volume <100cm3 and early reperfusion18, defined as at least 30% reduction in the PWI lesion volume at three to six hours after IV tPA administration. In the EPITHET trial, patients with a perfusion-diffusion mismatch >20% who underwent reperfusion, defined as greater than 90% reduction in the PWI lesion volume on the day three to five MRI scan, had significant infarct growth attenuation and better clinical outcomes19. In a third study of 113 patients, those who had a PWI-DWI mismatch of >20% and a shorter time to recanalization, as measured by transcranial doppler ultrasound for 2 hours after IV tPA administration, had a better three-month clinical outcome20. Our study extends these findings to proximal intracranial vessel occlusions treated with IAT.

By selecting patients on the basis of an acute DWI lesion volume threshold and early recanalization, we were able to identify a population of large vessel occlusion patients with a 64% rate of good clinical outcome. This rate is similar to the 67% rate of favorable clinical outcome in the Target Mismatch group with early reperfusion in the DEFUSE study18. It also compares favorably with published studies of IAT-treated patients. Recanalizers in the MERCI21 and Multi MERCI22 trials achieved good functional outcomes 46% and 49% of the time, respectively. Although the MERCI and Multi MERCI trials included patients with intracranial vertebral and basilar artery occlusions, there was no significant difference in outcomes between anterior and posterior circulation strokes in these studies.

This study supports the hypothesis that there is an acute DWI lesion volume threshold above which patients do poorly despite treatment. Our Futile group is similar to the “Malignant profile” group in the DEFUSE trial, which was defined as those patients having initial DWI lesion volumes >100cm3 and/or a PWI lesion volume >100cm3 with at least 8 seconds of Tmax delay18. Of six patients with a Malignant profile, only one had a favorable outcome despite early reperfusion in three. Unlike the Malignant profile group in which three patients had symptomatic intracranial hemorrhage, none of our Futile group patients had PH2 hemorrhage. Furthermore, the DWI threshold may be lower than the often used “one-third of the MCA territory,” or approximately 100cm3 23. Three recent studies have identified a volume of greater than 70cm3 as highly predictive of a poor clinical outcome57. Among our six patients with DWI lesion volume >70cm3(Futile group), all had a poor clinical outcome, despite a 50% recanalization rate. These patients also had the highest mortality rate(50%). In addition, the Futile group had a significantly larger mean MTT lesion volume compared to those subgroups with initial DWI volumes <70cm3. These findings suggest that the Futile group patients have the worst pial collateral flow, another factor that has been associated with functional outcome24.

A DWI lesion volume threshold does not imply that the initial infarct volume alone determines clinical outcome for all patients. In fact, the initial DWI lesion volume was not a predictor of outcome in univariate analysis(Table 2). This is because patients below the cutoff value of 70cm3 had both good and poor outcomes, depending on recanalization and time to recanalization. The majority of the Early recanalizers(64%) and a minority of the Late recanalizers(17%) had a good outcome, while none of the Non-recanalizers had a good outcome(p<0.016). This finding suggests that in selected patients (those below the threshold) recanalization may be necessary but not sufficient for a good outcome, and that earlier recanalization leads to better clinical outcomes.

While reperfusion status and time to reperfusion appear to be the major determinants of clinical outcome in patients with relatively small initial DWI lesions (<70cm3), 36% (4/11) of the Early recanalizers still had a poor outcome. This is likely related in part to the eloquence of the brain tissue that could not be salvaged in these patients. Of the four Early recanalizers that had a poor outcome, three had infarcts involving the basal ganglia and/or the motor strip resulting in dense hemiplegia. The fourth patient had an infarct involving the left inferior frontal gyrus and anterior operculum (Broca’s area) resulting in an expressive aphasia. In addition, co-morbidities probably play an important role, as one patient had long-standing Parkinson disease, and another had severe coronary artery disease complicated by cardiac arrest during the stroke admission.

An immediately available quantitative DWI lesion volume threshold would provide a more precise and discriminatory means over current criteria to select IAT-eligible patients who would likely benefit from reperfusion therapy. Thus far, excluding patients based on initial infarct size has been imprecise at best. The “greater than one-third of the MCA territory” rule used in studies of intravenous and intra-arterial therapies is determined by visual inspection of the lesion on a baseline noncontrast CT or DWI scan. The other commonly used MRI selection criterion is a PWI-DWI mismatch >20%. This does not have adequate discriminatory power in the setting of large vessel occlusion because most patients with terminal ICA and M1 segment occlusions have a >20% mismatch. In one study of patients with acute M1 occlusion, Jovin et al employed xenon-enhanced CT to demonstrate that the amount of noninfarcted, hypoperfused tissue(the mismatch) is relatively constant4.

Interestingly, there was no time point cutoff from symptom onset to vessel opening that was associated with a significantly better outcome for early versus late recanalizers. This suggests the possibility that time from imaging, rather than time from stroke symptom onset, may be more clinically meaningful for patients who are selected for IAT based on a favorable PWI-DWI profile. This finding is supported by the DEFUSE study where early reperfusion(based on MR imaging performed 3–6 hours after IV tPA administration, which occurred immediately after the initial MRI scan) essentially represented time from initial imaging rather than stroke onset18. Since the ischemic penumbra may persist in the majority of patients with proximal occlusions for up to 24 hours25, this finding may allow us to extend the time window for intra-arterial therapy. Imaging selection criteria may also have important implications for patients with wake-up strokes, whose times of symptom onset are unknown.

It is important to stress that the additional time required for DWI and PWI imaging never delayed treatment for our stroke patients. Because we have a MR scanner in the emergency department, our MRI evaluation for hyperacute stroke occurs within 10 minutes, which is within proposed guidelines10. We believe that institutions should not pursue MRI studies for hyperacute stroke if it will result in a delay in intra-arterial therapy. In the future, it may be possible to obtain information which is similar to that provided by DWI using processed CT perfusion maps.

In our study, follow-up imaging parameters mirrored the differences in clinical outcome between the four subgroups. There was significantly less infarct growth in patients who recanalized earlier versus later(p<0.03). This corroborates findings of the study by Delgado-Mederos et al, in which patients who took longer to recanalize had more DWI lesion growth at 36 to 48 hours20. The variation in the amount of infarct growth within each subgroup, especially the Non-recanalizers, is likely related in part to inter-individual differences in the strength of the collateral circulation. In addition, differences in the level of occlusion also may contribute to this variation. Both infarct growth(p<0.02) and final lesion volume(p<0.02) were associated with clinical outcome in univariate analysis in our study.

Among the baseline variables studied, the only significant difference between the four groups was the level of occlusion(p<0.001). All patients in the Futile group had ICA occlusions. This is consistent with one study which demonstrated that carotid-T occlusions present with larger initial infarct volumes than MCA occlusions26. Also, more ICA occlusions were seen in the Late recanalizers(8/12 patients) versus the Early recanalizers(1/11 patients). This is also in agreement with well-documented evidence that terminal ICA occlusions are more difficult to recanalize than MCA occlusions2628. It is probably for these reasons that terminal ICA occlusions historically have the poorest outcomes among anterior circulation strokes27, 28.

It is important to note that our study population had an unfavorable vessel occlusion profile, with the majority of patients having ICA occlusions(47%) and a small minority with M2 occlusions(9%). This likely contributes to our low rate of good clinical outcome (26%) despite good reperfusion rate (76%). In fact, the level of occlusion was significantly associated with clinical outcome (p<0.01). Patients with poor outcomes had more proximal occlusions.

An interesting and unexpected finding in this study was the significant association between the presence of diabetes mellitus type II and a good outcome. The literature is conflicting regarding the effect of diabetes on stroke outcome, with some studies demonstrating worse outcomes in diabetic patients and other studies that refute this.29 A direct influence of hyperglycemia at the time of ischemia is likely to be important. There are many studies that demonstrate that acute stroke patients with admission or pre-treatment hyperglycemia have worse outcomes, particularly in nonlacunar strokes where hyperglycemia may lead to lactic acid buildup and cell death in the ischemic penumbra.30, 31 However, in the absence of hyperglycemia, diabetes may actually limit infarct growth. In one study, diabetic rats undergoing 3 hours of MCA occlusion had less infarct expansion (and more hemorrhagic conversion) than similarly treated control rats.32 The authors hypothesized that this may be secondary to cerebrovascular remodeling as the diabetic rats also demonstrated an increased vascular tortuosity index. In our patients, it is potentially this second factor of limiting infarct growth that may explain the better outcomes in diabetic patients. There was no difference in admission glucose levels between patients who did well and those who did poorly. There was no increase in hemorrhagic conversion in the diabetic patients, as the one patient with PH2 hemorrhage in this study did not have diabetes.

The limitations of this study are primarily related to its retrospective design, as well as to the lack of control patients. In addition, the relatively small number of patients, especially those with larger initial DWI volumes, limited our ability to better characterize a DWI lesion volume threshold for patients undergoing IAT. This latter limitation is largely related to the small number of stroke patients who satisfy clinical criteria to undergo IAT. Furthermore, our patient population was heterogeneous with regards to the method of intra-arterial recanalization. While this limits evaluation of specific recanalization techniques, it reflects clinical practice where multiple techniques are routinely employed in order to achieve reperfusion.


This study provides further evidence for using an acute infarct volume threshold to identify patients who likely will not benefit from reperfusion therapy. This is particularly important for patients with proximal vessel occlusion, most of whom satisfy current imaging criteria of a PWI-DWI mismatch of >20%. Furthermore, this study reinforces the importance of early recanalization in achieving the best outcomes in selected patients. These findings need to be verified in larger studies addressing the role of advanced imaging in selecting patients for intra-arterial stroke therapies. Further investigation should also address whether we can prospectively identify which patients will recanalize early.

Acknowledgments and Funding

Albert J. Yoo, MD, was the 2007 recipient of the Neuroradiology Education and Research Foundation/Boston Scientific Fellowship in Cerebrovascular Disease Research. Luis A. Verduzco was a 2007 recipient of the Howard Hughes Medical Institute Research Training Fellowships for Medical Students. This study was supported in part by the National Institutes of Health through a grant from the National Institute of Neurological Disorders and Stroke NS050041 (to RGG).


Conflicts of Interest:

Albert J. Yoo, MD: None

Luis A. Verduzco: None

Pamela W. Schaefer: None

Joshua A. Hirsch, MD: Merci Registry Steering Committee (no financial compensation)

James D. Rabinov: None

R. Gilberto González: Bayer, GE


1. Schellinger PD, Thomalla G, Fiehler J, Kohrmann M, Molina CA, Neumann-Haefelin T, Ribo M, Singer OC, Zaro-Weber O, Sobesky J. Mri-based and ct-based thrombolytic therapy in acute stroke within and beyond established time windows: An analysis of 1210 patients. Stroke. 2007;38:2640–2645. [PubMed]
2. Thomalla G, Schwark C, Sobesky J, Bluhmki E, Fiebach JB, Fiehler J, Zaro Weber O, Kucinski T, Juettler E, Ringleb PA, Zeumer H, Weiller C, Hacke W, Schellinger PD, Rother J. Outcome and symptomatic bleeding complications of intravenous thrombolysis within 6 hours in mri-selected stroke patients: Comparison of a german multicenter study with the pooled data of atlantis, ecass, and ninds tpa trials. Stroke. 2006;37:852–858. [PubMed]
3. Ribo M, Molina CA, Rovira A, Quintana M, Delgado P, Montaner J, Grive E, Arenillas JF, Alvarez-Sabin J. Safety and efficacy of intravenous tissue plasminogen activator stroke treatment in the 3- to 6-hour window using multimodal transcranial doppler/mri selection protocol. Stroke. 2005;36:602–606. [PubMed]
4. Jovin TG, Yonas H, Gebel JM, Kanal E, Chang YF, Grahovac SZ, Goldstein S, Wechsler LR. The cortical ischemic core and not the consistently present penumbra is a determinant of clinical outcome in acute middle cerebral artery occlusion. Stroke. 2003;34:2426–2433. [PubMed]
5. Barak ERJ, Kamalian S, Rezai Gharai L, Gonzalez RG, Schaefer P. Does hyperacute diffusion and perfusion weighted imaging predict outcome in acute ischemic stroke. International Stroke Conference. 2008;39:607.
6. Sanak D, Nosal V, Horak D, Bartkova A, Zelenak K, Herzig R, Bucil J, Skoloudik D, Burval S, Cisarikova V, Vlachova I, Kocher M, Zapletalova J, Kurca E, Kanovsky P. Impact of diffusion-weighted mri-measured initial cerebral infarction volume on clinical outcome in acute stroke patients with middle cerebral artery occlusion treated by thrombolysis. Neuroradiology. 2006;48:632–639. [PubMed]
7. Arsava EMAH, Singhal AB, Wu Ona, Furie KL, Sorenso AG. An infarct volume threshold on early dwi to predict unfavorable clinical outcome. International Stroke Conference. 2008;39:619.
8. Østergaard L, Weisskoff RM, Chesler DA, Gyldensted C, Rosen BR. High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part i: Mathematical approach and statistical analysis. Magn Reson Med. 1996;36:715–725. [PubMed]
9. Adams HP, Jr, Brott TG, Furlan AJ, Gomez CR, Grotta J, Helgason CM, Kwiatkowski T, Lyden PD, Marler JR, Torner J, Feinberg W, Mayberg M, Thies W. Guidelines for thrombolytic therapy for acute stroke: A supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the stroke council, american heart association. Circulation. 1996;94:1167–1174. [PubMed]
10. Higashida RT, Furlan AJ, Roberts H, Tomsick T, Connors B, Barr J, Dillon W, Warach S, Broderick J, Tilley B, Sacks D. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke. 2003;34:e109–e137. [PubMed]
11. Gobin YP, Starkman S, Duckwiler GR, Grobelny T, Kidwell CS, Jahan R, Pile-Spellman J, Segal A, Vinuela F, Saver JL. Merci 1: A phase 1 study of mechanical embolus removal in cerebral ischemia. Stroke. 2004;35:2848–2854. [PubMed]
12. Mori E, Tabuchi M, Yoshida T, Yamadori A. Intracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke. 1988;19:802–812. [PubMed]
13. Arnold M, Nedeltchev K, Remonda L, Fischer U, Brekenfeld C, Keserue B, Schroth G, Mattle HP. Recanalisation of middle cerebral artery occlusion after intra-arterial thrombolysis: Different recanalisation grading systems and clinical functional outcome. J Neurol Neurosurg Psychiatry. 2005;76:1373–1376. [PMC free article] [PubMed]
14. Tomsick T, Broderick J, Carrozella J, Khatri P, Hill M, Palesch Y, Khoury J. Revascularization results in the interventional management of stroke ii trial. AJNR Am J Neuroradiol. 2008;29:582–587. [PMC free article] [PubMed]
15. Zaidat OO, Suarez JI, Sunshine JL, Tarr RW, Alexander MJ, Smith TP, Enterline DS, Selman WR, Landis DM. Thrombolytic therapy of acute ischemic stroke: Correlation of angiographic recanalization with clinical outcome. AJNR Am J Neuroradiol. 2005;26:880–884. [PubMed]
16. Berger C, Fiorelli M, Steiner T, Schabitz WR, Bozzao L, Bluhmki E, Hacke W, von Kummer R. Hemorrhagic transformation of ischemic brain tissue: Asymptomatic or symptomatic? Stroke. 2001;32:1330–1335. [PubMed]
17. Torres-Mozqueda F, He J, Yeh IB, Schwamm LH, Lev MH, Schaefer PW, Gonzalez RG. An acute ischemic stroke classification instrument that includes ct or mr angiography: The boston acute stroke imaging scale. AJNR Am J Neuroradiol. 2008;29:1111–1117. [PubMed]
18. Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E, Bammer R, Kakuda W, Lansberg MG, Shuaib A, Coplin W, Hamilton S, Moseley M, Marks MP. Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (defuse) study. Ann Neurol. 2006;60:508–517. [PubMed]
19. Davis SM, Donnan GA, Parsons MW, Levi C, Butcher KS, Peeters A, Barber PA, Bladin C, De Silva DA, Byrnes G, Chalk JB, Fink JN, Kimber TE, Schultz D, Hand PJ, Frayne J, Hankey G, Muir K, Gerraty R, Tress BM, Desmond PM. Effects of alteplase beyond 3 h after stroke in the echoplanar imaging thrombolytic evaluation trial (epithet): A placebo-controlled randomised trial. Lancet Neurol. 2008;7:299–309. [PubMed]
20. Delgado-Mederos R, Rovira A, Alvarez-Sabin J, Ribo M, Munuera J, Rubiera M, Santamarina E, Maisterra O, Delgado P, Montaner J, Molina CA. Speed of tpa-induced clot lysis predicts dwi lesion evolution in acute stroke. Stroke. 2007;38:955–960. [PubMed]
21. Smith WS, Sung G, Starkman S, Saver JL, Kidwell CS, Gobin YP, Lutsep HL, Nesbit GM, Grobelny T, Rymer MM, Silverman IE, Higashida RT, Budzik RF, Marks MP. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: Results of the merci trial. Stroke. 2005;36:1432–1438. [PubMed]
22. Smith WS, Sung G, Saver J, Budzik R, Duckwiler G, Liebeskind DS, Lutsep HL, Rymer MM, Higashida RT, Starkman S, Gobin YP, Frei D, Grobelny T, Hellinger F, Huddle D, Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE. Mechanical thrombectomy for acute ischemic stroke: Final results of the multi merci trial. Stroke. 2008;39:1205–1212. [PubMed]
23. van der Zwan A, Hillen B, Tulleken CA, Dujovny M. A quantitative investigation of the variability of the major cerebral arterial territories. Stroke. 1993;24:1951–1959. [PubMed]
24. Christoforidis GA, Mohammad Y, Kehagias D, Avutu B, Slivka AP. Angiographic assessment of pial collaterals as a prognostic indicator following intra-arterial thrombolysis for acute ischemic stroke. AJNR Am J Neuroradiol. 2005;26:1789–1797. [PubMed]
25. Copen WA, Rezai Gharai L, Barak ER, Schwamm LH, Wu O, Kamalian S, Gonzalez RG, Schaefer PW. Existence of the diffusion-perfusion mismatch within 24 hours after onset of acute stroke: Dependence on proximal arterial occlusion. Radiology. 2009 [PubMed]
26. Fiehler J, Knudsen K, Thomalla G, Goebell E, Rosenkranz M, Weiller C, Rother J, Zeumer H, Kucinski T. Vascular occlusion sites determine differences in lesion growth from early apparent diffusion coefficient lesion to final infarct. AJNR Am J Neuroradiol. 2005;26:1056–1061. [PubMed]
27. Eckert B, Kucinski T, Neumaier-Probst E, Fiehler J, Rother J, Zeumer H. Local intra-arterial fibrinolysis in acute hemispheric stroke: Effect of occlusion type and fibrinolytic agent on recanalization success and neurological outcome. Cerebrovasc Dis. 2003;15:258–263. [PubMed]
28. Arnold M, Nedeltchev K, Mattle HP, Loher TJ, Stepper F, Schroth G, Brekenfeld C, Sturzenegger M, Remonda L. Intra-arterial thrombolysis in 24 consecutive patients with internal carotid artery t occlusions. J Neurol Neurosurg Psychiatry. 2003;74:739–742. [PMC free article] [PubMed]
29. Kagansky N, Levy S, Knobler H. The role of hyperglycemia in acute stroke. Arch Neurol. 2001;58:1209–1212. [PubMed]
30. Ginsberg MD. Hyperglycemia and stroke outcome: Vindication of the ischemic penumbra. Ann Neurol. 2002;52:5–6. [PubMed]
31. Parsons MW, Barber PA, Desmond PM, Baird TA, Darby DG, Byrnes G, Tress BM, Davis SM. Acute hyperglycemia adversely affects stroke outcome: A magnetic resonance imaging and spectroscopy study. Ann Neurol. 2002;52:20–28. [PubMed]
32. Ergul A, Elgebaly MM, Middlemore ML, Li W, Elewa H, Switzer JA, Hall C, Kozak A, Fagan SC. Increased hemorrhagic transformation and altered infarct size and localization after experimental stroke in a rat model type 2 diabetes. BMC Neurol. 2007;7:33. [PMC free article] [PubMed]