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Neuroradiology |
1 From the Depts of Clinical Radiology (Y.L., J.O.K., R.L.V., A.K., S.S., H.J.A.) and Neurology (J.N.), Kuopio Univ Hosp, PO Box 1777, FIN-70211 Kuopio, Finland; Dept of Radiology, Mikkeli Central Hosp, Finland (J.O.K.); and Functional Brain Imaging Unit, Helsinki Brain Research Ctr, Finland (H.J.A.). From the 2002 RSNA scientific assembly. Received Apr 10, 2003; revision requested Jun 27; revision received Aug 7; accepted Oct 1. Supported by Kuopio University Hospital (EVO funding 307/97, 21/98, and 5063504), Radiological Society of Finland, Academy of Finland, Sigrid Juselius Foundation, Instrumentarium Science Foundation, Aarne Koskelo Foundation, and Paavo Nurmi Foundation. Address correspondence to Y.L. (e-mail: yawu.liu@kuh.fi).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSION REFERENCES |
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MATERIALS AND METHODS: Phase-contrast angiographic and diffusion-weighted images obtained 1 and 2 days after acute middle cerebral artery (MCA) stroke were assessed in 43 patients; 39 underwent perfusion-weighted imaging on day 1. Follow-up phase-contrast angiographic and T2-weighted images (n = 38) were obtained on day 8. Clinical outcome was assessed at 3 months. Patients were assigned to three groups according to angiographic findings on day 1: group 1, absence of flow in proximal MCA (M1 segment); group 2, internal carotid artery (ICA) occlusion with collateral M1 flow; group 3, flow in ICA and M1. Differences in lesion volumes on diffusion- and perfusion-weighted maps among groups were compared with one-way analysis of variance with Tukey post hoc multiple comparisons.
RESULTS: Patients in group 1 had significantly larger infarct growth, volumes of hypoperfusion on relative cerebral blood volume (rCBV) and relative cerebral blood flow maps, and initial and final infarct volumes than did other patients (P < .05). Initial perfusion deficits on mean transit time maps were significantly (P = .002) larger in group 2 than in group 3, but there were no significant differences in infarct growth (P = .977), final infarct volume on day 8 (P = .947), and clinical outcome (P = .969). Absence of M1 flow on day 1 was significantly associated with unfavorable clinical outcome (modified Rankin score 
3) at 3 months (P = .010, 
2 test). Discriminant analysis revealed that rCBV maps alone and combination of diffusion-weighted imaging and MR angiography yielded the highest accuracy in predicting an unfavorable clinical outcome.
CONCLUSION: Phase-contrast MR angiography can provide complementary information to that with diffusion- and perfusion- weighted imaging in predicting the outcome of patients with acute stroke.
© RSNA, 2004
Index terms: Blood vessels, MR, 17.12142, 17.12144 • Brain, infarction, 13.78 • Brain, MR, 13.121411, 13.121416, 13.12142, 13.12143, 13.12144 • Magnetic resonance (MR), diffusion study, 13.12144 • Magnetic resonance (MR), perfusion study, 13.12144 • Magnetic resonance (MR), phase imaging, 13.12149
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSION REFERENCES |
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Combined diffusion- and perfusion-weighted magnetic resonance (MR) imaging has shown great promise in the diagnosis of acute stroke (1–7). Diffusion-weighted imaging can depict ischemic tissue in rats after a middle cerebral artery (MCA) occlusion, with decreased diffusion within 5 minutes (8). Perfusion-weighted imaging permits the detection of hemodynamic changes (9). In many patients with acute ischemic stroke, the volume of hypoperfused tissue on perfusion-weighted maps is larger than the volume of tissue with decreased diffusion on diffusion-weighted images (1–7,10). This mismatch between the volumes of abnormal tissue on perfusion- and diffusion-weighted images (perfusion-diffusion mismatch) in the same imaging session can be considered as an estimate of the ischemic penumbra and thus may be a predictor of potential infarct growth (1,2,6,7).
Perfusion-weighted imaging offers information about perfusion at the microvascular level, but MR angiography can be used to obtain information about vascular anatomy and the dynamics of blood flow (11). By using the phase-contrast technique, the MR angiographic image can be acquired in less than 1 minute (12). There are only a few studies (4,13) that have focused on MR angiography as an adjunct to diffusion- and perfusion-weighted imaging in acute ischemic stroke. In those studies, the absence of flow in the proximal MCA (M1 segment) on MR angiograms helped predict greater infarct expansion (4,13) and unfavorable clinical outcome (13), but the relatively small study populations did not allow the authors to draw more definitive conclusions about the predictive value of MR angiography in acute ischemic stroke. Thus, the purpose of our study was to study the value of phase-contrast MR angiography and diffusion- and perfusion-weighted imaging in helping to predict the evolution of infarction and clinical outcome.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSION REFERENCES |
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Patient Treatment and Assessment
Patients were treated with aspirin and/or dipyridamole or anticoagulation therapy, and all received standard supportive therapy for ischemic stroke. Intraarterial or intravenous trombolysis was not registered for use in stroke in Finland at the time of patient enrollment. None of the patients received thrombolytic or experimental neuroprotective agents. Patients underwent initial MR imaging within 24 hours (mean, 11 hours ± 6 [SD]; 3–6 hours, eight patients; >6 hours, 35 patients) and 2 and 8 days after stroke onset. Before each MR examination, the neurologic status of the patients was assessed by a trained neurologist using the National Institutes of Health Stroke Scale (NIHSS). The initial NIHSS assessment was conducted by one of three trained neurologists (J.N. with 21 years experience in neurology and two other neurologists, each with more than 3 years experience in neurology). Follow-up NIHSS assessments were performed by one experienced neurologist (J.N.). Three months after stroke occurrence, the patient’s ability to perform daily activities was assessed by the experienced neurologist using the modified Rankin scale (21). Because the neurologist had access to MR imaging findings and/or reports during the treatment period, he was not necessarily blinded to the MR data when he made the assessment. The modified Rankin scale is a seven-point scale that helps assess the patient’s ability to perform daily activities. The absence of symptoms is rated as 0 and death is rated as 6. In general, a modified Rankin score of 3 or greater is considered as an unfavorable outcome.
MR Imaging
All MR studies were performed with a 1.5-T whole-body imager capable of echo-planar imaging (Magnetom Vision; Siemens Medical Systems, Erlangen, Germany) by using a head coil. One of four trained operators (three radiologists and one physicist) performed the MR examinations. Three had more than 5 years of experience in MR imaging, and one radiologist (J.O.K.) with 2 years experience in radiology had received 4 months of training in the diagnostic radiology of ischemic stroke. The patient’s head was fixed with the standard restraints that are used in routine clinical MR imaging. Our MR protocol has been published in detail in our previous studies (6,7,14–18). In brief, each MR examination at the three time points included diffusion- and perfusion-weighted imaging, two-dimensional (2D) phase-contrast MR angiography of the circle of Willis, transverse T2- and intermediate-weighted fast spin-echo imaging, and transverse T1-weighted spin-echo imaging performed before and after contrast material administration. The total imaging time was approximately 20 minutes.
Diffusion-weighted Imaging
Diffusion-weighted imaging was performed by using a single-shot echo- planar sequence (4,000–6,000/103 [repetition time msec/echo time msec]). Nineteen transverse sections tilted along the orbitomeatal line were obtained (5-mm section thickness, 1.5-mm intersection gap, 260-mm field of view, 96 x 128 matrix interpolated to 256 x 256). A T2-weighted image (b = 0 sec/mm2) and three diffusion-weighted images with orthogonally applied diffusion gradients (b = 1,000 sec/mm2) per section were obtained. Diffusion-weighted trace images were calculated on a pixel-by-pixel basis as the average signal intensity of all three diffusion-weighted images. We used diffusion-weighted trace images obtained 1 and 2 days after stroke to calculate the volumes of infarcted tissue because of the following reasons: (a) infarct borders are more clearly detectable on diffusion-weighted trace images than on apparent diffusion coefficient maps, especially in the case of small infarction; (b) there are few published observations of recovery of ischemic brain tissue with decreased diffusion in untreated patients; and (c) severe edema, which may cause overestimation of infarct volume, generally occurs between 2 and 7 days after a stroke (22).
Perfusion-weighted Imaging
Perfusion-weighted imaging was performed by using spin-echo echo-planar sequence (1,500/78, 260-mm field of view, 116 x 256 matrix). Seven 5-mm-thick sections with 1.5-mm gaps were obtained from the positions containing the core of the diffusion lesion. The set of seven sections was imaged 40 times every 1.5 seconds, which resulted in an imaging time of 1 minute. A dose of 0.2 mmol per kilogram of body weight of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany) was injected at a rate of 5 mL/sec into an antecubital vein with an MR-compatible power injector (Spectris; Medrad, Pittsburgh, Pa). Raw perfusion-weighted images were postprocessed to generate maps of relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT) with the nonparametric singular-value deconvolution method introduced by Østergaard et al (23,24). rCBV was determined on a voxel-by-voxel basis by means of a numeric integration of the first-pass concentration-time curve. The shape of the arterial input function was determined from the voxels located at a branch of the MCA showing large signal losses during the bolus passage. The tissue impulse response function was determined by deconvolving the tissue concentration-time curve with the arterial input function. rCBF was subsequently determined as the height of the deconvolved tissue impulse response. MTT was then calculated according to the central volume theorem as the CBV/CBF ratio.
MR Angiography of Circle of Willis
A 2D phase-contrast MR angiographic sequence was used (115/9, 12° flip angle, one signal acquired, 70-mm slab thickness, 240-mm field of view, and 224 x 256 matrix). Velocity encoding was set at 45 cm/sec. The acquisition time was 54 seconds.
The patients were assigned to the following three groups according to MR angiographic findings obtained 1 day after stroke: group 1, absence of flow in the M1 portion of the MCA; group 2, internal carotid artery (ICA) occlusion with collateral M1 flow; and group 3, presence of flow in both ICA and M1 with possible absence of flow distal to M1. Because of the relative low interobserver agreement in the assessment of distal MCA with 2D phase-contrast MR angiography (13), we did not analyze the patency of the distal MCA. If there were changes on any two of three MR angiograms during the week, the patient was considered to have a changing MR angiographic finding. The changes included recanalization of the ICA or M1, establishment of collateral M1 flow, and arterial dilatation. There were no cases of progressive thrombosis. The 2D phase-contrast MR angiograms were evaluated independently by a radiologist (Y.L., 13 years experience in radiology and 8 years experience in MR imaging at the time of interpretation) and a neuroradiologist (R.L.V., 16 years experience in radiology and 11 years experience in MR imaging at the time of interpretation) blinded to the findings of diffusion- and perfusion-weighted imaging. Hemorrhagic transformation was defined as any area of heterogeneous or homogeneous hypointense signal more than 1 cm2 in size within the area of ischemia on a T2- or diffusion-weighted images (25).
Comparison of MR Angiograms and Signal Void on T2-weighted Images
T2-weighted images obtained on the 1st day after stroke were reviewed to compare the loss of signal void with MR angiographic findings. Presence of signal void in M1 on T2-weighted images obtained 1 day after stroke was evaluated independently by two radiologists (at the time of interpretation J.O.K. had 8 years experience in radiology and 6 years experience in MR imaging and A.K. had 4 years experience in radiology and 2 months experience in neuroradiologic MR imaging) blinded to the MR angiographic findings but not to the symptomatic side of the patient. Nineteen transverse T2-weighted images identical to those used for diffusion-weighted imaging were obtained by using turbo spin-echo sequences. The parameters were 3,250/90, one signal acquired, 196 x 256 matrix, and 260-mm field of view.
Volume Measurements
Volumetric measurements were performed with commercial image analysis software (Cheshire; Hayden Image Processing Group, Boulder, Colo). The following volumes were measured: (a) the total volume of tissue with decreased diffusion on diffusion-weighted images obtained on days 1 and 2; (b) the volume of hypoperfused tissue on rCBV, rCBF, and MTT maps obtained on day 1; and (c) the total final infarct volume on T2-weighted images obtained on day 8 after stroke. To evaluate the relationship between perfusion-diffusion mismatch and the infarct growth, the following volumes were also measured: the volume of tissue with decreased diffusion on diffusion-weighted images limited to the seven sections comparable to that on perfusion-weighted images obtained on day 1 and the final infarct volume on T2-weighted images obtained on day 8 from the same section positions in which perfusion-weighted images had been obtained on day 1 after stroke. Infarct growths by 2 and 8 days after stroke were calculated by subtracting lesion volumes on diffusion-weighted images obtained on day 1 from those obtained on day 2 and by subtracting lesion volumes on diffusion-weighted images obtained on day 1 from the infarct volume on T2-weighted images obtained on day 8, respectively.
Three perfusion parameters were calculated, and thus three types of perfusion maps (rCBV, rCBF, and MTT) were generated. Consequently, from every perfusion-weighted imaging data set, we measured three volumes of decreased perfusion (hypoperfusion). By comparing separately each hypoperfusion volume with lesion volume on diffusion-weighted images in the same imaging session in the corresponding seven sections, three perfusion-diffusion mismatch volumes could be calculated: rCBV-diffusion mismatch volume, rCBF-diffusion mismatch volume, and MTT-diffusion mismatch volume. All analyses, including those of data derived from perfusion-weighted imaging (perfusion-weighted imaging hypoperfusion volume or perfusion-diffusion mismatch volumes), were performed threefold, and results are presented separately according to each perfusion parameter.
Volumes were measured by drawing the lesion areas (areas of decreased diffusion or perfusion) on the corresponding images and multiplying the lesion area by the section thickness. The intersection gap was estimated to contain a lesion of the same size as the section above it, and the lesion inside the gap was included in the volume calculation. Volume measurements on perfusion-weighted images (J.O.K., 3 years experience in radiology and 2 years experience in MR imaging at the time of measurement), infarct volume measurements on T2-weighted images (Y.L., 9 years experience in radiology and 4 years experience in MR imaging at the time of measurement), and volume measurements on diffusion-weighted images (J.O.K., Y.L.) were made by radiologists blinded to the clinical and MR angiographic data. The two radiologists independently drew the regions of interest and followed the same rules in including the tissue in the regions of interest.
Statistical Analyses
The 
statistic was used to assess interobserver agreement in the classification of MR angiograms and in judgment of M1 signal void on T2-weighted images. For disagreement, consensus was used for final statistical analysis after the observers had jointly reanalyzed the study findings. All volumes that were measured in each group proved to be normally distributed according to the Kolmogorov-Smirnov test and to be homoscedastic according to the F test. One-way analysis of variance was used to compare patient age and lesion volumes (volume of tissue with decreased diffusion on diffusion-weighted images obtained on days 1 and 2, hypoperfusion volume on perfusion maps obtained on day 1, volumes of rCBV-diffusion, rCBF-diffusion, and MTT-diffusion mismatches on day 1, final infarct volume on T2-weighted images obtained on day 8, and volume of infarct growth during the 1st week after stroke) among the three groups according to MR angiographic findings. Tukey post hoc multiple comparisons were conducted among the groups with overall significant probability value of analysis of variance. The 2 test was used to evaluate the possible differences in sex distribution among the three groups and the association between the absence of M1 flow and unfavorable clinical outcome at 3 months (modified Rankin score 3), as well as the association between the changes on MR angiograms and hemorrhagic transformation by day 8. Discriminant analysis was performed to define the cutoff values for large lesions on diffusion-weighted images and large hypoperfusion lesions on rCBV, rCBF, and MTT maps, which were used to evaluate the ability of MR angiography, diffusion-weighted imaging, and perfusion-weighted imaging in helping predict the clinical outcome. When the diagnostic performance in predicting substantial infarct growth of at least 50% was assessed, large rCBV-diffusion, rCBF-diffusion, and MTT-diffusion mismatches were defined as the volume of hypoperfusion on rCBV, rCBF, and MTT maps being at least 50% larger than the lesion volume on diffusion-weighted images in the corresponding seven sections in the same imaging session. The 
level for statistical significance was set at .05 for all tests.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSION REFERENCES |
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MR Angiographic Findings
In the interpretation of all MR angiograms obtained 1, 2, and 8 days after stroke, interobserver agreement occurred in 119 (98%) of 122 MR angiograms ( = 0.96). In three cases of disagreement (partial flow in M1), the MR angiograms were jointly reanalyzed, and a consensus was used for the final statistical analysis.
In the interpretation of the loss of signal void on T2-weighted images obtained on day 1, interobserver agreement occurred in 37 (90%) of 41 of cases ( = 0.72). Motion artifacts prevented interpretation in two cases. In four cases of disagreement, the T2-weighted images were jointly reanalyzed, and a consensus was reached.
Among the 41 patients who successfully underwent both MR angiography and T2-weighted MR imaging 1 day after stroke, both MR angiograms and T2-weighted images equally depicted the absence (n = 9) or presence (n = 27) of M1 flow in 36 (88%) patients. In four (10%) patients, MR angiograms showed complete absence of M1 flow, but T2-weighted images were interpreted to have a faint M1 signal. In (2%) one patient, M1 flow was depicted on the MR angiogram but there was absence of M1 signal void on T2-weighted images. In this patient, mild motion decreased the quality of T2-weighted images.
Among the 43 patients who successfully underwent MR angiography on day 1, 15 (35%, 10 women with mean age of 74 years [range, 63–89 years] and five men with mean age of 66 years [range, 56–72 years]) had absence of flow in the M1 (ICA occlusion without collateral M1 flow, n = 8; M1 occlusion with patent ICA, n = 7) (group 1). Seven (16%) patients (all men; mean age, 66 years; range, 57–78 years) had ICA occlusion with collateral M1 flow (group 2), and 21 patients (49%) (11 women with mean age of 72 years [range, 48–84 years] and 10 men with mean age of 71 years [range, 59–84 years]) had flow in both the ICA and M1 (group 3). No occlusion was found in the contralateral ICA or M1 in any patient. There was no significant difference in age (P = .260) and in delay (P = .151) from the onset of stroke to the initial MR imaging among the groups. However, sex distribution was significantly different (P = .013) among the three groups. All patients in group 2 were men. Because the sample sizes were modest, we did not evaluate the effect of sex in the present study.
Three patients had changes in their MR angiographic findings between 1 and 2 days after stroke. Two patients belonged to group 1 and had improvement of flow in M1 (establishment of collateral M1 flow while the ICA remained occluded in one patient and recanalization of M1 in one patient). One patient in group 3 showed dilatation of MCA on the ischemic side. Six patients, all in group 1, had changes in their MR angiographic findings between 2 and 8 days after stroke (establishment of collateral M1 flow while the ICA remained occluded in two patients and recanalization of the MCA in four patients). Patients in group 2 showed no changes in the MR angiographic findings during the 1st week.
Comparison of Ischemic Volumes among Groups according to MR Angiographic Findings
Of the 39 patients who successfully underwent perfusion-weighted imaging 1 day after stroke, 27 (69%) had diffusion lesions that were too large to be included in the seven diffusion-weighted sections that were matched with perfusion-weighted sections in the same imaging session. The mean lesion volume on diffusion-weighted images outside the seven sections was 16 cm3 ± 27 (SD). In the rest of the patients, the lesions on diffusion-weighted images were limited to the seven sections matched with perfusion-weighted images. The lesion volume on diffusion-weighted images in the seven sections correlated with the total lesion volume on diffusion-weighted images obtained 1 day after stroke (r = 0.984, P < .001, n = 39). The volumes of different imaging abnormalities are summarized in Table 1.
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.002). The differences were largest in group 1 (P .027); they did not differ significantly between groups 2 and 3 (P .999).
Analysis of variance also revealed that the volumes of tissue with decreased perfusion on perfusion maps obtained 1 day after stroke differed significantly among the three groups (P < .001). On rCBV and rCBF maps, the volumes of hypoperfusion in group 1 were larger than those of other patients (P .003) but were not significantly different between groups 2 and 3 (P .427). On the MTT maps, the volumes of hypoperfusion were not significantly different between groups 1 and 2 (P = .106), but the hypoperfusion volumes in groups 1 and 2 were significantly larger than those in group 3 (P .016) (Tables 1, 2).
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.007) (Tables 1, 2), being significantly larger in group 1 than in group 3 (P .008). The difference was significant for all three types of perfusion-diffusion mismatches. The volume of rCBV-diffusion mismatch was significantly larger in group 1 than in group 2 (P = .045), but the volumes of rCBF-diffusion and MTT-diffusion mismatches were not significantly different between groups 1 and 2 (P .456). The volume of MTT-diffusion mismatch was significantly larger in group 2 than in group 3, but the volumes of rCBV-diffusion and rCBF-diffusion mismatches were not significantly different between groups 2 and 3 (P .287).
The total volumes of the final infarction on T2-weighted images differed significantly among the three groups (P < .001). Patients in group 1 had significantly larger (P .011) final infarct volumes than patients in the other groups. There was no significant difference in the total volume of final infarction between groups 2 and 3 (P = .995).
Between 1 and 2 days after stroke, the total lesion volume on diffusion-weighted images (from the 19 sections) increased by 57 cm3 ± 48, 19 cm3 ± 17, and 17 cm3 ± 20 in groups 1, 2 and 3, respectively. The total volumes of infarct growth during the 1st week were 88 cm3 ± 73, 20 cm3 ± 11, and 17 cm3 ± 28 in groups 1, 2, and 3, respectively. The total volume of infarct growth differed significantly among the three groups (P = .001), again being largest in group 1 (P .016), but there were no significant difference between groups 2 and 3 (P = .992) (Figs 1, 2). The findings held when we studied the initial and final infarct volumes, and the volume of infarct growth on the seven sections matched with those on the perfusion-weighted sections.
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.261) between the patients with both ICA and MCA occlusion and the patients with only MCA occlusion.
Comparison of MR Angiograms and Perfusion- and Diffusion-weighted Images in Predicting Clinical Outcome
The clinical outcome assessed at 3 months differed significantly among the three groups (P = .004). Patients in group 1 had the worst clinical outcome, though their modified Rankin scores did not differ significantly from those in group 2 (P = .056). There were no significant differences in the clinical outcome between groups 2 and 3 (P = .929).
Of the 13 patients whose MR angiogram obtained 1 day after stroke showed absence of flow in M1 and whose 3-month modified Rankin scores were available, 12 (92%) experienced an unfavorable clinical outcome (modified Rankin score 3). Accordingly, of the 24 patients whose MR angiogram obtained 1 day after stroke showed presence of flow in M1 and whose 3-month modified Rankin scores were available, 12 (50%) proved to have an unfavorable clinical outcome. When the patients were dichotomized into two groups according to the presence or absence of M1 flow on MR angiograms obtained on day 1, the absence of M1 flow was significantly associated with an unfavorable clinical outcome (P = .010) and death (P = .024). Four (27%) of the 15 patients without M1 flow on the initial MR angiogram died during the first 3 months after stroke, whereas only one (4%) of 28 patients with M1 flow on the initial MR angiogram died during the first 3 months.
The sensitivity, specificity, and accuracy of imaging findings obtained 1 day after stroke in predicting the evolution of infarction and clinical outcome are summarized in Tables 3 and 4. The sensitivity and accuracy of MTT-diffusion mismatch in predicting substantial infarct growth were higher than those of MR angiography and rCBV-diffusion and rCBF-diffusion mismatches. However, the specificity of rCBV-diffusion mismatch was the highest, and the specificity of MR angiography was the second highest in predicting substantial infarct growth. Combining MR angiographic findings and perfusion-diffusion mismatches did not improve the accuracy in predicting substantial infarct growth. The combination of diffusion-weighted imaging and MR angiography yielded the highest sensitivity in predicting an unfavorable clinical outcome. The rCBV map alone and the combination of diffusion-weighted imaging and MR angiography yielded the highest overall accuracy (76%).
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4 points on the NIHSS score from baseline assessment). Among the 11 patients, an MR angiogram obtained 1 day after stoke showed absence of M1 flow in six patients, ICA occlusion with collateral M1 flow in one patient, and presence of ICA flow and M1 flow in four patients. Among the 15 patients in group 1, no MR angiographic change was observed during the 1st week in seven (40%) patients, and hemorrhagic transformation was observed at follow-up MR imaging in only one (14%) patient. In contrast, in five (63%) of the eight patients in group 1 with a change in MR angiographic finding (collateral M1 flow or recanalization), a hemorrhagic transformation was observed during the 1st week (Figs 3–5). Thus, the MR angiographic change during the 1st week was significantly associated with hemorrhagic transformation (P = .001). Patients in group 1 with a subsequent MR angiographic change had no significant differences in the final infarct volume, enlargement of infarction, and clinical outcome (P = .321), compared with patients in group 1 whose MR angiographic finding did not change. In group 1, the clinical outcome of patients with hemorrhagic transformation was not significantly different from the clinical outcome of patients without hemorrhagic transformation (P = .912).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSION REFERENCES |
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Another interesting finding is that larger lesion volumes on MTT maps and MTT-diffusion mismatch were found in patients in group 2 than in patients in group 3, but the volume of infarct growth was not significantly different between groups 2 and 3. Our results support that MTT causes overestimation of the risk of infarct growth, since it includes many different levels of ischemia and oligemia, even areas that may not process to infarction (2,26).
Findings of randomized trials have shown that intravenous and intraarterial thrombolytic therapies are efficient if performed within 3 (27,28) and 6 hours (29), respectively, of stroke onset. However, the recanalization rate with 0.8 or 1.0 mg/kg of intravenously administered recombinant tissue plasminogen activator is not more than 30% for large-vessel occlusion and that with 6 or 9 mg of intraarterially administered prourokinase is no better than 60% (29,30). It is not clear whether patients with acute stroke benefit from thrombolytic therapy as a result of direct recanalization of the occluded segment or lysis of thrombi within the microvasculature with some degree of collateral circulation (31,32). In the present study, a well-established collateral circulation to the M1 seemed to prevent the ischemic tissue from proceeding to infarction. Whether the intravenous thrombolytic agents work equally well in situations of insufficient and patent collateral circulation needs to be studied further.
Evaluation of Infarcted Tissue on Diffusion-weighted Images
Between 1 and 2 days after stroke, the infarction grew by 57, 19, and 17 cm3 in groups 1, 2, and 3, respectively. This finding supports the view that there can be salvageable tissue left in the area of ischemic tissue after the first 3–6 hours (33). Between 2 and 8 days, none or only minor infarct growth could be detected in groups 2 and 3. However, a more pronounced infarct growth was identified in group 1. The more extensive rCBV-diffusion mismatch in group 1 than in the other groups might account for this difference. Moreover, the secondary ischemia as a consequence of mechanical compression and microvascular congestion in large infarction might also contribute to the pronounced infarct growth in group 1 (34).
MR Angiography in Predicting Stroke Outcome
During the acute stage of ischemic stroke, MR angiography alone demonstrated the second highest specificity (80%) after rCBV-diffusion mismatch (90%) in predicting substantial infarct growth. Combined with total lesion volume at diffusion-weighted imaging, it provided the highest sensitivity (71%) in predicting unfavorable clinical outcome assessed at 3 months. In the present study, 43 patients successfully underwent MR angiography in the acute phase of ischemic stroke. However, perfusion-weighted imaging was not successfully performed in four (9%) of 43 patients. Short imaging time of less than 1 minute combined with the power to help predict ischemic stroke favors the use of 2D phase-contrast MR angiography.
It has been shown that the lesion volume on rCBV maps at acute stage is closest to the final infarct volume (14,26) and that the infarct volume is significantly related to the clinical outcome (35). In the present study, the combination of diffusion-weighted imaging and MR angiography yielded the highest sensitivity and was as accurate as the rCBV map in helping to predict an unfavorable clinical outcome. This suggests that knowledge of the patency of flow in large vessels with use of MR angiography combined with detection of severely ischemic and very likely permanently damaged tissue with diffusion-weighted imaging provides clinically robust means to predict the evolution of ischemic stroke in the MCA territory.
In a study with 26 patients, Barber et al (13) found that patients with absent M1 flow had larger lesion volumes on MTT maps, larger acute lesion volumes on diffusion-weighted images, larger final infarct volumes, and poorer clinical outcomes than patients with M1 flow. In that study, only one patient had ICA occlusion with collateral M1 flow. In the present study, the patients who had ICA occlusion with collateral M1 flow (group 2) did not have significantly smaller hypoperfusion volumes on MTT maps compared with patients without M1 flow (group 1), but they had significantly larger volumes of hypoperfusion on MTT maps and MTT-diffusion mismatch than did patients who had flow in both the ICA and M1 (group 3). In agreement with the findings of Barber et al (13), patients in group 1 had larger final infarct volumes and poorer clinical outcomes than did patients in groups 2 and 3.
Our results are further supported by studies conducted with CT (36,37). Findings of the studies suggested that the presence of a proximal hyperattenuating MCA sign is associated with a poor prognosis (36–38). Furthermore, findings of a recent study showed that five of 30 patients with an MCA or ICA occlusion on MR angiograms obtained within the first 6 hours of stroke had died within 3 months, and all five patients revealed no recanalization within the 1st day after onset, which suggests that the absence of M1 flow was significantly associated with death (39). However, in the present study, patients in groups 2 and 3 showed no significant differences in their acute lesion volumes on diffusion-weighted images, final infarct volumes, and clinical outcomes. This finding indicates that the patency of collateral circulation on day 1 plays an important role in preventing the ischemic tissue from proceeding to infarction, which emphasizes the usefulness of MR angiography when predicting the outcome of ischemic tissue.
Effects of Spontaneous Reperfusion after Acute Stage
The effects of reperfusion during the subacute stage are still a subject of debate (40–42). Different methodological and technical approaches probably account for most of the discrepancies. In the present study, among the 15 patients in group 1, eight patients showed collateral M1 flow or recanalization by day 8. They had no significant differences in their final infarct volumes, in the enlargement of infarction, or in the clinical outcome when compared with patients who had no MR angiographic change. It seemed that spontaneous reperfusion after the acute stage had no obvious beneficial effect in preventing ischemic tissue from proceeding to infarction or in improving the clinical outcome. However, an MR angiographic change was associated with nonsymptomatic hemorrhagic transformation. Those findings are supported by a study in which single-photon emission computed tomography was used (41).
Limitations of the Present Study
Our study has certain limitations. First, the mean delay from the onset of symptoms to the initial MR imaging was 11 hours. Only eight (19%) of 43 patients were imaged within the first 6 hours from the onset of symptoms. We probably were not able to identify all cases of early MR angiographic change (ie, early recanalization and establishment of collateral M1 flow). Considering the advocated treatment window, the predictive power of 2D phase-contrast MR angiography performed within 6 hours needs to be further studied. Second, it is well known that appropriate velocity-encoding value selection is essential for the visualization of blood vessels. We arbitrarily selected a single velocity-encoding value of 45 cm/sec, which can prevent detection of slow flow. In four (10%) of 41 patients, complete absence of M1 flow was demonstrated on MR angiograms, but T2-weighted images were interpreted to have a faint M1 signal void, reminding us of the possible limitations of 2D phase-contrast MR angiography. Another possible explanation for the dispersion is that the acute intraluminal clot might show hypointensity that results from the paramagnetic effects of hemoglobin degradation products (43). Moreover, the quality of 2D phase-contrast MR angiography in the present study did not allow assessment of occlusions more distal than the M1 because of low spatial resolution, and the accuracy of our MR angiographic technique was not confirmed with conventional angiography.
Time-of-flight MR angiography is the most commonly used angiographic technique in the evaluation of vessel patency. However, because the acquisition time is relatively longer than that of 2D phase-contrast MR angiography, we used 2D phase-contrast MR angiography, which enabled us to successfully obtain flow information in stroke patients whose situations are often unstable. Finally, because of the capability of the imager, perfusion and perfusion-diffusion mismatches were studied within the seven sections containing the lesion core on diffusion-weighted images. Limited coverage of perfusion-weighted imaging may cause underestimation of the tissue at risk. The cutoff values for determination of "large" or "small" perfusion deficits and diffusion abnormalities were retrospectively calculated in the population imaged within 24 hours of onset of stroke. Whether these arbitrarily selected threshold volumes are valid within the therapeutic window of 6 hours must be studied further.
In conclusion, 2D phase-contrast MR angiography can provide complementary information to that of diffusion- and perfusion-weighted imaging in helping to predict the outcome of patients with acute stroke.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, Y.L., H.J.A.; study concepts, all authors; study design, Y.L., H.J.A., R.L.V., J.O.K.; literature research, Y.L., R.L.V., J.O.K.; clinical studies, Y.L., R.L.V., J.O.K., J.N., A.K.; data acquisition, J.O.K., J.N.; data analysis/interpretation, Y.L., R.L.V., J.O.K., J.N., A.K.; statistical analysis, Y.L., R.L.V.; manuscript preparation, Y.L., R.L.V., J.O.K., H.J.A.; manuscript definition of intellectual content, Y.L., H.J.A., R.L.V.; manuscript editing, Y.L., R.L.V., J.O.K.; manuscript revision/review and final version approval, all authors
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