Journal of Neuroradiology (2015) 42, 255—260
Available online at
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ORIGINAL ARTICLE
Comparison of susceptibility-weighted and perfusion-weighted magnetic resonance imaging in the detection of penumbra in acute ischemic stroke Song Luo a,∗, Lijuan Yang b, Lijin Wang c a
Department of Neurology, the First Hospital of Bengbu Medical College, Bengbu 233004, China Department of Pediatrics, the First Hospital of Bengbu Medical College, Bengbu 233004, China c Department of Psychology, Bengbu Medical College, Bengbu 233000, China b
KEYWORDS Susceptibilityweighted imaging; Diffusion-weighted imaging; Perfusion-weighted imaging; Stroke; Penumbra
Summary Background and purpose: To investigate detection of ischemic penumbra in stroke patients with acute cerebral infarction by susceptibility-weighted imaging (SWI) in comparison with perfusion-weighted imaging (PWI). Materials and methods: This study included 18 stroke patients with acute infarction who underwent diffusion-weighted imaging (DWI), SWI, PWI, and magnetic resonance angiography (MRA) within 3 days after symptom onset. The Alberta Stroke Program Early CT Score (ASPECTS) was used to evaluate lesions on DWI, SWI, and PWI. DWI-SWI and DWI-PWI mismatches were calculated. Results: The DWI-SWI mismatch was not significantly different from the DWI-mean transit time (MTT) mismatch (P = 0.163) in evaluating ischemic penumbra. The susceptibility vessel sign (SVS) in SWI occurred in 11 (61%) of 18 patients with cerebral infarction. Stenosis or occlusion of the affected vessels was identified by MRA in 10 (91%) of the 11 SVS-positive patients. The SVS on SWI was significantly associated with the occurrence of damaged vessels or the presence of thrombus in the affected vessels (P = 0.047). Conclusions: DWI-SWI mismatch is a good marker for evaluating ischemic penumbra in stroke patients with cerebral infarction. SWI can detect thrombus in the affected vessels, and may be useful for guiding intra-arterial thrombolytic therapy. © 2014 Elsevier Masson SAS. All rights reserved.
∗ Corresponding author. Department of Neurology, the First Hospital of Bengbu Medical College, Bengbu 233004, China. Tel.: +86 0552 3086137; fax: +86 0552 3070260. E-mail address: [email protected] (S. Luo).
http://dx.doi.org/10.1016/j.neurad.2014.07.002 0150-9861/© 2014 Elsevier Masson SAS. All rights reserved.
256
Introduction Currently, the primary target for treatment of acute ischemic stroke is the ischemic penumbra, a brain area in which blood flow is reduced, but not to an extent sufficient to cause irreversible cell membrane failure [1,2]. The presence of a penumbra implies that early, appropriate therapy may salvage the damaged cells, thus improving the clinical outcome in patients with ischemic stroke [3,4]. However, the central necrotic area tends to increase in size as time elapses after the onset of ischemic stroke, which reduces the extent of the penumbra. Early identification and salvage of the penumbra are critical steps in the clinical treatment of patients with ischemic stroke. Some imaging techniques used to detect the ischemic penumbra, such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and perfusion-weighted imaging (PWI), require radionucleotides or contrast agents, which limits their clinical application [5]. Susceptibility-weighted imaging (SWI) is a relatively new high-resolution magnetic resonance imaging (MRI) technique that has been used to detect the penumbra in stroke patients [6—8]. SWI does not require administration of radionucleotides or contrast agents, but uses paramagnetic susceptibility effects to study metabolic changes in hypoperfused brain tissues [9—12]. SWI detects the paramagnetic susceptibility difference between deoxygenated and oxygenated hemoglobin (Hb), which reflects the oxygen extraction fraction (OEF) of brain tissues. In ischemic stroke, reduced cerebral perfusion pressure causes an increase in the Hb/HbO ratio by increasing OEF [13,14]. Therefore, we hypothesize that SWI provides information on metabolic changes in the ischemic brain area that can be used for early detection of the ischemic penumbra in stroke patients. In the present study, we evaluated 18 stroke patients with acute infarction using diffusion-weighted imaging (DWI), SWI, PWI, and magnetic resonance angiography (MRA). The purpose of this study was to evaluate the effectiveness of SWI in detection of ischemic penumbra compared with PWI.
Materials and methods Patients The Medical Ethics Committee of Jilin University approved the study, and all patients gave informed consent prior to inclusion. Eighteen stroke patients (15 males and 3 females) with acute cerebral infarction who were admitted to the Department of Neurology at the First Hospital of Jilin University between January 2012 and January 2013 were enrolled. The average patient age was 53.8 ± 8.8 years (range, 22—65 years). Inclusion criteria were: • a new infarction locus detected by DWI; • hospital admission within 3 days of symptom onset; • a first-ever ischemic stroke, or a previous stroke with hemiplegia sequelae that did not affect the neurological score; • male or female sex and 18—75 years of age; • a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20.
S. Luo et al. Exclusion criteria were: • cerebral hemorrhage, tumor, or trauma detected by head computed tomography (CT); • severe cardiovascular, renal, or hemorrhagic disease; • history of allergy; • pregnancy; • psychological or neurological diseases such as autism. All patients underwent cranial MRI, DWI, SWI, PWI, and magnetic resonance angiography (MRA) within 3 days of symptom onset. The severity of neurological damage was evaluated using NIHSS scores.
Imaging techniques MRI data were obtained with a 3.0 T Siemens Tim Trio whole-body MR imaging system (Siemens, Germany) by using a standard head coil. Each patient was given a conventional MRI, 3D time-of-flight magnetic resonance angiogram (3D-TOF-MRA), spin echo-echo planar imaging (SE-EPI), magnetic resonance perfusion (MRP), and SWI. The entire cranial anatomy was scanned in the sagittal, coronal and axial planes. The images were obtained in the following sequence: DWI, T1-weighted spin echo (T1-SE), T2-weighed fast spin echo (T2-FSE), and T2-weight fast fluid-attenuated inversion-recovery (T2-FLAIR). The following parameters were used: repetition time (TR), 93 ms, echo time (TE), 3800 ms for DWI; TR, 440 ms, TE, 2.5 ms for T1-SE; TR, 3000 ms, TE, 93 ms for T2-FSE; and TR, 8000 ms, TE, 93 ms, inversion time (TI), 2371.5 ms; slice thickness, 6 mm; interslice gap, 1.2 mm; field of view (FOV), 199 mm × 220 mm; matrix, 464 × 512. For SWI, the magnitude and phase images were obtained with the following parameters: TR/TE, 49/40; flip angle, 15◦ ; bandwidth, 80 kHz; slice thickness, 2 mm; 64 slices in a single slab; iPAT factor, 2; and matrix, 177 × 256 pixels. Post-processing was performed and 2-mm mIP images were generated. For MRP, patients received an intravenous bolus injection of gadolinium-DTPA (0.2 mmol/kg,) at a rate of 4.5—5.0 mL/s during the sixth SE-EPI scan, using a Medrad high-pressure syringe. MRP was performed using the following parameters: TR, 1400 ms; TE, 32 ms; inversion angle, 70◦ ; FOV, 23 cm × 23 cm; slice thickness, 5 mm; interslice gap, 1.5 mm; and matrix, 128 × 128 in one excitation.
Image analysis All images were collected as DICOM-format data and imported to an Osirix image viewer for analysis. For DWI, SWI, and PWI studies, the size of abnormal signal intensities or densities were evaluated in an observer-blind fashion by two neuroradiologists using the Alberta Stroke Program Early CT Score (ASPECTS) 10-point quantitative topographic CT scan score. For calculating ASPECTS scores, one point was subtracted from a maximum of 10 for each area of ischemic change, including restricted diffusion on DWI, prolonged mean transit time (MTT), and prominent vessels in SWI (Figs. 1 and 2). Mismatches were determined from the differences between the DWI and SWI ASPECTS scores or the DWI and MTT ASPECTS scores. The susceptibility vessel sign
MRI and penumbra in ischemic stroke
257
Figure 1 Representative images of a patient with acute cerebral infarction, who underwent DWI (A, B), PWI (C, D), and SWI (E, F). MTT (C, D) showed hypoperfusion in the affected area. SWI (E, F) showed prominent veins (PV) in the corresponding area in C, D.
(SVS), determined by hypointensities along the affected vessels on MRI, was used to detect the presence of a thrombus [15,16] (Figs. 1 and 2).
Statistical analysis Analyses were performed using SPSS 17.0. Because the data were not normally distributed, non-parametric tests were used for comparison. The values were presented as mean and standard deviation, median and range, or number and percentage. Wilcoxon signed-rank tests were used to compare the differences between DWI-SWI and DWI-MTT mismatches. Spearman correlation test was used to analyze the correlation of clinical data with DWI-SWI and DWE-MTT mismatches. The Chi2 goodness-of-fitness test was used to analyze the correlation of the SVS with the presence of thrombus in the vessels. A P-value less than 0.05 was considered statistically significant.
Results
DWI ASPECTS scores and SWI or MTT ASPECTS scores, i.e., DWI-SWI and DWI-MTT mismatches, were analyzed to compare SWI and MTT as indicators of the ischemic penumbra. Table 1 summarizes the correlation of clinical data with DWISWI and DWI-MTT mismatches. There were no significant correlations between clinical data and DWI-SWI and DWI-MTT mismatches. There was no significant difference between the DWI-SWI and DWI-MTT mismatches (P = 0.163, Table 2). In addition, the DWI-SWI mismatch was positively correlated with the DWI-MTT mismatches (r = 0.76, P < 0.001, Fig. 3). These findings suggested that similar to the DWI-MTT mismatch, the DWI-SWI mismatch could reflect the size of ischemic penumbra in patients with cerebral infarction. Table 3 shows that the SVS occurred in 11 (61%) of 18 patients with cerebral infarction on SWI. Stenosis or occlusion of the affected vessels was identified by MRA in 10 (91%) of the 11 SVS-positive patients. Chi2 goodness-of-fitness analysis showed that a finding of SVS on SWI was significantly associated with the occurrence of damaged vessels or the presence of thrombus in the affected vessels (P = 0.047).
Discussion We evaluated the ASPECT scores in 18 patients with cerebral ischemia by DWI, SWI and MTT as an indication of the size of the ischemic penumbra. Differences between
In the present study, we evaluated 18 stroke patients with acute cerebral infarction by DWI, PWI, and SWI. The
258
S. Luo et al.
Figure 2 Representative images of a stroke patient with left middle cerebral artery occlusion, who underwent DWI (A, B), PWI (C, D), MRA (E), and SWI (F). MTT (C, D) showed hypoperfusion in the brain region supplied by the left middle cerebral artery. MRA (E) indicated occlusion of the left middle cerebral artery. SWI minimal intensity projection (mIP) showed the susceptibility vessel sign (SVS) in the trunk of the middle cerebral artery (red arrow).
Table 1
The correlation of clinical data with DWI-SWI and DWI-MTT mismatches. P-value
Ages (years) Mean ± SD Median (range) Gender female n (%) Hypertension n (%) Diabetes mellitus n (%) Hyperlipidemia n (%) Hyperhomocysteinemia n (%) Smoke n (%) Drinking n (%)
53.28 ± 9.69 56 (22—65) 3 (17%) 9 (50%) 4 (22%) 7 (39%) 9 (50%) 10 (56%) 7 (3%)
DWI-SWI
DWI-MTT
0.457
0.482
0.167 0.695 0.834 0.560 0.066 0.568 0.591
0.380 0.515 0.716 0.448 0.095 0.761 0.930
DWI: diffusion-weighted imaging; SWI: susceptibility-weighted imaging; MTT: mean transit time; DWI-SWI: differences between the DWI and SWI ASPECTS scores; DWI-MTT: differences between the DWI and MTT ASPECTS scores. Spearman correlation test was used to analyze the correlation of clinical data with DWI-SWI and DWE-MTT mismatches.
MRI and penumbra in ischemic stroke Table 2
259
The DWI-SWI and DWI-MTT mismatches.
ASPECTS score Mean ± SD Median (range)
DWI
SWI
MTT
DWI-SWI
DWI-MTT
5.67 ± 1.645 5.7 (2—8)
3.28 ± 1.841 3 (1—9)
2.94 ± 1.589 2.64 (1—7)
2.39 ± 1.420 2.6 (—1—4)
2.72 ± 1.487 2.86 (0—5)
DWI: diffusion-weighted imaging; SWI: susceptibility-weighted imaging; MTT: mean transit time; DWI-SWI: differences between the DWI and SWI ASPECTS scores; DWI-MTT: differences between the DWI and MTT ASPECTS scores. P = 0.163 between DWI-SWI and DWI-MTT mismatches.
Table 3 The association of SVS with occlusion or stenosis of the affected vessels. Vessel occlusion SVS Positive 10 (55.5%) Negative 3 (16.7%) Total 13 (72.2%)
Vessel stenosis 1 (5.6%) 4 (22.2%) 5 (27.8%)
Total 11 (61.1%) 7 (38.9%) 18 (100%)
Occlusion or stenosis of the affected vessels was detected by MRA. The susceptibility vessel sign (SVS) was determined by hypointensities along the affected vessels on MRI, indicating the presence of a thrombus. SVS on SWI (susceptibilityweighted imaging) was significantly associated with the occurrence of damaged vessels or the presence of thrombus in the affected vessels (P = 0.047, Chi2 goodness-of-fitness analysis).
DWI-MTT mismatch is considered as a reliable measure of the ischemic penumbra in stroke patients [17]. Our finding that the DWI-SWI mismatch was similar to that indicated by DWI-MTT for detection of the penumbra suggested that the SWI could be used to evaluate patients with ischemic stroke. Consistent with our findings, Meoded et al. [6] reported that SWI could be used to evaluate the ischemic penumbra in pediatric ischemic cerebral stroke. In addition, we found
Figure 3 The scatter plot showing the correlation between the DWI-SWI mismatch and the DWI-MTT mismatch. The DWI-SWI mismatch was positively correlated with the DWI-MTT mismatch (Spearman test, r = 0.76, P < 0.001).
that some imaging features of SWI such as SVS were associated with damaged vessels or the presence of thrombi in the affected vessels. SWI could thus provide information on the status of blood vessels in patients with acute cerebral infarction in addition to that provided by other currently used imaging methods. Although use of the DWI-PWI mismatch to distinguish reversible and irreversible cerebral infarction is controversial, it is well accepted that the DWI-PWI mismatch represents the ischemic penumbra [18]. In the present study, we found that the DWI-SWI mismatch was similar to the DWIPWI mismatch in the detection of penumbra, suggesting that the DWI-SWI mismatch can be used to identify the ischemic penumbra. This finding is consistent with previous reports that DWI-SWI and DWI-PWI mismatches have a similar ability to predict stroke evolution [19,20]. SWI also shows prominent veins in acute infarction, possibly reflecting an increase in the Hb/HbO ratio caused by a hypoperfusion-induced increase in OEF [20,21]. SWI has been reported to be reliable and suitable method for quantitative measurement of deep cerebral veins [22]. In the present study, we also found prominent veins on SWI in the hypoperfused brain regions. It has been reported that prominent veins on SWI correlate with hypoperfused brain regions with a prolonged MTT on PW [23]. MTT is a very sensitive measurement of the ischemic condition of brain tissues, and has been used to define the ischemic range [24]. Several studies have demonstrated an association of elevated OEF and increased MTT [24—26]. Several studies have demonstrated an association of elevated OEF and increased MTT [25,26]. Since SWI is sensitive to OEF-associated change in deoxygenated hemoglobin, it can be used to provide metabolic information similar to MTT. This can explain our finding that the DWI-SWI and DWI-MTT mismatches were similar. Determining the position of an arterial thrombus is crucial for the success of thrombolytic therapy in acute cerebral infarction. In the present study, we found that the SVS, characterized by hypotensive signals in SWI, occurred in 11 of 18 patients with cerebral infarction, indicating the presence of thrombus in the affected artery of these patients. The identification of stenosis or occlusion in the corresponding artery by MRA also confirmed the presence of a thrombus in the affected vessels. Thrombus formation can lead to decreased oxygen saturation and subsequent increase in the concentration of deoxygenated hemoglobin, resulting in a short T2 signal on MRI. Through its detection of a thrombus-induced magnetic susceptibility effect, SWI has a high sensitivity for identifying the presence of thrombus. Santhosh et al. reported that the sensitivity and specificity of T2*-weighted sequences in identification of thrombus in the cerebral
260 artery were 83% and 100%, respectively, with no false positive results [16]. Similarly, we found that SWI identified the presence of thrombi in 11 (61%) of 18 patients, with no false positives, a sensitivity and specificity of 61% and 100%, respectively. In addition, SWI is able to identify thrombi in the distal part of the cerebral artery, which are difficult to detect by MRA [16]. Thrombi were not found in the distal ends of small arteries of patients in this series, possibly because of the small sample size. The finding that SWI could detect the occurrence of damaged vessels and the presence of thrombi, i.e., SVS, suggests that it can be used to indicate the presence of a thrombus in the affected vessels. This study has some limitations. First, the sample size of the study was small (n = 18). We only included patients who underwent all the imaging examinations, including MRI, DWI, SWI, PWI, and MRA. Many stroke patients administered into our hospital were excluded from this study mainly because of incomplete imaging data. Further studies with a large sample size are clearly needed to confirm the study results. Second, SWI was not performed to evaluate patients for intra-arterial thrombolytic therapy. Future studies are needed to investigate the role of SWI in guiding thrombolytic therapy in patients with acute infarction.
S. Luo et al.
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
Conclusion [15]
In conclusion, SWI is a non-traumatic imaging technique that can provide cerebral blood flow information comparable to MTT in patients with acute infarction. DWI-SWI mismatch is a sensitive marker for ischemic penumbra. SWI can show the presence of thrombus in the affected artery, thus providing important information for selecting and developing therapies and evaluating clinical outcomes in patients with acute cerebral infarction. SWI is potentially useful for assessing the survival of damaged brain tissue and guiding intraarterial thrombolytic therapy. It should be considered for routine use in patients with acute cerebral infarction.
[16]
[17]
[18]
Disclosure of interest
[19]
The authors declare that they have no conflicts of interest concerning this article.
[20]
References [1] Astrup J, Siesjö BK, Symon L. Thresholds in cerebral ischemiathe ischemic penumbra. Stroke 1981;12:723—5. [2] Donnan GA, Davis SM, Sharp FR. The ischemic penumbra: overview, definition, and criteria. In: Donnan GA, Davis SM, Sharp FR, editors. The Ischaemic penumbra: pathophysiology, imaging and therapy. New York: Informa Healthcare; 2007. p. 149—64. [3] Guadagno JV, Calautti C, Baron JC. Progress in imaging stroke: emerging clinical applications. Br Med Bull 2003;65:145—57. [4] Murphy BD, Fox AJ, Lee DH, et al. Identification of penumbra and infarct in acute ischemic stroke using computed tomography perfusion-derived blood flow and blood volume measurements. Stroke 2006;37:1771—7. [5] Lövblad KO, Altrichter S, Viallon M, et al. Neuro-imaging of cerebral ischemic stroke. J Neuroradiol 2008;35(4):197—209. [6] Meoded A, Poretti A, Benson JE, et al. Evaluation of the ischemic penumbra focusing on the venous drainage: the role
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Available online at
ScienceDirect www.sciencedirect.com
ORIGINAL ARTICLE
Comparison of susceptibility-weighted and perfusion-weighted magnetic resonance imaging in the detection of penumbra in acute ischemic stroke Song Luo a,∗, Lijuan Yang b, Lijin Wang c a
Department of Neurology, the First Hospital of Bengbu Medical College, Bengbu 233004, China Department of Pediatrics, the First Hospital of Bengbu Medical College, Bengbu 233004, China c Department of Psychology, Bengbu Medical College, Bengbu 233000, China b
KEYWORDS Susceptibilityweighted imaging; Diffusion-weighted imaging; Perfusion-weighted imaging; Stroke; Penumbra
Summary Background and purpose: To investigate detection of ischemic penumbra in stroke patients with acute cerebral infarction by susceptibility-weighted imaging (SWI) in comparison with perfusion-weighted imaging (PWI). Materials and methods: This study included 18 stroke patients with acute infarction who underwent diffusion-weighted imaging (DWI), SWI, PWI, and magnetic resonance angiography (MRA) within 3 days after symptom onset. The Alberta Stroke Program Early CT Score (ASPECTS) was used to evaluate lesions on DWI, SWI, and PWI. DWI-SWI and DWI-PWI mismatches were calculated. Results: The DWI-SWI mismatch was not significantly different from the DWI-mean transit time (MTT) mismatch (P = 0.163) in evaluating ischemic penumbra. The susceptibility vessel sign (SVS) in SWI occurred in 11 (61%) of 18 patients with cerebral infarction. Stenosis or occlusion of the affected vessels was identified by MRA in 10 (91%) of the 11 SVS-positive patients. The SVS on SWI was significantly associated with the occurrence of damaged vessels or the presence of thrombus in the affected vessels (P = 0.047). Conclusions: DWI-SWI mismatch is a good marker for evaluating ischemic penumbra in stroke patients with cerebral infarction. SWI can detect thrombus in the affected vessels, and may be useful for guiding intra-arterial thrombolytic therapy. © 2014 Elsevier Masson SAS. All rights reserved.
∗ Corresponding author. Department of Neurology, the First Hospital of Bengbu Medical College, Bengbu 233004, China. Tel.: +86 0552 3086137; fax: +86 0552 3070260. E-mail address: [email protected] (S. Luo).
http://dx.doi.org/10.1016/j.neurad.2014.07.002 0150-9861/© 2014 Elsevier Masson SAS. All rights reserved.
256
Introduction Currently, the primary target for treatment of acute ischemic stroke is the ischemic penumbra, a brain area in which blood flow is reduced, but not to an extent sufficient to cause irreversible cell membrane failure [1,2]. The presence of a penumbra implies that early, appropriate therapy may salvage the damaged cells, thus improving the clinical outcome in patients with ischemic stroke [3,4]. However, the central necrotic area tends to increase in size as time elapses after the onset of ischemic stroke, which reduces the extent of the penumbra. Early identification and salvage of the penumbra are critical steps in the clinical treatment of patients with ischemic stroke. Some imaging techniques used to detect the ischemic penumbra, such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and perfusion-weighted imaging (PWI), require radionucleotides or contrast agents, which limits their clinical application [5]. Susceptibility-weighted imaging (SWI) is a relatively new high-resolution magnetic resonance imaging (MRI) technique that has been used to detect the penumbra in stroke patients [6—8]. SWI does not require administration of radionucleotides or contrast agents, but uses paramagnetic susceptibility effects to study metabolic changes in hypoperfused brain tissues [9—12]. SWI detects the paramagnetic susceptibility difference between deoxygenated and oxygenated hemoglobin (Hb), which reflects the oxygen extraction fraction (OEF) of brain tissues. In ischemic stroke, reduced cerebral perfusion pressure causes an increase in the Hb/HbO ratio by increasing OEF [13,14]. Therefore, we hypothesize that SWI provides information on metabolic changes in the ischemic brain area that can be used for early detection of the ischemic penumbra in stroke patients. In the present study, we evaluated 18 stroke patients with acute infarction using diffusion-weighted imaging (DWI), SWI, PWI, and magnetic resonance angiography (MRA). The purpose of this study was to evaluate the effectiveness of SWI in detection of ischemic penumbra compared with PWI.
Materials and methods Patients The Medical Ethics Committee of Jilin University approved the study, and all patients gave informed consent prior to inclusion. Eighteen stroke patients (15 males and 3 females) with acute cerebral infarction who were admitted to the Department of Neurology at the First Hospital of Jilin University between January 2012 and January 2013 were enrolled. The average patient age was 53.8 ± 8.8 years (range, 22—65 years). Inclusion criteria were: • a new infarction locus detected by DWI; • hospital admission within 3 days of symptom onset; • a first-ever ischemic stroke, or a previous stroke with hemiplegia sequelae that did not affect the neurological score; • male or female sex and 18—75 years of age; • a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20.
S. Luo et al. Exclusion criteria were: • cerebral hemorrhage, tumor, or trauma detected by head computed tomography (CT); • severe cardiovascular, renal, or hemorrhagic disease; • history of allergy; • pregnancy; • psychological or neurological diseases such as autism. All patients underwent cranial MRI, DWI, SWI, PWI, and magnetic resonance angiography (MRA) within 3 days of symptom onset. The severity of neurological damage was evaluated using NIHSS scores.
Imaging techniques MRI data were obtained with a 3.0 T Siemens Tim Trio whole-body MR imaging system (Siemens, Germany) by using a standard head coil. Each patient was given a conventional MRI, 3D time-of-flight magnetic resonance angiogram (3D-TOF-MRA), spin echo-echo planar imaging (SE-EPI), magnetic resonance perfusion (MRP), and SWI. The entire cranial anatomy was scanned in the sagittal, coronal and axial planes. The images were obtained in the following sequence: DWI, T1-weighted spin echo (T1-SE), T2-weighed fast spin echo (T2-FSE), and T2-weight fast fluid-attenuated inversion-recovery (T2-FLAIR). The following parameters were used: repetition time (TR), 93 ms, echo time (TE), 3800 ms for DWI; TR, 440 ms, TE, 2.5 ms for T1-SE; TR, 3000 ms, TE, 93 ms for T2-FSE; and TR, 8000 ms, TE, 93 ms, inversion time (TI), 2371.5 ms; slice thickness, 6 mm; interslice gap, 1.2 mm; field of view (FOV), 199 mm × 220 mm; matrix, 464 × 512. For SWI, the magnitude and phase images were obtained with the following parameters: TR/TE, 49/40; flip angle, 15◦ ; bandwidth, 80 kHz; slice thickness, 2 mm; 64 slices in a single slab; iPAT factor, 2; and matrix, 177 × 256 pixels. Post-processing was performed and 2-mm mIP images were generated. For MRP, patients received an intravenous bolus injection of gadolinium-DTPA (0.2 mmol/kg,) at a rate of 4.5—5.0 mL/s during the sixth SE-EPI scan, using a Medrad high-pressure syringe. MRP was performed using the following parameters: TR, 1400 ms; TE, 32 ms; inversion angle, 70◦ ; FOV, 23 cm × 23 cm; slice thickness, 5 mm; interslice gap, 1.5 mm; and matrix, 128 × 128 in one excitation.
Image analysis All images were collected as DICOM-format data and imported to an Osirix image viewer for analysis. For DWI, SWI, and PWI studies, the size of abnormal signal intensities or densities were evaluated in an observer-blind fashion by two neuroradiologists using the Alberta Stroke Program Early CT Score (ASPECTS) 10-point quantitative topographic CT scan score. For calculating ASPECTS scores, one point was subtracted from a maximum of 10 for each area of ischemic change, including restricted diffusion on DWI, prolonged mean transit time (MTT), and prominent vessels in SWI (Figs. 1 and 2). Mismatches were determined from the differences between the DWI and SWI ASPECTS scores or the DWI and MTT ASPECTS scores. The susceptibility vessel sign
MRI and penumbra in ischemic stroke
257
Figure 1 Representative images of a patient with acute cerebral infarction, who underwent DWI (A, B), PWI (C, D), and SWI (E, F). MTT (C, D) showed hypoperfusion in the affected area. SWI (E, F) showed prominent veins (PV) in the corresponding area in C, D.
(SVS), determined by hypointensities along the affected vessels on MRI, was used to detect the presence of a thrombus [15,16] (Figs. 1 and 2).
Statistical analysis Analyses were performed using SPSS 17.0. Because the data were not normally distributed, non-parametric tests were used for comparison. The values were presented as mean and standard deviation, median and range, or number and percentage. Wilcoxon signed-rank tests were used to compare the differences between DWI-SWI and DWI-MTT mismatches. Spearman correlation test was used to analyze the correlation of clinical data with DWI-SWI and DWE-MTT mismatches. The Chi2 goodness-of-fitness test was used to analyze the correlation of the SVS with the presence of thrombus in the vessels. A P-value less than 0.05 was considered statistically significant.
Results
DWI ASPECTS scores and SWI or MTT ASPECTS scores, i.e., DWI-SWI and DWI-MTT mismatches, were analyzed to compare SWI and MTT as indicators of the ischemic penumbra. Table 1 summarizes the correlation of clinical data with DWISWI and DWI-MTT mismatches. There were no significant correlations between clinical data and DWI-SWI and DWI-MTT mismatches. There was no significant difference between the DWI-SWI and DWI-MTT mismatches (P = 0.163, Table 2). In addition, the DWI-SWI mismatch was positively correlated with the DWI-MTT mismatches (r = 0.76, P < 0.001, Fig. 3). These findings suggested that similar to the DWI-MTT mismatch, the DWI-SWI mismatch could reflect the size of ischemic penumbra in patients with cerebral infarction. Table 3 shows that the SVS occurred in 11 (61%) of 18 patients with cerebral infarction on SWI. Stenosis or occlusion of the affected vessels was identified by MRA in 10 (91%) of the 11 SVS-positive patients. Chi2 goodness-of-fitness analysis showed that a finding of SVS on SWI was significantly associated with the occurrence of damaged vessels or the presence of thrombus in the affected vessels (P = 0.047).
Discussion We evaluated the ASPECT scores in 18 patients with cerebral ischemia by DWI, SWI and MTT as an indication of the size of the ischemic penumbra. Differences between
In the present study, we evaluated 18 stroke patients with acute cerebral infarction by DWI, PWI, and SWI. The
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Figure 2 Representative images of a stroke patient with left middle cerebral artery occlusion, who underwent DWI (A, B), PWI (C, D), MRA (E), and SWI (F). MTT (C, D) showed hypoperfusion in the brain region supplied by the left middle cerebral artery. MRA (E) indicated occlusion of the left middle cerebral artery. SWI minimal intensity projection (mIP) showed the susceptibility vessel sign (SVS) in the trunk of the middle cerebral artery (red arrow).
Table 1
The correlation of clinical data with DWI-SWI and DWI-MTT mismatches. P-value
Ages (years) Mean ± SD Median (range) Gender female n (%) Hypertension n (%) Diabetes mellitus n (%) Hyperlipidemia n (%) Hyperhomocysteinemia n (%) Smoke n (%) Drinking n (%)
53.28 ± 9.69 56 (22—65) 3 (17%) 9 (50%) 4 (22%) 7 (39%) 9 (50%) 10 (56%) 7 (3%)
DWI-SWI
DWI-MTT
0.457
0.482
0.167 0.695 0.834 0.560 0.066 0.568 0.591
0.380 0.515 0.716 0.448 0.095 0.761 0.930
DWI: diffusion-weighted imaging; SWI: susceptibility-weighted imaging; MTT: mean transit time; DWI-SWI: differences between the DWI and SWI ASPECTS scores; DWI-MTT: differences between the DWI and MTT ASPECTS scores. Spearman correlation test was used to analyze the correlation of clinical data with DWI-SWI and DWE-MTT mismatches.
MRI and penumbra in ischemic stroke Table 2
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The DWI-SWI and DWI-MTT mismatches.
ASPECTS score Mean ± SD Median (range)
DWI
SWI
MTT
DWI-SWI
DWI-MTT
5.67 ± 1.645 5.7 (2—8)
3.28 ± 1.841 3 (1—9)
2.94 ± 1.589 2.64 (1—7)
2.39 ± 1.420 2.6 (—1—4)
2.72 ± 1.487 2.86 (0—5)
DWI: diffusion-weighted imaging; SWI: susceptibility-weighted imaging; MTT: mean transit time; DWI-SWI: differences between the DWI and SWI ASPECTS scores; DWI-MTT: differences between the DWI and MTT ASPECTS scores. P = 0.163 between DWI-SWI and DWI-MTT mismatches.
Table 3 The association of SVS with occlusion or stenosis of the affected vessels. Vessel occlusion SVS Positive 10 (55.5%) Negative 3 (16.7%) Total 13 (72.2%)
Vessel stenosis 1 (5.6%) 4 (22.2%) 5 (27.8%)
Total 11 (61.1%) 7 (38.9%) 18 (100%)
Occlusion or stenosis of the affected vessels was detected by MRA. The susceptibility vessel sign (SVS) was determined by hypointensities along the affected vessels on MRI, indicating the presence of a thrombus. SVS on SWI (susceptibilityweighted imaging) was significantly associated with the occurrence of damaged vessels or the presence of thrombus in the affected vessels (P = 0.047, Chi2 goodness-of-fitness analysis).
DWI-MTT mismatch is considered as a reliable measure of the ischemic penumbra in stroke patients [17]. Our finding that the DWI-SWI mismatch was similar to that indicated by DWI-MTT for detection of the penumbra suggested that the SWI could be used to evaluate patients with ischemic stroke. Consistent with our findings, Meoded et al. [6] reported that SWI could be used to evaluate the ischemic penumbra in pediatric ischemic cerebral stroke. In addition, we found
Figure 3 The scatter plot showing the correlation between the DWI-SWI mismatch and the DWI-MTT mismatch. The DWI-SWI mismatch was positively correlated with the DWI-MTT mismatch (Spearman test, r = 0.76, P < 0.001).
that some imaging features of SWI such as SVS were associated with damaged vessels or the presence of thrombi in the affected vessels. SWI could thus provide information on the status of blood vessels in patients with acute cerebral infarction in addition to that provided by other currently used imaging methods. Although use of the DWI-PWI mismatch to distinguish reversible and irreversible cerebral infarction is controversial, it is well accepted that the DWI-PWI mismatch represents the ischemic penumbra [18]. In the present study, we found that the DWI-SWI mismatch was similar to the DWIPWI mismatch in the detection of penumbra, suggesting that the DWI-SWI mismatch can be used to identify the ischemic penumbra. This finding is consistent with previous reports that DWI-SWI and DWI-PWI mismatches have a similar ability to predict stroke evolution [19,20]. SWI also shows prominent veins in acute infarction, possibly reflecting an increase in the Hb/HbO ratio caused by a hypoperfusion-induced increase in OEF [20,21]. SWI has been reported to be reliable and suitable method for quantitative measurement of deep cerebral veins [22]. In the present study, we also found prominent veins on SWI in the hypoperfused brain regions. It has been reported that prominent veins on SWI correlate with hypoperfused brain regions with a prolonged MTT on PW [23]. MTT is a very sensitive measurement of the ischemic condition of brain tissues, and has been used to define the ischemic range [24]. Several studies have demonstrated an association of elevated OEF and increased MTT [24—26]. Several studies have demonstrated an association of elevated OEF and increased MTT [25,26]. Since SWI is sensitive to OEF-associated change in deoxygenated hemoglobin, it can be used to provide metabolic information similar to MTT. This can explain our finding that the DWI-SWI and DWI-MTT mismatches were similar. Determining the position of an arterial thrombus is crucial for the success of thrombolytic therapy in acute cerebral infarction. In the present study, we found that the SVS, characterized by hypotensive signals in SWI, occurred in 11 of 18 patients with cerebral infarction, indicating the presence of thrombus in the affected artery of these patients. The identification of stenosis or occlusion in the corresponding artery by MRA also confirmed the presence of a thrombus in the affected vessels. Thrombus formation can lead to decreased oxygen saturation and subsequent increase in the concentration of deoxygenated hemoglobin, resulting in a short T2 signal on MRI. Through its detection of a thrombus-induced magnetic susceptibility effect, SWI has a high sensitivity for identifying the presence of thrombus. Santhosh et al. reported that the sensitivity and specificity of T2*-weighted sequences in identification of thrombus in the cerebral
260 artery were 83% and 100%, respectively, with no false positive results [16]. Similarly, we found that SWI identified the presence of thrombi in 11 (61%) of 18 patients, with no false positives, a sensitivity and specificity of 61% and 100%, respectively. In addition, SWI is able to identify thrombi in the distal part of the cerebral artery, which are difficult to detect by MRA [16]. Thrombi were not found in the distal ends of small arteries of patients in this series, possibly because of the small sample size. The finding that SWI could detect the occurrence of damaged vessels and the presence of thrombi, i.e., SVS, suggests that it can be used to indicate the presence of a thrombus in the affected vessels. This study has some limitations. First, the sample size of the study was small (n = 18). We only included patients who underwent all the imaging examinations, including MRI, DWI, SWI, PWI, and MRA. Many stroke patients administered into our hospital were excluded from this study mainly because of incomplete imaging data. Further studies with a large sample size are clearly needed to confirm the study results. Second, SWI was not performed to evaluate patients for intra-arterial thrombolytic therapy. Future studies are needed to investigate the role of SWI in guiding thrombolytic therapy in patients with acute infarction.
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[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
Conclusion [15]
In conclusion, SWI is a non-traumatic imaging technique that can provide cerebral blood flow information comparable to MTT in patients with acute infarction. DWI-SWI mismatch is a sensitive marker for ischemic penumbra. SWI can show the presence of thrombus in the affected artery, thus providing important information for selecting and developing therapies and evaluating clinical outcomes in patients with acute cerebral infarction. SWI is potentially useful for assessing the survival of damaged brain tissue and guiding intraarterial thrombolytic therapy. It should be considered for routine use in patients with acute cerebral infarction.
[16]
[17]
[18]
Disclosure of interest
[19]
The authors declare that they have no conflicts of interest concerning this article.
[20]
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