Abstract
Background
Fluid-attenuated inversion recovery vascular hyperintensity (FVH) outside of the diffusion-weighted imaging (DWI) lesion, termed FVH-DWI mismatch, may represent penumbral tissue with good collateral status.
Methods
Consecutive patients who underwent endovascular reperfusion therapy (EVT) for acute internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 occlusion were enrolled. FVH-DWI mismatch score was defined as the number of cortical Alberta Stroke Program Early CT Score areas (I and M1 to M6) that involved FVH but no DWI lesion (0 to 7 points). The outcome measure was set as good functional outcome, defined as a modified Rankin Scale score of 0 to 2, at 90 days after onset.
Results
Of 196 consecutive patients who underwent EVT for acute ICA or MCA-M1 occlusion, 32 without brain MRI before EVT were excluded, and the remaining 164 were analyzed. The median FVH-DWI mismatch score was 2 (interquartile range, 0 to 4). At 90 days after EVT, 2 patients were lost-to follow-up, and 73 had good functional outcome. The frequency of good functional outcome at 90 days after EVT increased significantly with increasing FVH-DWI mismatch score (P for trend <0.001). FVH-DWI mismatch score was independently associated with good functional outcome at 90 days after onset (adjusted odds ratio per 1 point,1.46; 95% confidence interval, 1.15–1.89).
Conclusions
Patients with large FVH-DWI mismatch had good functional outcome after EVT for acute ICA or MCA-M1 occlusion.
Keywords: endovascular reperfusion therapy, ischemic stroke, magnetic resonance imaging
Introduction
Patients with acute ischemic stroke often exhibit fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH) on brain magnetic resonance imaging (MRI).1–4 FVH represents retrograde slow blood flow through leptomeningeal collaterals distal to large-artery occlusion3,5,6 and is associated with good collateral status.7–9 On the other hand, the diffusion-weighted imaging (DWI) lesion represents infarct core. Therefore, FVH outside of the DWI lesion, termed FVH-DWI mismatch, 10 may represent penumbral tissue with good collateral status. We hypothesized that FVH-DWI mismatch is a predictor of functional outcome after endovascular reperfusion therapy (EVT) for acute ischemic stroke. To test this hypothesis, the association between FVH-DWI mismatch and functional outcome at 90 days after EVT for acute internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 occlusion was assessed in the present observational study.
Material and methods
Study population
Consecutive patients who underwent EVT for acute ICA or MCA-M1 occlusion at our hospital between July 2013 and February 2020 were enrolled. Acute ischemic stroke was diagnosed based on rapidly developing clinical signs of focal (or global) disturbance of cerebral function with no apparent cause other than that of vascular origin that was confirmed using brain MRI unless contraindicated or unavailable. The indication for EVT was based on recommendations provided in guidelines for mechanical thrombectomy in Japan.11–14 Patients without brain MRI before EVT were excluded. Informed consent was obtained from all patients.
FVH-DWI mismatch score
Brain MRI was performed using one of the following three MRI systems: a 1.5-T MRI system (Signa Infinity, GE Healthcare, Chicago, IL) with FLAIR imaging (repetition time, 8002 ms; echo time, 120.65 ms; field of view, 504 × 220 mm; matrix size, 224 × 256; slice thickness, 5 mm; and interslice gap, 1.5 mm) and DWI (repetition time, 7075 ms; echo time, 104.9 ms; field of view, 504 × 220 mm; matrix size, 128 × 128; slice thickness, 5 mm; interslice gap, 1.5 mm; and b-value, 1000 s/mm); a 1.5-T MRI system (Magnetom Symphony, Siemens, Munich, Germany) with FLAIR imaging (repetition time, 8000 ms; echo time, 95 ms; field of view, 504 × 220 mm; matrix size, 216 × 256; slice thickness, 5 mm; and interslice gap, 1.5 mm) and DWI (repetition time, 3.300 ms; echo time, 92 ms; field of view, 504 × 220 mm; matrix size, 128 × 128; slice thickness, 5 mm; interslice gap, 1.5 mm; and b-value, 1000 s/mm); and a 1.5-T MRI system (Achieva 1.5 T, Philips, Amsterdam, the Netherlands) with FLAIR imaging (repetition time, 10.000 ms; echo time, 140 ms; field of view, 527 × 230 mm; matrix size, 231 × 288; slice thickness, 5 mm; and interslice gap, 1.5 mm) and DWI (repetition time, 3500 ms; echo time, 75 ms; field of view, 527 × 230 mm; matrix size, 128 × 109; slice thickness, 5 mm; interslice gap, 1.5 mm; and b-value, 1.000 s/mm). FVH was defined as focal, tubular, or serpentine hyperintensity that corresponded to a typical arterial course on FLAIR imaging. 3 FVH-DWI mismatch score was defined as the number of cortical Alberta Stroke Program Early CT Score (ASPECTS) 15 areas (I and M1 to M6) that involved FVH but no DWI lesion (0 to 7 points). An example of FVH-DWI mismatch score rating is shown in Figure 1. Images were independently interpreted by 2 readers blinded to functional outcome at 90 days after EVT (K.T. and S.T.). Interrater reliability of FVH-DWI mismatch score assessed using the kappa statistic was excellent (κ = 0.82). Discrepancies were resolved by consensus.
Figure 1.
Example of fluid-attenuated inversion recovery (FLAIR) vascular hyperintensity (FVH)-diffusion-weighted imaging (DWI) mismatch score rating in a patient with acute left middle cerebral artery-m1 occlusion. a. Axial FLAIR imaging with FVH in all cortical Alberta Stroke Program Early CT Score (ASPECTS) areas (I and M1 to M6). b. Axial DWI with no lesion in any cortical ASPECTS area. In this case, FVH-DWI mismatch score was 7.
Endovascular reperfusion therapy
Procedures were performed via the femoral artery route under local anesthesia using biplane angiographic systems. EVT methods including mechanical thrombectomy with a stent retriever and/or an aspiration catheter, percutaneous transluminal angioplasty, stenting, and intraarterial thrombolysis were performed, as appropriate. Activated clotting time was checked hourly and was maintained between 250 and 300 s by intravenous injection of heparin.
Baseline characteristics
Data regarding FVH-DWI mismatch score, age, sex, premorbid modified Rankin Scale score, hypertension, dyslipidemia, diabetes mellitus, previous stroke, atrial fibrillation, initial National Institutes of Health Stroke Scale (NIHSS) score, DWI-ASPECTS, 16 intravenous thrombolysis, onset-to-door time, onset-to-puncture time, onset-to-reperfusion time, and reperfusion success were obtained from our single-center prospective database. Hypertension was diagnosed based on a systolic blood pressure of ≥140 mmHg or a diastolic blood pressure of ≥90 mmHg in the chronic stage or previous medical records. Dyslipidemia was diagnosed based on a low-density lipoprotein cholesterol level of ≥140 mg/dL, a high-density lipoprotein cholesterol level of <40 mg/dL, or a triglyceride level of ≥150 mg/dL on admission or previous medical records. Diabetes mellitus was diagnosed according to the diagnostic criteria of the Japan Diabetes Society 17 or based on previous medical records. Reperfusion success was defined as a modified Thrombolysis in Cerebral Ischemia grade of 2b to 3.
Outcome measure
The outcome measure was set as good functional outcome at 90 days after EVT. Good functional outcome was defined as a modified Rankin Scale score of 0 to 2. Follow-up to assess the outcome measure was performed at 90 days after EVT by an outpatient visit or a telephone survey for patients with too severe after effects to attend the outpatient clinic.
Statistical analysis
Baseline characteristics between patients dichotomized by the median FVH-DWI mismatch score were compared using the t-test, the chi-squared test, or the Mann-Whitney U test, as appropriate. The association between FVH-DWI mismatch score and good functional outcome at 90 days after EVT was assessed using the Cochran-Armitage test for trend and crude and adjusted logistic regression models. FVH-DWI mismatch score, age, sex, and variables with statistical significance in univariate analysis were entered into the adjusted model. All reported P values were two-sided. A P value of <0.05 was considered to indicate statistical significance. Statistical analyses were performed using JMP software (version 12.2.0, SAS Institute Inc., Cary, NC, USA).
Results
Of 196 consecutive patients who underwent EVT for acute ICA or MCA-M1 occlusion, 32 without brain MRI before EVT were excluded, and the remaining 164 were analyzed. The median FVH-DWI mismatch score was 2 (interquartile range, 0 to 4). Baseline characteristics between patients dichotomized by the median FVH-DWI mismatch score are shown in Table 1. Significant differences were identified in terms of initial NIHSS score (P <0.001), DWI-ASPECTS (P <0.001), and reperfusion success (P = 0.046). In addition, baseline characteristics between patients dichotomized by the presence or absence of FVH-DWI mismatch are shown in Supplemental table 1.
Table 1.
Baseline characteristics between patients dichotomized by the median FVH-DWI mismatch score.
| Baseline characteristic | Total (n = 164) | FVH-DWI mismatch score | P value | |
|---|---|---|---|---|
| ≤2 (n = 88) | >2 (n = 76) | |||
| Age, y | 76 ± 13 | 77 ± 12 | 74 ± 14 | 0.087 |
| Male sex | 81 (49) | 41 (47) | 40 (53) | 0.440 |
| Premorbid mRS score | 0 [0–2] | 0 [0–2] | 0 [0–2] | 0.054 |
| Hypertension | 110 (67) | 54 (61) | 56 (74) | 0.094 |
| Dyslipidemia | 69 (42) | 34 (39) | 35 (46) | 0.337 |
| Diabetes mellitus | 40 (24) | 18 (20) | 22 (29) | 0.207 |
| Previous stroke | 31 (19) | 15 (17) | 16 (21) | 0.513 |
| Atrial fibrillation | 82 (50) | 47 (53) | 34 (45) | 0.268 |
| Initial NIHSS score | 17 [12–23] | 20 [14–25] | 14 [10–22] | <0.001 |
| DWI-ASPECTS | 7 [4–9] | 5 [3–7] | 8 [7–9] | <0.001 |
| Intravenous thrombolysis | 56 (34) | 27 (31) | 29 (38) | 0.314 |
| Onset-to-door time, min | 161 [58–393] | 159 [69–476] | 170 [56–381] | 0.773 |
| Onset-to-puncture time, min | 226 [152–505] | 208 [152–550] | 256 [151–426] | 0.804 |
| Onset-to-reperfusion time, min | 305 [215–590] | 285 [205–628] | 335 [222–599] | 0.315 |
| Reperfusion success | 146 (89) | 75 (85) | 72 (95) | 0.046 |
Data are presented as mean ± standard deviation, n (%), or median [interquartile range].
ASPECTS indicates Alberta Stroke Program Early CT Score; DWI, diffusion-weighted imaging; FVH, fluid-attenuated inversion recovery vascular hyperintensity; mRS, modified Rankin Scale; and NIHSS, National Institutes of Health Stroke Scale.
At 90 days after EVT, 2 patients were lost-to follow-up, and 73 had good functional outcome. The frequency of good functional outcome at 90 days after EVT according to FVH-DWI mismatch score is shown in Figure 2. The frequency of good functional outcome at 90 days after EVT increased significantly with increasing FVH-DWI mismatch score (P for trend <0.001). Odds ratios for good functional outcome at 90 days after EVT in logistic regression models are shown in Table 2. FVH-DWI mismatch score was independently associated with good functional outcome at 90 days after onset (adjusted odds ratio per 1 point, 1.46; 95% confidence interval, 1.15–1.89).
Figure 2.
Frequency of good functional outcome at 90 days after endovascular reperfusion therapy (EVT) according to fluid-attenuated inversion recovery vascular hyperintensity (FVH)-diffusion-weighted imaging (DWI) mismatch score.
Table 2.
Odds ratios for good functional outcome at 90 days after endovascular reperfusion therapy in logistic regression models.
| Variable | Crude | Adjusted* | ||
|---|---|---|---|---|
| OR | 95% CI | OR | 95% CI | |
| FVH-DWI mismatch score (per 1 point) | 1.53 | 1.30–1.82 | 1.46 | 1.15–1.89 |
| Age (per decade) | 0.32 | 0.21–0.47 | 0.32 | 0.19–0.51 |
| Male sex | 2.76 | 1.46–5.28 | 1.67 | 0.68–4.15 |
| Initial NIHSS score (per 1 point) | 0.89 | 0.85–0.94 | 0.93 | 0.87–0.98 |
| DWI-ASPECTS (per 1 point) | 1.28 | 1.13–1.47 | 1.10 | 0.89–1.37 |
| Reperfusion success | 15.78 | 3.09–288.39 | 10.45 | 1.69–204.60 |
*Adjusted for FVH-DWI mismatch score, age, sex, initial NIHSS score, DWI-ASPECTS, and reperfusion success.
ASPECTS indicates Alberta Stroke Program Early CT Score; CI, confidence interval; DWI, diffusion-weighted imaging; FVH, fluid-attenuated inversion recovery vascular hyperintensity; NIHSS, National Institutes of Health Stroke Scale; and OR, odds ratio.
Discussion
To test the hypothesis that FVH-DWI mismatch is a predictor of functional outcome after EVT for acute ischemic stroke, the association between FVH-DWI mismatch and functional outcome at 90 days after EVT for acute ICA or MCA-M1 occlusion was assessed in the present observational study. The present results clearly showed a positive association between large FVH-DWI mismatch and good functional outcome after EVT.
Numerous previous studies assessed the prognostic value of FVH in patients with acute ischemic stroke.18–24 However, results of these studies lack consensus, which can be attributed to differences in study populations, outcome measures, and classifications of FVH. Of classifications of FVH, FVH-DWI mismatch was reported to have a good prognostic value especially in patients who underwent EVT for acute ischemic stroke.22–24 To the best of our knowledge, only one previous study treated FVH-DWI mismatch as a quantified variable. 22 Our method for quantifying FVH-DWI mismatch was more simple than the method used in this study but could show a positive association between large FVH-DWI mismatch and good functional outcome after EVT.
FVH represents retrograde slow blood flow through leptomeningeal collaterals distal to large-artery occlusion3,5,6 and is associated with good collateral status.7–9 For instance, a previous study showed a positive association between extended FVH and good collateral status on cerebral angiography defined as American Society of Interventional and Therapeutic Neuroradiology grade 25 3 to 4 in patients who underwent EVT for acute MCA-M1 occlusion. 9 On the other hand, the DWI lesion represents infarct core. Therefore, FVH-DWI mismatch may represent penumbral tissue with good collateral status. It seems reasonable that large FVH-DWI mismatch would be associated with good functional outcome after EVT for acute ischemic stroke because good collateral flow limits infarct growth and extends the therapeutic time window for EVT. 26 FVH-DWI mismatch may be useful for identifying good responders to EVT.
The present study has some limitations. First, the sample size was small (n = 164), as in previous similar studies.22–24 Second, 32 of 196 consecutive patients (16%) who underwent EVT for acute ICA or MCA-M1 occlusion were excluded due to lack of brain MRI before EVT. Third, the present findings might be specific to our techniques and machines because of the single-center study design. Fourth, both a small spotty lesion and a large diffuse lesion in an ASPECTS area are regarded as 1 point regardless of the size in the ASPECTS grading system. Finally, the present findings cannot be generalized to all patients who undergo EVT for acute ischemic stroke because the present study targeted those who underwent EVT for acute ICA or MCA-M1 occlusion.
Conclusions
Patients with large FVH-DWI mismatch had good functional outcome after EVT for acute ICA or MCA-M1 occlusion. The present findings indicate that FVH-DWI mismatch is a predictor of functional outcome after EVT for acute ischemic stroke.
Supplemental Material
Supplemental material, sj-docx-1-ine-10.1177_15910199221113900 for Fluid-attenuated inversion recovery vascular hyperintensity-diffusion-weighted imaging mismatch and functional outcome after endovascular reperfusion therapy for acute ischemic stroke by Keisuke Tokunaga, So Tokunaga, Kenta Hara, Masahiro Yasaka, Yasushi Okada, Takanari Kitazono and Tomoyuki Tsumoto in Interventional Neuroradiology
Footnotes
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical approval: Study procedures were reviewed and approved by the institutional review board of Kyushu Medical Center.
Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.
Supplemental material: Supplemental material for this article is available online.
ORCID iD: Keisuke Tokunagahttps://orcid.org/0000-0002-0701-3635
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Supplementary Materials
Supplemental material, sj-docx-1-ine-10.1177_15910199221113900 for Fluid-attenuated inversion recovery vascular hyperintensity-diffusion-weighted imaging mismatch and functional outcome after endovascular reperfusion therapy for acute ischemic stroke by Keisuke Tokunaga, So Tokunaga, Kenta Hara, Masahiro Yasaka, Yasushi Okada, Takanari Kitazono and Tomoyuki Tsumoto in Interventional Neuroradiology