Christian Federau1, Soren Christensen1, Michael Mlynash1, Jenny Tsai1, Sun Kim1, Greg Zaharchuk1, Matus Straka1, Nishant Mishra1, Maarten Lansberg1, and Greg Albers1
1Stanford University, Stanford, CA, United States
Synopsis
We studied the evolution of the infarct volume between
an early post-revascularization scan (within 24 h of symptom onset) and day 5 in
patients of the CRISP and DEFUSE 2 cohort studies. On the early post-revascularization scan, FLAIR
lesions were smaller compared to DWI, but were larger at day 5. The early post-revascularization
stroke volume on DWI, compared to FLAIR, was closer, and correlated better with
the day 5 DWI and FLAIR lesion volumes. Together, our findings suggest that DWI
is a better early surrogate marker of stroke volume. Target Audience
Neurologists,
neuroradiologists, and scientists with an interest in clinical stroke trials.
Introduction
The best time-point and imaging modality for assessment
of final infarct volume in patients with stroke is unclear. Follow-up scans
within 24h are easy to obtain, because the patients are most of the time still
hospitalized, but may underestimate final infarct size, particularly in
patients who do not reperfuse. Scans at a later time point might be more exact,
but are more difficult to obtain, as patients might already be discharged home.
We studied the evolution of the infarct volume assessed within 24 h of symptom
onset, to the volume of the infarct on day 5, as assessed on both DWI and FLAIR
MRI.
Methods
The CTP to predict Response to recanalization in
Ischemic Stroke Project (CRISP1), and the Diffusion and Perfusion
Imaging Evaluation for Understanding Stroke Evolution 22 (DEFUSE 2),
were two NIH funded multicenter cohort studies of consecutive acute stroke
patients who underwent intraarterial thrombectomy. The subset of patients of
those two studies, who had DWI and FLAIR imaging both early post-revascularization
and at day 5, were included in this study. Exclusion criteria were parenchymal
bleeding (ECASS3 PH1 or PH2), malignant profile (infarct core
>70ml), and technically inadequate studies. Regions of interest of the
volume of the stroke were outlined by an experienced neuroradiologist. Lesion volumes were evaluated using median, interquartile
range, and correlation plots. Statistical significance was assessed using
two-tailed Wilcoxon signed rank and rank
sum tests. We compared
correlated and independent correlations using Steiger’s and Fisher’s Z-tests
respectively. Significance level was set to α<0.05. Further,
probabilistic stroke lesion maps, to visualize the anatomical extend of the
lesions as function of time (early post-revascularization and day 5) and
modality (DWI and FLAIR), were generated as follows: images with lesions on the
left side were flipped, and all images, together with their regions of
interest, were coregistered to the MNI template brain4 using MINC5.
Finally, in the subset of patients with known stroke onset time, we evaluated
the time dependence of the lesion growth on both modalities. We dichotomized
the patients into groups according to the timing of their early post-revascularization
scan: ≥18h vs <18 h after stroke onset.
Results
146/339 patients from the CRISP (91/201) and DEFUSE
2 (55/138) studies had DWI and FLAIR images acquired both early post-revascularization
(median 18.0 [12.4-23.9] hours after symptom onset) and at day 5. Of these, 31
were excluded due to parenchymal bleeding, 2 due to malignant profile, and 4
due to technically inadequate images. Therefore 109 patients were included (Table 1). Early post-revascularization stroke
lesions were centered on the basal ganglia (Fig. 1). Median infarct volume was smaller on FLAIR (19.4ml; [IQR] 7.0-42.3),
compared to DWI (22.5ml; 11.3-63.0; p<0.0001). On day 5, median infarct
volume was larger on FLAIR (52.1ml; 20.7-117.2) compared to DWI (35.5ml; 15.9-90.6;
p<0.0001), and median volume growth was greater on FLAIR (28.9ml; 10.8-68.5)
compared to DWI (10.0ml; 1.9-36.8; p<0.0001). Correlation between DWI and
FLAIR lesion volumes was better at day 5 (r = 0.968) than early post-revascularization
(r=0.923; p<0.001). Lesion volumes correlated strongly between early post-revascularization
and day 5, but the correlation was significantly stronger for DWI than FLAIR
(r=0.883 vs r=0.782; p=0.013) (Fig. 2).
Further, early post-revascularization DWI volumes correlated better than FLAIR
volumes with both day 5 FLAIR volumes (r=0.880 vs. 0.782; p<0.001) and day 5
DWI volumes (r=0.883 vs. 0.774; p<0.001)
(Fig. 2). Finally regarding the
timing, median volume growth on DWI was significantly smaller when the early post-revascularization
scan was obtained ≥18h post stroke onset (4.6ml; -0.7-12.8), compared to <18h
(13.3ml; 1.6-46.7; p=0.03), but were not significantly different on FLAIR (≥18h:
26.1ml; 11.8-56.9; <18h: 21.2ml; 5.4-56.8; p=0.65) (Fig. 3).
Conclusion
This study
suggests that early post-revascularization DWI is better than FLAIR for
predicting day 5 stroke lesion volume.
Acknowledgements
CF is supported by the Swiss National Science Foundation.References
1. Lansberg
et al, Int Stroke Conf, Feb 2016, Los Angeles 2. Lansberg et al, The Lancet
Neurology 2012;11(10):860-867. 3. Larrue et al, Stroke 2001;32(2):438-441. 4.
Fonov et al, NeuroImage 2011;54(1):313-327. 5.
http://www.bic.mni.mcgill.ca/ServicesSoftware/MINC.