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T2 relaxation times identify acute ischaemic stroke patients within the thrombolysis treatment window with higher accuracy than T2-weighted signal intensities
Bryony McGarry1, Isabel Chew1, Robin Damion1, Michael Knight1, Rose Bosnell2, Peter Jezzard3, George Harston 3, Davide Carone 3, James Kennedy 3, Salwa El-Tawil 4, Jennifer Elliot4, Keith Muir4, Philip Clatworthy2, and Risto Kauppinen1

1School of Psychological Science, University of Bristol, Bristol, United Kingdom, 2North Bristol NHS Trust, Bristol, United Kingdom, 3University of Oxford, Oxford, United Kingdom, 4University of Glasgow, Glasgow, United Kingdom

Synopsis

Unknown symptom onset time is a common contraindication for thrombolysis of hyperacute ischaemic stroke. MRI may identify patients within the 4.5-hour thrombolysis treatment window, but it is unclear which parameter is most accurate. We compared the ability of hemispheric differences in quantitative T2 (qT2), ADC, and signal intensities of DWI, T2-weighted and T2-weighted FLAIR images at distinguishing between patients scanned within and beyond 4.5-hours. qT2 correlated significantly with time from onset (r = .491, p =.003) and had the highest and only significant AUC (0.77, p = .007). These data point to qT2 as a stroke timer.

Introduction

Unknown time of symptom onset is a common contraindication for thrombolysis of ischaemic stroke due to increased risk of haemorrhage and other clinically adverse events with time.1 Multiparametric MRI may help identify patients within the 4.5-hour thrombolysis treatment window.2 ADC declines immediately enabling detection of ischaemic tissue.3 Preclinical4-6 and patient7,8 studies found for some MR parameters, differences in signal between ischaemic and non-ischaemic tissue show time dependency, enabling stroke onset time to be estimated with varying levels of accuracy. We compared the ability of hemispheric differences in quantitative T2 (qT2), ADC, and signal intensities of DWI, T2-weighted (T2-w) and T2-w FLAIR images at distinguishing between cases scanned within and beyond 4.5-hours in the same patient cohort.

Methods

35 acute ischaemic stroke patients with onset time < 9 hours were scanned at 3T with a 32-channel head-coil. Protocol included DWI for ADC maps and localisation of ischaemia, multi-echo T2 for T2-w images and qT2 maps, T2-w FLAIR and 3DT1 for anatomical reference and co-registration. To produce a single T2-w image from the multi-echo sequence, all echoes of the TE series were summed to produce a ‘sum-over-echoes’ image. qT2 maps were computed from a voxel-wise mono-exponential fit to a logarithmic space. All images were resampled to 1mm isotropic resolution and co-registered to the T1-weighted image which was registered to MNI space to ensure correct alignment across the midline. Ischaemic VOIs were defined with ADC values > 0.2 – 0.4 um2 ms-1 and < 0.55 – 0.6 um2 ms-1, and < one HWHM from the median non-ischaemic ADC, and qT2 > 30ms and < 200ms to reduce CSF contribution. Hemispheric differences were determined by creating mirror VOIs and calculating relative signal intensity ratios (rSIs, Figure 1). The inverse rSI was used for ADC.

Results

Significant correlations with time from symptom onset were found for rqT2 (r = .491, p =.003) and T2-w (r = .364, p = .032), but not rADC (r = -.229, p =.186), rDWI (r =.247, p = .153) or rFLAIR (r =.056, p = .831). Figure 2 shows ROC curves and AUCs for distinguishing between scans performed within and beyond 4.5-hours. rqT2 had the highest and only significant AUC (0.77, p = .007). Non-parametric pairwise comparisons9 showed AUCs did not differ significantly (p > .05).

Discussion

The data support rqT2 as a MRI parameter for estimating stroke onset time. rqT2 shows time dependency and was the only parameter with a significant AUC, demonstrating an ability to distinguish between patients scanned within and beyond 4.5-hours. rqT2 results are consistent with studies involving preclinical stroke models4,5 and patients.8 rADC, rDWI, rFLAIR and rT2-w had non-significant AUCs, suggesting they may have low value in hyperacute stroke timing. It should be stressed that although T2 relaxation influences signal of T2-w images, there is added uncertainty caused by bias field problems and the influence of proton density and T1 relaxation, which also change during ischaemia.10

Conclusion

rqT2 shows promise for hyperacute stroke timing. qT2 is less prone to sources of confounding factors in hyperacute stroke, such as T1 and proton density, than respective weighted signals. ADC and qT2 can be acquired within a few minutes and post-processing can be easily automated to expedite clinical exploitation in stroke clinics.

Acknowledgements

The study is funded by the Dunhill Medical Trust (R385/1114). We acknowledge the support of Engineering and Physical Sciences Research Council (EPSRC) for PhD studentship funding as well as the support of the National Institute for Health Research Clinical Research Network (NIHR CRN).

References

1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 h after acute ischemic stroke. N Engl J Med. 2008; 359:1317–1329.

2. Thomalla G, Cheng B, Ebinger M, et al. DWI-FLAIR mismatch for the identification of patients with acute ischaemic stroke within 4·5 h of symptom onset (PRE-FLAIR): a multicentre observational study. Lancet Neurol. 2011; 10:978–986.

3. Knight RA, Dereski MO, Helpern JA, et al. Magnetic resonance imaging assessment of evolving focal cerebral ischemia. Comparison with histopathology in rats. Stroke. 1994; 25:1252–1261.

4. McGarry BL, Rogers HJ, Knight MJ, et al. Determining Stroke Onset Time Using Quantitative MRI: High Accuracy, Sensitivity and Specificity Obtained from Magnetic Resonance Relaxation Times. Cerebrovasc Dis Extra. 2016; 6:60-65.

5. McGarry BL, Rogers HJ, Knight MJ, et al. Stroke onset time estimation from multispectral quantitative magnetic resonance imaging in a rat model of focal permanent cerebral ischemia. Int J Stroke. 2016; 11(6), 677–682.

6. Liu S, Xu X, Cheng Q, et al. Simple quantitative measurement based on DWI to objectively judge DWI-FLAIR mismatch in a canine stroke model. Diagn Interv Radiol. 2015;21(4):348-54.

7. Song SS, Latour LL, Ritter CH, et al. A pragmatic approach using magnetic resonance imaging to treat ischemic strokes of unknown onset time in a thrombolytic trial. Stroke. 2012;43(9):2331-5.

8. Siemonsen S, Mouridsen K, Holst B, et al. Quantitative T2 values predict time from symptom onset in acute stroke patients. Stroke. 2009; 40:1612–1616.

9. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing areas under two or more correlated receiver operating characteristics curves: a nonparametric approach. Biometrics. 1988;44(3):837–845.

10. Kauppinen RA. Multiparametric magnetic resonance imaging of acute experimental brain ischaemia. Prog Nucl Magn Reson Spectrosc. 2014; 80:12-25.

Figures

Figure 1. Example of analysis steps from one patient (onset time = 6 hours 49 mins). 1. images were co-registered to the T1-w image (1mm isotropic, MNI co-coordinate frame). 2. Ischaemic VOI defined using ADC criteria described. 3. Mirror VOI created by reflecting ischaemic VOI across vertical axis. To avoid CSF, ADC and qT2 limits were applied and VOIs were manually edited if necessary. 4. To normalise data and allow cross-comparison between parameters, relative signal intensity ratios (rSIs) were computed. *SI = signal intensity, rSI = relative signal intensity ratio.

Figure 2. ROC curves and AUCs with 95% confidence intervals (CI) of each rSI for distinguishing between scans performed within and beyond 4.5 hours from symptom onset.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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