Role of MRI in acute stroke patients for thrombolysis

1. Role of MRI in acute stroke patients for thrombolysis D Šaňák, D Horák, A Bártková, I Vlachová, S Buřval, M Král, M Heřman, P Kaňovský Stroke Centre, Dept. Of Neurology and Radiology, University Hospital Olomouc

2. What we alreadyknow…. • MRI may help to identify patients, who have the most potential to benefit from thrombolytic therapy Rotta et al., N Eng J Med 1997; Schellinger et al., Stroke 2000; Ann Neur 2001;Fiebach et al., 2001; Röther et al., Stroke 2002; Shilh et all., Stroke 2003; Dávalos et al., Neurology 2004, Barber et al,J Neuroimaging 2004; Hacke et al., Stroke 2005; Ribo et al., Stroke 2005.

3. Nevertheless, up to date, few studies have evaluated the impact of „pre-treatment“ MRI parameters on the resulting clinical outcomeafter thrombolysis… Röther J et al. , Stroke 2002; Dávalos A et al. , Neurology 2004; Nighoghossian N et al., Stroke 2003. Derex L et al., J Neur Sci 2004, Prosser et al, Stroke 2005,

4. Is MRI really useful for thrombolysis?

5. Inspiration….. • MRI improves diagnostics of acute cerebral infarction • quantification of actual infarct volume • accurate infarctlocalization using diffusion-weighted images Warach et al., Neurology 1992; Ay et al., Neurology 1999; Oppenheimet al., Neuroradiology 2000, Stroke 2000;Jansen et al., 2002; Mullins et al., Radiology 2002, Am J Roentgenol 2000

6. Idea…. • Assess the influence of initial infarct volume on resulting clinical outcome in acute stroke patients with MCA occlusion, who underwent IVT/IAT • Does „mismatch“ between stroke severity (NIHSS) and infarct volume on DWI predict follow-up infarct progression and response to thrombolysis?

7. Study 1: design • 25 consecutive acute ischemic stroke patients with MCA occlusion (M1-2 segment) - detected on MR angiography • Underwent IVT or IATaccording the recent guidelines*between January and September 2005 • Stroke severity (NIHSS, mRS) • MRI stroke protocol (EPI-DWI, T2, FLAIR, MRA) • Infarct volume quantification on DWI (b-1000) *EUSI Recommendations for stroke management update 2003. Highasida RT, Furlan AJ. Trial design and reporting standards for intra-arterial cerebral thrombolysis for acute ischemic stroke. Stroke 2004.

8. MRI • Magnetom Symphony 1.5 T Maestro Class(Siemens, Erlangen, Germany), Quantum gradients (syngo2004A) • MRI protocol: • Localizer • T2TSE (Turbo Spin Echo) • FLAIR • EPI-DWI • 3D TOF MRA Total acquisition time: 11:28 min.

9. Subject demographicand clinical characteristics

10. Relation between initial infarct volume (VDWI-I) andstroke severity (NIHSS)

11. Analysis • Relation between the initial infarct volume and neurological deficit severity was assessed, defining a cut-off point for maximum VDWI-I associated still with a good clinical outcome • Several cut-off points of VDWI-I were subsequently tested with the goal to maximize both sensitivity and specificity for good clinical outcome (mRS 0-2)

12. Cut-off point of maximum VDWI-I still associated with a good clinical outcomeand corresponding tomaximum achieved sensitivity and specificity (80%)

13. Resulting cut-off point divided the patients into 2 subgroups (VDWI-I ≤ 70 ml; >70 ml)

14. Relationship between the initial infarct volume and 24-hour clinical outcome

15. Resulting cut-off point divided the patients into 2 subgroups (VDWI-I ≤ 70 ml; >70 ml)

16. Relationship between the initial infarct volume and 90-day clinical outcome

17. 90-day mortality • 71.5 % in Subgroup VDWI-I >70 ml versus 0 % in SubgroupVDWI-I ≤ 70 ml • All these patients died within first 7 days after thrombolysis • brain edema was the cause of death in all cases • additionally, intracranial hemorrhage occurred in 3 out of these patients.

18. Discussion • We did not find any direct relation between the initial infarct volume measured on DWI and the neurological deficit on admission • Two patients with the same severity of deficit and the same type of arterial occlusion (MCA, M1-2 segment) can have VDWI-I differing by as much as tens of ml • This difference is mainly caused by the individual actual state of cerebral collateral flow

19. Comparison of different initial infarct volumes in two patients with MCA occlusion on admission

20. Quantification of initial infarct volume could predict clinical outcome in acute stroke patients with MCA occlusion treated by intravenous/intra-arterial thrombolysis. • Patients with VDWI-I ≤ 70 ml had significantly better resulting outcome. Sanak et al., Neuroradiology 2006; 48: 632-639.

21. To be continued…

22. „Mismatch problem…..“ • Patients with PWI/DWI mismatch may have higher benefit from thrombolytic therapy even beyond 3 hours than patients without mismatch Alberts et al., Stroke 1999; Parsons et al., Ann Neurol 2002, Hacke et al., Neurology 1999; Shih et al., Stroke 2003

23. PWI/DWI mismatch concept DWI and PWI Lesions are equivalent PWI ischemia DWI infarction Mismatch: PWI > DWI Non-mismatch

24. PWI/DWI mismatch CBF DWI TTP CBV

25. „Mismatch problem…..“ • Although the PWI/DWI mismatch is largely used in stroke studies and clinical routine, the concept is still controversial: • Several different definitions of PWI/DWI mismatch are established • limitation of accuracy of PWI technique is still under discussion • PWI cannot also reliably distinguish the benign oligemia and real penumbra Barber et al., Neurology 1999; J Neuroimaging 2004; Chalela et al., Ann Neurol 2004; Hacke et al, Stroke 2005;Ribo et al, Stroke 2005; Simonsen et al, Magn Res Imaging 2000; Smith et al, Magn Res Imaging 2000; Zacharchuk et al, J Cereb Flow Met 2000; Grandin et al., Radiology 2000.

26. New approach: Clinical-DWI mismatch • Mismatch between stroke severity (assessed with NIHSS) and infarct volume on DWI predict follow-up infarct expansion and response to thrombolysis • An NIHSS  8 and DWI infarct volume  25 ml was defined as a clinical-diffusion mismatch (CDM) • CDM could besurrogate for PWI/DWI mismatch. Dávalos A et al. Neurology 2004; 62: 2187-2192. Prosser J et al. Stroke 2005; 36: 1700-1704.

27. Does the CDM predict good clinical outcome in acute stroke patients treated with IVT? • to compare acute ischemic stroke patients with and without CDM treated by intravenous thrombolysis (IVT) within 3 hours in: • infarct growth • clinical outcome • incidence of intracerebral hemorrhage

28. Study 2: design • Seventy-nine patients treated with IVT between IX/2004 and XII/2006 at our stroke unit • CDM was defined as NIHSS  8 and DWI volume ≤ 25 ml • non-CDM as NIHSS  8 and DWI > 25 ml. • DWI infarct volume was measured on DWI. • Neurological deficit was evaluated using NIHSS and mRS. • Independent Samples, Chi-Square and Fisher's exact test were used for statistical evaluation

29. Patient demographic and baseline characteristics

30. Results

31. CDM - discussion • CDM indicates the existence of a large volume of tissue at risk of infarction* • Patients with the CDM had significantly better 90day clinical outcome and less ICH* • Patients without CDM had higher infarct volume progression after 24 hours* • CDM should be prospectively tested as a predictor of response of thrombolysis between 3 and 6 hours from stroke onset *Sanak et al., Eur J Neurol 2007; 14 (Suppl 1): 69

32. Conclusions • Quantification of initial infarct volume could predict clinical outcome in acute stroke patients with MCA occlusion treated by IVT/IAT. • Patients with VDWI-I ≤ 70 ml had significantly betterresulting outcome • CDM may help identify patients with higher benefit from thrombolysis. • Patients with CDM had significantly better 90day clinical outcome and significantly less ICH.

33. Is MRI really useful for thrombolysis? Yes!Particularly beyond 3 hours*…… *EUSI Recommendations for Stroke Management.…..

34. Thank you for your attention!