ACUTE STROKE IMAGING

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1 ACUTE STROKE IMAGING Mahesh V. Jayaraman M.D. Director, Inter ventional Neuroradiology Associate Professor Depar tments of Diagnostic Imaging and Neurosurger y Alper t Medical School at Brown University

2 CME DISCLOSURE No financial conflicts of interest No off-label use will be discussed I have certain biases regarding value of NCCT, MRI, CT Perfusion and MR perfusion which should become apparent during this presentation

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4 BASIS OF STROKE IMAGING Need to understand the role of imaging in acute ischemic stroke Both CT and MRI play a vital role in these patients

5 ACUTE IMAGING (0-6H) Imaging is done to triage patients for revascularization therapy (IV or IA) Primary goal of imaging (CT or MR) is to exclude ineligible patients rather than include eligible patients ( rule out ) Exclude those with hemorrhage Exclude those with mass lesion Exclude those with large, completed infarction Imaging criteria for IV tpa will vary from those for IA therapy

6 CT: IT S ALL ABOUT THE DENSITY CT measures dif ferences in density between tissues What s in the brain? Water Fat (especially in white matter) Blood (in vessels, hopefully ) Acutely, changes on CT are reflective of either changes in the amount of water, or addition of hemorrhage

7 CT: NORMAL GREY-WHITE DENSIT Y

8 ACUTE STROKE: IMAGING ON CT Changes on CT scan are subtle, especially early on in stroke As cells in cortex infarct, they lose the ability to maintain membrane integrity and swell with water This results in loss of normal difference in density between grey and white matter Cytotoxic edema

9 STROKE: NONCONTRAST CT

10 LARGE VASCULAR TERRITORIES ACA MCA PCA

11 STROKE: EARLY SIGNS ON CT Slight hypodensity in cortex Slight loss of grey-white dif ferentiation Sulcal ef facement Dense vessel Loss of insular ribbon in MCA stroke Insular cortex farthest from pial collaterals

12 STROKE IMAGING: CT PEARLS Early findings are very subtle Only 10 Houndsfield units separate normal grey from white matter Large vessel ischemia easier to see with smaller images i.e., you are looking at the forest, not the trees!

13 STROKE CT: WINDOWING Window Width 80, Center 40 Window Width 20, Center 34

14 STROKE CT: SMALLER IMAGES

15 ANOTHER EXAMPLE

16 Acute hemorrhage NCCT: IV TPA EXCLUSIONS

17 NCCT: IV TPA EXCLUSIONS Acute Hemorrhage Mass with or without hemorrhage

18 NCCT: IV TPA EXCLUSIONS Acute Hemorrhage Mass with or without hemorrhage Large territorial infarction with edema

19 ACUTE STROKE: IMAGING ON MR Diffusion weighted MR is the most sensitive way to detect acute infarction Looks for lack of free water diffusion due to loss of normal Na+/K+ ATPase function In contrast to CT, these changes are readily seen

20 DIFFUSION MR: EXAMPLES

21 MR: PROS AND CONS Allows for easy identification of large territorial stroke (DWI) Similar sensitivity to CT for acute hemorrhage Can characterize lesions seen on NCCT Additional time to obtain imaging may delay therapy Not always available at all centers MR safety, cooperation and screening issues, especially with aphasic patient

22 IMAGING PRIOR TO IA THERAPY Intra-arterial therapy with mechanical thrombectomy remains a viable treatment option in many patients with acute large vessel occlusion Not all patients are eligible for IV tpa Some patients fail to improve after IV tpa Similar to imaging prior to IV tpa, imaging prior to IA is done to exclude ( rule out ) Some centers also use imaging modalities to include ( rule in )

23 THE CORE-PENUMBRA MODEL Infarct Core Ischemic Penumbra Penumbral tissue is not functioning due to lack of blood flow, but is salvageable. Patient s symptoms from both infarct core and penumbra.

24 WHICH PATIENT IS MOST LIKELY TO BENEFIT FROM IA THERAPY? Ischemic Penumbra Infarct Core Ischemic Penumbra Infarct Core Ischemic Penumbra Infarct Core Ischemic Penumbra

25 HOW DO YOU TELL THEM APART? Ischemic Penumbra Infarct Core NIHSS 10 AND Proximal Arterial Occlusive Lesion Ischemic Penumbra Infarct Core Ischemic Penumbra Infarct Core Ischemic Penumbra

26 HOW DO YOU TELL THEM APART? Ischemic Penumbra Infarct Core Ischemic Penumbra Infarct Core Major difference between these two patients is the size of the infarct core Ischemic Is there a critical core size beyond which reperfusion Penumbra Ischemic is not helpful? Infarct Core Penumbra How can that core be assessed using imaging?

27 INFARCT CORE: HOW BIG IS TOO BIG? Multiple studies using diffusion weighted imaging have shown that there exists a critical size beyond which reperfusion does not improve outcomes 100 ml Albers et al. DEFUSE (2006) 70 ml Yoo et al. (2009) 65 ml Parsons et al. EPITHET (2010) Ischemic Penumbra Infarct Core How big is 100 ml tissue? How can we measure this with imaging?

28 HOW MUCH IS 100ML TISSUE? Volume of the MCA territory estimated at ~300 cc tissue Current DWI based literature suggests that infarct core volume somewhere between 1/4 and 1/3 of the MCA is the point beyond which reperfusion may not help Haven t we known this? ECASS (1995) Patients with > 1/3 MCA territory abnormality on NCCT had high rates of symptomatic hemorrhage and did not appear to benefit from IV tpa PROACT (1998) 5/5 Patients with >1/3 hemisphere hypodensity on NCCT had hemorrhagic transformation and poor clinical outcomes

29 CAN YOU ESTIMATE THE LARGE CORE FROM NCCT ALONE? ASPECTS is a quick and easy method to quantify degree of abnormality on NCCT Scored = Normal 0 = Entire MCA territory infarcted Can you detect an ~70 ml DWI lesion using NCCT?

30 ESTIMATING 1/3 MCA INFARCTION USING ASPECTS Review of 40 CT scans in acute ischemic stroke patients. ASPECTS score compared against consensus of 5 Neuroradiologists on >1/3 MCA infarction. Demaerschalk et al. Can J Neurol Sci. May 2006

31 RESULTS - ROC Optimal cut point was ASPECTS of <7 for detecting 1/3 MCA infarction 94% Sens, 98% Spec No patients with ASPECTS >8 had 1/3 MCA infarction on NCCT Demaerschalk et al. Can J Neurol Sci. May 2006

32 ASPECTS EXAMPLE ASPECTS = 8 Points off for M2 and M5 cortical regions

33 ASPECTS = 5 Points off for posterior Insula, M2, M3, M5 and M6 cortical regions ASPECTS EXAMPLE

34 ASPECTS = 2 Points off for putamen, Insula, and all cortical regions ANOTHER EXAMPLE

35 CTA When CTA is used to confirm proximal vessel occlusion, the lack of distal vascular filling is a poor prognostic sign Absent filling of entire MCA territory beyond occlusion on CTA strongly predictive of >100 ml DWI abnormality Sousa et al. AJNR August 2012

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37 CTA 90 MINUTES AFTER ONSET

38 WHICH PATIENT IS MOST LIKELY TO BENEFIT FROM IA THERAPY? Ischemic Penumbra Infarct Core DWI Lesion 70 ml OR NCCT ASPECTS > 7 Ischemic Penumbra Infarct Core Ischemic Penumbra NIHSS 10 AND Proximal Arterial Occlusive Lesion Infarct Core Ischemic Penumbra

39 IS ASPECTS RELIABLE PREDICTOR OF GOOD OUTCOME? Retrospective analysis of prospectively randomized patients in PROACT II trial Patients with MCA occlusion were randomized to intra -arterial Pro-Urokinase or placebo infusion No IV tpa given (patients were primarily those beyond 3 hours or excluded from IV tpa) Dichotomized admission NCCT into ASPECTS > 7 or not Hill et al. Stroke 2003

40 ASPECTS IN PROACT ASPECTS 7 Recanalization ASPECTS > 7 Control Pro-UK Control Pro-UK 11.10% 22.20% 58.70% 69.50% ASPECTS 7 mrs 0-2 ASPECTS > 7 Control Pro-UK Control Pro-UK 16.20% 27.20% 33.60% Benefit of recanalization is greatly diminished in patients with baseline NCCT ASPECTS % Hill et al. Stroke 2003

41 MR-RESCUE: IMAGING BASED SELECTION? Randomized patients within 8 hours of onset to thrombectomy (Merci or Penumbra) or standard therapy IV treatment failures eligible All patients had pre-treatment CTP or MR Favorable pattern = Infarct core 90mL or less and proportion of predicted infarct 70% or less (~1/3 of territory infarcted) Imaging analyzed off site, treating local physicians blinded to penumbral or non-penumbral pattern Kidwell et al. NEJM Feb

42 MR-RESCUE Kidwell et al. NEJM Feb

43 MR-RESCUE Kidwell et al. NEJM Feb

44 MR-RESCUE Penumbral pattern does not help select patients for thrombectomy at late time windows (>6 hours) Using MR (or CT) based selection does not help select patients in the extended (>6h) time window Treating patients with large infarct core (>1/3 MCA) not beneficial Patients with persistent smaller infarct cores at late time windows may not go on to infarct Kidwell et al. NEJM Feb

45 IMAGING ADDS TIME No studies have shown improved outcomes with additional imaging Retrospective, multicenter analysis of relationship between pre-treatment imaging and time to treatment showed NCCT (n=286) CTP (n=190) MRI (n=80) Median time from imaging to groin access 61 minutes 114 minutes 124 minutes Successful reperfusion 61% 59% 54% Good outcome 37% 38% 32% Symptomatic Hemorrhage 7% 6% 5% Sheth et al. JNIS 2013

46 IMAGING BEFORE IA: WHAT WE KNOW Clinical assessment of patient (NIHSS) combined with a proximal arterial occlusion gives a robust assessment of volume of tissue at risk Use of imaging based selection does not appear to help select patients for IA therapy Key factor prior to IA therapy is likely the volume of infarct core Greater than 70 ml infarct core likely poor prognosis even with therapy Core volume can be calculated from DWI-MRI or estimated with ASPECTS on NCCT

47 EVOLUTION AND HEMORRHAGE

48 STROKE: SUBACUTE Imaging beyond the acute period is done for two main reasons: Look for progression of edema or midline shift from a large territorial infarction Determine presence or extent of hemorrhage following acute thrombolytic therapy

49 EVOLUTION OF INFARCTION Subtle gyral swelling leads to sulcal ef facement Swelling peaks at hours

50 HEMORRHAGE AFTER THROMBOYSIS New intracranial hemorrhage after thrombolysis is a feared complication But the term hemorrhagic transformation is generic No prognostic information ECASS classified hemorrhage into different types in the setting of recent ischemic stroke Not to be used for primary intracerebral hemorrhage

51 ECASS CLASSIFICATION Hemorrhagic Infarction HI1 HI2 Small petechial hemorrhage Commonly seen on MRI More confluent petechial hemorrhage Parenchymal hematoma PH1 Hemorrhage in <30% of infarcted area with minimal mass effect PH2 Large space occupying hematoma with mass effect

52 SELF-EVALUATION QUESTIONS

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55 SUMMARY

56 ACUTE STROKE IMAGING Imaging is primarily done to exclude ineligible patients from IV tpa Acute hemorrhage Mass Completed infarct with edema Key imaging factor prior to IA therapy is size of infarct core Core > 70 ml associated with poor prognosis This can be quantified with MRI or estimated with NCCT-ASPECTS Imaging based selection for IA therapy has not panned out May be taking those patients who are likely to do well!

57 THANK YOU!