1. Andrew W. Asimos, MD How Can We Use Advanced Neuroimaging in the ED to Optimize Treatment Options for Acute Stroke Patients?

2. Andrew W. Asimos, MD Andrew Asimos, MD Director of Emergency Stroke Care Carolinas Medical Center Charlotte, NC Adjunct Associate Professor Department of Emergency Medicine University of North Carolina School of Medicine at Chapel Hill

3. Andrew W. Asimos, MD Attending Physician Emergency Medicine Carolinas Medical Center Department of Emergency Medicine Charlotte, NC

4. Andrew W. Asimos, MD

5. Andrew Asimos, MD, FACEP Disclosure None related to the content of this presentation None related to the content of this presentation

6. Andrew Asimos, MD, FACEP Session Objectives Acknowledge latest guidelines and systematic review related to advanced neuroimaging Acknowledge latest guidelines and systematic review related to advanced neuroimaging Review important unenhanced CT concepts Review important unenhanced CT concepts Review CTA/CTP concepts and supporting data Review CTA/CTP concepts and supporting data Overview of latest MRI data Overview of latest MRI data

7. Andrew Asimos, MD, FACEP Clinical Questions What is the goal of initial neuroimaging for presumed acute stroke patients? How can CTP/CTA or MRI/MRA be utilized To optimize the use of IV tPA and the triage of ED stroke patients for advanced IR therapeutics? To detect the site of the vascular occlusion, and CTP (DWI/PWI) the size of the ischemic penumbra and the infarct core? To maximize the potential benefit and minimize risk when using IV tPA in ED stroke patients?

8. Andrew Asimos, MD, FACEP Clinical Questions What are perfusion scans, what do they demonstrate, and how are they interpreted? What software or technology is necessary for advanced neuroimaging? How can these capabilities be developed at my hospital? What usage of these advanced diagnostics is the standard of care in 2007?

9. Andrew Asimos, MD, FACEP Case: Patient presenting within 3 hour window 50 yo male 50 yo male CT less than 2 hours within symptom onset CT less than 2 hours within symptom onset Awake, alert, dysarthric Awake, alert, dysarthric Fixed right sided gaze Fixed right sided gaze Left sided weakness Left sided weakness

10. Andrew Asimos, MD, FACEP Case: Patient presenting within 3 hour window

11. Andrew Asimos, MD, FACEP Case: Patient presenting within 3 hour window BFBVTTPInitial

12. Andrew Asimos, MD, FACEP Case: “Wake up” Stroke 0735 at outside hospital

13. Andrew Asimos, MD, FACEP Case: “Wake up” Stroke

14. Andrew Asimos, MD, FACEP Case: “Wake up” Stroke 1030 at stroke center

15. Andrew Asimos, MD, FACEP Impact of Neuroimaging on Decision Making Both art and science to treatment decision making for acute stroke Both art and science to treatment decision making for acute stroke Lots of non-imaging related factors increase SICH risk after treatment with tPA Lots of non-imaging related factors increase SICH risk after treatment with tPA Average EM physician cannot keep up with advances in neuroradiologic technology and literature regarding its impact on decision making Average EM physician cannot keep up with advances in neuroradiologic technology and literature regarding its impact on decision making Guidelines cannot keep up Guidelines cannot keep up

16. Andrew Asimos, MD, FACEP Essential Imaging Questions Is there hemorrhage? Is there hemorrhage? Are findings consistent with acute ischemic stroke? Are findings consistent with acute ischemic stroke? Can this imaging modality’s results add to my risk/benefit analysis? Can this imaging modality’s results add to my risk/benefit analysis? Is there large vessel occlusion? Is there large vessel occlusion? Is there “irreversibly” infarcted core? Is there “irreversibly” infarcted core? Is there “salvageable” penumbra? Is there “salvageable” penumbra? Are other findings present that should be considered Are other findings present that should be considered Microbleeds Microbleeds Leukoaraiosis Leukoaraiosis

17. Andrew Asimos, MD, FACEP The Four P’s of Acute Stroke Imaging P arenchyma Assess early signs of acute stroke, rule out hemorrhage P ipes Assess intracranial and extracranial circulation for evidence of intravascular thrombus P erfusion Assess cerebral blood flow, blood volume, and mean transit time P enumbra Assess tissue at risk of dying if ischemia continues Rowley HA et al. Am J Neuroradiol 2001;22:599-601.

18. Andrew Asimos, MD, FACEP 2007 Imaging Guidelines Adams HP et al. Stroke 2007;38:1655-1711.

19. Andrew Asimos, MD, FACEP Systematic Review of DWI/PWI Mismatch and Thrombolysis in Acute Stroke

20. Andrew Asimos, MD, FACEP Class I Recommendations Imaging of the brain is recommended before initiating any specific therapy to treat acute ischemic stroke Imaging of the brain is recommended before initiating any specific therapy to treat acute ischemic stroke In most instances, CT will provide the information to make decisions about emergency management In most instances, CT will provide the information to make decisions about emergency management The brain imaging study should be interpreted by a physician with expertise in reading CT or MRI studies of the brain The brain imaging study should be interpreted by a physician with expertise in reading CT or MRI studies of the brain Some findings on CT, including the presence of a dense artery sign, are associated with poor outcomes after stroke Some findings on CT, including the presence of a dense artery sign, are associated with poor outcomes after stroke Multimodal CT and MRI may provide additional information that will improve diagnosis of ischemic stroke Multimodal CT and MRI may provide additional information that will improve diagnosis of ischemic stroke Adams HP et al. Stroke 2007;38:1655-1711.

21. Andrew Asimos, MD, FACEP Unenhanced CT: Beyond Hemorrhage

22. Andrew Asimos, MD, FACEP Unenhanced CT: HDMCA Sign Overall poor prognosis if HDMCA sign on CT Overall poor prognosis if HDMCA sign on CT Limited data suggest IV-t-PA ineffective in treating acute stroke in the setting of HDMCA sign Limited data suggest IV-t-PA ineffective in treating acute stroke in the setting of HDMCA sign Somford DM et al. Radiology 2002;223:667–671. Barber PA et al. Stroke 2001;32:84–88.

23. Andrew Asimos, MD, FACEP From the 2007 Guidelines “Several studies have suggested that perfusion CT may be able to differentiate thresholds of reversible and irreversible ischemia and thus identify the ischemic penumbra. 114,115 ” Klotz E et al. Eur J Radiol 1999; 30: 170–184. Wintermark M et al. Ann Neurol 2002; 51: 417–432.

24. Andrew Asimos, MD, FACEP Class II Recommendations Data are insufficient to state that, with the exception of hemorrhage, any specific CT finding (including evidence of ischemia affecting more than one third of a cerebral hemisphere) should preclude treatment with rtPA within 3 hours of onset of stroke Data are insufficient to state that, with the exception of hemorrhage, any specific CT finding (including evidence of ischemia affecting more than one third of a cerebral hemisphere) should preclude treatment with rtPA within 3 hours of onset of stroke Vascular imaging is necessary as a preliminary step for intra-arterial administration of pharmacological agents, surgical procedures, or endovascular interventions Vascular imaging is necessary as a preliminary step for intra-arterial administration of pharmacological agents, surgical procedures, or endovascular interventions Adams HP et al. Stroke 2007;38:1655-1711.

25. Andrew Asimos, MD, FACEP Unenhanced CT: ASPECTS System

26. Andrew Asimos, MD, FACEP ASPECTS Example

27. Andrew Asimos, MD, FACEP ASPECTS Score and Functional Outcome Weir NU et al. Neurology 2006;67(3):516-8.

28. Andrew Asimos, MD, FACEP Usefulness of ASPECTS Score at Predicting Outcome of Individual Patients Weir NU et al. Neurology 2006;67(3):516-8.

29. Andrew Asimos, MD, FACEP ASPECTS Score Applied to tPA Treated Patients Used ECASS II Database Used ECASS II Database 788 baseline CT scans 788 baseline CT scans 6 hour treatment window 6 hour treatment window Dzialowski I et al. Stroke 2006:37(4):973-8.

30. Andrew Asimos, MD, FACEP 90 Day Outcome by ASPECTS > 7 Dzialowski I et al. Stroke 2006:37(4):973-8.

31. Andrew Asimos, MD, FACEP Class III Recommendations Emergency treatment of stroke should not be delayed in order to obtain multimodal imaging studies Emergency treatment of stroke should not be delayed in order to obtain multimodal imaging studies Vascular imaging should not delay treatment of patients whose symptoms started <3 hours ago and who have acute ischemic stroke Vascular imaging should not delay treatment of patients whose symptoms started <3 hours ago and who have acute ischemic stroke Adams HP et al. Stroke 2007;38:1655-1711.

32. Andrew Asimos, MD, FACEP Therapeutic Window Time from ictus used for theoretical and practical reasons Time from ictus used for theoretical and practical reasons Increasingly will rely on imaging studies to determine tissue salvageability and clot burden Increasingly will rely on imaging studies to determine tissue salvageability and clot burden

33. Andrew Asimos, MD, FACEP Good Collateral Flow will Buy you Some Time and Brain

34. Andrew Asimos, MD, FACEP Advanced CT Imaging for Acute Stroke: CTP versus MRI ParametersDefinition of Penumbra AdvantagesLimitations CT Perfusion CBF, CBV, MTT, TTP MTT threshold at 145% Combined with plain CT Available Fast Limited brain coverage Poorly sensitive to posterior circulation Iodonated contrast DWI-PWI MRI CBF, CBV, MTT, TTP, ADC Relative TTP (or MTT) delay >45s and normal DWI Sensitive No radiation Limited availability Patient cooperation required Frequent contraindications Muir KW et al. Lancet Neurology 2006; 5:755-768

35. Andrew Asimos, MD, FACEP MRI/MRA in Acute MCA Ischemic Stroke Treated Successfully with t-PA

36. Andrew Asimos, MD, FACEP MRI/MRA in Acute MCA Ischemic Stroke Not Treated with t-PA

37. Andrew Asimos, MD, FACEP CT Perfusion Terminology Blood Flow Blood Volume Mean Transit Time or Time to Peak

38. Andrew Asimos, MD, FACEP Definitions Perfusion The steady-state delivery of blood to cerebral tissue through the capillaries CBF (Cerebral Blood Flow) Volume flow rate of blood through the cerebral vasculature per unit time CBV (Cerebral Blood Volume) Amount of blood in a given amount of tissue at any time MTT (Mean Transit Time) Average time it takes for blood to traverse from the arterial to the venous side of the cerebral vasculature

39. Andrew Asimos, MD, FACEP Changes in Cerebral Vascular Physiology with Worsening Circulatory Impairment CBFCBVMTT Salvageable Penumbra ↓ ↔↑↔↑↔↑↔↑↑ ↓ ↓ ↓↑ IrretrievableInfarct↓↓ ↑ ↑

40. Andrew Asimos, MD, FACEP Relationship between CBV, CBF, and MTT MTT= CBV/CBF Blood Flow Blood Volume Mean Transit Time or Time to Peak

41. Andrew Asimos, MD, FACEP Example of the Progression of Advanced Images

42. Andrew Asimos, MD, FACEP Pure Penumbra Parsons MW et al. Neurology 2007;68(10):730-6.

43. Andrew Asimos, MD, FACEP Core Infarct and Penumbra Parsons MW et al. Neurology 2007;68(10):730-6.

44. Andrew Asimos, MD, FACEP Largely Completed Infarction Parsons MW et al. Neurology 2007;68(10):730-6.

45. Andrew Asimos, MD, FACEP Are CTP Techniques Ready for Prime Time? CTP more accurate than unenhanced CT for detecting stroke and determining the extent of stroke CTP more accurate than unenhanced CT for detecting stroke and determining the extent of stroke Possible to distinguish penumbra from infarcted tissue Possible to distinguish penumbra from infarcted tissue Correlation between PCT/CTA and MRI is excellent Correlation between PCT/CTA and MRI is excellent Already used in DIAS and DEDAS Already used in DIAS and DEDAS Wintermark M et al. Am J Neuroradiol 2005;26(1):104-12. Wintermark M et al. Stroke 2006;37:979-985. Wintermark M et al. Neurology 2007;68(9):694-697.

46. Andrew Asimos, MD, FACEP Important Remaining CTP Questions What is the interrater reliability of visual estimation of lesion volumes? What is the interrater reliability of visual estimation of lesion volumes? Is that variability clinically important? Is that variability clinically important? Can computerization automate measurement of absolute perfusion thresholds and lesion volume in a clinically meaningful way? Can computerization automate measurement of absolute perfusion thresholds and lesion volume in a clinically meaningful way? Will the current perfusion thresholds for penumbra and infarct be maintained with rigorous future testing? Will the current perfusion thresholds for penumbra and infarct be maintained with rigorous future testing?

47. Andrew Asimos, MD, FACEP Relative MTT is the Best CTP Parameter for Identifying Penumbra Wintermark M et al. Stroke 2006;37:979-985

48. Andrew Asimos, MD, FACEP Absolute CBV is the Best CTP Parameter for Identifying Infarct Wintermark M et al. Stroke 2006;37:979-985

49. Andrew Asimos, MD, FACEP DEFUSE Study Prospective pilot study (n=74) Prospective pilot study (n=74) Patients treated with IV tPA 3-6 hours after symptom onset Patients treated with IV tPA 3-6 hours after symptom onset Goal to identify MRI patterns that predict the clinical response to early reperfusion Goal to identify MRI patterns that predict the clinical response to early reperfusion Albers GW et al. Ann Neurol 2006:60(5):508-17.

50. Andrew Asimos, MD, FACEP Key Results of the DEFUSE STUDY Target Mismatch pattern Target Mismatch pattern Identifies patients who appear to benefit substantially from early reperfusion Identifies patients who appear to benefit substantially from early reperfusion Malignant MRI pattern Malignant MRI pattern Predicts severe ICH following reperfusion Predicts severe ICH following reperfusion Small DWI and PWI lesions Small DWI and PWI lesions Associated with favorable outcomes Associated with favorable outcomes Albers GW et al. Ann Neurol 2006:60(5):508-17.

51. Andrew Asimos, MD, FACEP Target Mismatch Pattern Albers GW et al. Ann Neurol 2006:60(5):508-17.

52. Andrew Asimos, MD, FACEP Malignant Mismatch Pattern Albers GW et al. Ann Neurol 2006:60(5):508-17.

53. Andrew Asimos, MD, FACEP Case Conclusion: Patient presenting within 3 hour window BFBVTTP3 day fuInitial

54. Andrew Asimos, MD, FACEP Case Conclusion: “Wake up” Stroke

55. Andrew Asimos, MD, FACEP Proposed Imaging Algorithm

56. Andrew Asimos, MD, FACEPConclusions Advanced neuroimaging techniques will make symptom onset time increasingly obsolete Wake up stroke Onset time unclear Application of visual estimation of penumbral volumes versus automated measurement requires further study These techniques can Distinguish penumbra from infarct Will drive acute stroke care therapeutic decisions in the future

57. Andrew Asimos, MD, FACEP Questions? www.FERNE.org aasimos@carolinas.org 704 355 5296 ferne_pv_2007_asimos_neuroimaging _06152007_finalcd 8/6/2015 5:37 PM