1. Advances in Emergency Brain Imaging Andrew W. Asimos, MD Director of Emergency Stroke Care Carolinas Medical Center Charlotte, NC

2. Disclosure & Disclaimer: I am not a Neuroradiologist

3. Session Objectives l Focus on CT-based applications of neuroimaging in acute stroke l Overview of the acquisition and derivation of CTP images l Understand the theory behind the clinical application of CTP imaging in acute stroke l Discuss CTP parameters that suggest infarct l Discuss CTP parameters that suggest penumbra l Discuss use of CTA in acute ischemic and hemorrhagic stroke

4. Goal of Acute Stroke Imaging l Acute Ischemic Stroke l Identify patients with favorable imaging parameters for revascularization l < 3 hours (<4.5 hrs?) l 3-8 hours (of beyond) l Stuttering onset l “Wake up” strokes or unknown time of onset l Identify patients in whom the treatment may be futile or detrimental l Hemorrhagic Stroke l Predict hematoma enlargement or extension

5. Department of Emergency Medicine Journal Club October 15, 2008 “We are looking forward to moving away from rigid timeframes to treatment on the basis of imaging that can assess brain pathophysiology and tissue viability,“ G. Tsivgoulis and A.V.Alexandrov, Lancet October 11, 2008

6. Good collaterals will buy you some time

7. The Ideal Study l Available l Fast l Accurate l Consistent

8. Multimodal CT l Studies l Noncontrast CT (NCCT) l CT Angiography (CTA) l CT Perfusion - 4 slice ROI (CTP) l CBF l CBV l MTT or TTP

9. CT Perfusion l Tracks transient changes in brain parenchyma during the first passage of IV contrast l Allows quantitative assessment of CBF and CBV (MTT or TTP) l Except for dedicated software, no special equipment required l Quantitatively determined from a sequence of the time density curves of the passage of a small contrast bolus l Derived from postprocessing of axial source images obtained from continuous rapid scanning through a fixed levels

10. Radiation Exposure from CTP Cohnen M et al. Am J Neuroradiol 2006;27:1741-45.

11. Blood Flow (CBF) l Volume flow rate of blood through the cerebral vasculature per unit time l Computed and displayed as ml per 100 gram of tissue per minute l CBF=CBV/MTT

12. Blood Volume (CBV) l Amount of blood in a given amount of tissue at any time l Computed and displayed as ml per 100 gram of tissue

13. Mean Transit Time (MTT) l Average time it takes for blood to traverse from the arterial to the venous side of the cerebral vasculature l Computed and displayed in seconds l MTT=CBV/CBF

14. Acute Ischemic Stroke CBF – Decreased CBV – Variable MTT – Increased to maximize O 2 extraction

15. Theoretical Changes in CTP Parameters in Acute Ischemic Stroke CBFCBVMTT Salvageable Penumbra ↓ ↔↑↔↑↔↑↔↑↑ ↓ ↓ ↓↑ IrretrievableInfarct↓↓↑

16. Potential Scenarios Parsons MW et al. Neurology 2007;68(10):730-6. PurePenumbra Core Infarct & Penumbra LargelyCompletedInfarct NCCT CBF CBV MTT Day 3

17. Multimodal CT l CTA images l Source images l Post-processing l Volume rendered l Multiplanar reformatted l Maximum intensity projection (MIP) images l 3D reconstructions

18. CTA Alone: Capabilities & Benefits l Very fast l Relatively simple interpretation l Ischemic Stroke l Localizes vascular occlusion l Assesses collateral circulation l Detects large perfusion abnormalities l Hemorrhagic stroke l May identify patients at risk for ICH growth

19. CTA – Poor versus Good Collaterals Based on MIP images Case 1 Poor collaterals Case 2 Good collaterals Tan JC et al. Ann Neurol 2007; 61:533-543.

20. Are CTA Source Images an Adequate Index of Perfusion? Schellinger PD et al. Cerebrovasc Dis 2007;24(suppl 1):16-23 CTA Source Images NCCT MRI / DWI

21. CTP versus CTA Source Images for Detecting Infarct Core Tan JC et al. Ann Neurol 2007; 61:533-543.

22. Hematoma Expansion l Within 3 hours from onset: l 26% with 33% or greater growth in next hour l 12% with 33% or greater growth 1-20 hours l 72% experience some hematoma expansion over the first 24 hours Davis SM, et al. Neurology. 2006;66:1175-1181; Brott T, et al. Stroke. 1997;28:1-5.

23. Contrast Extravasation as a Marker for Hematoma Expansion l Contrast extravasation an independent predictor of hematoma expansion (OR 18, 95% CI 2.1 to 162) Goldstein J et al. Neurology 2007; 68(12):889-894. l Sensitivity 93% l Specificity 50% l PPV 24% l NPV 98%

24. “Spot Sign” as a Marker for Hematoma Expansion l 39 patients presenting < 3 hours from ictus l 28% with hematoma growth l “Spot Sign” Wada R et al. Stroke 2007; 38(4):1257-1262. l Sensitivity 91% l Specificity 89% l PPV 77% l NPV 96%

25. The SPOT Sign for Predicting and Treating ICH Growth Study (STOP-IT Study) l Randomize ICH patients within 6 hours of onset with a spot sign to treatment with rFVIIa vs placebo l Outcome measures l Sensitivity and specificity of the spot sign for predicting hematoma growth l Accuracy of site investigators for correct identification of the spot sign as compared to a blinded study neuroradiologist l Rate of hematoma growth among spot-positive subjects at 24 hours l rFVIIa versus placebo l Mortality at 90 days l Good (mRS 0-3) versus poor (mRS 4-6) functional outcome

27. The Future: 3-D thresholded studies delineating infarct from penumbra from unaffected tissue l Thresholding software that color codes l Tissue destined to infarct (red) l Tissue that may or may not recover, depending on the timing and success of reperfusion (yellow)

28. Important Remaining CTP Questions l Will the reproducibility of perfusion CT be fully validated? l Will the accuracy of quantitative values acquired with CTP be validated? l What is the interrater reliability of visual estimation of lesion volumes? l Do neuroimagers overestimate “tissue at risk” for infarction with our current visual interpretation of CBF and MTT maps l Will CTP parameters be identified that reliably predict the likelihood of hemorrhagic transformation?

29. Questions