1. Advanced Contrast-Enhanced MRI for Stroke Risk Assessment Bruce Wasserman, M.D. Director of Diagnostic Neurovascular Imaging Johns Hopkins Medical Institutions

2. Gadolinium-enhanced MR Imaging Objectives Identifying Vulnerable Plaque (Carotid)Identifying Vulnerable Plaque (Carotid) –Anatomic Features –Inflammation Extend to intracranial vesselsExtend to intracranial vessels

3. Identifying Vulnerable Plaque Lumen Lipid Core Fibrous Cap Rupture Plaque Rupture

4. Lumen Lipid Core Clot Thin cap Large core Fibrous Cap Rupture Plaque Rupture Identifying Vulnerable Plaque

5. PlaqueLumen Black Blood MRI

6. Gadolinium-enhanced Black Blood MRI (CEMRI) Core Pre - contrast MRI Black Blood MRI PlaqueLumen Post –Enhancement of fibrous tissue improves delineation of lipid core

7. Calcium Lumen Fibrocellular tissue Lipid core H&E Wasserman et al. Radiology 2002 PrecontrastPostcontrast Endarterectomy Specimen (Gadolinium–DPTA)

8. Technical Considerations Dedicated neck coil 3T –250µ in-plane resolution Delayed images –5 minutes after contrast administration 1.5T –500µ in-plane resolution –Acquire CE-MRA during injection

9. ICA ECA CCA Endarterectomy specimen CEMRA-Mask Image MRA Contrast-Enhanced MRA (MASK images) Qiao, Etesami, Malhotra, Astor, Virmani, Kolodgie, Trout, Wasserman. AJRN March, 2010 Red-staining IPH

10. ICA ECA CCA Endarterectomy specimen CEMRA-Mask Image MRA Contrast-Enhanced MRA (MASK images) Qiao, Etesami, Malhotra, Astor, Virmani, Kolodgie, Trout, Wasserman. AJRN March, 2010 Sensitivity Specificity PPV NPV Accuracy 87%99% 98% 91% 94% Intra- observer agreement: κ =0.94 (95% CI: 0.87-1.0) Inter-observer agreement: κ =0.91 (95% CI: 0.84-0.98) Intraplaque Hemorrhage ( ) IPH Detection Red-staining IPH

11. Indicates risk for prior plaque rupture 1,2 Indicates risk for future embolic events 3-6 IPH Detection Intraplaque Hemorrhage ( ) 1 Chu et al. Stroke 2004;35:1079-1084 2 Takaya et al. Circulation 2005;111:2768-2775 3 Altaf et al. J Vasc Surg 2008;47:337-342 4 Altaf et al. J Vasc Surg 2007;46:31-36 5 Singh et al. Radiology 2009;252:502-508 6 Takaya et al. Stroke 2006;37:818-823

12. 61 year old male with 2 year history of left hemisphere strokes Left Carotid MRA Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

13. January 13, 2003 November 5, 2003 October 2003  stroke Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

14. November 5, 2003 T1 Precontrast T1 Postcontrast Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

15. November 5, 2003 T1 Precontrast T1 Postcontrast Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

16. Sirius Red T1 Postcontrast November 5, 2003 Before After Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

17. Neovascularization Neovascularity  Symptomatic, ruptured plaques 1-5 Neovascularity  Intraplaque hemorrhage 1 –IPH stimulates plaque progression 6 1 Virmani. ATVB 2005;25:2054-61 2 Moreno. Circ 2004;110:2032-8 3 Jeziorska. J Pathol 1999;188:189-196 4 Fleiner. Circ 2004;110:2843-2850 5 Russell. Br J Surg 2008;95:576-581 6 Takaya. Circ 2005;111:2768-2775

18. Contrast-enhancement Neovessels in Adventitia Reader 1 012Total Reader 2 05409 1117725 2032124 Total6242858 Category 0: No enhancement Category 1: < 50% enhancement Category 2: ≥ 50% enhancement (Average adventitial enhancement for 5 adjacent slices) Weighted κ =0.81 (95% CI: 0.68-0.89) 5409 117725 032124 6242858 PrecontrastPostcontrast ICA Lumen Postcontrast Black Blood MRI Images : Wasserman BA. Stroke October, 2010

19. P=0.003 Association of IPH with recent ipsilateral Stroke/TIA P=0.001 58 consecutive contrast-enhanced black blood MRI exams for carotid stenosis 2 Readers blinded to clinical information 58 consecutive contrast-enhanced black blood MRI exams for carotid stenosis 2 Readers blinded to clinical information Association of Adventitial Enhancement with recent ipsilateral Stroke/TIA 45 males, 13 females; Mean age 73 years (49 – 89 years) 31 (53%) had recent ipsilateral stroke/TIA 32 (55%) had IPH Median stenosis = 65% 45 males, 13 females; Mean age 73 years (49 – 89 years) 31 (53%) had recent ipsilateral stroke/TIA 32 (55%) had IPH Median stenosis = 65% % of cases with stroke/TIA IPH absent IPH present % of cases with stroke/TIA Adventitial Enhancement AE Category (Neovascularity) Wasserman BA. Stroke October, 2010 01 2

20. Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA Wasserman BA. Stroke October, 2010 2 Readers AE Category IPH absentIPH present % of cases with stroke/TIA Adventitial Enhancement 01 2 Adventitial Enhancement 01 2

21. Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA Wasserman BA. Stroke October, 2010 Odds Ratios for Recent Stroke/TIA: 2 Readers AE Category IPH absentIPH present % of cases with stroke/TIA Adventitial Enhancement 01 2 Adventitial Enhancement 01 2

22. Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA Wasserman BA. Stroke October, 2010 Odds Ratios for Recent Stroke/TIA:

23. Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA Wasserman BA. Stroke October, 2010 Odds Ratios for Recent Stroke/TIA:

24. Intracranial CE-MRI Swartz RH, et al. Intracranial Arterial Wall Imaging Using High Resolution 3-Tesla Contrast-enhanced MRI. Neurology 2009;72(7):627-634. T2 FRFSE T1 FLAIR Precontrast T1 FLAIR Postcontrast

25. 13 patients with intracranial atherosclerosis and recent TIA or stroke –12 had focal eccentric wall enhancement of intracranial vessel supplying territory of acute infarct –Plaques in MCA, ACA, Basilar arteries –10 of 12 had enhancement only in vessel supplying area of acute infarct even when multiple plaques Swartz RH, et al. Intracranial Arterial Wall Imaging Using High Resolution 3-Tesla Contrast-enhanced MRI. Neurology 2009;72(7):627-634. Intracranial CE-MRI

26. Swartz RH, et al. Intracranial Arterial Wall Imaging Using High Resolution 3-Tesla Contrast-enhanced MRI. Neurology 2009;72(7):627-634. Intracranial CE-MRI T1 FLAIR Precontrast T1 FLAIR Postcontrast

27. 64 yo male with blurred vision, dizziness and dysarthria May 27, 2007

28. June 1, 2007

30. Sept 18, 2007 (3 months of statin use) Time

31. Sept 18, 2007 June 1, 2007 Sept 18, 2007 Time

32. June 1, 2007Sept 18, 2007 June 1, 2007 Sept 18, 2007 Time

33. June 1, 2007 Sept 18, 2007 Feb 06, 2008 Time

34. Sept 18, 2007 Feb 06, 2008 Sept 18, 2007 Feb 06, 2008 Time

35. Summary Contrast-enhanced Plaque MRI: Black blood images pre- and post-contrastBlack blood images pre- and post-contrast –Fibrous cap thickness, lipid core size, calcification –Adventitial enhancement score (i.e., neovascularity) CEMRA during arterial phaseCEMRA during arterial phase –Mask image - IPH

36. Summary Contrast-enhanced Plaque MRI: Determine plaque vulnerability Identify the culprit lesion Monitor therapeutic response

37. Acknowledgments Ye Qiao, PhDYe Qiao, PhD Maryam Etesami, MDMaryam Etesami, MD Brad Astor, PhDBrad Astor, PhD Matthias Stuber, PhDMatthias Stuber, PhD Steven R. Zeiler, MD, PhDSteven R. Zeiler, MD, PhD Robert Wityk, MDRobert Wityk, MD Victor Urrutia, MDVictor Urrutia, MD Hugh H. Trout, III, MDHugh H. Trout, III, MD Frank Kolodgie, PhDFrank Kolodgie, PhD Renu Virmani, MDRenu Virmani, MD