Advanced Contrast-Enhanced MRI for Stroke Risk Assessment

Bruce Wasserman, M.D.Director of Diagnostic Neurovascular ImagingJohns Hopkins Medical Institutions

Gadolinium-enhanced MR Imaging

Objectives• Identifying Vulnerable Plaque (Carotid)

– Anatomic Features– Inflammation

• Extend to intracranial vessels

Identifying Vulnerable Plaque

LumenLipidCore

Fibrous Cap Rupture

Plaque Rupture

LumenLipidCore

Clot

Thin capLarge core

Fibrous Cap Rupture

Plaque Rupture

Identifying Vulnerable Plaque

PlaqueLumen

Black Blood MRI

• Gadolinium-enhanced Black Blood MRI (CEMRI)

Core

Pre - contrast MRI

Black Blood MRI

PlaqueLumen

Post

–Enhancement of fibrous tissue improves delineation of lipid core

CalciumLumen

Fibrocellulartissue

Lipidcore

H&E

Wasserman et al. Radiology 2002

Precontrast PostcontrastEndarterectomy Specimen

(Gadolinium–DPTA)

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

ICA

ECA

CCAEndarterectomy

specimen

CEMRA-Mask ImageMRA

Contrast-Enhanced MRA (MASK images)

Qiao, Etesami, Malhotra, Astor, Virmani, Kolodgie, Trout, Wasserman. AJRN March, 2010

Red-staining IPH

ICA

ECA

CCAEndarterectomy

specimen

CEMRA-Mask ImageMRA

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

• Indicates risk for prior plaque rupture1,2

• Indicates risk for future embolic events3-6

IPH DetectionIntraplaque Hemorrhage ( )

1Chu et al. Stroke 2004;35:1079-10842Takaya et al. Circulation 2005;111:2768-27753Altaf et al. J Vasc Surg 2008;47:337-3424Altaf et al. J Vasc Surg 2007;46:31-365Singh et al. Radiology 2009;252:502-5086Takaya et al. Stroke 2006;37:818-823

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.

January 13, 2003

November 5, 2003

October 2003 stroke

Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

November 5, 2003

T1 Precontrast T1 Postcontrast

Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

November 5, 2003

T1 Precontrast T1 Postcontrast

Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

SiriusRed

T1 Postcontrast

November 5, 2003

Before After

Wasserman et al. Stroke. 2005 Nov;36(11):2504-13.

Neovascularization

• Neovascularity Symptomatic, ruptured plaques1-5

• Neovascularity Intraplaque hemorrhage1

– IPH stimulates plaque progression6

1Virmani. ATVB 2005;25:2054-612Moreno. Circ 2004;110:2032-83Jeziorska. J Pathol 1999;188:189-1964Fleiner. Circ 2004;110:2843-28505Russell. Br J Surg 2008;95:576-5816Takaya. Circ 2005;111:2768-2775

Contrast-enhancement

Neovessels in Adventitia

Reader 1

0 1 2 Total

Reader 2

0 5 4 0 9

1 1 17 7 25

2 0 3 21 24

Total 6 24 28 58

Category 0: No enhancementCategory 1: < 50% enhancementCategory 2: ≥ 50% enhancement

(Average adventitial enhancement for 5 adjacent slices)Weighted κ =0.81 (95% CI: 0.68-0.89)

5 4 0 9

1 17 7 25

0 3 21 24

6 24 28 58Precontrast Postcontrast

ICA LumenICA Lumen

Postcontrast Black Blood MRI Images:

Wasserman BA. Stroke October, 2010

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

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/TIA32 (55%) had IPH

Median stenosis = 65%

IPH absent IPH present0%

20%

40%

60%

80%

100%

% o

f cas

es w

ith st

roke

/TIA

IPH absent IPH present

% o

f cas

es w

ith st

roke

/TIA

adventitial enhancement

adventitial enhancement

0%

20%

40%

60%

80%

100%

0

1

2

Adventitial Enhancement

AE Category

(Neovascularity)

Wasserman BA. Stroke October, 2010

0 1 2

Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA

Wasserman BA. Stroke October, 2010

2 Readersadventitial enhancement adventitial enhancement0%

20%

40%

60%

80%

100%

012

AE Category

IPH absent IPH present

% o

f cas

es w

ith st

roke

/TIA

Adventitial Enhancement0 1 2

Adventitial Enhancement0 1 2

Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA

ORs 95% CIAge (years) 0.97 0.89 – 1.06

Female 0.18 0.02 – 1.42

Active smoker 2.15 0.22 – 21.00

HTN 0.35 0.06 – 2.15

DM 3.58 0.66 – 19.36

Hyperlipidemia 0.51 0.06 – 4.09

Statin use 3.41 0.39 – 30.13

ASA use 0.88 0.09 – 8.76

Wall thickness (mm) 1.62 0.61 – 4.30

AE (Category 1 vs 0) 11.82 2.48 – 56.30

AE (Category 2 vs 0) 58.13 10.12 – 333.87

IPH (present vs absent) 5.90 1.09 – 31.86

Stenosis (continuous) 0.09 0.01 – 4.54

Wasserman BA. Stroke October, 2010

Odds Ratios for Recent Stroke/TIA:

2 Readersadventitial enhancement adventitial enhancement0%

20%

40%

60%

80%

100%

012

AE Category

IPH absent IPH present

% o

f cas

es w

ith st

roke

/TIA

Adventitial Enhancement0 1 2

Adventitial Enhancement0 1 2

Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA

ORs 95% CIAge (years) 0.97 0.89 – 1.06

Female 0.18 0.02 – 1.42

Active smoker 2.15 0.22 – 21.00

HTN 0.35 0.06 – 2.15

DM 3.58 0.66 – 19.36

Hyperlipidemia 0.51 0.06 – 4.09

Statin use 3.41 0.39 – 30.13

ASA use 0.88 0.09 – 8.76

Wall thickness (mm) 1.62 0.61 – 4.30

AE (Category 1 vs 0) 11.82 2.48 – 56.30

AE (Category 2 vs 0) 58.13 10.12 – 333.87

IPH (present vs absent) 5.90 1.09 – 31.86

Stenosis (continuous) 0.09 0.01 – 4.54

Wasserman BA. Stroke October, 2010

Odds Ratios for Recent Stroke/TIA:

Association of Adventitial Enhancement (AE) and IPH with Stroke/TIA

ORs 95% CIAge (years) 0.97 0.89 – 1.06

Female 0.18 0.02 – 1.42

Active smoker 2.15 0.22 – 21.00

HTN 0.35 0.06 – 2.15

DM 3.58 0.66 – 19.36

Hyperlipidemia 0.51 0.06 – 4.09

Statin use 3.41 0.39 – 30.13

ASA use 0.88 0.09 – 8.76

Wall thickness (mm) 1.62 0.61 – 4.30

AE (Category 1 vs 0) 11.82 2.48 – 56.30

AE (Category 2 vs 0) 58.13 10.12 – 333.87

IPH (present vs absent) 5.90 1.09 – 31.86

Stenosis (continuous) 0.09 0.01 – 4.54

Wasserman BA. Stroke October, 2010

Odds Ratios for Recent Stroke/TIA:

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

• 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

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

64 yo male with blurred vision, dizziness and dysarthria

May 27, 2007

May 27, 2007June 1, 2007

June 1, 2007

June 1, 2007 Sept 18, 2007(3 months of statin use)Time

Sept 18, 2007

June 1, 2007 Sept 18, 2007

Time

June 1, 2007 Sept 18, 2007

June 1, 2007 Sept 18, 2007

Time

June 1, 2007 Sept 18, 2007

Sept 18, 2007 Feb 06, 2008

Feb 06, 2008

Time

Sept 18, 2007 Feb 06, 2008

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

Summary

Contrast-enhanced Plaque MRI:• Black blood images pre- and post-contrast

– Fibrous cap thickness, lipid core size, calcification– Adventitial enhancement score (i.e., neovascularity)

• CEMRA during arterial phase– Mask image - IPH

Summary

Contrast-enhanced Plaque MRI:Determine plaque vulnerability

Identify the culprit lesionMonitor therapeutic response

Acknowledgments• Ye Qiao, PhD• Maryam Etesami, MD• Brad Astor, PhD• Matthias Stuber, PhD• Steven R. Zeiler, MD, PhD• Robert Wityk, MD• Victor Urrutia, MD• Hugh H. Trout, III, MD• Frank Kolodgie, PhD• Renu Virmani, MD