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New Developments in High Resolution Imaging of the Arterial Wall

David Saloner, PhD

Department of Radiology and Biomedical Imaging, Surgery and Bioengineering

VA Medical Center/University of California San Francisco

I have no financial disclosures

Gd and Ferumoxytol are not approved as MRA imaging agents

Disclosures

Patients with vascular disease may present with similar geometric conditions.

Some progress rapidly with devastating sequellae –others remain stable over many years.

How do we determine what the drivers of vascular disease progression are?

Can we modify the paradigm for when to intervene and when to pursue “watchful waiting”?

Overview

Monitor progression of the lumen and wall over time –carotid atherosclerosis, intracranial aneurysms

Hemodynamics - visualization of MR measured velocity fields using experimental and computational methods

Wall inflammation

Correlation of morphologic change with hemodynamics

Overview

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Current Evaluation

Stenosis - reduction in diameter of lumen

a

b

stenosis = (b - a)/b x 100 %

� Why diameter stenosis? - because it is available

• Traditional assessment in terms of diameter narrowing

• Is geometry sufficient?

Disease conditions – Carotid Atherosclerosis

What is the risk factor associated with carotid disease?

a b c d

Disease conditions – Carotid Atherosclerosis

• Is geometry sufficient?

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High Resolution MRI ex vivo

Carotid disease advantage – specimen availability from endarterectomy surgery

Characterize compositional and geometric morphology – compare MR features with histo-pathologic gold standard

Longitudinal MRI

Transverse MRI

Carotid specimen

0

10

20

30

40

50

60

circular crescentic elliptic lobular

freq

uenc

y

Cross-section through maximal stenosis for 9 specimens

Stenosis shape

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What is the diameter of England?High Resolution MRI In Vivo

• Can we obtain similar data in vivo that will permit us to follow the progression of plaque bulk, geometry, and compositional features?

• Can we identify the features of the plaque that correlate with rapid progression in a prospective fashion?

• Can we identify the features of the plaque that confer neurological risk?

Calcification clearly noted

2D “black blood” vessel wall imagingIntraplaque hematoma

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Disease conditions – Carotid AtherosclerosisT1-weightedNon-contrast

T2-weightedNon-contrast

Is geometry & composition sufficient? fibrous cap and lipidic core

3T + bilateral 8-channel coils – improved SNR: deep & low

1.5T + bilateral 4-channel coils

Reduction in measurement error – �field strength

T1 T2

3D-TOF

T1-weighted T2-weighted

TOF-MRA – bright lumen

transverse reformat

3D Black Blood Imaging of Hemorrhage

Heavily T1-weighted; sensitive to methemoglobin

coronal reformat

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T1-weightedNon-contrast

T2-weightedNon-contrast

Carotid Atherosclerosis

Thromboembolism from plaque rupture

Pre rupture

Carotid Atherosclerosis

Thromboembolism from plaque rupture

Pre rupture Post rupture

MRV Can measure velocity field in addition to structural and compositional morphology

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Disease conditions – Carotid Atherosclerosis Disease conditions – Carotid Atherosclerosis

Disease conditions – Carotid Atherosclerosis

• MR powerful non-invasive method to monitor progression

• Flow limitation rarely of importance

• Can identify major components of plaque wall: calcification; lipid rich necrotic core; intra-plaque hemorrhage; fibrous cap

• 3D methods increasingly used at 3T

Ruptured aneurysms can have devastating clinical sequellae

Untreated aneurysms can continue to remodel, layer thrombus, or rupture

Little information is available on natural progression of untreated aneurysms

Role of hemodynamics in progression is undefined

Untreated Intracranial Aneurysms

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• Most current analyses of growth and rupture risk based on geometric considerations

• Absolute diameter, neck/diameter ratio …

• Is geometry sufficient?

Disease conditions –Intra-cranial Aneurysmal Disease

Longitudinal studies: MRA co-registration

Surfaces obtained from baseline and follow-up MRA are co-registered

• Quantitative measurement of the changes obtained by calculating the aneurysmal volume at each study

Aneurysm growth observed with CE-MRA studies over time

Flow computed with CFD

High Resolution Black Blood Intracranial Vessel Wall Imaging

3D SPACE – black blood vessel wall imaging

Suppress blood signal and obtain contrast between outer wall and adjacent tissue

0.5mmx0.5mmx0.6mm

10 mins

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Patient with a giant fusiform basilar artery aneurysm with heavy thrombus burden

Single slice from3D – black blood wall imaging 0.5mmx0.5mmx0.6mm

Single slice from3D – CE-MRA 0.7mmx0.7mmx0.7mm

Excellent wall visualization

Patient with a giant fusiform basilar artery aneurysm with heavy thrombus burden

Single slice from3D – black blood wall imaging 0.5mmx0.5mmx0.6mm

Single slice from3D – CE-MRA 0.7mmx0.7mmx0.7mm

Excellent wall visualization

Subject with ica terminus aneurysmSingle slice from3D – black blood wall imaging 0.5mmx0.5mmx0.6mm

Single slice from3D – CE-MRA 0.7mmx0.7mmx0.7mm

Good wall visualization

USPIO in the wall as a marker of inflammation?

Scavenged by macrophage

Potentially differentiate stable from active (growing) aneurysms

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Aortic Dissection – stable over 10 years

First pass –single slice Steady-state MI Ptrue versus false lumen

Aortic Dissection – stable over 10 years

Pre-uspio injection 5 days post

Aortic Dissection – rapid growth in AAA

Single slice sagittal Single slice corona lRepaired TAA AAA - thrombus

Aortic Dissection – rapid growth

Pre-uspio injection 5 days post

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Aortic Dissection – rapid growth

5 days post

T2* weighted image of aneurysm wall at the tip of the basilar artery imaged before (left) and five days following Ferumoxytol administration (right).

Uptake by inflammatory macrophage in the vessel wall (large red circle).

Intracranial Aneurysm– basilar tip

• Important to establish link to biomolecular and cellular pathways that are activated by adverse hemodynamics

• Establish presence of inflammatory agents in surgical specimens co-localized with hemodynamics

• Improved VWI at higher field strength (7T) and greater resolution

Future DirectionsRadiology Neurointerventional RadiologyVitaliy Rayz, PhD Randall Higashida, MD Chengcheng Zhu, PhD Van Halbach, MDAlastair Martin, PhD Chris Dowd, MDHenrik Haraldsson, PhD Steve Hetts, MDFarshid Farzaneh, MS BiostatisticsDonne Nieuwoudt, MD Chuck McCulloch, PhD

NeurosurgeryMichael Lawton, MD

Neurology Vascular SurgeryNerissa Ko, MD Joseph Rapp, MDWade Smith, MDAndy Josephson, MD Anthony Kim, MD Heather Fullerton, MD

Acknowledgments

FundingNIH (NINDS, NHLBI), VA Merit