Contrast Enhanced MRI of the Vulnerable Plaque,

Black or White? 

Maziar Azadpour, MDMorteza Naghavi, MD

Center for Vulnerable Plaque Research

One can divide intravascular MRI contrast media into three different phases:

• Arterial

• Blood pool • Extracellular

Arterial Phase is the most suitable one for angiography and needs rapid sequences with minimum TR to optimize the enhancement.

Blood Pool Phase is significant for highly vascular organs such as liver, which benefits the most from enhancement in this phase.

Extracellular Phase in which certain tissues such as fibrous tissue and inflammatory processes could be detected.Different MRI contrasts agents have their own unique property to affect each of the above mentioned phases.

Yuan et al. demonstrated that multi-spectral MRIWithout contrast media can produce high- resolution Images of carotid plaques and can discriminate between clinically relevant structural componentsOf atherosclerotic vessel wall.

Weiss, Cannon et al used positive enhancement Contrast media, Gadolinium-DTPA (Whitening) to Obtain double inversion recovery, fast spin echo images of the common carotid arteries and infrarenal aorta at 1.5 T both before and after injection in 52 subjects which 17 of whom had no risk factors for atherosclerosis and thus served as controls.

They hypothesized that arterial inflammation would cause increases in wall thickness, T2-weighted signal intensity, and/or arterial Wall gadolinium contrast enhancement Because Of enhanced endothelial permeability with Increased tissue water, cellular infiltration and Vasa vasorum dilation or neovascularization.

Levels of serum markers of inflammation in subjects with abnormalMRI compared to groups with normal MRI

Bar graphs show levels of serum markers of inflammation in 22 Subjects With abnormal MRI compared with 30 subjects with normal

MRI vascular studies. Weiss CR, Arai AE, Bui MN, Agyeman KO, Waclawiw MA, Balaban RS, Cannon RO 3rd. Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans. : J Magn Reson Imaging 2001 Dec

Levels of serum markers of inflammation in subjects with increased Wall thickness, normal wall thickness but increased postcontrastSignal intensity and/or T2-weighted and with normal MRI studies.

Weiss CR, Arai AE, Bui MN, Agyeman KO, Waclawiw MA, Balaban RS, Cannon RO 3rd. Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans. : J Magn Reson Imaging 2001 Dec

Bar graphs show levels of serum markers of inflammation in 14 subjectsWith increased wall thickness but increased postcontrast signal intensityAnd/or T2-weighted (Gd/T2), and 30 subjects with normal MRI studies.

• Weiss and colleagues suggested that MRI with gadolinium may permit the identificationOf inflammation, even in the absence of increasedWall thickness.

• They determined that T2-weighted and gadolinium contrast-enhanced properties Of MRI may identify arterial inflammation at an earlierStage than is manifested by increased thickness of the arterial wall.

• Also confirming the findings of Weiss et al,Wasserman and Colleagues recently presentedThat gadolinium enhancement of carotid arteries By MRI was associated with fibrocellular tissue In atherosclerotic plaque during subsequent Microscopic analysis following endarterectomy.

• Preliminary work indicates gadolinium accumulatesIn the arterial wall of patients with elevated serum Markers of inflammation and in more advanced Atheroma. Wasserman et al. determined that contrastAdministration (gadolinium) increased the MRI signal of atherosclerotic plaques in rabbits.

Recently Yuan et al also showed that the use of gadolinium improve the ability of MRI to detect Neovascularization in the carotid atheroscleroticPlaque and improve the differentiation of necroticCore from fibrous tissue in the plaque.

: Yuan C, Kerwin WS, Ferguson MS, Polissar N, Zhang S, Cai J, Hatsukami TSContrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization. Magn Reson Imaging. 2002 Jan

Ruehm,Schmitz and Naghavi independently reported a new method for MR imaging of inflammation in atheroscleroticPlaque using SPIO (super paramagnetic ironOxide). SPIO nanoparticles are FDA approved Negative (blackening) contrast media for cancerdetection and lymphography. They are avidly taken up by circulating monocytes and tissue macrophagesThereby creating irregular dark spot on the inflamedAtherosclerotic plaques.

Schmitz et al J. Inv. Radiol. 2000

Control

SPIO Injected

Schmitz et al J. Inv. Radiol. 2000

Conclusion:

1. Gadolinium accumulates in the inflamed region of arterial wall because of enhanced endothelialPermeability with increased tissue water, cellular Infiltration and vasa vasorum dilatation or Neovascularization.

2. This technique may provide additional Information related to activity of plaque, besides structural imaging.

Conclusion:

3. SPIO has shown promising pre-clinical results As an MRI contrast medium for the detection ofAtherosclerotic plaques, by providing negativeEnhancement (darkening) of the affected area.

4. Further clinical studies for both group of agentsAre required in order to confirm the hypothesisAnd apply this methods in the clinical settings.

References:

1. Lauenstein T, Holtmann G, Schoenfelder D, Bosk S, Ruehm SG, Debatin JFMR colonography without colonic cleansing: a new strategy to improve patient acceptance.AJR Am J Roentgenol. 2001 Oct;177(4):823-7.

2. Schmitz SA, Taupitz M, Wagner S, Wolf KJ, Beyersdorff D, Hamm B.Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles.J Magn Reson Imaging. 2001 Oct;

3. Morteza Naghavi, Mitra Rajabi, Mohammad Asif, Michael Quast, Jingna Wei,Daniel Chan, Mohammad Madjid, Khawar Gul, Samuel Ward Casscells III, James T. Willerson. Detection of Macrophage infiltration and intraplaque hemorrhage in Vulnerable atherosclerotic plaque using Magnetic Resonance Imaging contrast media, Super paramagnetic iron oxide (SPIO). Proc Intl Soc. Mag Reson Med9 (2001) 640.

4. Yuan C, Hatsukami TS, Obrien KDHigh-Resolution magnetic resonance imaging of normal and atherosclerotic human coronary arteries ex vivo: discrimination of plaque tissue

components.J Investig Med. 2001 Nov

References:

5. Yuan C, Mitsumori LM, Ferguson MS, Polissar NL, Echelard D, Ortiz G, Small R, Davies JW, Kerwin WS, Hatsukami TS.In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques, Circulation. 2001 Oct 23

6. Weiss CR, Arai AE, Bui MN, Agyeman KO, Waclawiw MA, Balaban RS, Cannon RO 3rd. Arterial wall MRI characteristics are associated with elevated serum markers of inflammation in humans.J Magn Reson Imaging. 2001 Dec

7. Wasserman BA, Haacke EM, Li D. Carotid plaque formation and its evaluation with angiography, ultrasound, and MR angiography.J Magn Reson Imaging. 1994 Jul-Aug