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Contrast Enhanced MRI of
the Vulnerable Plaque,
Black or White?
Maziar Azadpour, MD
Morteza 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 MRI
Without contrast media can produce high- resolution
Images of carotid plaques and can discriminate
between clinically relevant structural components
Of 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 abnormal
MRI 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 postcontrast
Signal 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 subjects
With increased wall thickness but increased postcontrast signal intensity
And/or T2-weighted (Gd/T2), and 30 subjects with normal MRI studies.
• Weiss and colleagues suggested that MRI
with gadolinium may permit the identification
Of inflammation, even in the absence of increased
Wall thickness.
• They determined that T2-weighted and
gadolinium contrast-enhanced properties Of MRI
may identify arterial inflammation at an earlier
Stage than is manifested by increased thickness
of the arterial wall.
• Also confirming the findings of Weiss et al,
Wasserman and Colleagues recently presented
That 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 accumulates
In the arterial wall of patients with elevated serum
Markers of inflammation and in more advanced
Atheroma. Wasserman et al. determined that contrast
Administration (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 atherosclerotic
Plaque and improve the differentiation of
necrotic
Core from fibrous tissue in the plaque.
: Yuan C, Kerwin WS, Ferguson MS, Polissar N, Zhang S, Cai J, Hatsukami TS
Contrast-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 atherosclerotic
Plaque using SPIO (super paramagnetic iron
Oxide). SPIO nanoparticles are FDA approved
Negative (blackening) contrast media for cancer
detection and lymphography. They are avidly taken
up by circulating monocytes and tissue macrophages
Thereby creating irregular dark spot on the inflamed
Atherosclerotic 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 endothelial
Permeability 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 of
Atherosclerotic plaques, by providing negative
Enhancement (darkening) of the affected area.
4. Further clinical studies for both group of agents
Are required in order to confirm the hypothesis
And apply this methods in the clinical settings.
References:
1. Lauenstein T, Holtmann G, Schoenfelder D, Bosk S, Ruehm SG, Debatin JF
MR 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 Med
9 (2001) 640.
4. Yuan C, Hatsukami TS, Obrien KD
High-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

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  • 1. Contrast Enhanced MRI of the Vulnerable Plaque, Black or White? Maziar Azadpour, MD Morteza Naghavi, MD Center for Vulnerable Plaque Research
  • 2. One can divide intravascular MRI contrast media into three different phases: • Arterial • Blood pool • Extracellular
  • 3. 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.
  • 4. Yuan et al. demonstrated that multi-spectral MRI Without contrast media can produce high- resolution Images of carotid plaques and can discriminate between clinically relevant structural components Of atherosclerotic vessel wall.
  • 5. 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.
  • 6. 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.
  • 7.
  • 8. Levels of serum markers of inflammation in subjects with abnormal MRI 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
  • 9. Levels of serum markers of inflammation in subjects with increased Wall thickness, normal wall thickness but increased postcontrast Signal 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 subjects With increased wall thickness but increased postcontrast signal intensity And/or T2-weighted (Gd/T2), and 30 subjects with normal MRI studies.
  • 10. • Weiss and colleagues suggested that MRI with gadolinium may permit the identification Of inflammation, even in the absence of increased Wall thickness. • They determined that T2-weighted and gadolinium contrast-enhanced properties Of MRI may identify arterial inflammation at an earlier Stage than is manifested by increased thickness of the arterial wall.
  • 11. • Also confirming the findings of Weiss et al, Wasserman and Colleagues recently presented That 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 accumulates In the arterial wall of patients with elevated serum Markers of inflammation and in more advanced Atheroma. Wasserman et al. determined that contrast Administration (gadolinium) increased the MRI signal of atherosclerotic plaques in rabbits.
  • 12. Recently Yuan et al also showed that the use of gadolinium improve the ability of MRI to detect Neovascularization in the carotid atherosclerotic Plaque and improve the differentiation of necrotic Core from fibrous tissue in the plaque. : Yuan C, Kerwin WS, Ferguson MS, Polissar N, Zhang S, Cai J, Hatsukami TS Contrast-enhanced high resolution MRI for atherosclerotic carotid artery tissue characterization. Magn Reson Imaging. 2002 Jan
  • 13. Ruehm,Schmitz and Naghavi independently reported a new method for MR imaging of inflammation in atherosclerotic Plaque using SPIO (super paramagnetic iron Oxide). SPIO nanoparticles are FDA approved Negative (blackening) contrast media for cancer detection and lymphography. They are avidly taken up by circulating monocytes and tissue macrophages Thereby creating irregular dark spot on the inflamed Atherosclerotic plaques.
  • 14. Schmitz et al J. Inv. Radiol. 2000 Control SPIO Injected
  • 15. Schmitz et al J. Inv. Radiol. 2000
  • 16. Conclusion: 1. Gadolinium accumulates in the inflamed region of arterial wall because of enhanced endothelial Permeability 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.
  • 17. Conclusion: 3. SPIO has shown promising pre-clinical results As an MRI contrast medium for the detection of Atherosclerotic plaques, by providing negative Enhancement (darkening) of the affected area. 4. Further clinical studies for both group of agents Are required in order to confirm the hypothesis And apply this methods in the clinical settings.
  • 18. References: 1. Lauenstein T, Holtmann G, Schoenfelder D, Bosk S, Ruehm SG, Debatin JF MR 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 Med 9 (2001) 640. 4. Yuan C, Hatsukami TS, Obrien KD High-Resolution magnetic resonance imaging of normal and atherosclerotic human coronary arteries ex vivo: discrimination of plaque tissue components. J Investig Med. 2001 Nov
  • 19. 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