SHAPE Society

1. Non-Invasive
Macrophage Imaging for
Detection of Vulnerable Plaque
Applications and Limitations
Amersham Oct 2003
Morteza Naghavi, MD

4. A
B

5. Which one is
vulnerable, A or B?
The one with
inflammation
(macrophage infiltration)

6. Morphology vs. Activity Imaging
Inactive and
non-inflamed
plaque
Active and
inflamed
plaque
Similar in
IVUS OCT MRI
w/o CM
Morphology
Different
Activity
Thermography, Spectroscopy,
immunoscintigraphy, MRI with
targeted contrast media…

7. Plaque Morphology
vs.
Plaque Activity
We Need Both

8. Imaging Inflammation
- by MRI
- by CT
Both are available today!

9. Imaging Inflammation
- by MRI
Pioneered in 1980s
Rummeny E, Weissleder R, Stark DD, Elizondo G, Ferrucci JT.
Radiologe. 1988 Aug;28(8):380-6.

10. SuperparamagneticSuperparamagnetic
andand
Ultra-superparamagneticUltra-superparamagnetic
Iron OxideIron Oxide
lBlood pool Magnetic resonance (MR)
imaging contrast media with a central
core of iron oxide generally coated by a
polysaccharide layer
Shortening MR relaxation time
Engulfed by and accumulated in cells
with phagocytic activity

11. Particle Core Size Particle Size Blood
(nm) (nm) Half-life
Combidex 5-6 20-30 8h
Feridex 4-6 35-50 2.4±0.2h
DDM 43/34/102 6.4 20-30 6h
Clariscan
MION 4-6 17 varies
Feruglose
--- --- --- ---
Examples of commercially available SPIOs

12. USPIOs Enter the AtheroscleroticUSPIOs Enter the Atherosclerotic
Plaque ThroughPlaque Through
lMacrophages that engulfed
them
lFissured or thin cap
l Extensive angiogenesis
l vasa vasorum leakage
l Intra plaque hemorrhage

13. In-vitro Study of Macrophage
SPIO Uptake
 In a series of in-vitro studies we have tested
the rate of SPIO uptake by human activated
monocytes in different conditions regarding
incubation time and concentration of SPIO.
All SPIO were labeled by a fluorescent dye
(DCFA).

14. FL-labeled SPIO Incubated Macrophages 24hr

15. Double DAPI Staining with Fluorescence-labeled SPIO Macrophages
after 24hr Incubation

16. Hypothesis

17. vasa vasorum
Over magnification is a major advantage of SPIO
Darkening property of SPIO in the white background of fat
and water of plaque is another advantage

18. SPIO and T2 Effect
In-vitro study to show the effect of
macrophage SPIO uptake on their
T2 relaxation time

20. 0
10
20
30
40
50
60
70
80
90
50 250 control
20 min
60 min
6 hours
24 hours
Macrophage Uptake of Feridex with Time
and Concentration Shown by T2 Reduction
Concentration µmol/ml

21. Histopathologic Studies of ApoE KO Mice
Injected with SPIO (Abdominal Aorta)
H&E staining
Iron Staining CD 68 staining
Iron particles