040 center for vulnerable plaque research
Post on 11-Apr-2017
16 Views
Preview:
Transcript
Center for Vulnerable Plaque ResearchCVPR
UT- HoustonTexas Heart Institute
How the World Dies Today?YLLS: Years of Life Lost
Everybody has atherosclerosis, the question is who has vulnerable plaqueSudden Cardiac DeathAcute MIVulnerablePlaque(s)
Plaque Eruption (Volcano!)
- Compensatory Enlargement of Human Atherosclerotic Coronary ArteriesN Engl J Med 1987 May 28;316(22):1371-5
How important is detection of vulnerable plaque?
In 50-70% of cases the first symptom of having a vulnerable plaque is sudden death out-of-hospital.
Kill It Before It Kills You!
Human Carotid PlaqueCourtesy of Dr. Chun Yuan University of Washington
We need MRI with vulnerable plaque targeted contrast media that identifies:1- Inflammation (macrophage infiltration),2- Fissured/Permeable Cap, 3- Leaking Angiogenesis and 4- Intra-Plaque Hemorrhage5- ?
Superparamagnetic and Ultra-superparamagnetic Iron OxideBlood pool magnetic resonance (MR) imaging contrast media with a central core of iron oxide generally coated by a polysaccharide layer Shortening MR relaxation timeEngulfed by and accumulated in cells with phagocytic activity
Particle Core Size Particle Size Blood (nm) (nm) Half-life
Combidex 5-6 20-30 8hFeridex 4-6 35-50 2.40.2hDDM 43/34/102 6.4 20-30 6h ClariscanMION 4-6 17 variesFeruglose --- --- --- --- Examples of commercially available SPIOs
Current applications of SPIO in MR imaging:
Detection of Hepatic Lesions
(primary and metastatic cancers)
Experimental Nephritic syndrome in Laboratory animals
Monitoring rejection of transplanted heart or kidney in
the animal model of allograft transplantation.
Experimental detection of CNS lesions in laboratory
animals.
USPIOs Enter the Atherosclerotic Plaque Through-Macrophages that engulfed them-Fissured or thin cap -Extensive angiogenesis -vasa vasorum leakage -Intra plaque hemorrhage
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 regardingincubation time and concentration of SPIO.All SPIO were labeled by a fluorescent dye(DCFA).
FL-labeled SPIO Incubated Macrophages 24hr
Double DAPI Staining with Fluorescence-labeled SPIO Macrophages after 24hr Incubation
HypothesisActive macrophages residing inside the inflamed vulnerable plaques can be visualized following injection of SPIO or USPIOs into the systemic circulation by virtue of a decrease in the magnetic resonance signal intensity of the plaque,and correlate with histopathologic characteristics of vulnerability to rupture.
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
SPIO and T2 EffectIn-vitro study to show the effect of macrophage SPIO uptake on their T2 relaxation time
Macrophage Uptake of Feridex with Time and Concentration Shown by T2 ReductionConcentration mol/ml
Histopathologic study of the Mouse injected With SPIO (Thoracic Aorta)ApoE KO mouse, Movat staining, proximal aortaCoronary Cross section
Atherosclerosisplaque
Histopathologic study of ApoE KO Mouse injected With SPIO (Thoracic Aorta)CD68 staining(aortic plaque)Iron Staining (aortic plaque)Iron Staining (coronary section)Iron particlesIron particles
Histopathologic study of ApoE KO Mouse injected With SPIO (Abdominal Aorta)H&E stainingIron Staining
CD 68 stainingIron particles
Histopathologic study of wild type Mouse injected With SPIO (Thoracic Aorta) H&E stainingCD68 stainingIron staining
Comparison of the Number of the Iron Particles (per HPF) in ApoE KO Mice Plaque vs. Normal Wall
Iron StainingH&E StainingApo E-deficient mouse injected with SPIO Cytokines added
MR Image of Abdominal Aorta After SPIO Injection in ApoE and Control Mice
ApoE deficient mouse
C57B1 (control) mouse
Before Injection
After Injection (5 Days )
Dark (negatively enhanced) aortic wall, full of iron particles
Bright aortic lumen and wall without negative enhancement and no significant number of iron particles in pathology
Typical in vivo MR images of a live mouse at the heart (left) and renal level (right). Various vessels and aortic arch can easily e seen in these images. The slice thickness is 0.5 mm and the in-plane resolution is 50 mm (7.1 T MR system).
We chose Watanabe Hereditary Hypercholesterolemic rabbits (WHHR) and New Zealand White rabbits (NZW) for this study.
We injected them with SPIO (Feridex)1 mMol Fe/kg and obtained baseline as well as 5-day post-SPIO injection MR images of the aorta (1.5 TeslaMRI system at the University of Texas, MD Anderson,Houston,Texas).
Then we compared the images in hypercholesterolemic rabbits with the normal,wild type NZW rabbits.Rabbit ex-vivo MRI studies:After the in-vivo MR images, we sacrificed the animals and excised the aorta.Then we put the isolated aorta in a gel medium, clamped both ends and anyside branches and injected gadolinium inside the lumen.
We did the same procedure for all rabbits. We also used 2 more rabbits, one WHHR and one NZW that were not injected with SPIO, as control, in the ex-vivo MR study.SPIO-Enhanced MRI study in rabbits
Histopathologic studies of Thoracic aorta in WatanabeHereditary Hypercholesterolemic rabbit after SPIO injectionH&E stainingIron stainingIron staining
Histopathologic studies of Thoracic aorta in Watanabe Hereditary Hypercholesterolemic rabbit after SPIO injectionH&E stainingIron stainingIron stainingIron particles
R=0.956Correlation between Iron positive cells in Iron staining and cell density in H&E staining in rabbitatherosclerotic aorta.
Chart1
35
0
12
6
24
17
9
8
8
10
18
22
8
0
5
6
12
3
50
24
10
40
2
35
4
10
52
1
Cell Denity in H&E staining
SPIO positive cell -Iron staining
Plaque Cell Density vs SPIO
Sheet1
HPFsNumber of nucleated cells per HPF(H&E staining)0.956113827
13735
270
32012
4106
52824
62617
7129
8118
9128
101810
111818
123322
1388
1430
15115
16146
171412
1853
196050
201424
211410
226540
2332
245035
2554
261010
276452
2821
574431
574431
Sheet1
Cell Denity in H&E staining
SPIO positive cell -Iron staining
Plaque Cell Density vs SPIO
Sheet2
Sheet3
MR Angiography 3D with Gadolinium-DTPA in Watanabe RabbitBefore SPIO injectionAfter SPIO injection
Ex-vivo MR study of the thoracic aorta in Watanabe and Wild type rabbit after SPIO injection compared to control.3D MR Angiography with Gadolinium-DTPAWatanabe rabbitPost-SPIOWatanabe rabbitcontrolNZW rabbitcontrolNZW rabbitPost-SPIO
Ex-vivo MR study of the thoracic aorta in Watanabe and Wild type rabbit after SPIO injection compared to control.(Gradient echo) Watanabe rabbitPost-SPIOWatanabe rabbitcontrol
NZW rabbitPost-SPIONZW rabbitcontrol
top related