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Hypothesis:
Monocyte-macrophages on or just
beneath the plaque surface are
detectable by the heat that they
produce.
Multiple
non-stenotic
coronary
plaques
In vivo live animal study
Marked temperature
heterogeneity observed with
Intravascular Thermosensor Basket Catheter
Volcano Therapeutics Inc
(prototype)
Stefanadis et al, 1999
First in vivo human intra-coronary
thermometry study
Stefanadis et al, 2000
Coronary Infrared Thermography Catheter
(prototype)
Apo-E aorta heated at 37C (staining for TUNEL and
DAPI)
Apo-E aorta heated at 42 C (TUNEL and DAPI staining)
TUNEL
DAPI
DNA isolation from atherosclerotic aorta of apo-E
mice by agarose gel electrophoresis
37C
37C
37C
42C
42C
42C
We hypothesized that plaque inflammation and
macrophage infiltration can be detected by:
1- Decreased plaque pH and
increa...
pH Distribution in 48 Human Carotid Plaques
pH
9.00
8.88
8.75
8.63
8.50
8.38
8.25
8.13
8.00
7.88
7.75
7.63
7.50
7.38
7.25
...
Correlation of pH and Temperature in
Human Carotid Plaques
Iron staining of mouse circulating
monocyte after 30 minutes
MR Image of Abdominal Aorta
After SPIO Injection in Mouse
Apo E
deficient
mouse
C57B1
(control)
mouse
Before injection Aft...
The Online Cardiovascular Research Community
www.VulnerablePlaque.org
Conclusions
1. Temperature at the lumen of living carotid
plaques correlates with density of inflammatory
cells, and inver...
Conclusions
continued
4. These temperature differences can be
detected by infrared cameras.
5. Compared to normal arteries...
Conclusions
continued
7. Stefanadis and colleagues have reported that hot
plaques confer higher risk; it will be important...
Conclusions
continued
10.10. Near-IR Spectroscopy can estimate plaqueNear-IR Spectroscopy can estimate plaque
protein/lipi...
www.HotPlaque.com
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
New insights into vulnerable plaque
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New insights into vulnerable plaque

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New insights into vulnerable plaque

  1. 1. Hypothesis: Monocyte-macrophages on or just beneath the plaque surface are detectable by the heat that they produce.
  2. 2. Multiple non-stenotic coronary plaques In vivo live animal study Marked temperature heterogeneity observed with
  3. 3. Intravascular Thermosensor Basket Catheter Volcano Therapeutics Inc (prototype)
  4. 4. Stefanadis et al, 1999 First in vivo human intra-coronary thermometry study
  5. 5. Stefanadis et al, 2000
  6. 6. Coronary Infrared Thermography Catheter (prototype)
  7. 7. Apo-E aorta heated at 37C (staining for TUNEL and DAPI)
  8. 8. Apo-E aorta heated at 42 C (TUNEL and DAPI staining) TUNEL DAPI
  9. 9. DNA isolation from atherosclerotic aorta of apo-E mice by agarose gel electrophoresis 37C 37C 37C 42C 42C 42C
  10. 10. We hypothesized that plaque inflammation and macrophage infiltration can be detected by: 1- Decreased plaque pH and increased pH heterogeneity and excessive lactate content 2- pH and temperature of plaque are inversely correlated
  11. 11. pH Distribution in 48 Human Carotid Plaques pH 9.00 8.88 8.75 8.63 8.50 8.38 8.25 8.13 8.00 7.88 7.75 7.63 7.50 7.38 7.25 7.13 7.00 6.88 6.75 6.63 Noofpointswiththesameph 140 120 100 80 60 40 20 0 There is a bimodal distribution of pH with a marked pH variation ranging from 6.5 to 8.9 (in 858 points)
  12. 12. Correlation of pH and Temperature in Human Carotid Plaques
  13. 13. Iron staining of mouse circulating monocyte after 30 minutes
  14. 14. MR Image of Abdominal Aorta After SPIO Injection in Mouse Apo E 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
  15. 15. The Online Cardiovascular Research Community www.VulnerablePlaque.org
  16. 16. Conclusions 1. Temperature at the lumen of living carotid plaques correlates with density of inflammatory cells, and inversely with cap thickness. 2. Differences of more than 0.3 C were seen in all specimens but only a minority had differences of 2o C or more. 3. Large differences in temperatures were more often found in patients who were younger, symptomatic, female, and not taking aspirin.
  17. 17. Conclusions continued 4. These temperature differences can be detected by infrared cameras. 5. Compared to normal arteries, inflamed and lipid-rich plaques are acidic, while calcified and thrombosed plaques are alkaline. 6. Plaque pH correlates moderately and inversely) with plaque temperature.
  18. 18. Conclusions continued 7. Stefanadis and colleagues have reported that hot plaques confer higher risk; it will be important to determine whether plaque prognosis is best determined by T, ∆T, pH, ∆pH or a combination. 8. Heating to 41o C decreases expression of pro- inflammatory genes. 9. Heating to 42-43o C causes apoptosis, mainly of macrophages.
  19. 19. Conclusions continued 10.10. Near-IR Spectroscopy can estimate plaqueNear-IR Spectroscopy can estimate plaque protein/lipid ratios and may also provideprotein/lipid ratios and may also provide inferences as to concentrations of plaqueinferences as to concentrations of plaque HH++ , NO, glucose, O, NO, glucose, O22 and oxidants.and oxidants. 11.11. IR and near IR may predict plaqueIR and near IR may predict plaque behaviour alone or in combination withbehaviour alone or in combination with ultrasound, angioscopy, magneticultrasound, angioscopy, magnetic resonance or immunoscintigraphyresonance or immunoscintigraphy
  20. 20. www.HotPlaque.com

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