Thermography has potential for identifying vulnerable atherosclerotic plaques by detecting regions of increased heat produced by inflammatory cells within plaques. Studies have found atherosclerotic plaques to have temperature heterogeneity not seen in healthy vessel walls, with warmer regions correlated with higher macrophage density. Clinical studies have shown increased temperature differences between plaques and healthy vessel walls are associated with increased inflammation and predict worse clinical outcomes. Thermography may help identify high risk plaques but needs further validation in clinical trials.

1. Editorial Slides
VP Watch, April 3, 2002, Volume 2, Issue 13
Thermography: a “Hot” Approach to Identify
Vulnerable Plaques
By: Mohammad Madjid, M.D.
University of Texas-Houston and Texas Heart Institute

2. Detection of vulnerable plaques has become
the holy grail of cardiology.
Atherosclerosis is an inflammatory disease.
Therefore it can be sought by signs of
inflammation.1

3. Cardinal Signs of Inflammation
PainPain
RednessRedness
HEATHEAT
SwellingSwelling
InflammationInflammation

4.  Casscells et al. have hypothesized
that vascular inflammation and
plaque vulnerability can be
identified by the heat released from
activated macrophages in the
plaque.2

5.  It is known that macrophages are metabolically
very active with a high turn-over rate of total ATP
content.
 Newsholme P. Biochem J. 1989;261:211-8
 This high metabolic rate can lead to increased
heat production in areas of macrophage
accumulation while it cannot be observed in
areas of smooth muscle cell accumulation in the
absence of inflammatory cell infiltration.
Bjornheden T. Arteriosclerosis. 1987;7:238-47

6. • In 1996, Casscells, Willerson, et al measured the intimal surface
temperatures at 20 sites in each of 50 samples of carotid artery taken
at endarterectomy from 48 patients.2
• They found several regions in which the surface temperatures varied
reproducibly by 0.2-0.3 degrees C, but 37% of plaques had
substantially warmer regions. While macrophage/monocytes density
was related to higher temperature, such a relation was not seen with
smooth muscle cell density. 2
• They were also able to show temperature heterogeneity of the
surface of human carotid plaques ex vivo by infrared camera. 2
• Later on, Naghavi et al. using a thermosensor catheter showed in
vivo temperature heterogeneity of atherosclerotic arteries in dogs and
rabbits. Also he found ex vivo that areas with high temperature have
low pH.3

7. Temperature Heterogeneity on the Surface
of An Endartherectomized Carotid Plaque
Casscells W et al. Lancet. 1996;347:1447-51

8. Infrared Thermography Confirmed Temperature
Heterogeneity of Atherosclerotic Plaques
Dog model of atherosclerosis develops
marked lesions in its coronary arteries (left
panel). Willerson et al observed significant
temperature heterogeneity along the
coronary arteries of these dogs using an
infrared camera (right panel). 4An infrared camera image
shows marked temperature
heterogeneity over the
surface of an atherosclerotic
carotid plaque

9. Inverse Correlation of pH and temperature (ºC)
in endartherectomized human carotid plaques
Naghavi et al. Atherosclerosis, 2002, in press

10. Naghavi et al developed a
multi-channel thermography
basket catheter to measure
temperature heterogeneity over
vessel wall of atherosclerotic
animals. They observed higher
average temperature as well as
temperature heterogeneity in
femoral arteries of
atherosclerotic dogs
compared to their carotid
arteries which are free of
disease. 5

11. Temperature Heterogeneity in Aorta of
Watanabe vs. Normal Rabbits
Temperature heterogeneity in
aortae of atherosclerotic
Watanabe rabbits
No temperature heterogeneity
in aortae of normal New
Zealand rabbits

12. • Stefanadis and colleagues from
Athens later used a
thermography catheter to
demonstrate in vivo thermal
heterogeneity in human
atherosclerotic coronary
arteries. They observed that
temperature was constant
within the arteries of the control
subjects, whereas most
atherosclerotic plaques showed
higher temperature compared
with the healthy vessel wall.
Temperature differences
between atherosclerotic plaque
and healthy vessel wall
increased progressively from
patients with stable angina to
those with acute myocardial
infarction. 6
Thermal Heterogeneity – Clinical SyndromeThermal Heterogeneity – Clinical Syndrome

13. • In subsequent studies, Stefanadis et al
studied 60 patients with coronary heart
disease (CHD) and 20 sex- and age-matched
controls without CHD. There found strong
correlations between C-reactive protein (CRP)
and serum amyloid A (SAA) with the
temperature differences.7

14. • Toutozas, Stefanadis and colleagues also reported a
good correlation between remodeling index and
temperature difference (DT) between the
atherosclerotic plaque and the healthy vessel wall in
patients with acute coronary syndromes. 8
• They also showed that serum MMP-9 concentration is
correlated with temperature difference in patients with
acute coronary syndromes. 9
• In another set of clinical studies on 86 patients
undergoing a successful percutaneous intervention,
Stefanadis et al found that during a follow-up period of
17.88 +/- 7.16 months, temperature difference between
the atherosclerotic plaque and the healthy vessel wall
was a strong predictor of adverse cardiac events. 10
• Of clinical importance, Stefanadis et al. found patients
on statins show significantly less temperature
heterogeneity comparing to those who did not receive
11

15.  As reported in this issue of VPWatch, Verheye et al
showed that in vivo temperature heterogeneity of rabbit
atherosclerotic plaques is determined by plaque
composition. 12
 They randomized New Zealand normal rabbits to either
normal or cholesterol-rich diet for 6 months. In control
animals, plaque formation and temperature
heterogeneity were absent. In hypercholesterolemic
rabbits, plaque formation was prominent in the thoracic
aorta.
 Temperature heterogeneity was markedly present and
increased with plaque thickness. Importantly, after 3
months of cholesterol lowering, plaque thickness
remained unchanged, but temperature heterogeneity
was significantly reduced. Plaque histology showed
significant loss of macrophages.12

16. Conclusion
• Intravascular thermography is a novel
approach in detection of inflamed
vulnerable plaques.
• If reproducibly proven in clinical trials,
coronary thermography may become an
addition to cath lab for risk stratification of
vulnerable patients.

17. Future:
A combination of
ultrasound and
thermography may
provide invaluable
information about
morphology as well
as activity of plaques.

18. Questions:
• How accurate is the measurement of vessel wall
temperature in presence of flowing blood?
• Is thermography per se enough to make clinical decision
or it has to be combined with other imaging data?
• Once a “hot plaque” is found, how we may know if it is
an inflamed plaque at risk of rupture or an inflamed
plaque which is already ruptured?
• What would be the treatment of choice once “hot
plaques” are found?

19. References
1. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340:115-26.
2. Casscells W, Hathorn B, David M, Krabach T, Vaughn WK, McAllister HA, Bearman G, Willerson JT. Thermal detection of cellular
infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis. Lancet. 1996;347:1447-51.)
3. Naghavi et al. Atherosclerosis, 2002, in press
4. Thermography: A Novel Approach to Identify Plaques at Risk of Rupture and/or Thrombosis. Mohammad Madjid, Morteza Naghavi,
James T. Willerson, Ward Casscells, In “The Vulnerable Atherosclerotic Plaque: Understanding, Identification and Modification” edited
by Valentin Fuster, Futura Co., NY, 2002
5. Gul K, O'Brien T, Siadaty S, Madjid M, Mohammadi RM, Tewatia T, Willerson JT, Casscells W, Naghavi M. Coronary thermosensor
basket catheter with thermographic imaging software for thermal detection of vulnerable atherosclerotic plaques. J Am Coll Cardiol.
2001;37:18A.
6. Stefanadis C, Diamantopoulos L, Vlachopoulos C, Tsiamis E, Dernellis J, Toutouzas K, Stefanadi E, Toutouzas P. Thermal
heterogeneity within human atherosclerotic coronary arteries detected in vivo: A new method of detection by application of a special
thermography catheter. Circulation. 1999;99:1965-71.
7. Stefanadis C, Diamantopoulos L, Dernellis J, Economou E, Tsiamis E, Toutouzas K, Vlachopoulos C, Toutouzas P. Heat production of
atherosclerotic plaques and inflammation assessed by the acute phase proteins in acute coronary syndromes. J Mol Cell Cardiol.
2000;32:43-52.
8. Toutouzas MK, Stefanadis CM, Vavuranakis MM, Tsiamis ME, Tsioufis MC, Pitsavos CM, P.M. T. Arterial remodeling in acute coronary
syndromes: correlation of IVUS characteristics with temperature of the culprit lesion. Circulation. 2000;102:II-707.
9. Toutouzas K, Stefanadis C, Tsiamis E, Vavuranakis M, Tsioufis C, Tsekoura D, Vaina S, P. T. The temperature of atherosclerotic
plaques is correlated with matrix metalloproteinases concentration in patients with acute coronary syndromes. J Am Coll Cardiol.
2001;37:356A.
10. Stefanadis C, Toutouzas K, Tsiamis E, Stratos C, Vavuranakis M, Kallikazaros I, Panagiotakos D, Toutouzas P. Increased local
temperature in human coronary atherosclerotic plaques: an independent predictor of clinical outcome in patients undergoing a
percutaneous coronary intervention. J Am Coll Cardiol. 2001;37:1277-83.
11. Stefanadis C, Toutouzas K, Tsiamis E, Vavouranakis M, Kallikazaros I, Toussoulis D, Vaina S, Voutsas A, Pitsavos C, Toutouzas P.
Patients with coronary artery disease under statin treatment have decreased heat release from culprit lesions: new insights in the
nonlipid effects of statins. Eur Heart J. 2001;22:28 C.
12. Verheye S, De Meyer GR, Van Langenhove G, Knaapen MW, Kockx MM. In vivo temperature heterogeneity of atherosclerotic plaques
is determined by plaque composition. Circulation 2002 Apr 2;105(13):1596-601