ADVANCES IN NONNUCLEAR IMAGING TECHNOLOGIES
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Over the last decade, significant scientific advances
have been achieved in the fields of atherosclerosis and
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the arterial surface creates a nidus for acute thrombus
formation.1 The paradigm of a modestly stenotic plaque,
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46ascular biology, yielding a greater understanding of the
echanisms of atherosclerotic coronary artery disease.
rogress in diagnosis, treatment, and prevention of cor-
nary atherosclerosis has been hampered by the lack of a
itable large animal model for atherosclerotic plaque
pture. This deficiency has concentrated interests in
athologic studies and imaging modalities to advance
ur understanding of the pathogenesis of vulnerable
laque.
Postmortem studies imply that myocardial infarction
sults from an acute process of plaque rupture or erosion
f modestly stenotic plaque. Disruption in the integrity of
which is prone to disruption, causing acute coronary
syndromes or sudden cardiac death, has rapidly gathered
momentum.2,3 The pathologic characteristics of rupture-
prone, or vulnerable, plaques include a thin fibrous cap
(
65 m), large lipid pool, and increased macrophage
activity (Figure 1).4-6 Cellular mechanisms thought to
predispose to plaque vulnerability include reduced col-
lagen synthesis, local overexpression of collagenase, and
smooth muscle cell apoptosis.7 These molecular changes
appear most prominent at the plaque shoulder, where
mechanical strain is maximized.8,9 Although plaque
rupture or erosion occurs throughout the vasculature,
only certain plaques form an occlusive thrombus causing
clinical syndromes.10 The factors that dictate the clinical
outcome remain unknown.
The concept that acute coronary events result from
lesions with modest coronary artery stenosis may explain
why targeting flow-limiting stenoses with traditional
strategies of revascularization has minimal impact in
reducing subsequent acute coronary events. Conversely,
studies of plaque regression achieve significant reduc-
tions in acute coronary events despite disappointing
regression of angiographically detected stenoses.7 A
current goal of cardiovascular research is to detect the
rom the Cardiology Divisiona and Wellman Center for Photomedi-
cine,b Massachusetts General Hospital, and Harvard Medical
School,c Boston, Mass, and Department of Cardiology,d Kinki
University School of Medicine, Osaka, Japan.
his study was funded in part by the Center for Integration of Medicine
and Innovative Technology (development of the imaging system
platform) and the Guidant Corporation.
eprint requests: Guillermo J. Tearney, MD, PhD, Wellman Labora-
tories of Photomedicine, Massachusetts General Hospital, BAR 703,
Boston, MA 02114; gtearney@partners.org.
71-3581/$30.00
opyright © 2005 by the American Society of Nuclear Cardiology.
i:10.1016/j.nuclcard.2005.05.013Intravascular optical cohe
Cellular imaging
Briain D. MacNeill, MB, MSc,abc Brett E. B
Hiroshi Yabushita, MD, PhD,bd Ik-Kyung J
Guillermo J. Tearney, MD, PhDbc
The vast majority of acute coronary event
or vulnerable plaques. Novel imaging techn
quiescent vulnerable features within coronary
monitor plaque progression, and target thera
is an intravascular imaging modality capable
in vivo. Recently, optical coherence tomograph
atherosclerotic plaque ex vivo was demonst
practice yields a hybrid image incorporating
activity. In a recently conducted clinical study
evidence supporting both the vulnerable p
inflammatory risk, linked by the common thre
found. These results suggest that elevated m
both in culprit lesions and at remote sites
Superimposed on this inflammatory backgr
particularly at the cap surface and at areas
instability of individual lesions. (J Nucl Cardi0ce tomography:
a, PhD,bc
MD, PhD,ac and
ttributed to rupture or erosion of high-risk
are being actively sought that can detect
ue and thereby identify populations at risk,
propriately. Optical coherence tomography
tecting and characterizing coronary plaque
ntification of macrophage infiltration within
Application of this technique to clinical
ue morphology with a measure of biologic
ssing macrophage distributions in patients,
model and the hypothesis of multifocal
increased macrophage infiltration, has been
cal coronary macrophage content, present
es as a background for heightened risk.
, local increases in macrophage content,
igh risk for rupture, further promote the
5;12:460-5.)

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Journal of Nuclear Cardiology MacNeill et al 461
Volume 12, Number 4;460-5 Intravascular optical coherence tomographyathophysiologic features of vulnerable plaques before
mptom development, in an effort to identify popula-
ons at risk, monitor plaque progression, and target
erapy appropriately. This review focuses on one intra-
ascular technique, optical coherence tomography
CT), particularly the use of OCT to characterize
ellular plaque composition and biologic activity.
OCT
Coronary angiography has long been accepted as the
old standard for coronary artery imaging. Angiography,
owever, is not capable of detecting vulnerable or high-risk
able 1. Comparison of noninvasive and invasive ima
f vulnerable plaque
Imaging
modality Resolution Penetration
Fibrous
cap
US 100 m Good 
ngioscopy UK Poor 
CT 10 m Modest 
ermography 0.5 mm Poor –
pectroscopy NA Modest 
travascular
MRI
160 m Good 
produced with permissionAQ2:AUTHOR: In Table 1, please verify
breviations CS, CA, CA*, and PCS do not appear in the table, so
ease clarify if necessary. from Lippincott Williams & Wilkins.14
US, Intravascular ultrasound; UK, unknown; NA, not applicable; M
nsitivity was as follows: greater than 90% (3 plus signs), 80% to
gn).
 Sensitivity 90%.
igure 1. Histologic analysis of a thin-capped lipid-rich, or
ulnerable, coronary plaque demonstrates typical features in-
uding a thin fibrous cap (arrowheads) and lipid core (L). Of
ote, the preserved lumen allows these plaques to go unnoticed
y conventional angiography.  sensitivity 80–90%;   sensitivity 50–80%;   sensitivity
50oted interest in alternative invasive or catheter-based
chniques to directly visualize the arterial wall and to
aracterize plaque composition (Table 1).14
One such novel technique, OCT, measures backscat-
red light or optical echoes derived from an infrared
ght source directed at the arterial wall.15 The resolution
f intracoronary OCT is on the order of 10 m, approx-
ately 10 times greater than that achieved with cur-
ntly available intravascular ultrasound systems. This
proved resolution enables characterization of various
therosclerotic plaque components, as demonstrated in a
istologic correlation that achieved a sensitivity and
ecificity of 92% and 94%, respectively, for lipid-rich
laque; 95% and 100%, respectively, for fibrocalcific
laque; and 87% and 97%, respectively, for fibrous
laque (Figure 2).16
In a comparison with intravascular ultrasound, in-
acoronary OCT has proven to be equivalent in detect-
g plaque and discerning fibrous or calcified plaque
orphologies and superior in identification of intimal
yperplasia, internal and external elastic laminae, and
gions of lipid-rich plaque.17 Clinical application of
CT in patients with a variety of clinical presentations of
oronary artery disease demonstrated a higher preva-
nce of lipid-rich plaque, significantly thinner caps, and
higher prevalence of thin-cap fibroatheromas in pa-
ents with acute coronary syndromes compared with
ose with stable angina.18
EX VIVO MACROPHAGE IMAGING
The knowledge that plaque instability is more closely
lated to biologic activity and cellular composition than
modalities for detection of individual characteristics
id core Inflammation Calcium Thrombus
 –  
 – – 
   
–  – –
   –
   
ference number listed in the footnote. Also, please note that the
finitions for these abbreviations were deleted from the footnote.
gnetic resonance imaging.
plus signs), 50% to 80% (1 plus sign), or less than 50% (minusplaques before disruption.11-13 These limitations have pro-
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