NEWS & VIEWS

I M AG I N G activity in the arteries altering the compo

sition of the surrounding fat. Second, the

Perivascular fat an unheralded

study suggests that this phenomenon might
be clinically useful, demonstrating that these
structural PVAT changes are detectable with
informant of coronary inflammation conventional CT imaging, thereby allowing
us to estimate coronary inflammation activ
MarcR.Dweck and ZahiA.Fayad ity. Although other imaging techniques, such
as 18F-PET3 and 68Ga-DOTATATE PET4, can
A novel image-analysis method using standard CT imaging demonstrates be used to identify inflamed and high-risk
coronary plaques, these approaches involve
that changes in the CT signal of coronary perivascular adipose tissue are
complex imaging protocols and are less widely
associated with the degree of inflammation in adjacent coronary plaques. available than CT imaging. The great advan
This exciting development might become a useful adjuvant clinical tool, tage of PVAT CT attenuation is that this analy
although further validation and prospective outcome studies are required. sis would be possible on standard CT images
that are increasingly being acquired in routine
Refers to Antonopoulos, A. S. etal. Detecting human coronary inflammation by imaging perivascular fat. Sci. Transl. Med. clinical practice, with potential added benefits
9, eaal2658 (2017) offered by dual-energy or multispectral CT
imaging 5. Translation of this novel approach
Inflammation is a crucial pathological process release cytokines that alter the composition of to patient care would, therefore, seem readily
driving the development and progression of the surrounding PVAT. The researchers sub feasible, assuming that the analysis costs do
atherosclerosis. Importantly, inflammation is sequently provide extensive and wide-ranging not prove to be prohibitive.
also strongly implicated in the development evidence to support their hypothesis2. This Although this new technique is in many
of acute plaque rupture, the pathological evidence included confirmation that inflamed ways exciting, several important caveats merit
process leading to myocardial infarction and human aortic tissues release cytokines, which attention. The first is whether invivo CT
stroke. Therefore, inflammation is a valu inhibit adipocyte proliferation and the matur imaging has the necessary spatial resolution to
able imaging target that might improve not ation of small pre-adipocytes into larger, lipid- detect changes in PVAT CT attenuation con
only our understanding of the pathophysio laden adipocytes. Moreover, using a novel sistently, given the small volume of this tissue
logy of atherosclerosis, but also our ability to parameter, the fat attenuation index (FAI), surrounding the coronary arteries. This issue
identify patients at increased risk of future the investigators demonstrated that these would seem particularly challenging in prox
cardiovascular events1. Advances that might reductions in PVAT lipid content could be imity to high CT-attenuation structures, such
enable the noninvasive detection of coro detected by monitoring alterations in theCT as intracoronary stents, which are notoriously
nary vascular inflammation are, therefore, attenuation (that is, the reduction in the associated with blooming artefact. Although
of major interest, particularly if these strat CTsignal) of PVAT. Indeed, Antonopoulos the investigators provide clinical data on the
egies employ routine and widely available and colleagues observed an inverse corre effect of stents in the CT FAI assessment,
imagingtechniques. lation between exvivo and invivo PVAT CT these data were derived from ~20patients
attenuation and both the degree of adipocyte with a mixture of clinical presentations.
differentiation and adipocyte size on histo
...inflamed coronary logy. Finally, the investigators demonstrated
Box 1 | Practice points
plaquesrelease cytokines that that FAI values were higher around culprit
coronary plaques after myocardial infarction Coronary inflammation induces structural
alter the composition of the (n=10) than in stented, nonculprit plaques changes in the surrounding perivascular
surrounding PVAT and stented lesions in stable patients(n=11)2. adipose tissue (PVAT)
Together, these data suggest that assess These changes can be detected on routine
ment of PVAT CT attenuation can be used as CT imaging on the basis of changes in CT
In this context, Antonopoulos and col a proxy of inflammation in the adjacent coro signal attenuation
leagues investigated whether information nary vasculature. This study is interesting on PVAT CT attenuation can, therefore,
about the degree of inflammation within coro two accounts. First, these findings inform us provide a surrogate measure of coronary
nary atherosclerotic plaques could be gleaned about the complex relationship between what inflammation
by imaging not the plaques themselves, but is happening in the coronary arteries and the This novel methodology could provide
instead the surrounding perivascular adi fat that surrounds them. Accumulating evi useful additional information from routine
clinical scans
pose tissue (PVAT) with the use of routine dence indicates that perivascular fat can influ
CT imaging 2 (BOX1). The rationale for this ence events within the arteries, but this study Further multicentre validation and
prospective outcome data are now required
approach was that inflamed coronary plaques suggests the opposite is also true, with disease

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NEWS & VIEWS

Finally, conventional CT imaging also ena 1. Dweck,M.R. etal. Imaging of coronary

...conventional CT imaging
also enables assessment of
various high-risk atherosclerotic
plaque characteristics
Therefore,further validation in a multicentre
setting is required to confirm the general
feasibility of this approach. Second, as the
investigators themselves acknowledge, these
are preliminary findings and whether CT FAI
assessments provide useful prognostic data has
not been established. However, this informa
tion should be readily available from existing
CTimaging registries and randomized, con
trolled trials that include prospective outcome
data. Such prognostic studies will be crucial
to the potential s uccess of this approach, and
are of particular relevance given recent dis
cussions about the clinical value of vulnerable
plaque identification6. Currently available
studies suggest that individual vulnerable
plaques are actually reasonably common, and
only rarely cause clinical events7. Strategies
to identify vulnerable plaques might, how
ever, prove to be more useful at the patient
level, for identifying individuals with a pro
pensity to develop plaques at risk of rupture,
and who are, therefore, more likely to sustain
futureevents1.
bles assessment of various high-riskathero
sclerotic plaque characteristics8. These plaque
characteristics include positive remodelling,
spotty calcification, and low CT attenuation.
Like PVAT CT attenuation, these features also
have a demonstrated association withcul
prit coronary plaques, but unlike with PVAT
CT attenuation, these associations are also
supported by prognostic data demonstrat
ing that patients with these features have
an increased risk of subsequent myocardial
infarction9. Can an indirect method such as
PVAT CT attenuation provide incremental
information to techniques used to examine
the composition of coronary plaques directly?
Further work in large, multicentre cohorts is
required to address these crucial issues, and to
assess the clinical implications of these exciting
initialobservations.
MarcR.Dweck is at the Centre for Cardiovascular
Science, University of Edinburgh,
LittleFranceCrescent, Edinburgh, EH164SB, UK.
ZahiA.Fayad is at the Translational and Molecular
Imaging Institute, Icahn School of Medicine at
MountSinai, 1470Madison Avenue, NewYork,
NewYork10029, USA.
Correspondence to Z.A.F.
zahi.fayad@mssm.edu
doi:10.1038/nrcardio.2017.127
Published online 24 Aug 2017
atherosclerosis - evolution towards new treatment
strategies. Nat. Rev. Cardiol. 13, 533548 (2016).
2. Antonopoulos,A.S. etal. Detecting human coronary
inflammation by imaging perivascular fat. Sci. Transl.
Med. 9, eaal2658 (2017).
3. Joshi,N.V. etal. 18Ffluoride positron emission
tomography for identification of ruptured and high-risk
coronary atherosclerotic plaques: a prospective clinical
trial. Lancet 383, 705713 (2014).
4. Tarkin,J.M. etal. Detection of atherosclerotic
inflammation by 68GaDOTATATE PET compared
to[18F]FDG PET imaging. J.Am. Coll. Cardiol. 69,
17741791 (2017).
5. Danad,I., Fayad,Z.A., Willemink,M.J. & Min,J.K.
New applications of cardiac computed tomography:
dual-energy, spectral, and molecular CT imaging.
JACCCardiovasc. Imaging 8, 710723 (2015).
6. Arbab-Zadeh,A. & Fuster,V. The myth of the
vulnerable plaque: transitioning from a focus on
individual lesions to atherosclerotic disease burden
forcoronary artery disease risk assessment. J.Am.
Coll. Cardiol. 65, 846855 (2015).
7. Stone,G.W. etal. A prospective natural-history study
of coronary atherosclerosis. N.Engl. J.Med. 364,
226235 (2011).
8. Dweck,M.R., Williams,M.C., Moss,A.J.,
Newby,D.E. & Fayad,Z.A. Computed tomography
and cardiac magnetic resonance in ischemic heart
disease. J.Am. Coll. Cardiol. 68, 22012216
(2016).
9. Motoyama,S. etal. Plaque characterization by
coronary computed tomography angiography
andthelikelihood of acute coronary events in
midterm followup. J.Am. Coll. Cardiol. 66, 337346
(2015).
Acknowledgements
M.R.D. is supported by the British Heart Foundation
(FS/14/78/31020), and is the recipient of the Sir Jules Thorn
Award for Biomedical Research 2015.Z.A.F. is supported
by N I H g ra n t s P 01 H L 1 31 4 7 8 , R 01 H L 0710 21 ,
R01HL128056, R01HL135878, and R01EB009638.
Competing interests statement
The authors declare no competing interests.

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