Imaging the heart’s brain: Simultaneous
innervation/perfusion analysis in the era of new
Riccardo Liga, MD,
and Alessia Gimelli, MD
Cardio-Thoracic and Vascular Department, University Hospital of Pisa, Pisa, Italy
Fondazione Toscana Gabriele Monasterio, Pisa, Italy
Received May 4, 2016; accepted May 4, 2016
See related article, pp. 1361–1369
The entire heart is surrounded and penetrated by a
dense mesh of autonomic nervous terminals that con-
stantly modulate its activity.
autonomic nervous system includes both a parasympa-
thetic and a sympathetic branch, which are equally
important and have specular effects on cardiac function.
As a general rule, the activation of the adrenergic system
causes a rapid increase of heart rate, blood pressure, and
While those actions may be
effective in the acute phase (i.e., during exercise), they
have a deleterious impact on cardiac hemodynamic in
the long run.
In particular, the sustained hyper-activa-
tion of the adrenergic nervous system, such as in the
case of heart failure, causes a chronic spillover of
norepinephrine from the sympathetic terminals with
down-regulation of both postsynaptic receptors and pre-
synaptic re-uptake mechanism and secondary myocar-
dial functional denervation.
Interestingly, despite the clear relevance of the
sympathetic nervous system (SNS) on cardiac patho-
physiology, in the clinical ﬁeld the evaluation of cardiac
adrenergic tone has been mainly performed through
indirect, modestly reproducible, indexes (i.e., barore-
ceptor activity and heart rate variability).
On the other hand, while nuclear cardiology has
classically offered the chance to directly evaluate car-
diac SNS activity and to derive some of the most
accurate measures of myocardial intrinsic adrenergic
tone, it has never gained a wide clinical acceptance.
fact, the heart-to-mediastinum (H/M) ratio and the
washout rate of
MIBG), as easily quantiﬁed through planar scintigraphy,
have long represented the backbone of the radionuclide
evaluation of myocardial adrenergic activity.
ever, despite solid prognostic evidence in favor of their
implementation in daily clinical routine, planar mea-
sures of cardiac SNS function have remained somehow
neglected, possibly due to the intrinsic rudimentariness
of the technique and to the ability to provide only a
global evaluation of adrenergic activity.
In this context, single-photon emission computed
tomography (SPECT) imaging has represented a long
awaited innovation in nuclear-based innervation imag-
ing, allowing obtaining semi-quantitative measures of
myocardial regional adrenergic heterogeneity, which
have been clearly shown to predict patients’ adverse
prognosis independently from standard planar
Speciﬁcally, an alteration of regio-
nal cardiac adrenergic innervation is typically present in
patients with post-ischemic left ventricular (LV) systolic
dysfunction, where the presence of signiﬁcant adrener-
gic denervation can be found even in the context of fully
viable myocardial regions.
Similarly, early after an
acute coronary syndrome (i.e., an acute myocardial
infarction), the presence of areas of abnormal
MIBG uptake on SPECT imaging has been shown to
correlate with the area at risk, speciﬁcally individuating
the myocardial regions with signiﬁcant edema.
On the other hand, SPECT imaging gives the
chance to perform a comprehensive assessment of
myocardial perfusion and sympathetic innervation,
evaluated with the same imaging modality and, fre-
quently, within the same imaging session.
Initial reports have shown that the combined
investigation of LV perfusion and adrenergic innerva-
tion may allow deriving prognostically relevant
Reprint requests: Alessia Gimelli, MD, Fondazione Toscana Gabriele
Monasterio, Via Moruzzi 1, 56124 Pisa, Italy; email@example.com
J Nucl Cardiol 2017;24:1374–7.
Copyright Ó 2016 American Society of Nuclear Cardiology.