Cadmium-zinc-telluride myocardial perfusion imaging: The dream of a single test gets nearer
Cadmium-zinc-telluride myocardial perfusion imaging: The dream of a single test gets nearer
Francesco Nudi 0 1 4 5
Giuseppe Biondi-Zoccai 0 1
MStat 0 1 2 3
0 Funding This work was supported by Etisan , Rome, Italy. Reprint requests: Francesco Nudi, MD , Service of Hybrid Cardio Imaging, Madonna della Fiducia Clinic , Via Giuseppe Mantellini 3, 00179, Rome , Italy
1 To infinity and beyond! Buzz Lightyear , Toy Story , Walt Disney Pictures
2 Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome , Latina , Italy
3 Department of AngioCardioNeurology, IRCCS Neuromed , Pozzilli , Italy
4 Ostia Radiologica , Rome , Italy
5 Service of Hybrid Cardio Imaging, Madonna della Fiducia Clinic , Rome , Italy
Non-invasive functional cardiovascular imaging is a cornerstone in the management of patients with suspected or established coronary artery disease (CAD), given its capability to simultaneously provide diagnostic insight, risk-prediction, and guidance to decision-making.1-3 Myocardial perfusion imaging (MPI) with singlephoton emission computed tomography (SPECT) embodies the key strengths of non-invasive functional cardiovascular tests, by combining the physiologic details provided by stress testing (exercise or pharmacologic) with accurate information on myocardial perfusion, viability, and contractility, thus justifying its historically prominent role in cardiovascular imaging.1,4-6 The traditional acquisition technology for SPECT is the Anger camera, which has good diagnostic and excellent prognostic accuracy, as demonstrated by several studies with large sample size, despite its evident limitations in terms of spatial and energy resolution, as well as acquisition times.7
The recent introduction of the
cadmium-zinc-telluride (CZT) cameras for SPECT has purportedly
revolutionized MPI, thanks to their superior spatial and
energy resolution.8,9 Given their groundbreaking
technical features and the differences between the two
available but competing suites (D-SPECT, Spectrum
Dynamics, Palo Alto, CA, USA; Discovery NM 530c or
Discovery NM/CT 570c with Alcyone technology, GE
Healthcare, Haifa, Israel), there are, however, ongoing
developments and refinements in the application of this
imaging technology to current cardiovascular
practice.10–12 Accordingly, the scholarly literature on CZT
MPI is continuing to expand momentously, as
demonstrated by the work by Jameria and colleagues published
in this issue of the Journal.13
Specifically, Jameria et al report hereby a
singlecenter retrospective observational study comparing
acquisition of MPI with CZT vs Anger cameras, and
focusing on several protocol subtleties such as
stressonly vs stress-rest acquisition, and upright vs supine
positioning, while using a D-SPECT suite and relying on
coronary angiography as gold standard.13 Notably, a
total of 740 subjects underwent MPI with both
DSPECT and Anger cameras, even if only 112 (15.1%)
patients had coronary angiographic details, with 48
(6.5%) of them eventually showing significant CAD at
angiography. In this series, moderate defects were
predominant, and all images were interpreted independently
by two different nuclear physicians, with varying
experience. The main finding of this work is that overall
predictive values were similar with D-SPECT and Anger
cameras, thus supporting a more widespread adoption of
this CZT suite. Conversely, only the interpretation of
DSPECT images by the more experienced operator
provided similar results for sensitivity, specificity, and
normalcy rate in comparison to Anger images, whereas
image interpretation by the less experienced physician
had lower diagnostic accuracy with D-SPECT than with
Anger cameras, especially in patients with reduced
systolic function. Intriguingly, adding rest images to
stress-only tests improved sensitivity of CZT MPI, by
enabling the correct reclassification of attenuation
artifacts (typically considered equivocal) into actual
perfusion defects in as many as 11 patients eventually
displaying significant CAD at angiography. In any case,
the main take home message of the contribution by
Jameria et al, notwithstanding the relatively small
sample study and the heterogeneity in operator
expertise, is that CZT MPI with D-SPECT is largely
equivalent in terms of diagnostic accuracy to Anger
cameras, even if a stress-only protocol is used.
Experience is important though, as adding rest images in case
of equivocal findings.
In light of the work of Jameria and colleagues, and
the total body of evidence on this topic,8–12 it is
important to highlight the current and future prospects of
CZT technology for MPI. First, it is paramount to
recognize that the two available embodiments of this
technology (Alcyone and D-SPECT) might not be
identical in performance, despite aggregate analyses
suggesting the contrary.12,14,15 Second, irrespective of
the chosen CZT technology, the spatial and energy
resolution of these cameras is significantly superior to
that of Anger cameras.8 These technical advantages
might translate into improvements in sensitivity and
specificity, after an adequate learning curve, on top of
providing some practical perks in testing procedures,
such as stress-only protocol for radiation exposure
reduction and dual-isotope imaging when a single
acquisition is appropriate.10,11 Exploitation of the
superior sensitivity of CZT technology means that we
can reduce acquisition time if radionuclide doses similar
to those used with Anger cameras are chosen, but, much
more importantly, that doses can be dramatically
reduced if acquisition times are only moderately
decreased. Indeed, longer acquisitions are likely going to
be crucial to treasure the advantages of CZT cameras
and achieving the goal of reducing (more than halving)
radiation dose (even to 1.7 mSv as reported by Sharir
et al).16 Aiming for the same goal, the impact of
operator experience is also crucial, as is dedicated training to
best exploit images obtained with CZT cameras. Indeed,
despite the possibility to use semiquantitative or
quantitative scores (as with positron emission tomography
[PET]), the role of the physician and his qualitative
interpretation remains paramount (as in Jameria and
colleagues, which highlights the operator dependency of
this type of analysis).13 Thus, a refined imaging of high
visual quality continues to be a very important goal
given that analysis relies significantly on such image
The heightened sensitivity of CZT detectors may
also open the room for an increase in stress-only exams
for a likely ‘‘shift’’ from equivocal results to exams
which are clearly negative, for two reasons. First, the
availability of a more reliable end-diastolic imaging
which completes exam interpretation. Second, we can
acquire left ventricular ejection fraction (LVEF) early
after stress and afterwards (even after 1 hour).17 The
presence of adequate perfusion also in the end-diastolic
phase and of a normal LVEF reserve reduces equivocal
exams increasing diagnostic true negatives and surely
prognostic true negatives.
The negative predictive value is already high with
Anger cameras, and thus the main advantage of using a
CZT camera lies in the increase in the number of
patients with negative tests, which translates into a more
accurate appraisal of the warranty period.18 Focusing on
positive tests, the expected pros of CZT are a more
correct classification of ischemic patients in terms of
ischemia severity (e.g., in keeping with the Maximal
Ischemia Score [MIS], distinguishing minimal, mild,
moderate or severe ischemia), extension, and
involvement of the corresponding coronary vessel, in particular,
the left anterior descending (e.g., single-vessel-related
ischemia [VRI] versus multiple VRI, with or without left
anterior descending involvement).4,5 Accordingly, we
may more accurately proceed with risk stratification and
choice of subsequent clinical management. Focusing on
the evaluation of end-diastolic perfusion, another
advantage of CZT is the possibility of significantly
reducing false-positive results in patients with left
bundle branch block (Figure 1), who typically display a
perfusion abnormality which is more severe in the
endsystolic phase than in the end-diastolic phase, at odds
with ischemic patients (Figure 2). Other unique
strengths of CZT cameras include the distinctively
highenergy resolution which enables dual-isotope
administration.19 For instance, two key clinical advantages can
be envisioned in the evaluation of patients with prior or
recent myocardial infarction (stress or rest Tc and
restdelay Tl) and in patients with heart failure (rest Tl plus
metaiodobenzylguanidine [MIBG]) to quantify
prognosis and the risk of sudden death.
Thanks to the advantage of a significant reduction
of radiation exposure, it is possible to acquire hybrid
imaging with coronary computed tomography (CT).20
For instance, the total radiation dose for a stress-only
CZT MPI study with associated coronary CT amounts to
2.1 mSv.21 Indeed, a specific suite (Discovery NM/CT
570c) already enables, with the same equipment, to
complete both exams, functional and anatomic. The
improved spatial resolution may lead to a more credible
relation between myocardial region and corresponding
coronary vessel. Two important clinical advantages can
be envisioned. First, assuming a negative MPI result, it
will be possible to distinguish among three competing
scenarios: the absence of coronary disease, the presence
of a non-significant coronary stenosis, or an
angiographically significant stenosis. This will be pivotal to
better define individual warranty period. The second
advantage lies in the evaluation of intermediate coronary
stenosis, which may show ample range of coronary
reserve, from normal to significantly reduced.
Another key and quite novel feature of CZT
technology is the possibility of appraising coronary flow
reserve (CFR).22 The sensitivity of MPI to recognize
CAD is in general higher in patients with multivessel
disease than in those with single-vessel disease, whereas
balanced ischemia remains rare. The drawback of MPI
may lie in the potential underestimation of ischemia
severity and vessel disease extent, if the area of the
highest myocardial activity is in itself depending on the
diseased vessel, as this is the region used to compare the
activities of the other regions, which may risk being
labeled as ‘‘less ischemic.’’ When the region with the
highest activity depends from a diseased vessel, both
stress myocardial blood flow (MBF, measured in mL/
min/g of myocardium) and CFR (the ratio between stress
[hyperemic] MBF and rest [basal] MBF) will be
reduced. Another intriguing indication to CFR is the
evaluation of mild perfusion defects in the regions
depending from the left anterior descending.
Accordingly, CZT cameras may eventually topple the
dominating role of coronary angiography, thus that the
old paradigm that the functional detail may
underestimate the anatomic detail will convert into the novel
paradigm that the anatomic detail may overestimate the
actual patient risk and cannot alone represent an
indication to coronary revascularization.
In conclusion, CZT MPI represents a major
breakthrough in the diagnostic, prognostic, and management
work-up of patients with suspected or established CAD,
and most interestingly, this development will open the
way for the potential application of MPI in the primary
prevention of cardiovascular disease in apparently
healthy subjects. Further studies are, however, necessary
to better understand and implement this promising
development in non-invasive functional cardiovascular
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