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C
URRENT
O
PINION
Assessment of myocardial viability using single-
photon emission computed tomography
myocardial perfusion imaging
Saurabh Malhotra
a,b
, Javier Gomez
a,b
, and Rami Doukky
a,b
Purpose of review
The assessment of myocardial viability continues to be a pressing and sometimes challenging clinical
question. Among other imaging modalities proven to be useful in the assessment of myocardial viability,
single-photon emission computed tomography (SPECT) instrumentation and expertise continue to be the
most widely available to the practicing physicians. Understanding the utility of SPECT myocardial perfusion
imaging in this domain is an enduring need.
Recent findings
A wealth of basic science and clinical data established the value of a variety of Tl-201 and Tc-99m SPECT
protocols in the assessment of myocardial viability. The diagnostic performance for Tl-201 and Tc-99m
imaging protocols for identifying viable myocardium is very good and is comparable for both agents.
Quantitative assessment of radiotracer uptake can predict, in an objective manner, the probability of
recovery of myocardial function following revascularization.
Summary
SPECT myocardial perfusion imaging with Tl-201 and Tc-99m tracers can provide an objective and
quantifiable assessment of myocardial viability, which can help predict the likelihood of myocardial
function recovery following coronary revascularization. Effective application of this imaging technique can
guide clinical decision-making for coronary revascularization.
Keywords
myocardial perfusion imaging, single photon computed tomography, technetium, thallium, viability
INTRODUCTION
Myocardial perfusion imaging (MPI) with single-
photon emission computed tomography (SPECT)
remains a cornerstone in the assessment of patients
with known or suspected coronary artery disease
(CAD) [1,2]. SPECT-MPI is often used in decision-
making when it comes to identifying patients who
would benefit from coronary angiography and
revascularization [3]. The decision to refer patients
with ischemic cardiomyopathy for coronary revas-
cularization is particularly critical [4], as the long-
term benefit of coronary revascularization, particu-
larly coronary artery bypass surgery (CABG), should
be carefully weighed against its risk [5,6]. Often
times, the decision to commit the patient with
ischemic cardiomyopathy to coronary revasculari-
zation hinges on the presence or absence of viable
myocardium that is likely to recover after revascu-
larization [7]. Unfortunately, the clinical data sup-
porting the value of myocardial viability assessment
in predicting the long-term benefit of CABG in
patients with ischemic cardiomyopathy is conflict-
ing [8,9]. However, the fact remains that the assess-
ment of myocardial viability is often a critical
element in the decision-making for referral to coro-
nary revascularization [7]. A variety of noninvasive
imaging tools have been shown to be valuable in
identifying viable dysfunctional myocardium that is
likely improve with coronary revascularization;
these modalities include dobutamine stress echocar-
diography, MRI, PET metabolism imaging, and
a
Division of Cardiology, Cook County Health and
b
Division of Cardiology,
Rush University Medical Center, Chicago, Illinois, USA
Correspondence to Rami Doukky, MD, Division of Cardiology, Cook
County Health, 1901 W. Harrison Street, Chicago, IL 60612, USA.
Tel: +1 312 864 3034; fax: +1 312 864 9349;
e-mail: rdoukky@cookcountyhhs.org
Curr Opin Cardiol 2019, 34:473– 483
DOI:10.1097/HCO.0000000000000646
0268-4705 Copyright ß2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-cardiology.com
REVIEW
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
SPECT-MPI. However, SPECT-MPI remains one of
the most widely available tools for this purpose. In
this review, we will discuss the application of SPECT-
MPI using Thallium-201 (Tl-201) and Technetium-
99m (Tc-99m) radiotracers in the assessment of
myocardial viability.
VIABILITY ASSESSMENT WITH THALLIUM-
201 SINGLE-PHOTON EMISSION
COMPUTED TOMOGRAPHY MYOCARDIAL
PERFUSION IMAGING
Tl-201 was first evaluated as a MPI agent in the
1970s. Due to its pharmacokinetic characteristics,
it became the predominant radiotracer used for
SPECT-MPI throughout the 1980s and early 1990s
[10,11]. Tl-201 is cyclotron produced and has a
relatively long half-life of 73 h. Its principal
photo-peaks are X-rays with an energy range of
69 –83 keV, and a smaller proportion of gamma
ray with energy peaks at 135 and 167 keV [12]. As
a radiotracer, Tl-201 behaves pharmacokinetically
like a potassium analog. Myocardial uptake of Tl-
201 is an active Na/K ATPase pump-dependent pro-
cess, which requires cell membrane integrity. Thus,
Tl-201 myocardial uptake is an indication of
regional perfusion, which is necessary for tracer
delivery and myocyte membrane integrity and met-
abolic activity (ATP production). The uptake of Tl-
201 by the myocardium depends upon myocardial
blood flow and the first-pass extraction fraction of
Tl-201, which is approximately 85% under resting
conditions. As the flow rate increases with physio-
logic or pharmacologic stress, the extraction of Tl-
201 increases linearly at low flow rate (2baseline)
but non-linearly at high flow rates (3– 4baseline),
a tracer characteristic known as the roll-off phenom-
enon (Fig. 1) [10,13,14].
A pivotal characteristic of Tl-201 myocardial
uptake is its redistribution property. This phenome-
non was initially described in the late 1970s, with
reports of stress-induced myocardial perfusion
defects that appeared to normalize on repeat imag-
ing at different time intervals [15]. This property is a
consequence of a constant exchange of the radio-
tracer between the myocardial cells, extracellular
space and subsequently the blood pool after the
initial myocardial uptake. As Tl-201 is washed out
of the myocardial cells, radiotracer uptake from the
blood pool continues to take place. In areas of
decreased perfusion or with diminished coronary
flow, the rate of Tl-201 extraction is slower than
in those with increased or normal blood flow, lead-
ing to perfusion defects in these area at initial stress
imaging, performed 10 –15 min following radio-
tracer injection. However, over-time, Tl-201 uptake
continues in areas with diminished blood flow,
whereas the radiotracer washes out from areas with
normal or increased initial blood flow. This constant
redistribution of Tl-201 manifest, on delayed imag-
ing (3–4 h following injection), with resolution of
the initial perfusion defect in areas that appeared to
have little or no tracer activity on initial stress
imaging. As Tl-201 uptake requires sarcolemmal
KEY POINTS
In patients with ischemic heart disease and impaired
myocardial function, SPECT myocardial perfusion
imaging is a valuable tool for the assessment of
myocardial viability and the prediction of functional
recovery after revascularization.
Variety of rest and stress/rest Tl-201 SPECT viability
imaging protocols rely on the redistribution property of
Tl-201.
Tc-99m sestamibi and tetrofosmin SPECT viability
imaging is underutilized in clinical practice.
The over-extraction of Tc-99m radiotracers at low flow
rates and the superior imaging characteristics of Tc-
99m favorably position Tc-99m based agents
compared with Tl-201.
The diagnostic performance of Tl-201 and Tc-99m
radiotracers for identifying myocardial viability
is comparable.
Quantitative assessment methods can better guide the
prediction of myocardial viability and
functional recovery.
FIGURE 1. Relationship between myocardial blood flow and
myocardial radiotracer uptake for single-photon emission
computed tomography myocardial perfusion imaging
tracers.
Imaging and heart failure: myocardial strain
474 www.co-cardiology.com Volume 34 Number 5 September 2019
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
membrane integrity, resolution or ‘reversibility’ of
perfusion abnormality is considered to represent
myocardial viability [16].
Thallium-201 viability assessment protocols
Stress/4 and 24 h delayed redistribution
protocol
During the 1980s, Tl-201 stress/4 h redistribution
became the standard protocol for assessment of
myocardial ischemia and to predict functional
recovery after coronary revascularization. However,
it was noted that up to half of the segments with
fixed perfusion defects on 4 h imaging demon-
strated normalization of perfusion or improvement
in function after revascularization [17,18]. This find-
ing suggests that under certain circumstances, Tl-
201 redistribution may take longer than 4 h, and
therefore, delayed imaging at 18–24 h could
improve the ability of the test to predict functional
recovery after coronary revascularization [19]. These
findings led to the use of Tl-201 stress/4 h redistri-
bution with delayed, 24 h imaging (Fig. 2a). This
FIGURE 2. Common Thallium-201 viability imaging protocols.
Viability assessment with SPECT MPI Malhotra et al.
0268-4705 Copyright ß2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-cardiology.com 475
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
protocol was shown to accurately predict viability in
up to 95% of segments with late redistribution,
demonstrating improved myocardial perfusion after
revascularization. However, the absence of late
redistribution underestimated the presence of viable
myocardium in up to 37% of segments that demon-
strate functional recovery after revascularization
[20]. Moreover, the routine use of 24 h delayed
imaging proved to be impractical in high-volume
nuclear laboratories and often yielded images with
poor signal-to-noise ratio because of radiotracer
washout and decay.
Stress/4 h reinjection protocol
To overcome the limitations of delayed imaging, a
series of investigations were conducted in the early
1990s by Dilsizian, Bonow, and others using low-
dose Tl-201 reinjection, 4 h after the initial dose.
These investigations demonstrated that nearly 50%
of the regions deemed to have irreversible defects on
conventional 4 h redistribution images had further
Tl-201 uptake after rest reinjection [21,22]. Addi-
tionally, these investigators demonstrated that no
further improvement in identification of viable
regions was achieved by re-imaging after 24 h. The
authors concluded that in contrast to Tl-201 stress/
4 h redistribution protocols, the Tl-201 stress/4 h
reinjection protocol detects most of the clinically
relevant information pertaining to myocardial via-
bility in regions with fixed defects. These data pro-
posed stress/4 h reinjection protocol (Fig. 2b) as a
reasonable alternative to identify regions that would
benefit from coronary revascularization [21,22].
Rest/4 h redistribution imaging protocol
Tl-201 rest/4 h redistribution imaging has also been
used and shown to be adequate for identification of
viable segments (Fig. 2c). When Tl-201 is injected at
resting state, delayed imaging at 18 –24 h does not
yield improved viability detection. In this setting,
the data suggest that a 10% absolute increase in
radiotracer uptake is indicative of significant viabil-
ity, which is predictive of functional improvement
after revascularization [23]. Figure 3a illustrates an
example of a patient with ischemic cardiomyopathy
with fixed perfusion defect in the inferior and
inferolateral segments on initial, 4 h and 24 h
delayed Tl-201 imaging, signifying lack of myocar-
dial viability in these segments.
Dual isotope protocols
Dual isotope protocols using rest Tl-201 and stress Tc-
99m tetrofosmin or sestamibi imaging have the
advantage of allowing delayed 24-h imaging to be
obtained if a fixed defect is identified on initial rest/
stress perfusion analysis (Fig. 2d). In 24 h, technetium
is almost completely decayed (half-life, 6 h), whereas
substantial remaining Tl-201 activity (half-life, 73 h)
would achieve full redistribution and can detect via-
ble regions, which may benefit from revasculariza-
tion. However, in current practice, dual-isotope
protocols are rarely used because of a significant
increase in radiation exposure when compared with
single-isotope protocols [24]. Figure 3b exemplifies a
case of ischemic cardiomyopathy demonstrating
fixed perfusion abnormalities in multivessel distribu-
tion on the initial dual-isotope rest/stress imaging,
but exhibited full reversibility on 24 h delayed Tl-201
imaging, indicating myocardial viability.
Prediction of myocardial function recovery
The sensitivity and specificity of Tl-201 for predict-
ing recovery of function has been evaluated in many
small studies and have been shown to be moderately
accurate. In a pooled analysis of 40 Tl-201 viability
imaging studies (1119 patients), Shinkel et al. found
that the weighted mean sensitivity and specificity to
predict recovery of regional function after revascu-
larization was 87 and 54%, respectively, with a
positive predictive value (PPV) and negative predic-
tive value (NPV) of 67 and 79%, respectively. In a
subset of 28 studies (776 patients) in which Tl-201
rest/redistribution imaging was used, the weighted
mean sensitivity and specificity for recovery of func-
tion were 87 and 56%, respectively, and the PPV and
NPV were 71 and 78%, respectively. On the other
hand, in the subset of 12 studies (343 patients)
where Tl-201 reinjection protocol was used, the
sensitivity and specificity were 87 and 50%, respec-
tively, with a PPV and NPV of 58 and 81%, respec-
tively. These findings led to the conclusion that Tl-
201 rest/redistribution imaging had a higher speci-
ficity and PPV than Tl-201 reinjection (P<0.05 for
both), with a similar sensitivity and NPV [25].
A quantitative rather than a dichotomized quali-
tative assessment of viability and prediction of func-
tional recovery has been proposed. Gibson et al.
evaluated 47 consecutive patients who underwent
coronary artery bypass surgery with preoperative
and postoperative Tl-201 stress/3 h redistribution
imaging with qualitative and quantitative assessment
of viability. The investigators showed that among 42
segments with persistent defects on qualitative assess-
ment thought to represent myocardial scar before
surgery, 19 (45%) demonstrated normal perfusion
postoperatively. On the other hand, 57% of the per-
sistent defects that showed a 25–50% decrease in
myocardial activity demonstrated normal thallium
uptake postoperatively, but only 21% of the persistent
defects with less than 50% myocardial activity dem-
onstrated improved perfusion (P¼0.02). The authors
Imaging and heart failure: myocardial strain
476 www.co-cardiology.com Volume 34 Number 5 September 2019
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
concluded that the preoperative distinction between
viable and nonviable myocardium can be established
by quantitating persistent reduction in thallium
uptake [17]. These data indicate that recovery of
function after revascularization is a continuum and
is coupled to the ratio of viable to scarred myocardium
within the dysfunctional myocardial region. There-
fore, the quantitative regional myocardial uptake
data should guide the estimation of the probability
of regional function recovery. Figure 4 illustrates
the relationship between percentage regional
Tl-201 uptake and recovery of function after
revascularization on rest/redistribution and stress/
redistribution/re-injection protocols [26,27].
Recent developments
For more than three decades, Tl-201 imaging has
been the cornerstone of SPECT myocardial viability
evaluation, but there has been a paucity of techno-
logical advances in this particular area. However,
with the advent of cadmium-zinc-telluride (CZT)
SPECT cameras and novel collimator designs and
reconstruction software, the use of ultra-low dose
FIGURE 3. Representative examples of Thallium-201 viability imaging. Panel a represents initial resting/4 h/24 h Tl-201
SPECT myocardial perfusion imaging in a patient with ischemic cardiomyopathy (ejection fraction 30%). The images
demonstrate a fixed perfusion abnormality indicating nonviable myocardium in the inferior and inferolateral segments. Panel b
represents dual-isotope rest Tl-201/stress Tc-99m tetrofosmin/24 h delayed Tl-201 redistribution in a patient with ischemic
cardiomyopathy (ejection fraction 35%). Note fixed perfusion abnormalities in multivessel coronary distribution on the initial
rest/stress imaging, with complete reversibility on the delayed 24 h Tl-201 redistribution images, indicating viable
myocardium. The patient underwent coronary artery bypass surgery with subsequent complete recovery of left ventricular
systolic function.
Viability assessment with SPECT MPI Malhotra et al.
0268-4705 Copyright ß2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-cardiology.com 477
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Tl-201 stress/redistribution imaging protocols have
become feasible [28
&&
,29
&
]. In a recent investigation,
Kincl et al. performed SPECT imaging in 124 patients
using 0.014 mCi/kg (0.5 MBq/kg) dose of Tl-201
(1.0 mCi in an average size person), achieving ade-
quate image quality with a calculated effective radia-
tion dose of 4 –5 mSv [30]. Additional research is
needed to assess the role of novel SPECT technologies
in Tl-201 myocardial perfusion and viability imaging.
VIABILITY ASSESSMENT WITH
TECHNETIUM-99M SINGLE-PHOTON
EMISSION COMPUTED TOMOGRAPHY-
MYOCARDIAL PERFUSION IMAGING
Tc-99m is a cationic tracer that is derived from a
molybdenum-100 generator. Tc-99m produces
higher energy photons (140 keV) than Tl-201, but
the shorter physical half-life of 6 h results in consid-
erably less radiation exposure. For myocardial per-
fusion imaging, Tc-99m is used in the form of Tc-
99m sestamibi or Tc-99m tetrofosmin. Compared
with Tl-201, Tc-99m tracers have inferior first-pass
extraction and linearity properties (Fig. 1). On the
other hand, Tc-99m tracers provide better image
resolution and over-all image quality than Tl-201
because of Tc-99m superior physical characteristics
that allow for less soft tissue attenuation (higher
photon energy) and higher count statistics (higher
administered dose). Following their extraction from
the blood, Tc-99m tracers bind to the mitochondria,
and thus results in a negligible washout or redistri-
bution. Table 1 outlines the basic differences in the
physical and imaging characteristics of Tl-201 and
Tc-99m tracers relevant to the assessment of
myocardial viability.
Table 1. Physical, imaging and clinical characteristics of Thallium-201 and Technetium-99m single-photon emission computed
tomography viability protocols
Thallium-201 Technetium-99m tracers
Radiotracer dose 3– 4 mCi
Additional 1 mCi for reinjection protocol
30 mCi if resting
10 þ30 mCi if both rest and stress imaging is performed
Radiation exposure 12– 16 mSv 10 mSv
Study duration 4– 5 h (rest and redistribution)
24 h if additional imaging is performed
1–2h
Functional information No Yes
Tracer properties Redistribution –
Needs repeat imaging to assess viability
No redistribution –
Perfusion is fixed at the time of injection
Image quality Inferior
Low energy photons, lower photon count (noise)
Superior
Higher energy photons, higher photon count (less noise)
Extracardiac activity Frequent lung uptake may reduce image quality Frequent liver and bowel uptake may delay acquisition or
cause artifacts
Contraindications None Resting hypotension – inability to administer nitroglycerine
FIGURE 4. Relationships between regional Tl-201 uptake and recovery of function after revascularization. Reproduced from [27].
Imaging and heart failure: myocardial strain
478 www.co-cardiology.com Volume 34 Number 5 September 2019
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Principle for assessment of viability with
Technetium-99m tracers
There have been several historical reports of the
applicability of Tc-99m SPECT for the assessment
of myocardial viability. Despite studies reporting a
diagnostic accuracy comparable to Tl-201 in the
assessment of myocardial viability, Tc-99m tracers
remain undervalued in this regard, perhaps because
of the perception that lack of redistribution property
prevents their use for this purpose. Although there is
lower Tc-99m extraction at normal flow states, there
is an over-extraction of Tc-99m at lower flow states,
as encountered in conditions of chronic ischemia.
The latter property along with superior image qual-
ity are the likely reasons for comparable diagnostic
value of Tc-99m to Tl-201 in the assessment of
myocardial viability.
Canby et al. [31] were among the first to report the
distribution of Tc-99m in comparison to Tl-201. In a
canine model (n¼15) of myocardial insult, both Tl-
201 and Tc-99m and radiolabeled microspheres were
administered at varying times after occlusion of the
left anterior descending coronary artery. After com-
pletion of the protocol, all dogs were sacrificed and
counts from the anterior wall and control (nonin-
farcted myocardium) were measured using a well
counter. The experiments revealed good correlation
between Tl-201 and Tc-99m counts and radiolabeled
microspheres (r¼0.74 for both tracers), suggesting a
similar distribution of Tc-99m and Tl-201 in an ani-
mal model. Following this report, several studies
evaluated the role of Tc-99m for the assessment of
myocardial viability in humans. Among 54 patients
with chronic ischemic cardiomyopathy and mean
ejection fraction of 34%, Dilsizian et al. [32] per-
formed stress/redistribution/reinjection Tl-201 and
rest/stress Tc-99m SPECT within 5 days of each other.
In this study, viability was defined by improvement of
perfusion defect on rest or redistribution images
when compared with stress images. Viability was also
quantified based on the degree of reduction in tracer
activity: mild-to-moderate reduction (51–85% of
peak tracer activity) and severe reduction (50% of
peak tracer activity). On the basis of qualitative assess-
ment, the overall concordance of Tl-201 and Tc-99m
for viability among all myocardial segments was 75%,
with underestimation of viability by Tc-99m SPECT.
However, when regions of fixed perfusion defects on
Tc-99m SPECT were classified based on the degree of
tracer uptake, with mild-to-moderate reduction in
relative sestamibi activity indicating viability (mean
counts >60%), there was a 93% concordance between
Tl-201 and Tc-99m studies. Similarly, in another
study of 48 patients with ischemic cardiomyopathy,
who underwent both resting Tl-201 and Tc-99m
SPECT, Tl-201 and Tc-99m tracer uptakes were
comparable in segments with normal and fixed
abnormal Tl-201 uptake on rest/redistribution imag-
ing. However, Tc-99m uptake was significantly lower
in segments with evidence of redistribution on Tl-201
imaging [33]. These studies were in contrast to subse-
quent ones that reported a comparable diagnostic
accuracy of Tc-99m and Tl-201 for viability, employ-
ing quantitation of tracer activities. Udelson et al. [34]
compared the regional activities of Tl-201 and Tc-
99m for predicting functional recovery among 31
patients. The authors reported good concordance
(87%) between regional Tl-201 redistribution activity
and regional Tc-99m activity by semiquantitative
visual analysis. Quantitative analysis of perfusion
for all segments showed significant correlation
(r¼0.86, P<0.001) between Tl-201 redistribution
and rest Tc-99m activity in individual segments. Seg-
ments that improved regional function (on echocar-
diography) after revascularization (viable) had similar
Tl-201 and Tc-99m regional activities (72 vs. 75%,
respectively; P¼NS). The activity levels were also
similar for nonviable segments (51 vs. 50%, P¼NS).
When considering 60% of peak activity as a threshold
for viability, the positive and negative predictive
values for functional recovery after revascularization
were 80 and 96%, respectively, for Tc-99m, and 75
and 92%, respectively, for redistribution Tl-201.
Subsequently, there were reports of myocardial
viability assessment with Tc-99m after administra-
tion of nitroglycerin. These investigations were
likely fueled by evidence of enhanced coronary per-
fusion by nitroglycerine through increased coronary
collateral flow in a canine model of myocardial
infarction (MI) [35]. In a study of 19 post-MI patients
with left ventricular (LV) dysfunction who were
scheduled for coronary revascularization, Bisi et al.
[36] performed two sets of high-dose Tc-99m studies
(25 mCi) 24-h apart – one at rest and one after 10 mg
of isosorbide dinitrate infusion 15 min prior to radio-
isotope injection, guided by SBP decrease by more
than 20 mmHg or was less than 90 mmHg. Baseline
and postrevascularization LV function was deter-
mined by echocardiography and radionuclide angio-
cardiography. There was a postrevascularization
improvement in LV function in seven patients in
whom there was a smaller extent of Tc-99m uptake
defect after nitrate administration when compared
with baseline SPECT. Among patients with no
improvement in LV function after revascularization,
there was no difference in Tc-99m perfusion defect at
rest and after nitrate infusion. In a subsequent study
of 28 patients with similar clinical characteristics
undergoing revascularization, isosorbide dinitrate
infusion-induced improvement in Tc-99m perfusion
showed excellent agreement with improvement in
LV function after revascularization (kappa ¼1.0;
Viability assessment with SPECT MPI Malhotra et al.
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
P<0.0005) [37]. In another study of 36 patients with
CAD, and LV dysfunction (mean ejection fraction
36%) undergoing revascularization, Sciagra et al. [38]
compared the ability of isosorbide dinitrate infusion-
enhanced Tc-99m SPECT to detect myocardial via-
bility with nonnitrate-enhanced Tc-99m SPECT and
rest-redistribution Tl-201 SPECT. In these patients,
abnormal myocardial wall motion at rest was present
in 56 coronary territories of which 30 improved
following revascularization (identified as viable
hibernating myocardium) with no improvement
in the remainder (identified as nonviable). The mean
resting Tl-201 and Tc-99m activities were 62.3 and
63.4%, respectively, which were significantly lower
than the mean redistribution Tl-201 (65.5%) and
nitrate-enhanced Tc-99m (65.5%). Among the viable
segments (n¼30), there was a significant increase in
tracer activity, postrevascularization, for both Tl-201
(71 vs. 66%; P<0.0002) and Tc-99m (70.6 vs. 66%,
P<0.0002). There was no significant change in
tracer activity levels in nonviable segments. The
nitrate-induced change in Tc-99m activity was sig-
nificantly higher in viable segments when compared
with nonviable segments (þ8 vs. 1%; P<0.0005),
with tracer activity after nitrate administration and
nitrate-induced increment in tracer activity being
predictive of postrevascularization recovery in
wall motion.
On the basis of recent quantitative data, nitrate-
enhanced Tc-99m SPECT is now considered as an
established method for assessment of myocardial
viability [39]. Although the seminal studies on
nitrate-enhanced Tc-99m viability used nitrate infu-
sion to induce vasodilation and a change in SBP as
an indicator for tracer injection [36– 38], such an
approach may be cumbersome in routine clinical
practice. Moreover, a change in SBP after nitrate
administration can vary. Positron emission tomog-
raphy-based studies have shown a significant
improvement in myocardial blood flow in viable
segments after a single dose of sublingual nitroglyc-
erine, and tracer injection in these studies was per-
formed 5– 10 min after sublingual nitrate
administration [40,41]. In our laboratory, we rou-
tinely perform nitrate-enhanced Tc-99m sestamibi
viability studies after administration of a single dose
of 0.4 mg sublingual nitroglycerine, followed by
tracer injection at 5 min. Although we measure
blood pressure prior to and 5 min after nitroglycer-
ine administration to confirm hemodynamic stabil-
ity, we do not time tracer injection based on a
change in SBP. Protocols for use of Tc-99m for
assessing myocardial viability are suggested in
Fig. 5. Given the equitable data when compared
with Tl-201 rest/redistribution imaging, nitrate-
enhanced Tc-99m does confer several advantages,
FIGURE 5. Myocardial viability imaging protocols for Technecium-99m radiotracers. SL NTG, sublingual nitroglycerin.
Imaging and heart failure: myocardial strain
480 www.co-cardiology.com Volume 34 Number 5 September 2019
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
namely, superior image quality because of high-
energy photons and high-count statistics that allow
for gated acquisition with simultaneous assessment
of global and regional functions. Administration of
nitroglycerine with rest imaging, followed by stress
testing, allows for assessment of both resting viabil-
ity and stress-induced ischemia. Additionally, when
assessment of myocardial viability is the only ques-
tion, then a nitrate-enhanced Tc-99m study can be
completed in approximately 1 h after tracer
administration, unlike Tl-201-based protocol,
which requires 4 h redistribution imaging. However,
when nitrate-enhanced resting Tc-99m protocol is
used, reliance on quantitative assessment of radio-
tracer activity is required, with segments less than
60% uptake to be considered as nonviable. More-
over, regional myocardial thickening, as assessed by
an increase in count density with systole, may also
signify viable myocardium. Myocardial thickening,
as a marker of myocardial viability, has not been
FIGURE 6. Representative images from resting nitrate-enhanced Tc-99m Sestamibi viability single-photon emission computed
tomography myocardial perfusion imaging and correlating coronary angiography. Panels a and b depict complete occlusion
of the left anterior descending (LAD) and right coronary artery (RCA), respectively. Panel c depicts nitrate-enhanced resting Tc-
99m SPECT myocardial perfusion imaging, which demonstrates significant tracer uptake in the anterior wall, lateral wall and
the septum, indicating viable myocardium in the LAD territory. The lack of significant tracer uptake in the inferior wall indicates
nonviable myocardium in the right coronary artery territory. SPECT, single-photon emission computed tomography.
Viability assessment with SPECT MPI Malhotra et al.
0268-4705 Copyright ß2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-cardiology.com 481
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
systematically evaluated for this purpose. Figure 6
shows representative images from a coronary
angiogram and nitrate-enhanced Tc-99m sestamibi
viability SPECT.
CONCLUSION
Assessment of myocardial viability is often critical in
the decision-making for coronary revascularization
in patients with ischemic cardiomyopathy. Several
SPECT-imaging protocols, using Tl-201 and Tc-99m
radiotracers, have been designed and validated for
this purpose. Tl-201-based protocols are pivoted on
the redistribution property of this agent. Despite the
lack of redistribution property and lower myocardial
extraction compared with Tl-201, Tc-99m radio-
tracers possesses important advantages that make
them suitable for the assessment of myocardial via-
bility, providing a diagnostic performance that is
similar to Tl-201. Quantitative assessment methods
can better guide the prediction of myocardial via-
bility and functional recovery.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
R.D. receives research funding from Astellas Pharma
Global Development (Northbrook, Illinois, USA). The
other authors have no conflicts to disclose.
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