Phase dyssynchrony and 123I-meta-iodobenzylguanidine innervation imaging towards standardization
123 Phase dyssynchrony and I-meta- iodobenzylguanidine innervation imaging towards standardization
Kenichi Nakajima 0 3
Koichi Okuda 1 3
Hein J. Verberne 3
0 Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University , Kanazawa , Japan
1 Department of Physics, Kanazawa Medical University , Uchinada, Kahoku , Japan
2 Department of Radiology and Nuclear Medicine, Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands
3 Reprint requests: Kenichi Nakajima , MD, PhD , Department of Nuclear Medicine, Kanazawa University Hospital, Kanazawa University , 13-1 Takara-machi, Kanazawa, ZIP 920-8641 , Japan
Over the last decades, semi-quantitative analysis
has become crucial in the assessment of myocardial
perfusion scintigraphy. Through widely available
software packages, electrocardiographically (ECG) gated
myocardial perfusion single-photon emission computed
tomography (SPECT) quantitative parameters of left
ventricular (LV) function are easily obtainable. These
software algorithms have increased worldwide
consistency and improved quality of myocardial perfusion
scintigraphy in the assessment of the total ischemic
burden, left ventricular (LV) volumes, and left
ventricular ejection fraction (LVEF). In general, these software
algorithms have standardized the interpretation of ECG
gated myocardial perfusion SPECT. However, for other
parameters of left ventricular function such as phase
analysis of ECG gated myocardial perfusion SPECT and
regional analysis of cardiac sympathetic imaging with
standardization is still not reached. This lack of standardization
hampers the widespread clinical use of the potentially
very valuable parameters obtained with phase analysis
and 123I-mIBG quantitation methods.
GLOBAL AND REGIONAL 123I-MIBG
MYOCARDIAL UPTAKE PARAMETERS
The necessity of standardizing global 123I-mIBG
myocardial uptake, has already been emphasized.1?3 In
particular for the assessment of the
heart-to-mediastinum ratio (HMR) on planar images, it has been
shown that the accuracy of the HMR is significantly
influenced by variations in camera-collimator systems.4
However, the recent development of a calibration
phantom-based standardization method provides optimal
conversion coefficients for most of the Anger-type
camera-collimator combinations.5,6 The standardization
method could be applied to cadmium-zinc-telluride
(CZT) cameras, either by empirical conversion equation
between two systems with a phantom study7,8 or
calibration phantom experiments as described for Anger
On the other hand, the assessment of regional
123ImIBG uptake with SPECT has not been standardized so
rigorously yet. Scoring methods as used in myocardial
perfusion SPECT with a 17-segment model and percent
of voxels with counts below the lower limit of normal
have been described.10,11 Important to realize is that the
normal distribution of 123I-mIBG on SPECT shows
lower uptake in the inferior and apical regions
(Figure 1). This lower uptake is not explained by attenuation
as seen in myocardial perfusion images. A number of
studies used a visual semi-quantitative approach partly
aided by percent uptake of each segment and mismatch
between perfusion and innervation as well.12,13 Normal
databases as commonly used in myocardial perfusion
SPECT could be an option for a standardized 123I-mIBG
SPECT analysis. However, the 123I-mIBG databases as
used by the Japanese Society of Nuclear Medicine
working groups have not been created for clinical use
outside of Japan.14 These databases would be of interest
as they use the same approach as used for myocardial
perfusion SPECT. However, when there is an overall
decreased 123I-mIBG myocardial uptake, myocardial
regions corresponding to 100% count cannot be
determined appropriately. In other words, this quantification
assumes that at least one myocardial region has normal
sympathetic activity. In this respect, imaging with CZT
could provide high resolution and sensitivity, which
could potentially enhance the accuracy of regional
scores based on 123I-mIBG SPECT imaging. 15
Obviously, nearly complete decreased 123I-mIBG uptake as
seen in Lewy-body disease and very severe heart failure
may result in the maximal defect score of 68 (17
segments 9 4 points). In addition, perfusion images
combined with 123I-mIBG images may be helpful for a
better risk analysis.12
Another approach for SPECT is the summation of
all myocardial slices to calculate myocardial uptake, and
then calculate the uptake in relation to the mediastinal
uptake, similar to the planar approach.11,16 Although
such whole-heart SPECT analysis has been reported, the
impact on the diagnosis or prognosis has not yet been
demonstrated.16 Most promising seems the use of x-ray
computed tomography-based attenuation and scatter
corrections resulting in absolute quantification in Bq/
cm3 for 123I-mIBG SPECT, similar to the standardized
uptake value as used in positron emission tomography.
However, the exact role of this exciting methodology for
the calculation of absolute 123I-mIBG uptake in
establishing diagnosis and prognosis needs to be investigated
first before it can be applied to clinical practice.
GLOBAL PHASE VS REGIONAL PHASE ANALYSIS
The principle of phase analysis was developed in
1980s, and subsequently applied to gated SPECT.17 The
application of phase analysis has also been described for
modern CZT technology-driven cameras.18 Whereas
phase dyssynchrony parameters have provided
potentially promising results, such as for the prediction of
response to cardiac resynchronization therapy,19 it is not
yet standardized. Variations of the phase values, namely
differences in timing of contraction, using standard
deviation (SD) and 95% bandwidth of the phase
histogram are most often included.20 Time-activity
curves in 17 segments may also be used to evaluate
regional variations of time to end-systole.21 Although
phase distribution is usually analyzed using a histogram,
peak phase value is influenced by the shape of regional
time-activity curves. When the shape is symmetric, the
peak value will be around 180 (for example, during
tachycardia), and when asymmetric (for example, low
heart rate with a long diastolic phase), the peak value
will be around 140 -160 . Therefore, SD and bandwidth
are commonly used for the dyssynchrony analysis.
However, all these parameters are influenced by the
administrated tracer dose, body weight, statistical noise,
sampling method over the myocardium, filtering, and the
number of bins used for the histogram.22
There are several commercial software programs
available, including Emory Cardiac Toolbox (Emory
University/Syntermed, Atlanta, GA, USA), QGS
(Cedars Sinai Medical Center, Los Angeles, CA,
USA), Corridor 4DM (INVIA Medical Imaging
Solutions, Ann Arbor, MI, USA), cardioREPO (FUJIFILM
RI Pharma, Tokyo, Japan), and Heart Function View (or
Heart Risk View-F, Nihon MediPhysics, Tokyo, Japan).
It is important to realize that normal values depend on
software programs.21 Therefore, the characteristics of
each software program including normal ranges should
be carefully established before use in clinical practice.23
Figure 2 shows phase maps created in a patient with a
myocardial infarction of the apical anterior wall and
apex. The images clearly show the variation between the
different software programs used.
In order to evaluate regional phase abnormalities,
deviance of the mean segmental value of a control
segment/region may be analyzed. This kind of analysis
may be used to identify the earliest phase in ventricular
pacing sites, may help to establish the presence of a
preexcitation syndrome, and to determine the latest phase in
a dyssynchronous area.15
COMPARISON BETWEEN 123I-MIBG AND PHASE
To integrate parameters of innervation, perfusion,
and phase values, various combinations could be
selected. When global 123I-mIBG and phase parameters
are compared, standardized HMR and ??standardized??
(but not yet validated) phase values such as SD,
bandwidth, and entropy may be used. In typical
situations of myocardial infarction, defect score is large,
HMR is decreased, 123I-mIBG defect score is high, and
phase variations will be large, resulting in some
correlation among these parameters.
When regional 123I-mIBG and perfusion are
compared, the simplest approach is visual analysis of match
and mismatch. In this issue of the Journal of Nuclear
Cardiology, Gimelli et al have compared different
parameters of perfusion, innervation, and
dyssynchrony.15 LV walls with delayed mechanical activation
showed a higher burden of innervation/perfusion
mismatch than normally contracting walls. The extent of
mismatch was the only predictor of delayed mechanical
activation. How this mismatch relates to specific
pathophysiology, diagnosis, or prognosis including
arrhythmogenicity needs to be further investigated.
While the results are intriguing, the dyssynchrony
analysis is dependent on the cut-off values used. More
importantly, variation between different software
algorithms makes extrapolation of the findings troublesome.
This only further stresses the necessity for standardized
approaches for myocardial perfusion imaging,
123ImIBG innervation imaging, and assessment of left
SPECT data were from Kanazawa University Hospital,
Kanazawa, Japan, and Kaga Medical Center, Kaga City,
K. Nakajima collaborates with FUJIFILM RI Pharma,
Tokyo, Japan to develop cardioREPO and 123I-mIBG software.
K. Okuda and H. Verberne have nothing to declare.
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