What is the value of motion and thickening in gated myocardial perfusion SPECT?
What is the value of motion and thickening in gated myocardial perfusion SPECT?
Tali Sharir 0
0 Reprint requests: Tali Sharir, MD, Nuclear Cardiology Department, Assuta Medical Center , 96 Igal Alon, C Building, 67891 Tel Aviv , Israel
1 Faculty of Health Sciences, Ben Gurion University of the Negev , Beer Sheba , Israel
2 Nuclear Cardiology Department, Assuta Medical Center , Tel Aviv , Israel
Myocardial perfusion SPECT imaging (MPI) is a
stress imaging modality, widely used in the detection
and evaluation of coronary artery disease (CAD). This
method is unique in providing simultaneous bi-modal
functional imaging of relative myocardial perfusion and
left ventricular (LV) function.1 While perfusion images
identify regions with relative hypoperfusion, gated
SPECT allows assessment of global and regional LV
function. The added prognostic information gained by
global LV function to myocardial perfusion findings has
been extensively shown.2,3 However, accurate regional
assessment of contractile function is also of great
importance, since it could enhance the detection of
CAD,4 and provide additional prognostic information in
predicting cardiac events.5,6
Similar to myocardial perfusion, regional motion
and thickening can be assessed using semi-quantitative
visual methods, based on segmental scoring. While
motion score simply reflects the extent of inward shift of
the ventricular wall, thickening is assessed as systolic
brightening of the myocardium occurring due to the
partial volume effect. This systolic apparent increase in
count density occurs since myocardial thickness is
commonly in the range up to 2 cm, less than twice the
full width at half maximum of the point spread function
of conventional gamma cameras with intrinsic spatial
resolution of *1 cm.7 Visual assessment of regional LV
contractile function is expert dependent, and suffers
from limited reproducibility with high inter- and
intraobserver variability.8 Therefore, several methods have
been developed and validated, which automatically
quantify motion and thickening, and provide useful and
reproducible assessment of regional function.9,10
Whether visually or automatically assessed, regional motion
and thickening have been shown as important adjunctive
parameters to perfusion in the diagnosis of CAD.
In the current issue of the Journal of Nuclear
Cardiology, Yang et al. used resting gated SPECT MPI
to demonstrate the relationship between myocardial
thickening and LV remodeling among patients with
history of myocardial infarction (MI). The 92 patients
included in the analysis were divided into subacute MI
(3-6 months before nuclear testing, n = 54) and old MI
([6 months before nuclear testing, n = 38) subgroups.
In addition, all patients underwent FDG-PET imaging to
identify myocardial viability as metabolic perfusion
mismatch, and a scar score was calculated. LV
remodeling was defined as end-diastolic volume index [62.53
ml/m2, derived as mean value ?2 standard deviations
from gated SPECT of another 95 patients who had
normal SPECT MPI and no evidence of CAD.
Compared to patients with subacute MI, those with old MI
had larger LV volume and worse cardiac function, larger
perfusion deficit, and higher summed thickening score
(STS). Interestingly, of all the demographic, clinical,
perfusion, and metabolic imaging parameters evaluated,
only the STS and the % of segments with reduced
thickening among segments with normal perfusion were
independently related to LV remodeling among the 92
patients in the analysis. Other imaging parameters
including total perfusion deficit (TPD), viable
myocardium, scar, and % reduced thickening segments
among decreased perfusion segments were significant
predictors of LV remodeling only in univariate analysis,
but were not independent predictors in multivariate
binary logistic regression. The importance of this study
is in showing another application for myocardial
thickening assessment. The authors demonstrated that not
only the global thickening abnormality is related to LV
enlargement, but abnormal thickening within normally
perfused regions was independently associated with
enlarged LV, as well. Whether abnormal thickening
within remote areas with normal perfusion consists of a
contributing factor to progressive post-MI LV
enlargement and remodeling process, or just secondary to large
LV volume is unclear. Remote thickening abnormality
might indicate obstructive CAD in remote vessels,
which might contribute to progressive LV enlargement
and remodeling. Data on the value of thickening in
predicting LV remodeling are conflicting. Ernade et al.
assessed the value of low-dose dobutamine Tc-99m
gated SPECT performed few days after PCI treated MI
in predicting early (6 months) post-MI remodeling of the
LV.11 Using visual analysis of perfusion and of regional
motion and thickening, these investigators demonstrated
that infarct severity at rest had the best predictive values
for LV remodeling with PPV 86% and NPV 88%,
whereas combined analysis of wall thickening score and
infarct severity did not improve prediction of LV
enlargement over infarct severity alone. Others
demonstrated the usefulness of wall thickening in addition to
perfusion in the assessment of post-MI myocardial
salvage, which might have implications in the prediction of
LV remodeling.12 Further assessment of the value of
STS and abnormal remote thickening in predicting
future LV enlargement and remodeling might illuminate
Previous studies have addressed the diagnostic
importance of regional myocardial thickening.
Attenuation artifacts often appear as a fixed or partially
reversible perfusion deficit, and comprise the most
common cause of a false-positive MPI. Motion and
thickening data may assist in discriminating between
attenuation artifacts and true regional hypoperfusion.
Normal motion and thickening of segments with a fixed
defect suggest attenuation artifact, whereas
non-reversible perfusion deficit coupled with abnormal motion
and thickening most likely comprise an old MI. Depuey
and Rozanski show that incorporation of regional
function data in the interpretation of perfusion imaging
reduced false-positive rate from 14% to 3%.13
Fleischman el al. demonstrated that among patients with no
clinical history of MI, 90% of cases with fixed perfusion
deficit but normal systolic function occurred in the
inferior wall among men (87%) and anterior wall among
women (3%), and concluded that these defects were
most likely due to attenuation artifacts.14 In the past 15
years, hybrid SPECT/CT technology has been developed
and increasingly used for attenuation correction of
SPECT data using CT transmission maps. However,
while increasing specificity in the evaluation of the right
coronary artery particularly among obese patients,15 CT
attenuation correction has been shown to reduce
specificity in the left anterior descending coronary artery
territory, was less effective in the correction of breast
artifacts,16 and frequently introduced apical artifacts.17
Moreover, the sensitivity in the RCA territory has been
shown to be reduced in CT attenuation corrected vs
noncorrected MPI.18 Therefore, regional motion/thickening
evaluation is still relevant in identifying attenuation
artifacts, even when CT attenuation correction is
Assessment of regional contractile function may
enhance the diagnostic value of MPI in the detection of
severe obstructive CAD. MPI generates relative
perfusion data, referenced to maximal tracer uptake within
the LV, and often identifies the most severe perfusion
abnormality. It has been well recognized that among
patients with extensive CAD, relative myocardial
perfusion might underestimate the extent and severity of the
disease due to global hypoperfusion.19 Although global
post-stress LV stunning adds important diagnostic
information to MPI,20 regional motion/thickening data
might be even more sensitive, detecting contractile
abnormalities at the segmental level.21 Several studies
demonstrated that abnormal motion/thickening data
increased the sensitivity of perfusion alone in detecting
severe multi-vessel CAD.22,23 Lima et al. determined
quantitative thickening fraction based on the partial
volume effect (ratio of end-diastolic counts over
endsystolic counts), a method which did not require
endocardial edge detection.23 They demonstrated that
combined perfusion/thickening data identified more
abnormal segments per patient than perfusion alone
among patients with three vessel CAD. Moreover, age
and the number of abnormal vascular territories by
perfusion/thickening analysis were the most powerful
predictors of 3-vessel disease. Other investigators
demonstrated low sensitivity but very high overall
specificity (100%) of reversible regional wall motion
abnormality in detecting [70% angiographic CAD, with
high specificity in three vascular territories (94%-97%).4
Moreover, reversible regional wall motion abnormality
distinguished between 50%-79% and 80%-99% stenosis
of the 3 coronary arteries with high positive predictive
value (77%-88%). Investigators from Cedars-Sinai
Medical Center developed a method of automatic
quantification of rest-stress motion and thickening
changes for assessing abnormal segmental function.24
This method is based on registration of endocardial
surfaces at end-diastolic and end-systolic frames,
determination of motion and thickening at any point of
the endocardial surface, and comparison to normal
limits. Using this approach, combined ischemic
perfusion deficit and motion? thickening rest-stress
change was more sensitive than ischemic perfusion
deficit alone in detecting 3-vessel CAD (52% vs 21%,
respectively, P \ 0.0001), but less specific (74%, vs
95%, respectively, P \ 0.0001) (Figure 1A). Similarly,
in identifying 2-vessel CAD, the hybrid approach of
perfusion and regional function was more sensitive than
perfusion alone but less specific (Figure 1B), whereas
among patients with 1-vessel CAD the combined
perfusion and function data had similar sensitivity and
specificity to perfusion alone (Figure 1C). Importantly,
all these studies demonstrated that motion-thickening
data identified abnormal regional function within remote
vascular territories with apparent normal perfusion
among patients with multi-vessel CAD, and enhanced
the diagnosis of extensive CAD.4,21-24
The use of Cadmium Zinc Telluride (CZT)
technology in nuclear cardiology in the past decade allowed
fast SPECT imaging combined with a considerable
reduction in injected radioisotope dose and patient
radiation exposure.25-28 Compared to conventional
SPECT cameras, CZT-SPECT systems are characterized
by improved photon sensitivity and higher spatial
resolution with a factor of 2, which translates into improved
image quality.25 However, the higher intrinsic spatial
resolution of CZT cameras might attenuate the
countdensity myocardial thickness relationship, characteristic
of the low-resolution conventional SPECT systems, and
limit this effect to smaller wall thickness values. Thus,
the accuracy of myocardial thickening assessment using
a CZT camera might be compromised due to the higher
spatial resolution. Indeed, several studies demonstrated a
significant underestimation of wall thickening assessed
by CZT SPECT compared to cardiac MR. Cochet et al.
demonstrated higher agreement with MR for wall
motion than wall thickening, with errors in wall
thickening measurement increasing at greater thicknesses.29
In a phantom study, Bailliez et al also demonstrated
underestimation of regional wall thickening by CZT
SPECT compared to cardiac MR, especially in patients
with increased wall thickness.30 Thus, using a CZT
camera, assessment of regional wall motion might be
preferred over thickening evaluation, particularly in
patients with left ventricular hypertrophy.
The integration of regional contractile assessment
with perfusion data in the interpretation of MPS
enhances the accuracy and provides valuable diagnostic
information. These data are useful in differentiation
between attenuation artifact and real perfusion deficit
and identify reduced regional motion and thickening
within myocardial areas with normal perfusion, remote
of perfusion deficit suggesting more extensive CAD than
seen by perfusion alone, and may predict progressive
LV enlargement and remodeling after MI.
Tali Sharir has no conflict of interest.
1. Palmas W , Friedman JD , Diamond GA , Silber H , Kiat H , Berman DS . Incremental value of simultaneous assessment of myocardial function and perfusion with technetium-99m sestamibi for prediction of extent of coronary artery disease . J Am Coll Cardiol . 1995 ; 25 : 1024 - 31 .
2. Sharir T , Germano G , Kavanagh PB , et al. Incremental prognostic value of post-stress left ventricular ejection fraction and volume by gated myocardial perfusion single photon emission computed tomography . Circulation . 1999 ; 100 : 1035 - 42 .
3. Sharir T , Germano G , Kang X , et al. Prediction of myocardial infarction versus cardiac death by gated myocardial perfusion SPECT: Risk stratification by the amount of stress-induced ischemia and the poststress ejection fraction . J Nucl Med . 2001 ; 42 : 831 - 7 .
4. Emmett L , Iwanochko RM , Freeman MR , Barolet A , Lee DS , Husain M. Reversible regional wall motion abnormalities on exercise technetium-99m-gated cardiac single photon emission computed tomography predict high-grade angiographic stenoses . J Am Coll Cardiol . 2002 ; 39 : 991 - 8 .
5. Kapetanopoulos A , Ahlberg AW , Taub CC , Katten DM , Heller GV . Regional wall-motion abnormalities on post-stress electrocardiographic-gated technetium-99m sestamibi single-photon emission computed tomography imaging predict cardiac events . J Nucl Cardiol . 2007 ; 14 : 810 - 7 .
6. Jeong HJ , Lee DS , Lee HY , Choi S , Han YH , Chung JK . Prognostic Value of Normal Perfusion but Impaired Left Ventricular Function in the Diabetic Heart on Quantitative Gated Myocardial Perfusion SPECT . Nucl Med Mol Imaging . 2013 ; 47 : 151 - 7 .
7. Hoffman EJ , Huang SC , Phelps ME . Quantitation in positron emission computed tomography: 1. Effect of object size . J Comput Assist Tomogr . 1979 ; 3 : 299 - 308 .
8. Xu Y , Hayes S , Ali I , et al. Automatic and visual reproducibility of perfusion and function measures for myocardial perfusion SPECT . J Nucl Cardiol . 2010 ; 17 : 1050 - 7 .
9. Slomka PJ , Berman DS , Xu Y , et al. Fully automated wall motion and thickening scoring system for myocardial perfusion SPECT: Method development and validation in large population . J Nucl Cardiol . 2012 ; 19 : 291 - 302 .
10. Germano G , Erel J , Lewin H , Kavanagh PB , Berman DS . Automatic quantitation of regional myocardial wall motion and thickening from gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography . J Am Coll Cardiol . 1997 ; 30 : 1360 - 7 .
11. Ernande L , Cachin F , Chabrot P , et al. Rest and low-dose dobutamine Tc-99m-mibi gated-SPECT for early prediction of left ventricular remodeling after a first reperfused myocardial infarction . J Nucl Cardiol . 2009 ; 16 : 597 - 604 .
12. Sotgia B , Sciagra ` R, Parodi G , et al. Estimate of myocardial salvage in late presentation acute myocardial infarction by comparing functional and perfusion abnormalities in predischarge gated SPECT . Eur J Nucl Med Mol Imaging . 2008 ; 35 : 906 - 11 .
13. DePuey EG , Rozanski A . Using gated technetium-99m-sestamibi SPECT to characterize fixed myocardial defects as infarct or artifact . J Nucl Med . 1995 ; 36 : 952 - 5 .
14. Fleischmann S , Koepfli P , Namdar M , Wyss CA , Jenni R , Kaufmann PA. Gated (99m)Tc-tetrofosmin SPECT for discriminating infarct from artifact in fixed myocardial perfusion defects . J Nucl Med . 2004 ; 45 : 754 - 9 .
15. Genovesi D , Giorgetti A , Gimelli A , et al. Impact of attenuation correction and gated acquisition in SPECT myocardial perfusion imaging: Results of the multicentre SPAG (SPECT Attenuation Correction vs Gated) study . Eur J Nucl Med Mol Imaging . 2011 ; 38 : 1890 - 8 .
16. Huang R , Li F , Zhao Z , et al. Hybrid SPECT/CT for attenuation correction of stress myocardial perfusion imaging . Clin Nucl Med . 2011 ; 36 : 344 - 9 .
17. Okuda K , Nakajima K , Matsuo S , Wakabayashi H , Taki J , Kinuya S. Cause of apical thinning on attenuation-corrected myocardial perfusion SPECT . Nucl Med Commun . 2011 ; 32 : 1033 - 9 .
18. Sharma P , Patel CD , Karunanithi S , Maharjan S , Malhotra A . Comparative accuracy of CT attenuation-corrected and non-attenuation-corrected SPECT myocardial perfusion imaging . Clin Nucl Med . 2012 ; 37 : 332 - 8 .
19. Berman DS , Kang X , Slomka PJ , et al. Underestimation of extent of ischemia by gated SPECT myocardial perfusion imaging in patients with left main coronary artery disease . J Nucl Cardiol . 2007 ; 14 : 521 - 8 .
20. Yamagishi H , Shirai N , Yoshiyama M , et al. Incremental value of left ventricular ejection fraction for detection of multivessel coronary artery disease in exercise (201)Tl gated myocardial perfusion imaging . J Nucl Med . 2002 ; 43 : 131 - 9 .
21. Shirai N , Yamagishi H , Yoshiyama M , et al. Incremental value of assessment of regional wall motion for detection of multivessel coronary artery disease in exercise (201)Tl gated myocardial perfusion imaging . J Nucl Med . 2002 ; 43 : 443 - 50 .
22. Sharir T , Bacher-Stier C , Dhar S , et al. Identification of severe and extensive coronary artery disease by postexercise regional wall motion abnormalities in Tc-99m sestamibi gated single-photon emission computed tomography . Am J Cardiol . 2000 ; 86 : 1171 - 5 .
23. Lima RS , Watson DD , Goode AR , et al. Incremental value of combined perfusion and function over perfusion alone by gated SPECT myocardial perfusion imaging for detection of severe threevessel coronary artery disease . J Am Coll Cardiol . 2003 ; 42 : 64 - 70 .
24. Karimi-Ashtiani S , Arsanjani R , Fish M , et al. Direct quantification of left ventricular motion and thickening changes using reststress myocardial perfusion SPECT . J Nucl Med . 2012 ; 53 : 1392 - 400 .
25. Gambhir SS , Berman DS , Ziffer J , et al. A novel high-sensitivity rapid-acquisition single-photon cardiac imaging camera . J Nucl Med . 2009 ; 50 : 635 - 43 .
26. Sharir T , Slomka PJ , Hayes SW , et al. Multicenter trial of highspeed versus conventional single-photon emission computed tomography imaging: Quantitative results of myocardial perfusion and left ventricular function . J Am Coll Cardiol . 2010 ; 55 : 1965 - 74 .
27. Duvall WL , Sweeny JM , Croft LB , Ginsberg E , Guma KA , Henzlova MJ . Reduced stress dose with rapid acquisition CZT SPECT MPI in a non-obese clinical population: Comparison to coronary angiography . J Nucl Cardiol . 2012 ; 19 : 19 - 27 .
28. Sharir T , Pinskiy M , Pardes A , et al. Comparison of the diagnostic accuracies of very low stress-dose with standard-dose myocardial perfusion imaging: Automated quantification of one-day, stressfirst SPECT using a CZT camera . J Nucl Cardiol . 2016 ; 23 : 11 - 20 .
29. Cochet H , Bullier E , Gerbaud E , et al. Absolute quantification of left ventricular global and regional function at nuclear MPI using ultrafast CZT SPECT: Initial validation versus cardiac MR . J Nucl Med . 2013 ; 54 : 556 - 63 .
30. Bailliez A , Blaire T , Mouquet F , et al. Segmental and global left ventricular function assessment using gated SPECT with a semiconductor Cadmium Zinc Telluride (CZT) camera: Phantom study and clinical validation vs cardiac magnetic resonance . J Nucl Cardiol . 2014 ; 21 : 712 - 22 .