Automated ejection fraction determination from gated myocardial FDG-PET data.
ABSTRACT The aim of this study was to determine the potential of the automated calculation of the left ventricular ejection fraction from gated myocardial positron emission tomography (PET) scans.
We retrospectively analyzed the data of 20 patients who underwent both gated fluorine 18 deoxyglucose (FDG)-PET and equilibrium radionuclide angiography (ERNA). Gated PET data were analyzed by 2 independent programs (ie, quantitative gated single photon emission computed tomography [QGS]) originally developed for gated single photon emission computed tomography studies and functional polarmap (FPM) originally developed for the analysis of (functional) dynamic PET studies. ERNA data were used as the gold standard.
Both QGS and FPM left ventricular ejection fraction results correlated highly with ERNA (y = 0.90 x x-5.9, r = 0.86, P < .0001; y = 0.80 x x+3.3, r = 0.84, P < .0001, respectively). The correlation between FPM and QGS left ventricular ejection fraction results was even higher (y = 0.89 x x+8.6, r = 0.97, P < .0001). Bland-Altman plots showed systematic differences in the left ventricular ejection fraction of -9.6% +/- 7.5% (QGS vs ERNA), -3.8% +/- 7.8% (FPM vs ERNA), and -5.8% +/- 3.5% (QGS vs FPM). Further comparison of the left ventricular volumes revealed systematic difference between QGS and FPM. Our results indicate that the correlation between the different left ventricular ejection fractions shows little sensitivity to errors in the left ventricular volumes; however, the exact relationship is influenced by these errors.
It is concluded that the automated determination of the left ventricular ejection fraction from gated PET data has significant potential; its results are highly and significantly correlated with ERNA. However, the methods presented here require additional calibration before final accuracy and clinical applicability can be determined.
- SourceAvailable from: Jg Meeder[show abstract] [hide abstract]
ABSTRACT: Most efficacy studies of cardiac PET in demonstrating myocardial ischemia and viability have been performed using one or more transversal static images of the heart. In contrast, in this paper we describe a method of functional imaging of the complete left ventricular myocardium for perfusion with nitrogen-13-ammonia, both at rest and during a dipyridamol stress test, and of glucose metabolism with 18F-fluorodeoxyglucose (18FDG). This was performed by using the data of each of 48 radial segments of 10 short-axis images as tissue data and LV cavity data of three basal planes as blood pool data. The study describes the results of 19 normal volunteers and 36 patients with coronary artery disease. From the data of the normal volunteers a 95% normal confidence interval was calculated for each imaging modality. These intervals were then used to describe the patient data as normal, ischemic or infarcted. The results of analysis of the parametric images was compared with the results of static analysis of the same patient data and found to be less dependant on the detection threshold used. The described method enables the routine application of functional PET imaging of the total myocardium by the semi-automatic construction of parametric flow and metabolism polar maps. It thus provides an increased performance in the diagnosis, quantification and localization of myocardial ischemia and viability over conventional PET imaging.Journal of Nuclear Medicine 02/1995; 36(1):153-8. · 5.77 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: We have developed a software suite that automatically selects, analyses, quantitates and displays all the key image data in a myocardial perfusion SPECT study. Methods: The files automatically selected (upon specification of the patient name) are rest and stress projections, rest and stress short axis and gated short axis files, and all snapshot files. The projection data sets are presented in cine mode for evaluation of patient motion, while the lung/heart ratio at rest and stress is calculated from regions of interest (ROIs) that are automatically derived and overlayed on the LAO 45 images. Left ventricular (LV) cavity volumes at rest and stress are calculated from the short axis data sets, and the related transient ischemic dilation (TID) ratio derived and displayed. Quantitative measurements of global (ejection fraction) and regional function parameters are performed from the gated short axis dataset. All algorithms use the C++, X-Windows and OSF-Motif standards. The overall suite executes in less than 1 minute on a SunSPARC5 with 32 Mb of RAM and no proprietary hardware. Results: The software was validated on 144 patients (118 rest201 Tl/post-stress 99mTc-sestamibi, 18 post-stress 99mTc-sestamibi, 8 rest 201Tl) acquired on a 90 dual detector (ADAC Vertex, 91 patients) and a triple detector camera (Picker Prism 3000, 53 patients). Overall, the individual algorithms for the analysis of projection, short axis and gated short axis images were successful in 622/660 (94.2%) of the images. In 80.5% of the patients (73/91+43/53) all algorithms executed successfully, without significant difference in success rates for201 Tl versus 99mTc-sestamibi images. Conclusion: Our automated approach to myocardial perfusion SPECT analysis and review is highly successful, intrinsically reproducible, and can produce time and cost savings while improving accuracy in a clinical or teleradiology-type environment.International Journal of Cardiac Imaging 07/1997; 13(4):337-346.
- [show abstract] [hide abstract]
ABSTRACT: We evaluated ECG-gated SPECT (g-SPECT)in the measurement of absolute left ventricular (LV) volume by comparing it with left ventriculography (LVG) and with cine-MRI. Methods: Projection data from 31 patients were acquired with a three-headed SPECT system in 12 min using a 64 x 64 matrix with 1.5 zoom (1 pixel = 4.27 mm). The R-R interval from simultaneously acquired EGGwas divided into eight frames. The end-diastolic and end-systolic vol umes (EDV; ESV) and LV mass were assessed by an area-length method with manual delineation of the epi- and endocardial LV borders using midventricular vertical and horizontal long-axis im ages. The stroke volume, LVEF and cardiac output (CO) were generated from the EDV, ESV and heart rate during the study. The g-SPECT LV values were compared with those of LVG (25 patients) and cine-MRI (18 patients). Results: The g-SPECT values correlated well with those from LVG (r = 0.83 to 0.92; p < 0.001) and cine-MRI (r = 0.76 to 0.99; p < 0.001). The g-SPECT technique provides an
Clinical Applications of
Positron Emission Tomography
in Coronary Atherosclerosis
© Copyright 2000 H.J. Siebelink
All rights are reserved. This publication is protected by copyright. No part
of it may be reproduced, stored in a retrieval system, or transmitted, in any
form or by any means — electronic, mechanical, photocopy, recording, or
otherwise — without the prior written permission of the author.
Vormgeving: P. van der Sijde, Groningen, The Netherlands
Druk: Ponsen en Looijen bv, Wageningen, The Netherlands
F inancial support by The Netherlands Heart F oundation and the
Rijksuniversiteit Groningen, The Netherlands, for the publication of this
thesis is gratefully acknowledged.
Publication of this thesis was also supported by generous contributions
Fornix Biosciences NV, Schering Nederland BV, Guerbet Nederland BV,
ASTA Medica BV, Yamanouchi Pharma BV, Bayer Nederland BV, Amersham
Cygne, Astra Zenica, Servier Nederland BV, PCH Nederland, Bristol-Meyers
Squibb BV, Boehringer Ingelheim BV.
Clinical Applications of
Positron Emission Tomography
in Coronary Atherosclerosis
ter verkrijging van het doctoraat in de
aan de Rijksuniversiteit Groningen
op gezag van de
Rector Magnificus, dr. D.F.J. Bosscher,
in het openbaar te verdedigen op
woensdag 20 december 2000
om 14.15 uur
Hans-Marc José Siebelink
geboren op 28 december 1969
Promotores : Prof. dr. H.J.G.M. Crijns
Prof. dr. E.E. van der Wall
Co-promotor: Dr. P.K. Blanksma
Referent:Dr. A.J. van Boven
Beoordelingscommissie:Prof. dr. W.H. van Gilst
Prof. dr. W. Vaalburg
Prof. dr. W. Wijns
Paranimfen: Drs. R.A. de Boer
Dr. A.F.M. van den Heuvel
To them the truth would be literally nothing
but the shadows of the images
Plato’s dialoges: The allegory of the cave
Voor Ben en Justine,
mijn vader en moeder
Part IIntroduction, aim and outline
Introduction, aim and outline of the thesis.
Part II Vascular function and intervention
Cholesterol-lowering therapy with fluvastatin improves myocardial perfusion
reserve in healthy humans with hypercholesterolemia.
PTCA but not atorvastatin normalises dipyridamole induced myocardial
perfusion and perfusion reserve in target vessel areas after 6 months. A
randomised study using positron emission tomography.
Part III Cardiac function
Automated ejection fraction determination from gated myocardial FDG-PET
Journal of Nuclear Cardiology 1999;6:577-582
Part IV Clinical management
Detecting hibernating myocardium: how and why?
International Journal of Cardiology 2000;73:209-211
No different cardiac event free survival in positron emission tomography and
single photon emission computed tomography guided patient management.
A prospective randomized comparison in patients with suspicion of jeopardized
In press : Journal of the American College of Cardiology
Part VSummary and future perspectives
Summary and future perspectives
Nederlandse samenvatting en conclusies
Introduction, aim and outline
Introduction, aim and outline
This thesis focuses on positron emission tomography, the cardiac blood flow,
the cardiac metabolism and their regulating mechanisms in relation to
pathological processes. For a better understanding, this introduction will
address the most important physiologic mechanisms of the cardiac blood
flow and the cardiac metabolism, and the pathophysiology in atherosclerosis.
PHYSIOLOGY OF THE CORONARY CIRCULATION
The coronary circulation consists of three different compartments. Although
their borders can not be distinguished exactly anatomically or histologically,
the three compartments differ in function. From the origin in the aorta we
discriminate consecutively the macrocirculation with epicardial conductive
vessels, and the microcirculation containing the prearteriolar, and the
The proximal compartment of the coronary circulation is represented by
the large epicardial conductance vessels which originate from the aorta
and extend to the entrance of the ventricular wall. Histologically epicardial
conductance vessels are characterized by a vessel wall to vessel lumen ratio
of 1:4 with a relatively large media of which 60% contains smooth muscle
cells. These smooth muscle cells control the vessel diameter and are
influenced by various stimuli. Adjacent to the vessel lumen the intima is
lined with endothelial cells necessary to induce vasomotor responses via
the underlying smooth muscle cell layer. The adventitia marks the outer
border of the vessel and is characterized by sparse connection between
nerves and smooth muscle cells, indicating minimal neural control in this
The most important functions of these vessels are to distribute the blood to
the myocardium and to increase capacity to store blood during systole. The
branching and tapering pattern of the proximal compartment enables the
distribution of blood to be carried out in an efficient way with minimal wall
shear stress and minimal loss of kinetic energy. The capacitance function is
illustrated by an increase of 25% in vessel volume during systole to store
the antegrade flow from the aorta and retrograde flow from the
intramyocardial vessels. The volume increase enhances elastic energy in
the vessel wall which is converted into kinetic energy at the beginning the
diastole and contributes to the opening of the intramyocardial vessels that
have been squeezed during systole. Capacitance is also increased by beta
adrenergic stimulation, an important mechanism involved in response to
exercise. As the microcirculation provides most of the vascular resistance,
conductance vessels have only minimal impact (25%) on vessel resistance1,2.
The most important function of the microcirculation is to regulate to coronary
vascular resistance and to respond to metabolic changes in the myocardium.
The latter function is mainly controlled in the arteriolae and capillaries,
whereas resistance is regulated predominantly in the prearteriolae.
However, both compartments demonstrate overlap in function, and
anatomical borders are not strictly separated. Anatomically and
histologically the prearteriolar compartment is not very much different from
the macrocirculation, except for a more dense innervation. Main function
of this compartment is to modulate resistance so that pressure at the origin
of the arteriolae can be maintained within a narrow range1.
The prearteriolae and arteriolae both provide resistance as illustrated in
experimental studies in cats: vessels with diameter greater than 170 µm
provided 25% of the resistance, vessels between 100-170 µm 25%, the venous
compartment 10%, thus leaving 40% of the resistance to vessels smaller
than 100µm2. Resistance is predominantly adjusted to changes in flow via
shear stress mediated release of endothelium derived relaxing factor, and
changes in pressure are followed by adjustment of the myogenic vessel tone.
The third and last compartment consists of the arteriolae and the capillaries.
Histologically arteriolae are characterized by a thick muscular vessel wall,
with a wall to lumen ratio of 2:3, and richly innervated. Main functions are
to provide resistance as mentioned previously and to adjust the blood flow
to the myocardial demand (described below).
Regulating mechanisms of the coronary circulation
The different mechanisms for the regulation of vasomotion control are not
equally important in the three components of the coronary circulation.
Metabolic regulation is predominantly present in the arteriolae, whereas
prearterioles and conduit arteries are mainly regulated by shear stress,
autonomic neural, and neurohumoral mechanisms.
Introduction, aim and outline
Metabolic regulation is the most important regulating mechanism in the
arteriolae and the capillaries. Adjustment to the myocardial demand is
predominantly carried out via vasodilatation or vasoconstriction in response
to changes in the interstitial metabolite concentration, reflecting the
metabolic state of the myocardial cells. The sensitivity to adjust metabolic
changes depends on the wall thickness of the vessel. An increased wall
thickness impairs diffusion of metabolites and consequently the
vasodilatatory response is diminished. In the microcirculation vessels with
a diameter smaller than 100 µm appear the most critical section, because
they show the greatest vasodilatation in metabolic regulation3. When the
balance between myocardial demand and supply is shifted to higher demand,
the oxygen consumption increases. Consequently, tissue oxygen pressure
decreases, and the concentration of metabolites and tissue carbon dioxide
rises. This causes a concentration dependent increase in smooth muscle
cell relaxation, which induces an increase in coronary blood flow so that
equilibrium is reset at a higher flow level. For a decrease in myocardial
demand a reverse process takes place.
Shear stress regulation
Shear stress to the vessel wall (τ) is presumed the most important regulating
factor in the prearteriolae to changes in coronary flow and is characterized
by a formula which includes radius of the vessel lumen (r), flow through
the vessel (Q), and blood viscosity (η).
τ = 4 * η * Q
π * r3
To remain shear stress constant at a minimal level in a nonpathological
state, changes in flow are compensated by subsequent change in radius,
presuming a constant blood viscosity. Shear stress regulated changes are
prominent when flow in the proximal compartment increases due to a
vasodilatation in the distal compartment, initiated by for example an
increased metabolic demand.
Different degrees of shear stress mediated regulation exist in the coronary
artery tree. The endothelium in the epicardial conductance vessel responds
to shear stress, but most pronounced responses are observed in the
prearteriolae. Further descending the coronary artery tree, responsiveness
to shear stress declines, as suggested by a more prominent shear stress
regulation in prearteriolae compared to the smaller arteriolae and
Endothelium Derived Relaxing Factors
Among endothelium derived relaxing factors (EDRF), nitric oxide is
produced by endothelial cells in response to changes in shear stress in
nonpathological conditions. Nitric oxide diffuses from the endothelial cell
to the vascular smooth muscle cell where it stimulates cyclic-
guaninemonophosphate production causing relaxation of the smooth muscle
which in turn dilatates the vessel. In pathological conditions such as in
atherosclerosis where the endothelium is injured, nitric oxide mediated
vasomotor control may be decreased or lost resulting in an impaired
vasodilatation or even a paradoxical vasoconstriction to increased shear
stress and to exogenous stimulation of nitric oxide production with
acetylcholine4. Other factors that influence vasomotion are prostaglandin
and endothelium derived hyperpolarization factor, stimulating cyclic-
adenosinemonophosphate and increasing intracellular potassium
concentration respectively, resulting in smooth muscle relaxation and
dilatation of the vessel. Experimental data suggest that endothelium derived
relaxing factor production is greater in resistive vessels compared to
epicardial conduit vessels5
Autonomic neural regulation
The autonomic nervous system can be divided into a parasympathetic and
a sympathetic component. Concerning the parasympathetic component,
general opinion is that its involvement in regulation of the coronary
vasomotion is minimal. Vagal stimulation results in release of acetylcholine
in parasympathetic nerve endings, which appeared to have no direct- or
indirect effect on coronary vasomotion in an experimental setting in dogs6
In humans vasodilatation after infusion of exogenous acetylcholine was
demonstrated, however this vasodilatation seemed predominantly due to
the acetylcholine induced flow mediated changes in the coronary
microcirculation, rather than due to a direct parasympathetic effect4.
Activation of the sympathetic component causes stimulation of both alpha
and beta adrenoceptors. In an experimental setting direct beta adrenoceptor
stimulation causes vasodilatation in epicardial conduit arteries exerted by
stimulation of beta 1 adrenoceptors and by beta 2 adrenoceptors in resistive
Introduction, aim and outline
vessels7,8. Through beta adrenoceptor activation an increase in myocardial
inotropic and chronotropic state is obtained, which enables the myocardium
to meet the increased metabolic demand during exercise9. Direct stimulation
of alpha adrenoceptors by cardiac sympathetic nerves result in modest
coronary vasoconstriction and greater vasoconstrictive effects are exerted
by circulating catecholamines10. However, the exact mechanisms are not
yet elucidated, because alpha adrenoceptors may also be involved in feed-
back control mechanisms influencing vasodilatatory responses in exercise11.
Moreover, there is controversy whether alpha 1 and 2 adrenoceptors are
heterogeneously distributed in the coronary circulation2,12,13.
Spillover fractions from cardiac terminal nerve endings constitute a major
source for circulating catecholamines. As previously mentioned the effect
of beta stimulation appears small, but circulating catecholamines exert a
significant alpha adrenergic constrictor effect14. In addition, there are other
vasoactive substances that may influence the coronary vasomotor tone like
bradykinin, angiotensin II, thromboxane, atrial natriuretic peptide, and
metabolites ↑, pCO2 ↑, pO2 ↓ in myocardium
metabolic mediated dilatation in arteriolae
flow increase in arteriolae
shear stress mediated dilatation prearteriolae
flow increase in prearteriolae
shear stress mediated dilatation conductance vessels
(to lesser extent than prearteriolae)
flow increase in conductance vessels
renewed equilibrium of flow relative to metabolic demand
Dynamic myocardial perfusion model
The metabolic and shearstress regulating mechanisms are integrated in a dynamic hypothetical
system that illustrates how the myocardium may respond to an increased myocardial metabolic
demand during exercise