Value of simultaneous assessment of cardiac functions by PET/MRI
Value of simultaneous assessment of cardiac functions by PET/MRI
Nagara Tamaki 0 1
Shigenori Matsushima 0 1
Motoki Nishimura 0
0 Reprint requests: Nagara Tamaki , MD, PhD , Department of Radiology, Kyoto Prefectural University of Medicine , 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566 , Japan; J Nucl Cardiol 1071-3581/$34.00 Copyright 2018 American Society of Nuclear Cardiology
1 Department of Radiology, Kyoto Prefectural University of Medicine , Kyoto , Japan
ADVANTAGES OF PET/MRI
Hybrid positron emission tomography (PET) and
computed tomography (CT) have been widely used in
the clinical setting. More recently, PET and magnetic
resonance imaging (MRI) have been introduced and
clinically used in several centers world-wide. The
integrated PET/MRI system should include special
photodetectors insensitive to the magnetic field. For this
purpose, either avalanche photodiodes or silicon
photomultiplier technology has been used for PET signal
detections. Such special requirements have also
increased the cost compared to PET/CT.
The PET/MRI has several advantages and
disadvantages compared to the widely used PET/CT
(Table 1). Attenuation correction can be done with
MRI collecting anatomical information similar to CT.1
The most striking advantage is simultaneous acquisition
of PET and MRI. Simultaneous acquisition by PET/MRI
does not cause motion artifacts which are often seen
with two sequential acquisitions of PET and CT using
PET/CT system. In addition, PET/MRI provides less
radiation burden than CT. Moreover, since MRI
provides a variety of anatomical and tissue functions,
including cellular and molecular studies.
PET/MRI has been applied in oncology,
neurosciences, infection, inflammation, and chronic pain
syndromes, in order to characterize lesion
microenvironment, such as information from liquid
biomarkers (circulating tumor cells and nucleic acids)
and pathology. Therefore, it can be integrated to give a
more complete characterization of disease phenotype.2
While PET/MRI provides valuable functional
parameters, imaging time tends to be longer as
compared to PET/CT. Generally speaking, a patient
throughput with PET/MRI is much less than PET/CT,
and therefore, PET/MRI has been more often applied for
investigative use rather than clinical use in daily
CARDIAC APPLICATIONS OF PET/MRI
Regarding cardiac applications, PET has been used
for viability assessment using FDG, and for stress-rest
perfusion assessment using N-13 ammonia, Rb-82 or
other flow/perfusion tracers. The combination of cardiac
PET and cardiac MRI in a single examination should be
beneficial, but is predominantly for research purposes
(Table 2). Due to higher spatial resolution, CT enables
precise assessment of coronary stenosis and vascular
vulnerability. With use of contrast agent under
pharmacological stress, stress myocardial perfusion imaging
may be available by both CT and MRI. However, such
information can also be acquired by PET perfusion
study. MRI has advantages of higher tissue contrast
resolution, lack of ionizing radiation, and is better
tolerated than contrast agent.3 Actually, MRI permits
assessment of perfusion abnormalities better than CT.
In addition, various tissue characterizations using
suitable acquisition modes are permitted with MRI, such
as tissue edema and fibrosis. Furthermore, MRI is
suitable to assess global and regional ventricular
functions, as well as flow dynamics. As a result, a combined
study of perfusion PET and functional MRI can be
obtained under a single stress study.4,5 The simultaneous
acquisition of PET and MRI is one of the strong
advantages of PET/MRI in the cardiovascular
applications. Moreover, MRI is commonly used for
identifying tissue fibrosis using delayed contrast
enhancement (DCE). Therefore, PET/MRI can be used
for ischemic as well as non-ischemic cardiomyopathy in
order to assess tissue viability, and cellular and
molecular alterations of the myocardium.
After acute myocardial infarction, it is important to
identify reversible dysfunctional area, such as
hibernating myocardium. PET/MRI may identify such
hibernating myocardium as an area of regional
dysfunction (wall motion or thickening abnormality) on MRI
with preserved glucose utilization by FDG-PET in a
single acquisition. Such dysfunctional but preserved
metabolic areas can be precisely identified on regional
basis with simultaneous acquisition using PET/MRI.5,6
Transient dysfunctional myocardium during stress may
also be identified by PET/MRI, as an area of regional
dysfunction on MRI with transient decrease in stress
perfusion by PET. Such transient dysfunction with stress
perfusion abnormality can be identified by PET/MRI
under a single stress test. Similarly, post-stress
dysfunction, so called stunned myocardium, may possibly be
identified with persistent regional dysfunction with
recovery of perfusion with use of serial assessment after
ischemia by PET/MRI. Thus, the simultaneous
acquisition by PET/MRI may hold a promise to characterize
precise assessment of temporal and regional changes (in
another word, four dimensional changes) during
ischemia as well as recovery of ischemia.
While imaging of the coronary arteries and plaque
remains the domain of CT angiography, there seem to be
increasing activity in the MR field. MRI holds a promise
to characterize vessel wall and plaque itself.3,7,8 In the
field of PET, several PET tracers have been used for
atherosclerosis imaging. The most frequently used PET
tracer is FDG, since increased FDG uptake is related to
intense macrophage infiltration, and thus, may represent
unstable plaque.9 Therefore, simultaneous acquisition of
PET/MRI enables plaque location and tissue
characterization in the assessment of atherosclerosis.
Based on the similar concepts, PET/MRI may hold
a promise for diagnosis and assessment of various
myocardial disorders, such as myocarditis and
sarcoidosis. MRI is increasingly being used for infiltrative
processes in acute myocarditis, using
gadolinium-enhanced fast-echo T2 and T1 weighted sequences.3,10 On
the other hand, FDG may accumulate in inflammatory
cells, and thus, may represent acute myocarditis. PET/
MRI may enhance diagnostic accuracy of acute
myocarditis and location of the inflammation.
Recently, PET/MRI has been used for tissue
function for cardiac sarcoidosis. FDG-PET enables
identifying active sarcoid lesions, while DCE-MRI
may show myocardial fibrosis as well as cardiac
function.11,12 These cellular dysfunctions identified by
PET and MRI seem to be independent and both are
valuable for predicting treatment effects and assessing
treatment monitoring. Thus, precise tissue
characterization is available by PET/MRI on regional basis for
characterizing this disease.
THE CURRENT PET/MRI STUDY
Barton et al assessed the dynamic relationship
between contractile function and metabolism during
normoxia followed by hypoxia in pig model.13 Hypoxic
stress induced a significant increase in heart rate, cardiac
output, left ventricular (LV) ejection fraction (EF), and
peak torsion with decrease in LV end-diastolic and
endsystolic volumes assessed by MRI associated with
decline in arterial SpO2 : Increased LV systolic function
was coupled with an increase in myocardial FDG uptake
(Ki) during hypoxic stress on dynamic PET study.
Their PET/MR study using continuous FDG
infusion nicely showed dynamic changes in both cardiac
metabolism and contractile function. They have
maximally applied advantages of simultaneous
acquisition and analysis for both function and metabolism in
sequential time points of hypoxia. A serial reduction in
LV-EDV without change in afterload may suggest
increased LV contractility, which was coupled with a
significant increase in glucose utilization during
hypoxia. The rise in arterial lactate concentration during
hypoxia demonstrates a global increase in anaerobic
Similar studies under serial changes with hypoxia
may not be feasible in clinical condition. In addition,
continuous infusion of FDG, which is quite a valuable
technique for quantitative assessment, may be applied
only in experimental setting, but not clinical setting.
However, this study highlighted pathophysiological
conditions with functional and metabolic changes under
hypoxia. In addition, it may provide optimal time point
for suitable study under ischemic conditions in clinical
A significant reduction of FDG uptake in skeletal
muscle is another attractive finding, although the authors
did not discuss potential reasons for this finding. A
striking reduction of blood pool of FDG might cause
reduced FDG uptake in the skeletal muscle. But skeletal
muscle may mainly use anaerobic glycolysis, and thus,
lactate increase may not inhibit skeletal glycolysis.
Striking shift from general skeletal muscle to cardiac
muscle under hypoxia should be discussed.
The continuous FDG infusion system in normoxia
and hypoxia over 60 minutes is attractive but should be
more carefully discussed. The paper showed gradual
increase in FDG myocardial uptake with decrease in
FDG skeletal muscle uptake in association with plasma
lactate in hypoxia. On the other hand, this model did not
create steady state condition since gradual FDG uptake
in the myocardium with gradual decrease in plasma
FDG concentration. Therefore, it may be rather difficult
to assess myocardium/plasma as well as skeletal/plasma
ratios over 60 minutes.
In order to assess quantitative oxidative myocardial
metabolism, C-11 acetate PET or O-15 gas may be
suitable; however, these PET tracers have not been
widely used, particularly not feasible under sequential
analysis. Magnetic resonance spectroscopy may be
another alternative for assessing myocardial hypoxic
condition. However, this requires quite long time for
measurement, and thus, it may not be suitable for serial
assessment as the current study.
The current study nicely analyzed a number of LV
strain parameters in normal and hypoxic condition.
While LV volume was reduced with increase in EF,
there were no significant differences in radial or
circumferential strain but only increases in peak rotation
and torsion under hypoxia. Radial circumferential
strains have recently been used with echocardiography
and MRI in clinical setting, but these parameters may
not be sensitive in animal experiments. Hypoxia may not
increase cardiac contractility but increase in EF by
volume reduction with increase torsion. More work has
to be done in this area.
One of the inherent limitations in the current
experimental study is the use of hypoxic model as
hypoxia, and stress-induced ischemia is somewhat
different. We do understand that hypoxia is a
wellestablished experimental model to analyze global LV
function with metabolic alteration. On the other hand,
there are a number of animal experiments with coronary
stenosis or occlusion to identify regional dysfunction
with altered metabolism under pharmacological stress.14
It would be nice to see serial changes of function and
metabolism using PET/MRI system under mild ischemia
vs moderate to severe ischemia in order to facilitate
understanding the close relationship of functional and
metabolic alteration under a single stress. Also some
compensatory function such as augmentation in
metabolism and function in the remote area may possibly be
seen with PET/MRI.
Again, we admire unique and nice experiments by
the authors to suggest dynamic change of metabolism
and cardiac function using PET/MRI in animal model to
provide valuable information under hypoxia. PET/MRI
study will surely provide us new changes for various
experiments as well as clinical findings in the near
Nagara Tamaki, Shigenori Matsushima, and Motoki
Nishimura have nothing to declare for this publication.
1. Vontobel J , Liga R , Possner M , Clerc OF , Mikulicic F , VeitHaibach P , et al. MR-based attenuation correction for cardiac FDG PET on a hybrid PET/MRI scanner: Comparison with standard CT attenuation correction . Eur J Nucl Med Mol Imaging . 2015 ; 42 : 1574 - 80 .
2. Bailey DL , Pichler BJ , Gu¨ckel B , et al. Combined PET/MRI: Global warming-Summary report of the 6th international workshop on PET/MRI. Mol Imaging Biol . 2018 ; 20 : 4 - 20 .
3. Rischpler C , Nekolla SG , Kunze KP , Schwaiger M. PET/MRI of the heart . Semin Nucl Med . 2015 ; 45 : 234 - 47 .
4. Kunze KP , Nekolla SG , Rischpler C , et al. Myocardial perfusion quantification using simultaneously acquired 13NH3-ammonia PET and dynamic contrast-enhanced MRI in patients at rest and stress . Magn Reson Med . 2018 . https://doi.org/10.1002/mrm. 27213.
5. Krumm P , Mangold S , Gatidis S , et al. Clinical use of cardiac PET/MRI: current state-of-the-art potential future applications . Jpn J Radiol . 2018 . https://doi.org/10.1007/s11604-018-0727-2.
6. Masuda A , Nemoto A , Yamaki T , Oriuchi N , Takenoshita S , Takeishi Y. Assessment of myocardial viability of a patient with old myocardial infarction by 18F-fluorodeoxyglucose PET/MRI . J Nucl Cardiol. 2017 . https://doi.org/10.1007/s12350-017-0941-9.
7. Fayad ZA , Fuster V , Fallon JT , et al. Noninvasive in vivo human coronary artery lumen and wall imaging using black blood magnetic resonance imaging . Circulation . 2000 ; 102 : 506 - 10 .
8. Kim WY , Stuber M , Bomert P , et al. Three-dimensional blackblood cardiac magnetic resonance coronary vessel wall imaging detects positive arterial remodeling in patients with nonsignificant coronary artery disease . Circulation . 2002 ; 106 : 296 - 9 .
9. Rudd JH , Warburton EA , Fryer TD , et al. Imaging atherosclerostic plaque inflammation with 18F-fluorodeoxyglucose positron emission tomography . Circulation . 2002 ; 105 : 2708 - 11 .
10. Sparrow PJ , Merchant N , Provost YL , et al. CT and MR imaging findings in patients with acquired heart disease at risk for sudden cardiac death . Radiographics . 2009 ; 29 : 805 - 23 .
11. Manabe O , Oyama-Manabe N , Ohira H , Tsutsui H , Tamaki N. Multimodality evaluation of cardiac sarcoidosis . J Nucl Cardiol . 2012 ; 19 : 621 - 4 .
12. Piekarski E , Benali K , Rouzet F. Nuclear imaging in sarcoidosis . Semin Nucl Med . 2018 ; 48 : 246 - 60 .
13. Barton GP , Vildberg L , Goss K , Aggarwal N , Eldridge M , McMillan AB . Simultaneous determination of dynamic cardiac metabolism and function using PET/MRI . J Nucl Cardiol. 2018 . https://doi.org/10.1007/s12350-018-1287-7.
14. Spuentrup E , Ruhl KM , Botnar RM , Wiethoff AJ , Buhl A , Jacques V , Greenfield MT , Krombach GA , Gu¨nther RW, Vangel MG , Caravan P . Molecular magnetic resonance imaging of myocardial perfusion with EP-3600, a collagen-specific contrast agent: Initial feasibility study in a swine model . Circulation . 2009 ; 119 : 1768 - 75 .