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3 Review ofCardiac Metabolism andFDG
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43
particularly unsuitable for myocardium with a
precarious oxygen supply. From a clinical perspective, the reliance of hibernating myocardium
on glucose metabolism is key for its visualization using viability imaging (Chap. 20).
Conclusion
Cardiomyocyte metabolism is a vast and complicated topic which remains an area of active study.
However, FDG-PET can serve as a useful probe
to help elucidate the mysteries of the
myocardium.
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Myocardial Suppression Protocols
https://t.me/medicina_free
MichaelT.Osborne, KenechukwuMezue,
andSanjayDivakaran
4
Abbreviations
18
F-FDG
JSNC Japanese Society of Nuclear
PET Positron Emission Tomogra-
SNMMI/ASNC Society of Nuclear Medicine
M. T. Osborne (*) ∙ K. Mezue
Cardiology Division, Department of Medicine,
Massachusetts General Hospital and Harvard Medical
School, Boston, MA, USA
Cardiovascular Imaging Research Center,
Massachusetts General Hospital and Harvard Medical
School, Boston, MA, USA
e-mail: mosborne@mgh.harvard.edu;
kmezue@mgh.harvard.edu
S. Divakaran
Cardiovascular Imaging Program, Departments of
Radiology and Medicine, Brigham and Women’s
Hospital and Harvard Medical School,
Boston, MA, USA
Division of Cardiovascular Medicine, Department of
Medicine, Brigham and Women’s Hospital and
Harvard Medical School, Boston, MA, USA
e-mail: sdivakaran@bwh.harvard.edu
18
F-uorodeoxyglucose
Cardiology
phy
and Molecular Imaging/
American Society of Nuclear
Cardiology
Introduction
One of the primary challenges in successful
18
F-uorodeoxyglucose positron emission
tomography (18F-FDG-PET) imaging of myocardial and intracardiac inammation is discerning pathologic 18F-FDG uptake from
physiologic uptake by background myocardium. Accordingly, patients undergoing cardiovascular 18F-FDG- PET for inammation
must undergo careful preparation prior to
imaging to optimize the diagnostic yield of the
modality. This chapter will describe the underlying physiology of myocardial and inammatory cell metabolism, examine the existing
evidence for the utility of various preparation
techniques, describe current evidence- based
consensus recommendations, and identify
future directions for further research to optimize inammatory myocardial 18F-FDG- PET
imaging.
Underlying Physiology
ofMyocardial andInammatory
Cell Glucose Metabolism
Normal myocytes are able to use both glucose
and free fatty acids for metabolism and have
variable avidity for glucose under different
metabolic conditions. Intake of carbohydrates
triggers insulin secretion, which leads to acti-
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2022
M. Pelletier-Galarneau, P. Martineau (eds.), FDG-PET/CT and PET/MR in Cardiovascular
Diseases, https://doi.org/10.1007/978-3-031-09807-9_4
47
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M. T. Osborne et al.
vation of GLUT4 channels in the myocardium
to augment glucose uptake. In the absence of
insulin, normal myocytes utilize free fatty
acids for metabolism [1]. Alternatively, inammatory cells are only able to utilize glucose for
metabolism through uptake via the constitutively expressed GLUT1 and GLUT3 channels
[2]. 18F-FDG, a radioactive glucose analog, is
phosphorylated upon entry into cells and
becomes trapped, allowing an assessment of
glucose metabolism using PET imaging. Thus,
by manipulating the metabolism of normal
myocardium to shift it away from glucose and
towards free fatty acids prior to 18F-FDG-PET
imaging it is possible to identify pathological
inammation that would otherwise be
obscured.
Inflammatory Cells
18
18
F-FDG and
glucose
F-FDG enters
cell via GLUT1 &
GLUT3
transporters
Goals ofPreparation for18F-FDGPET Imaging
To limit myocyte uptake of glucose and 18F-FDG,
the primary goal of patient preparation is to minimize insulin release and glucose availability prior
to 18F-FDG-PET imaging of myocardial and
intracardiac inammation. A secondary goal is to
augment free fatty acid availability to provide
adequate energy for the myocardium in a low
insulin state. Ultimately, the sensitivity for detecting highly metabolic inammatory cells within
cardiovascular tissues is optimized by maximally
suppressing 18F-FDG uptake by the myocardium.
The metabolism of normal myocardium and
inammatory cells and the impact of patient
preparation are summarized in Fig.4.1 [3].
18
F-FDG Uptak
Similar uptake occurs
under all conditions
e
18
F-FDG and
glucose
Fig. 4.1 Metabolism of inammatory cells and normal
myocytes under a variety of metabolic conditions and
impact of suppressing physiologic myocardial
Normal Myocytes
18
F-FDG enters
cell via GLUT4
transporter
18
F-FDG
18
F-FDG Uptak
↑insulin
↓FFA
Uptaker dependent
on insulin level/
metabolic state
uptake for inammatory imaging. FFA free fatty acids,
18
F-FDG 18F-uorodeoxyglucose. (Reprinted with per-
mission [3])
↓insulin
↑FFA
18
F-FDG Uptak
e
e
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49
Patterns ofMyocardial 18F-FDG
Uptake
ground of diffuse 18F-FDG myocardial uptake
can be seen with either poor suppression or with
incomplete suppression and superimposed
The appearance of optimally suppressed 18FFDG uptake by normal myocardium leads to a
relative paucity of myocardial tracer uptake compared to the blood pool to facilitate identication
of areas of abnormal 18F-FDG uptake.
Alternatively, a pattern of intense global myocardial uptake that obscures foci of abnormal 18FFDG uptake indicates poor suppression of
myocardial uptake. Between these extremes, a
nding of focally increased uptake on a back-
inammatory pathology. Lastly, focal 18F-FDG
uptake is often seen in the setting of inammatory pathology; however, focal myocardial 18FFDG uptake limited to the lateral wall and basal
ring has been reported as normal variants [4].
These patterns can be challenging to distinguish
from pathology and the physiology underlying
the patterns is not well understood. Images demonstrating these patterns are shown below
(Fig.4.2).
ab
cd
e
Fig. 4.2 Patterns of myocardial 18F-FDG uptake follow-
ing preparation for inammatory imaging. (a) Global suppression. (b) Diffuse uptake. (c) Focal on diffuse uptake.
(d) Focal uptake. (e) Lateral wall uptake (normal variant).
All panels display short axis images with perfusion imaging in the top row and metabolism (18F-FDG) in the bottom row
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M. T. Osborne et al.
Approaches toSuppress Myocardial
18
F-FDG Uptake
Dietary Strategies
Prolonged Fasting
Fasting has been widely studied and has become
a commonly implemented component of many
protocols to suppress myocardial 18F-FDG uptake
[3, 5]. The metabolic consequences of fasting
include lower insulin release and heightened
lipolysis, resulting in a shift towards myocardial
utilization of free fatty acids rather than glucose
[6]. Although current Society of Nuclear
Medicine and Molecular Imaging/American
Society of Nuclear Cardiology (SNMMI/ASNC)
recommendations support a fast of at least 4–12h
prior to 18F-FDG administration, more recent
data suggests that a longer fast of up to 18h may
provide even greater suppression of myocardial
18
F-FDG uptake [5, 7, 8]. Fasting for 18 h may
also provide the optimal method for myocardial
18
F-FDG uptake suppression in isolation for individuals with signicant dietary constraints (e.g.,
vegan and vegetarian diets) [5].
High-Fat Low-Carbohydrate Diet
A high-fat low-carbohydrate diet can be implemented to reduce insulin release and increase
available free fatty acids as a method of shifting
myocardial metabolism towards free fatty acids
rather than glucose. This strategy has been extensively researched, and several studies have shown
improved suppression of myocardial 18F-FDG
uptake with high-fat low-carbohydrate meals
combined with fasting compared to fasting alone
[3, 5]. Accordingly, current SNMMI/ASNC recommendations include having at least two meals
with >35g of fat and <3g carbohydrates on the
day prior to the 18F-FDG-PET exam [5]. The
Japanese Society of Nuclear Cardiology (JSNC)
also recommends a low carbohydrate diet (<5g)
prior to fasting but considers a high-fat diet to be
supplemental [8]. Table4.1 provides a guide of
optimal choices for dietary preparation [3].
High-Fat Drink
Multiple studies have evaluated the impact of
adding a high-fat drink to a dietary preparation
Table 4.1 Dietary recommendations for optimal suppression of myocardial uptake of 18F-FDG
Consume Meat fried in oil or butter without
breading or broiled (chicken, turkey,
bacon, meat-only sausage, hamburgers,
steak, sh)
Eggs (prepared without milk or cheese)
Oil (an option for patients who are
unable to eat and have enteral access or
vegan patients) and butter
Clear liquids (water, tea, coffee, diet
sodas, etc.)
Acceptable Some articial sweeteners (Sweet’N
low, equal, NutraSweet)
Fast of 18h or longer if unable to eat
with no enteral access or dietary
restrictions prevention consumption of
advised diet
Avoid Vegetables, beans, nuts, fruits, and juices
Bread, grain, rice, pasta, all baked goods
Sweetened, grilled or cured meats or
meat with carbohydrate-containing
additives (some sausages, ham,
sweetened bacon)
Dairy products aside from butter (milk,
cheese, etc.)
Candy, gum, lozenges, and sugar
Alcoholic beverages, soda, and sports
drinks
Mayonnaise, ketchup, tartar sauce,
mustard, and other condiments
Dextrose containing intravenous
medications
Reprinted with permission [3]
protocol several hours prior to imaging. This
strategy seeks to suppress myocardial 18F-FDG
uptake by augmenting free fatty acid availability.
While the results of several early studies do not
support broad implementation, a recent study
describes an effective preparation strategy that
includes a high-fat drink as part of a combined
approach [3, 5, 9].
Behavioral Strategies
Strenuous exercise triggers augmentation of
myocardial glucose uptake and metabolism
through activation of catecholaminergic pathways. Accordingly, patients should avoid exercising for 12–24 h before 18F-FDG
administration [1].
4 Myocardial Suppression Protocols
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Pharmacologic Strategies
Heparin
Intravenous heparin increases lipolysis and serum
free fatty acids [10]. As such, several institutions
administer heparin approximately 15min prior to
18
F-FDG administration as a component of a protocol of myocardial 18F-FDG uptake suppression.
The dose given is typically a 50 IU/kg bolus.
Nevertheless, the overall body of evidence
remains inconclusive and the current SNMMI/
ASNC recommendations suggest that heparin
administration may be benecial as an adjunctive
component of a preparation strategy while it is
not recommended by the JSNC [5, 8].
Calcium Channel Blockers
Intracellular calcium is a known contributor to
glucose and 18F-FDG uptake. Although calcium
channel blockers reduced myocardial uptake of
18
F-FDG in a murine model, they have not been
found to be incrementally effective in humans
[11].
Communication
It has proven useful to provide careful review of
preparation instructions with patients several
days in advance of imaging as well as evaluating
their adherence to the preparation strategy on the
day of imaging prior to radiotracer injection. This
allows patients to prepare well in advance of their
study as well as to identify patients who are
unlikely to have adequate suppression and permit
rescheduling without unnecessary radiation
exposure [5, 8].
Combination Strategies
Most institutions have preparation protocols that
employ more than one of the above approaches in
combination to prepare patients for myocardial
and intracardiac inammation imaging with
18
F-FDG-PET.The individual component strategies are summarized in Table4.2.
Table 4.2 Summary of different preparation strategies
for myocardial 18F-FDG-PET and their impacts on myocardial metabolism
Impacts on
myocardial
Strategy grouping Specic strategies
Dietary
techniques
Behavioral
technique
Pharmacologic
strategies
Communication Review of
Prolonged
fasting
High-fat
lowcarbohydrate
diet
High-fat drink Increased
Abstinence
from exercise
Heparin Increased
Calcium
channel
blockers
protocol before
preparation and
conrmation of
adherence prior
to imaging
metabolism
Reduced
glucose uptake
and increased
availability of
free fatty acids
Reduced
glucose uptake
and increased
availability of
free fatty acids
availability of
free fatty acids
Reduced
glucose uptake
availability of
free fatty acids
Reduced
glucose uptake
Enhance patient
understanding
and compliance
Laboratory Values
The relationship between serological measures of
glucose and fat metabolism and imaging ndings
in 18F-FDG-PET imaging of myocardial and
intracardiac inammation has been investigated
in several cohorts. The impact of different preparation strategies on serological measures of
metabolism has been largely inconsistent to date,
although there does appear to be a tendency
towards lower blood glucose prior to imaging
with a longer duration of fasting [3]. A recent
study of serial 18F-FDG-PET imaging showed
that the metabolic parameters on serial imaging
visits were similar but that these measurements
were unrelated to imaging ndings [12].
Alternatively, a subsequent single center study
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M. T. Osborne et al.
that evaluated the effectiveness of a preparation
protocol reported that there were signicant associations between markers of glucose metabolism
and the standardized uptake values of the blood
pool and myocardium and established normative
ranges of serological measures of metabolic
parameters for the study population [9]. Indeed,
given the heterogeneity of preparation strategies,
it may be that each unique protocol alters metabolism differently, and the establishment of normative values based on a given preparation
strategy in a particular population may be necessary to meaningfully assess a particular patient’s
metabolic state prior to imaging [9, 13].
Patient Populations Requiring
Special Considerations
While the above recommendations apply
broadly, several patient populations require additional consideration to optimize myocardial suppression of 18F-FDG uptake for inammation
imaging.
Patients with diabetes mellitus create a unique
challenge given the need to minimize insulin
administration to optimize imaging while balancing patient safety. Current recommendations
suggest that patients with diabetes undergo the
same preparation strategy as other patients.
Those with type I diabetes should receive basal
insulin but should minimize short-acting insulin
to the extent that it is safe, especially on the day
of the study. For those with type 2 diabetes, oral
medications and non-insulin injections should
be held on the day of the test. Similarly, insulin
administration should be minimized to the extent
that it is safe [5, 8].
It is important to exclude obstructive coronary
disease in patients prior to 18F-FDG-PET imaging if there is clinical suspicion. Ischemic and
hibernating myocardium is highly avid for glucose because it lacks the ability to metabolize
fatty acids. Accordingly, ischemic territories can
exhibit exuberant uptake of 18F-FDG even under
fasting conditions, and coronary artery disease
should be considered in any patient with 18F-FDG
uptake in a coronary distribution on a study
ordered to assess for inammation [14].
Advanced cardiomyopathy alters myocardial
metabolism by increasing glucose metabolism
relative to fatty acid metabolism. Although this
change in physiology merits consideration, there
are presently no recommendations to modify
preparation strategies in the setting of cardiomyopathy [15].
Additionally, inpatients who require 18F-FDGPET myocardial imaging for inammation also
require careful planning. Intravenous medications containing glucose should be avoided.
Furthermore, a multidisciplinary approach
involving nursing, dieticians, and imaging staff
should be employed, in addition to providing the
same instructions to the patients that would have
been provided in the outpatient setting. As with
outpatients, these individuals should be screened
carefully for errors in preparation prior to 18FFDG injection.
Current Recommendations
The most recent SNMMI/ASNC expert consensus document from 2017 provides recommendations to optimize patient preparation based on
current evidence. The document supports preparing patients with either: (a) at least two high
fat (>35g) and low carbohydrate (<3g) meals
the day prior to the study followed by a fast ranging from 4 to 12h or (b) a fast of >18h. The use
of heparin can be considered as an adjunct given
its uncertain role in suppressing myocardial glucose utilization. All patients should be contacted
with instructions well in advance of the study
and should document their meals and preparation for review with lab staff prior to 18F-FDG
injection [5]. Since publication of this most
recent consensus document, additional support
for longer duration fasting has emerged from
several centers. Accordingly, if possible, a fast
closer to 12 h as part of a combined approach
appears to be more favorable [7]. In fact, the
JSNC advocates for a longer fasting period of
12–18h preceded by a low carbohydrate meal in
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