OTHER USES OF CARDIAC NUCLEAR MEDICINE
Equilibrium Radionuclide Ventriculography (Multiple-Gated Acquisition Scan)
Multiple-gated acquisition (MUGA) scanning is an approach used to quantify both left and right ventricular function, based on images generated after the injection of 99mTc-labeled erythrocytes. The labeling procedure can be performed in vitro using a commercially available kit (UltraTag; Mallinckrodt, St. Paul, Minnesota), in vivo, or semi–in vitro. The in vitro method provides the highest labeling efficiency and best images, but it is the most laborious, time-consuming, and expensive technique. Once the circulating blood pool has been appropriately labeled, determination of wall motion abnormalities, left ventricular volumes, and EFs can be made. These measures are accurate, repeatable, and reproducible, and are often used for serial follow-up of EFs in patients who receive cardiotoxic drugs, particularly chemotherapeutic agents. In some cases, MUGA is used for the serial follow-up of HF patients.
An advantage of MUGA is the ability to do first-pass imaging, which
allows evaluation of the right ventricle, as well as quantitative shunt
analysis. Although the latter procedure is now predominantly done via
echocardiography, the former is still sometimes used in select patient
populations, such as congenital heart disease in the pediatric population, and
in some cases, combined with standard myocardial perfusion scans as an approach
to evaluating right ventricular function.
Stress MUGA scanning can be performed either with dobutamine or with an
exercise ergometer bicycle that is attached to a seat or the bed on which the
patient lies. It offers the ability to provide real-time EF imaging, as well as
imaging of any wall motion abnormalities that develop during the study (Fig.
10.5). Like echocardiography, ischemic changes can be detected by evaluating
wall motion changes from rest to stress. Newer approaches in MUGA include
performing SPECT, which enables a more accurate separation of the ventricles
from each of the other chambers (Fig. 10.5). Although in theory this should
yield better ventricular volumes and EFs than planar estimates, it has not been
validated like the planar techniques. For this reason and the emergence of competing technologies such as
echocardiography and MRI, this modality
is rarely used.
 |
FIG 10.5 Multiple-Gated
Acquisition (MUGA) and Stress-MUGA Scanning.
Viability
Because more patients survive myocardial infarctions (MIs) as a result of
advances in cardiology, detection of myocardial viability has become increasingly
important. Identifying a hibernating myocardium that is still viable but
chronically hypoperfused and ischemic is believed to be important for decision
making with respect to revascularization. However, because no survival benefit
has been shown with surgical intervention on areas identified as viable with
imaging, this is less frequently done. Nevertheless, viability imaging is still
occasionally done to answer specific questions and to manage difficult
scenarios, in part because the advances in
viability assessment available since the original studies are believed to be far superior and of greater clinical
benefit.
Because 201Tl is a potassium analogue, its exchange across a
mem- brane is a hallmark of a viable myocyte. Viability protocols make use of
the ability of 201Tl to undergo redistribution and involve imaging
at baseline, following redistribution, and often following repeat injection of
an extra dosage. Viable myocytes will take up 201Tl for as long as
24 hours after injection. A newer approach has been to use administration of
nitrates in conjunction with either 99mTc agents or 201Tl.
In theory, this approach causes vasodilation in areas that are otherwise
hypoperfused at baseline, causing increased flow to those regions, and
resulting in improved tracer uptake. The specificity of this procedure can be
improved by obtaining gated images with graded dobutamine infusion during
imaging.
Unlike 201Tl, which is used as a perfusion marker for SPECT, 18F,
2-deoxyglucose (FDG) is a marker of myocardial glucose metabolism that is
imaged with PET. Myocardial uptake of FDG is facilitated by previous
administration of glucose, often coupled with intravenous insulin
administration to drive glucose use by viable cardiomyocytes. In conjunction
with perfusion imaging, FDG imaging can provide useful information for the
assessment of myocardial viability, and is generally favored more than SPECT
techniques. In many cases, CMRI is preferred because of its better resolution
and similar accuracy as PET, and because it also provides anatomic details that
could be helpful in surgical planning. Nevertheless, PET can be used when MRI
may be contraindicated due to the presence of metal and cardiac devices, which
are frequent in this population of patients. An ideal approach would be to use
PET-MR, which could provide the best viability assessment in a single imaging session. This is under further
study.
FUTURE DIRECTIONS IN CLINICAL CARDIAC MOLECULAR IMAGING
Ventricular Dyssynchrony Assessment
Biventricular pacing has been shown to reduce symptoms in some patients
with advanced HF, presumably by improving dyssynchronous left ventricular
contraction. However, not all patients improve. It has been hypothesized that
the patients who obtain maximal benefit are those who have the greatest
restoration of synchronous contraction of the left ventricle. This has
stimulated research focused on using nuclear imaging (SPECT-MPI or other
modalities) to assess the effect of placing pacemaker leads in specific
locations in the right and left ventricles. Comparison of synchrony at baseline
and with pacing could facilitate optimization of lead placement and outcomes
from biventricular pacing in this setting.
Ischemic Memory
Fatty acid (FA) imaging has been proposed as a sensitive and specific
method to determine whether a patient presenting with a recent history of
ischemic symptoms did indeed have an ischemic event. Although cardiac
biomarkers such as creatinine kinase and cardiac troponins are sensitive
indicators of myocardial necrosis, there is no current test to confirm if a
recent event represented ischemia at a level insufficient to result in
measurable levels of these cardiac biomarkers.
Under fasting, ischemic, or hypoxic conditions, FA metabolism is
suppressed and glucose oxidation becomes increasingly important for myocardial
energy production. This finding has led to the notion that alterations in FA
metabolism could function as a sensitive marker for myocardial ischemia.
Radiopharmaceuticals such as iodine-123 15-(p-iodo-phenyl)-3-R,S-methylpentadecanoic
acid—an FA analogue—are being studied as a SPECT imaging agent. Because metabolic abnormalities usually persist
long after the ischemic event has
resolved, this type of radiotracer could be used to identify at-risk areas of
myocardium long after the symptoms of angina have abated in patients, and flow
has been restored, without having to repeat a stress test.
FDG with PET is another agent potentially capable of detecting recent
ischemia, but may be more limited by practical limitations compared with FA
imaging.
Cardiac
Neurotransmission Imaging
Radioiodine-labeled 123I-metaiodobenzylguanidine (mIBG) has
been studied as a SPECT imaging agent based on the notion that cardiac
receptors for neurotransmitters may be altered in certain disease states.
Alterations in mIBG uptake may identify myocardium that is mechanically
functional but highly sensitive to catecholamine stimulation and arrhythmogenic
on that basis. mIBG has been studied in patients with idiopathic ventricular
tachycardia and/or fibrillation, arrhythmogenic right ventricular dysplasia, and cardiac
dysautonomias, including diabetic neuropathy and drug-induced cardiotoxicity.
In conjunction with EF, brain natriuretic peptide, or some other variables,
mIBG scanning has been reported to accurately predict patients who will benefit
from ICD placement. Because of our current inability to distinguish between
patients with low EFs who require defibrillation for ventricular tachy- cardia
and/or fibrillation within 5 years of ICD placement and those who will not,
plus the high cost of ICD implantation, more precision in determining patients
at high risk and low risk, beyond assessment of left ventricular function, is
an attractive concept.
Imaging with mIBG is an independent prognostic predictor of overall
survival in patients with HF. When combined with other clinical variables, this
could prove to be a strong modality in affecting management of patients with
HF, in whom studies are ongoing.
Sarcoidosis and
Other Inflammatory Pathology
Cardiac sarcoid causes focal granulomatous inflammation at various
locations in the myocardium, which can result in electrical or functional
cardiac disturbances. In patients with cardiac sarcoid, 201Tl
imaging shows patchy defects that presumably correspond to areas of scarring
and/or inflammation. Because of the low resolution of 201Tl images,
small defects can be missed. Other SPECT tracers used include 67Ga-
citrate or 111In-octreotide, which can detect areas of active
inflammation in conjunction with a perfusion tracer. More recent uses of
fasting FDG-PET have also been successful in detecting inflammatory lesions
that have increased tracer uptake, and differentiating them from areas of
scarring without uptake.
There is evidence to show that FDG-PET can better localize inflammatory
etiologies such as endocarditis and myocarditis, which are both difficult
diseases to diagnose. Additional studies have shown the ability to risk
stratify aortic aneurysms; those that exhibit increased tracer localization are
associated with a worse prognosis, and these patients likely need more
immediate intervention.
Although clinical outcomes associated with MRI evaluations are very good,
nuclear imaging offers the possibility of detecting lesions with active
inflammation and those that respond to therapy. More recently, the introduction
of the octreotide analogue PET radiotracers 68Ga-DOTATATE, 68Ga-DOTATOC,
and 68Ga-DOTANOC, offers the chance
to develop this area even further, with the consideration of again combining
the respective strengths with PET-MR imaging.
The SPECT radioactive isotopes predominantly involved in cardiac amyloid
include 99mTc–3-diphosphono-1, 2-propanodicarboxylic acid (99mTc-DPD)
and 99mTc-pyrophosphate (99mTc-PYP), which can detect 123I-mIBG, which may detect cardiac denervation and autonomic dysfunction in
cardiac amyloid. An important aspect is to be able to identify the main types
of amyloid without cardiac biopsy: light chain (AL) and transthyretin (ATTR).
Both 99mTc-labeled agents have been shown to discriminate well
between the two forms, and can be used in lieu of an endocardial biopsy. This
is important because correct identification of the type of disease leads to
important differences in prognosis, and thus subsequent management of the
disease. However, there is a need to identify the role of these tracers in
tracking progression of disease and to monitor treatment response.
There are PET agents that are used for the detection of β-amyloid neural
plaques for the assessment of Alzheimer disease. One of the agents, 18F-florbetapir,
has been studied in cardiac amyloidosis, and holds some promise in detecting
the disease and potentially differentiating between the AL and ATTR variants.
Further usefulness of this agent in these
diseases is ongoing.
