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.
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.
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.