After myocardial infarction, optimal clinical management depends critically on cardiac imaging. Remodelling and heart failure, presence of inducible ischaemia, presence of dysfunctional viable myocardium, future risk of adverse events including risk of ventricular arrhythmias, need for anticoagulation, and other questions should be addressed by cardiac imaging. Strengths and weaknesses, recent developments, choice, and timing of the different non-invasive techniques are reviewed for this frequent clinical scenario.

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Cardiac imaging after myocardial infarction.

https://www.internationaljournalofcardiology.com/article/S0167-5273(12)01637-3/pdf

Assessment of myocardial perfusion and viability by Positron Emission Tomography

https://www.heartrhythmjournal.com/article/S1547-5271(08)00850-3/pdf

Integration of positron emission tomography/computed tomography with electroanatomical mapping: A novel approach for ablation of scar-related ventricular tachycardia

The ability to personalize medical care will require characterization of disease processes at a molecular level. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are generally considered the most practical molecular imaging methods in clinical practice. Both methods detect a tracer with high sensitivity and both provide information about the anatomical and temporal distribution of the isotope. These data are valuable in imaging a receptor ligand, detecting a metabolite transporter, or assessing tissue perfusion. Images of metabolic processes are one form of molecular imaging, but PET and SPECT images do not provide information about the chemical state of the tracer. Consequently the image reflects a combination of perfusion, transport of the tracer, and metabolism. The link between images of radiotracers and specific metabolic information is inherently limited.

The capacity of magnetic resonance to detect specific molecular information is well-known, but sensitivity under normal conditions is inadequate for clinical purposes. Consequently the introduction of hyperpolarized noble gas imaging in the mid-1990s (1, 2) generated considerable enthusiasm. This was followed by extraordinary progress in imaging hyperpolarized (HP) 13C at 1.5 T (3 –8). The development of dynamic nuclear polarization(DNP)and parahydrogen induced polarization (PHIP) for preparing HP 13C-enriched materials is a major advance because much of the technical evolution of MR over the past 50 years has focused on overcoming sensitivity constraints. High field magnets, cryoprobes, inverse detection schemes, etc., are valuable but no single method has even come close to providing a 100-fold gain in sensitivity in a single scan. DNP provides, routinely, ~10,000-fold gains. Fundamentally new MR imaging exams are enabled by this technology.

The seminal report demonstrating rapid dissolution DNP was published eight years ago (3). Since then, progress by multiple groups in a wide range of models has been rapid and, for this reason, optimism continues to build about the value of 13C DNP in animal models of disease and eventually in patients. Much of the early focus has been on cancer (9 –14), and the detection of glycolytically-produced lactate was an early motivation for developing DNP (5). The first in vivo cardiac studies in the pig (8) were followed quickly by studies in isolated rat hearts (15 –18) and the in vivo rat heart (19, 20). More recent studies have compared viability scans by MRI to 13C DNP (7), and introduced multislice 13C imaging which is essential for clinical applications (21). In addition to DNP, other techniques are available to hyperpolarize nuclei(22).

These early successes in multiple labs demonstrate the feasibility of imaging HP 13Cin the heart of large animals. Multiple imaging technologies are available in clinical cardiology, but even with the wealth of available methods it remains difficult to confidently select appropriate therapy in some circumstances. In this short commentary we explore the potential clinical value of cardiac 13C MRI for analysis of metabolism in the left ventricle. Although 13C MRI methods have been demonstrated for both vascular imaging and perfusion, alternative clinical methods are available. The focus here is on the information – intermediary metabolism – that cannot be obtained with alternative clinical methods.

Could 13C MRI assist clinical decision-making for patients with heart disease?

A series of fluorinated pyridazinone derivatives with IC50 values ranging from 8 to 4000 nM for the mitochondrial complex 1 (MC1) have been prepared. Structure–activity relationship (SAR) assessment indicated preference of the fluorine label to be incorporated on an alkyl side chain rather than directly on the pyridazinone moiety. Tissue distribution studies of a series of analogues ([18F] 22–28) in Sprague−Dawley (SD) rats identified [18F]27 as the most promising radiotracer with high uptake in cardiac tissue (3.41%ID/g; 30 min post injection) in addition to favorable heart to nontarget organ distribution ratios. MicroPET images of SD rats and nonhuman primates after [18F]27 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.

Synthesis and Biological Evaluation of Pyridazinone Analogues as Potential Cardiac Positron Emission Tomography Tracers

The assessment of myocardial viability has become an important aspect of the diagnostic and prognostic work-up of patients with ischemic cardiomyopathy. Although revascularization may be considered in patients with sufficient viable myocardium, patients with predominantly scar tissue should be treated medically. Patients with left ventricular dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischemia but at the same time benefit most from revascularization. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy (SPECT), whether using (201)thallium, (99m)Tc-sestamibi, or (99m)Tc-tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic and perfusion imaging with positron emission tomography (PET) radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularization. New techniques in the nuclear cardiology field, like attenuation corrected SPECT, dual isotope simultaneous acquisition (DISA) SPECT and gated FDG PET are promising and will further improve the detection of myocardial viability. Also the combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and non-invasive coronary angiography to myocardial perfusion imaging and quantification. Evaluation of the clinical role of these creative new possibilities warrants investigation.

Jeroen J. Bax

Papers

Imaging techniques in nuclear cardiology for the assessment of myocardial viability.