Antti Saraste

PET and MRI in cardiac imaging: from validation studies to integrated applications

IntroductionPositron emission tomography (PET) is the gold standard for non-invasive assessment of myocardial viability and allows accurate detection of coronary artery disease by assessment of myocardial perfusion. Magnetic resonance imaging (MRI) provides high resolution anatomical images that allow accurate evaluation of ventricular structure and function together with detection of myocardial infarction.ObjectivePotential hybrid PET/MR tomography may potentially facilitate the combination of information from these imaging modalities in cardiology. Furthermore, the combination of anatomical MRI images with the high sensitivity of PET for detecting molecular targets may extent the application of these modalities to the characterization of atherosclerotic plaques and to the evaluation of angiogenetic or stem cell therapies, for example.DiscussionThis article reviews studies using MRI and PET in parallel to compare their performance in cardiac applications together with the potential benefits and applications provided by hybrid PET/MRI systems.

Cardiovascular molecular imaging: an overview.

Molecular imaging is non-invasive visualization and measurement of biological processes at the molecular and cellular level within a living organism. This review provides a description of the various molecular imaging techniques for imaging cardiovascular targets and their potential clinical implications. Molecular imaging has relied mainly on nuclear imaging, but advances in nanoparticle probe development have made magnetic resonance imaging and ultrasound as emerging, radiation-free alternatives. Targeted imaging of vascular inflammation or thrombosis may allow improved risk assessment of atherosclerosis by detecting plaques at high risk of acute complications. Imaging probes detecting myocardial apoptosis, metabolic alterations, injury to extracellular matrix, angiogenesis, or innervation may provide tools for assessing risk of arrhythmias and left ventricular remodelling associated with progressive cardiac dysfunction and heart failure. Although clinical experience remains limited, careful evaluation of safety as well as validation of diagnostic and prognostic value of these techniques in clinical trials is still needed.

Contrast-enhanced magnetic resonance imaging in the assessment of myocardial infarction and viability.

Contrast-enhanced magnetic resonance imaging (MRI) can be used to visualize the transmural extent of myocardial infarction with high spatial resolution. The aim of this review is to provide an overview of the use of contrast-enhanced MRI for characterization of ischemic myocardial injury in comparison to other imaging methods and its relevance in clinical syndromes related to coronary artery disease. Infarcted myocardium appears hyperenhanced compared with normal myocardium when imaged by a delayed-enhancement MRI technique with the use of an inversion-prepared T1-weighted sequence after injection of gadolinium chelates, such as gadolinium-diethylenetriamine pentaacetic acid. Experimental and clinical studies indicate that the extent of delayed enhancement is reproducible and closely correlates with the size of myocardial necrosis or infarct scar as determined by established in vitro and in vivo methods. Furthermore, MRI appears to be more sensitive than other imaging methods in detecting small subendocardial infarctions. The transmural extent of delayed enhancement potentially predicts functional outcome after revascularization in acute myocardial infarction and chronic ischemic heart disease, indicating that it can accurately discriminate between infarction and dysfunctional but viable myocardium. Further experience from clinical trials is needed to understand the association of delayed enhancement with clinical outcomes.

Novel F-18–Labeled PET Myocardial Perfusion Tracers: Bench to Bedside

Myocardial perfusion imaging is a widely used approach to noninvasively identify myocardial ischemia and guide therapies. It is typically performed using single photon emission computed tomography. The competing technology positron emission tomography (PET) offers higher diagnostic accuracies but suffers from logistical limitations due to the use of short-lived radioisotopes. New 18F-labeled perfusion markers were introduced in the past years and offer simplified supply approaches, as known from oncologic PET imaging. This review summarizes the available literature especially from preclinical studies, but also very recent findings from early clinical trials. We discuss the consequences of long-lived radioisotopes in myocardial PET and the potential role of absolute blood flow quantification to establish efficient clinical protocols.

Nuclear cardiology needs new “blood”

Since introduction of cardiac catheterization to obtain x-ray pictures of coronary arteries, coronary angiography has been the primary tool to diagnose coronary artery disease (CAD). However, anatomical imaging, noninvasive or invasive, does not accurately indicate whether the detected coronary narrowing causes ischemia, which is the cause of symptoms and determined prognosis of the patients. As it is stated in numerous clinical practice guidelines, functional ischemia testing is needed to assess whether the coronary stenoses are hemodynamically significant. The importance of diagnostic tests to provide information that leads to more appropriate choice of therapy and thus, improved patient outcome has been re-emphasized in recent discussions related to the increasing use of noninvasive coronary angiography. Noninvasive scintigraphy using radioactive potassium analogue thallium-201 (Tl) to determine myocardial perfusion at rest and under stress was introduced in the 1970s. Appearance of single photon emission computed tomography (SPECT) in the 1980s provided major improvement in quality of images. New technetium-99m (Tc) labeled radiopharmaceuticals sestamibi and tetrofosmin also improved image quality and allowed efficient imaging protocols. More recently, ECG gating has become routine practice providing information on left ventricular function and assisting in discrimination of true perfusion abnormality from artifact. These methodological innovations together with extensive clinical validation have made myocardial perfusion scintigraphy (MPS) the most widely used and well-established method for detection of myocardial ischemia. The diagnostic accuracy of MPS for the detection of angiographically significant CAD is high (sensitivity 87-89% and specificity 73-75%) and normal MPS in patients with intermediate to high likelihood of CAD predicts a very low rate of cardiac death or nonfatal myocardial infarction (B1%/year). These features make MPS a strong technique to guide selection of patients for cardiac catheterization and treatment procedures, such as dilatation of coronary stenosis. Despite the success of MPS using SPECT there is a need for further improvement of tracers and instrumentation. Compared with Tl, Tc labeled tracer provide better count statistics and image quality due to their higher energy spectrum and shorter half-lives allowing image protocols with lower radiation exposure. However, they are limited by lower myocardial extraction fraction, resulting in underestimation of blood flow at high flow rates. Increasing number of patients are presenting with extensive, multivessel CAD or endothelial dysfunction that poses a diagnostic problem for perfusion techniques based on semi-quantitative assessment of relative differences in tracer distribution in SPECT images. Technical problems of SPECT are related to low spatial resolution and artifacts caused by soft tissue attenuation that affects the quality of images and confidence of reading. While the benefits of attenuation correction in SPECT still remain controversial, the resulting false positive or inconclusive test results lead to the need for further, unnecessary confirmatory tests, typically cardiac catheterization. There is increasing interest in MPS using positron emission tomography (PET). This is largely based on the recent exponential growth in the number of hybrid PET and computed tomography (CT) systems, attributable primarily to their wide spread use in clinical oncology, in combination with reimbursement of cardiac PET. Moreover, the generator produced flow tracer Rubidium (Rb) has made perfusion imaging possible at sites without onsite cyclotron. Compared with SPECT, PET offers several technical advantages. It can measure myocardial radioactivity concentrations with better spatial and contrast resolutions and it has accurate, well validated attenuation correction. It is the unique feature of PET that myocardial blood flow (MBF) and coronary flow reserve (CFR), i.e., the ratio between peak myocardial blood flow at stress and rest, can be quantified in absolute terms. Owing to high temporal resolution and correction of photon attenuation PET provides accurate From Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, München, Germany. Financial assistance for this project was provided by EC-FP6-project DiMI (LSHB-CT-2005-512146), Finnish Foundation for Cardiovascular Research, Bristol-Myers Squib Medical Imaging. Received for publication Dec 31, 2008; final revision accepted Jan 6, 2009. Reprint requests: Markus Schwaiger, MD, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger str. 22, 81675 München, Germany; markus.schwaiger@tum.de, m.schwaiger@lrz.tu-muenchen.de. J Nucl Cardiol 2009;16:180–3. 1071-3581/

Evaluation of the novel PET perfusion tracer 18F BMS747158-02 for measurement of myocardial infarct size in a rat model

34.00 Copyright 2009 by the American Society of Nuclear Cardiology. doi:10.1007/s12350-009-9055-3