Hyperpolarized magnetic resonance: a novel technique for the in vivo assessment of cardiovascular disease.

Cardiovascular disease is associated with high morbidity, mortality, and financial burden to healthcare services.1–3 In the United States, cardiovascular disease is the leading cause of death in both men and women, accounting for 1 in every 2.9 deaths in 2006, with coronary disease accounting for 1 in every 6 deaths.2 Noninvasive cardiac imaging increasingly plays a fundamental role in diagnosing, assessing prognosis, and monitoring therapy response in cardiovascular disease.1,4,5 Two-dimensional echocardiography is the most commonly used imaging modality to measure heart function because of its low cost and widespread accessibility. Computed tomography (CT), single photon emission CT, and positron emission tomography (PET) expose patients to ionizing radiation but have been used successfully for clinical assessment of coronary arteries, myocardial perfusion, and viability, respectively. Cardiovascular magnetic resonance (CMR) applies no ionizing radiation and is now considered the gold standard in assessing cardiac anatomy, function, and mass.1 CMR has also shown great potential for evaluating perfusion and viability with gadolinium-based contrast agents. MR spectroscopy (MRS) and MR-based molecular imaging methods have shown promise for evaluating cardiac metabolism. For example, phosphorus-31 MRS assesses high-energy phosphate content and energy reserve in the human heart (reviewed elsewhere6). Other implementations of multinuclear MRS, including oxygen-17, carbon-13, sodium-23, and proton MRS, have described measurement of oxygen consumption,7 substrate selection, and rates of metabolic flux,8 postinfarct sodium accumulation,9 and lipid accumulation,10 respectively, in ex vivo and in vivo experimental models of disease. MR-based molecular imaging of particles labeled with fluorine-19 nuclei has been used to study tracer and drug pharmacokinetics and metabolism.11 Combined PET–MR imaging (MRI) methods have been demonstrated in preclinical and noncardiac applications to assess cardiac parameters in an infarct mouse model12 and for structural, functional, and molecular imaging of patients with brain tumors.13 However, the use of all MR techniques to assess cardiac metabolism in people and to image myocardial perfusion and viability without gadolinium contrast has been limited by an intrinsically low sensitivity. Hyperpolarization with the dynamic nuclear polarization (DNP) technique can yield 10 000-fold signal increases in MR-active nuclei.14 When used with MRI and/or MRS, hyperpolarized C-labeled metabolic tracers allow unprecedented real-time visualization of the biochemical pathways of normal and abnormal metabolism.15 Alternately, the spatial distribution of hyperpolarized C-labeled agents can be imaged to achieve high contrast for perfusion and angiographic applications. In November 2010, hyperpolarized [1-C]pyruvate was administered to patients for the first time, with a view toward using metabolic MRI to characterize prostate cancer.16 No clinical application in patients with cardiovascular disease has been reported so far; however, given the recent studies in cancer and the experimental application in animal models of cardiovascular disease reported over the past few years, a review of the clinical potential of hyperpolarization techniques in cardiology seems timely. Here, we cover methods for generation of hyperpolarized C MR tracers and their experimental use, possible use of hyperpolarized C-labeled tracers for human cardiovascular disease, and recent and future technological advances needed for translation of cardiac hyperpolarized C MR into the clinic.