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ABSTRACT: Spatially resolved images of hyperpolarized (13) C substrates and their downstream products provide insight into real-time metabolic processes occurring in vivo. Recently, hyperpolarized (13) C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig, but accurate and reproducible measurements remain challenging due to the limited period available for imaging as well as physiological motion. In this article, time-resolved cardiac- and respiratory-gated images of [1-(13) C] pyruvate, [1-(13) C] lactate, and (13) C bicarbonate in the heart are acquired without the need for a breathhold. The robustness of these free-breathing measurements is demonstrated using the time-resolved data to produce a normalized metric of pyruvate dehydrogenase and lactate dehydrogenase activity in the heart. The values obtained are reproducible in a controlled metabolic state. In a 60-min ischemia/reperfusion model, significant differences in hyperpolarized bicarbonate and lactate, normalized using the left ventricular pyruvate signal, were detected between scans performed at baseline and 45 min after reperfusion. The sequence is anticipated to improve quantitative measurements of cardiac metabolism, leading to feasible validation studies using fewer subjects, and potentially improved diagnosis, serial monitoring, and treatment of cardiac disease in patients. © 2013 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 04/2013; 69(4):spcone. · 2.96 Impact Factor
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Marie A Schroeder, Angus Z Lau,
Albert P Chen,
Yiping Gu,
Jeevan Nagendran,
Jennifer Barry,
Xudong Hu,
Jason R B Dyck,
Damian J Tyler,
Kieran Clarke,
Kim A Connelly,
Graham A Wright,
Charles H Cunningham
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ABSTRACT: AIMS: Impaired energy metabolism has been implicated in the pathogenesis of heart failure. Hyperpolarized (13)C magnetic resonance (MR), in which (13)C-labelled metabolites are followed using MR imaging (MRI) or spectroscopy (MRS), has enabled non-invasive assessment of pyruvate metabolism. We investigated the hypothesis that if we serially examined a model of heart failure using non-invasive hyperpolarized [(13)C]pyruvate with MR, the profile of in vivo pyruvate oxidation would change throughout the course of the disease. METHODS AND RESULTS: Dilated cardiomyopathy (DCM) was induced in pigs (n = 5) by rapid pacing. Pigs were examined using MR at weekly time points: cine-MRI assessed cardiac structure and function; hyperpolarized [2-(13)C]pyruvate was administered intravenously, and (13)C MRS monitored [(13)C]glutamate production; (31)P MRS assessed cardiac energetics [phosphocreatine (PCr)/ATP]; and hyperpolarized [1-(13)C]pyruvate was administered for MRI of pyruvate dehydrogenase complex (PDC)-mediated pyruvate oxidation via [(13)C]bicarbonate production. Early in pacing, the cardiac index decreased by 25%, PCr/ATP decreased by 26%, and [(13)C]glutamate production decreased by 51%. After clinical features of DCM appeared, end-diastolic volume increased by 40% and [(13)C]bicarbonate production decreased by 67%. Pyruvate dehydrogenase kinase 4 protein increased by two-fold, and phosphorylated Akt decreased by half. Peroxisome proliferator-activated receptor-α and carnitine palmitoyltransferase-1 gene expression decreased by a half and a third, respectively. CONCLUSION: Despite early changes associated with cardiac energetics and (13)C incorporation into the Krebs cycle, pyruvate oxidation was maintained until DCM developed, when the heart's capacity to oxidize both pyruvate and fats was reduced. Hyperpolarized (13)C MR may be important to characterize metabolic changes that occur during heart failure progression.
European Journal of Heart Failure 12/2012; · 4.90 Impact Factor
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ABSTRACT: MR imaging using hyperpolarized (13) C substrates has become a promising tool to study real-time cardiac-metabolism in vivo. For such fast imaging of nonrecoverable prepolarized magnetization it is important to optimize the RF-coils to obtain the best signal-to-noise ratio possible, given the required coverage. In this work, three different receiver-coil configurations were computed in pig and human models. The sensitivity maps were demonstrated in phantoms and in vivo experiments performed in pigs. Signal-to-noise ratio in the posterior heart was increased up to 80% with the best multichannel coil as expected. These new coil configurations will allow imaging of the different metabolite signals even in the posterior regions of the myocardium, which is not possible with a single-channel surface-coil. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 08/2012; · 2.96 Impact Factor
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ABSTRACT: Spatially resolved images of hyperpolarized (13) C substrates and their downstream products provide insight into real-time metabolic processes occurring in vivo. Recently, hyperpolarized (13) C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig, but accurate and reproducible measurements remain challenging due to the limited period available for imaging as well as physiological motion. In this article, time-resolved cardiac- and respiratory-gated images of [1-(13) C] pyruvate, [1-(13) C] lactate, and (13) C bicarbonate in the heart are acquired without the need for a breathhold. The robustness of these free-breathing measurements is demonstrated using the time-resolved data to produce a normalized metric of pyruvate dehydrogenase and lactate dehydrogenase activity in the heart. The values obtained are reproducible in a controlled metabolic state. In a 60-min ischemia/reperfusion model, significant differences in hyperpolarized bicarbonate and lactate, normalized using the left ventricular pyruvate signal, were detected between scans performed at baseline and 45 min after reperfusion. The sequence is anticipated to improve quantitative measurements of cardiac metabolism, leading to feasible validation studies using fewer subjects, and potentially improved diagnosis, serial monitoring, and treatment of cardiac disease in patients. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 07/2012; · 2.96 Impact Factor
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ABSTRACT: (13)C MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of prepolarized [1-(13)C]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non-invasively. However, to allow investigation of Krebs cycle metabolism, the (13)C label must be placed on the C2 position of pyruvate. Thus, the utilization of either C1 or C2 labeled prepolarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the prepolarized pyruvate molecules were labeled at both C1 and C2 positions, then it would be possible to observe the downstream metabolites that were the results of both PDH flux ((13)CO(2) and H(13)CO(3)(-)) and Krebs cycle flux ([5-(13)C]glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the (13)CO(2) resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve (13)CO(2) detection, the feasibility of using dual-labeled hyperpolarized [1,2-(13)C(2)]pyruvate as a substrate for dynamic cardiac metabolic MRS studies to allow simultaneous investigation of PDH flux, Krebs cycle flux and pH, was demonstrated in vivo.
NMR in Biomedicine 07/2011; 25(2):305-11. · 3.21 Impact Factor
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ABSTRACT: Dynamic nuclear polarization and dissolution offer the exciting possibility of imaging biochemical reactions in vivo, including some of the key enzymatic reactions involved in cellular metabolism. The development of new pulse sequence strategies has been motivated by demanding applications, such as the imaging of hyperpolarized metabolite distributions in the heart. In this article, the key considerations surrounding the application of spectral-spatial imaging pulse sequences for hyperpolarized (13)C metabolic imaging in cardiac and cancer applications are explored. Spiral pulse sequences for multislice imaging of [1-(13)C]pyruvate in the heart were developed, as well as time-resolved, three-dimensional, echo-planar imaging sequences for the imaging of [1-(13)C]pyruvate-lactate exchange in cancer. The advantages and challenges associated with these sequences were determined by testing in pig and rat models.
NMR in Biomedicine 07/2011; 24(8):988-96. · 3.21 Impact Factor
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ABSTRACT: Hyperpolarization of (13) C labeled substrates via dynamic nuclear polarization has been used as a method to noninvasively study real-time metabolic processes occurring in vivo. In these studies, proper calibration of radiofrequency transmit power is required to efficiently observe rapidly decaying magnetization. Conventional transmit radiofrequency field (B₁⁺) mapping methods rely on placing magnetization in a fixed, known state prior to imaging, making them unsuitable for imaging of hyperpolarized magnetization. Recently, a phase-based B(1) mapping method based on the Bloch-Siegert shift has been reported. This method uses a B(1) -dependent shift in the resonance frequency of nuclei in the presence of an off-resonance radiofrequency pulse. In this article, we investigate the feasibility of Bloch-Siegert B(1) mapping and observation of metabolism of hyperpolarized [1-¹³C] pyruvate in vivo, in a single injection. The technique is demonstrated with phantom experiments, and in normal rat and pigs in vivo. This method is anticipated to improve quantitative measurements of hyperpolarized (13) C metabolism in vivo by enabling accurate flip-angle corrections. This work demonstrates the use of Bloch-Siegert B(1) mapping under challenging out-of-equilibrium imaging conditions.
Magnetic Resonance in Medicine 06/2011; 67(1):62-71. · 2.96 Impact Factor
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ABSTRACT: Hyperpolarization of spins via dynamic nuclear polarization (DNP) has been explored as a method to non-invasively study real-time metabolic processes occurring in vivo using (13)C-labeled substrates. Recently, hyperpolarized (13)C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig. Conventional 3D spectroscopic imaging methods require in excess of 100 excitations, making it challenging to acquire a full cardiac-gated, breath-held, whole-heart volume. In this article, the development of a rapid multislice cardiac-gated spiral (13)C imaging pulse sequence consisting of a large flip-angle spectral-spatial excitation RF pulse combined with a single-shot spiral k-space trajectory for rapid imaging of cardiac metabolism is described. This sequence permits whole-heart coverage (6 slices, 8.8-mm in-plane resolution) in any plane, allowing imaging of the metabolites of interest, [1-(13)C] pyruvate, [1-(13)C] lactate, and (13)C bicarbonate, within a single breathhold. Pyruvate and bicarbonate cardiac volumes were acquired, while lactate images were not acquired due to low lactate levels in the animal model studied. The sequence was demonstrated with phantom experiments and in vivo testing in a pig model.
Magnetic Resonance in Medicine 11/2010; 64(5):1323-31. · 2.96 Impact Factor
