Category Archives: clinical imaging

Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience

Dissolution DNP has come a long way.

Cunningham, C.H., et al., Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience. Circ Res, 2016. 119(11): p. 1177-1182.

https://www.ncbi.nlm.nih.gov/pubmed/27635086

RATIONALE: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. OBJECTIVE: To demonstrate the first hyperpolarized (13)C metabolic magnetic resonance imaging of the human heart. METHODS AND RESULTS: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by (13)C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-(13)C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported </=1 month post procedure. The [1-(13)C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed (13)C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-(13)C]lactate signal appeared both within the chambers and in the myocardium. The mean (13)C image signal:noise ratio was 115 for [1-(13)C]pyruvate, 56 for (13)C-bicarbonate, and 53 for [1-(13)C]lactate. CONCLUSIONS: These results represent the first (13)C images of the human heart. The appearance of (13)C-bicarbonate signal after administration of hyperpolarized [1-(13)C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.

Bastiaansen, J.A.M., M.E. Merritt, and A. Comment, Measuring changes in substrate utilization in the myocardium in response to fasting using hyperpolarized [1-13C]butyrate and [1-13C]pyruvate. Scientific Reports, 2016. 6: p. 25573.

http://dx.doi.org/10.1038/srep25573

Cardiac dysfunction is often associated with a shift in substrate preference for ATP production. Hyperpolarized (HP) 13C magnetic resonance spectroscopy (MRS) has the unique ability to detect realtime metabolic changes in vivo due to its high sensitivity and specificity. Here a protocol using HP [1-13C] pyruvate and [1-13C]butyrate is used to measure carbohydrate versus fatty acid metabolism in vivo. Metabolic changes in fed and fasted Sprague Dawley rats (n = 36) were studied at 9.4 T after tail vein injections. Pyruvate and butyrate competed for acetyl-CoA production, as evidenced by significant changes in [13C]bicarbonate (−48%), [1-13C]acetylcarnitine (+113%), and [5-13C]glutamate (−63%), following fasting. Butyrate uptake was unaffected by fasting, as indicated by [1-13C]butyrylcarnitine. Mitochondrial pseudoketogenesis facilitated the labeling of the ketone bodies [1-13C]acetoacetate and [1-13C]β-hydroxybutyryate, without evidence of true ketogenesis. HP [1-13C]acetoacetate was increased in fasting (250%) but decreased during pyruvate co-injection (−82%). Combining HP 13C technology and co-administration of separate imaging agents enables noninvasive and simultaneous monitoring of both fatty acid and carbohydrate oxidation. This protocol illustrates a novel method for assessing metabolic flux through different enzymatic pathways simultaneously and enables mechanistic studies of the changing myocardial energetics often associated with disease.

Continuous-flow DNP polarizer for MRI applications at 1.5 T

Denysenkov, V., et al., Continuous-flow DNP polarizer for MRI applications at 1.5 T. 2017. 7: p. 44010.

http://dx.doi.org/10.1038/srep44010

Here we describe a new hyperpolarization approach for magnetic resonance imaging applications at 1.5 T. Proton signal enhancements of more than 20 were achieved with a newly designed multimode microwave resonator situated inside the bore of the imager and used for Overhauser dynamic nuclear polarization of the water proton signal. Different from other approaches in our setup the hyperpolarization is achieved continuously by liquid water flowing through the polarizer under continuous microwave excitation. With an available flow rate of up to 1.5 ml/min, which should be high enough for DNP MR angiography applications in small animals like mice and rats. The hyperpolarized liquid cooled to physiological temperature can be routed by a mechanical switch to a quartz capillary for injection into the blood vessels of the target object. This new approach allows hyperpolarization of protons without the need of an additional magnet and avoids the losses arising from the transfer of the hyperpolarized solution between magnets. The signal-to-noise improvement of this method is demonstrated on two- and three-dimensional phantoms of blood vessels.

Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy

Day, S.E., M.I. Kettunen, F.A. Gallagher, D.-E. Hu, M. Lerche, J. Wolber, K. Golman, J.H. Ardenkjaer-Larsen, and K.M. Brindle, Nat Med, 13, (2007)

http://dx.doi.org/10.1038/nm1650

Measurements of early tumor responses to therapy have been shown, in some cases, to predict treatment outcome. We show in lymphoma-bearing mice injected intravenously with hyperpolarized [1-13C]pyruvate that the lactate dehydrogenase–catalyzed flux of13C label between the carboxyl groups of pyruvate and lactate in the tumor can be measured using 13C magnetic resonance spectroscopy and spectroscopic imaging, and that this flux is inhibited within 24 h of chemotherapy. The reduction in the measured flux after drug treatment and the induction of tumor cell death can be explained by loss of the coenzyme NAD(H) and decreases in concentrations of lactate and enzyme in the tumors. The technique could provide a new way to assess tumor responses to treatment in the clinic.

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