First hyperpolarized [2-13C]pyruvate MR studies of human brain metabolism.

We developed methods for the preparation of hyperpolarized (HP) sterile [2-13C]pyruvate to test its feasibility in first-ever human NMR studies following FDA-IND & IRB approval. Spectral results using this MR stable-isotope imaging approach demonstrated the feasibility of investigating human cerebral energy metabolism by measuring the dynamic conversion of HP [2-13C]pyruvate to [2-13C]lactate and [5-13C]glutamate in the brain of four healthy volunteers. Metabolite kinetics, signal-to-noise (SNR) and area-under-curve (AUC) ratios, and calculated [2-13C]pyruvate to [2-13C]lactate conversion rates (kPL) were measured and showed similar but not identical inter-subject values. The kPL measurements were equivalent with prior human HP [1-13C]pyruvate measurements.

[1]  H. Feng,et al.  The emerging role and targetability of the TCA cycle in cancer metabolism , 2017, Protein & Cell.

[2]  Jan Henrik Ardenkjaer-Larsen,et al.  Metabolic imaging by hyperpolarized 13C magnetic resonance imaging for in vivo tumor diagnosis. , 2006, Cancer research.

[3]  Albert P. Chen,et al.  Hyperpolarized 13C lactate, pyruvate, and alanine: noninvasive biomarkers for prostate cancer detection and grading. , 2008, Cancer research.

[4]  Shuyu Tang,et al.  Investigation of analysis methods for hyperpolarized 13C‐pyruvate metabolic MRI in prostate cancer patients , 2018, NMR in biomedicine.

[5]  Peder Larson,et al.  A comparison of coil combination strategies in 3D multi‐channel MRSI reconstruction for patients with brain tumors , 2018, NMR in biomedicine.

[6]  G. Radda,et al.  Real‐time assessment of Krebs cycle metabolism using hyperpolarized C magnetic resonance spectroscopy , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[7]  Azma Mareyam,et al.  Comparison between 8‐ and 32‐channel phased‐array receive coils for in vivo hyperpolarized 13C imaging of the human brain , 2019, Magnetic resonance in medicine.

[8]  J. Ardenkjær-Larsen,et al.  Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Hellmut Merkle,et al.  Dynamic Imaging of Glucose and Lactate Metabolism by 13C-MRS without Hyperpolarization , 2019, Scientific Reports.

[10]  F. Gallagher,et al.  Tumor imaging using hyperpolarized 13C magnetic resonance spectroscopy , 2011, Magnetic resonance in medicine.

[11]  Albert P. Chen,et al.  Hyperpolarized 13 C Metabolic MRI of the Human HeartNovelty and Significance : Initial Experience , 2016 .

[12]  Ilwoo Park,et al.  Development of methods and feasibility of using hyperpolarized carbon‐13 imaging data for evaluating brain metabolism in patient studies , 2018, Magnetic resonance in medicine.

[13]  D. Burz,et al.  Using Singular Value Decomposition to Characterize Protein–Protein Interactions by In‐cell NMR Spectroscopy , 2014, Chembiochem : a European journal of chemical biology.

[14]  G. Radda,et al.  The Cycling of Acetyl-Coenzyme A Through Acetylcarnitine Buffers Cardiac Substrate Supply: A Hyperpolarized 13C Magnetic Resonance Study , 2012, Circulation. Cardiovascular imaging.

[15]  J. Ardenkjær-Larsen.  On the present and future of dissolution-DNP. , 2016 .

[16]  Olaf Sporns,et al.  MR connectomics: Principles and challenges , 2010, Journal of Neuroscience Methods.

[17]  Rahul Aggarwal,et al.  Hyperpolarized 1-[13C]-Pyruvate Magnetic Resonance Imaging Detects an Early Metabolic Response to Androgen Ablation Therapy in Prostate Cancer. , 2017, European urology.

[18]  M. Marjańska,et al.  Brain metabolism under different anesthetic conditions using hyperpolarized [1‐13C]pyruvate and [2‐13C]pyruvate , 2018, NMR in Biomedicine.

[19]  Thomas Schultz,et al.  Visualization and Processing of Higher Order Descriptors for Multi-Valued Data , 2015 .

[20]  Y. Yen,et al.  Measuring mitochondrial metabolism in rat brain in vivo using MR Spectroscopy of hyperpolarized [2‐13C]pyruvate , 2013, NMR in biomedicine.

[21]  John Kurhanewicz,et al.  Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D Dynamic Imaging of Metabolism and Perfusion. , 2017, Cancer research.

[22]  P. Larson,et al.  Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate , 2013, Science Translational Medicine.

[23]  S. Weiss,et al.  IDH1 Mutation Induces Reprogramming of Pyruvate Metabolism. , 2015, Cancer research.