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Robin de Graaf, PhD

Professor of Radiology and Biomedical Imaging

Research Summary

The main focus of Dr. Robin de Graaf's research is the study of cerebral energy metabolism and its relationship to functional activation in human and animal brains. NMR spectroscopy (proton, (inverse) carbon-13, oxygen-17 and phosphorus-31) is the most important tool in the study of metabolic processes and fluxes, non-invasively in vivo. Besides studying brain energy metabolism, a significant part of the research is reserved for technological and methodological improvements to the technique of NMR spectroscopy. These include methods for better water suppression, spatial localization, spectral editing, quantification, and shimming. Dr. de Graaf's current research focus covers areas that are all related to tackling the challenges and grasping the opportunities of MR at very high magnetic fields. Developing methods to achieve magnetic field uniformity throughout the human and animal brain are central to the technological innovation of his research. The problem of magnetic field inhomogeneity is tackled through dynamic shimming and through the use of novel electrical coil element arrays. 13C NMR methods have been pioneered at the Yale MRRC and part of his research is to extend those methods to achieve 3D coverage, higher sensitivity (through 1H detection), and higher specificity (e.g., GABA turnover detection).

Specialized Terms: Cerebral energy metabolismenergy

Extensive Research Description

The main focus of Dr. Robin de Graaf's research is the study of cerebral energy metabolism and its relationship to functional activation in human and animal brains. NMR spectroscopy (proton, (inverse) carbon-13, oxygen-17 and phosphorus-31) is the most important tool in the study of metabolic processes and fluxes, non-invasively in vivo. Besides studying brain energy metabolism, a significant part of the research is reserved for technological and methodological improvements to the technique of NMR spectroscopy. These include methods for better water suppression, spatial localization, spectral editing, quantification, and shimming. Dr. de Graaf's current research focus covers areas that are all related to tackling the challenges and grasping the opportunities of MR at very high magnetic fields. Developing methods to achieve magnetic field uniformity throughout the human and animal brain are central to the technological innovation of his research. The problem of magnetic field inhomogeneity is tackled through dynamic shimming and through the use of novel electrical coil element arrays. 13C NMR methods have been pioneered at the Yale MRRC and part of his research is to extend those methods to achieve 3D coverage, higher sensitivity (through 1H detection), and higher specificity (e.g., GABA turnover detection).

Software Download:

1. Multi-coil shimming of the human brain at 7 T.

2. 3D metabolic flux mapping on rat brain in situ.

3. Development of 1H[13C] NMR methods at 7 T.

4. Compensation of gradient-related magnetic field perturbations.

5. 1H NMR-based metabolomics.

Coauthors

Research Interests

Biomedical Engineering; Energy Metabolism; Magnetic Resonance Spectroscopy; Radiology

Research Image

Selected Publications

  • NIMG-105. DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMASKim L, De Feyter H, de Graaf R, Fulbright R, Liu Y, Rothman D, Baehring J, Blondin N, Kim P, Omuro A, Chiang V, Moliterno J, Omay S, Piepmeier J, Corbin Z. NIMG-105. DEUTERIUM METABOLIC IMAGING (DMI) DETECTS A LARGER WARBURG EFFECT IN HIGH-GRADE BRAIN TUMORS AND IN IDH WILD TYPE GLIOMAS Neuro-Oncology 2022, 24: vii189-vii189. PMCID: PMC9660955, DOI: 10.1093/neuonc/noac209.723.
  • Flow-Based Visual Quality Enhancer for Super-Resolution Magnetic Resonance Spectroscopic ImagingDong S, Hangel G, Chen E, Sun S, Bogner W, Widhalm G, You C, Onofrey J, de Graaf R, Duncan J. Flow-Based Visual Quality Enhancer for Super-Resolution Magnetic Resonance Spectroscopic Imaging 2022, 13609: 3-13. DOI: 10.1007/978-3-031-18576-2_1.
  • Multi-scale Super-Resolution Magnetic Resonance Spectroscopic Imaging with Adjustable SharpnessDong S, Hangel G, Bogner W, Widhalm G, Rössler K, Trattnig S, You C, de Graaf R, Onofrey J, Duncan J. Multi-scale Super-Resolution Magnetic Resonance Spectroscopic Imaging with Adjustable Sharpness 2022, 13436: 410-420. DOI: 10.1007/978-3-031-16446-0_39.
  • BIMG-21. DEUTERIUM METABOLIC IMAGING (DMI), A NEW, MRI-BASED TECHNIQUE FOR MAPPING BRAIN TUMOR METABOLISM IN VIVOCorbin Z, Fulbright R, Rothman D, de Graaf R, De Feyter H. BIMG-21. DEUTERIUM METABOLIC IMAGING (DMI), A NEW, MRI-BASED TECHNIQUE FOR MAPPING BRAIN TUMOR METABOLISM IN VIVO Neuro-Oncology Advances 2021, 3: i5-i5. PMCID: PMC7994324, DOI: 10.1093/noajnl/vdab024.020.
  • Methods | 13C MRS Measurements of in Vivo Rates of the Glutamate/Glutamine and GABA/Glutamine Neurotransmitter CyclesRothman D, De Feyter H, Mason G, de Graaf R, Hyder F, Behar K. Methods | 13C MRS Measurements of in Vivo Rates of the Glutamate/Glutamine and GABA/Glutamine Neurotransmitter Cycles 2021, 688-700. DOI: 10.1016/b978-0-12-819460-7.00341-8.
  • NIMG-15. DEUTERIUM METABOLIC IMAGING (DMI) MEASURES THE WARBURG EFFECT IN BRAIN TUMORSCorbin Z, Prado I, Fulbright R, Rothman D, de Graaf R, De Feyter H. NIMG-15. DEUTERIUM METABOLIC IMAGING (DMI) MEASURES THE WARBURG EFFECT IN BRAIN TUMORS Neuro-Oncology 2019, 21: vi164-vi164. PMCID: PMC6847058, DOI: 10.1093/neuonc/noz175.687.
  • In Vivo NMR Spectroscopyde Graaf R. In Vivo NMR Spectroscopy 2018 DOI: 10.1002/9781119382461.
  • Production of 2-Hydroxyglutarate by IDH Mutant Malignancies Induces a BRCAness State That Can be Exploited By PARP Inhibitors and RadiationCorso C, Bindra R, Glazer P, Sulkowski P, Robinson N, Scanlon S, Purshouse K, Bai H, Liu Y, Sundaram R, Hegan D, Fons N, Breuer G, Song Y, Mishra-Gorur K, De Feyter H, de Graaf R, Surovtseva Y, Kachman M, Halene S, Gunel M. Production of 2-Hydroxyglutarate by IDH Mutant Malignancies Induces a BRCAness State That Can be Exploited By PARP Inhibitors and Radiation International Journal Of Radiation Oncology • Biology • Physics 2017, 99: e68. DOI: 10.1016/j.ijrobp.2017.06.754.
  • CHAPTER 4 B 0 Shimming Technologyde Graaf R, Juchem C. CHAPTER 4 B 0 Shimming Technology 2016, 166-207. DOI: 10.1039/9781782623878-00166.
  • ATPS-14KETOGENIC DIET-INDUCED INCREASE IN MCT1 FACILITATES KETONE BODY OXIDATION IN RAT GLIOMASDe Feyter H, Behar K, Ip K, Hyder F, Drewes L, de Graaf R, Rothman D. ATPS-14KETOGENIC DIET-INDUCED INCREASE IN MCT1 FACILITATES KETONE BODY OXIDATION IN RAT GLIOMAS Neuro-Oncology 2015, 17: v21-v21. PMCID: PMC4638437, DOI: 10.1093/neuonc/nov204.14.
  • Superconductor Analog-to-Digital Converter for High-Resolution Magnetic Resonance ImagingRadparvar M, Talalaevskii A, Webber R, Kadin A, Track E, de Graaf R, Nixon T, Rothman D. Superconductor Analog-to-Digital Converter for High-Resolution Magnetic Resonance Imaging IEEE Transactions On Applied Superconductivity 2015, 25: 1-5. DOI: 10.1109/tasc.2014.2361132.
  • Chapter 1.4 Spectral Editing and 2D NMRde Graaf R. Chapter 1.4 Spectral Editing and 2D NMR 2014, 40-48. DOI: 10.1016/b978-0-12-401688-0.00004-5.
  • Principles of 1H NMR Spectroscopy In Vivode Graaf R. Principles of 1H NMR Spectroscopy In Vivo 2011, 4: 133-147. DOI: 10.1007/978-1-4614-1788-0_5.
  • P151 In vivo 1H-[13C] MRS: A comprehensive tool to investigate the metabolic basis of brain function and diseasevan Eijsden P, Behar K, Mason G, Braun K, de Graaf R. P151 In vivo 1H-[13C] MRS: A comprehensive tool to investigate the metabolic basis of brain function and disease European Journal Of Paediatric Neurology 2009, 13: s67. DOI: 10.1016/s1090-3798(09)70209-0.
  • In Vivo NMR Spectroscopy – Techniques; Direct Detection; MRS; Kinetics and Labels; Fluxes; Concentrationsde Graaf R. In Vivo NMR Spectroscopy – Techniques; Direct Detection; MRS; Kinetics and Labels; Fluxes; Concentrations 2005, 7-29. DOI: 10.1002/0470011505.ch2.
  • Energetic costs associated with glutamatergic and gabaergic neurotransmissionde Graaf R, Patel A, Mason G, Rothman D, Shulman R, Behar K. Energetic costs associated with glutamatergic and gabaergic neurotransmission Cerebrovascular And Brain Metabolism Reviews 2005, 25: s706-s706. DOI: 10.1038/sj.jcbfm.9591524.0707.
  • Cerebral pyruvate carboxylase flux is unaltered during bicuculline‐seizuresPatel A, Chowdhury G, de Graaf R, Rothman D, Shulman R, Behar K. Cerebral pyruvate carboxylase flux is unaltered during bicuculline‐seizures Journal Of Neuroscience Research 2005, 80: 738-738. DOI: 10.1002/jnr.20554.
  • Techniques–MRS, fMRI, 13C NMR, Indirect Detection of 13Cde Graaf R. Techniques–MRS, fMRI, 13C NMR, Indirect Detection of 13C 2004, 31-52. DOI: 10.1002/0470020520.ch3.
  • Corrigendum to “A comparison of 13C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-13C]glucose” [Brain Research Protocols, 10 (2003) 181–190]☆Mason G, Petersen K, de Graaf R, Kanamatsu T, Otsuki T, Rothman D. Corrigendum to “A comparison of 13C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-13C]glucose” [Brain Research Protocols, 10 (2003) 181–190]☆ Brain Research 2003, 11: 143. DOI: 10.1016/s1385-299x(03)00021-7.
  • In vivo detection and quantification of scalar coupled 1H NMR resonancesde Graaf R, Rothman D. In vivo detection and quantification of scalar coupled 1H NMR resonances Concepts In Magnetic Resonance 2000, 13: 32-76. DOI: 10.1002/1099-0534(2001)13:1<32::aid-cmr4>3.0.co;2-j.
  • BRAIN ENERGY METABOLISM, ELECTROCORTICAL BRAIN ACTIVITY (ECBA), CEREBRAL BLOOD VOLUME (tHB) AND REGIONAL SATURATION (rSO2) OF NEWBORN PIGLETS FOLLOWING HYPOXIA-ISCHEMIA (HI)Ioroi T, Peeters C, Braun K, De Graaf R, V.D. Tweel E, Ioroi T, Nicolay K, Van Bel F, Groenendaal F. BRAIN ENERGY METABOLISM, ELECTROCORTICAL BRAIN ACTIVITY (ECBA), CEREBRAL BLOOD VOLUME (tHB) AND REGIONAL SATURATION (rSO2) OF NEWBORN PIGLETS FOLLOWING HYPOXIA-ISCHEMIA (HI) Pediatric Research 1999, 45: 904-904. DOI: 10.1203/00006450-199906000-00124.
  • ALLOPURINOL (ALLO), DEFEROXAMINE (DFO), AND BRAIN ENERGY METABOLISM OF NEWBORN PIGLETS FOLLOWING HYPOXIA-ISCHEMIAIoroi T, Peeters C, Braun K, de Graaf R, van den Tweel E, Ioroi T, Nicolay K, van Bel F, Groenendaal F. ALLOPURINOL (ALLO), DEFEROXAMINE (DFO), AND BRAIN ENERGY METABOLISM OF NEWBORN PIGLETS FOLLOWING HYPOXIA-ISCHEMIA Pediatric Research 1999, 45: 907-907. DOI: 10.1203/00006450-199906000-00142.
  • Cerebral Metabolism Measured Using Proton and Phosphorous Magnetic Resonance Spectroscopy (MRS) Following Hypoxia Ischemia (HI) and Administration of Allopurinol (ALLO) and Deferoxamine (DFO)Peeters C, Van Den Tweel E, De Graaf R, Braun K, Nicolay K, Van Bel F, Groenendaal F. Cerebral Metabolism Measured Using Proton and Phosphorous Magnetic Resonance Spectroscopy (MRS) Following Hypoxia Ischemia (HI) and Administration of Allopurinol (ALLO) and Deferoxamine (DFO) Pediatric Research 1999, 45: 345-345. DOI: 10.1203/00006450-199904020-02053.
  • CEREBRAL METABOLISM OF NEWBORN PIGLETS FOLLOWING HYPOXIA- ISCHEMIA AND NITRIC OXIDE SYNTHASE INHIBITION, EXAMINED USING PROTON AND PHOSPHOROUS MAGNETIC RESONANCE SPECTROSCOPY. • 1729Groenendaal F, De Graaf R, Nicolay K. CEREBRAL METABOLISM OF NEWBORN PIGLETS FOLLOWING HYPOXIA- ISCHEMIA AND NITRIC OXIDE SYNTHASE INHIBITION, EXAMINED USING PROTON AND PHOSPHOROUS MAGNETIC RESONANCE SPECTROSCOPY. • 1729 Pediatric Research 1997, 41: 291-291. DOI: 10.1203/00006450-199704001-01748.
  • Adiabatic rf pulses: Applications to in vivo NMRDe Graaf R, Nicolay K. Adiabatic rf pulses: Applications to in vivo NMR Concepts In Magnetic Resonance 1997, 9: 247-268. DOI: 10.1002/(sici)1099-0534(1997)9:4<247::aid-cmr4>3.0.co;2-z.
  • Multislice Imaging with Adiabatic Pulses Using Transverse Hadamard Encodingde Graaf R, Nicolay K. Multislice Imaging with Adiabatic Pulses Using Transverse Hadamard Encoding Journal Of Magnetic Resonance 1996, 113: 97-101. DOI: 10.1006/jmrb.1996.0162.
  • R. A. de Graaf, In vivo NMR spectroscopy. Principles and techniques, Second edition, John Wiley, Chichester (2008)R. A. de Graaf, In vivo NMR spectroscopy. Principles and techniques, Second edition, John Wiley, Chichester (2008)

Clinical Trials

ConditionsStudy Title
Diabetes Mellitus - Type 1; Diseases of the Endocrine System; Diseases of the Nervous SystemImpact of Hypoglycemia on Brain Ketone and Neurotransmitter Metabolism in Type 1 DM