Full member of GSISH

Contact Details

GE Global Research
Imaging Technologies Lab
Freisinger Landstrasse 50
85748 Garching
Germany

Phone: +49 (0)89.5528.3732
Fax:     +49 (0)89.5528.3185

E-Mail: khegai@ge.com

Project Details

Project:
Hyperpolarized 13C MR Data Acquisition and Interpretation

Interdisciplinary Project Group:
Hyperpolarized 13C MR Data Acquisition and Interpretation

Supervisors:
Prof. Dr. Steffen Glaser
Prof. Dr. Sibylle Ziegler
Dr. Florian Wiesinger

Start of PhD-work at GSISH:
March 2010

Project Description:
Hyperpolarized 13C MR imaging is an emerging method, which allows non-invasive investigation of in-vivo metabolism. This novel imaging technique, based on the combination of 13C (Carbon-13) marked endogenous molecules (biomarkers) and Magnetic Resonance Imaging (MRI), increases the sensitivity of the MRI experiment by >10,000-fold. Endogenous molecules such as pyruvate can be marked, hyperpolarized by Dynamic Nuclear Polarization (DNP) and then injected in vivo in order to measure metabolic flux of different substrates through the cellular metabolism. It has been demonstrated to be sensitive to pathologic changes such as tumors and myocardial infarction. As such it holds great potential to extend MRI from a morphologic imaging modality towards a more metabolic/functional one.

The hyperpolarized 13C signal and hence the metabolic information decays according to the T1 relaxation time. Under typical in-vivo conditions this opens an acquisition time on the order of one minute. Furthermore the relevant information is spread over fiver dimensions including space, time and chemical-shift frequency (, based on which the individual metabolites can be identified). Hence, there is an important need for careful sequence design and encoding optimization. The first goal of the thesis is to apply optimal control theory methods for MR pulse sequence optimization.

The obtained time-resolved metabolite maps needs to be related to underlying biology. Key parameters need to be identified, which allow quantitative statements. Kinetic modeling approaches known from other metabolic imaging modalities allow extraction of turnover rates with clear biological interpretation. The second goal of the thesis is to adapt existing kinetic modeling methods toward hyperpolarized 13C MR metabolic imaging for the unique extraction of quantitative, biological parameters.

 

Publications:

1.      Janich, M. A., M. I. Menzel, F. Wiesinger, E. Weidl, O. Khegai, J. H. Ardenkjaer-Larsen, S. J. Glaser, A. Haase, R. F. Schulte, and M. Schwaiger. “Effects of Pyruvate Dose on in Vivo Metabolism and Quantification of Hyperpolarized 13C Spectra.” NMR in Biomedicine 2012 doi: 10.1002/nbm.1726

2.      Wiesinger F, E Weidl, M I Menzel, M A Janich, O Khegai, S J Glaser, A Haase, M Schwaiger,  R F Schulte. “IDEAL Spiral CSI for Dynamic Metabolic MR Imaging of Hyperpolarized [1?13C]pyruvate.” Magnetic Resonance in Medicine 2012 doi: 10.1002/mrm.23212

3.      Schulte R.F, J. I. Sperl, E. Weidl, M. I. Menzel, M. A. Janich, O. Khegai, M. Durst, J. H. Ardenkjaer-Larsen, S. J. Glaser, A. Haase, M. Schwaiger, F. Wiesinger. „Saturation-Recovery Metabolic Exchange Rate Imaging with Hyperpolarised [1-13C]Pyruvate using Spectral-Spatial Excitation“ Magnetic Resonance in Medicine 2012 doi: 10.1002/mrm.24353

4.      Khegai O., A.M. Otto, M.A. Janich, R.F. Schulte, M.I. Menzel, E. Weidl, S.J. Glaser, S.I. Ziegler, A. Haase, M. Schwaiger, F. Wiesinger. “Quantification method for time-resolved hyperpolarized 13C metabolic imaging.” Proceedings of ESMRMB 2011 (Certificate of Merit)

5.      Gómez Damián P. A., J. I. Sperl, O. Khegai, M. A. Janich, F. Wiesinger, E. Weidl, S. J. Glaser, M. Schwaiger, R. F. Schulte, A. Haase, M. I. Menzel. „ Multi-side kinetic model to assess [1-13C]pyruvate in-vivo metabolism.“ Proceedings of ESMRMB 2011

6.      Durst M. T., R. F. Schulte, F. Schilling, E. Weidl, O. Khegai, M. A. Janich, J. I. Sperl, F. Wiesinger, M. Schwaiger, A. Haase. „Parallel spiral CSI for metabolic imaging with hyperpolarised 13C.“ Proceedings of ESMRMB 2011

7.      Schulte R.F, J. I. Sperl, M. Durst, A. Haase, M. Irkens, M. Manglberger, E. Weidl, M. A. Janich, O. Khegai, G. Kudielka, M. I. Menzel, S. J. Glaser, M. Schwaiger, F. Wiesinger. „Advanced Parallel Imaging Techniques for Metabolic Imaging with Hyperpolarised 13C.“

8.      Otto, A.M., Khegai, O., Wiesinger, F., Menzel, M.I., Schulte, R.F., Ziegler S.I., Glaser, S.J. „ Metabolic flux of tumor cell spheroids measured by nuclear magnetic resonance using hyperpolarized 13C-pyruvate.“ Proceedings of ISPDC 2011

9.      Scholz D. J., O. Khegai, E. Kubala, A. Otto, M. Schwaiger, R. F. Schulte, A. Haase, M. I. Menzel. „Hyperpolarization of 13C-bicarbonate for spatial MRI pH-detection.“ Proceedings of ISPDC 2011

10.   Wiesinger F., O. Khegai, J. I. Sperl, E. Weidl, A. Haase, M. Schwaiger, R. Schulte. „ Frequency-domain quantification and interpretation of dynamic hyperpolarized 13C metabolic imaging.“ Proceedings of ISMRM 2012

11.   Gómez Damián P. A., J. I. Sperl, O. Khegai, S. Grott, E. Weidl, M. Janich, F. Wiesinger, S. J. Glaser, A. Haase, M. Schwaiger, R. F. Schulte , M. I. Menzel. „Multi-side kinetic modeling of 13C metabolic MR using [1-13C]pyruvate.“ Proceedings of ISMRM 2012

12.   Menzel M.I., E. Weidl,  M. Janich, O. Khegai, F. Wiesinger, A. Haase, R. F. Schulte, M. Schwaiger. „ In vivo biochemical imaging of HCC tumor bearing rats using hyperpolarized 13C-pyruvate and 18F-FDG.“ Proceedings of ISMRM 2012

13.   Schulte R.F, J. I. Sperl, E. Weidl, M. I. Menzel, M. A. Janich, O. Khegai, M. Durst, J. H. Ardenkjaer-Larsen, S. J. Glaser, A. Haase, M. Schwaiger, F. Wiesinger. „Saturation-Recovery Metabolic Exchange Rate Imaging with Hyperpolarised [1-13C]Pyruvate using Spectral-Spatial Excitation.“ Proceedings of ISMRM 2012

14.   Durst M., R.F. Schulte, F. Schilling, E. Weidl, O. Khegai, M.A. Janich, J.I. Sperl, F. Wiesinger, M. Schwaiger, A. Haase. „Parallel Spiral CSI for Metabolic Imaging with Hyperpolarised 13C.“ Proceedings of ISMRM 2012

15.   Weidl, E., Menzel, M., Janich, M., Khegai, O., Wiesinger, F., Nekolla, S. G., Haase, A., Schulte, R., Schwaiger, M. „ In vivo detection of tumor metabolism with 18F-FDG PET and hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging.“ Proceedings of SNM 2012

16.   Schulte R.F, J. I. Sperl, E. Weidl, M. I. Menzel, M. A. Janich, O. Khegai, M. Durst, J. H. Ardenkjaer-Larsen, S. J. Glaser, A. Haase, M. Schwaiger, F. Wiesinger. „Quantitative metabolic imaging methods for hyperpolarised 13C.“ Proceedings of EUROMAR 2012

17.   Wiesinger F., O. Khegai, E. Weidl, A. Haase, M. Schwaiger, R. Schulte. „ Metabolic rate constant mapping using hyperpolarized 13C spectroscopic MR imaging.“ Proceedings of WMIC 2012

18.   Khegai O., A. M. Otto, R. F. Schulte, P. T. Sipilae, M. I. Menzel, S. J. Glaser, S. I. Ziegler, A. Haase, M. Schwaiger, F. Wiesinger. „In vitro measurement of pyruvate metabolism using hyperpolarized 13C MRS.“ Proceedings of ICMRBS 2012

19.   Scholz D.J., O. Khegai, A. Otto, R.F. Schulte, M. Schwaiger, S. Ziegler, A. Haase, M.I. Menzel "Quantitative pH analysis with sodium 13C-Bicarbonate at small pH variations" Proceedings of ESMRMB 2012

20.   Khegai O., R. F. Schulte, M. A. Janich, M. I. Menzel, E. Weidl, A. M. Otto, S. J. Glaser, S. I. Ziegler, A. Haase, M. Schwaiger and F. Wiesinger. „In vivo Mapping of Metabolic Rate Constants with Hyperpolarized [1-13C]pyruvate” The Third International Workshop on Metabolic Imaging 2012, Philadelphia

21.   Otto, A.M., Khegai, O., Wiesinger, F., Menzel, M.I., Schulte „ Effects of extracellular pH on the activity of pyruvate kinase and lactate dehydrogenase in MCF-7 cells.“ Proceedings of ISPDC 2012

 

submitted:

22.   Khegai O., R. F. Schulte, M. A. Janich, M. I. Menzel, E. Weidl, A. M. Otto, S. J. Glaser, S. I. Ziegler, A. Haase, M. Schwaiger and F. Wiesinger. „In vivo Mapping of Metabolic Rate Constants with Hyperpolarized [1-13C]pyruvate” (submitted to Magnetic Resonance in Medicine)

23.   Gómez Damián P. A., J. I. Sperl, O. Khegai, S. Grott, E. Weidl, M. Janich, F. Wiesinger, S. J. Glaser, A. Haase, M. Schwaiger, R. F. Schulte , M. I. Menzel. „Multi-side kinetic modeling of 13C metabolic MR using [1-13C]pyruvate“ (submitted to NMR in Biomedicine)

24.   Menzel M.I., E V. Farrell, M A. Janich, O Khegai, F Wiesinger, S Nekolla, S van Marwick, A Otto, A Haase, R F. Schulte, M Schwaiger. „ Multimodal assessment of in vivo biochemistry: Hyperpolarized [1-13C]MRS and 18F-FDG-PET imaging in HCC tumor bearing rats “ (submitted to Journal of Nuclear Medicine)

 

Personal Details:

03/2010 - present:
PhD Student at the Graduate School of Information Science in Health (GSISH) / General Electric Global Research - Europe

10/2005 - 10/2009:
Graduate in physics at Technical University of Munich
(Diploma thesis: Optimization of  spectral-spatial imaging sequences for hyperpolarized 13C MR imaging)

05/2006 - 08/2008:
Working student at Institute of Radiation Protection, Helmholtz Zentrum München