Full member of GSISH

Contact Details

IMETUM - Zentralinstitut für Medizintechnik
TU München
Boltzmannstraße 11
85748 München
Germany

Phone: +49 (0)89.289.10841
Fax:     +49 (0)89.289.10805

E-Mail: johannes.scholz@tum.de
GE Global Research Europe
Research Center
Freisinger Landstr. 50
85748 Garching
Germany

Phone: +49(0).89.5528.3679
E-mail: scholzj@ge.com

Project Details

Project:
Quantitative pH-detection in vivo via ¹³C magnetic resonance
Supervisors:
Prof. Dr. rer. nat. Univ. Axel Haase
Prof. Dr. Sybille Ziegler
Dr. Marion I. Menzel

Start of PhD-work at GSISH:
May 2011

Project Description:
In vivo determination of the spatial distribution of pH is a challenging task. So far no established clinical tool is available for the spatial detection of pH and its associated information about the biochemical und medical causes. Metabolic magnetic resonance imaging using hyperpolarized bicarbonate (H13CO3-) may help to close this clinically important gap. For the detection of the 13Carbon nuclei via magnetic resonance, the sample is prepared with the Dynamic Nuclear Polarization (DNP) which increases the MR-signal by >10000 fold at 3T. This gives the opportunity to detect 13-carbon nuclei, which only has a natural abundance of 1.1%.
As an important intra and extracellular buffer, bicarbonate helps to regulate the pH-value in mammalian tissue tightly. Under acidic conditions it acts as a proton acceptor and forms carbonic acid (H2CO3), which dissociates to water (H2O) and carbon dioxide (CO2). This reversible reaction is catalyzed by the enzyme carbonic anhydrase up to 106 reactions per second. Thus equilibrium of injected bicarbonate to metabolized dioxide is set nearly instantaneously. The ratio of the two levels of bicarbonate and dioxide can be used to determine the spatial distribution of the environmental pH-value of the investigated sample with the help of the Henderson-Hasselbalch equation.
pH includes information on type and severity of multiple diseases. As an example tumor tissue is, due to lactate secretion and partially poorer perfusion, more acidic, which is known as Warburg effect. Therefore it can be distinguished from the surrounding healthy tissue.
The PhD-Thesis divides basically into two parts: First, there is the biochemical part, namely the preparation of the hyperpolarized bicarbonate, where several parameters need to be matched for a successful hyperpolarization and subsequent dissolution. Also the underlying biological background of the targets, like tumor biology, needs to be integrated in the work. The second part deals with the physics, ranging from the theory and application of DNP and MRI to programming of custom made pulse sequences for data acquisition and analysis. For the successful development of the method, a close collaboration between the natural sciences (physicists, chemists, biologists) on the one hand and the medical disciplines (medical doctors, veterinarians) on the other hand, is essential.
The final goal of the thesis is the time resolved, spatial detection of pH in vivo to improve diagnosis and treatment for a wide variety of diseases.

Publications:

D. J. Scholz, O. Khegai, A. M. Otto, R. F. Schulte, M. Schwaiger, S. Ziegler, A. Haase, M. I. Menzel, 1st international Kick-Off meeting „German Medical Imaging in Motion“ (GMIM), 2012, Johns Hopkins University, Baltimore, (poster and oral)

D. J. Scholz, M. A. Janich, A. M. Otto, F. Schilling, A. Haase, M.I. Menzel, 4th ISPDC Meeting, Garching, 2013,  "Quantified pH detection with hyperpolarized 13C-Bicarbonate“, (oral)

D. J. Scholz, M. A. Janich, A. M. Otto, F. Schilling, A. Haase, M.I. Menzel, Frontiers in Pharmacology, "Quantified pH detection with hyperpolarized 13C-Bicarbonate“, (abstract article)

D. J. Scholz, M. A. Janich, A. Frank, U. Köllisch, J. H. Ardenkjaer-Larsen, R. F. Schulte, M. Schwaiger, A. Haase, M.I. Menzel, Annual Meeting International Society of Magnetic Resonance in Medicine (ISMRM), 2014, Milan, “Quantified pH imaging with hyperpolarized 13C-Bicarbonate” (oral)

D. J. Scholz, M. A. Janich, U. Köllisch, R. F. Schulte, J. H. Ardenkjaer-Larsen, A. Frank, A. Haase, M. Schwaiger, M. I. Menzel, Magnetic Resonance in Medicine, 2014, “Quantitative pH mapping with hyperpolarized 13C-Bicarbonate”, (full paper)

D.J. Scholz, O. Khegai, A. Otto, R.F. Schulte, M. Schwaiger, S. Ziegler, A. Haase, M. I. Menzel,, Proceedings ESMRMB Conference 2012 Lisbon, 2012, abstract 774 - "Quantitative pH analysis with sodium 13C-Bicarbonate at small pH variations" (paper poster)

D.J. Scholz, O. Khegai, E. Kubala, A. Otto, R. F. Schulte, S. Ziegler, A. Haase, M. I. Menzel , 2nd ISPDC Meeting Nice, 2011 - “Hyperpolarization of 13C-bicarbonate for spatial MRI pH-detection” (oral)