In vivo NMR spectroscopy and CEST imaging

Research group headed by Prof. Dr. Peter Bachert

Contact

Prof. Dr. rer. nat. Peter Bachert
Medical Physics in Radiology
NMR spectroscopy and CEST imaging

Phone: +49 (0)6221 42 2527
Fax: +49 (0)6221 42 2531
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The research group explores detection techniques at clinical imaging systems with the aim to characterize tumor tissue non–invasively by means of biochemical markers and physiological parameters. The group focuses on experimental techniques of high–resolution NMR spectroscopy (MRS), MR spectroscopic imaging (SI), and chemical exchange saturation transfer imaging (CEST–MRI).

Open positions

We are looking for students (physics, chemistry, biology) interested in performing the work for their master (M.Sc.) or doctoral thesis (Dr. rer. nat.) in the field of medical physics and biophysics.

An actual project we can offer explores the potential of phosphorus (31P) and carbon (13C) NMR spectroscopy (MRS, spectroscopic imaging) at 7 Tesla for studies of tumor biochemistry. If you are interested in these topics, please contact us.

Technical equipment

Studies and experiments are performed on clinical whole–body MR tomographs with (magnetic field inductions B0 = 1.5 T, 3 T, and 7 T) and on a MR–PET whole–body scanner (B0 = 3 T).

1 MRS

NMR (nuclear magnetic resonance) has been applied to many fields of science and technology, with particular success in chemistry, biochemistry, and diagnostic imaging. NMR spectroscopy (MRS) enables non–invasive observation of metabolic processes in living tissue (in vivo), while using extremely low–energy electromagnetic radiation (radiofrequency range).
An exemplary MRS application is the clinical monitoring of tumor patients during radiotherapy and chemotherapy. In cooperation with other medical research groups (within the research program "Imaging and Radiooncology" of DKFZ [Deutsches Krebsforschungszentrum, German Cancer Research Center] and with external groups, in particular at the Medical Faculty of the University of Heidelberg), patients are examined by means of MRS/SI on whole–body MR tomographs during routine diagnostic and clinical studies. In order to perform these measurements, the research group develops methods for detection of small metabolites, fast spectroscopic imaging for functional studies, and detection of rare nuclei in living tissue such as 31P or 13C (Figure 1).

© dkfz.de

Figure 1: Upper row: Localized in vivo 31P NMR spectrum from human calf muscle obtained with echo–planar spectroscopic imaging (EPSI) at B0 = 7 T from the voxel indicated by the red box (nominal voxel size: 37.5 x 37.5 x 30.0 mm³). (PCr, phosphocreatine; ATP, adenosine 5’–triphosphate; Pi; inorganic phosphate) [Korzowski et al., Proc. ISMRM: 1434 (2014)]. Lower row: In vivo 13C NMR spectrum from human calf muscle obtained with continuous–wave 1H–decoupling at B0 = 7 T (localization: sensitive volume of 8–cm–diameter surface coil). The high–resolution spectrum shows the different methylene resonances of triacylglycerides [Platt et al., Proc. ISMRM: 1436 (2014)].

Research Topics

•    High–resolution in vivo NMR spectroscopy (nuclei: 1H, 13C, 31P)
•    MR spectroscopic imaging (SI)
•    Hyperpolarization: Hyp–129Xe imaging
•    Studies of combined MR–PET techniques

2 CEST imaging

Chemical exchange saturation transfer (CEST) of protons (1H) in small metabolites and macromolecules that undergo exchange processes with the water protons enables a new contrast mechanism for magnetic resonance imaging (MRI). The CEST image contrast depends both on physical and physiological parameters. The latter characterize the microenvironment in tissue and cells such as temperature, pH, and metabolite concentration. Unfortunately, CEST imaging in vivo is a complex phenomenon because of multiple interferences of entangled effects, such as direct water saturation (spillover effect), the involvement of several exchanging pools, the presence of macromolecular systems (magnetization transfer, MT), and nuclear Overhauser effects (NOE). Moreover, there is a strong dependence of these effects on the employed technical parameters, in particular those of the radiofrequency irradiation scheme for selective saturation, which makes the unequivocal interpretation of the measured signals very difficult. Find more about CEST on www.cest-sources.org.
The aims of the project group are (i) to get insight into and understand and describe theoretically CEST phenomena and the equivalent off–resonant spinlock (SL) experiments by considering analytical solutions of the Bloch–McConnell equation system. By understanding the influence of saturation parameters on the acquired Z–spectrum (= the result of a CEST experiment) and how the different effects interfere we obtain an isolated and pure CEST imaging contrast. (ii) This pure CEST methodology is applied to studies of living tissue to obtain information on the cellular and molecular level of proteins, energy state of the cells, and tissue pH, as well as information about the microenvironment. These new contrast mechanisms are explored as new markers to characterize pathologies, e.g. brain tumors in human patients (Figure 2).

Figure 2: Contrast–enhanced (a) and CEST–MRI (b, c) of a patient with brain tumor. Both the endogeneous amide–CEST contrast (chemical exchange saturation transfer of amide protons) (b) and the NOE–CEST contrast (nuclear Overhauser effect of neighboring dipolar–coupled protons) (c) label the tumor region delineated in the conventional Gadolinium–enhanced MR image (a). [Zaiss et al., Proc. ISMRM #0766 (2014): Inverse Z–spectrum analysis for clean–NOE– and amide–CEST–MRI – application to human glioma.]

Research Topics

•    Development and optimization of pulse sequences at B0 = 3 T and 7 T
•    Application to clinical studies with tumor patients
•    Theory of CEST phenomena, relaxation compensation, quantitative CEST
•    amide–proton transfer (APT), nuclear Overhauser effect (NOE) imaging
•    Creatine–CEST, other small–metabolite–CEST
•    Absolute–pH mapping
•    Protein–CEST, MRI of protein folding

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