NMR spectroscopy and CEST imaging

Head of research group

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

Phone: +49 (0) 6221 42 2527
E-Mail

The research group explores detection techniques for clinical imaging systems with the aim to characterize tumor tissue non–invasively by means of physiological, in particular biochemical, markers and image contrasts. The group focuses on experimental techniques of high-resolution NMR spectroscopy (MRS), MR spectroscopic imaging (MRSI), and chemical exchange saturation transfer (CEST) MR imaging.

 

Open positions

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

In vivo NMR spectroscopy

Fig. 1. In vivo ³¹P MRSI of the human calf at 7 Tesla: UHF enables in vivo imaging of rare nuclei. MRSI of ³¹P yields maps of intracellular pH (upper left) and phospho–creatine PCr (upper right). Center: A representative in vivo phosphorus NMR spectrum of the calf muscle. Resonances of “high-energy” phosphates are well resolved.
© dkfz.de

NMR spectroscopy (MRS) enables the detection of signals of atomic nuclei with spin I≠0 bound to biomolecules. Without polarization techniques the abundance of those compounds in living tissue must be quite high to resolve the resonances – the detection limit for in vivo NMR is a concentration of ≥0.1 mM. The biochemical information is obtained non-invasively and without ionizing radiation.

Several spin species yield interesting multiline in vivo NMR spectra in acquisition times of a few minutes, for example spin-½ nuclei like 1H (proton; information about brain metabolites) and 31P (information about energy metabolism, membrane phospholipid turnover and intracellular pH).

The combination of MRS with MR imaging (MRI) techniques leads to MR spectroscopic imaging (MRSI), which yields maps of the regional abundance and distribution of metabolites in tissue. Compared to conventional 1H MRI of tissue water, 1H MRSI of small intracellular metabolites suffers from an at least 104-times smaller sensitivity.

The introduction of ultrahigh–field (UHF) MR scanners (magnetic field strength B0 ≥ 7 Tesla) opened new perspectives for MRI, MRS, and MRSI owing to increased sensitivity and spectral resolution. To promote clinical applicability of spectroscopy, our research group focuses on the development of high-resolution MRS and MRSI at UHF, where specific technical challenges occur.

CEST imaging

Fig. 2. CEST signals of different molecular entities in living tissue: The “Z-spectrum” is the normalized water proton signal obtained after selective radiofrequency irradiation across a range of offset-frequencies Δω (water protons resonate at Δω = 0). The CEST signal of each molecular entity can be visualized as an individual MR image.
© dkfz.de

Metabolites of low molecular mass (e.g. creatine and glucose), proteins, and other macromolecular structures carry weakly bound protons (1H nuclei) at their surface which can exchange with protons in neighboring bulk water molecules. This process, named chemical exchange (CE), occurs spontaneously and depends on concentration, pH, temperature, and other properties of the solution.

Exchanging protons can resonate at different frequencies (“chemical shifts”) in the 1H NMR spectrum. Hence, they can be labeled selectively (e.g. by resonant radiofrequency irradiation) to induce equal population of the two 1H spin states in a magnetic field – this technique is called saturation. Chemical exchange pumps this information into the water pool. Ongoing irradiation accumulates saturation in the water pool and produces the CEST effect (chemical exchange saturation transfer), i.e. a detectable reduction of the NMR signal of water protons. The amplification effect can make up several orders of magnitude. Note that in contrast to conventional NMR spectroscopy (MRS), which acquires the signal of tightly bound, hence non-exchanging nuclei (1H, 13C, 19F, 31P...), CEST employs the water signal to detect indirectly the signal of weakly bound protons in biomolecules.

When CEST is combined with MR imaging (MRI) techniques, different entities of cellular compounds – as illustrated in Fig. 2 – can be scanned in living tissue (in vivo) with a sensitivity comparable to conventional MRI. Since the discovery of the phenomenon in the year 2000, CEST-MRI has been applied to diagnostic imaging of various diseases (e.g. tumors, stroke, neurodegenerative disorders). These studies revealed new information about those pathologies on a molecular level.

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