DZF-Project: Joachim Seelig

Development of Magnetic Resonance Imaging and Spectroscopy as Non-Invasive Tools for Animal Diagnostics

Prof. Dr. Joachim Seelig

Biozentrum, Div. of Biophysical Chemistry, Klingelbergstrasse 50/70, 4056 Basel, Switzerland


Keywords: Magnetic Resonance imaging, MR-spectroscopy, carbon-13 labelling, mouse brain metabolism

Begin and End of the Project: 1.4.1996 – 31.3.1999

Background and Aim

Background: Magnetic Resonance is a non-invasive tool to obtain images and molecular insight into the metabolism of animals.

Aim: To develop this method for improved analytical methods to reduce animal experimentation

Methods and Results

A number of publications appeared which describe different non-invasive measurements of the rat metabolism.

E. Küstermann, J. Seelig, and B. Künnecke
Ascorbic acid, a vitamin, is observed by in vivo 13C-nmr spectroscopy of rat liver.
Am. J. Physiol. 274 (Endocrinol. Metab. 37), E65-E71 (1998)

B. Künnecke and J. Seelig
In vivo 13C-, 15N-, and 19F-Magnetic resonance spectroscopy of the brain.
Proceedings of the International School of Physics "Enrico Fermi"
Course CXXXIX, B. Maraviglia (Ed.) IOS Press, Amsterdam 1999, p. 31-43

B. Künnecke, E. Küstermann, and J. Seelig
Simultaneous in vivo monitoring of hepatic glucose and glucose-6-phosphate by 13C-NMR spectroscopy.
Magn. Res. Med. 44, 556-62 (2000)

E. Seifritz, D. Bilecen, D. Hänggi, R. Haselhorst, E.W. Radü, S. Wetzel, J. Seelig, and K. Scheffler
Effect of ethanol on BOLD response to acoustic stimulation: Implications for neuropharmacological fMRI.
Psych. Res.: Neuroimag. 99, 1-13 (2000)

Conclusions and Relevance for 3R

Magnetic Resonance (MR) has helped to reduce the number of animal experiments since the animal can be measured non-invasively over an extended period of time and needs not to be sacrificed. For example, the treatment of an animal tumor can be followed with magnetic resonance imaging (MRI). The response of the tumor to a particular treatment can be monitored by measuring the volume of the tissue with MRI. This allows the testing of new drugs with only a few animals. The methods developed in Basel and elsewhere have found wide applications in pharmaceutical industry. In Basel alone, our research has led to the installation of 4 new instruments at Novartis and F. Hoffmann-La Roche. In the particular fields of research (brain infarct, cardiology, arthritis) this has led to a reduction of animals by about a factor of 100.

In addition to a reduction in the number of animal experiments, the MR investigation is harmless and involves only a mild anesthesia of the animal. Finally, conventional, invasive methods have been replaced by MR investigation. It is fair to say, that all major drug companies involved in research in the central nervous system and stroke have installed NMR units.

There is an increasing awareness for the usefulness of magnetic resonance also among policy makers. We have been invited on a number of occasions to describe our methods to governmental agencies and discussions have started to allow or even request MR investigations as additional or alternative tools