Marie-Curie Fellow
Research & Training Network
F. Nielsen (ER)

Marie Curie Fellow (ER) of the FAST project
Katholieke Universiteit Leuven, Belgium
Contact
 

• T2 Acquisition
  Task 2 exploits the strong synergy between signal processing and MR methodology to reduce the MRSI acquisition-time. It shall use the latest technical developments and (confidential) expertise of our Industrial partners Philips and Siemens concerning high-speed gradients, coil arrays, novel pulse sequence designs for extending the limits of spatial resolution, temporal resolution, and SNR. T2 and T4 also investigate and develop advanced, innovative ways of acquiring MRSI data, at the forefront of MR-methodology. This is a highly challenging task exploring uncharted paths. Data of patients with brain, prostate and breast cancer, diabetes, etc., and of healthy controls will be acquired, co-registered and evaluated with MRI.

• T4 Signal processing
  Task 4 focuses on MRSI signal processing proper of Gigabytes of data. The ultimate goal is reliable quantitation of metabolites. The required computing times are long and will eventually need grid-computing.

  • T4.1 led by KU Leuven, concerns time-domain processing. This is a daunting task for many reasons:
    1. MRSI signals contain a strong non-parametric part from `macromolecules' that perturbs the wanted, parametric, part from metabolites. This requires a semi-parametric approach which is still under development, worldwide.

• T6 Applications
  Task 6 judges and criticizes/approves FAST's innovations in preclinical and clinical settings. T6 also improves knowledge about diseases and metabolomics, gathered through MRSI. In essence, metabolomics pertains to identification of as many metabolites as possible and to understand each in its own biochemical context. MRSI can measure metabolite concentrations, chemical shifts, pH, etc. non-invasively and therefore has a huge potential for this task. Through time, much more emphasis will be placed on diagnosing and treating symptoms before secondary symptoms occur -- prevention rather than the cure of a (potential) disease. The role of Industrial partner Sanofi-Aventis is important in this task.

Current activities and responsibilities:
Interface between activities of the Biomedical NMR Unit, Katholieke Universiteit Leuven (KUL) and the signal processing engineers at ESAT KUL. This concerns in particular biochemical profiling of tissue in-vivo. More applied aspects include the generation of experimental data sets for the evaluation of analysis, quantification and classification approaches at ESAT. Methodological/experimental activities involve testing and optimizing of Single Voxel Spectroscopy (SVS) pulse sequences on the 9.4T Bruker Biospec small animal MRI scanner for experimental models and implementation of inversion recovery SVS methods. The objective of the latter is the detection of the Macro Molecular baseline, which will be added to the metabolite date bases used by Quest in jMRUI for each in-vivo study. This data base will further be completed by the acquisition of metabolite signals from prepared solutions.

The first biochemical profile of a disease model to be studied will be a mouse model of a neuro-degenerative disease.

Activities also concern the set-up of jMRUI in our laboratory and to some extent being involved in the jMRUI processing of spectroscopy data obtained from brain tumour patients in the department of Radiology, KUL as well as training of respective staff/ PhD students.

Thomas Breidahl, Flemming U. Nielsen, Hans Stødkilde-Jørgensen, Ross J Maxwell and Michael R. Horseman. “The effects of the vascular disrupting agents combretastatin A-4 disodium phosphate, 5,6-dimethylxanthenone-4-acetic acid and ZD6126 in a murine tumour: a comparative assessment using MRI and MRS”. Acta Oncol. 45 (3): 306-16 (2006)

Silvio Aime, Alessandro Barge, Daniela Delli Castelli, Franco Fedeli, Armando Mortillaro, Flemming U. Nielsen and Enzo Terreno. “Paramagnetic Lanthanide(III) Complexes as pH-Sensitive Chemical Exchange Saturation transfer (CEST) Contrast Agents for MRI Applications. Magn. Reson. Med. 47.639-648 (2002).

Flemming U. Nielsen, Preben Daugaard, Hans Stødkilde-Jørgensen, Jens Overgaard, Michael R. Horsman, Ross J. Maxwell. “Effect of changing tumor oxygenation on glycolytic metabolism in a murine C3H mammary carcinoma assessed by in vivo Nuclear Magnetic Resonance spectroscopy”. Cancer Res. Jul 1; 61(13): 5318-25 (2001).

M.R. Horsman, R. Murata, T. Breidahl, F.U. Nielsen, R.J. Maxwell, H. Støklide-Jørgensen and J. Overgaard. “Combretastatins: novel vascular targeting drugs for improving anti-cancer therapy”. In: Angiogenesis: From the molecular to integrative pharmacology. M. M. Maragoudakis, ed. Kluwer Academic/Plenum Publishers, New York, vol. 476, 311-323, (2000).

Nielsen F.U., Topp S., Horseman M.R. Overgaard, J., Stødkilde-Jørgensen, H. and Maxwell R.J., “Localized in vivo 1H NMR spectroscopy of murine tumours: effect of blood flow reduction”. NMR in Biomedicine, 12, 175-183, (1999).

R.J. Maxwell, F.U. Nielsen, T. Breidahl, H. Stødkilde-Jørgensen, M.R. Horseman. “Effects of Combretastatin on Murine Tumours Monitored by 31P, 1H and 1H MRI”. Int. J. Radiat. Oncol. Biol. Phys., vol. 42, No. 4, 891-894, (1998).

Lesot P., Nielsen F. U., Ouvrard J. M. and Courtieu J. “Multiple-Pulse COSY NMR of Oriented Molecules in Thermotropic Cholesterics”. J. Phys. Chem., vol. 98, No. 49, (1994).