Computational Medicine

T. Tukiainen, T. Tynkkynen, V.-P. Mäkinen, P. Jylänki, A. Kangas, J. Hokkanen, A. Vehtari, O. Gröhn, M. Hallikainen, H. Soininen, M. Kivipelto, P.-H. Groop, K. Kaski, R. Laatikainen, P. Soininen, T. Pirttilä, M. Ala-Korpela A multi-metabolite analysis of serum by 1H NMR spectroscopy: early systemic signs of Alzheimer's disease Biochemical and Biophysical Research Communications 375, 356-361, 2008

T. Liimatainen, J. M. Hakumäki, R. A. Kauppinen, M. Ala-Korpela Monitoring of gliomas in vivo by diffusion MRI and 1H MRS during gene therapy induced apoptosis – interrelationships between water diffusion and mobile lipids NMR in Biomedicine 2008, in press

The measurement of water diffusion by diffusion-weighted MRI (DWI) in vivo offers a non-invasive methodology to assess tissue responses to anti-cancer therapies. A pathway for cell death following anti-cancer treatments is often apoptosis which leads to accumulation of mobile lipids detectable by 1H MRS in vivo. However, it is not known how these discrete MR markers of cell death relate to each other. Here, in a rodent tumour model, i.e., ganciclovir-treated herpes simplex thymidine kinase (HSV-tk) gene transfected BT4C gliomas; we studied the interrelationships between water diffusion (Trace{D}) and mobile lipids during apoptosis. The water diffusion and the waterreferenced concentrations of the mobile lipids showed clearly increasing and interconnected trends during treatment. Of the accumulating 1H MRS-visible lipids, the fatty acid –CH=CH– groups and the cholesterol compounds showed the strongest associations with the water diffusion (r2 = 0.30; p < 0.05 and r2 = 0.48; p < 0.01, respectively). These results indicate that the tumour histopathology and apoptotic processes during tumour shrinkage can be interrelated in vivo via DWI of tissue water and 1H MRS of the mobile lipids, respectively. However, there was considerable individual variation in the associations, particularly at the end of the treatment period and in the relative composition of the accumulating NMR-visible lipids. The findings suggest that, the assessment of individual treatment response in vivo may benefit from the combination of DWI and 1H MRS. The absolute and relative changes in the mobile lipids could indicate initiation of tumour shrinkage even though changes in the tissue water diffusion are still small. Conversely, heavily increased water diffusion most likely indicates that substantial cell decomposition has taken place in the tumour tissue when the 1H MRS resonances of mobile lipids alone can no longer give a reliable estimate on tissue conditions.

V.-P. Mäkinen, C. Forsblom, L. Thorn, J. Wadén, D. Gordin, O. Heikkilä, K. Hietala, L. Kyllönen, J. Kytö, M. Rosengård-Bärlund, M. Saraheimo, N. Tolonen, M. Parkkonen, K. Kaski, M. Ala-Korpela, P.-H. Groop Metabolic phenotypes, vascular complications and premature deaths in a population of 4,197 patients with type 1 diabetes Diabetes 57, 2480-2487, 2008

L. S. Kumpula, J. M. Kumpula, M.-R. Taskinen, M. Jauhiainen, K. Kaski, M. Ala-Korpela Reconsideration of hydrophobic lipid distributions in lipoprotein particles Chemistry and Physics of Lipids 155, 57-62, 2008

S. M. Mäkelä, M. Jauhiainen, M. Ala-Korpela, J. Metso, T. M. Lehto, M. J. Savolainen, M. L. Hannuksela HDL2 of heavy alcohol drinkers enhances cholesterol efflux from RAW-macrophages via enlarged phospholipid-rich HDL2b particles Alcoholism: Clinical and Experimental Research 32, 991-1000, 2008

V.-P. Mäkinen, P. Soininen, C. Forsblom, M. Parkkonen, P. Ingman, K. Kaski, P.-H. Groop, M. Ala-Korpela 1H NMR metabonomics approach to the disease continuum of diabetic complications and premature death Molecular Systems Biology 4, 167 (1-12), 2008

Featured article of the month in February 2008.

M. Ala-Korpela Critical evaluation of 1H NMR metabonomics of serum as a methodology for disease risk assessment and diagnostics Clinical Chemistry and Laboratory Medicine 46, 27-42, 2008

M. Ala-Korpela The potential role of body fluid 1H NMR metabonomics as a prognostic and diagnostic tool Expert Review of Molecular Diagnostics 7, 761-773, 2007

P. Soininen, K. Öörni, H. Maaheimo, R. Laatikainen, P. T. Kovanen, K. Kaski, M. Ala-Korpela 1H NMR at 800 MHz Facilitates Detailed Phospholipid Follow-Up during Atherogenic Modifications in Low Density Lipoproteins Biochemical and Biophysical Research Communications 360, 290-294, 2007

A. Vehtari, V.-P. Mäkinen, P. P. Soininen. Ingman, S. M. Mäkelä, M. J. Savolainen, M. L. Hannuksela, K. Kaski, M. Ala-Korpela A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data BMC Bioinformatics 8, (Suppl 2):S8, 2007

V.-P. Mäkinen, P.-H. Groop, M. Ala-Korpela Metabonomik – på väg mot individuell riskbedömning (in Swedish) Finska Läkaresällskapets Handlingar 167, 40-46, 2007

T. Suna, A. Salminen, P. Soininen, R. Laatikainen, P. Ingman, S. Mäkelä, M. J. Savolainen, M. L. Hannuksela, M. Jauhiainen, M.-R. Taskinen, K. Kaski, M. Ala-Korpela 1H NMR metabonomics of plasma lipoprotein subclasses - elucidation of metabolic clustering by self-organising maps NMR in Biomedicine 20, 658-672, 2007

M. Ala-Korpela, N. Lankinen, A. Salminen, T. Suna, P. Soininen, R. Laatikainen, P. Ingman, M. Jauhiainen, M.- R. Taskinen, K. Héberger, K. Kaski The inherent accuracy of 1H NMR spectroscopy to quantify plasma lipoproteins is subclass dependent Atherosclerosis 190, 352-358, 2007

V.-P. Mäkinen, P. Soininen, C. Forsblom, M. Parkkonen, P. Ingman, K. Kaski, P.-H. Groop, M. Ala-Korpela Diagnosing diabetic nephropathy by 1H NMR metabonomics of serum Magnetic Resonance Materials in Physics, Biology and Medicine 19, 281-296, 2006

T. Liimatainen, K. Lehtimäki, M. Ala-Korpela, J. Hakumäki Identification of mobile cholesterol compounds in experimental gliomas by 1H MRS in vivo: effects of ganciclovir-induced apoptosis on lipids FEBS Letters 580, 4746-4750, 2006

M. Ala-Korpela, P. Sipola, K. Kaski Molecular detection and characterisation of atherothrombosis by magnetic resonance - potential tools for individual risk assessment and diagnostics Annals of Medicine 38, 322-336, 2006

T. Suna, M. Hardey, J. Huhtinen, Y. Hiltunen, K. Kaski, J. Heikkonen, M. Ala-Korpela Self-organising map approach to individual profiles: age, sex and culture in Internet dating Sociological Research Online 11, Issue 1, 2006

K. Öörni, P. Posio, M. M. Ala-Korpela. Jauhiainen, P. T. Kovanen Sphingomyelinase induces aggregation and fusion of small VLDL and IDL particles and increases their retention to human arterial proteoglycans Arteriosclerosis, Thrombosis, and Vascular Biology 25, 1678-1683, 2005

In relation to this paper, Arteriosclerosis, Thrombosis, and Vascular Biology published an editorial by Kevin Jon Williams and Ira Tabas entitled Lipoprotein retention — and clues for atheroma regression; Arterioscler Thromb Vasc Biol 25, 1536–1540, 2005. (Article in PubMed)

More information

Dr Mika Ala-Korpela
Group Leader in Computational Medicine

The Academy of Finland Centre of Excellence in Computational Complex Systems Research 2006-2011

Helsinki University of Technology
Faculty of Information and Natural Sciences
Department of Biomedical Engineering and Computational Science
P.O. Box 9203
FI-02015 HUT
Finland &

The Folkhälsan Research Center
Institute of Genetics, Department of Diabetes Genetics
The FinnDiane Study Group
P.O. Box 63, Biomedicum
00014 University of Helsinki
Finland &

Helsinki University Central Hospital, Department of Medicine,
Division of Nephrology, Helsinki, Finland

Mobile: + 358 50 35 35 457
E-mail: