In Vivo NMR Spectroscopy

Often the information on NMR relaxation parameters carried by image contrast is insufficient to address a particular problem. We can then look to the rich information content of the spectrum itself. Generally, spectroscopy of the entire body is not of much value, and in vivo spectroscopy is usually carried out as localized spectroscopy, that is, over a part of the body. There are various ways of restricting the operation of the spectrometer to a particular region, and they fall into two broad classes those that depend on the physical dimensions of the rf coil and those that use field gradients in the pulse sequences. Often these approaches are combined. At this time, the use of spectroscopic examinations has not become part of the repertoire of clinical practice, despite a history of in vivo spectroscopy almost as old as MRI itself. In vivo spectroscopy has had a number of landmark successes in solving problems in metabolism research in both animals and humans, but there have been no spectroscopic applications that have been demonstrated to be more effective than other methods for the routine diagnosis of disease. 

One of the most common applications of surface coil spectroscopy is in 3IP spectroscopy. It turns out that only a small 

The most downfield resonance is that of inorganic phosphate ion, (P04)v (abbreviated P,). When cells carry out their normal metabolic function, phosphate is cleaved from ATP to produce P,. The energy status of cells may therefore be gauged by measuring, for instance, the PCr/P, ratio. Cells with a low value of this ratio are energy depleted, which might result from insufficient blood supply (ischemia) or some metabolic disorder. 

A useful feature of 1 P spectroscopy is that the resonances are pH sensitive. All of the observable phosphates can be 

The normal H spectrum of tissue consists of the dominant resonance of water at about 4.7 ppm and a weaker resonance from the methylene of lipid (fat) at about 0.9 ppm. This spectrum never changes significantly and is therefore usually uninteresting. However, by suppressing these resonances, many others, much weaker in intensity but far more diagnostically useful, are revealed. There are a number of suppression techniques. A frequency-selective pulse may first be applied to saturate the unwanted resonances. Water, being by far the 

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R. A. de Graaf, In Vivo NMR Spectroscopy, John Wiley, Chichester, 1998, 372-406. 

F. Melzner, C. Bock and H.-O. Fortner, Critical temperatures in the cephalopod Sepia officinalis investigated using in vivo NMR spectroscopy. /. Exp. Biol, 2006, 209, 891-906. 

R.A. de Graff, In Vivo NMR Spectroscopy Principles and Techniques, John Willey Sons, Sussex, 2010. 

De Graaf R. 2008. In vivo nmr spectroscopy Principles and techniques. Chichester, West Sussex Wiley-Interscience. 

P.-M. L. Robitaille, In Vivo NMR Spectroscopy A Unique Approach in the Dynamic Analysis of Tricarboxylic Acid Cycle Flux and Substrate Selection , p. 215 vol. 16... 

A better method could be in vivo NMR spectroscopy, which would be noninvasive. But the extremely low sensitivity of NMR is in general a severe drawback to explore anaboHc or catabolic events. However, that disadvantage could probably be overcome by multiple labeling with radioactive ( H, " C) or stable isotopes such as H, N, or It might be a... 

In vivo NMR spectroscopy has enabled the investigation and monitoring of metabolic changes in living tissues in situ. Unlike many other biochemical techniques, it is noninvasive, facilitating studies on previously inaccessible tissues such as the brain. 

Choi I-Y, Tkac I, and Gruetter R (2000) Single-shot, three-dimensional non-echo localisation method for in-vivo NMR spectroscopy. Magnetic Resonance in Medicine 44 387-394. 

Figure 6 A H MRS spectrum from normal human brain at 7T. An 8 ml VOI was localized in the parietal white matter using STEAM with effective TE 6 ms, repetition time 5 s, TM 32 ms, and the collection of 160 averaged echoes. Outer volume suppression, employing SECH pulses, was used and FASTMAP was used to shim the VOI. Peaks undefined in the main text are myoinositol - myo-lns taurine - Tau glutathione - GSH aspartate -ASP A/-acetylaspartylglutamate - NAAG macromolecule - MM. (Reprinted with permission from Tkac I, Anderson P, Adriany G, et at. (2001) In vivo NMR spectroscopy of the human brain at 7 Tesla. Magnetic Resonance in Medicine 46 451-456 Wiley-Liss, a subsidiary of Wiley.)...

Keevil SF, Barbiroli B, Brooks JCW, et al. (1998) Absolute metabolite quantification by in vivo NMR spectroscopy II. A multicentre trial of protocols for in vivo localised proton studies of human brain. Magnetic Resonance Imaging 16 1093-1106. 

Tkac I, Anderson P, Andriany G, et al. (1995) Quality Assessment in in vivo NMR spectroscopy Results of a concerted research project of the Eurpoean Economic Community. Magnetic Resonance Imaging 13 117-176. 

The traditional qualitative uses of Ln + complexes to simplify complex NMR spectra in organic solvents, reviewed extensively, have been replaced by the use of high magnetic fields and two- and three-dimensional NMR methods. Applications of chiral SRs have also been extensively reviewed. This chapter describes LIS methodologies for those who wish to apply them to their particular systems, and their recent quantitative applications as NMR structural probes in aqueous solution of small Ln + complexes including some of their supramolecular constructs, as well as of small biological molecules and proteins, and as SRs for in vivo NMR spectroscopy. 

The use of in vitro and in vivo NMR spectroscopy for the study of the metabolic characteristics of genetic disorders has been reviewed. ... 

Unknown metabolite observed by in vivo NMR spectroscopy (or other technique). 

R 524 A.H. Trabesinger, D. Meier and P. Boesiger, In vivo NMR Spectroscopy of Individual Human Brain Metabolites at Moderate Field Strengths , Magn.Reson.Imaging, 2003,21,1295... 

In vivo NMR spectroscopy can be used repetitively on the same patient since it is noninvasive. The ability to monitor the pharmacokinetic of a drug and to evaluate the potential modifications in drug metabolism could prove extremely valuable in patient management. 

Nowadays, the bulk of publications on in vivo NMR spectroscopy are concerned with H NMR spectroscopy of human brain. Many small molecule metabolites have been detected and much effort has gone into attempts to quantify these components. Many studies are concerned with altered levels of metabolites in various brain diseases. A typical H NMR spectrum of human brain acquired in vivo is shown in Figure 2. 

In vivo NMR spectroscopy can be a very useful technique for monitoring the distribution of fluori-nated drugs and their metabolites. These include the PET agent 2-fluoro-2-deoxyglucose, the study of its 3-fluoro-isomer as a probe of aldose reductase activity in brain, the elimination from the brain of fluori-nated anaesthetics, metabolism of halothane in the liver, the distribution and catabolism of the anticancer drug 5-fluorouracil and the uptake of trifluoro-methylthymidine into mouse tumours. 

A number of reports of the use of in vivo NMR spectroscopy are in the literature. These include studies of lipid deposits, glycogen and its breakdown in the liver and the monitoring of the metabolism of C-labelled substances such as C-glucose in various tissues such as the brain. 

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