Detection of proton chemical exchange between metabolites and water in biological tissues.

Metabolites in proton chemical exchange with water were detected via the water proton signal using saturation transfer techniques in model systems and biological tissues. The metabolites were selectively saturated and the resulting decrease in the much larger water proton pool was used to monitor the metabolite. This indirect detection scheme can result in a several orders of magnitude increase in sensitivity for metabolites over direct detection methods. A control irradiation scheme was devised to compensate for macromolecular/water magnetization transfer. Using this approach, significant chemical exchange regions at approximately 1 and 2.5 ppm were detected in kidney medulla. Using a difference imaging technique between a control irradiation above (-1.74 ppm) and below (+1.74 ppm) the water resonance, a chemical exchange image of the kidney was calculated. These data revealed a linear gradient of chemical exchange increasing from the cortex to the medulla. Studies on medullary acid extracts and urine revealed that the exchange observed in the kidney was predominantly with low molecular weight metabolites. Urea (1 ppm) was identified as contributing to the kidney/urine chemical exchange; however, other unidentified metabolites may also contribute to this effect. These studies demonstrate that tissue metabolites can be detected and imaged via the water protons using the signal amplification properties of saturation transfer in the presence of water/macromolecule magnetization transfer.

[1]  S. Forsén,et al.  Transient and Steady‐State Overhauser Experiments in the Investigation of Relaxation Processes. Analogies between Chemical Exchange and Relaxation , 1966 .

[2]  A. D. Bain,et al.  A new way of measuring NMR spin-spin relaxation times (T2) , 1981 .

[3]  N. V. Lyulina,et al.  Combination of 31P-NMR magnetization transfer and radioisotope exchange methods for assessment of an enzyme reaction mechanism: rate-determining steps of the creatine kinase reaction. , 1990, Biochimica et biophysica acta.

[4]  R G Shulman,et al.  NMR studies of enzymatic rates in vitro and in vivo by magnetization transfer , 1984, Quarterly Reviews of Biophysics.

[5]  R. Balaban,et al.  Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo , 1989, Magnetic resonance in medicine.

[6]  E. McFarland,et al.  Chemical exchange magnetic resonance imaging (CHEMI). , 1988, Magnetic resonance imaging.

[7]  B. Schmidt-nielsen,et al.  INTRARENAL DISTRIBUTION OF UREA AND RELATED COMPOUNDS: EFFECTS OF NITROGEN INTAKE. , 1964, The American journal of physiology.

[8]  K. Uğurbil Magnetization-transfer measurements of individual rate constants in the presence of multiple reactions , 1985 .

[9]  J A Frank,et al.  Perfusion imaging with compensation for asymmetric magnetization transfer effects , 1996, Magnetic resonance in medicine.

[10]  R. Balaban,et al.  A novel approach for the determination of fast exchange rates , 1991 .

[11]  P J Sadler,et al.  Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine. , 1984, Clinical chemistry.

[12]  Gottfried Otting,et al.  Proton exchange rates from amino acid side chains— implications for image contrast , 1996, Magnetic resonance in medicine.

[13]  Sidney A. Simon,et al.  Dynamic and chemical factors affecting water proton relaxation by macromolecules , 1992 .

[14]  I. Smith,et al.  Magnetic resonance spectroscopy in biology and medicine. , 1989, Clinical biochemistry.

[15]  31P imaging of in Vivo creatine kinase reaction rates , 1987 .

[16]  W. T. Dixon Simple proton spectroscopic imaging. , 1984, Radiology.