Measuring biochemical reaction rates in vivo with magnetization transfer

Research output: Contribution to journalArticlepeer-review

Abstract

Spin memory and its transferability through space and chemical bonds allow labeled NMR nuclei on a reacting moiety, A, in a reversible biochemical reaction, to be subsequently detected as a product moiety, B. The chemical reaction rates are measured in NMR units of spin-lattice relaxation time, T 1. Bloch equation analysis shows that the magnetization recovers at a new apparent T 1 rate which comprises the sum of the moiety's chemical exchange rate and the 'intrinsic T 1' rate that assumes no exchange. Two types of NMR labeling experiments are conceivable wherein A is observed while B is either selectively saturated -called saturation transfer (ST), or selectively inverted -called inversion transfer (IT). The analysis can be extended to three-site reactions, which require further experiments to differentiate intertwined rates and intrinsic T 1s. The main in vivo applications of ST and IT are in 31P MRS measurements of the creatine kinase (CK) reaction -a critical source of cellular adenosine triphosphate (ATP) energy -and the three-site reaction in which ATP is consumed. The ST experiment requires fully relaxed measures of A without (control) and with B saturated, and the apparent T 1 of A measured with B saturated. Conventional ST approaches that measure the apparent T 1 by progressive saturation, partial saturation, inversion recovery, or saturation recovery are inefficient and generally unsuitable for spatially localized studies of patients and larger animals. More efficient approaches -FAST, FASTer, FASTest, TRiST, optimized progressive saturation, and TWiST -reduce the total number of acquisitions to 4, 3, or 2 using minimum-acquisition T 1 measurements and/or short repetition times to predict the fully relaxed magnetization. 'Spillover' contamination of A during selective irradiation of B affects all methods, and corrections have been developed for ST. Such methods provide a truly unique noninvasive window to the living chemistry of cellular energy delivery in healthy and diseased living cells, tissues, organs, animals, and humans.

Original languageEnglish (US)
Pages (from-to)843-858
Number of pages16
JournaleMagRes
Volume5
Issue number1
DOIs
StatePublished - 2016

Keywords

  • Creatine kinase reaction
  • Inversion transfer
  • Magnetization transfer
  • Metabolite
  • MRS
  • Phosphocreatine
  • Quantification
  • Reaction rates
  • Saturation transfer

ASJC Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy
  • Biomedical Engineering
  • Biochemistry
  • Radiology Nuclear Medicine and imaging

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