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 language | English (US) |
|---|---|
| Pages (from-to) | 843-858 |
| Number of pages | 16 |
| Journal | eMagRes |
| Volume | 5 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2016 |
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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
Cite this
Measuring biochemical reaction rates in vivo with magnetization transfer. / Bottomley, Paul A.
In: eMagRes, Vol. 5, No. 1, 2016, p. 843-858.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Measuring biochemical reaction rates in vivo with magnetization transfer
AU - Bottomley, Paul A
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Creatine kinase reaction
KW - Inversion transfer
KW - Magnetization transfer
KW - Metabolite
KW - MRS
KW - Phosphocreatine
KW - Quantification
KW - Reaction rates
KW - Saturation transfer
UR - http://www.scopus.com/inward/record.url?scp=85021371063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021371063&partnerID=8YFLogxK
U2 - 10.1002/9780470034590.emrstm1487
DO - 10.1002/9780470034590.emrstm1487
M3 - Article
AN - SCOPUS:85021371063
VL - 5
SP - 843
EP - 858
JO - eMagRes
JF - eMagRes
SN - 2055-6101
IS - 1
ER -