Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI

In the past decade, it has become possible to use the nuclear (proton, 1 H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by expl...

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Bibliographic Details
Published in:Nature medicine Vol. 9; no. 8; pp. 1085 - 1090
Main Authors: Zhou, Jinyuan, Payen, Jean-Francois, Wilson, David A, Traystman, Richard J, van Zijl, Peter C M
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.08.2003
Nature Publishing Group
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Brain - anatomy & histology
Cancer Research
Hydrogen
Hydrogen-Ion Concentration
Infectious Diseases
Ischemia - metabolism
Magnetic Resonance Imaging - methods
Metabolic Diseases
Molecular Medicine
Neurosciences
Peptides
Peptides - chemistry
Physiology
Proteins - chemistry
Protons
Rats
Rats, Sprague-Dawley
Spectroscopy
technical-report
Water - chemistry
ISSN:1078-8956, 1546-170X
Online Access:Get full text
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Summary:In the past decade, it has become possible to use the nuclear (proton, 1 H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by exploiting the exchange between the hydrogen atoms of water and the amide hydrogen atoms of endogenous mobile cellular proteins and peptides. Although amide proton concentrations are in the millimolar range, we achieved a detection sensitivity of several percent on the water signal (molar concentration). The pH dependence of the signal was calibrated in situ , using phosphorus spectroscopy to determine pH, and proton exchange spectroscopy to measure the amide proton transfer rate. To show the potential of amide proton transfer (APT) contrast for detecting acute stroke, pH effects were noninvasively imaged in ischemic rat brain. This observation opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, as diagnostic tools in clinical imaging.
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ISSN:1078-8956
1546-170X
DOI:10.1038/nm907