Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI
Jinyuan Zhou1, Jean-Francois Payen, David A Wilson
1Division of MRI Research, Department of Radiology, Johns Hopkins University School of Medicine, 217 Traylor Building, 720 Rutland Avenue, Baltimore, Maryland 21205, USA. jzhou@mri.jhu.edu
Abstract:
In the past decade, it has become possible to use the nuclear (proton, 1H) 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.
Insights
Researchers developed a new pH-sensitive magnetic resonance imaging (MRI) contrast method using amide proton transfer (APT) to detect changes in pH and protein content, showing potential for acute stroke diagnosis.
Area of Science:
- Biomedical Imaging
- Biophysics
- Medical Physics
Background:
- Magnetic resonance imaging (MRI) traditionally uses water proton signals for physiological assessment.
- Developing novel MRI contrast mechanisms is crucial for advanced diagnostics.
Purpose of the Study:
- To demonstrate pH-sensitive MRI contrast using amide proton transfer (APT).
- To explore APT's potential for detecting acute stroke via pH changes.
Main Methods:
- Exploited exchange between water protons and endogenous mobile protein/peptide amide protons.
- Calibrated pH dependence using phosphorus spectroscopy and proton exchange spectroscopy.
- Noninvasively imaged pH effects in ischemic rat brain.
Main Results:
- Achieved sensitive detection of pH changes via amide proton transfer (APT).
- Demonstrated successful in vivo imaging of pH alterations in a rat stroke model.
- Established a link between pH, protein content, and MRI signal.
Conclusions:
- Amide proton transfer (APT) MRI provides intrinsic pH contrast.
- APT offers potential for diagnostic tools in clinical imaging, including stroke detection.
- This technique can also provide protein- and/or peptide-content contrast.
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