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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| Vydáno v: | Nature medicine Ročník 9; číslo 8; s. 1085 - 1090 |
|---|---|
| Hlavní autoři: | , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
New York
Nature Publishing Group US
01.08.2003
Nature Publishing Group |
| Témata: | |
| ISSN: | 1078-8956, 1546-170X |
| On-line přístup: | Získat plný text |
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| Abstract | 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. |
|---|---|
| AbstractList | 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.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. 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. In the past decade, it has become possible to use the nuclear (proton, super(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. 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. |
| Audience | Academic |
| Author | Payen, Jean-Francois Wilson, David A van Zijl, Peter C M Traystman, Richard J Zhou, Jinyuan |
| Author_xml | – sequence: 1 givenname: Jinyuan surname: Zhou fullname: Zhou, Jinyuan email: jzhou@mri.jhu.edu organization: Division of MRI Research, Department of Radiology, Johns Hopkins University School of Medicine, 217 Traylor Building, F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute – sequence: 2 givenname: Jean-Francois surname: Payen fullname: Payen, Jean-Francois organization: Division of MRI Research, Department of Radiology, Johns Hopkins University School of Medicine, 217 Traylor Building, Department of Anesthesiology, The Grenoble University School of Medicine – sequence: 3 givenname: David A surname: Wilson fullname: Wilson, David A organization: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1408 Blalock Building – sequence: 4 givenname: Richard J surname: Traystman fullname: Traystman, Richard J organization: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 1408 Blalock Building – sequence: 5 givenname: Peter C M surname: van Zijl fullname: van Zijl, Peter C M email: pvanzijl@mri.jhu.edu organization: Division of MRI Research, Department of Radiology, Johns Hopkins University School of Medicine, 217 Traylor Building, F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/12872167$$D View this record in MEDLINE/PubMed |
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| References | SW Englander (BFnm907_CR8) 1972; 41 E Liepinsh (BFnm907_CR9) 1996; 35 RM Torack (BFnm907_CR21) 1976; 35 JM Hakumaki (BFnm907_CR27) 2000; 25 S Mori (BFnm907_CR11) 1998; 40 K Wuthrich (BFnm907_CR12) 1986 RA Kauppinen (BFnm907_CR15) 1992; 58 PP Fatouros (BFnm907_CR22) 1991; 17 SD Wolff (BFnm907_CR13) 1989; 10 JR Ewing (BFnm907_CR26) 1999; 41 SD Wolff (BFnm907_CR17) 1990; 86 TD Scholz (BFnm907_CR23) 1993; 29 J Pekar (BFnm907_CR18) 1996; 35 KM Ward (BFnm907_CR3) 2000; 44 KL Behar (BFnm907_CR16) 1993; 30 N Goffeney (BFnm907_CR4) 2001; 123 RB Moon (BFnm907_CR7) 1973; 248 S Mori (BFnm907_CR10) 1997; 119 HI Makela (BFnm907_CR25) 2002; 22 S Zhang (BFnm907_CR5) 2001; 123 J Zhou (BFnm907_CR19) 1998; 40 AK Covington (BFnm907_CR24) 1966; 70 W Lin (BFnm907_CR20) 2000; 20 KM Ward (BFnm907_CR2) 2000; 143 RM Henkelman (BFnm907_CR14) 2001; 14 JA Helpern (BFnm907_CR1) 1987; 5 S Aime (BFnm907_CR6) 2002; 47 |
| References_xml | – volume: 14 start-page: 57 year: 2001 ident: BFnm907_CR14 publication-title: NMR Biomed. doi: 10.1002/nbm.683 – volume: 41 start-page: 903 year: 1972 ident: BFnm907_CR8 publication-title: Annu. Rev. Biochem. doi: 10.1146/annurev.bi.41.070172.004351 – volume: 20 start-page: 37 year: 2000 ident: BFnm907_CR20 publication-title: J. Cereb. Blood Flow Metab. doi: 10.1097/00004647-200001000-00007 – volume: 58 start-page: 967 year: 1992 ident: BFnm907_CR15 publication-title: J. Neurochem. doi: 10.1111/j.1471-4159.1992.tb09350.x – volume: 35 start-page: 70 year: 1996 ident: BFnm907_CR18 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910350110 – volume: 40 start-page: 712 year: 1998 ident: BFnm907_CR19 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910400511 – volume: 29 start-page: 352 year: 1993 ident: BFnm907_CR23 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910290311 – volume: 35 start-page: 385 year: 1976 ident: BFnm907_CR21 publication-title: J. Neuropathol. Exp. Neurol. doi: 10.1097/00005072-197607000-00001 – volume: 123 start-page: 1517 year: 2001 ident: BFnm907_CR5 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja005820q – volume: 40 start-page: 36 year: 1998 ident: BFnm907_CR11 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910400105 – volume: 86 start-page: 164 year: 1990 ident: BFnm907_CR17 publication-title: J. Magn. Reson. – volume: 30 start-page: 38 year: 1993 ident: BFnm907_CR16 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910300107 – volume: 119 start-page: 6844 year: 1997 ident: BFnm907_CR10 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja963351f – volume: 123 start-page: 8628 year: 2001 ident: BFnm907_CR4 publication-title: J. Am. Chem. Soc. doi: 10.1021/ja0158455 – volume-title: NMR of proteins and nucleic acids year: 1986 ident: BFnm907_CR12 doi: 10.1051/epn/19861701011 – volume: 70 start-page: 3820 year: 1966 ident: BFnm907_CR24 publication-title: J. Phys. Chem. doi: 10.1021/j100884a011 – volume: 22 start-page: 547 year: 2002 ident: BFnm907_CR25 publication-title: J. Cereb. Blood Flow Metab. doi: 10.1097/00004647-200205000-00006 – volume: 10 start-page: 135 year: 1989 ident: BFnm907_CR13 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910100113 – volume: 5 start-page: 302 year: 1987 ident: BFnm907_CR1 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910050313 – volume: 47 start-page: 639 year: 2002 ident: BFnm907_CR6 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.10106 – volume: 17 start-page: 402 year: 1991 ident: BFnm907_CR22 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910170212 – volume: 41 start-page: 696 year: 1999 ident: BFnm907_CR26 publication-title: Magn. Reson. Med. doi: 10.1002/(SICI)1522-2594(199904)41:4<696::AID-MRM7>3.0.CO;2-5 – volume: 248 start-page: 7276 year: 1973 ident: BFnm907_CR7 publication-title: J. Biol. Chem. doi: 10.1016/S0021-9258(19)43389-9 – volume: 35 start-page: 30 year: 1996 ident: BFnm907_CR9 publication-title: Magn. Reson. Med. doi: 10.1002/mrm.1910350106 – volume: 44 start-page: 799 year: 2000 ident: BFnm907_CR3 publication-title: Magn. Reson. Med. doi: 10.1002/1522-2594(200011)44:5<799::AID-MRM18>3.0.CO;2-S – volume: 143 start-page: 79 year: 2000 ident: BFnm907_CR2 publication-title: J. Magn. Reson. doi: 10.1006/jmre.1999.1956 – volume: 25 start-page: 357 year: 2000 ident: BFnm907_CR27 publication-title: TIBS |
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H) signal of the hydrogen atoms in water for noninvasive assessment of functional and... 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... In the past decade, it has become possible to use the nuclear (proton, super(1)H) signal of the hydrogen atoms in water for noninvasive assessment of... |
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