title: Imaging of endogenous exchangeable proton signals in the human brain using frequency labeled exchange transfer imaging.
abstract: OBJECTIVE
  To image endogenous exchangeable proton signals in the human brain using a recently reported method called frequency labeled exchange transfer (FLEX) MRI.
  
  
  METHODS
  As opposed to labeling exchangeable protons using saturation (i.e., chemical exchange saturation transfer, or CEST), FLEX labels exchangeable protons with their chemical shift evolution. The use of short high-power frequency pulses allows more efficient labeling of rapidly exchanging protons, while time domain acquisition allows removal of contamination from semi-solid magnetization transfer effects.
  
  
  RESULTS
  FLEX-based exchangeable proton signals were detected in human brain over the 1-5 ppm frequency range from water. Conventional magnetization transfer contrast and the bulk water signal did not interfere in the FLEX spectrum. The information content of these signals differed from in vivo CEST data in that the average exchange rate of these signals was 350-400 s(-1) , much faster than the amide signal usually detected using direct saturation (∼30 s(-1) ). Similarly, fast exchanging protons could be detected in egg white in the same frequency range where amide and amine protons of mobile proteins and peptides are known to resonate.
  
  
  CONCLUSIONS
  FLEX MRI in the human brain preferentially detects more rapidly exchanging amide/amine protons compared to traditional CEST experiments, thereby changing the information content of the exchangeable proton spectrum. This has the potential to open up different types of endogenous applications as well as more easy detection of rapidly exchanging protons in diaCEST agents or fast exchanging units such as water molecules in paracest agents without interference of conventional magnetization transfer contrast.
authors: Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Nirbhay N
authors: NN
authors: Yadav
authors: Craig K
authors: CK
authors: Jones
authors: Jun
authors: J
authors: Hua
authors: Jiadi
authors: J
authors: Xu
authors: Peter C M
authors: PC
authors: van Zijl
mesh_terms: D000465:Algorithms; D001921:Brain / Q000033:anatomy & histology*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011522:Protons; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D011522:Protons
references: Nat Med. 2011 Jan;17(1):130-4
references: 21170048
references: Magn Reson Med. 2013 Mar 1;69(3):760-70
references: 22577042
references: Magn Reson Med. 2000 Nov;44(5):799-802
references: 11064415
references: Nat Med. 2003 Aug;9(8):1085-90
references: 12872167
references: Nat Med. 2012 Jan 22;18(2):302-6
references: 22270722
references: Magn Reson Med. 2012 Apr;67(4):906-11
references: 22287162
references: Magn Reson Med. 2010 Sep;64(3):638-44
references: 20632402
references: J Cereb Blood Flow Metab. 2007 Jun;27(6):1129-36
references: 17133226
references: Acc Chem Res. 2003 Oct;36(10):783-90
references: 14567712
references: Magn Reson Med. 2009 Jun;61(6):1441-50
references: 19358232
references: NMR Biomed. 2012 Nov;25(11):1305-9
references: 22431193
references: Mol Imaging. 2012 Feb;11(1):47-57
references: 22418027
references: Angew Chem Int Ed Engl. 2011 Feb 18;50(8):1798-800
references: 21328642
references: Magn Reson Med. 2012 Oct;68(4):1048-55
references: 22837066
references: J Magn Reson. 2000 Mar;143(1):79-87
references: 10698648
references: Appl Magn Reson. 2012 Apr;42(3):393-402
references: 23243339
references: Magn Reson Med. 2012 Jun;67(6):1579-89
references: 22083645
references: Magn Reson Med. 1994 Sep;32(3):335-41
references: 7984066
references: Front Biosci. 2008 Jan 01;13:1733-52
references: 17981664
references: Magn Reson Med. 2012 Dec;68(6):1764-73
references: 23074027
references: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2266-70
references: 18268341
references: Acc Chem Res. 2009 Jul 21;42(7):822-31
references: 19534516
references: Annu Rev Biomed Eng. 2008;10:391-411
references: 18647117
references: NMR Biomed. 2009 Dec;22(10):1003-13
references: 19504521
references: Magn Reson Med. 2006 Sep;56(3):585-92
references: 16892186
references: Magn Reson Med. 2011 Apr;65(4):927-48
references: 21337419
references: J Am Chem Soc. 2010 Feb 17;132(6):1813-5
references: 20095603