title: 1H/31P polarization transfer at 9.4 Tesla for improved specificity of detecting phosphomonoesters and phosphodiesters in breast tumor models.
abstract: OBJECTIVE
  To assess the ability of a polarization transfer (PT) magnetic resonance spectroscopy (MRS) technique to improve the detection of the individual phospholipid metabolites phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC), and glycerophosphoethanolamine (GPE) in vivo in breast tumor xenografts.
  
  
  METHODS
  The adiabatic version of refocused insensitive nuclei enhanced by polarization transfer (BINEPT) MRS was tested at 9.4 Tesla in phantoms and animal models. BINEPT and pulse-acquire (PA) 31P MRS was acquired consecutively from the same orthotopic MCF-7 (n = 10) and MDA-MB-231 (n = 10) breast tumor xenografts. After in vivo MRS measurements, animals were euthanized, tumors were extracted and high resolution (HR)-MRS was performed. Signal to noise ratios (SNRs) and metabolite ratios were compared for BINEPT and PA MRS, and were also measured and compared with that from HR-MRS.
  
  
  RESULTS
  BINEPT exclusively detected metabolites with 1H-31P coupling such as PC, PE, GPC, and GPE, thereby creating a significantly improved, flat baseline because overlapping resonances from immobile and partly mobile phospholipids were removed without loss of sensitivity. GPE and GPC were more accurately detected by BINEPT in vivo, which enabled a reliable quantification of metabolite ratios such as PE/GPE and PC/GPC, which are important markers of tumor aggressiveness and treatment response.
  
  
  CONCLUSIONS
  BINEPT is advantageous over PA for detecting and quantifying the individual phospholipid metabolites PC, PE, GPC, and GPE in vivo at high magnetic field strength. As BINEPT can be used clinically, alterations in these phospholipid metabolites can be assessed in vivo for cancer diagnosis and treatment monitoring.
authors.affiliation: Johns Hopkins University In vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Department of Radiology, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Jannie P
authors.initials: JP
authors.lastname: Wijnen
authors.affiliation: Johns Hopkins University In vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Johns Hopkins University In vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: Greenwood
authors.affiliation: Department of Radiology, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Wybe J M
authors.initials: WJ
authors.lastname: van der Kemp
authors.affiliation: Department of Radiology, University Medical Centre Utrecht, Utrecht, Netherlands.
authors.forename: Dennis W J
authors.initials: DW
authors.lastname: Klomp
authors.affiliation: Johns Hopkins University In vivo Cellular and Molecular Imaging Center, The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America; Sidney Kimmel Comprehensive Cancer, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D010743:Phospholipids / Q000378:metabolism*; D010759:Phosphorus Isotopes; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*
chemical_list: D010743:Phospholipids; D010759:Phosphorus Isotopes