title: Ultrashort echo time for improved positive-contrast manganese-enhanced MRI of cancer.
abstract: OBJECTIVE
  Manganese (Mn) is a positive magnetic resonance imaging (MRI) contrast agent that has been used to obtain physiological, biochemical, and molecular biological information. There is great interest to broaden its applications, but a major challenge is to increase detection sensitivity. Another challenge is distinguishing regions of Mn-related signal enhancement from background tissue with inherently similar contrast. To overcome these limitations, this study investigates the use of ultrashort echo time (UTE) and subtraction UTE (SubUTE) imaging for more sensitive and specific determination of Mn accumulation.
  
  
  METHODS
  Simulations were performed to investigate the feasibility of UTE and SubUTE for Mn-enhanced MRI and to optimize imaging parameters. Phantoms containing aqueous Mn solutions were imaged on a MRI scanner to validate simulations predictions. Breast cancer cells that are very aggressive (MDA-MB-231 and a more aggressive variant LM2) and a less aggressive cell line (MCF7) were labeled with Mn and imaged on MRI. All imaging was performed on a 3 Tesla scanner and compared UTE and SubUTE against conventional T1-weighted spoiled gradient echo (SPGR) imaging.
  
  
  RESULTS
  Simulations and phantom imaging demonstrated that UTE and SubUTE provided sustained and linearly increasing positive contrast over a wide range of Mn concentrations, whereas conventional SPGR displayed signal plateau and eventual decrease. Higher flip angles are optimal for imaging higher Mn concentrations. Breast cancer cell imaging demonstrated that UTE and SubUTE provided high sensitivity, with SubUTE providing background suppression for improved specificity and eliminating the need for a pre-contrast baseline image. The SubUTE sequence allowed the best distinction of aggressive breast cancer cells.
  
  
  CONCLUSIONS
  UTE and SubUTE allow more sensitive and specific positive-contrast detection of Mn enhancement. This imaging capability can potentially open many new doors for Mn-enhanced MRI in vascular, cellular, and molecular imaging.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Joris Tchouala
authors.initials: JT
authors.lastname: Nofiele
authors.forename: Hai-Ling Margaret
authors.initials: HL
authors.lastname: Cheng
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis*; D003287:Contrast Media / Q000032:analysis*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D016014:Linear Models; D061986:MCF-7 Cells; D008279:Magnetic Resonance Imaging / Q000295:instrumentation / Q000379:methods*; D008345:Manganese / Q000032:analysis; D019047:Phantoms, Imaging; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D003287:Contrast Media; D008345:Manganese