title: Assessing tumor cytoarchitecture using multiecho DSC-MRI derived measures of the transverse relaxivity at tracer equilibrium (TRATE).
abstract: OBJECTIVE
  In brain tumor dynamic susceptibility contrast (DSC)-MRI studies, multiecho acquisition methods are used to quantify the dynamic changes in T1 and T2 * that occur when contrast agent (CA) extravasates. Such methods also enable the estimation of the effective tissue CA transverse relaxivity. The goal of this study was to evaluate the sensitivity of the transverse relaxivity at tracer equilibrium (TRATE) to tumor cytoarchitecture.
  
  
  METHODS
  Computational and in vitro studies were used to evaluate the biophysical basis of TRATE. In 9L, C6, and human brain tumors, TRATE, the apparent diffusion coefficient (ADC), the CA transfer constant (K(trans) ), the extravascular extracellular volume fraction (ve ), and histological data were compared.
  
  
  RESULTS
  Simulations and in vitro results indicate that TRATE is highly sensitive to variations in cellular properties such as cell size and density. The histologic cell density and TRATE values were significantly higher in 9L tumors as compared to C6 tumors. In animal and human tumors, a voxel-wise comparison of TRATE with ADC, ve , and K(trans) maps showed low spatial correlation.
  
  
  CONCLUSIONS
  The assessment of TRATE is clinically feasible and its sensitivity to tissue cytoarchitectural features not present in other imaging methods indicate that it could potentially serve as a unique structural signature or "trait" of cancer.
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Natenael B
authors.initials: NB
authors.lastname: Semmineh
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Junzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Skinner
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Jingping
authors.initials: J
authors.lastname: Xie
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Ayers
authors.affiliation: Institute of Imaging Science, Vanderbilt University, Nashville, Tennessee, USA.|Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA.|Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.|Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: C Chad
authors.initials: CC
authors.lastname: Quarles
mesh_terms: D000368:Aged; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D003198:Computer Simulation; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar
chemical_list: D003287:Contrast Media
keywords: cellular structures; contrast agent equilibrium; contrast agent leakage; dynamic susceptibility contrast; transverse relaxation; vascular structures