title: Comparison of tumor histology to dynamic contrast enhanced magnetic resonance imaging-based physiological estimates.
abstract: OBJECTIVE
  The purpose of this study was to compare histologically determined cellularity and extracellular space to dynamic contrast-enhanced magnetic resonance imaging (DCE MRI)-based maps of a two-compartment model's parameters describing tumor contrast agent extravasation, specifically tumor extravascular extracellular space (EES) volume fraction (ve), tumor plasma volume fraction (vp) and volume-normalized contrast agent transfer rate between tumor plasma and interstitium (KTRANS/VT).
  
  
  METHODS
  Obtained ve, vp and KTRANS/VT maps were estimated from gadolinium diethylenetriamine penta-acetic acid DCE T1-weighted gradient-echo images at resolutions of 469, 938 and 2500 microm. These parameter maps were compared at each resolution to histologically determined tumor type, and the high-resolution 469-microm maps were compared with automated cell counting using Otsu's method and a color-thresholding method for estimated intracellular (Vintracellular) and extracellular (Vextracellular) space fractions.
  
  
  RESULTS
  The top five KTRANS/VT values obtained from each tumor at 469 and 938 microm resolutions are significantly different from those obtained at 2500 microm (P<.0001) and from one another (P=.0014). Using these top five KTRANS/VT values and the corresponding tumor EES volume fractions ve, we can statistically differentiate invasive ductal carcinomas from noninvasive papillary carcinomas for the 469- and 938-microm resolutions (P=.0017 and P=.0047, respectively), but not for the 2500-microm resolution (P=.9008). The color-thresholding method demonstrated that ve measured by DCE MRI is statistically similar to histologically determined EES. The Vextracellular obtained from the color-thresholding method was statistically similar to the ve measured with DCE MRI for the top 10 KTRANS/VT values (P>.05). DCE MRI-based KTRANS/VT estimates are not statistically correlated with histologically determined cellularity.
  
  
  CONCLUSIONS
  DCE MRI estimates of tumor physiology are a limited representation of tumor histological features. Extracellular spaces measured by both DCE MRI and microscopic analysis are statistically similar. Tumor typing by DCE MRI is spatial resolution dependent, as lower resolutions average out contributions to voxel-based estimates of KTRANS/VT. Thus, an appropriate resolution window is essential for DCE MRI tumor diagnosis. Within this resolution window, the top KTRANS/VT values with corresponding ve are diagnostic for the tumor types analyzed in this study.
authors.affiliation: Department of Nuclear, Plasma and Radiological Engineering, Beckman Institute Biomedical Imaging Center, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aref
authors.forename: Amir R
authors.initials: AR
authors.lastname: Chaudhari
authors.forename: Keith L
authors.initials: KL
authors.lastname: Bailey
authors.forename: Susanne
authors.initials: S
authors.lastname: Aref
authors.forename: Erik C
authors.initials: EC
authors.lastname: Wiener
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D015674:Mammary Neoplasms, Animal / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA