Comparison of tumor histology to dynamic contrast enhanced magnetic resonance imaging-based physiological estimates

Purpose: 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 (v(e)), tumor plasma volume fraction (v(p)) and volume-normalized contrast agent transfer rate between tumor plasma and interstitium (K-TRANS/V-T) Materials and Methods: Obtained v(e), v(p) and K-TRANS/V-T maps were estimated from gadolinium diethylenetriamine penta-acetic acid DCE T-1-weighted gradient-echo images at resolutions of 469, 938 and 2500 mu m. These parameter maps were compared at each resolution to histologically determined tumor type, and the high-resolution 469-mu m maps were compared with automated cell counting using Otsu's method and a color-thresholding method for estimated intracellular (V-intracellular) and extracellular (V-extracellular) space fractions. Results: The top five K-TRANS/V-T values obtained from each tumor at 469 and 938 mu m resolutions are significantly different from those obtained at 2500 pm (P <.0001) and from one another (P=.0014). Using these top five K-TRANS/V-T values and the corresponding tumor EES volume fractions v(e) we can statistically differentiate invasive ductal carcinomas from noninvasive papillary carcinomas for the 469- and 938-mu m resolutions (P=.0017 and P=.0047, respectively), but not for the 2500-mu m resolution (P=.9008). The color-thresholding method demonstrated that v, measured by DCE MRI is statistically similar to histologically determined EES. The V-extracellular obtained from the color-thresholding method was statistically similar to the v(e) measured with DCE MRI for the top 10 K-TRANS/V-T values (P >.05). DCE MRI-based K-TRANS/V-T estimates are not statistically correlated with histologically determined cellularity. Conclusion: DCE MRI estimates of tumor physiology are a limited representation Of tumor histological features. Extracellular spaces measured by both DCE M RI 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 K-TRANS/V-T. Thus, an appropriate resolution window is essential for DCE MRI tumor diagnosis. Within this resolution window, the top K-TRANS/V-T values with corresponding v(e) are diagnostic for the tumor types analyzed in this study. (c) 2008 Published by Elsevier Inc.