  Background : Supratentorial diffuse low-grade gliomas in adults extend beyond
maximal visible MRI-defined abnormalities, and a gap exists between the imaging
signal changes and the actual tumor margins. Direct quantitative comparisons
between imaging and histological analyses are lacking to date. However, they
are of the utmost importance if one wishes to develop realistic models for
diffuse glioma growth.
  Methods : In this study, we quantitatively compare the cell concentration and
the edema fraction from human histological biopsy samples (BSs) performed
inside and outside imaging abnormalities during serial imaging-based
stereotactic biopsy of diffuse low-grade gliomas.
  Results : The cell concentration was significantly higher in BSs located
inside (1189 $\pm$ 378 cell/mm$^2$) than outside (740 $\pm$ 124 cell/mm$^2$)
MRI-defined abnormalities (p=0.0003). The edema fraction was significantly
higher in BSs located inside (mean, 45 $\pm$ 23%) than outside (mean, 5 $\pm$
9%) MRI-defined abnormalities (p<0.0001). At borders of the MRI-defined
abnormalities, 20% of the tissue surface area was occupied by edema, and only
3% by tumor cells. The cycling cell concentration was significantly higher in
BSs located inside (10 $\pm$ 12 cell/mm$^2$) compared to outside (0.5 $\pm$ 0.9
cell/mm$^2$) MRI-defined abnormalities (p=0.0001).
  Conclusions : We show that the margins of T2-weighted signal changes are
mainly correlated with the edema fraction. In 62.5% of patients, the cycling
tumor cell fraction (defined as the ratio of the cycling tumor cell
concentration to the total number of tumor cells) was higher at the limits of
the MRI-defined abnormalities than closer to the center of the tumor. In the
remaining patients, the cycling tumor cell fraction increased towards the
center of the tumor.
