MR-derived cerebral blood volume maps: Issues regarding histological validation and assessment of tumor angiogenesis

In an effort to develop MRI methods for the evaluation of tumor angiogenesi s (new blood vessel formation), MRI-derived cerebral blood volume (CBV) inf ormation has been compared to histologic measures of microvessel density (M VD). Although MVD is a standard marker of angiogenesis, it is not a direct correlate of the volume measurements made with MRI, and therefore inappropr iate for the development and validation of the MR techniques. Therefore, th e goal of this study was to develop an approach by which MR measurements of CBV can be directly correlated. To this end, dynamic susceptibility contra st (DSC) MRI experiments were performed in six Fisher rats implanted with 9 L gliosarcoma brain tumors. Subsequently, the circulation was perfused with a latex compound (Microfil (R)), after which 50-mum tissue sections were a nalyzed for vessel count, diameter, and the fraction of area comprised of v essels. The results demonstrate that while fractional area (FA) does not pr ovide a good measure of CBV, FA corrected for section thickness eff acts do es. Whereas the FA in normal brain was found to be 13.03 +/- 1.83% the corr ected FA, or fractional volume (FV), was 1.89 +/- 0.39%, a value in agreeme nt with those reported in the literature for normal brain. Furthermore, whi le no significant difference was found between normal brain and tumor FA (P = 0.55), the difference was significant for FV (P = 0.036), as would be ex pected. And only with FV does a correlation with the MRI-derived CBV become apparent (r(S) = 0.74). There was strong correlation (r(s) = 0.886) betwee n the tumor/normal blood volume ratios as estimated by each technique, alth ough the MR-ratio (1.56 +/- 0.29) underestimated the histologic-ratio (2.35 +/- 0.75). Thus, the correlation of MRI CBV methods requires a measurement of fractional vessel area and correction of this area for section thicknes s effects. This new independent correlative measure should enable efficient and accurate progress in the development of MRI methods to evaluate tumor angiogenesis. (C) 2001 Wiley-Liss, Inc.