Heterogeneity in malignant gliomas: a magnetic resonance analysis of spatial distribution of metabolite changes and regional blood volume.

First-pass contrast-enhanced dynamic perfusion imaging provides information about the regional cerebral blood volume (rCBV), an increase of which indicates neovascularization. MR spectroscopic imaging informs about metabolite changes in brain tumors, with elevated choline (Cho) values revealing cell proliferation and density, and the glial metabolite creatine (Cr) representing high-energy storage. This study investigates metabolite changes within the tumor voxel of maximal rCBV value (rCBVmax). Anatomically coregistered parameter maps of rCBV, Cho and Cr were evaluated in 36 patients with primary or recurrent WHO grade III or IV gliomas. Apart from Cho and Cr values within the voxel of rCBVmax (Choperf, Crperf), the maximal Cho and Cr values of the tumor tissue were recorded (Chomax, Crmax). The correlation between these parameters was analyzed with Spearman’s rho test while a binomial test was performed to check whether Chomax = Choperf and Crmax = Crperf. We found that, in 29 of the 36 patients, neither Cho nor Cr had their maxima in the voxel of rCBVmax (Choperf, Crperf < Chomax, Crmax, P < 0.001). However, Choperf was highly correlated with Chomax (r = 0.76, P < 0.001) and Crperf with Crmax (r = 0.47, P < 0.001). Further Choperf correlated with Crperf (r = 0.55, P < 0.001). Neither of the spectroscopic parameters (Chomax, Crmax, Choperf, Crperf,) correlated with rCBVmax. In conclusion, in WHO grade III and IV gliomas the voxel with maximal rCBV often differs from the voxel with the maximal Cho and Cr, indicating the spatial divergence between neovascularization and tumor cell proliferation, cell density and glial processes. However, tCho and tCr changes within the area of neovascularization are positively correlated with the maximal increase within the tumor tissue. These results demonstrate aspects of regional tumor heterogeneity as characterized by different MR modalities that, apart from histopathological grading might be crucial for neurosurgical biopsy as well as for antiangiogenetic and future molecular therapies.