Glioma are highly malignant brain tumors that depend on neoangiogenesis. Currently, various antiangiogenic treatment regimes are in clinical trials for glioma treatment. Until now direct mapping of the tumor vasculature has been difficult. Novel imaging methods are needed to assess vascularization status, treatment effects and disease progression. We present a combined magnetic resonance and ultramicroscopy (UM) vascularization “tool kit” to study neoangiogenesis in mouse glioma models1.

100.000 Gl261 cells were engrafted incranially in black6 wildtype mice. For the S24 glioma model, 50.000 S24:td-tomato cells (stably transduced by lentivirus) were transplanted orthotopically in 8-10 week old male NMRI nude mice (Charles River, Sulzfeld, Germany, n=3 mice)2. T2* post contrast imaging at high field is used to follow vessel formation over time (9.4 T Bruker Biospin MRI scanner, 80 µm isotropic resolution)3. USPIO or Gd-DTPA are used as contrast agents for blood pool imaging. UM of post mortem cleared brains (3DISCO or FluoClearBABB...

T2* imaging after Gd or USPIO-based contrast agent administration identifies single vessels in glioma development (Fig. 1). Single arterioles and venules can be tracked over time. We find a massive ingrowth of tumor vessels following the angiogenic switch in the Gl261 glioma model (3.5-fold increase of the vascularized area within one week; p<0.05). VEGF antibody blockage inhibited neovessel formation without affecting tumor growth (p>0.05). The resolution of MR was however limited to 80 µm in our study. To further resolve the microvasculature we performed ultramicroscopy...

Combined MR-UM allows the quantification of macro- and microvessels in the two employed glioma models (Gl261 vs. S24) which exhibit different growth and angiogenesis patterns. MR-UM can be used for treatment monitoring and facilitate the pre-clinical development of more effective antiangiogenic agents. 3D MR and optical datasets can be viewed side-by-side and yield complementary information.

1. Breckwoldt M.O.*, Bode J.*, Kurz F.T., Hoffmann A., Ochs K., Ott M., Deumelandt K., Krüwel T., Schwarz D., Fischer M., Helluy X., Milford D., Kirschbaum K., Solecki G., Chiblak S., Abdollahi A., Winkler F., Wick W., Platten M., Heiland S., Bendszus M.*and Tews B.*Correlated magnetic resonance imaging and ultramicroscopy (MR-UM) is a tool kit to assess the dynamics of glioma angiogenesis. eLIFE. Accepted, *equal contribution 2.Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J, et al. Brain tumour cells interconnect to...