Figure 1.

Multimodal IVM-MRI imaging to visualize dynamics of the brain TME over multiple weeks

(A) Schematic showing the experimental design used to investigate TME dynamics during tumor progression and in response to BLZ945 treatment in Ink4a/Arf-deficient and p53-deficient GBMs. Mice were imaged weekly to assess tumor growth by MRI and to monitor TME dynamics by IVM. The dashed gray line indicates a representative tumor growth curve of a GBM-bearing mouse.

(B) In order to obtain visual access to the brain tumor and perform multimodal IVM-MRI, a CIW was surgically implanted in the mouse skull at the site of tumor induction (left). The incorporation of metal-free components enabled the concomitant use of MRI (right). The dashed orange circle indicates the position of the CIW on the top of the tumor (green).

(C) Representative example of longitudinal multimodal imaging of the same mouse by MRI and IVM before and after treatment with the CSF-1R inhibitor BLZ945 (treatment initiated at day 0). The upper MRI images show the anatomical location of the tumor (green line) and the projection of the CIW position (dashed orange circle). The lower panels show matching two-photon microscopy tile scans visualizing the dynamics of GFP-positive cancer cells (green) and brain-resident TAMs (red) through the CIW (dashed orange circle). The blue squares indicate an example of the location of two FOVs that were used to record time-lapses throughout the duration of the longitudinal IVM-MRI imaging experiment. Scale bars: 400 μm. Brain silhouette in (B) was sourced from https://scidraw.io/. See also Figures S1 and S2.