Quantitative live imaging reveals region-dependent medulloblastoma disseminationin the zebrafish brain

Medulloblastoma, the most common malignant pediatric brain tumor, often relapses due to tumor spread within the central nervous system. In this study, human medulloblastoma cells were orthotopically transplanted into larval zebrafish to observe the dynamics of tumor dissemination in vivo. The researchers used high-resolution confocal imaging to track individual xenografts over time.

Among the tumors, those originating from the hindbrain showed particularly robust dissemination, spreading into the developing cerebellum in 81.5% of larvae, compared to only a fraction for tumors originating from the forebrain or midbrain. These disseminating cells extended along brain-surface and leptomeningeal-like regions, frequently associating with the cerebral vasculature.

The study also employed quantitative analysis to measure various parameters of tumor growth and spatial complexity, including tumor area, perimeter, compactness, convex hull area, and fractal dimension. These metrics captured the changes in growth and spatial behavior of the tumors over time. Notably, the drug dasatinib showed a reducing effect on tumor expansion and dissemination-related features in a concentration-dependent manner.

However, higher doses of the drug revealed host toxicity. Overall, this research establishes a robust in vivo model for studying medulloblastoma dissemination and assessing therapeutic responses in a zebrafish brain model.