Trimodal ultrasound imaging of brain-tumor interaction.

Brain tumors cause debilitating neurological dysfunction by disrupting brain tissue and altering local and global neurovascular activity and blood flow. Studying tumor-brain interactions in animal models is challenging, as no single method captures tumor growth, neurovascular activity, and vascular remodeling over time. Here, we overcome this limitation with a multimodal ultrasound platform combining nonlinear imaging of acoustic reporter gene-expressing tumors, functional hemodynamic imaging of brain activity, and super-resolution vascular microscopy. Applying it to a U87 glioblastoma xenograft model, we followed individual animals across their disease lifetimes. Co-registration of all three readouts linked the displacement and weakening of the lateral geniculate nucleus to the molecularly defined tumor and the vascular remodeling around it. We also identified a tumor-intrinsic hemodynamic signal, spatially uniform and uncoupled from surrounding networks, that hemodynamic imaging alone could not distinguish from displaced tissue. This platform provides a foundation for mechanistic studies in more invasive glioma models.