In vivo characterization and analysis of glioblastoma at different stages using multiscale photoacoustic molecular imaging

Simultaneous spatio-temporal description of tumor microvasculature, blood-brain barrier, and immune activity is pivotal to understanding the evolution mechanisms of highly aggressive glioblastoma, one of the most common primary brain tumors in adults. However, the existing intravital imaging modalities are still difficult to achieve it in one step. Here, we present a dual-scale multi-wavelength photoacoustic imaging approach cooperative with/ without unique optical dyes to overcome this dilemma. Label-free photoacoustic imaging depicted the multiple heterogeneous features of neovascularization in tumor progression. In combination with classic Evans blue assay, the microelectromechanical system based photoacoustic microscopy enabled dynamic quantification of BBB dysfunction. Concurrently, using self-fabricated targeted protein probe (alpha CD11b-HSA@A1094) for tumor-associated myeloid cells, unparalleled imaging contrast of cells infiltration associated with tumor progression was visualized by differential photoacoustic imaging in the second near-infrared window at dual scale. Our photoacoustic imaging approach has great potential for tumor-immune microenvironment visualization to sys-tematically reveal the tumor infiltration, heterogeneity, and metastasis in intracranial tumors.

Automated summary

Simultaneously describing the tumor microvasculature, blood-brain barrier, and immune activity is crucial for understanding the evolution mechanisms of highly aggressive glioblastoma. However, current imaging modalities are not able to achieve this in one step. In this study, a dual-scale multi-wavelength photoacoustic imaging approach was presented to overcome this challenge. This approach has the potential to visualize the tumor-immune microenvironment and reveal tumor infiltration, heterogeneity, and metastasis in intracranial tumors.