Figure 1. Triple-modality MPR concept.

Top: MPRs are injected intravenously into a mouse bearing an orthotopic brain tumor. As the nanoparticles circulate in the blood stream, they diffuse through the disrupted blood-brain-barrier and are then sequestered and retained by the tumor. The MPRs are too large to cross the intact blood-brain-barrier and therefore cannot accumulate in healthy brain. Bottom: Concept of proposed eventual clinical use. Detectability by MRI allows pre-operative detection and surgical planning. Due to the retention of the probe, only one injection is necessary and the probe can be detected in the tumor during surgery several days later. Photoacoustic imaging with its relatively high resolution and deep tissue penetration is then able to guide bulk tumor resection intra-operatively. Raman imaging with its ultrahigh sensitivity and spatial resolution can then be used to remove residual microscopic tumor burden. Resected specimen can subsequently be examined with a Raman probe ex vivo to verify clear margins.