The vexing difficulty in delineating brain tumor margins represents a major obstacle toward better outcome of brain tumor patients. Current imaging methods are often limited by inadequate sensitivity, specificity, and spatial resolution. Here we show that a unique triple-modality Magnetic resonance imaging - Photoacoustic imaging – surface enhanced Raman scattering (SERS) nanoparticle (MPR) can accurately help delineate the margins of brain tumors in living mice both pre- and intra-operatively. The MPRs were detected by all three modalities with at least picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to specific MPR accumulation and retention by the tumors, allowing for non-invasive tumor delineation by all three modalities through the intact skull. Raman imaging allowed guidance of intra-operative tumor resection, and histological correlation validated that Raman imaging is accurately delineating brain tumor margins. This novel triple-modality nanoparticle approach holds promise to enable more accurate brain tumor imaging and resection.
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