A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle

Abstract

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.

Application of nanoparticles in cancer detection by Raman scattering based techniques

“…In response to this demand, Kircher et al applied innovative triple modality MRI, photoacoustic imaging, and Raman imaging nanoparticle (MPR nanoparticle) which can precisely depict the interface of brain tumors in living mice [87]. A combination of tumor localization, the macroscopic delineation ability of MRI, high spatial resolution, three-dimensional photoacoustic imaging, high sensitivity, high specificity and the high resolution surface imaging potential of RS produces a powerful and accurate method for delineating tumor margins.…”

“…The particles then were modified with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid in complex with Gd 3+ ((DOTA)-Gd 3+ ) using a maleimide linkage (maleimide-DOTA-Gd). By using this method, the authors subsequently demonstrated not only its ability to yield high resolution brain tumor imaging and visualization of the margins of an invasive tumor, but also its use intraoperatively for brain tumor resection and to check unremoved malignant remainders as a probe [85,87]. Diaz and his coworker applied transcranial focused ultrasound to achieve maximal surgical resection and facilitate passing of a multifunctional designed gold nanoparticle (this was created by them to label and track glioblastoma cells through blood brain barrier (BBB) which serves as a barrier to nanoparticle transition from the vascular lumen to the brain parenchyma).…”

High-resolution contrast-enhanced optical coherence tomography in mice retinae

“…Following our development of numerous imaging agents for specifically labeling target proteins of interest in living mice, [3][4][5][6] we recently designed a new OCT-based imaging system for the retina by developing nanoparticles based on gold nanorods (GNRs), which produce a strong OCT signal. GNRs have been recently used to enhance OCT signals in tissue mimicking phantoms, [7][8][9][10][11] excised porcine eyes, 8 vitreous of mice eyes, 12 anterior chambers and cornea of mice eyes, 13 and in mouse mammary tumors.…”

Novel Quantitative Techniques in Hybrid (PET-MR) Imaging of Brain Tumors

“…In a recent study, combining MR, photoacoustics, and Raman imaging has been shown to provide promising results in identifying brain tumor margins in animal models. 2 PET-MR has shown to be superior to CT, PET, or MR alone, mainly because it allows for molecular, anatomic, and functional imaging with uncompromised quality. 3 Tumor delineation using the PET component with the help of highresolution MR has proved to be advantageous compared with the use of a single modality, given the complementary information provided by each one.…”