title: A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle.
abstract: The difficulty in delineating brain tumor margins is a major obstacle in the path toward better outcomes for patients with brain tumors. 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-Raman imaging nanoparticle (termed here MPR nanoparticle) can accurately help delineate the margins of brain tumors in living mice both preoperatively and intraoperatively. The MPRs were detected by all three modalities with at least a picomolar sensitivity both in vitro and in living mice. Intravenous injection of MPRs into glioblastoma-bearing mice led to MPR accumulation and retention by the tumors, with no MPR accumulation in the surrounding healthy tissue, allowing for a noninvasive tumor delineation using all three modalities through the intact skull. Raman imaging allowed for guidance of intraoperative tumor resection, and a histological correlation validated that Raman imaging was accurately delineating the brain tumor margins. This new triple-modality-nanoparticle approach has promise for enabling more accurate brain tumor imaging and resection.
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, California, USA.
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Kircher
authors.forename: Adam
authors.initials: A
authors.lastname: de la Zerda
authors.forename: Jesse V
authors.initials: JV
authors.lastname: Jokerst
authors.forename: Cristina L
authors.initials: CL
authors.lastname: Zavaleta
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kempen
authors.forename: Erik
authors.initials: E
authors.lastname: Mittra
authors.forename: Ken
authors.initials: K
authors.lastname: Pitter
authors.forename: Ruimin
authors.initials: R
authors.lastname: Huang
authors.forename: Carl
authors.initials: C
authors.lastname: Campos
authors.forename: Frezghi
authors.initials: F
authors.lastname: Habte
authors.forename: Robert
authors.initials: R
authors.lastname: Sinclair
authors.forename: Cameron W
authors.initials: CW
authors.lastname: Brennan
authors.forename: Ingo K
authors.initials: IK
authors.lastname: Mellinghoff
authors.forename: Eric C
authors.initials: EC
authors.lastname: Holland
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D061088:Photoacoustic Techniques / Q000379:methods*; D013059:Spectrum Analysis, Raman / Q000379:methods*