am9b00227_si_001.pdf (1.09 MB)
Surface-Enhanced Resonance Raman Scattering-Guided Brain Tumor Surgery Showing Prognostic Benefit in Rat Models
journal contribution
posted on 2019-03-21, 00:00 authored by Limei Han, Wenjia Duan, Xinwei Li, Cong Wang, Ziyi Jin, Yuting Zhai, Chong Cao, Luo Chen, Wenjing Xu, Ying Liu, Yong-Yan Bi, Jianfeng Feng, Ying Mao, Qi Yue, Xiao-Yong Zhang, Cong LiGlioma is the most
frequent form of malignant brain tumors. Surgical debulking is a major
strategy for glioma treatment. However, there is a great challenge
for the neurosurgeons to intraoperatively identify the true margins
of glioma because of its infiltrative nature. Tumor residues or microscopic
satellite foci left in the resection bed are the main reasons leading
to early recurrence as well as poor prognosis. In this study, a surface-enhanced
resonance Raman scattering (SERRS) probe was developed to intraoperatively
guide glioma resection. In this probe, molecular reporters with absorptive
maxima at the near-infrared wavelength range were covalently functionalized
on the surface of gold nanostars. This SERRS probe demonstrated an
ultrahigh sensitivity with a detection limit of 5.0 pM in aqueous
solution. By the development of glioma xenografts in a mouse dorsal
skin window chamber, extravasation of this probe from leaky tumor
vasculature as functions of time and distance to tumor boundary was
investigated. Importantly, the invasive margin of the tumor xenograft
was demarcated by this probe with a high signal-to-background ratio.
Preoperative magnetic resonance imaging (MRI) first defined the position
of orthotopic glioma xenografts in the brain of rat models, and the
craniotomy plan was designed. The brain tumor was then excised intraoperatively
step-by-step with the assistance of a handheld Raman scanner till
the Raman signals of the probe completely disappeared in the resection
bed. Notably, longitudinal MRI showed that SERRS-guided surgery significantly
reduced the tumor recurrence rate and improved the overall survival
of rat models compared with the white light-guided surgery. Overall,
this work demonstrates the prognostic benefit of SERRS-guided glioma
surgery in animal models. Because delineation of tumor-invasive margins
is a common challenge faced by the surgeons, this SERRS probe with
a picomolar detection limit holds the promise in improving the surgical
outcome of different types of infiltrated tumors.
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Keywords
surface-enhanced resonance RamanRat Models GliomaMRISERRS probeintraoperatively guide glioma resectionresection bedpicomolar detection limitmouse dorsal skin window chamberSurface-Enhanced Resonance Raman Scattering-Guided Brain Tumor SurgerySERRS-guided glioma surgerytumor recurrence raterat modelsnear-infrared wavelength rangeorthotopic glioma xenografts
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