Detection of glioma infiltration at the tumor margin using quantitative stimulated Raman scattering histology

Melike Pekmezci,Mitchel S Berger,Ramin A Morshed,Pranathi Chunduru,Manish K Aghi,Balaji Pandian,Tarik Tihan,Emily A Sloan,Javier E Villanueva-Meyer,Shawn L Hervey-Jumper,Jacob Young,Annette M Molinaro

doi:10.1038/s41598-021-91648-8

Abstract

In the management of diffuse gliomas, the identification and removal of tumor at the infiltrative margin remains a central challenge. Prior work has demonstrated that fluorescence labeling tools and radiographic imaging are useful surgical adjuvants with macroscopic resolution. However, they lose sensitivity at the tumor margin and have limited clinical utility for lower grade histologies. Fiber-laser based stimulated Raman histology (SRH) is an optical imaging technique that provides microscopic tissue characterization of unprocessed tissues. It remains unknown whether SRH of tissues taken from the infiltrative glioma margin will identify microscopic residual disease. Here we acquired glioma margin specimens for SRH, histology, and tumor specific tissue characterization. Generalized linear mixed models were used to evaluate agreement. We find that SRH identified residual tumor in 82 of 167 margin specimens (49%), compared to IHC confirming residual tumor in 72 of 128 samples (56%), and H&E confirming residual tumor in 82 of 169 samples (49%). Intraobserver agreements between all 3 modalities were confirmed. These data demonstrate that SRH detects residual microscopic tumor at the infiltrative glioma margin and may be a promising tool to enhance extent of resection.

Highlights

In the management of diffuse gliomas, the identification and removal of tumor at the infiltrative margin remains a central challenge
We examined glioma samples obtained from infiltrative tumor margins in order to determine whether stimulated Raman histology (SRH) may identify microscopic residual disease
Each tumor margin section was sectioned for hematoxylin and eosin (H&E) (Fig. 1E–H), and IHC using either p53 (Fig. 1I–L) or IDH1 (Fig. 1M–P), with each sample scored for the presence or absence of tumor

Summary

Introduction

In the management of diffuse gliomas, the identification and removal of tumor at the infiltrative margin remains a central challenge. Fiber-laser based stimulated Raman histology (SRH) is an optical imaging technique that provides microscopic tissue characterization of unprocessed tissues It remains unknown whether SRH of tissues taken from the infiltrative glioma margin will identify microscopic residual disease. Intraobserver agreements between all 3 modalities were confirmed These data demonstrate that SRH detects residual microscopic tumor at the infiltrative glioma margin and may be a promising tool to enhance extent of resection. Stimulated Raman scattering histology (SRH) is a non-destructive, rapid, label-free technique that provides imaging of unprocessed surgical tissues at microscopic r esolutions[9] It relies on the Raman effect, which occurs when light temporarily changes a bond’s polarizability and causes a change in the vibrational frequency leading to a change in the energy of the scattered photon. While the analysis of postmortem tissues has suggested the ability of SRH to detect glioma infiltration with high sensitivity and specificity[10,11], there are no data assessing SRH within the operating room setting to quantify infiltrating tumor cells at the glioma resection cavity margins

Methods

Results

Conclusion