Neuropathological interpretation of stimulated Raman histology images of brain and spine tumors: part B

Jakob Straehle,Rainer Schmelzeisen,Daniel Erny,Boris Mizaikoff,Marco Prinz,Volker Arnd Coenen,Dieter Henrik Heiland,Nicolas Neidert,Vlad Sacalean,David Steybe,Jürgen Beck,Oliver Schnell,Andreas Vlachos,Amir El Rahal,Peter Christoph Reinacher

doi:10.1007/s10143-021-01711-1

Abstract

Intraoperative histopathological examinations are routinely performed to provide neurosurgeons with information about the entity of tumor tissue. Here, we quantified the neuropathological interpretability of stimulated Raman histology (SRH) acquired using a Raman laser imaging system in a routine clinical setting without any specialized training or prior experience. Stimulated Raman scattering microscopy was performed on 117 samples of pathological tissue from 73 cases of brain and spine tumor surgeries. A board-certified neuropathologist — novice in the interpretation of SRH — assessed image quality by scoring subjective tumor infiltration and stated a diagnosis based on the SRH images. The diagnostic accuracy was determined by comparison to frozen hematoxylin–eosin (H&E)-stained sections and the ground truth defined as the definitive neuropathological diagnosis. The overall SRH imaging quality was rated high with the detection of tumor cells classified as inconclusive in only 4.2% of all images. The accuracy of neuropathological diagnosis based on SRH images was 87.7% and was non-inferior to the current standard of fast frozen H&E-stained sections (87.3 vs. 88.9%, p = 0.783). We found a substantial diagnostic correlation between SRH-based neuropathological diagnosis and H&E-stained frozen sections (κ = 0.8). The interpretability of intraoperative SRH imaging was demonstrated to be equivalent to the current standard method of H&E-stained frozen sections. Further research using this label-free innovative alternative vs. conventional staining is required to determine to which extent SRH-based intraoperative decision-making can be streamlined in order to facilitate the advancement of surgical neurooncology.

Highlights

State-of-the-art intraoperative histopathological diagnosis in a neurosurgical setting is routinely performed using fast frozen section and H&E staining. This technique is limited by the amount of samples that can be processed in real-time in a routine clinical setting, as for a single sample there is a delay of 15–30 min from tissue removal to histopathological diagnosis
We report the first experience at our institution with the neuropathological interpretation of ex vivo stimulated Raman histology (SRH) images, conducted in a routine clinical scenario without any specialized training
Compared to other novel tools for intraoperative histological examination in vivo such as fluorescein-assisted confocal laser endomicroscopy [8, 14] and hand-held Raman spectroscopy probes [3, 10], the ex vivo SRH approach described here is limited by the fact that the tissue must be removed

Summary

Introduction

State-of-the-art intraoperative histopathological diagnosis in a neurosurgical setting is routinely performed using fast frozen section and H&E staining. This technique is limited by the amount of samples that can be processed in real-time in a routine clinical setting, as for a single sample there is a delay of 15–30 min from tissue removal to histopathological diagnosis. An exhaustive histopathological sampling of tumor margins to assist neurosurgical decision-making in real-time is currently not available during routine tumor resections. Compared to conventional H&E staining, SRH has several advantages such as the ease of use, the time of data processing, and the digital nature of the obtained images. Digitalization allows remote consultations and image processing using automated classifiers and machine learning routines [9]

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