Abstract

Distinguishing tumors from normal brain cells is important but challenging in glioma surgery due to the lack of clear interfaces between the two. The ability of label-free third harmonic generation (THG) microscopy in combination with automated image analysis to quantitatively detect glioma infiltration in fresh, unprocessed tissue in real time is assessed. The THG images reveal increased cellularity in grades II–IV glioma samples from 23 patients, as confirmed by subsequent hematoxylin and eosin histology. An automated image quantification workflow is presented for quantitative assessment of the imaged cellularity as a reflection of the degree of glioma invasion. The cellularity is validated in three ways: 1) Quantitative comparison of THG imaging with fluorescence microscopy of nucleus-stained samples demonstrates that THG reflects the true tissue cellularity. 2) Thresholding of THG cellularity differentiates normal brain from glioma infiltration, with 96.6% sensitivity and 95.5% specificity, in nearly perfect (93%) agreement with pathologists. 3) In one patient, a good correlation between THG cellularity and preoperative magnetic resonance and positron emission tomography imaging is demonstrated. In conclusion, quantitative real-time THG microscopy accurately assesses glioma infiltration in ex vivo human brain samples, and therefore holds strong potential for improving the accuracy of surgical resection.
Original languageEnglish
Article number1900163
JournalAdvanced Science
Volume6
Issue number11
DOIs
Publication statusPublished - 5 Jun 2019

Cite this

@article{d4d2ab7f3e44449d99a84cc8ab61f239,
title = "Quantitative Third Harmonic Generation Microscopy for Assessment of Glioma in Human Brain Tissue",
abstract = "Distinguishing tumors from normal brain cells is important but challenging in glioma surgery due to the lack of clear interfaces between the two. The ability of label-free third harmonic generation (THG) microscopy in combination with automated image analysis to quantitatively detect glioma infiltration in fresh, unprocessed tissue in real time is assessed. The THG images reveal increased cellularity in grades II–IV glioma samples from 23 patients, as confirmed by subsequent hematoxylin and eosin histology. An automated image quantification workflow is presented for quantitative assessment of the imaged cellularity as a reflection of the degree of glioma invasion. The cellularity is validated in three ways: 1) Quantitative comparison of THG imaging with fluorescence microscopy of nucleus-stained samples demonstrates that THG reflects the true tissue cellularity. 2) Thresholding of THG cellularity differentiates normal brain from glioma infiltration, with 96.6{\%} sensitivity and 95.5{\%} specificity, in nearly perfect (93{\%}) agreement with pathologists. 3) In one patient, a good correlation between THG cellularity and preoperative magnetic resonance and positron emission tomography imaging is demonstrated. In conclusion, quantitative real-time THG microscopy accurately assesses glioma infiltration in ex vivo human brain samples, and therefore holds strong potential for improving the accuracy of surgical resection.",
keywords = "glioma infiltration, label-free microscopy, neuropathology, neurosurgery, third harmonic generation",
author = "Zhiqing Zhang and {de Munck}, {Jan C.} and Niels Verburg and Rozemuller, {Annemieke J.} and Willem Vreuls and Pinar Cakmak and {van Huizen}, {Laura M. G.} and Sander Idema and Eleonora Aronica and {de Witt Hamer}, {Philip C.} and Pieter Wesseling and Groot, {Marie Louise}",
year = "2019",
month = "6",
day = "5",
doi = "10.1002/advs.201900163",
language = "English",
volume = "6",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "11",

}

Quantitative Third Harmonic Generation Microscopy for Assessment of Glioma in Human Brain Tissue. / Zhang, Zhiqing; de Munck, Jan C.; Verburg, Niels; Rozemuller, Annemieke J.; Vreuls, Willem; Cakmak, Pinar; van Huizen, Laura M. G.; Idema, Sander; Aronica, Eleonora; de Witt Hamer, Philip C.; Wesseling, Pieter; Groot, Marie Louise.

In: Advanced Science, Vol. 6, No. 11, 1900163, 05.06.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Quantitative Third Harmonic Generation Microscopy for Assessment of Glioma in Human Brain Tissue

AU - Zhang, Zhiqing

AU - de Munck, Jan C.

AU - Verburg, Niels

AU - Rozemuller, Annemieke J.

AU - Vreuls, Willem

AU - Cakmak, Pinar

AU - van Huizen, Laura M. G.

AU - Idema, Sander

AU - Aronica, Eleonora

AU - de Witt Hamer, Philip C.

AU - Wesseling, Pieter

AU - Groot, Marie Louise

PY - 2019/6/5

Y1 - 2019/6/5

N2 - Distinguishing tumors from normal brain cells is important but challenging in glioma surgery due to the lack of clear interfaces between the two. The ability of label-free third harmonic generation (THG) microscopy in combination with automated image analysis to quantitatively detect glioma infiltration in fresh, unprocessed tissue in real time is assessed. The THG images reveal increased cellularity in grades II–IV glioma samples from 23 patients, as confirmed by subsequent hematoxylin and eosin histology. An automated image quantification workflow is presented for quantitative assessment of the imaged cellularity as a reflection of the degree of glioma invasion. The cellularity is validated in three ways: 1) Quantitative comparison of THG imaging with fluorescence microscopy of nucleus-stained samples demonstrates that THG reflects the true tissue cellularity. 2) Thresholding of THG cellularity differentiates normal brain from glioma infiltration, with 96.6% sensitivity and 95.5% specificity, in nearly perfect (93%) agreement with pathologists. 3) In one patient, a good correlation between THG cellularity and preoperative magnetic resonance and positron emission tomography imaging is demonstrated. In conclusion, quantitative real-time THG microscopy accurately assesses glioma infiltration in ex vivo human brain samples, and therefore holds strong potential for improving the accuracy of surgical resection.

AB - Distinguishing tumors from normal brain cells is important but challenging in glioma surgery due to the lack of clear interfaces between the two. The ability of label-free third harmonic generation (THG) microscopy in combination with automated image analysis to quantitatively detect glioma infiltration in fresh, unprocessed tissue in real time is assessed. The THG images reveal increased cellularity in grades II–IV glioma samples from 23 patients, as confirmed by subsequent hematoxylin and eosin histology. An automated image quantification workflow is presented for quantitative assessment of the imaged cellularity as a reflection of the degree of glioma invasion. The cellularity is validated in three ways: 1) Quantitative comparison of THG imaging with fluorescence microscopy of nucleus-stained samples demonstrates that THG reflects the true tissue cellularity. 2) Thresholding of THG cellularity differentiates normal brain from glioma infiltration, with 96.6% sensitivity and 95.5% specificity, in nearly perfect (93%) agreement with pathologists. 3) In one patient, a good correlation between THG cellularity and preoperative magnetic resonance and positron emission tomography imaging is demonstrated. In conclusion, quantitative real-time THG microscopy accurately assesses glioma infiltration in ex vivo human brain samples, and therefore holds strong potential for improving the accuracy of surgical resection.

KW - glioma infiltration

KW - label-free microscopy

KW - neuropathology

KW - neurosurgery

KW - third harmonic generation

UR - http://www.scopus.com/inward/record.url?scp=85063917824&partnerID=8YFLogxK

U2 - 10.1002/advs.201900163

DO - 10.1002/advs.201900163

M3 - Article

VL - 6

JO - Advanced Science

JF - Advanced Science

SN - 2198-3844

IS - 11

M1 - 1900163

ER -