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Theranostics 2019; 9(10):2827-2842. doi:10.7150/thno.33823 This issue Cite

Research Paper

Dual-modality optical diagnosis for precise in vivo identification of tumors in neurosurgery

Mingyu Zhu^1#, Wei Chang^1#, Linkai Jing^2#, Yingwei Fan¹, Ping Liang², Xinran Zhang¹, Guihuai Wang^2✉, Hongen Liao^1✉

1. Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China
2. Department of Neurosurgery, Beijing Tsinghua Changgung Hospital, Beijing 102218, China
^# These authors contributed equally to this manuscript.

✉ Corresponding authors: Prof. Hongen Liao, Email: liaoedu.cn and Dr. Guihuai Wang, Email: youngneurosurgeoncom

Abstract

In neurosurgery, the precise diagnosis and treatment of tumor diseases are challenging to realize. Current clinical diagnoses lack fast and accurate intraoperative information. Therefore, the development of new methods and techniques to assist neurosurgeons intraoperatively is necessary. Optical diagnosis is a promising method to provide accurate information about biological tissues in a short time. Therefore, in this study, we proposed a dual-modality optical diagnostic method through point-to-face registration fusion in the optical system. We incorporated quantitative autofluorescence spectroscopy and optical coherence tomography (OCT) and evaluated our methods in an animal model.

Methods: A mouse model consisting of 16 nude mice was built by injecting the mouse brains with human glioma cells. Preoperative bioluminescence imaging was used to evaluate the growth states of tumors and locate the tumor sites. Quantitative autofluorescence spectroscopy, which provided local biochemical information with single-point detection, and OCT, which provided relatively global structural information with en face mapping scanning, were combined using the point-to-face registration fusion method to provide precise diagnostic information for identifying the brain tumors. Postoperative pathology was performed to evaluate the sensitivity and specificity of optical diagnosis.

Results: Ex vivo quantitative autofluorescence spectroscopy and OCT imaging were first performed in eight mice to acquire the optimal measuring parameters for tumor staging and identification. We then performed in vivo quantitative autofluorescence spectroscopy and OCT imaging. The results showed that tumor staging could be realized through quantitative autofluorescence spectroscopy, and fusion images could be used to precisely identify tumors. The autofluorescence spectral map, OCT en face map, and fused diagnostic map had average sensitivities of 91.7%, 86.1%, and 95.9% and specificities of 93.2%, 96.0%, and 88.7%, respectively, for tumor identification.

Conclusion: The dual-modality optical point-to-face registration fusion method and system we proposed could provide both biochemical information and structural information. The in vivo experimental results validated that the sensitivity (95.9%) of the fused map was higher than that of either single diagnostic modality (86.1% or 91.7%). Tumor staging was realized through quantitative autofluorescence spectroscopy. The proposed method will be applicable to future intelligent theranostic systems and improve many clinical neurosurgeries.

Keywords: dual-modality optical diagnosis, quantitative autofluorescence spectroscopy, optical coherence tomography, neurosurgery, brain tumor

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