The Value of Optical Coherence Tomography in Glioma Surgery David Jaehyun Park, MD, PhD¹, Jae Sung Park, MD¹, Ji Sun Woo, PhD2, Seong Muk Kim, PhD2, Yong Joon Joo, PhD3, Tae Joong Eom,PhD3, Sin-Soo Jeun, MD, PhD¹ ¹Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea 2Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, Korea 3Advanced Photonics Research Institute, Gwangju Institute of Science and Technology, Gwangju, Korea David Jaehyun Park, MD, PhD Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 137-701, Korea. Tel: +82-2-2258-6353, Fax: +82-2-594-4248, E-mail: jhyun@catholic.ac.kr The Value of Optical Coherence Tomography in Glioma Surgery Slide 1 of 12

Introduction Image-guided surgery Functional neuroimaging To maximize the extent of tumor resection & minimize the surgical morbidity Image-guided surgery Intraoperative imaging Introduction A number of different methods to localize a glioma intraoperatively have been introduced. Neuronavigation, intraoperative MRI, Intraoperative sonography, and 5-aminolevulinic acid are those methods. As brain shifts after opening dura, not only localization but also detection of residual tumor have an important role in glioma surgery. Functional neuroimaging Intraoperative brain mapping The Value of Optical Coherence Tomography in Glioma Surgery Slide 2 of 12

Introduction Preoperative imaging preop navigation image Tumor at beginning of surgery preop navigation image Introduction A number of different methods to localize a glioma intraoperatively have been introduced. Neuronavigation, intraoperative MRI, Intraoperative sonography, and 5-aminolevulinic acid are those methods. As brain shifts after opening dura, not only localization but also detection of residual tumor have an important role in glioma surgery. The Value of Optical Coherence Tomography in Glioma Surgery Slide 3 of 12

Intraoperative imaging Introduction Preoperative imaging Intraoperative imaging Tomographic imaging Biological imaging Introduction A number of different methods to localize a glioma intraoperatively have been introduced. Neuronavigation, intraoperative MRI, Intraoperative sonography, and 5-aminolevulinic acid are those methods. As brain shifts after opening dura, not only localization but also detection of residual tumor have an important role in glioma surgery. The Value of Optical Coherence Tomography in Glioma Surgery Slide 4 of 12

Optical Coherence Tomography Purpose Optical Coherence Tomography Purpose In the present study, we focused on optical coherence tomography (OCT). OCT is a non-invasive and non-contact imaging technology. It allows discrimination of normal brain, solid tumor tissue, and diffusely invaded brain tumor tissue. OCT imaging allowed acquisition of 2D and 3D data arrays for multi-planar analysis of the tumor to brain interface. The Value of Optical Coherence Tomography in Glioma Surgery Slide 5 of 12

Material & Methods 150 mm Handheld OCT imaging probe In this study, we made U87-Luc human glioma cell xenograft mouse models to check the intraoperative usefulness of OCT imaging in glioma surgery. To extend OCT imaging depth, we developed an OCT system with 1300 nm wavelength range. The OCT system enhanced image contrast difference between gliomas and normal brain tissue. Fluorescence imaging and OCT imaging were done and accuracy of the images was analyzed. Moreover, hematoxylin and eosin (H&E) staining was done for each xenograft mouse model to confirm the margin of glioma. Both ex-vivo and in-vivo experiments were performed. Handheld OCT imaging probe Size : 150x50x30 mm Weight : <500g OCT scan range : 4 x 4 mm (Horizontal) x 3mm (Depth) 2D image frame rate : ~20 frame/sec The Value of Optical Coherence Tomography in Glioma Surgery Slide 6 of 12

Material & Methods Material & Methods In this study, we made U87-Luc human glioma cell xenograft mouse models to check the intraoperative usefulness of OCT imaging in glioma surgery. To extend OCT imaging depth, we developed an OCT system with 1300 nm wavelength range. The OCT system enhanced image contrast difference between gliomas and normal brain tissue. Fluorescence imaging and OCT imaging were done and accuracy of the images was analyzed. Moreover, hematoxylin and eosin (H&E) staining was done for each xenograft mouse model to confirm the margin of glioma. Both ex-vivo and in-vivo experiments were performed. The Value of Optical Coherence Tomography in Glioma Surgery Slide 7 of 12

Material & Methods Material & Methods In this study, we made U87-Luc human glioma cell xenograft mouse models to check the intraoperative usefulness of OCT imaging in glioma surgery. To extend OCT imaging depth, we developed an OCT system with 1300 nm wavelength range. The OCT system enhanced image contrast difference between gliomas and normal brain tissue. Fluorescence imaging and OCT imaging were done and accuracy of the images was analyzed. Moreover, hematoxylin and eosin (H&E) staining was done for each xenograft mouse model to confirm the margin of glioma. Both ex-vivo and in-vivo experiments were performed. The Value of Optical Coherence Tomography in Glioma Surgery Slide 8 of 12

Results Noninvasive OCT imaging of tumor In vivo 3D OCT imaging 1 mm Margins of the gliomas in xenograft mouse models were compared with both fluorescence images and OCT images. Comparing both images, OCT imaging for glioma was highly accurate. The margin of glioma was confirmed by H&E staining. The Value of Optical Coherence Tomography in Glioma Surgery Slide 9 of 12

Results Comparing maximum area by “ImageJ” : 0.43±0.69㎟ OCT Pathology Margins of the gliomas in xenograft mouse models were compared with both fluorescence images and OCT images. Comparing both images, OCT imaging for glioma was highly accurate. The margin of glioma was confirmed by H&E staining. 1 2 3 4 5 6 7 8 9 10 OCT 1.03 3.17 2.47 1.11 2.14 2.97 3.20 1.87 1.04 0.88 Pathology 1.79 3.90 3.44 1.72 2.92 3.66 2.89 1.53 2.33 0.00 The Value of Optical Coherence Tomography in Glioma Surgery Slide 10 of 12

Conclusion This technology could be a new innovative tool This feasibility study has demonstrated that intraoperative use of OCT imaging can discriminate clearly between remnant tumor and normal brain. This technology could be a new innovative tool for intraoperative imaging in glioma surgery. Conclusion This feasibility study has demonstrated that intraoperative use of OCT imaging can discriminate clearly between remnant tumor and normal brain. This technology could be a new innovative tool for intraoperative imaging in glioma surgery The Value of Optical Coherence Tomography in Glioma Surgery Slide 11 of 12

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