Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma
Surgical management of basal cell carcinoma (BCC) typically involves surgical excision with post-operative margin assessment using the bread-loafing technique; or gold-standard Mohs micrographic surgery (MMS), where margins are iteratively examined for residual cancer after tumour removal, with addi...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/178985 |
| _version_ | 1826116659512868864 |
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| author | Tan, Yingrou Zhang, Yuning Li, Jackson Liang Yao Chia, Hui Yi Tan, Melissa Wee Ping Ebel, Gernot Leong, Keith Weng Kit Lim, Eiffer Ying Qi Chong, Kylia Kai Ling Lee, Bernett Teck Kwong Ng, Lai Guan Tey, Hong Liang |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Tan, Yingrou Zhang, Yuning Li, Jackson Liang Yao Chia, Hui Yi Tan, Melissa Wee Ping Ebel, Gernot Leong, Keith Weng Kit Lim, Eiffer Ying Qi Chong, Kylia Kai Ling Lee, Bernett Teck Kwong Ng, Lai Guan Tey, Hong Liang |
| author_sort | Tan, Yingrou |
| collection | NTU |
| description | Surgical management of basal cell carcinoma (BCC) typically involves surgical excision with post-operative margin assessment using the bread-loafing technique; or gold-standard Mohs micrographic surgery (MMS), where margins are iteratively examined for residual cancer after tumour removal, with additional excisions performed upon detecting residual tumour at margins. There is limited sampling of resection margins with bread loafing, with detection of positive margins 44% of the time using 2 mm intervals. To resolve this, we have developed three-dimensional (3D) Tissue Imaging for: (1) complete examination of cancer margins and (2) detection of tumour proximity to nerves and blood vessels. 3D Tissue optical clearing with a light sheet imaging protocol was developed for margin assessment in two datasets assessed by two independent evaluators: (1) 48 samples from 29 patients with varied BCC subtypes, sizes and pigmentation levels; (2) 32 samples with matching Mohs' surgeon reading of tumour margins using two-dimensional haematoxylin & eosin-stained sections. The 3D Tissue Imaging protocol permits a complete examination of deeper and peripheral margins. Two independent evaluators achieved negative predictive values of 92.3% and 88.24% with 3D Tissue Imaging. Images obtained from 3D Tissue Imaging recapitulates histological features of BCC, such as nuclear crowding, palisading and retraction clefting and provides a 3D context for recognising normal skin adnexal structures. Concurrent immunofluorescence labelling of nerves and blood vessels allows visualisation of structures closer to tumour-positive regions, which may have a higher risk for neural and vascular infiltration. Together, this method provides more information in a 3D spatial context, enabling better cancer management by clinicians. |
| first_indexed | 2024-10-01T04:14:57Z |
| format | Journal Article |
| id | ntu-10356/178985 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:14:57Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1789852024-07-21T15:38:02Z Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma Tan, Yingrou Zhang, Yuning Li, Jackson Liang Yao Chia, Hui Yi Tan, Melissa Wee Ping Ebel, Gernot Leong, Keith Weng Kit Lim, Eiffer Ying Qi Chong, Kylia Kai Ling Lee, Bernett Teck Kwong Ng, Lai Guan Tey, Hong Liang Lee Kong Chian School of Medicine (LKCMedicine) Singapore Immunology Network, A*STAR National Skin Centre Skin Research Institute of Singapore, A*STAR Medicine, Health and Life Sciences Basal cell carcinoma Light sheet microscopy Surgical management of basal cell carcinoma (BCC) typically involves surgical excision with post-operative margin assessment using the bread-loafing technique; or gold-standard Mohs micrographic surgery (MMS), where margins are iteratively examined for residual cancer after tumour removal, with additional excisions performed upon detecting residual tumour at margins. There is limited sampling of resection margins with bread loafing, with detection of positive margins 44% of the time using 2 mm intervals. To resolve this, we have developed three-dimensional (3D) Tissue Imaging for: (1) complete examination of cancer margins and (2) detection of tumour proximity to nerves and blood vessels. 3D Tissue optical clearing with a light sheet imaging protocol was developed for margin assessment in two datasets assessed by two independent evaluators: (1) 48 samples from 29 patients with varied BCC subtypes, sizes and pigmentation levels; (2) 32 samples with matching Mohs' surgeon reading of tumour margins using two-dimensional haematoxylin & eosin-stained sections. The 3D Tissue Imaging protocol permits a complete examination of deeper and peripheral margins. Two independent evaluators achieved negative predictive values of 92.3% and 88.24% with 3D Tissue Imaging. Images obtained from 3D Tissue Imaging recapitulates histological features of BCC, such as nuclear crowding, palisading and retraction clefting and provides a 3D context for recognising normal skin adnexal structures. Concurrent immunofluorescence labelling of nerves and blood vessels allows visualisation of structures closer to tumour-positive regions, which may have a higher risk for neural and vascular infiltration. Together, this method provides more information in a 3D spatial context, enabling better cancer management by clinicians. National Medical Research Council (NMRC) National Research Foundation (NRF) Submitted/Accepted version Y.T. and H.L.T. are supported by the Clinician Scientist Awards(NMRC/CSA-INV/0023/2017 and CSAINV20nov- 0003) and Y.T. issupported by the Centre Grant Programme (CG21APR1018) fromthe National Medical Research Council of Singapore. Access tothe Ultramicroscope II was made possible thanks to the A*STAR Microscopy Platform which is supported by the HMBS IAF-PP grant(H1701a0004) and the National Research Foundation's SharedInfrastructure Support grant for SingaScope—a Singapore-wide microscopy infrastructure network (NRF2017_SISFP10) 2024-07-15T06:41:40Z 2024-07-15T06:41:40Z 2024 Journal Article Tan, Y., Zhang, Y., Li, J. L. Y., Chia, H. Y., Tan, M. W. P., Ebel, G., Leong, K. W. K., Lim, E. Y. Q., Chong, K. K. L., Lee, B. T. K., Ng, L. G. & Tey, H. L. (2024). Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma. Experimental Dermatology, 33(6), e15097-. https://dx.doi.org/10.1111/exd.15097 0906-6705 https://hdl.handle.net/10356/178985 10.1111/exd.15097 38840370 2-s2.0-85195340882 6 33 e15097 en NMRC/CSA-INV/0023/2017 CSAINV20nov- 0003) CG21APR1018 H1701a0004 NRF2017_SISFP10 Experimental Dermatology © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at http://doi.org/10.1111/exd.15097. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Basal cell carcinoma Light sheet microscopy Tan, Yingrou Zhang, Yuning Li, Jackson Liang Yao Chia, Hui Yi Tan, Melissa Wee Ping Ebel, Gernot Leong, Keith Weng Kit Lim, Eiffer Ying Qi Chong, Kylia Kai Ling Lee, Bernett Teck Kwong Ng, Lai Guan Tey, Hong Liang Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma |
| title | Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma |
| title_full | Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma |
| title_fullStr | Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma |
| title_full_unstemmed | Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma |
| title_short | Visualising cancer in 3D: 3-Dimensional tissue imaging for management of cutaneous basal cell carcinoma |
| title_sort | visualising cancer in 3d 3 dimensional tissue imaging for management of cutaneous basal cell carcinoma |
| topic | Medicine, Health and Life Sciences Basal cell carcinoma Light sheet microscopy |
| url | https://hdl.handle.net/10356/178985 |
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