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1
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Yu XY, Chen J, Li LY, Chen FE, He Q. Rapid pathologic grading-based diagnosis of esophageal squamous cell carcinoma via Raman spectroscopy and a deep learning algorithm. World J Gastroenterol 2025; 31:104280. [PMID: 40248385 PMCID: PMC12001190 DOI: 10.3748/wjg.v31.i14.104280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/23/2025] [Accepted: 03/24/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer. Many molecular genetic changes are associated with its occurrence. Raman spectroscopy has become a new method for the early diagnosis of tumors because it can reflect the structures of substances and their changes at the molecular level. AIM To detect alterations in Raman spectral information across different stages of esophageal neoplasia. METHODS Different grades of esophageal lesions were collected, and a total of 360 groups of Raman spectrum data were collected. A 1D-transformer network model was proposed to handle the task of classifying the spectral data of esophageal squamous cell carcinoma. In addition, a deep learning model was applied to visualize the Raman spectral data and interpret their molecular characteristics. RESULTS A comparison among Raman spectral data with different pathological grades and a visual analysis revealed that the Raman peaks with significant differences were concentrated mainly at 1095 cm-1 (DNA, symmetric PO, and stretching vibration), 1132 cm-1 (cytochrome c), 1171 cm-1 (acetoacetate), 1216 cm-1 (amide III), and 1315 cm-1 (glycerol). A comparison among the training results of different models revealed that the 1D-transformer network performed best. A 93.30% accuracy value, a 96.65% specificity value, a 93.30% sensitivity value, and a 93.17% F1 score were achieved. CONCLUSION Raman spectroscopy revealed significantly different waveforms for the different stages of esophageal neoplasia. The combination of Raman spectroscopy and deep learning methods could significantly improve the accuracy of classification.
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Affiliation(s)
- Xin-Ying Yu
- Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Jian Chen
- Department of Cancer Prevention Center, Feicheng People’s Hospital, Feicheng 271000, Shandong Province, China
| | - Lian-Yu Li
- Department of Electronic Information and Communication, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Feng-En Chen
- Department of Chemistry, Tsinghua University, Beijing 100080, China
| | - Qiang He
- Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
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2
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Wang H, Guo S, Zhang R, Yao J, Tian W, Wang J. Feasibility Study of Label-Free Raman Spectroscopy for Parathyroid Gland Identification. JOURNAL OF BIOPHOTONICS 2025; 18:e202400220. [PMID: 39529361 DOI: 10.1002/jbio.202400220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 10/18/2024] [Accepted: 10/22/2024] [Indexed: 11/16/2024]
Abstract
We aim to evaluate the feasibility of Raman spectroscopy for parathyroid gland (PG) identification during thyroidectomy. Using a novel side-viewing handheld Raman probe, a total of 324 Raman spectra of four tissue types (i.e., thyroid, lymph node, PG, and lipid) commonly encountered during thyroidectomy were rapidly (< 3 s) acquired from 80 tissue sites (thyroid [n = 10], lymph node [n = 10], PG [n = 40], lipid [n = 20]) of 10 euthanized Wistar rats. Two partial least-squares (PLS)-discriminant analysis (DA) detection models were developed, differentiating the lipid and nonlipid (i.e., thyroid, lymph node, and PG) tissues with an accuracy of 100%, and PG, lymph node, and thyroid could be detected with an accuracy of 98.4%, 93.9%, and 95.4% respectively. This work demonstrates the feasibility of Raman spectroscopy technique for PG identification and protection during thyroidectomy at the molecular level.
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Affiliation(s)
- Hao Wang
- School of Optics and Photonics, Beijing Institute of Technology, Beijing, China
| | - Sisi Guo
- School of Optics and Photonics, Beijing Institute of Technology, Beijing, China
| | - Ruoyu Zhang
- School of Medical Technology, Beijing Institute of Technology, Beijing, China
| | - Jing Yao
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wen Tian
- Department of General Surgery, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jianfeng Wang
- School of Optics and Photonics, Beijing Institute of Technology, Beijing, China
- Leibniz Institute of Photonic Technology Jena, Jena, Germany
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3
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Vasquez DL, Kreft C, Latka I, Popp J, Mantke R, Schie IW. Colon Tumor Discrimination Combining Independent Endoscopic Probe-Based Raman Spectroscopy and Optical Coherence Tomography Modalities with Bayes Rule. Int J Mol Sci 2024; 25:13306. [PMID: 39769072 PMCID: PMC11677020 DOI: 10.3390/ijms252413306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 12/02/2024] [Accepted: 12/06/2024] [Indexed: 01/11/2025] Open
Abstract
Colorectal cancer is one of the most prevalent forms of cancer globally. The most common routine diagnostic methods are the examination of the interior of the colon during colonoscopy or sigmoidoscopy, which frequently includes the removal of a biopsy sample. Optical methods, such as Raman spectroscopy (RS) and optical coherence tomography (OCT), can help to improve diagnostics and reduce the number of unnecessary biopsies. For in vivo use, we have developed fiber-optic probes, one for single-point Raman measurements and one for volumetric OCT. Here, we present the results of a clinical study using these fiber-optic probes in an ex vivo setting. The goal was to evaluate the beneficial effect of combining these two modalities on the AUC ROC score of the machine learning models for the discrimination of cancerous and healthy tissue. In the initial stage of the investigation, both modalities were validated separately using linear discriminant analysis. RS was subjected to spectral preprocessing, while OCT underwent texture feature extraction. Subsequently, both modalities were integrated using the Bayes rule, resulting in an enhanced area under the curve score of 0.93, representing an improvement over the 0.77 score for Raman spectroscopy and 0.86 for OCT.
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Affiliation(s)
- David L. Vasquez
- Leibniz-Institute of Photonic Technology (Leibniz-IPHT), Albert-Einstein-Str. 9, 07745 Jena, Germany; (D.L.V.); (I.L.); (J.P.)
| | - Calvin Kreft
- Department of Medical Engineering and Biotechnology, University of Applied Sciences—Jena, Carl-Zeiss-Promenade 2, 07745 Jena, Germany;
| | - Ines Latka
- Leibniz-Institute of Photonic Technology (Leibniz-IPHT), Albert-Einstein-Str. 9, 07745 Jena, Germany; (D.L.V.); (I.L.); (J.P.)
| | - Jürgen Popp
- Leibniz-Institute of Photonic Technology (Leibniz-IPHT), Albert-Einstein-Str. 9, 07745 Jena, Germany; (D.L.V.); (I.L.); (J.P.)
- Institute of Physical Chemistry (IPC), Abbe Center of Photonics (ACP), Friedrich-Schiller-University Jena, Helmholtzweg 4, 07743 Jena, Germany
| | - René Mantke
- Clinic for General and Visceral Surgery, University Hospital Brandenburg an der Havel, Brandenburg Medical School, 14770 Brandenburg an der Havel, Germany;
- Faculty of Health Sciences Brandenburg, Brandenburg Medical School, 14770 Brandenburg an der Havel, Germany
| | - Iwan W. Schie
- Leibniz-Institute of Photonic Technology (Leibniz-IPHT), Albert-Einstein-Str. 9, 07745 Jena, Germany; (D.L.V.); (I.L.); (J.P.)
- Department of Medical Engineering and Biotechnology, University of Applied Sciences—Jena, Carl-Zeiss-Promenade 2, 07745 Jena, Germany;
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4
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Fang S, Xu P, Wu S, Chen Z, Yang J, Xiao H, Ding F, Li S, Sun J, He Z, Ye J, Lin LL. Raman fiber-optic probe for rapid diagnosis of gastric and esophageal tumors with machine learning analysis or similarity assessments: a comparative study. Anal Bioanal Chem 2024; 416:6759-6772. [PMID: 39322799 DOI: 10.1007/s00216-024-05545-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/09/2024] [Accepted: 09/13/2024] [Indexed: 09/27/2024]
Abstract
Gastric and esophageal cancers, the predominant forms of upper gastrointestinal malignancies, contribute significantly to global cancer mortality. Routine detection methods, including medical imaging, endoscopic examination, and pathological biopsy, often suffer from drawbacks such as low sensitivity and laborious and complex procedures. Raman spectroscopy is a non-invasive and label-free optical technique that provides highly sensitive biomolecular information to facilitate effective tumor identification. In this work, we report the use of fiber-optic Raman spectroscopy for the accurate and rapid diagnosis of gastric and esophageal cancers. Using a database of 14,000 spectra from 140 ex vivo tissue pieces of both tumor and normal tissue samples, we compare the random forest (RF) and our established Euclidean distance Raman spectroscopy (EDRS) model. The RF analysis achieves a sensitivity of 85.23% and an accuracy of 83.05% in diagnosing gastric tumors. The EDRS algorithm with improved diagnostic transparency further increases the sensitivity to 92.86% and accuracy to 89.29%. When these diagnostic protocols are extended to esophageal tumors, the RF and EDRS models achieve accuracies of 71.27% and 93.18%, respectively. Finally, we demonstrate that fewer than 20 spectra are sufficient to achieve good Raman diagnostic accuracy for both tumor tissues. This optimizes the balance between acquisition time and diagnostic performance. Our work, although conducted on ex vivo tissue models, offers valuable insights for in vivo in situ endoscopic Raman diagnosis of gastric and esophageal cancer lesions in the future. Our study provides a robust, rapid, and convenient method as a new paradigm in in vivo endoscopic medical diagnostics that integrates spectroscopic techniques and a Raman probe for detecting upper gastrointestinal malignancies.
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Affiliation(s)
- Shiyan Fang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China
| | - Pei Xu
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Siyi Wu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China
| | - Zhou Chen
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China
| | - Junqing Yang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China
| | - Haibo Xiao
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Fangbao Ding
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China
| | - Shuchun Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Jin Sun
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Zirui He
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Jian Ye
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
- Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China.
- Shanghai Key Laboratory of Gynecologic Oncology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, 200127, China.
| | - Linley Li Lin
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.
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5
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Guo S, Zhang R, Wang T, Wang J. Comparative study of machine-and deep-learning based classification algorithms for biomedical Raman spectroscopy (RS): case study of RS based pathogenic microbe identification. ANAL SCI 2024; 40:2101-2109. [PMID: 39207655 DOI: 10.1007/s44211-024-00645-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 08/01/2024] [Indexed: 09/04/2024]
Abstract
One key aspect pushing the frontiers of biomedical RS is dedicated machine- or deep- learning (ML or DL) algorithms. Yet, systematic comparative study between ML and DL algorithms has not been conducted for biomedical RS, largely due to the limited availability of open-source and large Raman spectra dataset. Therefore we compared typical ML partial least square-discriminant analysis (PLS-DA) and DL one dimensional convolution neural network (1D-CNN) based pathogenic microbe identification on 12,000 Raman spectra from six species of microbe (i.e., K. aerogenes (Klebsiella aerogenes), C. albicans (Candida albicans), C. glabrata (Candida glabrata), Group A Strep. (Group A Streptococcus), E. coli1 (Escherichia coli1), E. coli2 (Escherichia coli2)) when 100%, 75%, 50% and 25% of the 12,000 Raman spectra were retained. The total Raman dataset was analyzed with 80% split for training and 20% for testing. The 100% retained testing dataset accuracy, area under curve (AUC) of the receiver operating characteristic (ROC) curve were 95.25% and 0.997 for 1D-CNN, which are higher than those (89.42% and 0.979) of PLS-DA. Yet, PLS-DA outperforms 1D-CNN for 75%, 50% and 25% retained testing dataset. The resultant accuracies and AUCs demonstrated the performance reliance of PLS-DA and 1D-CNN on Raman spectra number. Besides, both loadings on the latent variables of PLS-DA and the saliency maps of 1D-CNN largely captured Raman peaks arising from DNA and proteins with comparable interpretability. The results of the current work indicated that both ML and DL algorithms should be explored for application-wise Raman spectra identification to select whichever with higher accuracies and AUCs.
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Affiliation(s)
- Sisi Guo
- Key Laboratory of Photoelectronic Imaging Technology and System of Ministry of Education of China, School of Optics and Photonics, Beijing Institute of Technology, Beijing, 100081, China
| | - Ruoyu Zhang
- School of Medical Technology, Beijing Institute of Technology, Beijing, 100081, China
| | - Tao Wang
- Department of Gastroenterology, the First Medical Center of PLA General Hospital, Beijing, 100853, China.
| | - Jianfeng Wang
- Key Laboratory of Photoelectronic Imaging Technology and System of Ministry of Education of China, School of Optics and Photonics, Beijing Institute of Technology, Beijing, 100081, China.
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6
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Jain GK, Verma R, Chougule A, Singh B. Scientific Advances in Cancer Detection Using Raman Spectroscopy. Asian Pac J Cancer Prev 2024; 25:3977-3986. [PMID: 39611922 PMCID: PMC11996111 DOI: 10.31557/apjcp.2024.25.11.3977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 11/27/2024] [Indexed: 11/30/2024] Open
Abstract
AIM The present study is focused to investigate the role of Raman spectroscopy (RM) for cancer detection. METHODS In this review, we explored a number of scientific databases including PubMed, Web of Science, Embase and Google Scholar for research studies on Raman spectroscopy for diagnosing cancer. We reported key outcomes of research studies conducted involving Raman spectroscopy for diagnosis of cancer and highlighting the potential of novel Raman spectroscopy for diagnosing cancer in our review. RESULTS Based on the available evidence it can be strongly concluded that Raman spectroscopy provide significant information for diagnosing cancer. Numerous comprehensive studies involving living cells in vitro, in-vivo animal models and ex-vivo human tissues pre-clinical Raman experiments are conducted on biological specimens for almost every type of cancer for diagnosing cancer demonstrating the potential for clinical use of Raman spectroscopy. Furthermore, the in-vivo Raman handheld probes are developed and experimentally used for real time detection of human breast and brain tumors with significant sensitivity and specificity. However, it will be important and challenging to explore relevant Raman biomarkers for other types of cancer as well, to distinguish cancer. CONCLUSION Raman spectroscopy is an effective method and valuable tool in the field of cancer diagnostics. The Raman spectroscopy deserves a place for future in clinics for rapid cancer diagnostics.
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Affiliation(s)
- Gourav Kumar Jain
- Department of Radiological Physics, SMS Medical College & Hospital, Jaipur-302004, India.
| | - Rajni Verma
- Department of Radiological Physics, SMS Medical College & Hospital, Jaipur-302004, India.
| | - Arun Chougule
- Swasthya Kalyan group of Institutions, Jaipur-302022, India.
| | - Bharti Singh
- Department of Chemistry, Indian Institute of Technology Delhi, New Delhi-110016, India.
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7
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Yang J, Xu P, Wu S, Chen Z, Fang S, Xiao H, Hu F, Jiang L, Wang L, Mo B, Ding F, Lin LL, Ye J. Raman spectroscopy for esophageal tumor diagnosis and delineation using machine learning and the portable Raman spectrometer. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2024; 317:124461. [PMID: 38759393 DOI: 10.1016/j.saa.2024.124461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 05/02/2024] [Accepted: 05/11/2024] [Indexed: 05/19/2024]
Abstract
Esophageal cancer is one of the leading causes of cancer-related deaths worldwide. The identification of residual tumor tissues in the surgical margin of esophageal cancer is essential for the treatment and prognosis of cancer patients. But the current diagnostic methods, either pathological frozen section or paraffin section examination, are laborious, time-consuming, and inconvenient. Raman spectroscopy is a label-free and non-invasive analytical technique that provides molecular information with high specificity. Here, we report the use of a portable Raman system and machine learning algorithms to achieve accurate diagnosis of esophageal tumor tissue in surgically resected specimens. We tested five machine learning-based classification methods, including k-Nearest Neighbors, Adaptive Boosting, Random Forest, Principal Component Analysis-Linear Discriminant Analysis, and Support Vector Machine (SVM). Among them, SVM shows the highest accuracy (88.61 %) in classifying the esophageal tumor and normal tissues. The portable Raman system demonstrates robust measurements with an acceptable focal plane shift of up to 3 mm, which enables large-area Raman mapping on resected tissues. Based on this, we finally achieve successful Raman visualization of tumor boundaries on surgical margin specimens, and the Raman measurement time is less than 5 min. This work provides a robust, convenient, accurate, and cost-effective tool for the diagnosis of esophageal cancer tumors, advancing toward Raman-based clinical intraoperative applications.
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Affiliation(s)
- Junqing Yang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Pei Xu
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Siyi Wu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Zhou Chen
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Shiyan Fang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China
| | - Haibo Xiao
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Fengqing Hu
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Lianyong Jiang
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Lei Wang
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Bin Mo
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China
| | - Fangbao Ding
- Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No 1665 Kongjiang Road, Yangpu District, Shanghai 200092, China.
| | - Linley Li Lin
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
| | - Jian Ye
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Medical Robotics, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
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8
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Helal KM, Cahyadi H, Taylor JN, Okajima A, Tabata K, Kumamoto Y, Mochizuki K, Itoh Y, Takamatsu T, Tanaka H, Fujita K, Komatsuzaki T, Harada Y. Raman imaging of rat nonalcoholic fatty liver tissues reveals distinct biomolecular states. FEBS Lett 2023. [PMID: 36807196 DOI: 10.1002/1873-3468.14600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 12/24/2022] [Accepted: 01/08/2023] [Indexed: 02/20/2023]
Abstract
An essential challenge in diagnosing states of nonalcoholic fatty liver disease (NAFLD) is the early prediction of progression from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) before the disease progresses. Histological diagnoses of NAFLD rely on the appearance of anomalous tissue morphologies, and it is difficult to segment the biomolecular environment of the tissue through a conventional histopathological approach. Here, we show that hyperspectral Raman imaging provides diagnostic information on NAFLD in rats, as spectral changes among disease states can be detected before histological characteristics emerge. Our results demonstrate that Raman imaging of NAFLD can be a useful tool for histopathologists, offering biomolecular distinctions among tissue states that cannot be observed through standard histopathological means.
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Affiliation(s)
- Khalifa Mohammad Helal
- Graduate School of Life Science, Transdisciplinary Life Science Course, Hokkaido University, Sapporo, Japan.,Department of Mathematics, Comilla University, Cumilla, Bangladesh
| | - Harsono Cahyadi
- Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Japan
| | - J Nicholas Taylor
- Research Institute for Electronic Science, Hokkaido University, Sapporo, Japan
| | - Akira Okajima
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Japan
| | - Koji Tabata
- Research Institute for Electronic Science, Hokkaido University, Sapporo, Japan
| | - Yasuaki Kumamoto
- Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Japan
| | - Kentaro Mochizuki
- Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Japan
| | - Yoshito Itoh
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Japan
| | - Tetsuro Takamatsu
- Department of Medical Photonics, Kyoto Prefectural University of Medicine, Japan
| | - Hideo Tanaka
- Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Japan
| | - Katsumasa Fujita
- Department of Applied Physics, Osaka University, Japan.,Transdimensional Life Imaging Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Japan.,Advanced Photonics and Biosensing Open Innovation Laboratory, AIST-Osaka University, Japan
| | - Tamiki Komatsuzaki
- Graduate School of Life Science, Transdisciplinary Life Science Course, Hokkaido University, Sapporo, Japan.,Research Institute for Electronic Science, Hokkaido University, Sapporo, Japan.,Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR 6303 CNRS-Univ. Bourgogne Franche-Comté, Dijon Cedex, France
| | - Yoshinori Harada
- Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine, Japan
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Wang J, Zhang G. Side‐viewing handheld confocal Raman probe coupled with an off‐axis parabolic mirror for superficial epithelial Raman measurements of luminal organs. TRANSLATIONAL BIOPHOTONICS 2022. [DOI: 10.1002/tbio.202200010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Affiliation(s)
- Jianfeng Wang
- Key Laboratory of Photoelectronic Imaging Technology and System of Ministry of Education of China, School of Optics and Photonics Beijing Institute of Technology Beijing China
- Institute of Engineering Medicine, Beijing Institute of Technology Beijing China
| | - Guling Zhang
- College of Science Minzu University of China Beijing China
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10
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Wang J. Real-time calibrating polarization-sensitive diffuse reflectance handheld probe characterizes clinically relevant anatomical locations of oral tissue in vivo. BIOMEDICAL OPTICS EXPRESS 2022; 13:105-116. [PMID: 35154857 PMCID: PMC8803026 DOI: 10.1364/boe.443652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/15/2021] [Accepted: 11/29/2021] [Indexed: 05/10/2023]
Abstract
We report on the development of a unique real-time calibrating polarization-sensitive diffuse reflectance (rcPS-DR) handheld probe, and demonstrate its diagnostic potential through in-depth characterization and differentiation of clinically relevant anatomical locations of the oral cavity (i.e., alveolar process, lateral tongue and floor of mouth that account for 80% of all cases of oral squamous cell carcinoma) in vivo. With an embedded calibrating polytetrafluoroethylene (PTFE) optical diffuser, the PS-DR spectra bias arising from instrument response, time-dependent intensity fluctuation and fiber bending is calibrated through real-time measurement of the PS-DR system response function. A total of 554 in vivo rcPS-DR spectra were acquired from different oral tissue sites (alveolar process, n = 226, lateral tongue, n = 150 and floor of mouth, n = 178) of 14 normal subjects. Significantly (P<0.05, unpaired 2-sided Student's t-test) different spectral ratio (I 540/I 575) representing oxygenated hemoglobin contents were found among the alveolar process, lateral tongue and floor of mouth. Further partial least squares discriminant analysis (PLS-DA) and leave-one-out, cross validation (LOOCV) show that, synergizing the complementary information of the two real-time calibrated orthogonal-polarized PS-DR spectra, the rcPS-DR technique is found to better differentiate alveolar process, lateral tongue, and the floor of mouth (accuracies of 88.2%, 83.9%, 84.4%, sensitivities of 80.5%, 75.8%, 78% and specificities of 93.5%, 87.7%, 86.8%) than standard DR (accuracies of 80.8%, 72.9%, 68.5%, sensitivities of 63.2%, 41.5%, 81.3% and specificities of 92.9%, 87.7%, 63.8%) without PS detection. This work showed the feasibility of the rcPS-DR probe as a tool for studying oral cavity lesions in real clinical applications.
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Affiliation(s)
- Jianfeng Wang
- Key Laboratory of Photoelectronic Imaging Technology and System of Ministry of Education of China, School of Optics and Photonics, Beijingy Institute of Technology, Beijing 100081, China
- Institute of Engineering Medicine, Beijing Institute of Technology, Beijing 100081, China
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11
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Lim D, Renteria ES, Sime DS, Ju YM, Kim JH, Criswell T, Shupe TD, Atala A, Marini FC, Gurcan MN, Soker S, Hunsberger J, Yoo JJ. Bioreactor design and validation for manufacturing strategies in tissue engineering. Biodes Manuf 2021; 5:43-63. [PMID: 35223131 PMCID: PMC8870603 DOI: 10.1007/s42242-021-00154-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore, maintain or improve tissue function following disease or injury. To maximize the biological function of a tissue-engineered clinical product, specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation. Specifically, the bioreactor should be designed to mimic the mechanical, electrochemical and biochemical environment that the product will be exposed to in vivo. Real-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management process. The present review provides a brief overview of bioreactor engineering considerations. In addition, strategies for bioreactor automation, in-line product monitoring and quality assurance are discussed.
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Affiliation(s)
- Diana Lim
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Eric S. Renteria
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Drake S. Sime
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Young Min Ju
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Ji Hyun Kim
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Tracy Criswell
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Thomas D. Shupe
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Frank C. Marini
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Metin N. Gurcan
- Center for Biomedical Informatics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Shay Soker
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Joshua Hunsberger
- RegenMed Development Organization (ReMDO), Winston Salem, NC 27106, USA
| | - James J. Yoo
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
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12
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Horgan CC, Bergholt MS, Thin MZ, Nagelkerke A, Kennedy R, Kalber TL, Stuckey DJ, Stevens MM. Image-guided Raman spectroscopy probe-tracking for tumor margin delineation. JOURNAL OF BIOMEDICAL OPTICS 2021; 26:JBO-200321R. [PMID: 33715315 PMCID: PMC7960531 DOI: 10.1117/1.jbo.26.3.036002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 02/17/2021] [Indexed: 06/01/2023]
Abstract
SIGNIFICANCE Tumor detection and margin delineation are essential for successful tumor resection. However, postsurgical positive margin rates remain high for many cancers. Raman spectroscopy has shown promise as a highly accurate clinical spectroscopic diagnostic modality, but its margin delineation capabilities are severely limited by the need for pointwise application. AIM We aim to extend Raman spectroscopic diagnostics and develop a multimodal computer vision-based diagnostic system capable of both the detection and identification of suspicious lesions and the precise delineation of disease margins. APPROACH We first apply visual tracking of a Raman spectroscopic probe to achieve real-time tumor margin delineation. We then combine this system with protoporphyrin IX fluorescence imaging to achieve fluorescence-guided Raman spectroscopic margin delineation. RESULTS Our system enables real-time Raman spectroscopic tumor margin delineation for both ex vivo human tumor biopsies and an in vivo tumor xenograft mouse model. We then further demonstrate that the addition of protoporphyrin IX fluorescence imaging enables fluorescence-guided Raman spectroscopic margin delineation in a tissue phantom model. CONCLUSIONS Our image-guided Raman spectroscopic probe-tracking system enables tumor margin delineation and is compatible with both white light and fluorescence image guidance, demonstrating the potential for our system to be developed toward clinical tumor resection surgeries.
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Affiliation(s)
- Conor C. Horgan
- Imperial College London, Department of Materials, London, United Kingdom
- Imperial College London, Department of Bioengineering, London, United Kingdom
- Imperial College London, Institute of Biomedical Engineering, London, United Kingdom
| | - Mads S. Bergholt
- Imperial College London, Department of Materials, London, United Kingdom
- Imperial College London, Department of Bioengineering, London, United Kingdom
- Imperial College London, Institute of Biomedical Engineering, London, United Kingdom
| | - May Zaw Thin
- University College London, Centre for Advanced Biomedical Imaging, London, United Kingdom
| | - Anika Nagelkerke
- Imperial College London, Department of Materials, London, United Kingdom
- Imperial College London, Department of Bioengineering, London, United Kingdom
- Imperial College London, Institute of Biomedical Engineering, London, United Kingdom
| | - Robert Kennedy
- King’s College London, Guy’s and St Thomas’ NHS Foundation Trust, Oral/Head and Neck Pathology Laboratory, London, United Kingdom
| | - Tammy L. Kalber
- University College London, Centre for Advanced Biomedical Imaging, London, United Kingdom
| | - Daniel J. Stuckey
- University College London, Centre for Advanced Biomedical Imaging, London, United Kingdom
| | - Molly M. Stevens
- Imperial College London, Department of Materials, London, United Kingdom
- Imperial College London, Department of Bioengineering, London, United Kingdom
- Imperial College London, Institute of Biomedical Engineering, London, United Kingdom
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13
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He Z, Wang P, Ye X. Novel endoscopic optical diagnostic technologies in medical trial research: recent advancements and future prospects. Biomed Eng Online 2021; 20:5. [PMID: 33407477 PMCID: PMC7789310 DOI: 10.1186/s12938-020-00845-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 12/23/2020] [Indexed: 12/20/2022] Open
Abstract
Novel endoscopic biophotonic diagnostic technologies have the potential to non-invasively detect the interior of a hollow organ or cavity of the human body with subcellular resolution or to obtain biochemical information about tissue in real time. With the capability to visualize or analyze the diagnostic target in vivo, these techniques gradually developed as potential candidates to challenge histopathology which remains the gold standard for diagnosis. Consequently, many innovative endoscopic diagnostic techniques have succeeded in detection, characterization, and confirmation: the three critical steps for routine endoscopic diagnosis. In this review, we mainly summarize researches on emerging endoscopic optical diagnostic techniques, with emphasis on recent advances. We also introduce the fundamental principles and the development of those techniques and compare their characteristics. Especially, we shed light on the merit of novel endoscopic imaging technologies in medical research. For example, hyperspectral imaging and Raman spectroscopy provide direct molecular information, while optical coherence tomography and multi-photo endomicroscopy offer a more extensive detection range and excellent spatial-temporal resolution. Furthermore, we summarize the unexplored application fields of these endoscopic optical techniques in major hospital departments for biomedical researchers. Finally, we provide a brief overview of the future perspectives, as well as bottlenecks of those endoscopic optical diagnostic technologies. We believe all these efforts will enrich the diagnostic toolbox for endoscopists, enhance diagnostic efficiency, and reduce the rate of missed diagnosis and misdiagnosis.
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Affiliation(s)
- Zhongyu He
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, People's Republic of China
| | - Peng Wang
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, People's Republic of China
| | - Xuesong Ye
- Biosensor National Special Laboratory, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310027, People's Republic of China.
- State Key Laboratory of CAD and CG, Zhejiang University, Hangzhou, 310058, People's Republic of China.
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14
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Horgan CC, Bergholt MS, Nagelkerke A, Thin MZ, Pence IJ, Kauscher U, Kalber TL, Stuckey DJ, Stevens MM. Integrated photodynamic Raman theranostic system for cancer diagnosis, treatment, and post-treatment molecular monitoring. Theranostics 2021; 11:2006-2019. [PMID: 33408795 PMCID: PMC7778600 DOI: 10.7150/thno.53031] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 11/25/2020] [Indexed: 12/16/2022] Open
Abstract
Theranostics, the combination of diagnosis and therapy, has long held promise as a means to achieving personalised precision cancer treatments. However, despite its potential, theranostics has yet to realise significant clinical translation, largely due the complexity and overriding toxicity concerns of existing theranostic nanoparticle strategies. Methods: Here, we present an alternative nanoparticle-free theranostic approach based on simultaneous Raman spectroscopy and photodynamic therapy (PDT) in an integrated clinical platform for cancer theranostics. Results: We detail the compatibility of Raman spectroscopy and PDT for cancer theranostics, whereby Raman spectroscopic diagnosis can be performed on PDT photosensitiser-positive cells and tissues without inadvertent photosensitiser activation/photobleaching or impaired diagnostic capacity. We further demonstrate that our theranostic platform enables in vivo tumour diagnosis, treatment, and post-treatment molecular monitoring in real-time. Conclusion: This system thus achieves effective theranostic performance, providing a promising new avenue towards the clinical realisation of theranostics.
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Affiliation(s)
- Conor C. Horgan
- Department of Materials, Imperial College London, London SW7 2AZ, UK
- Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
- Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK
| | - Mads S. Bergholt
- Department of Materials, Imperial College London, London SW7 2AZ, UK
- Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
- Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK
| | - Anika Nagelkerke
- Department of Materials, Imperial College London, London SW7 2AZ, UK
- Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
- Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK
| | - May Zaw Thin
- Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK
| | - Isaac J. Pence
- Department of Materials, Imperial College London, London SW7 2AZ, UK
- Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
- Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK
| | - Ulrike Kauscher
- Department of Materials, Imperial College London, London SW7 2AZ, UK
- Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
- Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK
| | - Tammy L. Kalber
- Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK
| | - Daniel J. Stuckey
- Centre for Advanced Biomedical Imaging, University College London, London WC1E 6DD, UK
| | - Molly M. Stevens
- Department of Materials, Imperial College London, London SW7 2AZ, UK
- Department of Bioengineering, Imperial College London, London SW7 2AZ, UK
- Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, UK
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15
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Heng HPS, Shu C, Zheng W, Lin K, Huang Z. Advances in real‐time fiber‐optic Raman spectroscopy for early cancer diagnosis: Pushing the frontier into clinical endoscopic applications. TRANSLATIONAL BIOPHOTONICS 2020. [DOI: 10.1002/tbio.202000018] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
- Howard Peng Sin Heng
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering National University of Singapore Singapore Singapore
- NUS Graduate School for Integrative Sciences and Engineering National University of Singapore Singapore Singapore
| | - Chi Shu
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering National University of Singapore Singapore Singapore
| | - Wei Zheng
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering National University of Singapore Singapore Singapore
| | - Kan Lin
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering National University of Singapore Singapore Singapore
| | - Zhiwei Huang
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering National University of Singapore Singapore Singapore
- NUS Graduate School for Integrative Sciences and Engineering National University of Singapore Singapore Singapore
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16
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Ralbovsky NM, Dey P, Galfano A, Dey BK, Lednev IK. Diagnosis of a model of Duchenne muscular dystrophy in blood serum of mdx mice using Raman hyperspectroscopy. Sci Rep 2020; 10:11734. [PMID: 32678134 PMCID: PMC7366916 DOI: 10.1038/s41598-020-68598-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 06/29/2020] [Indexed: 11/14/2022] Open
Abstract
Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and affects boys in infancy or early childhood. Current methods for diagnosing DMD are often laborious, expensive, invasive, and typically diagnose the disease late in its progression. In an effort to improve the accuracy and ease of diagnosis, this study focused on developing a novel method for diagnosing DMD which combines Raman hyperspectroscopic analysis of blood serum with advanced statistical analysis. Partial least squares discriminant analysis was applied to the spectral dataset acquired from blood serum of a mouse model of Duchenne muscular dystrophy (mdx) and control mice. Cross-validation showed 95.2% sensitivity and 94.6% specificity for identifying diseased spectra. These results were verified via external validation, which achieved 100% successful classification accuracy at the donor level. This proof-of-concept study presents Raman hyperspectroscopic analysis of blood serum as an easy, fast, non-expensive, and minimally invasive detection method for distinguishing control and mdx model mice, with a strong potential for clinical diagnosis of DMD.
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Affiliation(s)
- Nicole M Ralbovsky
- Department of Chemistry, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA.,The RNA Institute, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA
| | - Paromita Dey
- The RNA Institute, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA
| | - Andrew Galfano
- Department of Chemistry, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA
| | - Bijan K Dey
- The RNA Institute, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA. .,Department of Biological Sciences, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA.
| | - Igor K Lednev
- Department of Chemistry, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA. .,The RNA Institute, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA. .,Department of Biological Sciences, University At Albany, SUNY, 1400 Washington Avenue, Albany, NY, 12222, USA.
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17
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Hubbard TJE, Shore A, Stone N. Raman spectroscopy for rapid intra-operative margin analysis of surgically excised tumour specimens. Analyst 2020; 144:6479-6496. [PMID: 31616885 DOI: 10.1039/c9an01163c] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Raman spectroscopy, a form of vibrational spectroscopy, has the ability to provide sensitive and specific biochemical analysis of tissue. This review article provides an in-depth analysis of the suitability of different Raman spectroscopy techniques in providing intra-operative margin analysis in a range of solid tumour pathologies. Surgical excision remains the primary treatment of a number of solid organ cancers. Incomplete excision of a tumour and positive margins on histopathological analysis is associated with a worse prognosis, the need for adjuvant therapies with significant side effects and a resulting financial burden. The provision of intra-operative margin analysis of surgically excised tumour specimens would be beneficial for a number of pathologies, as there are no widely adopted and accurate methods of margin analysis, beyond histopathology. The limitations of Raman spectroscopic studies to date are discussed and future work necessary to enable translation to clinical use is identified. We conclude that, although there remain a number of challenges in translating current techniques into a clinically effective tool, studies so far demonstrate that Raman Spectroscopy has the attributes to successfully perform highly accurate intra-operative margin analysis in a clinically relevant environment.
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18
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Ross CA, MacLachlan DG, Smith BJE, Beck RJ, Shephard JD, Weston N, Thomson RR. A Miniature Fibre-Optic Raman Probe Fabricated by Ultrafast Laser-Assisted Etching. MICROMACHINES 2020; 11:mi11020185. [PMID: 32053957 PMCID: PMC7074630 DOI: 10.3390/mi11020185] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/06/2020] [Accepted: 02/08/2020] [Indexed: 01/20/2023]
Abstract
Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices, particularly in a way suitable for large scale adoption, remains a critical challenge. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy-based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser-assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3% ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.
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Affiliation(s)
- Calum A. Ross
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
- Correspondence:
| | - David G. MacLachlan
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
| | | | - Rainer J. Beck
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
| | - Jonathan D. Shephard
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
| | | | - Robert R. Thomson
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
- EPSRC IRC Hub, MRC Centre for Inflammation Research, Queen’s Medical Research Institute (QMRI), University of Edinburgh, Edinburgh EH16 4TJ, UK
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19
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Krafft C, Popp J. Medical needs for translational biophotonics with the focus on Raman‐based methods. TRANSLATIONAL BIOPHOTONICS 2019. [DOI: 10.1002/tbio.201900018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
| | - Jürgen Popp
- Leibniz Institute of Photonic Technology Jena Germany
- Institute of Physical Chemistry and Abbe Center of PhotonicsFriedrich Schiller University Jena Jena Germany
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20
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Hiremath G, Locke A, Sivakumar A, Thomas G, Mahadevan-Jansen A. Clinical translational application of Raman spectroscopy to advance Benchside biochemical characterization to bedside diagnosis of esophageal diseases. J Gastroenterol Hepatol 2019; 34:1911-1921. [PMID: 31124184 DOI: 10.1111/jgh.14738] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 05/17/2019] [Accepted: 05/20/2019] [Indexed: 12/14/2022]
Abstract
Esophageal diseases result in significant mortality, morbidity, and health care costs worldwide. Current approaches to detect and monitor esophageal diseases have severe limitations. Advanced imaging technologies are being developed to complement current approaches to improve diagnostic, therapeutic and surveillance protocols in order to advance the field. Raman spectroscopy-based technologies hold promise to increase the sensitivity for detection of diseased and high-risk lesions in vitro and in vivo in real time. This technique allows for the investigation of microstructural changes and also facilitates the discovery of disease-specific biochemical alterations with the potential to provide novel insights into the pathobiology of these conditions. Raman spectroscopy has been increasingly applied in precancerous and cancerous esophageal conditions. However, its application in benign esophageal diseases is still in the early stages. Continuing its application in cancerous and precancerous conditions and expanding its use to benign esophageal disorders could lay a foundation for integration of this technology in clinical practice and diagnostic paradigms and development of an accurate and cost-effective tool for use in a clinical setting. Furthermore, Raman spectroscopy can also be used as an innovative technique to advance our understanding of the biochemical transformations associated with esophageal diseases and answer a myriad of fundamental questions in the field. In this review, we described the principles of Raman spectroscopy and instrumentation while providing an overview of current applications, challenges, and future directions in the context of esophageal diseases with an emphasis on its clinical translational application.
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Affiliation(s)
- Girish Hiremath
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, Tennessee, USA.,Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Andrea Locke
- Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Adithya Sivakumar
- Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Giju Thomas
- Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
| | - Anita Mahadevan-Jansen
- Vanderbilt Biophotonics Center, Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA
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21
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Zúñiga WC, Jones V, Anderson SM, Echevarria A, Miller NL, Stashko C, Schmolze D, Cha PD, Kothari R, Fong Y, Storrie-Lombardi MC. Raman Spectroscopy for Rapid Evaluation of Surgical Margins during Breast Cancer Lumpectomy. Sci Rep 2019; 9:14639. [PMID: 31601985 PMCID: PMC6787043 DOI: 10.1038/s41598-019-51112-0] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 09/20/2019] [Indexed: 12/21/2022] Open
Abstract
Failure to precisely distinguish malignant from healthy tissue has severe implications for breast cancer surgical outcomes. Clinical prognoses depend on precisely distinguishing healthy from malignant tissue during surgery. Laser Raman spectroscopy (LRS) has been previously shown to differentiate benign from malignant tissue in real time. However, the cost, assembly effort, and technical expertise needed for construction and implementation of the technique have prohibited widespread adoption. Recently, Raman spectrometers have been developed for non-medical uses and have become commercially available and affordable. Here we demonstrate that this current generation of Raman spectrometers can readily identify cancer in breast surgical specimens. We evaluated two commercially available, portable, near-infrared Raman systems operating at excitation wavelengths of either 785 nm or 1064 nm, collecting a total of 164 Raman spectra from cancerous, benign, and transitional regions of resected breast tissue from six patients undergoing mastectomy. The spectra were classified using standard multivariate statistical techniques. We identified a minimal set of spectral bands sufficient to reliably distinguish between healthy and malignant tissue using either the 1064 nm or 785 nm system. Our results indicate that current generation Raman spectrometers can be used as a rapid diagnostic technique distinguishing benign from malignant tissue during surgery.
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Affiliation(s)
- Willie C Zúñiga
- Harvey Mudd College, Department of Physics, 301 Platt Blvd., Claremont, CA, 91711, USA
| | - Veronica Jones
- Harvey Mudd College, Department of Engineering, 301 Platt Blvd., Claremont, CA, 91711, USA.
| | - Sarah M Anderson
- Harvey Mudd College, Department of Engineering, 301 Platt Blvd., Claremont, CA, 91711, USA
| | - Alex Echevarria
- Harvey Mudd College, Department of Physics, 301 Platt Blvd., Claremont, CA, 91711, USA
| | - Nathaniel L Miller
- Harvey Mudd College, Department of Engineering, 301 Platt Blvd., Claremont, CA, 91711, USA
| | - Connor Stashko
- Harvey Mudd College, Department of Engineering, 301 Platt Blvd., Claremont, CA, 91711, USA
| | - Daniel Schmolze
- City of Hope National Medical Center, Department of Surgery, 1500 E. Duarte Rd, Duarte, CA, 91010, USA
| | - Philip D Cha
- Harvey Mudd College, Department of Engineering, 301 Platt Blvd., Claremont, CA, 91711, USA
| | - Ragini Kothari
- City of Hope National Medical Center, Department of Surgery, 1500 E. Duarte Rd, Duarte, CA, 91010, USA
- Harvey Mudd College, Department of Engineering, 301 Platt Blvd., Claremont, CA, 91711, USA
| | - Yuman Fong
- City of Hope National Medical Center, Department of Surgery, 1500 E. Duarte Rd, Duarte, CA, 91010, USA
| | - Michael C Storrie-Lombardi
- Harvey Mudd College, Department of Physics, 301 Platt Blvd., Claremont, CA, 91711, USA
- Kinohi Institute, Inc., 530S. Lake Avenue, Pasadena, CA, 91101, USA
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22
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Ralbovsky NM, Lednev IK. Raman spectroscopy and chemometrics: A potential universal method for diagnosing cancer. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2019; 219:463-487. [PMID: 31075613 DOI: 10.1016/j.saa.2019.04.067] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 04/20/2019] [Accepted: 04/24/2019] [Indexed: 05/14/2023]
Abstract
Cancer is the second-leading cause of death worldwide. It affects an unfathomable number of people, with almost 16 million Americans currently living with it. While many cancers can be detected, current diagnostic efforts exhibit definite room for improvement. It is imperative that a person be diagnosed with cancer as early on in its progression as possible. An earlier diagnosis allows for the best treatment and intervention options available to be presented. Unfortunately, existing methods for diagnosing cancer can be expensive, invasive, inconclusive or inaccurate, and are not always made during initial stages of the disease. As such, there is a crucial unmet need to develop a singular universal method that is reliable, cost-effective, and non-invasive and can diagnose all forms of cancer early-on. Raman spectroscopy in combination with advanced statistical analysis is offered here as a potential solution for this need. This review covers recently published research in which Raman spectroscopy was used for the purpose of diagnosing cancer. The benefits and the risks of the methodology are presented; however, there is overwhelming evidence that suggests Raman spectroscopy is highly suitable for becoming the first universal method to be used for diagnosing cancer.
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Affiliation(s)
- Nicole M Ralbovsky
- Department of Chemistry, University at Albany, SUNY, 1400 Washington Avenue, Albany, NY 12222, USA
| | - Igor K Lednev
- Department of Chemistry, University at Albany, SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.
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23
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Žuvela P, Lin K, Shu C, Zheng W, Lim CM, Huang Z. Fiber-Optic Raman Spectroscopy with Nature-Inspired Genetic Algorithms Enhances Real-Time in Vivo Detection and Diagnosis of Nasopharyngeal Carcinoma. Anal Chem 2019; 91:8101-8108. [PMID: 31135136 DOI: 10.1021/acs.analchem.9b00173] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Raman spectroscopy is an optical vibrational spectroscopic technique capable of probing specific biochemical structures and conformation of tissue and cells in biomedical systems. This work aims to assess the clinical utility of a fiber-optic Raman spectroscopy with nature-inspired genetic algorithms for enhancing in vivo detection and diagnosis of nasopharyngeal carcinoma (NPC) patients. The Raman diagnostic platform is developed based on simultaneous fingerprint (FP) and high-wavenumber (HW) fiber-optic Raman endoscopy associated with genetic algorithms-partial least-squares-linear discriminant analysis (GA-PLS-LDA). A total of 2126 in vivo FP/HW Raman spectra (598 NPC, 1528 normal) acquired from 113 tissue sites of 14 NPC patients and 48 healthy subjects during nasopharyngeal endoscopic examinations. Distinct Raman peaks have been identified (853 cm-1 - proteins, 1209 cm-1 - phenylalanine, 1265 cm-1 - proteins, 1335 cm-1 - proteins and nucleic acids, 1554 cm-1 - tryptophan, porphyrin, 2885 cm-1 - lipids, 2940 cm-1 - proteins, 3009 cm-1 - lipids, and 3250 cm-1 - water) that are related to the significant biochemical changes ( p < 1 × 10-5) in NPC compared to normal tissue. Raman diagnostic performance is evaluated through the leave-one-object (tissue site)-out cross-validation (LOOCV) method. A statistically significant GA-PLS-LDA model ( p < 1 × 10-5) on FP/HW Raman yields a CV diagnostic accuracy of 98.23% (111/113), sensitivity of 93.33% (28/30), and specificity of 100% (83/83) for NPC classification. This work demonstrates that the fiber-optic FP/HW Raman diagnostic platform developed has great promise for improving real-time in vivo detection and diagnosis of NPC at the molecular level during clinical nasopharyngeal endoscopy.
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Affiliation(s)
- Petar Žuvela
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering , National University of Singapore , 9 Engineering Drive 1 , Singapore 117576
| | - Kan Lin
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering , National University of Singapore , 9 Engineering Drive 1 , Singapore 117576
| | - Chi Shu
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering , National University of Singapore , 9 Engineering Drive 1 , Singapore 117576
| | - Wei Zheng
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering , National University of Singapore , 9 Engineering Drive 1 , Singapore 117576
| | - Chwee Ming Lim
- Department of Otolaryngology, Head and Neck Surgery , National University of Singapore and National University Health System , Singapore 119074
| | - Zhiwei Huang
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering , National University of Singapore , 9 Engineering Drive 1 , Singapore 117576
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Santos IP, Barroso EM, Bakker Schut TC, Caspers PJ, van Lanschot CGF, Choi DH, van der Kamp MF, Smits RWH, van Doorn R, Verdijk RM, Noordhoek Hegt V, von der Thüsen JH, van Deurzen CHM, Koppert LB, van Leenders GJLH, Ewing-Graham PC, van Doorn HC, Dirven CMF, Busstra MB, Hardillo J, Sewnaik A, Ten Hove I, Mast H, Monserez DA, Meeuwis C, Nijsten T, Wolvius EB, Baatenburg de Jong RJ, Puppels GJ, Koljenović S. Raman spectroscopy for cancer detection and cancer surgery guidance: translation to the clinics. Analyst 2018; 142:3025-3047. [PMID: 28726868 DOI: 10.1039/c7an00957g] [Citation(s) in RCA: 107] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Oncological applications of Raman spectroscopy have been contemplated, pursued, and developed at academic level for at least 25 years. Published studies aim to detect pre-malignant lesions, detect cancer in less invasive stages, reduce the number of unnecessary biopsies and guide surgery towards the complete removal of the tumour with adequate tumour resection margins. This review summarizes actual clinical needs in oncology that can be addressed by spontaneous Raman spectroscopy and it provides an overview over the results that have been published between 2007 and 2017. An analysis is made of the current status of translation of these results into clinical practice. Despite many promising results, most of the applications addressed in scientific studies are still far from clinical adoption and commercialization. The main hurdles are identified, which need to be overcome to ensure that in the near future we will see the first Raman spectroscopy-based solutions being used in routine oncologic diagnostic and surgical procedures.
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Affiliation(s)
- Inês P Santos
- Center for Optical Diagnostics and Therapy, Department of Dermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
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25
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Masson LE, O'Brien CM, Pence IJ, Herington JL, Reese J, van Leeuwen TG, Mahadevan-Jansen A. Dual excitation wavelength system for combined fingerprint and high wavenumber Raman spectroscopy. Analyst 2018; 143:6049-6060. [PMID: 30420993 PMCID: PMC6295447 DOI: 10.1039/c8an01989d] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
A fiber optic probe-based Raman spectroscopy system using a single laser module with two excitation wavelengths, at 680 and 785 nm, has been developed for measuring the fingerprint and high wavenumber regions using a single detector. This system is simpler and less expensive than previously reported configurations of combined fingerprint and high wavenumber Raman systems, and its probe-based implementation facilitates numerous in vivo applications. The high wavenumber region of the Raman spectrum ranges from 2800-3800 cm-1 and contains valuable information corresponding to the molecular vibrations of proteins, lipids, and water, which is complimentary to the biochemical signatures found in the fingerprint region (800-1800 cm-1), which probes DNA, lipids, and proteins. The efficacy of the system is demonstrated by tracking changes in water content in tissue-mimicking phantoms, where Voigtian decomposition of the high wavenumber water peak revealed a correlation between the water content and type of water-tissue interactions in the samples. This dual wavelength system was then used for in vivo assessment of cervical remodeling during mouse pregnancy, a physiologic process with known changes in tissue hydration. The system shows that Raman spectroscopy is sensitive to changes in collagen content in the fingerprint region and hydration state in the high wavenumber region, which was verified using an ex vivo comparison of wet and dry weight. Simultaneous fingerprint and high wavenumber Raman spectroscopy will allow precise in vivo quantification of tissue water content in the high wavenumber region, paired with the high biochemical specificity of the fingerprint region.
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Affiliation(s)
- Laura E Masson
- Department of Biomedical Engineering, Vanderbilt University, Nashville, USA.
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26
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Ikeda H, Ito H, Hikita M, Yamaguchi N, Uragami N, Yokoyama N, Hirota Y, Kushima M, Ajioka Y, Inoue H. Raman spectroscopy for the diagnosis of unlabeled and unstained histopathological tissue specimens. World J Gastrointest Oncol 2018; 10:439-448. [PMID: 30487955 PMCID: PMC6247109 DOI: 10.4251/wjgo.v10.i11.439] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 09/06/2018] [Accepted: 10/17/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the possibility of diagnosing gastric cancer from an unstained pathological tissue using Raman spectroscopy, and to compare the findings to those obtained with conventional histopathology.
METHODS We produced two consecutive tissue specimens from areas with and without cancer lesions in the surgically resected stomach of a patient with gastric cancer. One of the two tissue specimens was stained with hematoxylin and eosin and used as a reference for laser irradiation positioning by the spectroscopic method. The other specimen was left unstained and used for Raman spectroscopy analysis.
RESULTS A significant Raman scattering spectrum could be obtained at all measurement points. Raman scattering spectrum intensities of 725 cm-1 and 782 cm-1, are associated with the nucleotides adenine and cytosine, respectively. The Raman scattering spectrum intensity ratios of 782 cm-1/620 cm-1, 782 cm-1/756 cm-1, 782 cm-1/1250 cm-1, and 782 cm-1/1263 cm-1 in the gastric adenocarcinoma tissue were significantly higher than those in the normal stomach tissue.
CONCLUSION The results of this preliminary experiment suggest the feasibility of our spectroscopic method as a diagnostic tool for gastric cancer using unstained pathological specimens.
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Affiliation(s)
- Haruo Ikeda
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Hiroaki Ito
- Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Muneaki Hikita
- Stem Cell Business Development Department, Nikon Corporation, Sakae-ku, Yokohama, Kanagawa 2448533, Japan
| | - Noriko Yamaguchi
- Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Naoyuki Uragami
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Noboru Yokoyama
- Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Yuko Hirota
- Department of Pathology, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Miki Kushima
- Department of Pathology, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Yoichi Ajioka
- Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City, Niigata 9518510, Japan
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
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Aubertin K, Desroches J, Jermyn M, Trinh VQ, Saad F, Trudel D, Leblond F. Combining high wavenumber and fingerprint Raman spectroscopy for the detection of prostate cancer during radical prostatectomy. BIOMEDICAL OPTICS EXPRESS 2018; 9:4294-4305. [PMID: 30615702 PMCID: PMC6157766 DOI: 10.1364/boe.9.004294] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 07/16/2018] [Accepted: 08/02/2018] [Indexed: 05/14/2023]
Abstract
For prostate cancer (PCa) patients, radical prostatectomy (complete removal of the prostate) is the only curative surgical option. To date, there is no clinical technique allowing for real-time assessment of surgical margins to minimize the extent of residual cancer. Here, we present a tissue interrogation technique using a dual excitation wavelength Raman spectroscopy system capable of sequentially acquiring fingerprint (FP) and high wavenumber (HWN) Raman spectra. Results demonstrate the ability of the system to detect PCa in post-prostatectomy specimens. In total, 477 Raman spectra were collected from 18 human prostate slices. Each area measured with Raman spectroscopy was characterized as either normal or cancer based on histopathological analyses, and each spectrum was classified based on supervised learning using support vector machines (SVMs). Based on receiver operating characteristic (ROC) analysis, FP (area under the curve [AUC] = 0.89) had slightly superior cancer detection capabilities compared with HWN (AUC = 0.86). Optimal performance resulted from combining the spectral information from FP and HWN (AUC = 0.91), suggesting that the use of these two spectral regions may provide complementary molecular information for PCa detection. The use of leave-one-(spectrum)-out (LOO) or leave-one-patient-out (LOPO) cross-validation produced similar classification results when combining FP with HWN. Our findings suggest that the application of machine learning using multiple data points from the same patient does not result in biases necessarily impacting the reliability of the classification models.
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Affiliation(s)
- Kelly Aubertin
- Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Institut du cancer Montréal (ICM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
| | - Joannie Desroches
- Polytechnique Montréal, Department of Engineering Physics, CP 6079, Succ. Centre-Ville, Montréal, Quebec H3C 3A7, Canada
| | - Michael Jermyn
- Polytechnique Montréal, Department of Engineering Physics, CP 6079, Succ. Centre-Ville, Montréal, Quebec H3C 3A7, Canada
- Dartmouth College, Thayer School of Engineering, 14 Engineering Drive, Hanover, NH 03755, USA
| | - Vincent Quoc Trinh
- Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Institut du cancer Montréal (ICM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Centre hospitalier de l’Université de Montréal (CHUM), Laboratoire de pathologie et cytologie, 1100 rue Sanguinet, Montréal, Quebec H2X 0C2, Canada
- Université de Montréal, Department of Pathology and Cellular Biology, 2900 Boulevard Edouard-Montpetit, Montréal, Quebec H3T 1J4, Canada
| | - Fred Saad
- Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Institut du cancer Montréal (ICM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Centre hospitalier de l’Université de Montréal (CHUM), Division of Urology, 1051 rue Sanguinet, Montréal, Quebec H2X 0C1, Canada
- Université de Montréal, Department of Surgery, 2900 Boulevard Edouard-Montpetit, Montréal, Quebec H3T 1J4, Canada
| | - Dominique Trudel
- Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Institut du cancer Montréal (ICM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Centre hospitalier de l’Université de Montréal (CHUM), Laboratoire de pathologie et cytologie, 1100 rue Sanguinet, Montréal, Quebec H2X 0C2, Canada
- Université de Montréal, Department of Pathology and Cellular Biology, 2900 Boulevard Edouard-Montpetit, Montréal, Quebec H3T 1J4, Canada
| | - Frédéric Leblond
- Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), 900 rue St-Denis, Montréal, Quebec H2X 0A9, Canada
- Polytechnique Montréal, Department of Engineering Physics, CP 6079, Succ. Centre-Ville, Montréal, Quebec H3C 3A7, Canada
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Raman Spectroscopy and Imaging for Cancer Diagnosis. JOURNAL OF HEALTHCARE ENGINEERING 2018; 2018:8619342. [PMID: 29977484 PMCID: PMC6011081 DOI: 10.1155/2018/8619342] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Accepted: 05/12/2018] [Indexed: 12/20/2022]
Abstract
Raman scattering has long been used to analyze chemical compositions in biological systems. Owing to its high chemical specificity and noninvasive detection capability, Raman scattering has been widely employed in cancer screening, diagnosis, and intraoperative surgical guidance in the past ten years. In order to overcome the weak signal of spontaneous Raman scattering, coherent Raman scattering and surface-enhanced Raman scattering have been developed and recently applied in the field of cancer research. This review focuses on innovative studies of the use of Raman scattering in cancer diagnosis and their potential to transition from bench to bedside.
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Cordero E, Latka I, Matthäus C, Schie I, Popp J. In-vivo Raman spectroscopy: from basics to applications. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-23. [PMID: 29956506 DOI: 10.1117/1.jbo.23.7.071210] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 05/23/2018] [Indexed: 05/20/2023]
Abstract
For more than two decades, Raman spectroscopy has found widespread use in biological and medical applications. The instrumentation and the statistical evaluation procedures have matured, enabling the lengthy transition from ex-vivo demonstration to in-vivo examinations. This transition goes hand-in-hand with many technological developments and tightly bound requirements for a successful implementation in a clinical environment, which are often difficult to assess for novice scientists in the field. This review outlines the required instrumentation and instrumentation parameters, designs, and developments of fiber optic probes for the in-vivo applications in a clinical setting. It aims at providing an overview of contemporary technology and clinical trials and attempts to identify future developments necessary to bring the emerging technology to the clinical end users. A comprehensive overview of in-vivo applications of fiber optic Raman probes to characterize different tissue and disease types is also given.
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Affiliation(s)
- Eliana Cordero
- Leibniz-Institut für Photonische Technologien e.V., Germany
| | - Ines Latka
- Leibniz-Institut für Photonische Technologien e.V., Germany
| | - Christian Matthäus
- Leibniz-Institut für Photonische Technologien e.V., Germany
- Institut für Physikalische Chemie, Friedrich-Schiller-Univ. Jena, Germany
- Abbe Ctr. of Photonics, Germany
| | - Iwan Schie
- Leibniz-Institut für Photonische Technologien e.V., Germany
| | - Jürgen Popp
- Leibniz-Institut für Photonische Technologien e.V., Germany
- Institute für Physikalische Chemie, Friedrich-Schiller-Univ. Jena, Germany
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Shi Y, Huang XX, Chen GB, Wang Y, Zhi Q, Liu YS, Wu XL, Wang LF, Yang B, Xiao CX, Xing HQ, Ren JL, Xia Y, Guleng B. Dragon (RGMb) induces oxaliplatin resistance in colon cancer cells. Oncotarget 2018; 7:48027-48037. [PMID: 27384995 PMCID: PMC5216997 DOI: 10.18632/oncotarget.10338] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 06/12/2016] [Indexed: 02/01/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.
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Affiliation(s)
- Ying Shi
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Xiao-Xiao Huang
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Guo-Bin Chen
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.,Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China
| | - Ying Wang
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Qiang Zhi
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Yuan-Sheng Liu
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Xiao-Ling Wu
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Li-Fen Wang
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Bing Yang
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Chuan-Xing Xiao
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Hui-Qin Xing
- Department of Basic Medical Sciences, Institute of Neuroscience, Medical College of Xiamen University, Xiamen, China
| | - Jian-Lin Ren
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China
| | - Yin Xia
- School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.,School of Biomedical Sciences Core Laboratory, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China
| | - Bayasi Guleng
- Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, China.,State Key Laboratory of Cellular Stress Biology, Xiamen University, Xiamen, China
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Wang J, Zheng W, Lin K, Huang Z. Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique. JOURNAL OF BIOPHOTONICS 2018; 11. [PMID: 28985038 DOI: 10.1002/jbio.201700113] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 10/04/2017] [Indexed: 05/08/2023]
Abstract
This study aims to characterize biochemical and morphological variations of the clinically relevant anatomical locations of in vivo oral tissue (ie, alveolar process, lateral tongue and floor of the mouth) by using hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) technique. A total of 1049 in vivo fingerprint (FP: 800-1800 cm-1 ) and high wavenumber (HW: 2800-3600 cm-1 ) Raman spectra were acquired from different oral tissue (alveolar process = 331, lateral tongue = 339 and floor of mouth = 379) of 26 normal subjects in the oral cavity under the OCT imaging guidance. The total Raman dataset were split into 2 parts: 80% for training and 20% for testing. Tissue optical attenuation coefficients of alveolar process, lateral tongue and the floor of the mouth were derived from OCT images, revealing the inter-anatomical morphological differences; while RS uncovers subtle FP/HW Raman spectral differences among different oral tissues that can be attributed to the differences in inter- and intra-cellular proteins, lipids, DNA and water structures and conformations, enlightening biochemical variability of different oral tissues at the molecular level. Partial least squares-discriminant analysis implemented on the training dataset show that the integrated tissue optical attenuation coefficients and FP/HW Raman spectra provide diagnostic sensitivities of 99.6%, 82.3%, 50.2%, and specificities of 97.0%, 75.1%, 92.1%, respectively, which are superior to using either RS (sensitivities of 90.2%, 77.5%, 48.8%, and specificities of 95.8%, 72.1%, 88.8%) or optical attenuation coefficients derived from OCT (sensitivities of 75.0%, 78.2%, 47.2%, and specificities of 96.2%, 67.7%, 85.0%) for the differentiation among alveolar process, lateral tongue and the floor of the mouth. Furthermore, the diagnostic algorithms applied to the independent testing dataset based on hybrid RS-OCT technique gives predictive diagnostic sensitivities of 100%, 76.5%, 51.3%, and specificities of 95.1%, 77.6%, 89.6%, respectively, for the classifications among alveolar process, lateral tongue and the floor of the mouth, which performs much better than either RS or optical attenuation coefficient derived from OCT imaging. This work suggests that inter-anatomical morphological and biochemical variability are significant which should be considered as an important parameter in the interpretation and rendering of hybrid RS-OCT technique for oral tissue diagnosis and characterization.
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Affiliation(s)
- Jianfeng Wang
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore
| | - Wei Zheng
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
| | - Kan Lin
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
| | - Zhiwei Huang
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore
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32
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Upchurch E, Isabelle M, Lloyd GR, Kendall C, Barr H. An update on the use of Raman spectroscopy in molecular cancer diagnostics: current challenges and further prospects. Expert Rev Mol Diagn 2018; 18:245-258. [DOI: 10.1080/14737159.2018.1439739] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Emma Upchurch
- Department of Upper GI Surgery, Gloucestershire Royal Hospital, Gloucester
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Gloucester
| | | | - Gavin Rhys Lloyd
- Phenome Centre Birmingham, School of Biosciences, University of Birmingham
| | - Catherine Kendall
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Gloucester
| | - Hugh Barr
- Department of Upper GI Surgery, Gloucestershire Royal Hospital, Gloucester
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Gloucester
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Lin K, Zheng W, Lim CM, Huang Z. Real-time In vivo Diagnosis of Nasopharyngeal Carcinoma Using Rapid Fiber-Optic Raman Spectroscopy. Am J Cancer Res 2017; 7:3517-3526. [PMID: 28912892 PMCID: PMC5596440 DOI: 10.7150/thno.16359] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Accepted: 07/23/2017] [Indexed: 12/17/2022] Open
Abstract
We report the utility of a simultaneous fingerprint (FP) (i.e., 800-1800 cm-1) and high-wavenumber (HW) (i.e., 2800-3600 cm-1) fiber-optic Raman spectroscopy developed for real-time in vivo diagnosis of nasopharyngeal carcinoma (NPC) at endoscopy. A total of 3731 high-quality in vivo FP/HW Raman spectra (normal=1765; cancer=1966) were acquired in real-time from 204 tissue sites (normal=95; cancer=109) of 95 subjects (normal=57; cancer=38) undergoing endoscopic examination. FP/HW Raman spectra differ significantly between normal and cancerous nasopharyngeal tissues that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in NPC. Principal components analysis (PCA) and linear discriminant analysis (LDA) together with leave-one subject-out, cross-validation (LOO-CV) were implemented to develop robust Raman diagnostic models. The simultaneous FP/HW Raman spectroscopy technique together with PCA-LDA and LOO-CV modeling provides a diagnostic accuracy of 93.1% (sensitivity of 93.6%; specificity of 92.6%) for nasopharyngeal cancer identification, which is superior to using either FP (accuracy of 89.2%; sensitivity of 89.9%; specificity of 88.4%) or HW (accuracy of 89.7%; sensitivity of 89.0%; specificity of 90.5%) Raman technique alone. Further receiver operating characteristic (ROC) analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for in vivo diagnosis of NPC. This work demonstrates for the first time that simultaneous FP/HW fiber-optic Raman spectroscopy technique has great promise for enhancing real-time in vivo cancer diagnosis in the nasopharynx during endoscopic examination.
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Krafft C, Schmitt M, Schie IW, Cialla-May D, Matthäus C, Bocklitz T, Popp J. Markerfreie molekulare Bildgebung biologischer Zellen und Gewebe durch lineare und nichtlineare Raman-spektroskopische Ansätze. Angew Chem Int Ed Engl 2017. [DOI: 10.1002/ange.201607604] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Christoph Krafft
- Leibniz-Institut für Photonische Technologien; Albert-Einstein-Straße 9 07745 Jena Deutschland
| | - Michael Schmitt
- Institut für Physikalische Chemie und Abbe Center of Photonics; Friedrich-Schiller-Universität Jena; Helmholtzweg 4 07743 Jena Deutschland
| | - Iwan W. Schie
- Leibniz-Institut für Photonische Technologien; Albert-Einstein-Straße 9 07745 Jena Deutschland
| | - Dana Cialla-May
- Leibniz-Institut für Photonische Technologien; Albert-Einstein-Straße 9 07745 Jena Deutschland
- Institut für Physikalische Chemie und Abbe Center of Photonics; Friedrich-Schiller-Universität Jena; Helmholtzweg 4 07743 Jena Deutschland
| | - Christian Matthäus
- Leibniz-Institut für Photonische Technologien; Albert-Einstein-Straße 9 07745 Jena Deutschland
- Institut für Physikalische Chemie und Abbe Center of Photonics; Friedrich-Schiller-Universität Jena; Helmholtzweg 4 07743 Jena Deutschland
| | - Thomas Bocklitz
- Leibniz-Institut für Photonische Technologien; Albert-Einstein-Straße 9 07745 Jena Deutschland
- Institut für Physikalische Chemie und Abbe Center of Photonics; Friedrich-Schiller-Universität Jena; Helmholtzweg 4 07743 Jena Deutschland
| | - Jürgen Popp
- Leibniz-Institut für Photonische Technologien; Albert-Einstein-Straße 9 07745 Jena Deutschland
- Institut für Physikalische Chemie und Abbe Center of Photonics; Friedrich-Schiller-Universität Jena; Helmholtzweg 4 07743 Jena Deutschland
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35
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Krafft C, Schmitt M, Schie IW, Cialla-May D, Matthäus C, Bocklitz T, Popp J. Label-Free Molecular Imaging of Biological Cells and Tissues by Linear and Nonlinear Raman Spectroscopic Approaches. Angew Chem Int Ed Engl 2017; 56:4392-4430. [PMID: 27862751 DOI: 10.1002/anie.201607604] [Citation(s) in RCA: 152] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Revised: 11/04/2016] [Indexed: 12/20/2022]
Abstract
Raman spectroscopy is an emerging technique in bioanalysis and imaging of biomaterials owing to its unique capability of generating spectroscopic fingerprints. Imaging cells and tissues by Raman microspectroscopy represents a nondestructive and label-free approach. All components of cells or tissues contribute to the Raman signals, giving rise to complex spectral signatures. Resonance Raman scattering and surface-enhanced Raman scattering can be used to enhance the signals and reduce the spectral complexity. Raman-active labels can be introduced to increase specificity and multimodality. In addition, nonlinear coherent Raman scattering methods offer higher sensitivities, which enable the rapid imaging of larger sampling areas. Finally, fiber-based imaging techniques pave the way towards in vivo applications of Raman spectroscopy. This Review summarizes the basic principles behind medical Raman imaging and its progress since 2012.
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Affiliation(s)
- Christoph Krafft
- Leibniz-Institut für Photonische Technologien, Albert-Einstein-Strasse 9, 07745, Jena, Germany
| | - Michael Schmitt
- Institut für Physikalische Chemie und Abbe Center für Photonics, Friedrich Schiller Universität Jena, Helmholtzweg 4, 07743, Jena, Germany
| | - Iwan W Schie
- Leibniz-Institut für Photonische Technologien, Albert-Einstein-Strasse 9, 07745, Jena, Germany
| | - Dana Cialla-May
- Leibniz-Institut für Photonische Technologien, Albert-Einstein-Strasse 9, 07745, Jena, Germany.,Institut für Physikalische Chemie und Abbe Center für Photonics, Friedrich Schiller Universität Jena, Helmholtzweg 4, 07743, Jena, Germany
| | - Christian Matthäus
- Leibniz-Institut für Photonische Technologien, Albert-Einstein-Strasse 9, 07745, Jena, Germany.,Institut für Physikalische Chemie und Abbe Center für Photonics, Friedrich Schiller Universität Jena, Helmholtzweg 4, 07743, Jena, Germany
| | - Thomas Bocklitz
- Leibniz-Institut für Photonische Technologien, Albert-Einstein-Strasse 9, 07745, Jena, Germany.,Institut für Physikalische Chemie und Abbe Center für Photonics, Friedrich Schiller Universität Jena, Helmholtzweg 4, 07743, Jena, Germany
| | - Jürgen Popp
- Leibniz-Institut für Photonische Technologien, Albert-Einstein-Strasse 9, 07745, Jena, Germany.,Institut für Physikalische Chemie und Abbe Center für Photonics, Friedrich Schiller Universität Jena, Helmholtzweg 4, 07743, Jena, Germany
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Abstract
Despite significant effort, cancer still remains a leading cause of death worldwide. In order to reduce its burden, the development and improvement of noninvasive strategies for early detection and diagnosis of cancer are urgently needed. Raman spectroscopy, an optical technique that relies on inelastic light scattering arising from molecular vibrations, is one such strategy, as it can noninvasively probe cancerous markers using only endogenous contrast. In this review, spontaneous, coherent and surface enhanced Raman spectroscopies and imaging, as well as the fundamental principles governing the successful use of these techniques, are discussed. Methods for spectral data analysis are also highlighted. Utilization of the discussed Raman techniques for the detection and diagnosis of cancer in vitro, ex vivo and in vivo is described. The review concludes with a discussion of the future directions of Raman technologies, with particular emphasis on their clinical translation.
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Affiliation(s)
- Lauren A Austin
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA.
| | - Sam Osseiran
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA. and Harvard-MIT Division of Health Sciences and Technology, 77 Massachusetts Avenue E25-519, Cambridge, Massachusetts 02139, USA
| | - Conor L Evans
- Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA.
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Jermyn M, Desroches J, Aubertin K, St-Arnaud K, Madore WJ, De Montigny E, Guiot MC, Trudel D, Wilson BC, Petrecca K, Leblond F. A review of Raman spectroscopy advances with an emphasis on clinical translation challenges in oncology. Phys Med Biol 2016; 61:R370-R400. [DOI: 10.1088/0031-9155/61/23/r370] [Citation(s) in RCA: 81] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Lin K, Zheng W, Lim CM, Huang Z. Real-time in vivo diagnosis of laryngeal carcinoma with rapid fiber-optic Raman spectroscopy. BIOMEDICAL OPTICS EXPRESS 2016; 7:3705-3715. [PMID: 27699131 PMCID: PMC5030043 DOI: 10.1364/boe.7.003705] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 08/23/2016] [Accepted: 08/23/2016] [Indexed: 05/05/2023]
Abstract
We assess the clinical utility of a unique simultaneous fingerprint (FP) (i.e., 800-1800 cm-1) and high-wavenumber (HW) (i.e., 2800-3600 cm-1) fiber-optic Raman spectroscopy for in vivo diagnosis of laryngeal cancer at endoscopy. A total of 2124 high-quality in vivo FP/HW Raman spectra (normal = 1321; cancer = 581) were acquired from 101 tissue sites (normal = 71; cancer = 30) of 60 patients (normal = 44; cancer = 16) undergoing routine endoscopic examination. FP/HW Raman spectra differ significantly between normal and cancerous laryngeal tissue that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in the larynx. Partial least squares-discriminant analysis and leave-one tissue site-out, cross-validation were employed on the in vivo FP/HW tissue Raman spectra acquired, yielding a diagnostic accuracy of 91.1% (sensitivity: 93.3% (28/30); specificity: 90.1% (64/71)) for laryngeal cancer identification, which is superior to using either FP (accuracy: 86.1%; sensitivity: 86.7% (26/30); specificity: 85.9% (61/71)) or HW (accuracy: 84.2%; sensitivity: 76.7% (23/30); specificity: 87.3% (62/71)) Raman technique alone. Further receiver operating characteristic analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for laryngeal cancer diagnosis. We demonstrate for the first time that the simultaneous FP/HW Raman spectroscopy technique can be used for improving real-time in vivo diagnosis of laryngeal carcinoma during endoscopic examination.
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Affiliation(s)
- Kan Lin
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117576 Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, 119260 Singapore
| | - Wei Zheng
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117576 Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, 119260 Singapore
| | - Chwee Ming Lim
- Department of Otolaryngology, Head and Neck Surgery, National University of Singapore and National University Health System, 119074 Singapore
| | - Zhiwei Huang
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 117576 Singapore
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Wang J, Zheng W, Lin K, Huang Z. Development of a hybrid Raman spectroscopy and optical coherence tomography technique for real-time in vivo tissue measurements. OPTICS LETTERS 2016; 41:3045-8. [PMID: 27367097 DOI: 10.1364/ol.41.003045] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/22/2023]
Abstract
We report on the development of a unique sideview handheld hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) technique for real-time in vivo tissue measurements. A sideview handheld RS-OCT optical probe is designed to coalign the optical paths of RS and OCT sampling arms, whereby a compact long-pass dichroic mirror (LPDM) is utilized to transmit the OCT signal through a gradient index rod lens and a reflection mirror, whereas the LPDM deflects the tissue Raman signal by 90°, leading to coaligned RS/OCT optical samplings on the tissue. Further study shows that the hybrid RS and OCT technique developed is capable of simultaneously acquiring both morphological and biochemical information about the oral tissue in vivo, facilitating real-time, in vivo tissue diagnoses and characterizations in the oral cavity.
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40
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Wang J, Zheng W, Lin K, Huang Z. Integrated Mueller-matrix near-infrared imaging and point-wise spectroscopy improves colonic cancer detection. BIOMEDICAL OPTICS EXPRESS 2016; 7:1116-26. [PMID: 27446640 PMCID: PMC4929626 DOI: 10.1364/boe.7.001116] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Revised: 02/27/2016] [Accepted: 02/27/2016] [Indexed: 05/03/2023]
Abstract
We report the development and implementation of a unique integrated Mueller-matrix (MM) near-infrared (NIR) imaging and Mueller-matrix point-wise diffuse reflectance (DR) spectroscopy technique for improving colonic cancer detection and diagnosis. Point-wise MM DR spectra can be acquired from any suspicious tissue areas indicated by MM imaging. A total of 30 paired colonic tissue specimens (normal vs. cancer) were measured using the integrated MM imaging and point-wise MM DR spectroscopy system. Polar decomposition algorithms are employed on the acquired images and spectra to derive three polarization metrics including depolarization, diattentuation and retardance for colonic tissue characterization. The decomposition results show that tissue depolarization and retardance are significantly decreased (p<0.001, paired 2-sided Student's t-test, n = 30); while the tissue diattentuation is significantly increased (p<0.001, paired 2-sided Student's t-test, n = 30) associated with colonic cancer. Further partial least squares discriminant analysis (PLS-DA) and leave-one tissue site-out, cross validation (LOSCV) show that the combination of the three polarization metrics provide the best diagnostic accuracy of 95.0% (sensitivity: 93.3%, and specificity: 96.7%) compared to either of the three polarization metrics (sensitivities of 93.3%, 83.3%, and 80.0%; and specificities of 90.0%, 96.7%, and 80.0%, respectively, for the depolarization, diattentuation and retardance metrics) for colonic cancer detection. This work suggests that the integrated MM NIR imaging and point-wise MM NIR diffuse reflectance spectroscopy has the potential to improve the early detection and diagnosis of malignant lesions in the colon.
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Lin K, Wang J, Zheng W, Ho KY, Teh M, Yeoh KG, Huang Z. Rapid Fiber-optic Raman Spectroscopy for Real-Time In Vivo Detection of Gastric Intestinal Metaplasia during Clinical Gastroscopy. Cancer Prev Res (Phila) 2016; 9:476-83. [PMID: 27034388 DOI: 10.1158/1940-6207.capr-15-0213] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Accepted: 03/16/2016] [Indexed: 11/16/2022]
Abstract
We report a unique simultaneous fingerprint (FP) and high-wavenumber (HW) Raman spectroscopy technique coupled with a beveled fiber-optic Raman probe for improving in vivo detection of gastric intestinal metaplasia (IM)-precancerous lesions in real-time during clinical gastroscopy. A total of 4,520 high-quality in vivo FP/HW gastric Raman spectra (normal = 4,178; IM = 342) were acquired from 157 gastric patients undergoing endoscopic examination. Multivariate diagnostic algorithms based on principal components analysis and linear discriminant analysis together with the leave-one tissue site-out, cross-validation on in vivo tissue Raman spectra yield the diagnostic sensitivities of 89.3%, 89.3%, and 75.0%; specificities of 92.2%, 84.4%, and 82.0%; positive predictive values of 52.1%, 35.2%, and 28.4%; and negative predictive values of 98.9%, 98.8%, and 97.2%, respectively, by using the integrated FP/HW, FP, and HW Raman techniques for identifying IM from normal gastric tissue. Further, ROC curves generated show that the integrated FP/HW Raman technique gives the integration area under the ROC curve of 0.92 for IM classification, which is superior to either FP (0.89) or HW Raman (0.86) technique alone. This work demonstrates for the first time that the simultaneous FP/HW fiber-optic Raman spectroscopy has great potential to enhance early diagnosis of gastric precancer in vivo during routine endoscopic examination. Cancer Prev Res; 9(6); 476-83. ©2016 AACR.
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Affiliation(s)
- Kan Lin
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
| | - Jianfeng Wang
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore
| | - Wei Zheng
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
| | - Khek Yu Ho
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
| | - Ming Teh
- Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
| | - Khay Guan Yeoh
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore
| | - Zhiwei Huang
- Optical Bioimaging Laboratory, Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, Singapore.
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Shi H, Chen SY, Lin K. Raman spectroscopy for early real-time endoscopic optical diagnosis based on biochemical changes during the carcinogenesis of Barrett's esophagus. World J Gastrointest Endosc 2016; 8:273-275. [PMID: 26981179 PMCID: PMC4781908 DOI: 10.4253/wjge.v8.i5.273] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 12/16/2015] [Accepted: 01/08/2016] [Indexed: 02/05/2023] Open
Abstract
Raman spectroscopy is a spectroscopic technique based on the inelastic scattering of monochromatic light that represents the molecular composition of the interrogated volume to provide a direct molecular fingerprint. Several investigations have revealed that confocal Raman spectroscopy can differentiate non-dysplastic Barrett's esophagus from esophageal high-grade dysplasia and adenocarcinoma with high sensitivity and specificity. An automated on-line Raman spectral diagnostic system has made it possible to use Raman spectroscopy to guide accurate target biopsy instead of multiple random forceps-biopsies, this novel system is expected to improve in vivo precancerous diagnosis and tissue characterization of Barrett's esophagus.
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Wang J, Lin K, Zheng W, Ho KY, Teh M, Yeoh KG, Huang Z. Fiber-optic Raman spectroscopy for in vivo diagnosis of gastric dysplasia. Faraday Discuss 2016; 187:377-392. [DOI: 10.1039/c5fd00151j] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
This study aims to assess the clinical utility of a rapid fiber-optic Raman spectroscopy technique developed for enhancingin vivodiagnosis of gastric precancer during endoscopic examination. We have developed a real-time fiber-optic Raman spectroscopy system capable of simultaneously acquiring both fingerprint (FP) (i.e., 800–1800 cm−1) and high-wavenumber (HW) (i.e., 2800–3600 cm−1) Raman spectra from gastric tissuein vivoat endoscopy. A total of 5792 high-qualityin vivoFP/HW Raman spectra (normal (n= 5160); dysplasia (n= 155), and adenocarcinoma (n= 477)) were acquired in real-time from 441 tissue sites (normal (n= 396); dysplasia (n= 11), and adenocarcinoma (n= 34)) of 191 gastric patients (normal (n= 172); dysplasia (n= 6), and adenocarcinoma (n= 13)) undergoing routine endoscopic examinations. Partial least squares discriminant analysis (PLS-DA) together with leave-one-patient-out cross validation (LOPCV) were implemented to develop robust spectral diagnostic models. The FP/HW Raman spectra differ significantly between normal, dysplasia and adenocarcinoma of the stomach, which can be attributed to changes in proteins, lipids, nucleic acids, and the bound water content. PLS-DA and LOPCV show that the fiber-optic FP/HW Raman spectroscopy provides diagnostic sensitivities of 96.0%, 81.8% and 88.2%, and specificities of 86.7%, 95.3% and 95.6%, respectively, for the classification of normal, dysplastic and cancerous gastric tissue, superior to either the FP or HW Raman techniques alone. Further dichotomous PLS-DA analysis yields a sensitivity of 90.9% (10/11) and specificity of 95.9% (380/396) for the detection of gastric dysplasia using FP/HW Raman spectroscopy, substantiating its clinical advantages over white light reflectance endoscopy (sensitivity: 90.9% (10/11), and specificity: 51.0% (202/396)). This work demonstrates that the fiber-optic FP/HW Raman spectroscopy technique has great promise for enhancingin vivodiagnosis of gastric precancer during routine endoscopic examination.
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Affiliation(s)
- Jianfeng Wang
- Optical Bioimaging Laboratory
- Department of Biomedical Engineering
- Faculty of Engineering
- National University of Singapore
- Singapore 117576
| | - Kan Lin
- Optical Bioimaging Laboratory
- Department of Biomedical Engineering
- Faculty of Engineering
- National University of Singapore
- Singapore 117576
| | - Wei Zheng
- Optical Bioimaging Laboratory
- Department of Biomedical Engineering
- Faculty of Engineering
- National University of Singapore
- Singapore 117576
| | - Khek Yu Ho
- Department of Medicine
- Yong Loo Lin School of Medicine
- National University of Singapore
- National University Health System
- Singapore 119260
| | - Ming Teh
- Department of Pathology
- Yong Loo Lin School of Medicine
- National University of Singapore
- National University Health System
- Singapore 119074
| | - Khay Guan Yeoh
- Department of Medicine
- Yong Loo Lin School of Medicine
- National University of Singapore
- National University Health System
- Singapore 119260
| | - Zhiwei Huang
- Optical Bioimaging Laboratory
- Department of Biomedical Engineering
- Faculty of Engineering
- National University of Singapore
- Singapore 117576
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