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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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Slodička P, Falt P, Ranc V, Zoundjiekpon VD, Urban O. Raman spectroscopy in the diagnosis of malignant biliary stricture: A feasibility study. Hepatobiliary Pancreat Dis Int 2025; 24:211-216. [PMID: 39603958 DOI: 10.1016/j.hbpd.2024.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024]
Affiliation(s)
- Peter Slodička
- 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Olomouc, Czech Republic; Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Přemysl Falt
- 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Olomouc, Czech Republic; Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Václav Ranc
- Institute of Molecular and Translational Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
| | - Vincent Dansou Zoundjiekpon
- 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Olomouc, Czech Republic; Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Ondřej Urban
- 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Olomouc, Czech Republic; Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
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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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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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Liu C, Wang J, Shen J, Chen X, Ji N, Yue S. Accurate and rapid molecular subgrouping of high-grade glioma via deep learning-assisted label-free fiber-optic Raman spectroscopy. PNAS NEXUS 2024; 3:pgae208. [PMID: 38860145 PMCID: PMC11164103 DOI: 10.1093/pnasnexus/pgae208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 05/17/2024] [Indexed: 06/12/2024]
Abstract
Molecular genetics is highly related with prognosis of high-grade glioma. Accordingly, the latest WHO guideline recommends that molecular subgroups of the genes, including IDH, 1p/19q, MGMT, TERT, EGFR, Chromosome 7/10, CDKN2A/B, need to be detected to better classify glioma and guide surgery and treatment. Unfortunately, there is no preoperative or intraoperative technology available for accurate and comprehensive molecular subgrouping of glioma. Here, we develop a deep learning-assisted fiber-optic Raman diagnostic platform for accurate and rapid molecular subgrouping of high-grade glioma. Specifically, a total of 2,354 fingerprint Raman spectra was obtained from 743 tissue sites (astrocytoma: 151; oligodendroglioma: 150; glioblastoma (GBM): 442) of 44 high-grade glioma patients. The convolutional neural networks (ResNet) model was then established and optimized for molecular subgrouping. The mean area under receiver operating characteristic curves (AUC) for identifying the molecular subgroups of high-grade glioma reached 0.904, with mean sensitivity of 83.3%, mean specificity of 85.0%, mean accuracy of 83.3%, and mean time expense of 10.6 s. The diagnosis performance using ResNet model was shown to be superior to PCA-SVM and UMAP models, suggesting that high dimensional information from Raman spectra would be helpful. In addition, for the molecular subgroups of GBM, the mean AUC reached 0.932, with mean sensitivity of 87.8%, mean specificity of 83.6%, and mean accuracy of 84.1%. Furthermore, according to saliency maps, the specific Raman features corresponding to tumor-associated biomolecules (e.g. nucleic acid, tyrosine, tryptophan, cholesteryl ester, fatty acid, and collagen) were found to contribute to the accurate molecular subgrouping. Collectively, this study opens up new opportunities for accurate and rapid molecular subgrouping of high-grade glioma, which would assist optimal surgical resection and instant post-operative decision-making.
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Affiliation(s)
- Chang Liu
- Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Xueyuan Road 37, Beijing 100191, China
| | - Jiejun Wang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, South Fourth Ring West Road 119, Beijing 100050, China
| | - Jianghao Shen
- Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Xueyuan Road 37, Beijing 100191, China
| | - Xun Chen
- Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Xueyuan Road 37, Beijing 100191, China
- School of Engineering Medicine, Beihang University, Xueyuan Road 37, Beijing 100191, China
| | - Nan Ji
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, South Fourth Ring West Road 119, Beijing 100050, China
| | - Shuhua Yue
- Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education, Institute of Medical Photonics, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Xueyuan Road 37, Beijing 100191, China
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El-Sharkawy YH. Advancements in non-invasive hyperspectral imaging: Mapping blood oxygen levels and vascular health for clinical and research applications. Vascul Pharmacol 2024; 155:107380. [PMID: 38806138 DOI: 10.1016/j.vph.2024.107380] [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: 02/19/2024] [Revised: 05/14/2024] [Accepted: 05/16/2024] [Indexed: 05/30/2024]
Abstract
Oxygen content is crucial for the functioning of human body organs, as it plays a vital role in cellular respiration, which generates energy necessary for life-sustaining functions. The absence of adequate oxygen leads to cellular dysfunction and eventual organismal death due to energy deprivation. In this study, we designed a rapid, non-invasive, and non-contact custom hyperspectral imaging system to assess blood perfusion in arteries, capillaries, and veins across various human organs, including the arm, eye, and leg. The system recorded cube images consisting of multispectral image ranges, capturing spectral information in both the visible and infrared spectra. Segmentation of the visible spectrum (400 to 700 nm) and the infrared spectrum (700 to 1000 nm) facilitated the mapping of blood oxygen levels in the investigated samples. The estimated oxygen levels were calculated using the custom hyperspectral imaging system and associated algorithm, with validation and calibration performed against the gold standard pulse oximeter. Our results demonstrate that the custom hyperspectral imaging system accurately mapped blood perfusion and oxygen levels in organs, showing strong agreement with pulse oximeter measurements. This study underscores the utility of custom hyperspectral imaging in non-invasively assessing blood oxygenation and perfusion in human organs, offering a promising avenue for clinical diagnostics and monitoring of vascular health.
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Farooq A, Wood CD, Ladbury JE, Evans SD. On-chip Raman spectroscopy of live single cells for the staging of oesophageal adenocarcinoma progression. Sci Rep 2024; 14:1761. [PMID: 38242991 PMCID: PMC10799027 DOI: 10.1038/s41598-024-52079-3] [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: 08/22/2023] [Accepted: 01/12/2024] [Indexed: 01/21/2024] Open
Abstract
The absence of early diagnosis contributes to oesophageal cancer being the sixth most common cause of global cancer-associated deaths, with a 5-year survival rate of < 20%. Barrett's oesophagus is the main pre-cancerous condition to adenocarcinoma development, characterised by the morphological transition of oesophageal squamous epithelium to metaplastic columnar epithelium. Early tracking and treatment of oesophageal adenocarcinoma could dramatically improve with diagnosis and monitoring of patients with Barrett's Oesophagus. Current diagnostic methods involve invasive techniques such as endoscopies and, with only a few identified biomarkers of disease progression, the detection of oesophageal adenocarcinoma is costly and challenging. In this work, single-cell Raman spectroscopy was combined with microfluidic techniques to characterise the development of oesophageal adenocarcinoma through the progression of healthy epithelial, Barrett's oesophagus and oesophageal adenocarcinoma cell lines. Principal component analysis and linear discriminant analysis were used to classify the different stages of cancer progression. with the ability to differentiate between healthy and cancerous cells with an accuracy of 97%. Whilst the approach could also separate the dysplastic stages from healthy or cancer with high accuracy-the intra-class separation was approximately 68%. Overall, these results highlight the potential for rapid and reliable diagnostic/prognostic screening of Barrett's Oesophagus patients.
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Affiliation(s)
- Alisha Farooq
- School of Physics and Astronomy, University of Leeds, Leeds, UK
- School of Molecular and Cellular Biology, University of Leeds, Leeds, UK
| | - Christopher D Wood
- School of Electronic and Electrical Engineering, University of Leeds, Leeds, UK
| | - John E Ladbury
- School of Molecular and Cellular Biology, University of Leeds, Leeds, UK
| | - Stephen D Evans
- School of Physics and Astronomy, University of Leeds, Leeds, UK.
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Vaddi A, Tadinada A, Lurie A, Deymier A. Evaluation of near-infrared Raman spectroscopy in the differentiation of cortical bone, trabecular bone, and Bio-Oss bone graft: an ex-vivo study. Oral Surg Oral Med Oral Pathol Oral Radiol 2023; 136:632-639. [PMID: 37394288 DOI: 10.1016/j.oooo.2023.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 05/18/2023] [Accepted: 05/20/2023] [Indexed: 07/04/2023]
Abstract
OBJECTIVE We evaluated the ability of near-infrared Raman spectroscopy (near-IR RS) to differentiate among cortical bone, trabecular bone, and Bio-Oss, a bovinebone-based graft material. STUDY DESIGN We obtained a thinly sliced section of the mandible to collect cortical and trabecular bone samples and placed compacted Bio-Oss bone graft into a partially edentulous mandible in a dry human skull to obtain a comparable Bio-Oss sample. We performed near-IR RS of the 3 samples and evaluated the resultant Raman spectra to evaluate their differences. RESULTS We identified 3 sets of spectroscopic markers that differentiated Bio-Oss from human bone. The first consisted of significant shifts in the location of the 960 cm-1 phosphate (PO43-) peak and a reduction in its width, suggesting that Bio-Oss is more crystalline than bone. The second was the reduced carbonate content of Bio-Oss compared to bone, as determined from the 1070 cm-1/960 cm-1 peak area ratio. The final marker was the lack of collagen-associated peaks in Bio-Oss compared to cortical and trabecular bone. CONCLUSIONS Near-IR RS can reliably differentiate human cortical and trabecular bone from Bio-Oss via 3 sets of spectral markers associated with mineral crystallinity, carbonate content, and collagen content that differ significantly between them. Integrating this modality into dental practice may assist in implant treatment planning.
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Affiliation(s)
- Anusha Vaddi
- Section of Oral and Maxillofacial Radiology, Division of Oral and Maxillofacial Diagnostic Sciences, UConn School of Dental Medicine, UConn Health, Farmington, CT, USA.
| | - Aditya Tadinada
- Section of Oral and Maxillofacial Radiology, Division of Oral and Maxillofacial Diagnostic Sciences, UConn School of Dental Medicine, UConn Health, Farmington, CT, USA
| | - Alan Lurie
- Section of Oral and Maxillofacial Radiology, Division of Oral and Maxillofacial Diagnostic Sciences, UConn School of Dental Medicine, UConn Health, Farmington, CT, USA
| | - Alix Deymier
- Department of Biomedical Engineering, UConn School of Dental Medicine, UConn Health, Farmington, CT, USA
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Zhang L, Zhou Y, Wu B, Zhang S, Zhu K, Liu CH, Yu X, Alfano RR. A Handheld Visible Resonance Raman Analyzer Used in Intraoperative Detection of Human Glioma. Cancers (Basel) 2023; 15:cancers15061752. [PMID: 36980638 PMCID: PMC10046110 DOI: 10.3390/cancers15061752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/08/2023] [Accepted: 03/10/2023] [Indexed: 03/17/2023] Open
Abstract
There is still a lack of reliable intraoperative tools for glioma diagnosis and to guide the maximal safe resection of glioma. We report continuing work on the optical biopsy method to detect glioma grades and assess glioma boundaries intraoperatively using the VRR-LRRTM Raman analyzer, which is based on the visible resonance Raman spectroscopy (VRR) technique. A total of 2220 VRR spectra were collected during surgeries from 63 unprocessed fresh glioma tissues using the VRR-LRRTM Raman analyzer. After the VRR spectral analysis, we found differences in the native molecules in the fingerprint region and in the high-wavenumber region, and differences between normal (control) and different grades of glioma tissues. A principal component analysis–support vector machine (PCA-SVM) machine learning method was used to distinguish glioma tissues from normal tissues and different glioma grades. The accuracy in identifying glioma from normal tissue was over 80%, compared with the gold standard of histopathology reports of glioma. The VRR-LRRTM Raman analyzer may be a new label-free, real-time optical molecular pathology tool aiding in the intraoperative detection of glioma and identification of tumor boundaries, thus helping to guide maximal safe glioma removal and adjacent healthy tissue preservation.
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Affiliation(s)
- Liang Zhang
- Department of Neurosurgery, Medical School of Nankai University, Tianjin 300071, China
- Department of Neurosurgery, PLA General Hospital, Beijing 100853, China
| | - Yan Zhou
- Department of Neurosurgery, Air Force Medical Center, Beijing 100142, China
- Correspondence: (Y.Z.); (X.Y.)
| | - Binlin Wu
- Physics Department and CSCU Center for Nanotechnology, Southern Connecticut State University, New Haven, CT 06515, USA
| | | | - Ke Zhu
- Institute of Physics, Chinese Academy of Sciences (CAS), Beijing 100190, China
| | - Cheng-Hui Liu
- Institute for Ultrafast Spectroscopy and Lasers, Department of Physics, The City College of the City University of New York, New York, NY 10031, USA
| | - Xinguang Yu
- Department of Neurosurgery, Medical School of Nankai University, Tianjin 300071, China
- Department of Neurosurgery, PLA General Hospital, Beijing 100853, China
- Correspondence: (Y.Z.); (X.Y.)
| | - Robert R. Alfano
- Institute for Ultrafast Spectroscopy and Lasers, Department of Physics, The City College of the City University of New York, New York, NY 10031, USA
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10
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Huang W, Shang Q, Xiao X, Zhang H, Gu Y, Yang L, Shi G, Yang Y, Hu Y, Yuan Y, Ji A, Chen L. Raman spectroscopy and machine learning for the classification of esophageal squamous carcinoma. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2022; 281:121654. [PMID: 35878494 DOI: 10.1016/j.saa.2022.121654] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 07/15/2022] [Accepted: 07/17/2022] [Indexed: 02/05/2023]
Abstract
Early diagnosis of esophageal squamous cell carcinoma (ESCC), a common malignant tumor with a low overall survival rate due to metastasis and recurrence, is critical for effective treatment and improved prognosis. Raman spectroscopy, an advanced detection technology for esophageal cancer, was developed to improve diagnosis sensitivity, specificity, and accuracy. This study proposed a novel, effective, and noninvasive Raman spectroscopy technique to differentiate and classify ESCC cell lines. Seven ESCC cell lines and tissues of an ESCC patient with staging of T3N1M0 and T3N2M0 at low and high differentiation levels were investigated through Raman spectroscopy. Raman spectral data analysis was performed with four machine learning algorithms, namely principal components analysis (PCA)- linear discriminant analysis (LDA), PCA-eXtreme gradient boosting (XGB), PCA- support vector machine (SVM), and PCA- (LDA, XGB, SVM)-stacked Gradient Boosting Machine (GBM). Four machine learning algorithms were able to classifiy ESCC cell subtypes from normal esophageal cells. The PCA-XGB model achieved an overall predictive accuracy of 85% for classifying ESCC and adjacent tissues. Moreover, an overall predictive accuracy of 90.3% was achieved in distinguishing low differentiation and high differentiation ESCC tissues with the same stage when PCA-LDA, XGM, and SVM models were combined. This study illustrated the Raman spectral traits of ESCC cell lines and esophageal tissues related to clinical pathological diagnosis. Future studies should investigate the role of Raman spectral features in ESCC pathogenesis.
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Affiliation(s)
- Wenhua Huang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Qixin Shang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xin Xiao
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Hanlu Zhang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yimin Gu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Lin Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Guidong Shi
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yushang Yang
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yang Hu
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yong Yuan
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Aifang Ji
- Heping Hospital Affiliated to Changzhi Medical University, No. 161 Jiefang East Street, Changzhi 046000, China.
| | - Longqi Chen
- Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
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11
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In Situ Identification of Unknown Crystals in Acute Kidney Injury Using Raman Spectroscopy. NANOMATERIALS 2022; 12:nano12142395. [PMID: 35889619 PMCID: PMC9323692 DOI: 10.3390/nano12142395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/09/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022]
Abstract
Raman spectroscopy is a well-established and powerful tool for in situ biomolecular evaluation. Type 2 crystal nephropathies are characterized by the deposition of crystalline materials in the tubular lumen, resulting in rapid onset of acute kidney injury without specific symptoms. Timely crystal identification is essential for its diagnosis, mechanism exploration and therapy, but remains challenging. This study aims to develop a Raman spectroscopy-based method to assist pathological diagnosis of type 2 crystal nephropathies. Unknown crystals in renal tissue slides from a victim suffered extensive burn injury were detected by Raman spectroscopy, and the inclusion of crystals was determined by comparing Raman data with established database. Multiple crystals were scanned to verify the reproducibility of crystal in situ. Raman data of 20 random crystals were obtained, and the distribution and uniformity of substances in crystals were investigated by Raman imaging. A mouse model was established to mimic the crystal nephropathy to verify the availability of Raman spectroscopy in frozen biopsy. All crystals on the human slides were identified to be calcium oxalate dihydrate, and the distribution and content of calcium oxalate dihydrate on a single crystal were uneven. Raman spectroscopy was further validated to be available in identification of calcium oxalate dihydrate crystals in the biopsy specimens. Here, a Raman spectroscopy-based method for in situ identification of unknown crystals in both paraffin-embedded tissues and biopsy specimens was established, providing an effective and promising method to analyze unknown crystals in tissues and assist the precise pathological diagnosis in both clinical and forensic medicine.
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12
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Schiemer R, Furniss D, Phang S, Seddon AB, Atiomo W, Gajjar KB. Vibrational Biospectroscopy: An Alternative Approach to Endometrial Cancer Diagnosis and Screening. Int J Mol Sci 2022; 23:ijms23094859. [PMID: 35563249 PMCID: PMC9102412 DOI: 10.3390/ijms23094859] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/25/2022] [Accepted: 04/26/2022] [Indexed: 01/27/2023] Open
Abstract
Endometrial cancer (EC) is the sixth most common cancer and the fourth leading cause of death among women worldwide. Early detection and treatment are associated with a favourable prognosis and reduction in mortality. Unlike other common cancers, however, screening strategies lack the required sensitivity, specificity and accuracy to be successfully implemented in clinical practice and current diagnostic approaches are invasive, costly and time consuming. Such limitations highlight the unmet need to develop diagnostic and screening alternatives for EC, which should be accurate, rapid, minimally invasive and cost-effective. Vibrational spectroscopic techniques, Mid-Infrared Absorption Spectroscopy and Raman, exploit the atomic vibrational absorption induced by interaction of light and a biological sample, to generate a unique spectral response: a “biochemical fingerprint”. These are non-destructive techniques and, combined with multivariate statistical analysis, have been shown over the last decade to provide discrimination between cancerous and healthy samples, demonstrating a promising role in both cancer screening and diagnosis. The aim of this review is to collate available evidence, in order to provide insight into the present status of the application of vibrational biospectroscopy in endometrial cancer diagnosis and screening, and to assess future prospects.
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Affiliation(s)
- Roberta Schiemer
- Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham NG5 1PB, UK;
- Correspondence:
| | - David Furniss
- Mid-Infrared Photonics Group, George Green Institute for Electromagnetics Research, Faculty of Engineering, University of Nottingham, Nottingham NG7 2RD, UK; (D.F.); (S.P.); (A.B.S.)
| | - Sendy Phang
- Mid-Infrared Photonics Group, George Green Institute for Electromagnetics Research, Faculty of Engineering, University of Nottingham, Nottingham NG7 2RD, UK; (D.F.); (S.P.); (A.B.S.)
| | - Angela B. Seddon
- Mid-Infrared Photonics Group, George Green Institute for Electromagnetics Research, Faculty of Engineering, University of Nottingham, Nottingham NG7 2RD, UK; (D.F.); (S.P.); (A.B.S.)
| | - William Atiomo
- College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai P.O. Box 505055, United Arab Emirates;
| | - Ketankumar B. Gajjar
- Division of Child Health, Obstetrics and Gynaecology, University of Nottingham, Nottingham NG5 1PB, UK;
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13
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Cialla-May D, Krafft C, Rösch P, Deckert-Gaudig T, Frosch T, Jahn IJ, Pahlow S, Stiebing C, Meyer-Zedler T, Bocklitz T, Schie I, Deckert V, Popp J. Raman Spectroscopy and Imaging in Bioanalytics. Anal Chem 2021; 94:86-119. [PMID: 34920669 DOI: 10.1021/acs.analchem.1c03235] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Dana Cialla-May
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany.,InfectoGnostics Research Campus Jena, Center of Applied Research, Philosophenweg 7, 07743 Jena, Germany
| | - Christoph Krafft
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany
| | - Petra Rösch
- Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany
| | - Tanja Deckert-Gaudig
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany
| | - Torsten Frosch
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany
| | - Izabella J Jahn
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany
| | - Susanne Pahlow
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany.,InfectoGnostics Research Campus Jena, Center of Applied Research, Philosophenweg 7, 07743 Jena, Germany
| | - Clara Stiebing
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany
| | - Tobias Meyer-Zedler
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany
| | - Thomas Bocklitz
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany
| | - Iwan Schie
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Ernst-Abbe-Hochschule Jena, University of Applied Sciences, Department of Biomedical Engineering and Biotechnology, Carl-Zeiss-Promenade 2, 07745 Jena, Germany
| | - Volker Deckert
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany
| | - Jürgen Popp
- Leibniz-Institute of Photonic Technology, Member of the Leibniz Research Alliance - Leibniz Health Technologies, Albert-Einstein-Str. 9, 07745 Jena, Germany.,Institute of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University, Helmholtzweg 4, 07743 Jena, Germany.,InfectoGnostics Research Campus Jena, Center of Applied Research, Philosophenweg 7, 07743 Jena, Germany
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14
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Sloan-Dennison S, Laing S, Graham D, Faulds K. From Raman to SESORRS: moving deeper into cancer detection and treatment monitoring. Chem Commun (Camb) 2021; 57:12436-12451. [PMID: 34734952 PMCID: PMC8609625 DOI: 10.1039/d1cc04805h] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Raman spectroscopy is a non-invasive technique that allows specific chemical information to be obtained from various types of sample. The detailed molecular information that is present in Raman spectra permits monitoring of biochemical changes that occur in diseases, such as cancer, and can be used for the early detection and diagnosis of the disease, for monitoring treatment, and to distinguish between cancerous and non-cancerous biological samples. Several techniques have been developed to enhance the capabilities of Raman spectroscopy by improving detection sensitivity, reducing imaging times and increasing the potential applicability for in vivo analysis. The different Raman techniques each have their own advantages that can accommodate the alternative detection formats, allowing the techniques to be applied in several ways for the detection and diagnosis of cancer. This feature article discusses the various forms of Raman spectroscopy, how they have been applied for cancer detection, and the adaptation of the techniques towards their use for in vivo cancer detection and in clinical diagnostics. Despite the advances in Raman spectroscopy, the clinical application of the technique is still limited and certain challenges must be overcome to enable clinical translation. We provide an outlook on the future of the techniques in this area and what we believe is required to allow the potential of Raman spectroscopy to be achieved for clinical cancer diagnostics.
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Affiliation(s)
- Sian Sloan-Dennison
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, UK.
| | - Stacey Laing
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, UK.
| | - Duncan Graham
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, UK.
| | - Karen Faulds
- Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G1 1RD, UK.
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15
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Hakert H, Eibl M, Tillich M, Pries R, Hüttmann G, Brinkmann R, Wollenberg B, Bruchhage KL, Karpf S, Huber R. Time-encoded stimulated Raman scattering microscopy of tumorous human pharynx tissue in the fingerprint region from 1500-1800 cm -1. OPTICS LETTERS 2021; 46:3456-3459. [PMID: 34264237 DOI: 10.1364/ol.424726] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 06/14/2021] [Indexed: 06/13/2023]
Abstract
Stimulated Raman scattering (SRS) microscopy for biomedical analysis can provide a molecular localization map to infer pathological tissue changes. Compared to spontaneous Raman, SRS achieves much faster imaging speeds at reduced spectral coverage. By targeting spectral features in the information dense fingerprint region, SRS allows fast and reliable imaging. We present time-encoded (TICO) SRS microscopy of unstained head-and-neck biopsies in the fingerprint region with molecular contrast. We combine a Fourier-domain mode-locked (FDML) laser with a master oscillator power amplifier (MOPA) to cover Raman transitions from 1500-1800cm-1. Both lasers are fiber-based and electronically programmable making this fingerprint TICO system robust and reliable. The results of our TICO approach were cross-checked with a spontaneous Raman micro-spectrometer and show good agreement, paving the way toward clinical applications.
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16
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Ogawa H, Hashimoto M. Avoidance of four-wave mixing in optical fiber bundle for coherent anti-Stokes Raman scattering endomicroscopy. OPTICS LETTERS 2021; 46:3356-3359. [PMID: 34264212 DOI: 10.1364/ol.425644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 06/14/2021] [Indexed: 06/13/2023]
Abstract
We propose and demonstrate a method of suppressing four-wave mixing (FWM) in an optical fiber bundle to realize coherent anti-Stokes Raman scattering (CARS) endomicroscopy, which is the leading candidate for a definitive diagnosis of gastrointestinal cancer. Two excitation laser beams with different wavelengths are delivered via different cores to suppress FWM and are then combined with a polarization prism and a dual-wavelength wave plate and are focused to a spot. The background emission from the optical fiber bundle was suppressed to 1/3289, and we demonstrated CARS imaging of a polystyrene bead using the proposed method.
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17
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Plesia M, Stevens OA, Lloyd GR, Kendall CA, Coldicott I, Kennerley AJ, Miller G, Shaw PJ, Mead RJ, Day JCC, Alix JJP. In Vivo Fiber Optic Raman Spectroscopy of Muscle in Preclinical Models of Amyotrophic Lateral Sclerosis and Duchenne Muscular Dystrophy. ACS Chem Neurosci 2021; 12:1768-1776. [PMID: 33950665 PMCID: PMC8154326 DOI: 10.1021/acschemneuro.0c00794] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 04/30/2021] [Indexed: 12/13/2022] Open
Abstract
Neuromuscular diseases result in muscle weakness, disability, and, in many instances, death. Preclinical models form the bedrock of research into these disorders, and the development of in vivo and potentially translational biomarkers for the accurate identification of disease is crucial. Spontaneous Raman spectroscopy can provide a rapid, label-free, and highly specific molecular fingerprint of tissue, making it an attractive potential biomarker. In this study, we have developed and tested an in vivo intramuscular fiber optic Raman technique in two mouse models of devastating human neuromuscular diseases, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy (SOD1G93A and mdx, respectively). The method identified diseased and healthy muscle with high classification accuracies (area under the receiver operating characteristic curves (AUROC): 0.76-0.92). In addition, changes in diseased muscle over time were also identified (AUROCs 0.89-0.97). Key spectral changes related to proteins and the loss of α-helix protein structure. Importantly, in vivo recording did not cause functional motor impairment and only a limited, resolving tissue injury was seen on high-resolution magnetic resonance imaging. Lastly, we demonstrate that ex vivo muscle from human patients with these conditions produced similar spectra to those observed in mice. We conclude that spontaneous Raman spectroscopy of muscle shows promise as a translational research tool.
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Affiliation(s)
- Maria Plesia
- Sheffield
Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
| | - Oliver A. Stevens
- Interface
Analysis Centre, School of Physics, University
of Bristol, Bristol BS8 1TL, UK
| | - Gavin R. Lloyd
- Phenome
Centre Birmingham, University of Birmingham, Birmingham B15 2TT, UK
- Biophotonics
Research Unit, Gloucestershire Hospitals
NHS Foundation Trust, Gloucester GL1 3NN, UK
| | - Catherine A. Kendall
- Biophotonics
Research Unit, Gloucestershire Hospitals
NHS Foundation Trust, Gloucester GL1 3NN, UK
| | - Ian Coldicott
- Sheffield
Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
| | | | - Gaynor Miller
- Department
of Oncology and Metabolism, University of
Sheffield, Sheffield S10 2RX, UK
| | - Pamela J. Shaw
- Sheffield
Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
- Cross-Faculty
Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK
| | - Richard J. Mead
- Sheffield
Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
- Cross-Faculty
Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK
| | - John C. C. Day
- Interface
Analysis Centre, School of Physics, University
of Bristol, Bristol BS8 1TL, UK
| | - James J. P. Alix
- Sheffield
Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
- Cross-Faculty
Neuroscience Institute, University of Sheffield, Sheffield S10 2HQ, UK
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18
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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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19
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Identifying metastatic ability of prostate cancer cell lines using native fluorescence spectroscopy and machine learning methods. Sci Rep 2021; 11:2282. [PMID: 33500529 PMCID: PMC7838178 DOI: 10.1038/s41598-021-81945-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 01/08/2021] [Indexed: 12/20/2022] Open
Abstract
Metastasis is the leading cause of mortalities in cancer patients due to the spreading of cancer cells to various organs. Detecting cancer and identifying its metastatic potential at the early stage is important. This may be achieved based on the quantification of the key biomolecular components within tissues and cells using recent optical spectroscopic techniques. The aim of this study was to develop a noninvasive label-free optical biopsy technique to retrieve the characteristic molecular information for detecting different metastatic potentials of prostate cancer cells. Herein we report using native fluorescence (NFL) spectroscopy along with machine learning (ML) to differentiate prostate cancer cells with different metastatic abilities. The ML algorithms including principal component analysis (PCA) and nonnegative matrix factorization (NMF) were used for dimension reduction and feature detection. The characteristic component spectra were used to identify the key biomolecules that are correlated with metastatic potentials. The relative concentrations of the molecular spectral components were retrieved and used to classify the cancer cells with different metastatic potentials. A multi-class classification was performed using support vector machines (SVMs). The NFL spectral data were collected from three prostate cancer cell lines with different levels of metastatic potentials. The key biomolecules in the prostate cancer cells were identified to be tryptophan, reduced nicotinamide adenine dinucleotide (NADH) and hypothetically lactate as well. The cancer cells with different metastatic potentials were classified with high accuracy using the relative concentrations of the key molecular components. The results suggest that the changes in the relative concentrations of these key fluorophores retrieved from NFL spectra may present potential criteria for detecting prostate cancer cells of different metastatic abilities.
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20
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Nicolson F, Kircher MF. Theranostics: Agents for Diagnosis and Therapy. Mol Imaging 2021. [DOI: 10.1016/b978-0-12-816386-3.00040-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
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21
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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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22
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Maitra I, Date RS, Martin FL. Towards screening Barrett's oesophagus: current guidelines, imaging modalities and future developments. Clin J Gastroenterol 2020; 13:635-649. [PMID: 32495144 PMCID: PMC7519897 DOI: 10.1007/s12328-020-01135-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 05/21/2020] [Indexed: 02/07/2023]
Abstract
Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma (OAC). Although guidelines on the screening and surveillance exist in Barrett's oesophagus, the current strategies are inadequate. Oesophagogastroduodenoscopy (OGD) is the gold standard method in screening for Barrett's oesophagus. This invasive method is expensive with associated risks negating its use as a current screening tool for Barrett's oesophagus. This review explores current definitions, epidemiology, biomarkers, surveillance, and screening in Barrett's oesophagus. Imaging modalities applicable to this condition are discussed, in addition to future developments. There is an urgent need for an alternative non-invasive method of screening and/or surveillance which could be highly beneficial towards reducing waiting times, alleviating patient fears and reducing future costs in current healthcare services. Vibrational spectroscopy has been shown to be promising in categorising Barrett's oesophagus through to high-grade dysplasia (HGD) and OAC. These techniques need further validation through multicentre trials.
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Affiliation(s)
- Ishaan Maitra
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE UK
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23
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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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24
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Soh YSA, Lee YY, Gotoda T, Sharma P, Ho KY. Challenges to diagnostic standardization of Barrett's esophagus in Asia. Dig Endosc 2019; 31:609-618. [PMID: 30892742 DOI: 10.1111/den.13402] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 03/13/2019] [Indexed: 12/14/2022]
Abstract
Barrett's esophagus (BE), a premalignant condition of the lower esophagus, is increasingly prevalent in Asia. However, endoscopic and histopathological criteria vary widely between studies across Asia, making it challenging to assess comparability between geographical regions. Furthermore, guidelines from various societies worldwide provide differing viewpoints and definitions, leading to diagnostic challenges that affect prognostication of the condition. In this review, the authors discuss the controversies surrounding the diagnosis of BE, particularly in Asia. Differences between guidelines worldwide are summarized with further discussion regarding various classifications of BE used, different definitions of gastroesophageal junction used across geographical regions and the clinical implications of intestinal metaplasia in the setting of BE. Although many guidelines recommend the Seattle protocol as the preferred approach regarding dysplasia surveillance in BE, some limitations exist, leading to poor adherence. Newer technologies, such as acetic acid-enhanced magnification endoscopy, narrow band imaging, Raman spectroscopy, molecular approaches and the use of artificial intelligence appear promising in addressing these problems, but further studies are required before implementation into routine clinical practice. The Asian Barrett's Consortium also outlines its ongoing plans to tackle the challenge of standardizing the diagnosis of BE in Asia.
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Affiliation(s)
- Yu Sen Alex Soh
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Prateek Sharma
- Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, USA.,Gastroenterology, University of Kansas, School of Medicine, Kansas City, USA
| | - Khek-Yu Ho
- Department of Gastroenterology and Hepatology, National University Hospital, Singapore.,Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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25
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de Oliveira MAS, Campbell M, Afify AM, Huang EC, Chan JW. Hyperspectral Raman microscopy can accurately differentiate single cells of different human thyroid nodules. BIOMEDICAL OPTICS EXPRESS 2019; 10:4411-4421. [PMID: 31565498 PMCID: PMC6757446 DOI: 10.1364/boe.10.004411] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 06/24/2019] [Accepted: 07/08/2019] [Indexed: 05/07/2023]
Abstract
We report on the use of line-scan hyperspectral Raman microscopy in combination with multivariate statistical analyses for identifying and classifying single cells isolated from clinical samples of human thyroid nodules based on their intrinsic Raman spectral signatures. A total of 248 hyperspectral Raman images of single cells from benign thyroid (n = 127) and classic variant of papillary carcinoma (n = 121) nodules were collected. Spectral differences attributed to phenylalanine, tryptophan, proteins, lipids, and nucleic acids were identified for benign and papillary carcinoma cells. Using principal component analysis and linear discriminant analysis, cells were identified with 97% diagnostic accuracy. In addition, preliminary data of cells from follicular adenoma (n = 20), follicular carcinoma (n = 25), and follicular variant of papillary carcinoma (n = 18) nodules suggest the feasibility of further discrimination of subtypes. Our findings indicate that hyperspectral Raman microscopy can potentially be developed into an objective approach for analyzing single cells from fine needle aspiration (FNA) biopsies to enable the minimally invasive diagnosis of "indeterminate" thyroid nodules and other challenging cases.
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Affiliation(s)
- Marcos A. S. de Oliveira
- Department of Pathology & Laboratory Medicine, Univ. of California Davis, Sacramento, CA 95817, USA
| | - Michael Campbell
- Department of Surgery, Univ. of California Davis, Sacramento, CA 95817, USA
| | - Alaa M. Afify
- Department of Pathology & Laboratory Medicine, Univ. of California Davis, Sacramento, CA 95817, USA
| | - Eric C. Huang
- Department of Pathology, Univ. of Washington, Seattle, WA 98104, USA
- ECH and JWC contributed equally as senior authors
| | - James W. Chan
- Department of Pathology & Laboratory Medicine, Univ. of California Davis, Sacramento, CA 95817, USA
- ECH and JWC contributed equally as senior authors
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26
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Zhou Y, Liu CH, Wu B, Yu X, Cheng G, Zhu K, Wang K, Zhang C, Zhao M, Zong R, Zhang L, Shi L, Alfano RR. Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy. JOURNAL OF BIOMEDICAL OPTICS 2019; 24:1-12. [PMID: 31512439 PMCID: PMC6997631 DOI: 10.1117/1.jbo.24.9.095001] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 07/26/2019] [Indexed: 05/06/2023]
Abstract
Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins.
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Affiliation(s)
- Yan Zhou
- PLA Air Force Medical Center, Department of Neurosurgery, Beijing, China
| | - Cheng-Hui Liu
- City University of New York, Institute for Ultrafast Spectroscopy and Lasers, Department of Physics of the City College, New York, United States
| | - Binlin Wu
- Southern Connecticut State University, CSCU Center for Nanotechnology, Physics Department, New Haven, Connecticut, United States
| | - Xinguang Yu
- PLA General Hospital, Department of Neurosurgery, Beijing, China
| | - Gangge Cheng
- PLA Air Force Medical Center, Department of Neurosurgery, Beijing, China
| | - Ke Zhu
- Chinese Academy of Sciences, Institute of Physics, Beijing, China
| | - Kai Wang
- Jilin University, State Key Laboratory of Superhard Materials, Changchun, China
| | - Chunyuan Zhang
- City University of New York, Institute for Ultrafast Spectroscopy and Lasers, Department of Physics of the City College, New York, United States
| | - Mingyue Zhao
- PLA Air Force Medical Center, Department of Neurosurgery, Beijing, China
| | - Rui Zong
- PLA General Hospital, Department of Neurosurgery, Beijing, China
| | - Lin Zhang
- City University of New York, Institute for Ultrafast Spectroscopy and Lasers, Department of Physics of the City College, New York, United States
| | - Lingyan Shi
- University of California San Diego, Department of Bioengineering, La Jolla, California, United States
| | - Robert R. Alfano
- City University of New York, Institute for Ultrafast Spectroscopy and Lasers, Department of Physics of the City College, New York, United States
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27
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Czamara K, Majka Z, Fus A, Matjasik K, Pacia MZ, Sternak M, Chlopicki S, Kaczor A. Raman spectroscopy as a novel tool for fast characterization of the chemical composition of perivascular adipose tissue. Analyst 2019; 143:5999-6005. [PMID: 30334021 DOI: 10.1039/c8an01307a] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
One of the new targets of untapped therapeutic potential is perivascular adipose tissue (pVAT). pVAT releases a plethora of pro- and anti-inflammatory agents and is involved in the inflammatory response of the vascular wall, playing a key role in various cardiovascular pathologies. Both fiber optic Raman spectroscopy with a high-spatial resolution probe and Raman microscopy were applied to study various types of adipose tissue with the emphasis on pVATs of the thoracic and abdominal aorta and the mesenteric artery, as well as epididymal and interscapular adipose tissue for comparison. Our results demonstrated that the lipid unsaturation degree was clearly distinct in various types of adipose tissue and was influenced by the age of animals. In particular, the basal unsaturation level of pVATs of the abdominal aorta and the mesenteric artery was considerably higher than that of the thoracic aorta and a significant increase of the unsaturation level of pVAT with age was observed showing that aging has a considerable impact on the pVAT's chemical composition. Overall, our results show that Raman spectroscopy is a sensitive tool to determine the perivascular adipose tissue chemical composition that appears to be vascular-bed specific.
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Affiliation(s)
- Krzysztof Czamara
- Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, 14 Bobrzynskiego Str., 30-348 Krakow, Poland.
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28
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Label-free Evaluation of Myocardial Infarct in Surgically Excised Ventricular Myocardium by Raman Spectroscopy. Sci Rep 2018; 8:14671. [PMID: 30279495 PMCID: PMC6168494 DOI: 10.1038/s41598-018-33025-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 09/20/2018] [Indexed: 12/20/2022] Open
Abstract
Understanding the viability of the ischemic myocardial tissue is a critical issue in determining the appropriate surgical procedure for patients with chronic heart failure after myocardial infarction (MI). Conventional MI evaluation methods are; however, preoperatively performed and/or give an indirect information of myocardial viability such as shape, color, and blood flow. In this study, we realize the evaluation of MI in patients undergoing cardiac surgery by Raman spectroscopy under label-free conditions, which is based on intrinsic molecular constituents related to myocardial viability. We identify key signatures of Raman spectra for the evaluation of myocardial viability by evaluating the infarct border zone myocardium that were excised from five patients under surgical ventricular restoration. We also obtain a prediction model to differentiate the infarcted myocardium from the non-infarcted myocardium by applying partial least squares regression-discriminant analysis (PLS-DA) to the Raman spectra. Our prediction model enables identification of the infarcted tissues and the non-infarcted tissues with sensitivities of 99.98% and 99.92%, respectively. Furthermore, the prediction model of the Raman images of the infarct border zone enabled us to visualize boundaries between these distinct regions. Our novel application of Raman spectroscopy to the human heart would be a useful means for the detection of myocardial viability during surgery.
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29
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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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30
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Isabelle M, Dorney J, Lewis A, Lloyd GR, Old O, Shepherd N, Rodriguez-Justo M, Barr H, Lau K, Bell I, Ohrel S, Thomas G, Stone N, Kendall C. Multi-centre Raman spectral mapping of oesophageal cancer tissues: a study to assess system transferability. Faraday Discuss 2018; 187:87-103. [PMID: 27048868 DOI: 10.1039/c5fd00183h] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The potential for Raman spectroscopy to provide early and improved diagnosis on a wide range of tissue and biopsy samples in situ is well documented. The standard histopathology diagnostic methods of reviewing H&E and/or immunohistochemical (IHC) stained tissue sections provides valuable clinical information, but requires both logistics (review, analysis and interpretation by an expert) and costly processing and reagents. Vibrational spectroscopy offers a complimentary diagnostic tool providing specific and multiplexed information relating to molecular structure and composition, but is not yet used to a significant extent in a clinical setting. One of the challenges for clinical implementation is that each Raman spectrometer system will have different characteristics and therefore spectra are not readily compatible between systems. This is essential for clinical implementation where classification models are used to compare measured biochemical or tissue spectra against a library training dataset. In this study, we demonstrate the development and validation of a classification model to discriminate between adenocarcinoma (AC) and non-cancerous intraepithelial metaplasia (IM) oesophageal tissue samples, measured on three different Raman instruments across three different locations. Spectra were corrected using system transfer spectral correction algorithms including wavenumber shift (offset) correction, instrument response correction and baseline removal. The results from this study indicate that the combined correction methods do minimize the instrument and sample quality variations within and between the instrument sites. However, more tissue samples of varying pathology states and greater tissue area coverage (per sample) are needed to properly assess the ability of Raman spectroscopy and system transferability algorithms over multiple instrument sites.
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Affiliation(s)
- M Isabelle
- Biophotonics Research Unit and Pathology Department, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.
| | - J Dorney
- Biomedical Spectroscopy, School of Physics, University of Exeter, UK
| | - A Lewis
- Department of Cell and Developmental Biology, University College London, London, UK
| | - G R Lloyd
- Biophotonics Research Unit and Pathology Department, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.
| | - O Old
- Biophotonics Research Unit and Pathology Department, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.
| | - N Shepherd
- Biophotonics Research Unit and Pathology Department, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.
| | - M Rodriguez-Justo
- Department of Cell and Developmental Biology, University College London, London, UK
| | - H Barr
- Biophotonics Research Unit and Pathology Department, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.
| | - K Lau
- Spectroscopy Products Division, Renishaw plc, Wotton-Under-Edge, Gloucestershire, UK
| | - I Bell
- Spectroscopy Products Division, Renishaw plc, Wotton-Under-Edge, Gloucestershire, UK
| | - S Ohrel
- Spectroscopy Products Division, Renishaw plc, Wotton-Under-Edge, Gloucestershire, UK
| | - G Thomas
- Department of Cell and Developmental Biology, University College London, London, UK
| | - N Stone
- Biomedical Spectroscopy, School of Physics, University of Exeter, UK
| | - C Kendall
- Biophotonics Research Unit and Pathology Department, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.
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31
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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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32
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Daniel A, Prakasarao A, Ganesan S. Near-infrared Raman spectroscopy for estimating biochemical changes associated with different pathological conditions of cervix. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2018; 190:409-416. [PMID: 28954253 DOI: 10.1016/j.saa.2017.09.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 07/23/2017] [Accepted: 09/08/2017] [Indexed: 06/07/2023]
Abstract
The molecular level changes associated with oncogenesis precede the morphological changes in cells and tissues. Hence molecular level diagnosis would promote early diagnosis of the disease. Raman spectroscopy is capable of providing specific spectral signature of various biomolecules present in the cells and tissues under various pathological conditions. The aim of this work is to develop a non-linear multi-class statistical methodology for discrimination of normal, neoplastic and malignant cells/tissues. The tissues were classified as normal, pre-malignant and malignant by employing Principal Component Analysis followed by Artificial Neural Network (PC-ANN). The overall accuracy achieved was 99%. Further, to get an insight into the quantitative biochemical composition of the normal, neoplastic and malignant tissues, a linear combination of the major biochemicals by non-negative least squares technique was fit to the measured Raman spectra of the tissues. This technique confirms the changes in the major biomolecules such as lipids, nucleic acids, actin, glycogen and collagen associated with the different pathological conditions. To study the efficacy of this technique in comparison with histopathology, we have utilized Principal Component followed by Linear Discriminant Analysis (PC-LDA) to discriminate the well differentiated, moderately differentiated and poorly differentiated squamous cell carcinoma with an accuracy of 94.0%. And the results demonstrated that Raman spectroscopy has the potential to complement the good old technique of histopathology.
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Affiliation(s)
- Amuthachelvi Daniel
- Department of Medical Physics, Anna University, Sardar Patel Road, Chennai 600025, India.
| | - Aruna Prakasarao
- Department of Medical Physics, Anna University, Sardar Patel Road, Chennai 600025, India
| | - Singaravelu Ganesan
- Department of Medical Physics, Anna University, Sardar Patel Road, Chennai 600025, India
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Hirose K, Aoki T, Furukawa T, Fukushima S, Niioka H, Deguchi S, Hashimoto M. Coherent anti-Stokes Raman scattering rigid endoscope toward robot-assisted surgery. BIOMEDICAL OPTICS EXPRESS 2018; 9:387-396. [PMID: 29552380 PMCID: PMC5854045 DOI: 10.1364/boe.9.000387] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 12/16/2017] [Accepted: 12/18/2017] [Indexed: 05/16/2023]
Abstract
Label-free visualization of nerves and nervous plexuses will improve the preservation of neurological functions in nerve-sparing robot-assisted surgery. We have developed a coherent anti-Stokes Raman scattering (CARS) rigid endoscope to distinguish nerves from other tissues during surgery. The developed endoscope, which has a tube with a diameter of 12 mm and a length of 270 mm, achieved 0.91% image distortion and 8.6% non-uniformity of CARS intensity in the whole field of view (650 μm diameter). We demonstrated CARS imaging of a rat sciatic nerve and visualization of the fine structure of nerve fibers.
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Affiliation(s)
- K. Hirose
- Graduate School of Engineering Science, Osaka University, Osaka,
Japan
| | - T. Aoki
- Graduate School of Engineering Science, Osaka University, Osaka,
Japan
| | - T. Furukawa
- Faculty of Engineering, Yokohama National University, Yokohama,
Japan
| | - S. Fukushima
- Graduate School of Engineering Science, Osaka University, Osaka,
Japan
| | - H. Niioka
- Graduate School of Engineering Science, Osaka University, Osaka,
Japan
| | - S. Deguchi
- Graduate School of Engineering Science, Osaka University, Osaka,
Japan
| | - M. Hashimoto
- Graduate School of Information Science and Technology, Hokkaido University, Hokkaido,
Japan
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34
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Pacia MZ, Czamara K, Zebala M, Kus E, Chlopicki S, Kaczor A. Rapid diagnostics of liver steatosis by Raman spectroscopyviafiber optic probe: a pilot study. Analyst 2018; 143:4723-4731. [DOI: 10.1039/c8an00289d] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Raman spectroscopyviafiber optic probes enables assessment of the liver condition and rapid quantification of liver steatosis, thus, this technique has the potential as a diagnostic tool.
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Affiliation(s)
- Marta Z. Pacia
- Jagiellonian Centre for Experimental Therapeutics (JCET)
- Jagiellonian University
- 30-348 Krakow
- Poland
- Faculty of Chemistry
| | - Krzysztof Czamara
- Jagiellonian Centre for Experimental Therapeutics (JCET)
- Jagiellonian University
- 30-348 Krakow
- Poland
- Faculty of Chemistry
| | - Magdalena Zebala
- Jagiellonian Centre for Experimental Therapeutics (JCET)
- Jagiellonian University
- 30-348 Krakow
- Poland
- Faculty of Chemistry
| | - Edyta Kus
- Jagiellonian Centre for Experimental Therapeutics (JCET)
- Jagiellonian University
- 30-348 Krakow
- Poland
| | - Stefan Chlopicki
- Jagiellonian Centre for Experimental Therapeutics (JCET)
- Jagiellonian University
- 30-348 Krakow
- Poland
- Chair of Pharmacology
| | - Agnieszka Kaczor
- Jagiellonian Centre for Experimental Therapeutics (JCET)
- Jagiellonian University
- 30-348 Krakow
- Poland
- Faculty of Chemistry
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Abramczyk H, Brozek-Pluska B. Apical-basal polarity of epithelial cells imaged by Raman microscopy and Raman imaging: Capabilities and challenges for cancer research. J Mol Liq 2017. [DOI: 10.1016/j.molliq.2017.05.142] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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36
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Kim YI, Jeong S, Jun BH, Lee YS, Lee YS, Jeong DH, Lee DS. Endoscopic imaging using surface-enhanced Raman scattering. EUROPEAN JOURNAL OF NANOMEDICINE 2017. [DOI: 10.1515/ejnm-2017-0005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AbstractIn this review, we assessed endoscopic imaging using surface-enhanced Raman scattering (SERS). As white-light endoscopy, the current standard for gastrointestinal endoscopy, is limited to morphology, Raman endoscopy using surface-enhanced Raman scattering nanoparticles (SERS endoscopy) was introduced as one of the novel functional modalities. SERS endoscopy has multiplex capability and high sensitivity with low autofluorescence and photobleaching. As a result, multiple molecular characteristics of the lesion can be accurately evaluated in real time while performing endoscopy using SERS probes and appropriate instrumentation. Especially, recently developed dual modality of fluorescence and SERS endoscopy offers easy localization with identification of multiple target molecules. For clinical use of SERS endoscopy in the future, problems of limited field of view and cytotoxicity should be addressed by fusion imaging, topical administration, and non-toxic coating of nanoparticles. We expect SERS endoscopic imaging would be an essential endoscopic technique for diagnosis of cancerous lesions, assessment of resection margins and evaluation of therapeutic responses.
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37
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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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38
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Brusatori M, Auner G, Noh T, Scarpace L, Broadbent B, Kalkanis SN. Intraoperative Raman Spectroscopy. Neurosurg Clin N Am 2017; 28:633-652. [PMID: 28917291 DOI: 10.1016/j.nec.2017.05.014] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Surgical excision of brain tumors provides a means of cytoreduction and diagnosis while minimizing neurologic deficit and improving overall survival. Despite advances in functional and three-dimensional stereotactic navigation and intraoperative MRI, delineating tissue in real time with physiologic confirmation is challenging. Raman spectroscopy has potential to be an important modality in the intraoperative evaluation of tissue during surgical resection. In vitro experimental studies have shown that this technique can be used to differentiate normal brain tissue from tissue with infiltrating cancer cells and dense cancerous masses with high specificity, indicating the feasibility of this method for in vivo application.
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Affiliation(s)
- Michelle Brusatori
- Department of Surgery, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA; Department of Biomedical Engineering, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA; Department of Smart Sensors and Integrated Microsystems, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA
| | - Gregory Auner
- Department of Surgery, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA; Department of Biomedical Engineering, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA; Department of Smart Sensors and Integrated Microsystems, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA; The Detroit Institute of Ophthalmology, Henry Ford Health System, 15415 E. Jefferson Avenue, Grosse Pointe Park, MI 48230, USA
| | - Thomas Noh
- Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Josephine Ford Cancer Center, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA
| | - Lisa Scarpace
- Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA
| | - Brandy Broadbent
- Department of Surgery, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA; Department of Biomedical Engineering, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA; Department of Smart Sensors and Integrated Microsystems, Wayne State University, 5050 Anthony Wayne Drive, Detroit, MI 48202, USA
| | - Steven N Kalkanis
- Department of Neurosurgery, Hermelin Brain Tumor Center, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Josephine Ford Cancer Center, Henry Ford Health System, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
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Lim L, Streutker CJ, Marcon N, Cirocco M, Lao A, Iakovlev VV, DaCosta R, Wilson BC. A feasibility study of photoacoustic imaging of ex vivo endoscopic mucosal resection tissues from Barrett's esophagus patients. Endosc Int Open 2017; 5:E775-E783. [PMID: 28791328 PMCID: PMC5546898 DOI: 10.1055/s-0043-111790] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 05/02/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Accurate endoscopic detection of dysplasia in patients with Barrett's esophagus (BE) remains a major clinical challenge. The current standard is to take multiple biopsies under endoscopic image guidance, but this leaves the majority of the tissue unsampled, leading to significant risk of missing dysplasia. Furthermore, determining whether there is submucosal invasion is essential for proper staging. Hence, there is a clinical need for a rapid in vivo wide-field imaging method to identify dysplasia in BE, with the capability of imaging beyond the mucosal layer. We conducted an ex vivo feasibility study using photoacoustic imaging (PAI) in patients undergoing endoscopic mucosal resection (EMR) for known dysplasia. The objective was to characterize the esophageal microvascular pattern, with the long-term goal of performing in vivo endoscopic PAI for dysplasia detection and therapeutic guidance. MATERIALS AND METHODS EMR tissues were mounted luminal side up. The tissues were scanned over a field of view of 14 mm (width) by 15 mm (depth) at 680, 750, and 850 nm (40 MHz acoustic central frequency). Ultrasound and photoacoustic images were simultaneously acquired. Tissues were then sliced and fixed in formalin for histopathology with hematoxylin and eosin staining. A total of 13 EMR specimens from eight patients were included in the analysis, which consisted of co-registration of the photoacoustic images with corresponding pathologist-classified histological images. We conducted mean difference test of the total hemoglobin distribution between tissue classes. RESULTS Dysplastic and nondysplastic BE can be distinguished from squamous tissue in 84 % of region-of-interest comparisons (42/50). However, the ability of intrinsic PAI to distinguish dysplasia from NDBE, which is the clinically important challenge, was only about 33 % (10/30). CONCLUSION We demonstrated the technical feasibility of this approach. Based on our ex vivo data, changes in total hemoglobin content from intrinsic PAI (i. e. without exogenous contrast) can differentiate BE from squamous esophageal mucosa. However, most likely intrinsic PAI is unable to differentiate dysplastic from nondysplastic BE with adequate sensitivity for clinical translation.
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Affiliation(s)
- Liang Lim
- Princess Margaret Cancer Centre, Toronto, Ontario, Canada,Corresponding author Liang Lim, PhD University Health Network – Princess Margaret Cancer Centre101 College StreetPMCRT #15-301V TorontoOntario M5G 1L7Canada
| | | | | | | | | | | | - Ralph DaCosta
- Princess Margaret Cancer Centre, Toronto, Ontario, Canada
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Lim L, Mastragostino R, Ng K, Zheng G, Wilson BC. Can photoacoustic imaging quantify surface-localized J-aggregating nanoparticles? JOURNAL OF BIOMEDICAL OPTICS 2017; 22:76008. [PMID: 28703256 DOI: 10.1117/1.jbo.22.7.076008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 06/21/2017] [Indexed: 05/07/2023]
Abstract
We investigate the feasibility of photoacoustic (PA) imaging to quantify the concentration of surface-localized nanoparticles, using tissue-mimicking phantoms and imaging with a commercial PA instrument at 815 nm and a linear-array transducer at a center frequency of 40 MHz. The nanoparticles were J-aggregating porphysomes (JNP) comprising self-assembling, all-organic porphyrin-lipid micelles with a molar absorption coefficient of 8.7×108 cm−1 M−1 at this wavelength. The PA signal intensity versus JNP areal concentration followed a sigmoidal curve with a reproducible linear range of ∼17 fmol/mm2 to 11 pmol/mm2, i.e., ∼3 orders of magnitude with ±34% error. For physiologically-relevant conditions (i.e., optical scattering-dominated tissues: transport albedo >0.8) and JNP concentrations above ∼330 fmol/mm2, the PA signal depends only on the nanoparticle concentration. Otherwise, independent measurement of the optical absorption and scattering properties of the underlying tissue is required for accurate quantification. The implications for surface PA imaging, such as in the use of targeted nanoparticles applied topically to tissue as in endoscopic diagnosis, are considered.
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Affiliation(s)
- Liang Lim
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Robert Mastragostino
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Kenneth Ng
- University of Toronto, Department of Medical Biophysics, Toronto, Ontario, Canada
| | - Gang Zheng
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, CanadabUniversity of Toronto, Department of Medical Biophysics, Toronto, Ontario, Canada
| | - Brian C Wilson
- University Health Network, Princess Margaret Cancer Centre, Toronto, Ontario, CanadabUniversity of Toronto, Department of Medical Biophysics, Toronto, Ontario, Canada
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Hatta W, Tong D, Lee YY, Ichihara S, Uedo N, Gotoda T. Different time trend and management of esophagogastric junction adenocarcinoma in three Asian countries. Dig Endosc 2017; 29 Suppl 2:18-25. [PMID: 28425657 DOI: 10.1111/den.12808] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 01/11/2017] [Indexed: 02/06/2023]
Abstract
Esophagogastric junction (EGJ) adenocarcinoma has been on the increase in Western countries. However, in Asian countries, data on the incidence of EGJ adenocarcinoma are evidently lacking. In the present review, we focus on the current clinical situation of EGJ adenocarcinoma in three Asian countries: Japan, Hong Kong, and Malaysia. The incidence of EGJ adenocarcinoma has been reported to be gradually increasing in Malaysia and Japan, whereas it has stabilized in Hong Kong. However, the number of cases in these countries is comparatively low compared with Western countries. A reason for the reported difference in the incidence and time trend of EGJ adenocarcinoma among the three countries may be explained by two distinct etiologies: one arising from chronic gastritis similar to distal gastric cancer, and the other related to gastroesophageal reflux disease similar to esophageal adenocarcinoma including Barrett's adenocarcinoma. This review also shows that there are several concerns in clinical practice for EGJ adenocarcinoma. In Hong Kong and Malaysia, many EGJ adenocarcinomas have been detected at a stage not amenable to endoscopic resection. In Japan, histological curability criteria for endoscopic resection cases have not been established. We suggest that an international collaborative study using the same definition of EGJ adenocarcinoma may be helpful not only for clarifying the characteristics of these cancers but also for improving the clinical outcome of these patients.
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Affiliation(s)
- Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Daniel Tong
- Division of Esophageal and Upper Gastrointestinal Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Yeong Yeh Lee
- Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia
| | - Shin Ichihara
- Department of Surgical Pathology, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Noriya Uedo
- Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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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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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: 153] [Impact Index Per Article: 19.1] [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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Old OJ, Isabelle M, Barr H. Staging Early Esophageal Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 908:161-81. [PMID: 27573772 DOI: 10.1007/978-3-319-41388-4_9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Staging esophageal cancer provides a standardized measure of the extent of disease that can be used to inform decisions about therapy and guide prognosis. For esophageal cancer, the treatment pathways vary greatly depending on stage of disease, and accurate staging is therefore crucial in ensuring the optimal therapy for each patient. For early esophageal cancer (T1 lesions), endoscopic resection can be curative and simultaneously gives accurate staging of depth of invasion. For tumors invading the submucosa or more advanced disease, comprehensive investigation is required to accurately stage the tumor and assess suitability for curative resection. A combined imaging approach of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) offers complementary diagnostic information and gives the greatest chance of accurate staging. Staging laparoscopy can identify peritoneal disease and small superficial liver lesions that could be missed on CT or PET, and alters management in up to 20 % of patients. Optical diagnostic techniques offer the prospect of further extending the possibilities of endoscopic staging in real time. Optical coherence tomography can image superficial lesions and could provide information on depth of invasion for these lesions. Real-time lymph node analysis using optical diagnostics such as Raman spectroscopy could be used to support immediate endoscopic therapy without waiting for results of cytology or further investigations.
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Affiliation(s)
- O J Old
- Upper GI Surgery Department, Gloucestershire Royal Hospital, Gloucester, UK. .,Biophotonics Research Unit, Gloucestershire Royal Hospital, Gloucester, UK.
| | - M Isabelle
- Biophotonics Research Unit, Gloucestershire Royal Hospital, Gloucester, UK
| | - H Barr
- Upper GI Surgery Department, Gloucestershire Royal Hospital, Gloucester, UK
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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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Sharma N, Takeshita N, Ho KY. Raman Spectroscopy for the Endoscopic Diagnosis of Esophageal, Gastric, and Colonic Diseases. Clin Endosc 2016; 49:404-407. [PMID: 27653440 PMCID: PMC5066404 DOI: 10.5946/ce.2016.100] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 08/23/2016] [Accepted: 08/24/2016] [Indexed: 12/14/2022] Open
Abstract
Globally white-light endoscopy with biopsy sampling is the gold standard diagnostic modality for esophageal, gastric, and colonic pathologies. However, there is overwhelming evidence to highlight the deficiencies of an approach based predominantly on eyeball visualization. Biopsy sampling is also problematic due in part to excessive sampling and hence attendant cost. Various innovations are currently taking place in the endoscopic domain to aid operators in diagnosis forming. These include narrow band imaging which aims to enhance the surface anatomy and vasculature, and confocal laser endomicroscopy which provides real time histological information. However, both of these tools are limited by the skill of the operator and the extensive learning curve associated with their use. There is a gap therefore for a new form of technology that relies solely on an objective measure of disease and reduces the need for biopsy sampling. Raman spectroscopy (RS) is a potential platform that aims to satisfy these criteria. It enables a fingerprint capture of tissue in relation to the protein, DNA, and lipid content. This focused review highlights the strong potential for the use of RS during endoscopic gastroenterological examination.
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Affiliation(s)
- Neel Sharma
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Nobuyoshi Takeshita
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Khek Yu Ho
- Division of Gastroenterology and Hepatology, National University Health System, Singapore
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Shining light on neurosurgery diagnostics using Raman spectroscopy. J Neurooncol 2016; 130:1-9. [PMID: 27522510 DOI: 10.1007/s11060-016-2223-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 07/22/2016] [Indexed: 12/20/2022]
Abstract
Surgical excision of brain tumors provides a means of cytoreduction and diagnosis while minimizing neurologic deficit and improving overall survival. Despite advances in functional and three-dimensional stereotactic navigation and intraoperative magnetic resonance imaging, delineating tissue in real time with physiological confirmation is challenging. Raman spectroscopy is a promising investigative and diagnostic tool for neurosurgery, which provides rapid, non-destructive molecular characterization in vivo or in vitro for biopsy, margin assessment, or laboratory uses. The Raman Effect occurs when light temporarily changes a bond's polarizability, causing change in the vibrational frequency, with a corresponding change in energy/wavelength of the scattered photon. The recorded inelastic scattering results in a "fingerprint" or Raman spectrum of the constituent under investigation. The amount, location, and intensity of peaks in the fingerprint vary based on the amount of vibrational bonds in a molecule and their ensemble interactions with each other. Distinct differences between various pathologic conditions are shown as different intensities of the same peak, or shifting of a peak based on the binding conformation. Raman spectroscopy has potential for integration into clinical practice, particularly in distinguishing normal and diseased tissue as an adjunct to standard pathologic diagnosis. Further, development of fiber-optic Raman probes that fit through the instrument port of a standard endoscope now allows researchers and clinicians to utilize spectroscopic information for evaluation of in vivo tissue. This review highlights the need for such an instrument, summarizes neurosurgical Raman work performed to date, and discusses the future applications of neurosurgical Raman spectroscopy.
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Blattmann M, Kretschmer S, Thiele S, Ataman C, Zappe H, Herkommer A, Seifert A. Bimodal endoscopic probe combining white-light microscopy and optical coherence tomography. APPLIED OPTICS 2016; 55:4261-4269. [PMID: 27411158 DOI: 10.1364/ao.55.004261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
We present a novel bimodal endoscopic imaging probe that can simultaneously provide full-field white-light video microscopy and confocal optical coherence tomography (OCT) depth scans. The two modalities rely on spectrally separated optical paths that run partially in parallel through a micro-optical bench system, which has a cross-section of only 2 mm×2.76 mm and is realized via standard silicon micromachining techniques. With a numerical aperture of 0.061, the video modality has a resolution and field of view of 9.3 and 1240 μm×1080 μm, respectively. The resolution is limited by the pixel spacing of the coherent fiber bundle, which relays the acquired image from the distal to the proximal end. A custom-designed diffractive optical element placed within the video imaging path significantly improves the image contrast by up to 45% in the medium frequency range. The OCT modality is optimized for 830 nm center wavelength, and works in a confocal arrangement with an NA of 0.018. It provides single-point depth probing at the center of the video image with a lateral resolution of 20 μm. Through its compact footprint and enhanced functionality, the probe can provide depth-resolved guiding capability for existing laparoscopes and represents a major step toward a new class of multimodal endoscopic imaging probes.
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Smith R, Wright KL, Ashton L. Raman spectroscopy: an evolving technique for live cell studies. Analyst 2016; 141:3590-600. [PMID: 27072718 DOI: 10.1039/c6an00152a] [Citation(s) in RCA: 193] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
One of the most exciting developments in Raman spectroscopy in the last decade has been its application to cells and tissues for diagnostic and pharmaceutical applications, and in particular its use in the analysis of cellular dynamics. Raman spectroscopy is rapidly advancing as a cell imaging method that overcomes many of the limitations of current techniques and is earning its place as a routine tool in cell biology. In this review we focus on important developments in Raman spectroscopy that have evolved into the exciting technique of live-cell Raman microscopy and highlight some of the most recent and significant applications to cell biology.
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Affiliation(s)
- Rachael Smith
- Department of Chemistry, Lancaster University, LA1 4YG, UK.
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Naveed M, Dunbar KB. Endoscopic imaging of Barrett’s esophagus. World J Gastrointest Endosc 2016; 8:259-266. [PMID: 26981177 PMCID: PMC4781906 DOI: 10.4253/wjge.v8.i5.259] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 09/14/2015] [Accepted: 12/18/2015] [Indexed: 02/05/2023] Open
Abstract
The incidence of esophageal adenocarcinoma (EAC) has dramatically increased in the United States as well as Western European countries. The majority of esophageal adenocarcinomas arise from a backdrop of Barrett’s esophagus (BE), a premalignant lesion that can lead to dysplasia and cancer. Because of the increased risk of EAC, GI society guidelines recommend endoscopic surveillance of patients with BE. The emphasis on early detection of dysplasia in BE through surveillance endoscopy has led to the development of advanced endoscopic imaging technologies. These techniques have the potential to both improve mucosal visualization and characterization and to detect small mucosal abnormalities which are difficult to identify with standard endoscopy. This review summarizes the advanced imaging technologies used in evaluation of BE.
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