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Yu XY, Chen J, Li LY, Chen FE, He Q. Rapid pathologic grading-based diagnosis of esophageal squamous cell carcinoma via Raman spectroscopy and a deep learning algorithm. World J Gastroenterol 2025; 31:104280. [PMID: 40248385 PMCID: PMC12001190 DOI: 10.3748/wjg.v31.i14.104280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/23/2025] [Accepted: 03/24/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Esophageal squamous cell carcinoma is a major histological subtype of esophageal cancer. Many molecular genetic changes are associated with its occurrence. Raman spectroscopy has become a new method for the early diagnosis of tumors because it can reflect the structures of substances and their changes at the molecular level. AIM To detect alterations in Raman spectral information across different stages of esophageal neoplasia. METHODS Different grades of esophageal lesions were collected, and a total of 360 groups of Raman spectrum data were collected. A 1D-transformer network model was proposed to handle the task of classifying the spectral data of esophageal squamous cell carcinoma. In addition, a deep learning model was applied to visualize the Raman spectral data and interpret their molecular characteristics. RESULTS A comparison among Raman spectral data with different pathological grades and a visual analysis revealed that the Raman peaks with significant differences were concentrated mainly at 1095 cm-1 (DNA, symmetric PO, and stretching vibration), 1132 cm-1 (cytochrome c), 1171 cm-1 (acetoacetate), 1216 cm-1 (amide III), and 1315 cm-1 (glycerol). A comparison among the training results of different models revealed that the 1D-transformer network performed best. A 93.30% accuracy value, a 96.65% specificity value, a 93.30% sensitivity value, and a 93.17% F1 score were achieved. CONCLUSION Raman spectroscopy revealed significantly different waveforms for the different stages of esophageal neoplasia. The combination of Raman spectroscopy and deep learning methods could significantly improve the accuracy of classification.
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Affiliation(s)
- Xin-Ying Yu
- Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
| | - Jian Chen
- Department of Cancer Prevention Center, Feicheng People’s Hospital, Feicheng 271000, Shandong Province, China
| | - Lian-Yu Li
- Department of Electronic Information and Communication, Huazhong University of Science and Technology, Wuhan 430000, Hubei Province, China
| | - Feng-En Chen
- Department of Chemistry, Tsinghua University, Beijing 100080, China
| | - Qiang He
- Department of Gastroenterology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100071, China
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2
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Ravera F, Efeoglu E, Byrne HJ. A comparative analysis of stem cell differentiation on 2D and 3D substrates using Raman microspectroscopy. Analyst 2024; 149:4041-4053. [PMID: 38973486 DOI: 10.1039/d4an00315b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
Chondrogenesis is a complex cellular process that involves the transformation of mesenchymal stem cells (MSCs) into chondrocytes, the specialised cells that form cartilage. In recent years, three-dimensional (3D) culture systems have emerged as a promising approach to studying cell behaviour and development in a more physiologically relevant environment compared to traditional two-dimensional (2D) cell culture. The use of these systems provided insights into the molecular mechanisms that regulate chondrogenesis and has the potential to revolutionise the development of new therapies for cartilage repair and regeneration. This study demonstrates the successful application of Raman microspectroscopy (RMS) as a label-free, non-destructive, and sensitive method to monitor the chondrogenic differentiation of bone marrow-derived rat mesenchymal stem cells (rMSCs) in a collagen type I hydrogel, and explores the potential benefits of 3D hydrogels compared to conventional 2D cell culture environments. rMSCs were cultured on 3D substrates for 3 weeks and their differentiation was monitored by measuring the spectral signatures of their subcellular compartments. Additionally, the evolution of high-density micromass cultures was investigated to provide a comprehensive understanding of the process and complex interactions between cells and their surrounding extracellular matrix. For comparison, rMSCs were induced into chondrogenesis in identical medium conditions for 21 days in monolayer culture. Raman spectra showed that rMSCs cultured in a collagen type I hydrogel are able to undergo a distinct chondrogenic differentiation pathway at a significantly higher rate than the 2D culture cells. 3D cultures expressed stronger and more homogeneous chondrogenesis-associated peaks such as collagens, glycosaminoglycans (GAGs), and aggrecan while manifesting changes in proteins and lipidic content. These results suggest that 3D type I collagen hydrogel substrates are promising for in vitro chondrogenesis studies, and that RMS is a valuable tool for monitoring chondrogenesis in 3D environments.
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Affiliation(s)
- F Ravera
- FOCAS Research Institute, Technological University Dublin, City Campus, Dublin 8, Ireland.
| | - E Efeoglu
- NICB (National Institute for Cellular Biotechnology) at Dublin City University, Dublin 9, Ireland
| | - H J Byrne
- FOCAS Research Institute, Technological University Dublin, City Campus, Dublin 8, Ireland.
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3
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Ehsan U, Nawaz H, Irfan Majeed M, Rashid N, Ali Z, Zulfiqar A, Tariq A, Shahbaz M, Meraj L, Naheed I, Sadaf N. Surface-enhanced Raman spectroscopy of centrifuged blood serum samples of diabetic type II patients by using 50KDa filter devices. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2023; 293:122457. [PMID: 36764165 DOI: 10.1016/j.saa.2023.122457] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 02/03/2023] [Indexed: 06/18/2023]
Abstract
Blood serum contains essential biochemical information which are used for early disease diagnosis. Blood serum consisted of higher molecular weight fractions (HMWF) and lower molecular weight fractions (LMWF). The disease biomarkers are lower molecular weight fraction proteins, and their contribution to disease diagnosis is suppressed due to higher molecular weight fraction proteins. To diagnose diabetes in early stages are difficult because of the presence of huge amount of these HMWF. In the current study, surface-enhanced Raman spectroscopy (SERS) are employed to diagnose diabetes after centrifugation of serum samples using Amicon ultra filter devices of 50 kDa which produced two fractions of whole blood serum of filtrate, low molecular weight fraction, and residue, high molecular weight fraction. Furthermore SERS is employed to study the LMW fractions of healthy and diseased samples. Some prominent SERS bands are observed at 725 cm-1, 842 cm-1, 1025 cm-1, 959 cm-1, and 1447 cm-1 due to small molecular weight proteins, and these biomarkers helped to diagnose the disease early stage. Moreover, chemometric techniques such as principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) are employed to check the potential of surface-enhanced Raman spectroscopy for the differentiation and classifications of the blood serum samples. SERS can be employed for the early diagnosis and screening of biochemical changes during type II diabetes.
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Affiliation(s)
- Usama Ehsan
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Haq Nawaz
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan.
| | - Muhammad Irfan Majeed
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan.
| | - Nosheen Rashid
- Department of Chemistry, University of Education, Faisalabad Campus, Faisalabad 38000, Pakistan.
| | - Zain Ali
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Anam Zulfiqar
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Ayesha Tariq
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Muhammad Shahbaz
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Lubna Meraj
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Iqra Naheed
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
| | - Nimra Sadaf
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad 38000, Pakistan
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4
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Milligan K, Van Nest SJ, Deng X, Ali-Adeeb R, Shreeves P, Punch S, Costie N, Pavey N, Crook JM, Berman DM, Brolo AG, Lum JJ, Andrews JL, Jirasek A. Raman spectroscopy and supervised learning as a potential tool to identify high-dose-rate-brachytherapy induced biochemical profiles of prostate cancer. JOURNAL OF BIOPHOTONICS 2022; 15:e202200121. [PMID: 35908273 DOI: 10.1002/jbio.202200121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/14/2022] [Accepted: 07/08/2022] [Indexed: 06/15/2023]
Abstract
High-dose-rate-brachytherapy (HDR-BT) is an increasingly attractive alternative to external beam radiation-therapy for patients with intermediate risk prostate cancer. Despite this, no bio-marker based method currently exists to monitor treatment response, and the changes which take place at the biochemical level in hypo-fractionated HDR-BT remain poorly understood. The aim of this pilot study is to assess the capability of Raman spectroscopy (RS) combined with principal component analysis (PCA) and random-forest classification (RF) to identify radiation response profiles after a single dose of 13.5 Gy in a cohort of nine patients. We here demonstrate, as a proof-of-concept, how RS-PCA-RF could be utilised as an effective tool in radiation response monitoring, specifically assessing the importance of low variance PCs in complex sample sets. As RS provides information on the biochemical composition of tissue samples, this technique could provide insight into the changes which take place on the biochemical level, as result of HDR-BT treatment.
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Affiliation(s)
- Kirsty Milligan
- Department of Physics, University of British Columbia, Kelowna, Canada
| | - Samantha J Van Nest
- Trev and Joyce Deeley Research Centre, BC Cancer-Victoria, Victoria, Canada
- Department of Radiation Oncology, Weill Cornell Medicine, New York, New York, USA
| | - Xinchen Deng
- Department of Physics, University of British Columbia, Kelowna, Canada
| | - Ramie Ali-Adeeb
- Department of Physics, University of British Columbia, Kelowna, Canada
| | - Phillip Shreeves
- Department of Mathematics and Statistics, University of British Columbia, Kelowna, Canada
| | - Samantha Punch
- Trev and Joyce Deeley Research Centre, BC Cancer-Victoria, Victoria, Canada
| | - Nathalie Costie
- Trev and Joyce Deeley Research Centre, BC Cancer-Victoria, Victoria, Canada
| | - Nils Pavey
- Trev and Joyce Deeley Research Centre, BC Cancer-Victoria, Victoria, Canada
| | - Juanita M Crook
- Sindi Ahluwalia Hawkins Centre for the Southern Interior, BC Cancer, Kelowna, Canada
- Department of Radiation Oncology, University of British Columbia, Kelowna, Canada
| | - David M Berman
- Department of Pathology and Molecular Medicine, Queens University, Kingston, Canada
| | | | - Julian J Lum
- Trev and Joyce Deeley Research Centre, BC Cancer-Victoria, Victoria, Canada
- Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada
| | - Jeffrey L Andrews
- Department of Mathematics and Statistics, University of British Columbia, Kelowna, Canada
| | - Andrew Jirasek
- Department of Physics, University of British Columbia, Kelowna, Canada
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Barik AK, M SP, Lukose J, Upadhya R, Pai MV, Kartha VB, Chidangil S. In vivo spectroscopy: optical fiber probes for clinical applications. Expert Rev Med Devices 2022; 19:657-675. [PMID: 36175393 DOI: 10.1080/17434440.2022.2130046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Fiber optic probe based in-vivo spectroscopy techniques are fast and highly objective methods for intraoperative diagnoses and minimally invasive surgical interventions for all procedures where endoscopic observations are carried out for cancers of different types. The Raman spectral features provide molecular fingerprint-type information and can reveal the subjects' pathological state in label-free manner, making endoscopy multiplexed fiber optic probe-based devices with the potential for translation from bench to bedside for routine applications. AREAS COVERED This review provides a general overview of different fiber-optic probes for in-vivo measurements with emphasis on Raman spectroscopy for biomedical application. Various aspects such as fiber-optic probe, radiation source, detector, and spectrometer for extracting optimum spectral features have also been discussed. EXPERT OPINION : Optical spectroscopy-based fiber probe systems with "Chip-on-Tip" technology, combined with machine learning, can in the near future, become a complimentary diagnostic tool to magnetic resonance imaging (MRI), computed tomography (CT) scan, ultrasound, etc. Hyperspectral imaging and fluorescence-based devices are in the advanced stage of technology readiness level (TRL), and with advances in lasers and miniature spectroscopy systems, probe-based Raman devices are also coming up.
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Affiliation(s)
- Ajaya Kumar Barik
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education -576104, Manipal, India
| | - Sanoop Pavithran M
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education -576104, Manipal, India
| | - Jijo Lukose
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education -576104, Manipal, India
| | - Rekha Upadhya
- Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education -576104, Manipal, India
| | - Muralidhar V Pai
- Department of Obstetrics and Gynaecology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education -576104, Manipal, India
| | - V B Kartha
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education -576104, Manipal, India
| | - Santhosh Chidangil
- Centre of Excellence for Biophotonics, Department of Atomic and Molecular Physics, Manipal Academy of Higher Education -576104, Manipal, India
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Senger RS, Sayed Issa A, Agnor B, Talty J, Hollis A, Robertson JL. Disease-Associated Multimolecular Signature in the Urine of Patients with Lyme Disease Detected Using Raman Spectroscopy and Chemometrics. APPLIED SPECTROSCOPY 2022; 76:284-299. [PMID: 35102746 DOI: 10.1177/00037028211061769] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
A urine-based screening technique for Lyme disease (LD) was developed in this research. The screen is based on Raman spectroscopy, iterative smoothing-splines with root error adjustment (ISREA) spectral baselining, and chemometric analysis using Rametrix software. Raman spectra of urine from 30 patients with positive serologic tests (including the US Centers for Disease Control [CDC] two-tier standard) for LD were compared against subsets of our database of urine spectra from 235 healthy human volunteers, 362 end-stage kidney disease (ESKD) patients, and 17 patients with active or remissive bladder cancer (BCA). We found statistical differences (p < 0.001) between urine scans of healthy volunteers and LD-positive patients. We also found a unique LD molecular signature in urine involving 112 Raman shifts (31 major Raman shifts) with significant differences from urine of healthy individuals. We were able to distinguish the LD molecular signature as statistically different (p < 0.001) from the molecular signatures of ESKD and BCA. When comparing LD-positive patients against healthy volunteers, the Rametrix-based urine screen performed with 86.7% for overall accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. When considering patients with ESKD and BCA in the LD-negative group, these values were 88.7% (accuracy), 83.3% (sensitivity), 91.0% (specificity), 80.7% (PPV), and 92.4% (NPV). Additional advantages to the Raman-based urine screen include that it is rapid (minutes per analysis), is minimally invasive, requires no chemical labeling, uses a low-profile, off-the-shelf spectrometer, and is inexpensive relative to other available LD tests.
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Affiliation(s)
- Ryan S Senger
- Department of Biological Systems Engineering, 1757Virginia Tech, Blacksburg, Virginia, USA
- DialySensors Inc., Blacksburg, Virginia, USA
| | | | - Ben Agnor
- Department of Biological Systems Engineering, 1757Virginia Tech, Blacksburg, Virginia, USA
| | - Janine Talty
- Neuromusculoskeletal Medicine & OMM, Roanoke, Virginia, USA
| | | | - John L Robertson
- DialySensors Inc., Blacksburg, Virginia, USA
- Department of Biomedical Engineering and Mechanics, 1757Virginia Tech, Blacksburg, Virginia, USA
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7
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Rafiq S, Majeed MI, Nawaz H, Rashid N, Yaqoob U, Batool F, Bashir S, Akbar S, Abubakar M, Ahmad S, Ali S, Kashif M, Amin I. Surface-enhanced Raman spectroscopy for analysis of PCR products of viral RNA of hepatitis C patients. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2021; 259:119908. [PMID: 33989976 DOI: 10.1016/j.saa.2021.119908] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 04/22/2021] [Accepted: 05/02/2021] [Indexed: 06/12/2023]
Abstract
In the current study, for a qualitative and quantitative study of Polymerase Chain Reaction (PCR) products of viral RNA of Hepatitis C virus (HCV) infection, surface-enhanced Raman spectroscopy (SERS) methodology has been developed. SERS was used to identify the spectral features associated with the PCR products of viral RNA of Hepatitis C in various samples of HCV-infected patients with predetermined viral loads. The measurements for SERS were performed on 30 samples of PCR products, which included three PCR products of RNA of healthy individuals, six negative controls, and twenty-one HCV positive samples of varying viral loads (VLs) using Silver nanoparticles (Ag NPs) as a SERS substrates. Additionally, on SERS spectral data, the multivariate data analysis methods including Principal Component Analysis (PCA) and Partial Least Squares Regression (PLSR) were also carried out which help to illustrate the diagnostic capabilities of this method. The PLSR model is designed to predict HCV viral loads based on biochemical changes observed as SERS spectral features which can be associated directly with HCV RNA. Several SERS characteristic features are observed in the RNA of HCV which are not detected in the spectra of healthy RNA/controls. PCA is found helpful to differentiate the SERS spectral data sets of HCV RNA samples from healthy and negative controls. The PLSR model is found to be 99% accurate in predicting VLs of HCV RNA samples of unknown samples based on SERS spectral changes associated with the Hepatitis C development.
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Affiliation(s)
- Sidra Rafiq
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | | | - Haq Nawaz
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan.
| | - Nosheen Rashid
- Department of Chemistry, University of Central Punjab, Faisalabad Campus, Pakistan
| | - Umer Yaqoob
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Fatima Batool
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Saba Bashir
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Saba Akbar
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Muhammad Abubakar
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Shamsheer Ahmad
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Saqib Ali
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Muhammad Kashif
- Department of Chemistry, University of Agriculture, Faisalabad 38040, Pakistan
| | - Imran Amin
- PCR Laboratory, PINUM Hospital, Faisalabad, Pakistan
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Keogan A, Nguyen TNQ, Phelan JJ, O'Farrell N, Lynam‐Lennon N, Doyle B, O'Toole D, Reynolds JV, O'Sullivan J, Meade AD. Chemical imaging and machine learning for sub‐classification of oesophageal tissue histology. TRANSLATIONAL BIOPHOTONICS 2021. [DOI: 10.1002/tbio.202100004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Abigail Keogan
- Radiation and Environmental Science Centre Focas Research Institute, Technological University Dublin Dublin Ireland
| | - Thi Nguyet Que Nguyen
- Radiation and Environmental Science Centre Focas Research Institute, Technological University Dublin Dublin Ireland
- School of Physics and Clinical and Optometric Sciences Technological University Dublin Dublin Ireland
| | - James J. Phelan
- Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland
| | - Naoimh O'Farrell
- Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland
| | - Niamh Lynam‐Lennon
- Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland
| | - Brendan Doyle
- Department of Histopathology Beaumont Hospital Dublin Ireland
| | - Dermot O'Toole
- School of Clinical Medicine Trinity College Dublin Dublin Ireland
| | - John V. Reynolds
- Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland
| | - Jacintha O'Sullivan
- Department of Surgery Trinity Translational Medicine Institute, Trinity College Dublin Dublin Ireland
| | - Aidan D. Meade
- Radiation and Environmental Science Centre Focas Research Institute, Technological University Dublin Dublin Ireland
- School of Physics and Clinical and Optometric Sciences Technological University Dublin Dublin Ireland
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Wang H, Li J, Qin J, Li J, Chen Y, Song D, Zeng H, Wang S. Confocal Raman microspectral analysis and imaging of the drug response of osteosarcoma to cisplatin. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2021; 13:2527-2536. [PMID: 34008598 DOI: 10.1039/d1ay00626f] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Confocal Raman microspectral analysis and imaging were used to elucidate the drug response of osteosarcoma (OS) to cisplatin. Raman spectral data were obtained from OS cells that were untreated (UT group) and treated with 20 µM (20T group) and 40 µM (40T group) cisplatin for 24 hours. Statistical analysis of the changes in specific Raman signals was performed using a one-way ANOVA and multiple Tukey's honest significant difference (HSD) post hoc tests. Principal component analysis-linear discriminant analysis (PCA-LDA) was used to highlight the featured cellular drug responses based on the obtained spectral information. For spectral imaging analysis, k-means cluster analysis (KCA) was adopted to clarify the effect of cisplatin dose changes on the subcellular structure and its biochemical composition. The results suggest that the major biochemical changes induced by cisplatin in OS cells undergoing apoptosis are reduced protein and nucleic acid content. Through univariate analysis, the changes in the distribution of nucleic acids in OS cells induced by different doses of cisplatin were obtained. The combination of Raman spectroscopy and multivariate analysis shows that cisplatin mainly acts on the nucleus and causes changes in the secondary structure of proteins. These results indicate that Raman imaging technology has the potential to offer the basis of dose optimization for personalized cancer treatment by helping to understand in vitro cellular drug interactions.
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Affiliation(s)
- Haifeng Wang
- State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, #1 Xuefu Avenue, Guodu Education and Technology Industrial Zone Chang'an District, Xi'an, Shaanxi 710127, China.
| | - Jing Li
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Jie Qin
- Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Jie Li
- State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, #1 Xuefu Avenue, Guodu Education and Technology Industrial Zone Chang'an District, Xi'an, Shaanxi 710127, China.
| | - Yishen Chen
- State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, #1 Xuefu Avenue, Guodu Education and Technology Industrial Zone Chang'an District, Xi'an, Shaanxi 710127, China.
| | - Dongliang Song
- State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, #1 Xuefu Avenue, Guodu Education and Technology Industrial Zone Chang'an District, Xi'an, Shaanxi 710127, China.
| | - Haishan Zeng
- Imaging Unit - Integrative Oncology Department, BC Cancer Research Center, Vancouver, BC V5Z1L3, Canada
| | - Shuang Wang
- State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, #1 Xuefu Avenue, Guodu Education and Technology Industrial Zone Chang'an District, Xi'an, Shaanxi 710127, China.
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10
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Fraser-Miller SJ, Rooney JS, Lau M, Gordon KC, Schultz M. Can Coupling Multiple Complementary Methods Improve the Spectroscopic Based Diagnosis of Gastrointestinal Illnesses? A Proof of Principle Ex Vivo Study Using Celiac Disease as the Model Illness. Anal Chem 2021; 93:6363-6374. [PMID: 33844904 DOI: 10.1021/acs.analchem.0c04963] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Spectroscopic methods are a promising approach for providing a point-of-care diagnostic method for gastrointestinal mucosa associated illnesses. Such a tool is desired to aid immediate decision making and to provide a faster pathway to appropriate treatment. In this pilot study, Raman, near-infrared, low frequency Raman, and autofluoresence spectroscopic methods were explored alone and in combination for the diagnosis of celiac disease. Duodenal biopsies (n = 72) from 24 participants were measured ex vivo using the full suite of studied spectroscopic methods. Exploratory principal component analysis (PCA) highlighted the origin of spectral differences between celiac and normal tissue with celiac biopsies tending to have higher protein relative to lipid signals and lower carotenoid spectral signals than the samples with normal histology. Classification of the samples based on the histology and overall diagnosis was carried out for all combinations of spectroscopic methods. Diagnosis based classification (majority rule of class per participant) yielded sensitivities of 0.31 to 0.77 for individual techniques, which was increased up to 0.85 when coupling multiple techniques together. Likewise, specificities of 0.50 to 0.67 were obtained for individual techniques, which was increased up to 0.78 when coupling multiple techniques together. It was noted that the use of antidepressants contributed to false positives, which is believed to be associated with increased serotonin levels observed in the gut mucosa in both celiac disease and the use of selective serotonin reuptake inhibitors (SSRIs); however, future work with greater numbers is required to confirm this observation. Inclusion of two additional spectroscopic methods could improve the accuracy of diagnosis (0.78) by 7% over Raman alone (0.73). This demonstrates the potential for further exploration and development of a multispectroscopic system for disease diagnosis.
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Affiliation(s)
- Sara J Fraser-Miller
- Dodd-Walls Centre for Photonic and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin 9054, New Zealand
| | - Jeremy S Rooney
- Dodd-Walls Centre for Photonic and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin 9054, New Zealand
| | - Michael Lau
- Southern Community Laboratories, Dunedin 9016, New Zealand
| | - Keith C Gordon
- Dodd-Walls Centre for Photonic and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin 9054, New Zealand
| | - Michael Schultz
- Gastroenterology Research Unit, Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand.,Mercy Hospital, Dunedin 9010, New Zealand.,Gastroenterology Department, Southern District Health Board, Dunedin 9016, New Zealand
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11
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Morrish R, Yim KHW, Pagliara S, Palombo F, Chahwan R, Stone N. Single Cell Label-Free Probing of Chromatin Dynamics During B Lymphocyte Maturation. Front Cell Dev Biol 2021; 9:646616. [PMID: 33842468 PMCID: PMC8033168 DOI: 10.3389/fcell.2021.646616] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 03/08/2021] [Indexed: 01/11/2023] Open
Abstract
Large-scale intracellular signaling during developmental growth or in response to environmental alterations are largely orchestrated by chromatin within the cell nuclei. Chemical and conformational modifications of the chromatin architecture are critical steps in the regulation of differential gene expression and ultimately cell fate determination. Therefore, establishing chemical properties of the nucleus could provide key markers for phenotypic characterization of cellular processes on a scale of individual cells. Raman microscopy is a sensitive technique that is capable of probing single cell chemical composition—and sub-cellular regions—in a label-free optical manner. As such, it has great potential in both clinical and basic research. However, perceived limitations of Raman spectroscopy such as low signal intensity and the difficulty in linking alterations in vibrational signals directly with ensuing biological effects have hampered advances in the field. Here we use immune B lymphocyte development as a model to assess chromatin and transcriptional changes using confocal Raman microscopy in combination with microfluidic devices and correlative transcriptomics, thereby linking changes in chemical and structural properties to biological outcomes. Live B lymphocytes were assessed before and after maturation. Multivariate analysis was applied to distinguish cellular components within each cell. The spectral differences between non-activated and activated B lymphocytes were then identified, and their correlation with known intracellular biological changes were assessed in comparison to conventional RNA-seq analysis. Our data shows that spectral analysis provides a powerful tool to study gene activation that can complement conventional molecular biology techniques and opens the way for mapping the dynamics in the biochemical makeup of individual cells.
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Affiliation(s)
- Rikke Morrish
- School of Physics and Astronomy, University of Exeter, Exeter, United Kingdom.,Living Systems Institute and School of Biosciences, University of Exeter, Exeter, United Kingdom
| | - Kevin Ho Wai Yim
- Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
| | - Stefano Pagliara
- Living Systems Institute and School of Biosciences, University of Exeter, Exeter, United Kingdom
| | - Francesca Palombo
- School of Physics and Astronomy, University of Exeter, Exeter, United Kingdom
| | - Richard Chahwan
- Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
| | - Nicholas Stone
- School of Physics and Astronomy, University of Exeter, Exeter, United Kingdom
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12
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Tiwari D, Jakhmola S, Pathak DK, Kumar R, Jha HC. Temporal In Vitro Raman Spectroscopy for Monitoring Replication Kinetics of Epstein-Barr Virus Infection in Glial Cells. ACS OMEGA 2020; 5:29547-29560. [PMID: 33225186 PMCID: PMC7676301 DOI: 10.1021/acsomega.0c04525] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 10/21/2020] [Indexed: 05/17/2023]
Abstract
Raman spectroscopy can be used as a tool to study virus entry and pathogen-driven manipulation of the host efficiently. To date, Epstein-Barr virus (EBV) entry and altered biochemistry of the glial cell upon infection are elusive. In this study, we detected biomolecular changes in human glial cells, namely, HMC-3 (microglia) and U-87 MG (astrocytes), at two variable cellular locations (nucleus and periphery) by Raman spectroscopy post-EBV infection at different time points. Two possible phenomena, one attributed to the response of the cell to viral attachment and invasion and the other involved in duplication of the virus followed by egress from the host cell, are investigated. These changes corresponded to unique Raman spectra associated with specific biomolecules in the infected and the uninfected cells. The Raman signals from the nucleus and periphery of the cell also varied, indicating differential biochemistry and signaling processes involved in infection progression at these locations. Molecules such as cholesterol, glucose, hyaluronan, phenylalanine, phosphoinositide, etc. are associated with the alterations in the cellular biochemical homeostasis. These molecules are mainly responsible for cellular processes such as lipid transport, cell proliferation, differentiation, and apoptosis in the cells. Raman signatures of these molecules at distinct time points of infection indicated their periodic involvement, depending on the stage of virus infection. Therefore, it is possible to discern the details of variability in EBV infection progression in glial cells at the biomolecular level using time-dependent in vitro Raman scattering.
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Affiliation(s)
- Deeksha Tiwari
- Discipline
of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, 453552 Indore, India
| | - Shweta Jakhmola
- Discipline
of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, 453552 Indore, India
| | - Devesh K. Pathak
- Discipline
of Physics, Indian Institute of Technology
Indore, Simrol, 453552 Indore, India
| | - Rajesh Kumar
- Discipline
of Physics, Indian Institute of Technology
Indore, Simrol, 453552 Indore, India
- Centre
for Advanced Electronics, Indian Institute
of Technology Indore, Simrol, 453552 Indore, India
| | - Hem Chandra Jha
- Discipline
of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Simrol, 453552 Indore, India
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13
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Chalapathi D, Padmanabhan S, Manjithaya R, Narayana C. Surface-Enhanced Raman Spectroscopy as a Tool for Distinguishing Extracellular Vesicles under Autophagic Conditions: A Marker for Disease Diagnostics. J Phys Chem B 2020; 124:10952-10960. [PMID: 33095582 DOI: 10.1021/acs.jpcb.0c06910] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Extracellular vesicles (EVs) laden with lipids, proteins, DNA, and micro-RNAs play important biological functions in intercellular communication and have pivotal roles in pathophysiological conditions. Characterization of the EVs has always been a multistep process involving large volumes, and they are heterogeneous in size and properties. A multitude of approaches is used to distinguish the EVs. Here, we report simple citrate reduced silver nanoparticles assisted surface-enhanced Raman spectroscopy (SERS) as a tool to distinguish EVs extracted from several cell lines isolated under autophagic conditions (nitrogen starvation). This study is the first report of its kind in characterizing EVs from cells under autophagic conditions using SERS. We used two cancerous cell lines, HeLa, its corresponding autophagy-deficient cell line (Atg5-/-), and a noncancerous cell line, HEK293, to isolate EVs. Our study helps in the facile detection and differentiation of EVs isolated between two closely related human cell lines that differ by their autophagic ability. The principal component analysis (PCA) of the SERS spectra of these EVs consistently showed the presence of distinct chemical compositions of the EVs. SERS of EVs can help in probing more into the molecular level information from EVs and could become a powerful tool once coupled with improved microscopy techniques for diagnosis and therapy.
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14
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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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15
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Arcobacter Identification and Species Determination Using Raman Spectroscopy Combined with Neural Networks. Appl Environ Microbiol 2020; 86:AEM.00924-20. [PMID: 32801186 DOI: 10.1128/aem.00924-20] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 08/05/2020] [Indexed: 12/23/2022] Open
Abstract
Rapid and accurate identification of Arcobacter is of great importance because it is considered an emerging food- and waterborne pathogen and potential zoonotic agent. Raman spectroscopy can differentiate bacteria based on Raman scattering spectral patterns of whole cells in a fast, reagentless, and easy-to-use manner. We aimed to detect and discriminate Arcobacter bacteria at the species level using confocal micro-Raman spectroscopy (785 nm) coupled with neural networks. A total of 82 reference and field isolates of 18 Arcobacter species from clinical, environmental, and agri-food sources were included. We determined that the bacterial cultivation time and growth temperature did not significantly influence the Raman spectral reproducibility and discrimination capability. The genus Arcobacter could be successfully differentiated from the closely related genera Campylobacter and Helicobacter using principal-component analysis. For the identification of Arcobacter to the species level, an accuracy of 97.2% was achieved for all 18 Arcobacter species using Raman spectroscopy combined with a convolutional neural network (CNN). The predictive capability of Raman-CNN was further validated using an independent data set of 12 Arcobacter strains. Furthermore, a Raman spectroscopy-based fully connected artificial neural network (ANN) was constructed to determine the actual ratio of a specific Arcobacter species in a bacterial mixture ranging from 5% to 100% by biomass (regression coefficient >0.99). The application of both CNN and fully connected ANN improved the accuracy of Raman spectroscopy for bacterial species determination compared to the conventional chemometrics. This newly developed approach enables rapid identification and species determination of Arcobacter within an hour following cultivation.IMPORTANCE Rapid identification of bacterial pathogens is critical for developing an early warning system and performing epidemiological investigation. Arcobacter is an emerging foodborne pathogen and has become more important in recent decades. The incidence of Arcobacter species in the agro-ecosystem is probably underestimated mainly due to the limitation in the available detection and characterization techniques. Raman spectroscopy combined with machine learning can accurately identify Arcobacter at the species level in a rapid and reliable manner, providing a promising tool for epidemiological surveillance of this microbe in the agri-food chain. The knowledge elicited from this study has the potential to be used for routine bacterial screening and diagnostics by the government, food industry, and clinics.
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Hubbard TJE, Shore A, Stone N. Raman spectroscopy for rapid intra-operative margin analysis of surgically excised tumour specimens. Analyst 2020; 144:6479-6496. [PMID: 31616885 DOI: 10.1039/c9an01163c] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Raman spectroscopy, a form of vibrational spectroscopy, has the ability to provide sensitive and specific biochemical analysis of tissue. This review article provides an in-depth analysis of the suitability of different Raman spectroscopy techniques in providing intra-operative margin analysis in a range of solid tumour pathologies. Surgical excision remains the primary treatment of a number of solid organ cancers. Incomplete excision of a tumour and positive margins on histopathological analysis is associated with a worse prognosis, the need for adjuvant therapies with significant side effects and a resulting financial burden. The provision of intra-operative margin analysis of surgically excised tumour specimens would be beneficial for a number of pathologies, as there are no widely adopted and accurate methods of margin analysis, beyond histopathology. The limitations of Raman spectroscopic studies to date are discussed and future work necessary to enable translation to clinical use is identified. We conclude that, although there remain a number of challenges in translating current techniques into a clinically effective tool, studies so far demonstrate that Raman Spectroscopy has the attributes to successfully perform highly accurate intra-operative margin analysis in a clinically relevant environment.
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Ross CA, MacLachlan DG, Smith BJE, Beck RJ, Shephard JD, Weston N, Thomson RR. A Miniature Fibre-Optic Raman Probe Fabricated by Ultrafast Laser-Assisted Etching. MICROMACHINES 2020; 11:mi11020185. [PMID: 32053957 PMCID: PMC7074630 DOI: 10.3390/mi11020185] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/06/2020] [Accepted: 02/08/2020] [Indexed: 01/20/2023]
Abstract
Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices, particularly in a way suitable for large scale adoption, remains a critical challenge. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy-based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser-assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3% ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.
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Affiliation(s)
- Calum A. Ross
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
- Correspondence:
| | - David G. MacLachlan
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
| | | | - Rainer J. Beck
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
| | - Jonathan D. Shephard
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
| | | | - Robert R. Thomson
- Scottish Universities Physics Alliance (SUPA), Institute of Photonics and Quantum Sciences (IPaQS), Heriot-Watt University, Edinburgh EH14 4AS, UK
- EPSRC IRC Hub, MRC Centre for Inflammation Research, Queen’s Medical Research Institute (QMRI), University of Edinburgh, Edinburgh EH16 4TJ, UK
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18
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Bury D, Morais CLM, Martin FL, Lima KMG, Ashton KM, Baker MJ, Dawson TP. Discrimination of fresh frozen non-tumour and tumour brain tissue using spectrochemical analyses and a classification model. Br J Neurosurg 2019; 34:40-45. [PMID: 31642351 DOI: 10.1080/02688697.2019.1679352] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Introduction: In order for brain tumours to be successfully treated, maximal resection is beneficial. A method to detect infiltrative tumour edges intraoperatively, improving on current methods would be clinically useful. Vibrational spectroscopy offers the potential to provide a handheld, reagent-free method for tumour detection.Purpose: This study was designed to determine the ability of both Raman and Fourier-transform infrared (FTIR) spectroscopy towards differentiating between normal brain tissue, glioma or meningioma.Method: Unfixed brain tissue, which had previously only been frozen, comprising normal, glioma or meningioma tissue was placed onto calcium fluoride slides for analysis using Raman and attenuated total reflection (ATR)-FTIR spectroscopy. Matched haematoxylin and eosin slides were used to confirm tumour areas. Analyses were then conducted to generate a classification model.Results: This study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to discriminate tumour from non-tumour fresh frozen brain tissue with 94% and 97.2% of cases correctly classified, with sensitivities of 98.8% and 100%, respectively. This decreases when spectroscopy is used to determine tumour type.Conclusion: The study demonstrates the ability of both Raman and ATR-FTIR spectroscopy to detect tumour tissue from non-tumour brain tissue with a high degree of accuracy. This demonstrates the ability of spectroscopy when targeted for a cancer diagnosis. However, further improvement would be required for a classification model to determine tumour type using this technology, in order to make this tool clinically viable.
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Affiliation(s)
- Danielle Bury
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK
| | - Camilo L M Morais
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK
| | - Francis L Martin
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK
| | - Kássio M G Lima
- Biological Chemistry and Chemometrics, Institute of Chemistry, Federal University of Rio Grande do Norte, Natal, Brazil
| | - Katherine M Ashton
- Department of Neuropathology, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Trust, Preston, UK
| | - Matthew J Baker
- WestCHEM, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow, UK
| | - Timothy P Dawson
- Department of Neuropathology, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Trust, Preston, UK
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19
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Laimer J, Henn R, Helten T, Sprung S, Zelger B, Zelger B, Steiner R, Schnabl D, Offermanns V, Bruckmoser E, Huck CW. Amalgam tattoo versus melanocytic neoplasm - Differential diagnosis of dark pigmented oral mucosa lesions using infrared spectroscopy. PLoS One 2018; 13:e0207026. [PMID: 30399191 PMCID: PMC6219804 DOI: 10.1371/journal.pone.0207026] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Accepted: 10/22/2018] [Indexed: 12/14/2022] Open
Abstract
Background Dark pigmented lesions of the oral mucosa can represent a major diagnostic challenge. A biopsy is usually required to determine the nature of such intraoral discolorations. This study investigates the potential use of infrared spectroscopy for differential diagnosis of amalgam tattoos versus benign or malignant melanocytic neoplasms. Materials and methods For this retrospective study, formalin-fixed paraffin-embedded tissue (FFPE) specimens of dark pigmented lesions concerning the oral mucosa or the lip were investigated using mid infrared spectroscopy. The samples were chosen from patients who had undergone a mucosal biopsy at the University Hospital Innsbruck (Austria) between the years 2000 and 2017. Principal component analysis was used for data exploration. Evaluation was based on the superimposition of the recorded spectra and the corresponding histologic slides. Results In total, 22 FFPE specimens were analyzed. Clear differences were found between amalgam and non-amalgam samples. A general weakening of the penetrating infrared radiation allowed for unspecific discrimination between these two classes. An overall accuracy in predicting the correct class of 95.24% was achieved. Conclusion Infrared spectroscopy appears to be a suitable technique to differentiate between amalgam tattoos and melanocytic lesions in FFPE samples. It could potentially be applied in vivo, too, serving as a non-invasive diagnostic tool for intraoral dark pigmented lesions.
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Affiliation(s)
- Johannes Laimer
- University Hospital for Craniomaxillofacial and Oral Surgery, Innsbruck, Austria
| | - Raphael Henn
- Institute of Analytical Chemistry and Radiochemistry, Innsbruck, Austria
| | - Tom Helten
- University Hospital for Craniomaxillofacial and Oral Surgery, Innsbruck, Austria
| | - Susanne Sprung
- Institute of Pathology, Medical University, Innsbruck, Austria
| | - Bettina Zelger
- Institute of Pathology, Medical University, Innsbruck, Austria
| | - Bernhard Zelger
- University Hospital for Dermatology, Venereology and Allergology, Innsbruck, Austria
| | - René Steiner
- University Hospital for Dental Prosthetics and Restorative Dentistry, Innsbruck, Austria
| | - Dagmar Schnabl
- University Hospital for Dental Prosthetics and Restorative Dentistry, Innsbruck, Austria
| | - Vincent Offermanns
- University Hospital for Craniomaxillofacial and Oral Surgery, Innsbruck, Austria
| | | | - Christian W. Huck
- Institute of Analytical Chemistry and Radiochemistry, Innsbruck, Austria
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20
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Bury D, Faust G, Paraskevaidi M, Ashton KM, Dawson TP, Martin FL. Phenotyping Metastatic Brain Tumors Applying Spectrochemical Analyses: Segregation of Different Cancer Types. ANAL LETT 2018. [DOI: 10.1080/00032719.2018.1479412] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Danielle Bury
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK
| | - Guy Faust
- Department of Oncology, University Hospitals of Leicester NHS Trust, Leicester, Leicestershire, UK
| | - Maria Paraskevaidi
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK
| | - Katherine M. Ashton
- Department of Neuropathology, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Trust, Preston, UK
| | - Timothy P. Dawson
- Department of Neuropathology, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Trust, Preston, UK
| | - Francis L. Martin
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, UK
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21
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Raman Spectroscopy and Imaging for Cancer Diagnosis. JOURNAL OF HEALTHCARE ENGINEERING 2018; 2018:8619342. [PMID: 29977484 PMCID: PMC6011081 DOI: 10.1155/2018/8619342] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/31/2018] [Accepted: 05/12/2018] [Indexed: 12/20/2022]
Abstract
Raman scattering has long been used to analyze chemical compositions in biological systems. Owing to its high chemical specificity and noninvasive detection capability, Raman scattering has been widely employed in cancer screening, diagnosis, and intraoperative surgical guidance in the past ten years. In order to overcome the weak signal of spontaneous Raman scattering, coherent Raman scattering and surface-enhanced Raman scattering have been developed and recently applied in the field of cancer research. This review focuses on innovative studies of the use of Raman scattering in cancer diagnosis and their potential to transition from bench to bedside.
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Cordero E, Latka I, Matthäus C, Schie I, Popp J. In-vivo Raman spectroscopy: from basics to applications. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-23. [PMID: 29956506 DOI: 10.1117/1.jbo.23.7.071210] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2018] [Accepted: 05/23/2018] [Indexed: 05/20/2023]
Abstract
For more than two decades, Raman spectroscopy has found widespread use in biological and medical applications. The instrumentation and the statistical evaluation procedures have matured, enabling the lengthy transition from ex-vivo demonstration to in-vivo examinations. This transition goes hand-in-hand with many technological developments and tightly bound requirements for a successful implementation in a clinical environment, which are often difficult to assess for novice scientists in the field. This review outlines the required instrumentation and instrumentation parameters, designs, and developments of fiber optic probes for the in-vivo applications in a clinical setting. It aims at providing an overview of contemporary technology and clinical trials and attempts to identify future developments necessary to bring the emerging technology to the clinical end users. A comprehensive overview of in-vivo applications of fiber optic Raman probes to characterize different tissue and disease types is also given.
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Affiliation(s)
- Eliana Cordero
- Leibniz-Institut für Photonische Technologien e.V., Germany
| | - Ines Latka
- Leibniz-Institut für Photonische Technologien e.V., Germany
| | - Christian Matthäus
- Leibniz-Institut für Photonische Technologien e.V., Germany
- Institut für Physikalische Chemie, Friedrich-Schiller-Univ. Jena, Germany
- Abbe Ctr. of Photonics, Germany
| | - Iwan Schie
- Leibniz-Institut für Photonische Technologien e.V., Germany
| | - Jürgen Popp
- Leibniz-Institut für Photonische Technologien e.V., Germany
- Institute für Physikalische Chemie, Friedrich-Schiller-Univ. Jena, Germany
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23
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Diem M, Ergin A, Remiszewski S, Mu X, Akalin A, Raz D. Infrared micro-spectroscopy of human tissue: principles and future promises. Faraday Discuss 2018; 187:9-42. [PMID: 27075634 DOI: 10.1039/c6fd00023a] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This article summarizes the methods employed, and the progress achieved over the past two decades in applying vibrational (Raman and IR) micro-spectroscopy to problems of medical diagnostics and cellular biology. During this time, several research groups have verified the enormous information contained in vibrational spectra; in fact, information on protein, lipid and metabolic composition of cells and tissues can be deduced by decoding the observed vibrational spectra. This decoding process is aided by the availability of computer workstations and advanced algorithms for data analysis. Furthermore, commercial instrumentation for the fast collection of both Raman and infrared micro-spectral data has enabled the collection of images of cells and tissues based solely on vibrational spectroscopic data. The progress in the field has been manifested by a steady increase in the number and quality of publications submitted by established and new research groups in vibrational spectroscopy in the biological and biomedical arenas.
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Affiliation(s)
- Max Diem
- Laboratory for Spectral Diagnosis (LSpD), Department of Chemistry and Chemical Biology, Northeastern University, 316 Hurtig Hall, 360 Huntington Ave, Boston, MA, USA. and Cireca Theranostics, LLC, 19 Blackstone St, Cambridge, MA, USA
| | - Ayşegül Ergin
- Cireca Theranostics, LLC, 19 Blackstone St, Cambridge, MA, USA
| | | | - Xinying Mu
- Cireca Theranostics, LLC, 19 Blackstone St, Cambridge, MA, USA and Department of Mathematics and Statistics and Program in Bioinformatics, Boston University, Boston, MA, USA
| | - Ali Akalin
- Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA
| | - Dan Raz
- Division of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA
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24
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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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25
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Wan QS, Wang T, Zhang KH. Biomedical optical spectroscopy for the early diagnosis of gastrointestinal neoplasms. Tumour Biol 2017; 39:1010428317717984. [PMID: 28671054 DOI: 10.1177/1010428317717984] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Gastrointestinal cancer is a leading contributor to cancer-related morbidity and mortality worldwide. Early diagnosis currently plays a key role in the prognosis of patients with gastrointestinal cancer. Despite the advances in endoscopy over the last decades, missing lesions, undersampling and incorrect sampling in biopsies, as well as invasion still result in a poor diagnostic rate of early gastrointestinal cancers. Accordingly, there is a pressing need to develop non-invasive methods for the early detection of gastrointestinal cancers. Biomedical optical spectroscopy, including infrared spectroscopy, Raman spectroscopy, diffuse scattering spectroscopy and autofluorescence, is capable of providing structural and chemical information about biological specimens with the advantages of non-destruction, non-invasion and reagent-free and waste-free analysis and has thus been widely investigated for the diagnosis of oesophageal, gastric and colorectal cancers. This review will introduce the advances of biomedical optical spectroscopy techniques, highlight their applications for the early detection of gastrointestinal cancers and discuss their limitations.
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Affiliation(s)
- Qin-Si Wan
- Department of Gastroenterology, Jiangxi Institute of Gastroenterology & Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ting Wang
- Department of Gastroenterology, Jiangxi Institute of Gastroenterology & Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Kun-He Zhang
- Department of Gastroenterology, Jiangxi Institute of Gastroenterology & Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Ding H, Dupont AW, Singhal S, Scott LD, Guha S, Younes M, Ye Y, Bi X. Effect of physiological factors on the biochemical properties of colon tissue – an in vivo Raman spectroscopy study. JOURNAL OF RAMAN SPECTROSCOPY 2017; 48:902-909. [DOI: 10.1002/jrs.5140] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/03/2025]
Abstract
Raman spectroscopy provides diagnostic information by detecting disease‐associated subtle biochemical changes in the tissue. Yet the physiological variations among normal subjects could confound data interpretation and thus compromise the sensitivity in disease discrimination. We analyzed Raman spectra acquired from colon tissue in vivo through an endoscopic Raman system and evaluated potential physiological factors affecting tissue biochemistry. Fifty‐six healthy patients scheduled for colonoscopy screening were enrolled in the study. Intra‐subject variability was evaluated via univariate analysis by comparing the intensities of major Raman bands from different anatomical locations. Inter‐subject variability was investigated based on various physiological variables, such as age, gender, ethnicity (White/Caucasian, African American, and Hispanic), and body mass index (BMI). Both univariate analysis and principal component analysis‐based multivariate analysis were implemented for the investigation of inter‐subject variability. The differences among certain physiological variables were further analyzed after accounting for intra‐subject variation by generalized estimating equation method due to its advantage in handling repeated measurements. The results showed that physiological factors including gender, ethnicity, age, BMI, and anatomical locations along the colon were significant sources of variability, resulting from different abundance in lipids and proteins. Further correlation analysis revealed that the variability from gender, ethnicity, and age is significantly associated with that from BMI, indicating that BMI might be the key contributor to the inter‐subject variability in the spectra. This study suggested the importance of including normal variability, especially BMI and anatomical locations, into the interpretation of Raman spectra for in vivo application. Copyright © 2017 John Wiley & Sons, Ltd.
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Affiliation(s)
- Hao Ding
- Center for Precision Biomedicine, Institute of Molecular Medicine, McGovern Medical School The University of Texas Health Science Center at Houston 1881 East Road Houston TX 77054 USA
| | - Andrew W. Dupont
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, McGovern Medical School The University of Texas Health Science Center at Houston 6431 Fannin Houston TX 77030 USA
| | - Shashideep Singhal
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, McGovern Medical School The University of Texas Health Science Center at Houston 6431 Fannin Houston TX 77030 USA
| | - Larry D. Scott
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, McGovern Medical School The University of Texas Health Science Center at Houston 6431 Fannin Houston TX 77030 USA
| | - Sushovan Guha
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, McGovern Medical School The University of Texas Health Science Center at Houston 6431 Fannin Houston TX 77030 USA
| | - Mamoun Younes
- Department of Pathology and Laboratory Medicine, McGovern Medical School The University of Texas Health Science Center at Houston 6431 Fannin Street Houston TX 77030 USA
| | - Yuanqing Ye
- Department of Epidemiology The University of Texas MD Anderson Cancer Center 1155 Pressler Street Houston TX 77030 USA
| | - Xiaohong Bi
- Center for Precision Biomedicine, Institute of Molecular Medicine, McGovern Medical School The University of Texas Health Science Center at Houston 1881 East Road Houston TX 77054 USA
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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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Diem M, Miljković M, Bird B, Mazur AI, Schubert JM, Townsend D, Laver N, Almond M, Old O. Cancer screening via infrared spectral cytopathology (SCP): results for the upper respiratory and digestive tracts. Analyst 2017; 141:416-28. [PMID: 26421636 DOI: 10.1039/c5an01751c] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Instrumental advances in infrared micro-spectroscopy have made possible the observation of individual human cells and even subcellular structures. The observed spectra represent a snapshot of the biochemical composition of a cell; this composition varies subtly but reproducibly with cellular effects such as progression through the cell cycle, cell maturation and differentiation, and disease. The aim of this summary is to provide a synopsis of the progress achieved in infrared spectral cytopathology (SCP) - the combination of infrared micro-spectroscopy and multivariate methods of analysis - for the detection of abnormalities in exfoliated human cells of the upper respiratory and digestive tract, namely the oral and nasopharyngeal cavities, and the esophagus.
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Affiliation(s)
- Max Diem
- Laboratory for Spectral Diagnosis (LSpD), Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA and Cireca Theranostics, LLC, 19 Blackstone St, Cambridge, MA 02139, USA.
| | - Miloš Miljković
- Laboratory for Spectral Diagnosis (LSpD), Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
| | - Benjamin Bird
- Laboratory for Spectral Diagnosis (LSpD), Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
| | - Antonella I Mazur
- Laboratory for Spectral Diagnosis (LSpD), Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
| | - Jen M Schubert
- Laboratory for Spectral Diagnosis (LSpD), Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
| | - Douglas Townsend
- Laboratory for Spectral Diagnosis (LSpD), Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA
| | - Nora Laver
- Department of Pathology, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA
| | - Max Almond
- Biophotonics Research Unit, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester, UK
| | - Oliver Old
- Biophotonics Research Unit, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester, UK
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29
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Ngernsutivorakul T, Cipolla CM, Dugan CE, Jin S, Morris MD, Kennedy RT, Esmonde-White FWL. Design and microfabrication of a miniature fiber optic probe with integrated lenses and mirrors for Raman and fluorescence measurements. Anal Bioanal Chem 2017; 409:275-285. [PMID: 27766359 PMCID: PMC5203949 DOI: 10.1007/s00216-016-9999-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 09/19/2016] [Accepted: 09/30/2016] [Indexed: 12/22/2022]
Abstract
Fiber optics coupled to components such as lenses and mirrors have seen extensive use as probes for Raman and fluorescence measurements. Probes can be placed directly on or into a sample to allow for simplified and remote application of these optical techniques. The size and complexity of such probes however limits their application. We have used microfabrication in polydimethylsiloxane (PDMS) to create compact probes that are 0.5 mm thick by 1 mm wide. The miniature probes incorporate pre-aligned mirrors, lenses, and two fiber optic guides to allow separate input and output optical paths suitable for Raman and fluorescence spectroscopy measurements. The fabricated probe has 70 % unidirectional optical throughput and generates no spectral artifacts in the wavelength range of 200 to 800 nm. The probe is demonstrated for measurement of fluorescence within microfluidic devices and collection of Raman spectra from a pharmaceutical tablet. The fluorescence limit of detection was 6 nM when using the probe to measure resorufin inside a 150-μm inner diameter glass capillary, 100 nM for resorufin in a 60-μm-deep × 100-μm-wide PDMS channel, and 11 nM for fluorescein in a 25-μm-deep × 80-μm-wide glass channel. It is demonstrated that the same probe can be used on different sample types, e.g., microfluidic chips and tablets. Compared to existing Raman and fluorescence probes, the microfabricated probes enable measurement in smaller spaces and have lower fabrication cost. Graphical abstract A microfabricated spectroscopic probe with integrated optics was developed for chemical detection in small spaces and in remote applications.
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Affiliation(s)
| | - Cynthia M Cipolla
- Department of Chemistry, University of Michigan, 930 N. University Ave, Ann Arbor, MI, 48109, USA
| | - Colleen E Dugan
- Department of Chemistry, University of Michigan, 930 N. University Ave, Ann Arbor, MI, 48109, USA
| | - Shi Jin
- Department of Chemistry, University of Michigan, 930 N. University Ave, Ann Arbor, MI, 48109, USA
| | - Michael D Morris
- Department of Chemistry, University of Michigan, 930 N. University Ave, Ann Arbor, MI, 48109, USA
| | - Robert T Kennedy
- Department of Chemistry, University of Michigan, 930 N. University Ave, Ann Arbor, MI, 48109, USA.
- Department of Pharmacology, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA.
| | - Francis W L Esmonde-White
- Department of Chemistry, University of Michigan, 930 N. University Ave, Ann Arbor, MI, 48109, USA
- Kaiser Optical Systems Inc, 371 Parkland Plaza, Ann Arbor, MI, 48103, USA
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30
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das Chagas E Silva de Carvalho LF, Pereira TM, Magrini TD, Cavalcante ASR, da Silva Martinho H, Almeida JD. Optical diagnosis of actinic cheilitis by infrared spectroscopy. Photodiagnosis Photodyn Ther 2016; 16:27-34. [PMID: 27491855 DOI: 10.1016/j.pdpdt.2016.07.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 06/28/2016] [Accepted: 07/30/2016] [Indexed: 01/28/2023]
Abstract
Actinic cheilitis (AC) is considered a potentially malignant disorder of the lip. Biomolecular markers study is important to understand malignant transformation into squamous cell carcinoma. Fourier transform infra red (FT-IR) spectroscopy was used to analyze AC in this study. OBJECTIVES The aim of the study was to evaluate if FT-IR spectral regions of nucleic acids and collagen can help in early diagnosis of malignant transformation. METHODS Tissues biopsies of 14 patients diagnosed with AC and 14 normal tissues were obtained. FT-IR spectra were measured at five different points resulting in 70 spectra of each. Analysis of Principal components analysis (PCA) and linear discrimination analysis (LDA) model were also used. In order to verify the statistical difference in the spectra, Mann-Whitney U test was performed in each variable (wavenumber) with p-value <0.05. RESULTS After the Mann-Whitney U test the vibrational modes of CO (Collagen 1), PO2 (Nucleic Acids) and CO asymmetric (Triglycerides/Lipids) were observed as a possible spectral biomarker. These bands were chosen because they represent the vibrational modes related to collagen and DNA, which are supposed to be changed in AC samples. Based on the PCA-LDA results, the predictive model corresponding to the area under the curve was 0.91 for the fingerprint region and 0.83 for the high wavenumber region, showing the greater accuracy of the test. CONCLUSIONS FT-IR changes in collagen and nucleic acids could be used as molecular biomarkers for malignant transformation.
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Affiliation(s)
| | - Thiago Martini Pereira
- Instituto de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos campos, São Paulo, Brazil
| | - Taciana Depra Magrini
- Laboratory of Biomedical Vibrational Spectroscopy, Universidade do Vale do Paraíba, São José dos Campos, São Paulo, Brazil
| | - Ana Sueli Rodrigues Cavalcante
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Univ Estadual Paulista (UNESP), São José dos Campos, São Paulo, Brazil
| | | | - Janete Dias Almeida
- Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Univ Estadual Paulista (UNESP), São José dos Campos, São Paulo, Brazil
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31
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Stevens O, Iping Petterson IE, Day JCC, Stone N. Developing fibre optic Raman probes for applications in clinical spectroscopy. Chem Soc Rev 2016; 45:1919-34. [PMID: 26956027 DOI: 10.1039/c5cs00850f] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Raman spectroscopy has been shown by various groups over the last two decades to have significant capability in discriminating disease states in bodily fluids, cells and tissues. Recent development in instrumentation, optics and manufacturing approaches has facilitated the design and demonstration of various novel in vivo probes, which have applicability for myriad of applications. This review focusses on key considerations and recommendations for application specific clinical Raman probe design and construction. Raman probes can be utilised as clinical tools able to provide rapid, non-invasive, real-time molecular analysis of disease specific changes in tissues. Clearly the target tissue location, the significance of spectral changes with disease and the possible access routes to the region of interest will vary for each clinical application considered. This review provides insight into design and construction considerations, including suitable probe designs and manufacturing materials compatible with Raman spectroscopy.
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Affiliation(s)
- Oliver Stevens
- Biomedical Physics, School of Physics and Astronomy, University of Exeter, Exeter, Devon EX4 4QL, UK.
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32
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Bocklitz TW, Guo S, Ryabchykov O, Vogler N, Popp J. Raman Based Molecular Imaging and Analytics: A Magic Bullet for Biomedical Applications!? Anal Chem 2015; 88:133-51. [DOI: 10.1021/acs.analchem.5b04665] [Citation(s) in RCA: 65] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Thomas W. Bocklitz
- Institute
of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany
- Leibniz Institute of Photonic Technology (IPHT), Albert-Einstein-Strasse 9, 07745 Jena, Germany
| | - Shuxia Guo
- Institute
of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany
- Leibniz Institute of Photonic Technology (IPHT), Albert-Einstein-Strasse 9, 07745 Jena, Germany
- InfectoGnostics
Forschungscampus Jena e.V., Zentrum für Angewandte Forschung, Philosophenweg 7, 07743 Jena, Germany
| | - Oleg Ryabchykov
- Institute
of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany
- Leibniz Institute of Photonic Technology (IPHT), Albert-Einstein-Strasse 9, 07745 Jena, Germany
- InfectoGnostics
Forschungscampus Jena e.V., Zentrum für Angewandte Forschung, Philosophenweg 7, 07743 Jena, Germany
| | - Nadine Vogler
- Institute
of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany
- Leibniz Institute of Photonic Technology (IPHT), Albert-Einstein-Strasse 9, 07745 Jena, Germany
- InfectoGnostics
Forschungscampus Jena e.V., Zentrum für Angewandte Forschung, Philosophenweg 7, 07743 Jena, Germany
| | - Jürgen Popp
- Institute
of Physical Chemistry and Abbe Center of Photonics, Friedrich Schiller University Jena, Helmholtzweg 4, 07743 Jena, Germany
- Leibniz Institute of Photonic Technology (IPHT), Albert-Einstein-Strasse 9, 07745 Jena, Germany
- InfectoGnostics
Forschungscampus Jena e.V., Zentrum für Angewandte Forschung, Philosophenweg 7, 07743 Jena, Germany
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33
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Coda S, Siersema PD, Stamp GWH, Thillainayagam AV. Biophotonic endoscopy: a review of clinical research techniques for optical imaging and sensing of early gastrointestinal cancer. Endosc Int Open 2015; 3:E380-92. [PMID: 26528489 PMCID: PMC4612244 DOI: 10.1055/s-0034-1392513] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 05/07/2015] [Indexed: 02/08/2023] Open
Abstract
Detection, characterization, and staging constitute the fundamental elements in the endoscopic diagnosis of gastrointestinal diseases, but histology still remains the diagnostic gold standard. New developments in endoscopic techniques may challenge histopathology in the near future. An ideal endoscopic technique should combine a wide-field, "red flag" screening technique with an optical contrast or microscopy method for characterization and staging, all simultaneously available during the procedure. In theory, biophotonic advances have the potential to unite these elements to allow in vivo "optical biopsy." These techniques may ultimately offer the potential to increase the rates of detection of high risk lesions and the ability to target biopsies and resections, and so reduce the need for biopsy, costs, and uncertainty for patients. However, their utility and sensitivity in clinical practice must be evaluated against those of conventional histopathology. This review describes some of the most recent applications of biophotonics in endoscopic optical imaging and metrology, along with their fundamental principles and the clinical experience that has been acquired in their deployment as tools for the endoscopist. Particular emphasis has been placed on translational label-free optical techniques, such as fluorescence spectroscopy, fluorescence lifetime imaging microscopy (FLIM), two-photon and multi-photon microscopy, second harmonic generation (SHG) and third harmonic generation (THG) imaging, optical coherence tomography (OCT), diffuse reflectance, Raman spectroscopy, and molecular imaging.
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Affiliation(s)
- Sergio Coda
- Section of Gastroenterology and Hepatology, Department of Medicine, Imperial College London, London, United Kingdom,Photonics Group, Department of Physics, Imperial College London, London, United Kingdom,Endoscopy Unit, Department of Gastroenterology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom,Department of Endoscopy, North East London NHS Treatment Centre, Care UK, London, United Kingdom,Corresponding author Sergio Coda, MD, PhD Imperial College London – Medicine and PhysicsPrince Consort RoadLondon SW7 2AZUnited Kingdom+44-20-75947714
| | - Peter D. Siersema
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Gordon W. H. Stamp
- Photonics Group, Department of Physics, Imperial College London, London, United Kingdom,Experimental Histopathology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom,Department of Histopathology, Imperial College London, London, United Kingdom
| | - Andrew V. Thillainayagam
- Section of Gastroenterology and Hepatology, Department of Medicine, Imperial College London, London, United Kingdom,Photonics Group, Department of Physics, Imperial College London, London, United Kingdom,Endoscopy Unit, Department of Gastroenterology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
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34
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Townsend D, Miljković M, Bird B, Lenau K, Old O, Almond M, Kendall C, Lloyd G, Shepherd N, Barr H, Stone N, Diem M. Infrared micro-spectroscopy for cyto-pathological classification of esophageal cells. Analyst 2015; 140:2215-23. [PMID: 25594077 DOI: 10.1039/c4an01884b] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
We report results from a study utilizing infrared spectral cytopathology (SCP) to detect abnormalities in exfoliated esophageal cells. SCP has been developed over the past decade as an ancillary tool to classical cytopathology. In SCP, the biochemical composition of individual cells is probed by collecting infrared absorption spectra from each individual, unstained cell, and correlating the observed spectral patterns, and the variations therein, against classical diagnostic methods to obtain an objective, machine-based classification of cells. In the past, SCP has been applied to the analysis and classification of cells exfoliated from the cervix and the oral cavity. In these studies, it was established that SCP can distinguish normal and abnormal cell types. Furthermore, SCP can differentiate between truly normal cells, and cells with normal morphology from the vicinity of abnormalities. Thus, SCP may be a valuable tool for the screening of early stages of dysplasia and pre-cancer.
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Affiliation(s)
- Douglas Townsend
- Laboratory for Spectral Diagnosis, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
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35
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Kumar P, Bhattacharjee T, Ingle A, Maru G, Krishna CM. Raman Spectroscopy of Experimental Oral Carcinogenesis: Study on Sequential Cancer Progression in Hamster Buccal Pouch Model. Technol Cancer Res Treat 2015; 15:NP60-72. [PMID: 26272064 DOI: 10.1177/1533034615598622] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 07/01/2015] [Indexed: 01/06/2023] Open
Abstract
Oral cancers suffer from poor 5-year survival rates, owing to late detection of the disease. Current diagnostic/screening tools need to be upgraded in view of disadvantages like invasiveness, tedious sample preparation, long output times, and interobserver variances. Raman spectroscopy has been shown to identify many disease conditions, including oral cancers, from healthy conditions. Further studies in exploring sequential changes in oral carcinogenesis are warranted. In this Raman spectroscopy study, sequential progression in experimental oral carcinogenesis in Hamster buccal pouch model was investigated using 3 approaches-ex vivo, in vivo sequential, and in vivo follow-up. In all these studies, spectral changes show lipid dominance in early stages while later stages and tumors showed increased protein to lipid ratio and nucleic acids. On similar lines, early weeks of 7,12-dimethylbenz(a)anthracene-treated and control groups showed higher overlap and low classification. The classification efficiency increased progressively, reached a plateau phase and subsequently increased up to 100% by 14 weeks. The misclassifications between treated and control spectra suggested some changes in controls as well, which was confirmed by a careful reexamination of histopathological slides. These findings suggests Raman spectroscopy may be able to identify microheterogeneity, which may often go unnoticed in conventional biochemistry wherein tissue extracts are employed, as well as in histopathology. In vivo findings, quite comparable to gold-standard supported ex vivo findings, give further proof of Raman spectroscopy being a promising label-free, noninvasive diagnostic adjunct for future clinical applications.
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Affiliation(s)
- Piyush Kumar
- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
| | - Tanmoy Bhattacharjee
- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
| | - Arvind Ingle
- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
| | - Girish Maru
- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
| | - C Murali Krishna
- Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India
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36
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Farhane Z, Bonnier F, Casey A, Maguire A, O'Neill L, Byrne HJ. Cellular discrimination using in vitro Raman micro spectroscopy: the role of the nucleolus. Analyst 2015. [DOI: 10.1039/c5an01157d] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Raman micro spectroscopy is employed to discriminate between cell lines. Results show the importance of the nuclear sub-cellular organelle, the nucleoli, to differentiate between cancer cell lines with high specificity and sensitivity.
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Affiliation(s)
- Z. Farhane
- FOCAS Research Institute
- Dublin Institute of Technology
- Dublin 8
- Ireland
| | - F. Bonnier
- Université François-Rabelais de Tours
- Faculty of Pharmacy
- 37200 Tours
- France
| | - A. Casey
- FOCAS Research Institute
- Dublin Institute of Technology
- Dublin 8
- Ireland
| | - A. Maguire
- FOCAS Research Institute
- Dublin Institute of Technology
- Dublin 8
- Ireland
| | - L. O'Neill
- FOCAS Research Institute
- Dublin Institute of Technology
- Dublin 8
- Ireland
| | - H. J. Byrne
- FOCAS Research Institute
- Dublin Institute of Technology
- Dublin 8
- Ireland
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37
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Devpura S, Barton KN, Brown SL, Palyvoda O, Kalkanis S, Naik VM, Siddiqui F, Naik R, Chetty IJ. Vision 20/20: the role of Raman spectroscopy in early stage cancer detection and feasibility for application in radiation therapy response assessment. Med Phys 2014; 41:050901. [PMID: 24784365 DOI: 10.1118/1.4870981] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Raman spectroscopy is an optical technique capable of identifying chemical constituents of a sample by their unique set of molecular vibrations. Research on the applicability of Raman spectroscopy in the differentiation of cancerous versus normal tissues has been ongoing for many years, and has yielded successful results in the context of prostate, breast, brain, skin, and head and neck cancers as well as pediatric tumors. Recently, much effort has been invested on developing noninvasive "Raman" probes to provide real-time diagnosis of potentially cancerous tumors. In this regard, it is feasible that the Raman technique might one day be used to provide rapid, minimally invasive real-time diagnosis of tumors in patients. Raman spectroscopy is relatively new to the field of radiation therapy. Recent work involving cell lines has shown that the Raman technique is able to identify proteins and other markers affected by radiation therapy. Although this work is preliminary, one could ask whether or not the Raman technique might be used to identify molecular markers that predict radiation response. This paper provides a brief review of Raman spectroscopic investigations in cancer detection, benefits and limitations of this method, advances in instrument development, and also preliminary studies related to the application of this technology in radiation therapy response assessment.
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Affiliation(s)
- Suneetha Devpura
- Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202
| | - Kenneth N Barton
- Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202
| | - Stephen L Brown
- Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202
| | - Olena Palyvoda
- College of Engineering, Wayne State University, Detroit, Michigan 48202
| | - Steven Kalkanis
- Department of Neurosurgery, Henry Ford Hospital, Detroit, Michigan 48202
| | - Vaman M Naik
- Department of Natural Sciences, University of Michigan-Dearborn, Dearborn, Michigan 48128
| | - Farzan Siddiqui
- Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202
| | - Ratna Naik
- Department of Physics and Astronomy, Wayne State University, Detroit, Michigan 48201
| | - Indrin J Chetty
- Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202
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Wood JJ, Kendall C, Hutchings J, Lloyd GR, Stone N, Shepherd N, Day J, Cook TA. Evaluation of a confocal Raman probe for pathological diagnosis during colonoscopy. Colorectal Dis 2014; 16:732-8. [PMID: 24836008 DOI: 10.1111/codi.12664] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2014] [Accepted: 04/06/2014] [Indexed: 12/26/2022]
Abstract
AIM Raman spectroscopy of human tissue can provide a unique biochemical 'fingerprint' that alters with disease progression. Light incident on tissue is scattered and may be altered in wavelength, which can be represented as a Raman spectrum. A confocal fibreoptic Raman probe designed to fit down the accessory channel of a colonoscope has been constructed. This in-vitro study evaluated the accuracy of pathological diagnosis in the colon using probe-based Raman spectroscopy. METHOD Biopsy samples were collected at colonoscopy, snap frozen and stored at -80 °C. Raman spectra with 10-s and 1-s acquisition periods were measured with the probe tip in contact with the mucosal surface of thawed specimens. Mathematical modelling using principal component analysis followed by linear discriminant analysis was used to correlate Raman spectra with histopathological diagnoses. RESULTS Three-hundred and seventy-five Raman spectra were measured from a total of 356 colon biopsies (81 of normal colon mucosa, 79 of hyperplastic polyps, 92 of adenomatous polyps, 64 of adenocarcinoma and 40 of ulcerative colitis) from 177 patients. Spectral classification accuracies comparing pathology pairs ranged from 72.1 to 95.9% for 10-s acquisitions and from 61.5 to 95.1% for 1-s acquisitions. For a three-group model of normal, adenomatous and adenocarcinoma tissue, accuracies were 74.1% for 10-s acquisitions and 63.5% for 1-s acquisitions. CONCLUSION The confocal Raman probe system can distinguish between different colorectal pathologies. The probe has potential to establish Raman spectroscopy as a clinical tool for instant diagnosis at colonoscopy.
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Affiliation(s)
- J J Wood
- Department of Surgery, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK; Biophotonics Research Unit, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
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Sattlecker M, Stone N, Bessant C. Current trends in machine-learning methods applied to spectroscopic cancer diagnosis. Trends Analyt Chem 2014. [DOI: 10.1016/j.trac.2014.02.016] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Diem M, Mazur A, Lenau K, Schubert J, Bird B, Miljković M, Krafft C, Popp J. Molecular pathology via IR and Raman spectral imaging. JOURNAL OF BIOPHOTONICS 2013; 6:855-86. [PMID: 24311233 DOI: 10.1002/jbio.201300131] [Citation(s) in RCA: 133] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2013] [Accepted: 09/03/2013] [Indexed: 05/21/2023]
Abstract
During the last 15 years, vibrational spectroscopic methods have been developed that can be viewed as molecular pathology methods that depend on sampling the entire genome, proteome and metabolome of cells and tissues, rather than probing for the presence of selected markers. First, this review introduces the background and fundamentals of the spectroscopies underlying the new methodologies, namely infrared and Raman spectroscopy. Then, results are presented in the context of spectral histopathology of tissues for detection of metastases in lymph nodes, squamous cell carcinoma, adenocarcinomas, brain tumors and brain metastases. Results from spectral cytopathology of cells are discussed for screening of oral and cervical mucosa, and circulating tumor cells. It is concluded that infrared and Raman spectroscopy can complement histopathology and reveal information that is available in classical methods only by costly and time-consuming steps such as immunohistochemistry, polymerase chain reaction or gene arrays. Due to the inherent sensitivity toward changes in the bio-molecular composition of different cell and tissue types, vibrational spectroscopy can even provide information that is in some cases superior to that of any one of the conventional techniques.
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Affiliation(s)
- Max Diem
- Laboratory for Spectral Diagnosis LSpD, Department of Chemistry & Chemical Biology, Northeastern University, Boston, MA 02115, USA
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Kallaway C, Almond LM, Barr H, Wood J, Hutchings J, Kendall C, Stone N. Advances in the clinical application of Raman spectroscopy for cancer diagnostics. Photodiagnosis Photodyn Ther 2013; 10:207-19. [PMID: 23993846 DOI: 10.1016/j.pdpdt.2013.01.008] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2012] [Revised: 01/26/2013] [Accepted: 01/30/2013] [Indexed: 12/20/2022]
Abstract
Light interacts with tissue in a number of ways including, elastic and inelastic scattering, reflection and absorption, leading to fluorescence and phosphorescence. These interactions can be used to measure abnormal changes in tissue. Initial optical biopsy systems have potential to be used as an adjunct to current investigative techniques to improve the targeting of blind biopsy. Future prospects with molecular-specific techniques may enable objective optical detection providing a real-time, highly sensitive and specific measurement of the histological state of the tissue. Raman spectroscopy has the potential to identify markers associated with malignant change and could be used as diagnostic tool for the early detection of precancerous and cancerous lesions in vivo. The clinical requirements for an objective, non-invasive, real-time probe for the accurate and repeatable measurement of pathological state of the tissue are overwhelming. This paper discusses some of the recent advances in the field.
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Affiliation(s)
- Charlotte Kallaway
- Biophotonics Research Unit, Gloucestershire Hospitals NHS Foundation Trust, Great Western Road, Gloucester GL1 3NN, UK
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Lloyd GR, Orr LE, Christie-Brown J, McCarthy K, Rose S, Thomas M, Stone N. Discrimination between benign, primary and secondary malignancies in lymph nodes from the head and neck utilising Raman spectroscopy and multivariate analysis. Analyst 2013; 138:3900-8. [DOI: 10.1039/c2an36579k] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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da Paz MC, Santos MDFMA, Santos CMB, da Silva SW, de Souza LB, Lima ECD, Silva RC, Lucci CM, Morais PC, Azevedo RB, Lacava ZGM. Anti-CEA loaded maghemite nanoparticles as a theragnostic device for colorectal cancer. Int J Nanomedicine 2012; 7:5271-82. [PMID: 23055733 PMCID: PMC3468277 DOI: 10.2147/ijn.s32139] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Nanosized maghemite particles were synthesized, precoated (with dimercaptosuccinic acid) and surface-functionalized with anticarcinoembryonic antigen (anti-CEA) and successfully used to target cell lines expressing the CEA, characteristic of colorectal cancer (CRC) cells. The as-developed nanosized material device, consisting of surface decorated maghemite nanoparticles suspended as a biocompatible magnetic fluid (MF) sample, labeled MF-anti-CEA, was characterized and tested against two cell lines: a high-CEA expressing cell line (LS174T) and a low-CEA expressing cell line (HCT116). Whereas X-ray diffraction was used to assess the average core size of the as-synthesized maghemite particles (average 8.3 nm in diameter), dynamic light scattering and electrophoretic mobility measurements were used to obtain the average hydrodynamic diameter (550 nm) and the zeta-potential (−38 mV) of the as-prepared and maghemite-based nanosized device, respectively. Additionally, surface-enhanced Raman spectroscopy (SERS) was used to track the surface decoration of the nanosized maghemite particles from the very first precoating up to the attachment of the anti-CEA moiety. The Raman peak at 1655 cm−1, absent in the free anti-CEA spectrum, is the signature of the anti-CEA binding onto the precoated magnetic nanoparticles. Whereas MTT assay was used to confirm the low cell toxicity of the MF-anti-CEA device, ELISA and Prussian blue iron staining tests performed with both cell lines (LS174T and HCT116) confirm that the as-prepared MF-anti- CEA is highly specific for CEA-expressing cells. Finally, transmission electron microscopy analyses show that the association with anti-CEA seems to increase the number of LS174T cells with internalized maghemite nanoparticles, whereas no such increase seems to occur in the HCT116 cell line. In conclusion, the MF-anti-CEA sample is a biocompatible device that can specifically target CEA, suggesting its potential use as a theragnostic tool for CEA-expressing tumors, micrometastasis, and cancer-circulating cells.
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Pudney PDA, Bonnist EYM, Caspers PJ, Gorce JP, Marriot C, Puppels GJ, Singleton S, van der Wolf MJG. A new in vivo Raman probe for enhanced applicability to the body. APPLIED SPECTROSCOPY 2012; 66:882-91. [PMID: 22800645 DOI: 10.1366/12-06640] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
This paper describes a new in vivo Raman probe that allows investigation of areas of the body that are otherwise difficult to access. It is coupled to a previously described commercially available in vivo Raman spectrometer that samples the skin through an optical flat. In the work presented here, the laser light emerges from a smaller pen-shaped probe. It thus works on the same principles as the original spectrometer, while its relative performance in terms of signal-to-noise ratio of the spectra and obtained spatial resolution is only slightly diminished. It allows the window to be placed against the subject in more curved and recessed areas of subject's body and also for them to be more comfortable while the measurements take place. Results from three areas of the body that have previously been very difficult to study are described, the mouth, axilla, and scalp. Results from the scalp and axilla strata cornea (SC) show significant differences from the "normal" SC of the volar forearm. For instance, the scalp is observed to have lower amounts of natural moisturizing factors (NMF) compared to the volar forearm within the same subjects. Also for both the axilla and scalp the lipids show a change in order as compared to the lipids in the volar forearm and also differences from each other. The potential significance of these observations is discussed. Further, we show how we can probe the mouth, in this case observing the presence of the astringent tea polyphenol epigallocatechin gallate within the oral mucosa.
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Affiliation(s)
- Paul D A Pudney
- Unilever Discover, Colworth Laboratory, Sharnbrook, Bedfordshire, UK.
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Applications of Infrared and Raman Microspectroscopy of Cells and Tissue in Medical Diagnostics: Present Status and Future Promises. ACTA ACUST UNITED AC 2012. [DOI: 10.1155/2012/848360] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
This paper summarizes the progress achieved over the past fifteen years in applying vibrational (Raman and IR) spectroscopy to problems of medical diagnostics and cellular biology. During this time, a number of research groups have verified the enormous information content of vibrational spectra; in fact, genomic, proteomic, and metabolomic information can be deduced by decoding the observed vibrational spectra. This decoding process is aided enormously by the availability of high-power computer workstations and advanced algorithms for data analysis. Furthermore, commercial instrumentation for the fast collection of both Raman and infrared microspectral data has rendered practical the collection of images based solely on spectral data. The progress in the field has been manifested by a steady increase in the number and quality of publications submitted by established and new research groups in vibrational biological and biomedical arenas.
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Abstract
Cancer is one of the leading causes of death throughout the world. Advancements in early and improved diagnosis could help prevent a significant number of these deaths. Raman spectroscopy is a vibrational spectroscopic technique which has received considerable attention recently with regards to applications in clinical oncology. Raman spectroscopy has the potential not only to improve diagnosis of cancer but also to advance the treatment of cancer. A number of studies have investigated Raman spectroscopy for its potential to improve diagnosis and treatment of a wide variety of cancers. In this paper the most recent advances in dispersive Raman spectroscopy, which have demonstrated promising leads to real world application for clinical oncology are reviewed. The application of Raman spectroscopy to breast, brain, skin, cervical, gastrointestinal, oral, and lung cancers is reviewed as well as a special focus on the data analysis techniques, which have been employed in the studies.
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Kiesslich R, Goetz M, Hoffman A, Galle PR. New imaging techniques and opportunities in endoscopy. Nat Rev Gastroenterol Hepatol 2011; 8:547-53. [PMID: 21894196 DOI: 10.1038/nrgastro.2011.152] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Gastrointestinal endoscopy is undergoing major improvements, which are driven by new available technologies and substantial refinements of optical features. In this Review, we summarize available and evolving imaging technologies that could influence the clinical algorithm of endoscopic diagnosis. Detection, characterization and confirmation are essential steps required for proper endoscopic diagnosis. Optical and nonoptical methods can help to improve each step; these improvements are likely to increase the detection rate of neoplasias and reduce unnecessary endoscopic treatments. Furthermore, functional and molecular imaging are emerging as new diagnostic tools that could provide an opportunity for personalized medicine, in which endoscopy will define disease outcome or predict the response to targeted therapy.
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Affiliation(s)
- Ralf Kiesslich
- Department of Internal Medicine, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
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Tay LL, Tremblay RG, Hulse J, Zurakowski B, Thompson M, Bani-Yaghoub M. Detection of acute brain injury by Raman spectral signature. Analyst 2011; 136:1620-6. [DOI: 10.1039/c0an00897d] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Kendall C, Hutchings J, Barr H, Shepherd N, Stone N. Exploiting the diagnostic potential of biomolecular fingerprinting with vibrational spectroscopy. Faraday Discuss 2011; 149:279-90; discussion 333-56. [PMID: 21413186 DOI: 10.1039/c005379a] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/01/2025]
Abstract
There is immense clinical need for techniques that can detect the biochemical changes associated with pre-malignancy. The ideal diagnostic test would provide rapid, non-invasive diagnosis at the point of care with high throughput and without prior tissue processing. Over the past decade vibrational spectroscopy techniques have demonstrated their ability to provide non-destructive, rapid, clinically relevant diagnostic information. Biochemical fingerprints of tissues measured using Raman and infrared spectroscopy analysed in conjunction with advanced chemometrics have shown great potential in the diagnostic assessment of biological material. Development of Raman probes is enabling the potential of in vivo clinical measurements to be realised. A novel probe design has been evaluated in clinical studies to identify and classify the subtle pre-malignant biochemical changes related to the carcinogenesis process. Exciting recent developments have enabled the probing of tissue samples at depth with huge potential for breast and prostate cancer diagnostics. Furthermore, the potential of vibrational spectroscopy to provide prognostic information is tantalising. Raman spectral data acquired on oesophageal biopsy samples analysed in conjunction with patient outcome data has shown the power of spectral biomolecular fingerprinting in predicting the outcome of patients with high-grade dysplasia in Barrett's oesophagus. Raman mapping can also be used to analyse thin tissue sections on calcium fluoride slides enabling the distribution of tissue constituents to be realised. The spectral data acquired effectively enables multiplexing of digital tissue stains since a whole array of information is gathered simultaneously. Technological developments are bringing the technologies closer to the clinical reality of spectral pathology and high-throughput non-destructive measurement with high resolution.
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Affiliation(s)
- Catherine Kendall
- Biophotonics Research Unit, Gloucestershire Hospitals NHS Foundation Trust, Leadon House, Great Western Road, Gloucester, UK.
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