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Liu C, Xiu C, Zou Y, Wu W, Huang Y, Wan L, Xu S, Han B, Zhang H. Cervical cancer diagnosis model using spontaneous Raman and Coherent anti-Stokes Raman spectroscopy with artificial intelligence. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2025; 327:125353. [PMID: 39481169 DOI: 10.1016/j.saa.2024.125353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 08/16/2024] [Accepted: 10/26/2024] [Indexed: 11/02/2024]
Abstract
Cervical cancer is the fourth most common cancer worldwide. Histopathology, which is currently considered the gold standard for cervical cancer diagnosis, can be time-consuming and subjective. Therefore, there is an urgent need for a rapid, objective, and non-destructive cervical cancer detection technique. In this study, high-wavenumber spontaneous Raman spectroscopy was used to detect cervical squamous cell carcinoma and normal tissues. The levels of lipids, fatty acids, and proteins in cervical cancerous tissues were found to be higher than those in normal tissues. Raman difference spectroscopy revealed the most significant difference at 2928 cm-1. Additionally, a Coherent anti-Stokes Raman spectroscopy (CARS) instrument was employed to enhance the wavenumber signal intensity and sensitivity. The intrinsic relationship between CARS imaging and cervical lesions was established. The CARS images indicated that the intensity of normal cervical squamous cells was zero, whereas the intensities of keratinized and non-keratinized cervical squamous cell carcinoma tissues were significantly higher. Consequently, diagnostic outcomes could be obtained by observing CARS images with the naked eye. Furthermore, the characteristic structure of keratin pearls in keratinized cervical cancer could serve as a marker for subdividing cervical cancer types. Finally, a ConvNeXt network, a machine-learning model built from CARS images, was utilized to classify different types of tissue images. The results indicated a verification accuracy of 100 %, with a loss function of 0.0927. These findings suggest that the diagnostic model established using CARS images could efficiently diagnose cervical cancer, providing novel insights into the pathological diagnosis of this disease.
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Affiliation(s)
- Chenyang Liu
- The Department of Gynecology, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun 130000, China.
| | - Caifeng Xiu
- The Department of Cadre's Wards Ultrasound Diagnostics, Ultrasound Diagnostic Center, The First Hospital of Jilin University, Changchun 130000, China.
| | - Yongfang Zou
- The Department of Radiology, Changchun Infectious Disease Hospital, Changchun 130000, China.
| | - Weina Wu
- The Department of Gynecology, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun 130000, China.
| | - Yizhi Huang
- The Department of Gynecology, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun 130000, China.
| | - Lili Wan
- The Department of Gynecology, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun 130000, China.
| | - Shuping Xu
- State Key Laboratory of Supramolecular Structure and Materials, Institute of Theoretical Chemistry of Jilin University, Changchun 130000, China.
| | - Bing Han
- The Department of Breast Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun 130000, China.
| | - Haipeng Zhang
- The Department of Gynecology, Obstetrics and Gynecology Center, The First Hospital of Jilin University, Changchun 130000, China.
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Georgiannakis A, Chapman CAR, Paraskevopoulos D. Surgical identification of brain tumour margins through impedance monitoring and electrocorticography and the potential for their combined use: A systematic review. Neurosurg Rev 2024; 47:888. [PMID: 39638915 PMCID: PMC11621190 DOI: 10.1007/s10143-024-03134-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 11/04/2024] [Accepted: 11/30/2024] [Indexed: 12/07/2024]
Abstract
CONTEXT Primary central nervous system tumours have poor survival outcomes. Surgery, the first-line treatment, presents technical limitations, such as visualising the whole tumour border. Intracranial impedance monitoring and electrocorticography techniques provide insights into the local field potential characteristics, resistance and capacitance properties of brain tissue. We hypothesised that measurements obtained by either modality can distinguish between tumour and healthy brain tissue intraoperatively. METHODS A "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA)-compliant systematic review was conducted, searching PubMed, Ovid, Scopus, Cochrane and Web of Science. Studies on electrocorticography and impedance monitoring in patients with brain tumours were included. Data on patient demographics, technical details, obtained results and safety were extracted and analysed in Excel. RESULTS Eighteen studies involving 286 patients in total were identified. Ten impedance studies showed that brain tumour tissue has significantly different values than healthy tissue, while its resistivity varies, being either higher or lower. Eight electrocorticography studies indicated increased high gamma power and altered connectivity in tumour tissue. No studies integrated impedance monitoring and electrocorticography in one device. CONCLUSION Impedance and electrocorticography measurements have the potential of differentiating between tumour and unaffected issues intra-operatively. Larger studies with standardised protocols are needed to validate these findings. Additionally, the combination of these two modalities has the potential for improved specificity with a single device. Future research should explore the role of these modalities in enhancing tumour margin identification across different tumour subtypes and in improving survival outcomes.
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Affiliation(s)
| | | | - Dimitrios Paraskevopoulos
- Blizard Institute, Queen Mary University of London, London, UK.
- Department of Neurosurgery, The Royal London Hospital, Barts Health NHS Trust, London, UK.
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Goff NK, Ashby L, Ashour R. Meta-Analysis of the Efficacy of Raman Spectroscopy and Machine-Learning-Based Identification of Glioma Tissue. World Neurosurg 2024; 189:26-32. [PMID: 38796149 DOI: 10.1016/j.wneu.2024.05.112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 05/17/2024] [Indexed: 05/28/2024]
Abstract
Intraoperative Raman spectroscopy (RS) has been identified as a potential tool for surgeons to rapidly and noninvasively differentiate between diseased and normal tissue. Since the previous meta-analysis on the subject was published in 2016, improvements in both spectroscopy equipment and machine learning models used to process spectra may have led to an increase in RS efficacy. Therefore, we decided to conduct a meta-analysis to determine the efficacy of RS when differentiating between glioma tissue and normal brain tissue. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed while conducting this meta-analysis. A search was conducted on PubMed and Web of Science for prospective and retrospective studies published between 2016 and 2022 using intraoperative RS and standard histology methods to differentiate between glioma and normal brain tissue. Meta-analyses of log odds ratios, sensitivity, and specificity were conducted in JASP using the random-effects model with restricted maximum likelihood estimation. A total of 9 studies met our inclusion criteria, comprising 673 patients and 8319 Raman spectra. Meta-analysis of log diagnostic odds ratios revealed high heterogeneity (I2 = 79.83%) and yielded a back-transformed diagnostic odds ratio of 76.71 (95% confidence interval: 39.57-148.71). Finally, meta-analysis for sensitivity and specificity of RS for glioma tissue showed high heterogeneity (I2 = 99.37% and 98.21%, respectively) and yielded an overall sensitivity of 95.3% (95% confidence interval: 91.0%-99.6%) and an overall specificity of 71.2% (95% confidence interval: 54.8%-87.6%). Calculation of a summary receiver operating curve yielded an overall area under the curve of 0.9265. Raman spectroscopy represents a promising tool for surgeons to quickly and accurately differentiate between healthy brain tissue and glioma tissue.
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Affiliation(s)
- Nicolas K Goff
- Department of Neurosurgery, The University of Texas at Austin Dell Medical School, Austin, Texas, USA.
| | - Landon Ashby
- Department of Neurosurgery, The University of Texas at Austin Dell Medical School, Austin, Texas, USA
| | - Ramsey Ashour
- Department of Neurosurgery, The University of Texas at Austin Dell Medical School, Austin, Texas, USA
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Aradhye P, Jha S, Saha P, Patwardhan RS, Noothalapati H, Krishna CM, Patwardhan S. Distinct spectral signatures unfold ECM stiffness-triggered biochemical changes in breast cancer cells. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2024; 311:123994. [PMID: 38354672 DOI: 10.1016/j.saa.2024.123994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 01/08/2024] [Accepted: 01/31/2024] [Indexed: 02/16/2024]
Abstract
Cancer progression often accompanies the stiffening of extracellular matrix (ECM) in and around the tumor, owing to extra deposition and cross-linking of collagen. Stiff ECM has been linked with poor prognosis and is known to fuel invasion and metastasis, notably in breast cancer. However, the underlying biochemical or metabolic changes and the cognate molecular signatures remain elusive. Here, we explored Raman spectroscopy to unveil the spectral fingerprints of breast cancer cells in response to extracellular mechanical cues. Using stiffness-tuneable hydrogels, we showed that cells grown on stiff ECM displayed morphological changes with high proliferation. We further demonstrated that Raman Spectroscopy, a label-free and non-invasive technique, could provide comprehensive information about the biochemical environment of breast cancer cells in response to varying ECM stiffness. Raman spectroscopic analysis classified the cells into distinct clusters based on principal component-based linear discriminant analysis (PC-LDA). Multivariate curve resolution-alternating least squares (MCR-ALS) analysis indicated that cells cultured on stiff ECM exhibited elevated nucleic acid content and lesser lipids. Interestingly, increased intensity of Raman bands corresponding to cytochrome-c was also observed in stiff ECM conditions, suggesting mitochondrial modulation. The key findings harboured by spectral profiles were also corroborated by transmission electron microscopy, confirming altered metabolic status as reflected by increased mitochondria number and decreased lipid droplets in response to ECM stiffening. Collectively, these findings not only give the spectral signatures for mechanoresponse but also provide the landscape of biochemical changes in response to ECM stiffening.
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Affiliation(s)
- Prasad Aradhye
- Patwardhan Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India
| | - Shubham Jha
- Patwardhan Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India
| | - Panchali Saha
- Chilakapati Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India
| | - Raghavendra S Patwardhan
- Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India
| | - Hemanth Noothalapati
- Department of Life and Environmental Sciences, Shimane University, Matsue, 690-8504, Japan
| | - C Murali Krishna
- Chilakapati Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India
| | - Sejal Patwardhan
- Patwardhan Laboratory, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India.
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Tołpa B, Paja W, Trojnar E, Łach K, Gala-Błądzińska A, Kowal A, Gumbarewicz E, Frączek P, Cebulski J, Depciuch J. FT-Raman spectra in combination with machine learning and multivariate analyses as a diagnostic tool in brain tumors. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2024; 57:102737. [PMID: 38341010 DOI: 10.1016/j.nano.2024.102737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/28/2023] [Accepted: 01/31/2024] [Indexed: 02/12/2024]
Abstract
Brain tumors are one of the most dangerous, because the position of these are in the organ that governs all life processes. Moreover, a lot of brain tumor types were observed, but only one main diagnostic method was used - histopathology, for which preparation of sample was long. Consequently, a new, quicker diagnostic method is needed. In this paper, FT-Raman spectra of brain tissues were analyzed by Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), four different machine learning (ML) algorithms to show possibility of differentiating between glioblastoma G4 and meningiomas, as well as two different types of meningiomas (atypical and angiomatous). Obtained results showed that in meningiomas additional peak around 1503 cm-1 and higher level of amides was noticed in comparison with glioblastoma G4. In the case of meningiomas differentiation, in angiomatous meningiomas tissues lower level of lipids and polysaccharides were visible than in atypical meningiomas. Moreover, PCA analyses showed higher distinction between glioblastoma G4 and meningiomas in the FT-Raman range between 800 cm-1 and 1800 cm-1 and between two types of meningiomas in the range between 2700 cm-1 and 3000 cm-1. Decision trees showed, that the most important peaks to differentiate glioblastoma and meningiomas were at 1151 cm-1 and 2836 cm-1 while for angiomatous and atypical meningiomas - 1514 cm-1 and 2875 cm-1. Furthermore, the accuracy of obtained results for glioblastoma G4 and meningiomas was 88 %, while for meningiomas - 92 %. Consequently, obtained data showed possibility of using FT-Raman spectroscopy in diagnosis of different types of brain tumors.
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Affiliation(s)
- Bartłomiej Tołpa
- Department of Neurosurgery, Clinical Hospital No 2 in Rzeszów, Lwowska 60, 35-309 Rzeszów, Poland
| | - Wiesław Paja
- Institute of Computer Science, College of Natural Sciences, University of Rzeszów, Poland
| | - Elżbieta Trojnar
- Clinical Department of Pathomorphology, Clinical Hospital No 2, Rzeszów, Poland
| | - Kornelia Łach
- Department of Pediatrics, Institute of Medical Sciences, University of Rzeszów, 35-310 Rzeszów, Poland
| | | | - Aneta Kowal
- Doctoral School, Institute of Medical Sciences, University of Rzeszów, 35-310 Rzeszów, Poland
| | - Ewelina Gumbarewicz
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland
| | - Paulina Frączek
- Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszów University, University of Rzeszów, Rzeszów, Poland
| | - Józef Cebulski
- Institute of Physics, College of Natural Sciences, University of Rzeszów, PL-35959 Rzeszów, Poland
| | - Joanna Depciuch
- Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland; Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, Poland.
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Ranc V, Pavlacka O, Kalita O, Vaverka M. Discrimination of resected glioma tissues using surface enhanced Raman spectroscopy and Au@ZrO 2 plasmonic nanosensor. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2024; 305:123521. [PMID: 37862838 DOI: 10.1016/j.saa.2023.123521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 10/06/2023] [Accepted: 10/11/2023] [Indexed: 10/22/2023]
Abstract
Gliomas present one of the most prevalent malignant tumors related to the central nervous system. Surgical extraction is still a preferred route for glioma treatment. Nonetheless, neurosurgeons still have a considerable challenge to detect actual margins of the targeted glioma intraoperatively and correctly because of its great natural infiltration. Here we evaluated the possibility of using surface-enhanced Raman spectroscopy to analyze freshly resected brain tissues. The developed method is based on the application of Au@ZrO2 nanosensor. The plasmonic properties of the sensor were first tested on the analysis of Rhodamine 6G, where concentrations down to 10-7 mol/L can be successfully detected. We also compared the performance of the nanosensor with silver plasmonic nanoparticles, where similar results were obtained regarding the reduction of the fluorescence background and enhancement of the intensity of the measured analytical signal. However, application of silver nanospheres led to increased variations in spectral data due to its probable aggregation. Applied ZrO2@Au nanosensor thus dramatically lowers the fluorescence present in the Raman data, and considerably improves the quality of the measured signal. The developed method allows for rapid discrimination between the glioma's periphery and central parts, which could serve as a steppingstone toward highly precise neurosurgery.
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Affiliation(s)
- Vaclav Ranc
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University and Faculty Hospital Olomouc, Hněvotínská 5, 775 15, Olomouc, Czech Republic.
| | - Ondrej Pavlacka
- Department of Mathematical Analysis and Applications of Mathematics, Faculty of Science, Palacký, University Olomouc, 17. Listopadu 12, Olomouc, Czech Republic
| | - Ondrej Kalita
- Department of Neurosurgery, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20, Olomouc, Czechia; Department of Health Care Science, Faculty of Humanities, T. Bata University in Zlín, Štefanikova 5670, 760 01 Zlín, Czechia
| | - Miroslav Vaverka
- Department of Neurosurgery, Faculty Hospital Olomouc, I.P. Pavlova 6, 775 20, Olomouc, Czechia
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Tipatet K, Du Boulay I, Muir H, Davison-Gates L, Ellederová Z, Downes A. Raman spectroscopy of brain and skin tissue in a minipig model of Huntington's disease. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:253-261. [PMID: 38108410 DOI: 10.1039/d3ay00970j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2023]
Abstract
We applied Raman spectroscopy to brain and skin tissues from a minipig model of Huntington's disease. Differences were observed between measured spectra of tissues with and without Huntington's disease, for both brain tissue and skin tissue. There are linked to changes in the chemical composition between tissue types. Using machine learning we correctly classified 96% of test spectra as diseased or wild type, indicating that the test would have a similar accuracy when used as a diagnostic tool for the disease. This suggests the technique has great potential in the rapid and accurate diagnosis of Huntington's and other neurodegenerative diseases in a clinical setting.
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Affiliation(s)
- Kevin Tipatet
- a, Institute for Bioengineering, School of Engineering, University of Edinburgh, King's Buildings, Edinburgh EH9 3DW, UK.
| | - Isla Du Boulay
- a, Institute for Bioengineering, School of Engineering, University of Edinburgh, King's Buildings, Edinburgh EH9 3DW, UK.
| | - Hamish Muir
- a, Institute for Bioengineering, School of Engineering, University of Edinburgh, King's Buildings, Edinburgh EH9 3DW, UK.
| | - Liam Davison-Gates
- a, Institute for Bioengineering, School of Engineering, University of Edinburgh, King's Buildings, Edinburgh EH9 3DW, UK.
| | - Zdenka Ellederová
- a, Institute for Bioengineering, School of Engineering, University of Edinburgh, King's Buildings, Edinburgh EH9 3DW, UK.
- Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Rumburská 89, 277 21 Liběchov, UK
| | - Andrew Downes
- a, Institute for Bioengineering, School of Engineering, University of Edinburgh, King's Buildings, Edinburgh EH9 3DW, UK.
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Olbrich K, Setkowicz Z, Kawon K, Czyzycki M, Janik-Olchawa N, Carlomagno I, Aquilanti G, Chwiej J. Vibrational spectroscopy methods for investigation of the animal models of glioblastoma multiforme. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2023; 303:123230. [PMID: 37586277 DOI: 10.1016/j.saa.2023.123230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 06/26/2023] [Accepted: 08/01/2023] [Indexed: 08/18/2023]
Abstract
Glioblastoma multiforme (GBM) is the most common and devastating primary brain tumor among adults. It is highly lethal disease, as only 25% of patients survive longer than 1 year and only 5% more than 5 years from the diagnosis. To search for the new, more effective methods of treatment, the understanding of mechanisms underlying the process of tumorigenesis is needed. The new light on this problem may be shed by the analysis of biochemical anomalies of tissues affected by tumor growth. Therefore, in the present work, we applied the Fourier transform infrared (FTIR) and Raman microspectroscopy to evaluate changes in the distribution and structure of biomolecules appearing in the rat brain as a result of glioblastoma development. In turn, synchrotron X-ray fluorescence microscopy was utilized to determine the elemental anomalies appearing in the nervous tissue. To achieve the assumed goals of the study animal models of GBM were used. The rats were subjected to the intracranial implantation of glioma cells with different degree of invasiveness. For spectroscopic investigation brain slices taken from the area of cancer cells administration were used. The obtained results revealed, among others, the decrease content of lipids and compounds containing carbonyl groups, compositional and structural changes of proteins as well as abnormalities in the distribution of low atomic number elements within the region of tumor.
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Affiliation(s)
- Karolina Olbrich
- Faculty of Physics and Applied Computer Science, AGH University of Krakow, Krakow, Poland
| | - Zuzanna Setkowicz
- Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
| | - Kamil Kawon
- Faculty of Physics and Applied Computer Science, AGH University of Krakow, Krakow, Poland
| | - Mateusz Czyzycki
- Institute for Photon Science and Synchrotron Radiation, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
| | - Natalia Janik-Olchawa
- Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland
| | | | | | - Joanna Chwiej
- Faculty of Physics and Applied Computer Science, AGH University of Krakow, Krakow, Poland.
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Murugappan S, Tofail SAM, Thorat ND. Raman Spectroscopy: A Tool for Molecular Fingerprinting of Brain Cancer. ACS OMEGA 2023; 8:27845-27861. [PMID: 37576695 PMCID: PMC10413827 DOI: 10.1021/acsomega.3c01848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Accepted: 07/12/2023] [Indexed: 08/15/2023]
Abstract
Brain cancer is one of those few cancers with very high mortality and low five-year survival rate. First and foremost reason for the woes is the difficulty in diagnosing and monitoring the progression of brain tumors both benign and malignant, noninvasively and in real time. This raises a need in this hour for a tool to diagnose the tumors in the earliest possible time frame. On the other hand, Raman spectroscopy which is well-known for its ability to precisely represent the molecular markers available in any sample given, including biological ones, with great sensitivity and specificity. This has led to a number of studies where Raman spectroscopy has been used in brain tumors in various ways. This review article highlights the fundamentals of Raman spectroscopy and its types including conventional Raman, SERS, SORS, SRS, CARS, etc. are used in brain tumors for diagnostics, monitoring, and even theragnostics, collating all the major works in the area. Also, the review explores how Raman spectroscopy can be even more effectively used in theragnostics and the clinical level which would make them a one-stop solution for all brain cancer needs in the future.
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Affiliation(s)
- Sivasubramanian Murugappan
- Department of Physics, Bernal
Institute and Limerick Digital Cancer Research Centre (LDCRC)
University of Limerick, Castletroy, Limerick V94T9PX, Ireland
| | - Syed A. M. Tofail
- Department of Physics, Bernal
Institute and Limerick Digital Cancer Research Centre (LDCRC)
University of Limerick, Castletroy, Limerick V94T9PX, Ireland
| | - Nanasaheb D. Thorat
- Department of Physics, Bernal
Institute and Limerick Digital Cancer Research Centre (LDCRC)
University of Limerick, Castletroy, Limerick V94T9PX, Ireland
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Baria E, Giordano F, Guerrini R, Caporalini C, Buccoliero AM, Cicchi R, Pavone FS. Dysplasia and tumor discrimination in brain tissues by combined fluorescence, Raman, and diffuse reflectance spectroscopies. BIOMEDICAL OPTICS EXPRESS 2023; 14:1256-1275. [PMID: 36950232 PMCID: PMC10026567 DOI: 10.1364/boe.477035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Revised: 12/19/2022] [Accepted: 12/19/2022] [Indexed: 06/18/2023]
Abstract
Identification of neoplastic and dysplastic brain tissues is of paramount importance for improving the outcomes of neurosurgical procedures. This study explores the combined application of fluorescence, Raman and diffuse reflectance spectroscopies for the detection and classification of brain tumor and cortical dysplasia with a label-free modality. Multivariate analysis was performed to evaluate classification accuracies of these techniques-employed both in individual and multimodal configuration-obtaining high sensitivity and specificity. In particular, the proposed multimodal approach allowed discriminating tumor/dysplastic tissues against control tissue with 91%/86% sensitivity and 100%/100% specificity, respectively, whereas tumor from dysplastic tissues were discriminated with 89% sensitivity and 86% specificity. Hence, multimodal optical spectroscopy allows reliably differentiating these pathologies using a non-invasive, label-free approach that is faster than the gold standard technique and does not require any tissue processing, offering the potential for the clinical translation of the technology.
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Affiliation(s)
- Enrico Baria
- National Institute of Optics, National Research Council, Via Nello Carrara 1, Sesto Fiorentino 50019, Italy
- European Laboratory for Non-Linear Spectroscopy, University of Florence, Via Nello Carrara 1, Sesto Fiorentino 50019, Italy
| | - Flavio Giordano
- Division of Neurosurgery, Department of Neuroscience I, "A. Meyer" Children's Hospital, Viale Gaetano Pieraccini 24, Florence 50141, Italy
| | - Renzo Guerrini
- Division of Neurosurgery, Department of Neuroscience I, "A. Meyer" Children's Hospital, Viale Gaetano Pieraccini 24, Florence 50141, Italy
| | - Chiara Caporalini
- Division of Pathology, Department of Critical Care Medicine and Surgery, University of Florence, Viale Giovanni Battista Morgagni 85, Florence 50134, Italy
| | - Anna Maria Buccoliero
- Division of Pathology, Department of Critical Care Medicine and Surgery, University of Florence, Viale Giovanni Battista Morgagni 85, Florence 50134, Italy
| | - Riccardo Cicchi
- National Institute of Optics, National Research Council, Via Nello Carrara 1, Sesto Fiorentino 50019, Italy
- European Laboratory for Non-Linear Spectroscopy, University of Florence, Via Nello Carrara 1, Sesto Fiorentino 50019, Italy
| | - Francesco Saverio Pavone
- National Institute of Optics, National Research Council, Via Nello Carrara 1, Sesto Fiorentino 50019, Italy
- European Laboratory for Non-Linear Spectroscopy, University of Florence, Via Nello Carrara 1, Sesto Fiorentino 50019, Italy
- Department of Physics and Astrophysics, University of Florence, Via Sansone 1, Sesto Fiorentino 50019, Italy
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Kuppler P, Strenge P, Lange B, Spahr-Hess S, Draxinger W, Hagel C, Theisen-Kunde D, Brinkmann R, Huber R, Tronnier V, Bonsanto MM. The neurosurgical benefit of contactless in vivo optical coherence tomography regarding residual tumor detection: A clinical study. Front Oncol 2023; 13:1151149. [PMID: 37139150 PMCID: PMC10150702 DOI: 10.3389/fonc.2023.1151149] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 03/13/2023] [Indexed: 05/05/2023] Open
Abstract
Purpose In brain tumor surgery, it is crucial to achieve complete tumor resection while conserving adjacent noncancerous brain tissue. Several groups have demonstrated that optical coherence tomography (OCT) has the potential of identifying tumorous brain tissue. However, there is little evidence on human in vivo application of this technology, especially regarding applicability and accuracy of residual tumor detection (RTD). In this study, we execute a systematic analysis of a microscope integrated OCT-system for this purpose. Experimental design Multiple 3-dimensional in vivo OCT-scans were taken at protocol-defined sites at the resection edge in 21 brain tumor patients. The system was evaluated for its intraoperative applicability. Tissue biopsies were obtained at these locations, labeled by a neuropathologist and used as ground truth for further analysis. OCT-scans were visually assessed with a qualitative classifier, optical OCT-properties were obtained and two artificial intelligence (AI)-assisted methods were used for automated scan classification. All approaches were investigated for accuracy of RTD and compared to common techniques. Results Visual OCT-scan classification correlated well with histopathological findings. Classification with measured OCT image-properties achieved a balanced accuracy of 85%. A neuronal network approach for scan feature recognition achieved 82% and an auto-encoder approach 85% balanced accuracy. Overall applicability showed need for improvement. Conclusion Contactless in vivo OCT scanning has shown to achieve high values of accuracy for RTD, supporting what has well been described for ex vivo OCT brain tumor scanning, complementing current intraoperative techniques and even exceeding them in accuracy, while not yet in applicability.
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Affiliation(s)
- Patrick Kuppler
- Department of Neurosurgery, University Medical Center Schleswig-Holstein, Luebeck, Germany
- *Correspondence: Patrick Kuppler,
| | | | | | - Sonja Spahr-Hess
- Department of Neurosurgery, University Medical Center Schleswig-Holstein, Luebeck, Germany
| | | | - Christian Hagel
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | | | - Ralf Brinkmann
- Medical Laser Center Luebeck, Luebeck, Germany
- Institute of Biomedical Optics, University of Luebeck, Luebeck, Germany
| | - Robert Huber
- Institute of Biomedical Optics, University of Luebeck, Luebeck, Germany
| | - Volker Tronnier
- Department of Neurosurgery, University Medical Center Schleswig-Holstein, Luebeck, Germany
| | - Matteo Mario Bonsanto
- Department of Neurosurgery, University Medical Center Schleswig-Holstein, Luebeck, Germany
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12
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Cutler CB, King P, Khan M, Olowofela B, Lucke-Wold B. Innovation in Neurosurgery: Lessons Learned, Obstacles, and Potential Funding Sources. NEURONS AND NEUROLOGICAL DISORDERS 2022; 1:003. [PMID: 36848305 PMCID: PMC9956204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Figures] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
Innovation is central to neurosurgery and has dramatically increased over the last twenty years. Although the specialty innovates as a whole, only 3-4.7% of practicing neurosurgeons hold patents. Various roadblocks to innovation impede this process such as lack of understanding, increasing regulatory complexity, and lack of funding. Newly emerging technologies allow us to understand how to innovate and how to learn from other medical specialties. By further understanding the process of innovation, and the funding that supports it, Neurosurgery can continue to hold innovation as one of its's central tenets.
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Affiliation(s)
| | - Patrick King
- Rosalind Franklin University of Medicine and Science, Chicago, IL, USA
| | - Majid Khan
- University of Nevada, Reno School of Medicine, Reno, NV, USA
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13
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Wang J, Zhang G. Side‐viewing handheld confocal Raman probe coupled with an off‐axis parabolic mirror for superficial epithelial Raman measurements of luminal organs. TRANSLATIONAL BIOPHOTONICS 2022. [DOI: 10.1002/tbio.202200010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Affiliation(s)
- Jianfeng Wang
- Key Laboratory of Photoelectronic Imaging Technology and System of Ministry of Education of China, School of Optics and Photonics Beijing Institute of Technology Beijing China
- Institute of Engineering Medicine, Beijing Institute of Technology Beijing China
| | - Guling Zhang
- College of Science Minzu University of China Beijing China
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14
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Stevens AR, Stickland CA, Harris G, Ahmed Z, Goldberg Oppenheimer P, Belli A, Davies DJ. Raman Spectroscopy as a Neuromonitoring Tool in Traumatic Brain Injury: A Systematic Review and Clinical Perspectives. Cells 2022; 11:1227. [PMID: 35406790 PMCID: PMC8997459 DOI: 10.3390/cells11071227] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 04/01/2022] [Accepted: 04/04/2022] [Indexed: 12/22/2022] Open
Abstract
Traumatic brain injury (TBI) is a significant global health problem, for which no disease-modifying therapeutics are currently available to improve survival and outcomes. Current neuromonitoring modalities are unable to reflect the complex and changing pathophysiological processes of the acute changes that occur after TBI. Raman spectroscopy (RS) is a powerful, label-free, optical tool which can provide detailed biochemical data in vivo. A systematic review of the literature is presented of available evidence for the use of RS in TBI. Seven research studies met the inclusion/exclusion criteria with all studies being performed in pre-clinical models. None of the studies reported the in vivo application of RS, with spectral acquisition performed ex vivo and one performed in vitro. Four further studies were included that related to the use of RS in analogous brain injury models, and a further five utilised RS in ex vivo biofluid studies for diagnosis or monitoring of TBI. RS is identified as a potential means to identify injury severity and metabolic dysfunction which may hold translational value. In relation to the available evidence, the translational potentials and barriers are discussed. This systematic review supports the further translational development of RS in TBI to fully ascertain its potential for enhancing patient care.
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Affiliation(s)
- Andrew R. Stevens
- Neuroscience, Trauma and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; (Z.A.); (A.B.); (D.J.D.)
- NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, UK
| | - Clarissa A. Stickland
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK; (C.A.S.); (G.H.); (P.G.O.)
| | - Georgia Harris
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK; (C.A.S.); (G.H.); (P.G.O.)
| | - Zubair Ahmed
- Neuroscience, Trauma and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; (Z.A.); (A.B.); (D.J.D.)
- NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, UK
- Centre for Trauma Science Research, University of Birmingham, Birmingham B15 2TT, UK
| | - Pola Goldberg Oppenheimer
- School of Chemical Engineering, University of Birmingham, Birmingham B15 2TT, UK; (C.A.S.); (G.H.); (P.G.O.)
| | - Antonio Belli
- Neuroscience, Trauma and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; (Z.A.); (A.B.); (D.J.D.)
- NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, UK
- Centre for Trauma Science Research, University of Birmingham, Birmingham B15 2TT, UK
| | - David J. Davies
- Neuroscience, Trauma and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK; (Z.A.); (A.B.); (D.J.D.)
- NIHR Surgical Reconstruction and Microbiology Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, UK
- Centre for Trauma Science Research, University of Birmingham, Birmingham B15 2TT, UK
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15
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Beton K, Wysocki P, Brozek-Pluska B. Mevastatin in colon cancer by spectroscopic and microscopic methods - Raman imaging and AFM studies. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2022; 270:120726. [PMID: 34979441 DOI: 10.1016/j.saa.2021.120726] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 11/23/2021] [Accepted: 12/05/2021] [Indexed: 06/14/2023]
Abstract
One of the most important areas of medical science is oncology, which is responsible for both the diagnostics and treatment of cancer diseases. Simultaneously one of the main challenges of oncology is the development of modern drugs effective in the fight against cancer. Statins are a group of biologically active compounds with the activity of 3-hydroxy-3-methyl glutaryl-CoA reductase inhibitors, an enzyme catalyzing the reduction of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) to mevalonic acid. By acting on this enzyme, statins inhibit the endogenous cholesterol synthesis which in turn causes the reduction of its systemic concentrations. However, in vitro and in vivo studies confirm also the cytostatic and cytotoxic effects of statins against various types of cancer cells including colon cancer. In the presented studies the influence of mevastatin on cancerous colon cells CaCo-2 by Raman spectroscopy and imaging is discussed and compared with biochemistry characteristic for normal colon cells CCD-18Co. Based on vibrational features of colon cells: normal cells CCD-18Co, cancerous cells CaCo-2 and cancerous cells CaCo-2 treated by mevastatin in different concentrations and incubation times we have confirmed the influence of this statin on biochemistry composition of cancerous human colon cells. Moreover, the spectroscopic results for colon normal cells and cancerous cells based on data typical for nucleic acids, proteins, lipids have been compared. The cytotoxisity of mevastatin was determined by using XTT tests.
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Affiliation(s)
- K Beton
- Lodz University of Technology, Institute of Applied Radiation Chemistry, Laboratory of Laser Molecular Spectroscopy, Wroblewskiego 15, 93-590 Lodz, Poland.
| | - P Wysocki
- Lodz University of Technology, Institute of Applied Radiation Chemistry, Laboratory of Laser Molecular Spectroscopy, Wroblewskiego 15, 93-590 Lodz, Poland
| | - B Brozek-Pluska
- Lodz University of Technology, Institute of Applied Radiation Chemistry, Laboratory of Laser Molecular Spectroscopy, Wroblewskiego 15, 93-590 Lodz, Poland.
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16
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Gerritsen JKW, Broekman MLD, De Vleeschouwer S, Schucht P, Nahed BV, Berger MS, Vincent AJPE. Safe Surgery for Glioblastoma: Recent Advances and Modern Challenges. Neurooncol Pract 2022; 9:364-379. [PMID: 36127890 PMCID: PMC9476986 DOI: 10.1093/nop/npac019] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
One of the major challenges during glioblastoma surgery is balancing between maximizing extent of resection and preventing neurological deficits. Several surgical techniques and adjuncts have been developed to help identify eloquent areas both preoperatively (fMRI, nTMS, MEG, DTI) and intraoperatively (imaging (ultrasound, iMRI), electrostimulation (mapping), cerebral perfusion measurements (fUS)), and visualization (5-ALA, fluoresceine)). In this review, we give an update of the state-of-the-art management of both primary and recurrent glioblastomas. We will review the latest surgical advances, challenges, and approaches that define the onco-neurosurgical practice in a contemporary setting and give an overview of the current prospective scientific efforts.
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Affiliation(s)
| | | | | | - Philippe Schucht
- Department of Neurosurgery, University Hospital Bern, Switzerland
| | - Brian Vala Nahed
- Department of Neurosurgery, Massachusetts General Hospital/Harvard Medical School, Boston MA, USA
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17
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Doran CE, Frank CB, McGrath S, Packer RA. Use of Handheld Raman Spectroscopy for Intraoperative Differentiation of Normal Brain Tissue From Intracranial Neoplasms in Dogs. Front Vet Sci 2022; 8:819200. [PMID: 35155651 PMCID: PMC8825786 DOI: 10.3389/fvets.2021.819200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 12/16/2021] [Indexed: 11/13/2022] Open
Abstract
The aim of this study was to assess feasibility and accuracy of a hand-held, intraoperative Raman spectroscopy device as a neuronavigation aid to accurately detect neoplastic tissue from adjacent normal gray and white matter. Although Raman spectra are complicated fingerprints of cell signature, the relative shift corresponding to lipid and protein content (2,845 and 2,930 cm−1, respectively), can provide a rapid assessment of whether tissue is normal white or gray matter vs. neoplasia for real-time guidance of tumor resection. Thirteen client-owned dogs were initially enrolled in the study. Two were excluded from final analysis due to incomplete data acquisition or lack of neoplastic disease. The diagnoses of the remaining 11 dogs included six meningiomas, two histiocytic sarcomas, and three gliomas. Intraoperatively, interrogated tissues included normal gray and/or white matter and tumor. A total of five Raman spectra readings were recorded from the interrogated tissues, and samples were submitted for confirmation of Raman spectra by histopathology. A resultant total of 24 samples, 13 from neoplastic tissue and 11 from normal gray or white matter, were used to calculate sensitivity and specificity of Raman spectra compared to histopathology. The handheld Raman spectroscopy device had sensitivity of 85.7% and specificity of 90% with a positive predictive value of 92.3% and negative predictive value of 81.6%. The Raman device was feasible to use intraoperatively with rapid interpretation of spectra. Raman spectroscopy may be useful for intraoperative guidance of tumor resection.
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Affiliation(s)
- Caitlin E. Doran
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
- *Correspondence: Caitlin E. Doran
| | - Chad B. Frank
- Department of Microbiology, Immunology, Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Stephanie McGrath
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
| | - Rebecca A. Packer
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
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18
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Intraoperative discrimination of native meningioma and dura mater by Raman spectroscopy. Sci Rep 2021; 11:23583. [PMID: 34880346 PMCID: PMC8654829 DOI: 10.1038/s41598-021-02977-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 11/25/2021] [Indexed: 01/10/2023] Open
Abstract
Meningiomas are among the most frequent tumors of the central nervous system. For a total resection, shown to decrease recurrences, it is paramount to reliably discriminate tumor tissue from normal dura mater intraoperatively. Raman spectroscopy (RS) is a non-destructive, label-free method for vibrational analysis of biochemical molecules. On the microscopic level, RS was already used to differentiate meningioma from dura mater. In this study we test its suitability for intraoperative macroscopic meningioma diagnostics. RS is applied to surgical specimen of intracranial meningiomas. The main purpose is the differentiation of tumor from normal dura mater, in order to potentially accelerate the diagnostic workflow. The collected meningioma and dura mater samples (n = 223 tissue samples from a total of 59 patients) are analyzed under untreated conditions using a new partially robotized RS acquisition system. Spectra (n = 1273) are combined with the according histopathological analysis for each sample. Based on this, a classifier is trained via machine learning. Our trained classifier separates meningioma and dura mater with a sensitivity of 96.06 \documentclass[12pt]{minimal}
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\begin{document}$$\pm $$\end{document}± 0.02% for internal fivefold cross validation and 100% and 93.97% if validated with an external test set. RS is an efficient method to discriminate meningioma from healthy dura mater in fresh tissue samples without additional processing or histopathological imaging. It is a quick and reliable complementary diagnostic tool to the neuropathological workflow and has potential for guided surgery. RS offers a safe way to examine unfixed surgical specimens in a perioperative setting.
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19
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Le Reste P, Pilalis E, Aubry M, McMahon M, Cano L, Etcheverry A, Chatziioannou A, Chevet E, Fautrel A. Integration of Raman spectra with transcriptome data in glioblastoma multiforme defines tumour subtypes and predicts patient outcome. J Cell Mol Med 2021; 25:10846-10856. [PMID: 34773369 PMCID: PMC8642677 DOI: 10.1111/jcmm.16902] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 08/13/2021] [Accepted: 08/20/2021] [Indexed: 12/24/2022] Open
Abstract
Raman spectroscopy is an imaging technique that has been applied to assess molecular compositions of living cells to characterize cell types and states. However, owing to the diverse molecular species in cells and challenges of assigning peaks to specific molecules, it has not been clear how to interpret cellular Raman spectra. Here, we provide firm evidence that cellular Raman spectra (RS) and transcriptomic profiles of glioblastoma can be computationally connected and thus interpreted. We find that the dimensions of high-dimensional RS and transcriptomes can be reduced and connected linearly through a shared low-dimensional subspace. Accordingly, we were able to predict global gene expression profiles by applying the calculated transformation matrix to Raman spectra and vice versa. From these analyses, we extract a minimal gene expression signature associated with specific RS profiles and predictive of disease outcome.
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Affiliation(s)
- Pierre‐Jean Le Reste
- Department of NeurosurgeryUniversity HospitalRennesFrance
- INSERM U1242University of RennesRennesFrance
- REACT – Rennes Brain Cancer TeamRennesFrance
| | | | - Marc Aubry
- REACT – Rennes Brain Cancer TeamRennesFrance
- IGDR CNRSUniversity of RennesRennesFrance
| | - Mari McMahon
- INSERM U1242University of RennesRennesFrance
- REACT – Rennes Brain Cancer TeamRennesFrance
- Centre de Lutte Contre le Cancer Eugene MarquisRennesFrance
| | - Luis Cano
- H2P2 PlatformUMS CNRS 3480 – INSERM 018University of RennesRennesFrance
| | - Amandine Etcheverry
- REACT – Rennes Brain Cancer TeamRennesFrance
- IGDR CNRSUniversity of RennesRennesFrance
| | | | - Eric Chevet
- INSERM U1242University of RennesRennesFrance
- REACT – Rennes Brain Cancer TeamRennesFrance
- Centre de Lutte Contre le Cancer Eugene MarquisRennesFrance
| | - Alain Fautrel
- H2P2 PlatformUMS CNRS 3480 – INSERM 018University of RennesRennesFrance
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20
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Lim D, Renteria ES, Sime DS, Ju YM, Kim JH, Criswell T, Shupe TD, Atala A, Marini FC, Gurcan MN, Soker S, Hunsberger J, Yoo JJ. Bioreactor design and validation for manufacturing strategies in tissue engineering. Biodes Manuf 2021; 5:43-63. [PMID: 35223131 PMCID: PMC8870603 DOI: 10.1007/s42242-021-00154-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The fields of regenerative medicine and tissue engineering offer new therapeutic options to restore, maintain or improve tissue function following disease or injury. To maximize the biological function of a tissue-engineered clinical product, specific conditions must be maintained within a bioreactor to allow the maturation of the product in preparation for implantation. Specifically, the bioreactor should be designed to mimic the mechanical, electrochemical and biochemical environment that the product will be exposed to in vivo. Real-time monitoring of the functional capacity of tissue-engineered products during manufacturing is a critical component of the quality management process. The present review provides a brief overview of bioreactor engineering considerations. In addition, strategies for bioreactor automation, in-line product monitoring and quality assurance are discussed.
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Affiliation(s)
- Diana Lim
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Eric S. Renteria
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Drake S. Sime
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Young Min Ju
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Ji Hyun Kim
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Tracy Criswell
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Thomas D. Shupe
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Frank C. Marini
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Metin N. Gurcan
- Center for Biomedical Informatics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Shay Soker
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
| | - Joshua Hunsberger
- RegenMed Development Organization (ReMDO), Winston Salem, NC 27106, USA
| | - James J. Yoo
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
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21
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Tipatet KS, Davison-Gates L, Tewes TJ, Fiagbedzi EK, Elfick A, Neu B, Downes A. Detection of acquired radioresistance in breast cancer cell lines using Raman spectroscopy and machine learning. Analyst 2021; 146:3709-3716. [PMID: 33969839 DOI: 10.1039/d1an00387a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Radioresistance-a living cell's response to, and development of resistance to ionising radiation-can lead to radiotherapy failure and/or tumour recurrence. We used Raman spectroscopy and machine learning to characterise biochemical changes that occur in acquired radioresistance for breast cancer cells. We were able to distinguish between wild-type and acquired radioresistant cells by changes in chemical composition using Raman spectroscopy and machine learning with 100% accuracy. In studying both hormone receptor positive and negative cells, we found similar changes in chemical composition that occur with the development of acquired radioresistance; these radioresistant cells contained less lipids and proteins compared to their parental counterparts. As well as characterising acquired radioresistance in vitro, this approach has the potential to be translated into a clinical setting, to look for Raman signals of radioresistance in tumours or biopsies; that would lead to tailored clinical treatments.
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Affiliation(s)
- Kevin Saruni Tipatet
- Institute for BioEngineering, University of Edinburgh, UK. and Faculty of Life Sciences, Rhine Waal University of Applied Sciences, Kleve, Germany
| | | | - Thomas Johann Tewes
- Faculty of Life Sciences, Rhine Waal University of Applied Sciences, Kleve, Germany
| | | | | | - Björn Neu
- Faculty of Life Sciences, Rhine Waal University of Applied Sciences, Kleve, Germany
| | - Andrew Downes
- Institute for BioEngineering, University of Edinburgh, UK.
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22
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Robert C, Tsiampali J, Fraser-Miller SJ, Neumann S, Maciaczyk D, Young SL, Maciaczyk J, Gordon KC. Molecular monitoring of glioblastoma's immunogenicity using a combination of Raman spectroscopy and chemometrics. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2021; 252:119534. [PMID: 33588367 DOI: 10.1016/j.saa.2021.119534] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 01/18/2021] [Accepted: 01/22/2021] [Indexed: 06/12/2023]
Abstract
Raman spectroscopy (RS) has been used as a powerful diagnostic and non-invasive tool in cancer diagnosis as well as in discrimination of cancer and immune cells. In this study RS in combination with chemometrics was applied to cellular Raman spectral data to distinguish the phenotype of T-cells and monocytes after incubation with media conditioned by glioblastoma stem-cells (GSCs) showing different molecular background. For this purpose, genetic modulations of epithelial-to-mesenchymal transition (EMT) process and expression of immunomodulator CD73 were introduced. Principal component analysis of the Raman spectral data showed that T-cells and monocytes incubated with tumour-conditioned media (TCMs) of GSCs with inhibited EMT activator ZEB1 or CD73 formed distinct clusters compared to controls highlighting their differences. Further discriminatory analysis performed using linear discriminant analysis (LDA) and support vector machine classification (SVM), yielded sensitivities and specificities of over 70 and 67% respectively upon validation against an independent test set. Supporting those results, flow cytometric analysis was performed to test the influence of TCMs on cytokine profile of T-cells and monocytes. We found that ZEB1 and CD73 influence T-cell and monocyte phenotype and promote monocyte differentiation into a population of mixed pro- and anti-tumorigenic macrophages (MΦs) and dendritic cells (DCs) respectively. In conclusion, Raman spectroscopy in combination with chemometrics enabled tracking T-cells and monocytes.
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Affiliation(s)
- Chima Robert
- Dodd-Walls Centre for Photonics and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin, New Zealand
| | - Julia Tsiampali
- Neurosurgery Department, University Hospital Duesseldorf, 40225 Duesseldorf, Germany
| | - Sara J Fraser-Miller
- Dodd-Walls Centre for Photonics and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin, New Zealand
| | - Silke Neumann
- Department of Pathology, University of Otago, Dunedin, New Zealand
| | - Donata Maciaczyk
- Department of Pathology, University of Otago, Dunedin, New Zealand
| | - Sarah L Young
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Jaroslaw Maciaczyk
- Department of Neurosurgery, University Hospital Bonn, 53179 Bonn, Germany; Department of Surgical Sciences, University of Otago, Dunedin, New Zealand.
| | - Keith C Gordon
- Dodd-Walls Centre for Photonics and Quantum Technologies, Department of Chemistry, University of Otago, Dunedin, New Zealand.
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23
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Al-Salihi M, Yi R, Wang S, Wu Q, Lin F, Qu J, Liu L. Quantitative laser-induced breakdown spectroscopy for discriminating neoplastic tissues from non-neoplastic ones. OPTICS EXPRESS 2021; 29:4159-4173. [PMID: 33771001 DOI: 10.1364/oe.410878] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 11/20/2020] [Indexed: 06/12/2023]
Abstract
In this paper, we present a method to distinguish neoplastic tissues from non-neoplastic ones using calibration-free laser-induced breakdown spectroscopy (CF-LIBS). For this propose, plasma emission was collected from neoplastic and non-neoplastic tissues taken from the ovarian cancer mice models. Results were obtained by utilizing the characteristic plasma emission lines of different elements that have been confirmed in the investigated samples. From the temporal evolution of plasma emission, the optimum temporal-observation-windows are identified for LIBS investigation. The concentrations of the detected elements in tissues were measured by a calibration-free approach based on data process of plasma parameters at the local thermodynamic equilibrium. The neoplastic specimens provided more energetic plasma than non-neoplastic ones that resulting in higher peaks intensities, electron density and electron temperature especially in the early windows (between 0.1 µs to 0.8 µs). Results demonstrated higher concentrations of major and trace elements such as Mg, Fe, Ca, Na, and K in the neoplastic tissues. Finally, the results using CF-LIBS method were found to be in good agreement with that of Inductive coupled plasma-optical emission spectroscopy (ICP-OES).
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Klamminger GG, Gérardy JJ, Jelke F, Mirizzi G, Slimani R, Klein K, Husch A, Hertel F, Mittelbronn M, Kleine-Borgmann FB. Application of Raman spectroscopy for detection of histologically distinct areas in formalin-fixed paraffin-embedded glioblastoma. Neurooncol Adv 2021; 3:vdab077. [PMID: 34355170 PMCID: PMC8331050 DOI: 10.1093/noajnl/vdab077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Although microscopic assessment is still the diagnostic gold standard in pathology, non-light microscopic methods such as new imaging methods and molecular pathology have considerably contributed to more precise diagnostics. As an upcoming method, Raman spectroscopy (RS) offers a "molecular fingerprint" that could be used to differentiate tissue heterogeneity or diagnostic entities. RS has been successfully applied on fresh and frozen tissue, however more aggressively, chemically treated tissue such as formalin-fixed, paraffin-embedded (FFPE) samples are challenging for RS. METHODS To address this issue, we examined FFPE samples of morphologically highly heterogeneous glioblastoma (GBM) using RS in order to classify histologically defined GBM areas according to RS spectral properties. We have set up an SVM (support vector machine)-based classifier in a training cohort and corroborated our findings in a validation cohort. RESULTS Our trained classifier identified distinct histological areas such as tumor core and necroses in GBM with an overall accuracy of 70.5% based on the spectral properties of RS. With an absolute misclassification of 21 out of 471 Raman measurements, our classifier has the property of precisely distinguishing between normal-appearing brain tissue and necrosis. When verifying the suitability of our classifier system in a second independent dataset, very little overlap between necrosis and normal-appearing brain tissue can be detected. CONCLUSION These findings show that histologically highly variable samples such as GBM can be reliably recognized by their spectral properties using RS. As conclusion, we propose that RS may serve useful as a future method in the pathological toolbox.
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Affiliation(s)
| | - Jean-Jacques Gérardy
- National Center of Pathology (NCP), Laboratoire national de santé (LNS), Dudelange, Luxembourg
- Luxembourg Center of Neuropathology (LCNP), Dudelange, Luxembourg
| | - Finn Jelke
- Saarland University Medical Center and Faculty of Medicine, Homburg, Germany
- National Center of Neurosurgery, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg
| | - Giulia Mirizzi
- Saarland University Medical Center and Faculty of Medicine, Homburg, Germany
- National Center of Neurosurgery, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg
| | - Rédouane Slimani
- Department of Oncology (DONC), Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg
- Doctoral School in Science and Engineering (DSSE), University of Luxembourg (UL), Esch-sur-Alzette, Luxembourg
| | - Karoline Klein
- Saarland University Medical Center and Faculty of Medicine, Homburg, Germany
- National Center of Neurosurgery, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg
| | - Andreas Husch
- Luxembourg Centre of Systems Biomedicine (LCSB), University of Luxembourg (UL), Esch-sur-Alzette, Luxembourg
| | - Frank Hertel
- Saarland University Medical Center and Faculty of Medicine, Homburg, Germany
- National Center of Neurosurgery, Centre Hospitalier de Luxembourg (CHL), Luxembourg, Luxembourg
- Luxembourg Centre of Systems Biomedicine (LCSB), University of Luxembourg (UL), Esch-sur-Alzette, Luxembourg
| | - Michel Mittelbronn
- National Center of Pathology (NCP), Laboratoire national de santé (LNS), Dudelange, Luxembourg
- Luxembourg Center of Neuropathology (LCNP), Dudelange, Luxembourg
- Department of Oncology (DONC), Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg
- Luxembourg Centre of Systems Biomedicine (LCSB), University of Luxembourg (UL), Esch-sur-Alzette, Luxembourg
| | - Felix B Kleine-Borgmann
- Saarland University Medical Center and Faculty of Medicine, Homburg, Germany
- Luxembourg Center of Neuropathology (LCNP), Dudelange, Luxembourg
- Department of Oncology (DONC), Luxembourg Institute of Health (LIH), Luxembourg, Luxembourg
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Brozek-Pluska B. Statistics assisted analysis of Raman spectra and imaging of human colon cell lines – Label free, spectroscopic diagnostics of colorectal cancer. J Mol Struct 2020. [DOI: 10.1016/j.molstruc.2020.128524] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Baria E, Pracucci E, Pillai V, Pavone FS, Ratto GM, Cicchi R. In vivo detection of murine glioblastoma through Raman and reflectance fiber-probe spectroscopies. NEUROPHOTONICS 2020; 7:045010. [PMID: 33274251 PMCID: PMC7707056 DOI: 10.1117/1.nph.7.4.045010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 10/14/2020] [Indexed: 05/29/2023]
Abstract
Significance: Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. With a worldwide incidence rate of 2 to 3 per 100,000 people, it accounts for more than 60% of all brain cancers; currently, its 5-year survival rate is < 5 % . GBM treatment relies mainly on surgical resection. In this framework, multimodal optical spectroscopy could provide a fast and label-free tool for improving tumor detection and guiding the removal of diseased tissues. Aim: Discriminating healthy brain from GBM tissues in an animal model through the combination of Raman and reflectance spectroscopies. Approach: EGFP-GL261 cells were injected into the brains of eight laboratory mice for inducing murine GBM in these animals. A multimodal optical fiber probe combining fluorescence, Raman, and reflectance spectroscopy was used to localize in vivo healthy and tumor brain areas and to collect their spectral information. Results: Tumor areas were localized through the detection of EGFP fluorescence emission. Then, Raman and reflectance spectra were collected from healthy and tumor tissues, and later analyzed through principal component analysis and linear discriminant analysis in order to develop a classification algorithm. Raman and reflectance spectra resulted in 92% and 93% classification accuracy, respectively. Combining together these techniques allowed improving the discrimination between healthy and tumor tissues up to 97%. Conclusions: These preliminary results demonstrate the potential of multimodal fiber-probe spectroscopy for in vivo label-free detection and delineation of brain tumors, and thus represent an additional, encouraging step toward clinical translation and deployment of fiber-probe spectroscopy.
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Affiliation(s)
- Enrico Baria
- University of Florence, Department of Physics, Sesto Fiorentino, Italy
- European Laboratory for Non-Linear Spectroscopy, Sesto Fiorentino, Italy
| | - Enrico Pracucci
- Scuola Normale Superiore, National Enterprise for Nanoscience and Nanotechnology, Pisa, Italy
| | - Vinoshene Pillai
- Scuola Normale Superiore, National Enterprise for Nanoscience and Nanotechnology, Pisa, Italy
| | - Francesco S. Pavone
- University of Florence, Department of Physics, Sesto Fiorentino, Italy
- European Laboratory for Non-Linear Spectroscopy, Sesto Fiorentino, Italy
- National Institute of Optics – National Research Council, Sesto Fiorentino, Italy
| | - Gian M. Ratto
- Scuola Normale Superiore, National Enterprise for Nanoscience and Nanotechnology, Pisa, Italy
| | - Riccardo Cicchi
- European Laboratory for Non-Linear Spectroscopy, Sesto Fiorentino, Italy
- National Institute of Optics – National Research Council, Sesto Fiorentino, Italy
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Brozek-Pluska B, Jarota A, Kania R, Abramczyk H. Zinc Phthalocyanine Photochemistry by Raman Imaging, Fluorescence Spectroscopy and Femtosecond Spectroscopy in Normal and Cancerous Human Colon Tissues and Single Cells. Molecules 2020; 25:E2688. [PMID: 32531903 PMCID: PMC7321347 DOI: 10.3390/molecules25112688] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/08/2020] [Accepted: 06/09/2020] [Indexed: 01/01/2023] Open
Abstract
Photodynamic therapy is a clinically approved alternative method for cancer treatment in which a combination of nontoxic drugs known as photosensitizers and oxygen is used. Despite intensive investigations and encouraging results, zinc phthalocyanines (ZnPcs) have not yet been approved as photosensitizers for clinical use. Label-free Raman imaging of nonfixed and unstained normal and cancerous colon human tissues and normal human CCD18-Co and cancerous CaCo-2 cell lines, without and after adding ZnPcS4 photosensitizer, was analyzed. The biochemical composition of normal and cancerous colon tissues and colon cells without and after adding ZnPcS4 at the subcellular level was determined. Analyzing the fluorescence/Raman signals of ZnPcS4, we found that in normal human colon tissue samples, in contrast to cancerous ones, there is a lower affinity to ZnPcS4 phthalocyanine. Moreover, a higher concentration in cancerous tissue was concomitant with a blue shift of the maximum peak position specific for the photosensitizer from 691-695 nm to 689 nm. Simultaneously for both types of samples, the signal was observed in the monomer region, confirming the excellent properties of ZnPcS4 for photo therapy (PDT). For colon cell experiments with a lower concentration of ZnPcS4 photosensitizer, c = 1 × 10-6 M, the phthalocyanine was localized in mitochondria/lipid structures; for a higher concentration, c = 9 × 10-6 M, localization inside the nucleus was predominant. Based on time-resolved experiments, we found that ZnPcS4 in the presence of biological interfaces features longer excited-state lifetime photosensitizers compared to the aqueous solution and bare ZnPcS4 film on CaF2 substrate, which is beneficial for application in PDT.
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Affiliation(s)
- Beata Brozek-Pluska
- Laboratory of Laser Molecular Spectroscopy, Institute of Applied Radiation Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, Poland; (A.J.); (R.K.); (H.A.)
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DePaoli D, Lemoine É, Ember K, Parent M, Prud’homme M, Cantin L, Petrecca K, Leblond F, Côté DC. Rise of Raman spectroscopy in neurosurgery: a review. JOURNAL OF BIOMEDICAL OPTICS 2020; 25:1-36. [PMID: 32358930 PMCID: PMC7195442 DOI: 10.1117/1.jbo.25.5.050901] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 04/10/2020] [Indexed: 05/21/2023]
Abstract
SIGNIFICANCE Although the clinical potential for Raman spectroscopy (RS) has been anticipated for decades, it has only recently been used in neurosurgery. Still, few devices have succeeded in making their way into the operating room. With recent technological advancements, however, vibrational sensing is poised to be a revolutionary tool for neurosurgeons. AIM We give a summary of neurosurgical workflows and key translational milestones of RS in clinical use and provide the optics and data science background required to implement such devices. APPROACH We performed an extensive review of the literature, with a specific emphasis on research that aims to build Raman systems suited for a neurosurgical setting. RESULTS The main translatable interest in Raman sensing rests in its capacity to yield label-free molecular information from tissue intraoperatively. Systems that have proven usable in the clinical setting are ergonomic, have a short integration time, and can acquire high-quality signal even in suboptimal conditions. Moreover, because of the complex microenvironment of brain tissue, data analysis is now recognized as a critical step in achieving high performance Raman-based sensing. CONCLUSIONS The next generation of Raman-based devices are making their way into operating rooms and their clinical translation requires close collaboration between physicians, engineers, and data scientists.
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Affiliation(s)
- Damon DePaoli
- Université Laval, CERVO Brain Research Center, Québec, Canada
- Université Laval, Centre d’optique, Photonique et Lasers, Québec, Canada
| | - Émile Lemoine
- Polytechnique Montréal, Department of Engineering Physics, Montréal, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Canada
| | - Katherine Ember
- Polytechnique Montréal, Department of Engineering Physics, Montréal, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Canada
| | - Martin Parent
- Université Laval, CERVO Brain Research Center, Québec, Canada
| | - Michel Prud’homme
- Hôpital de l’Enfant-Jésus, Department of Neurosurgery, Québec, Canada
| | - Léo Cantin
- Hôpital de l’Enfant-Jésus, Department of Neurosurgery, Québec, Canada
| | - Kevin Petrecca
- McGill University, Montreal Neurological Institute-Hospital, Department of Neurology and Neurosurgery, Montreal, Canada
| | - Frédéric Leblond
- Polytechnique Montréal, Department of Engineering Physics, Montréal, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Canada
| | - Daniel C. Côté
- Université Laval, CERVO Brain Research Center, Québec, Canada
- Université Laval, Centre d’optique, Photonique et Lasers, Québec, Canada
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Lemoine É, Dallaire F, Yadav R, Agarwal R, Kadoury S, Trudel D, Guiot MC, Petrecca K, Leblond F. Feature engineering applied to intraoperative in vivo Raman spectroscopy sheds light on molecular processes in brain cancer: a retrospective study of 65 patients. Analyst 2020; 144:6517-6532. [PMID: 31647061 DOI: 10.1039/c9an01144g] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Raman spectroscopy is a promising tool for neurosurgical guidance and cancer research. Quantitative analysis of the Raman signal from living tissues is, however, limited. Their molecular composition is convoluted and influenced by clinical factors, and access to data is limited. To ensure acceptance of this technology by clinicians and cancer scientists, we need to adapt the analytical methods to more closely model the Raman-generating process. Our objective is to use feature engineering to develop a new representation for spectral data specifically tailored for brain diagnosis that improves interpretability of the Raman signal while retaining enough information to accurately predict tissue content. The method consists of band fitting of Raman bands which consistently appear in the brain Raman literature, and the generation of new features representing the pairwise interaction between bands and the interaction between bands and patient age. Our technique was applied to a dataset of 547 in situ Raman spectra from 65 patients undergoing glioma resection. It showed superior predictive capacities to a principal component analysis dimensionality reduction. After analysis through a Bayesian framework, we were able to identify the oncogenic processes that characterize glioma: increased nucleic acid content, overexpression of type IV collagen and shift in the primary metabolic engine. Our results demonstrate how this mathematical transformation of the Raman signal allows the first biological, statistically robust analysis of in vivo Raman spectra from brain tissue.
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Affiliation(s)
- Émile Lemoine
- Department of Engineering Physics, Polytechnique Montreal, Montreal, Quebec, Canada.
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Kowalska AA, Berus S, Szleszkowski Ł, Kamińska A, Kmiecik A, Ratajczak-Wielgomas K, Jurek T, Zadka Ł. Brain tumour homogenates analysed by surface-enhanced Raman spectroscopy: Discrimination among healthy and cancer cells. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2020; 231:117769. [PMID: 31787534 DOI: 10.1016/j.saa.2019.117769] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 11/04/2019] [Accepted: 11/04/2019] [Indexed: 05/13/2023]
Abstract
One of the biggest challenge for modern medicine is to make a discrimination among healthy and cancerous tissues. Therefore, nowadays big effort of scientist are devoted to find a new way for as fast as possible diagnosis with as much as possible accuracy in distinguishing healthy from cancerous tissues. That issues are probably the most important in the case of brain tumours, when the diagnosis time plays a great role. Herein we present the surface-enhanced Raman spectroscopy (SERS) together with the principal component analysis (PCA) used to identify the spectra of different brain specimens, healthy and tumour tissues homogenates. The presented analyses include three sets of brain tissues as control samples taken from healthy objects (one set consists of samples from four brain lobes and both hemispheres; eight samples) and the brain tumours from five patients (two Anaplastic Astrocytoma and three Glioblastoma samples). Results prove that tumour brain samples can be discriminated well from the healthy tissues by using only three main principal components, with 96% of accuracy. The largest influence onto the calculated separation is attributed to the spectral regions corresponding in SERS spectra to vibrations of the L-Tryptophan (1450, 1278 cm-1), protein (1300 cm-1), phenylalanine and Amide-I (1005, 1654 cm-1). Therefore, the presented method may open the way for the probable application as a very fast diagnosis tool alternative for conventionally used histopathology or even more as an intraoperative diagnostic tool during brain tumour surgery.
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Affiliation(s)
- Aneta Aniela Kowalska
- Institute of Physical Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
| | - Sylwia Berus
- Institute of Physical Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - Łukasz Szleszkowski
- Department of Forensic Medicine, Forensic Medicine Unit, Wroclaw Medical University, ul. Mikulicza-Radeckiego 4, 50-386 Wroclaw, Poland
| | - Agnieszka Kamińska
- Institute of Physical Chemistry Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
| | - Alicja Kmiecik
- Department of Human Morphology and Embryology, Histology and Embryology Division, Wroclaw Medical University, ul. Chalubinskiego 6a, 50-368 Wroclaw, Poland
| | - Katarzyna Ratajczak-Wielgomas
- Department of Human Morphology and Embryology, Histology and Embryology Division, Wroclaw Medical University, ul. Chalubinskiego 6a, 50-368 Wroclaw, Poland
| | - Tomasz Jurek
- Department of Forensic Medicine, Forensic Medicine Unit, Wroclaw Medical University, ul. Mikulicza-Radeckiego 4, 50-386 Wroclaw, Poland
| | - Łukasz Zadka
- Department of Human Morphology and Embryology, Histology and Embryology Division, Wroclaw Medical University, ul. Chalubinskiego 6a, 50-368 Wroclaw, Poland
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Baj J, Sitarz R, Łokaj M, Forma A, Czeczelewski M, Maani A, Garruti G. Preoperative and Intraoperative Methods of Parathyroid Gland Localization and the Diagnosis of Parathyroid Adenomas. Molecules 2020; 25:E1724. [PMID: 32283730 PMCID: PMC7181220 DOI: 10.3390/molecules25071724] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/03/2020] [Accepted: 04/08/2020] [Indexed: 02/05/2023] Open
Abstract
Accurate pre-operative determination of parathyroid glands localization is critical in the selection of minimally invasive parathyroidectomy as a surgical treatment approach in patients with primary hyperparathyroidism (PHPT). Its importance cannot be overemphasized as it helps to minimize the harmful side effects associated with damage to the parathyroid glands such as in hypocalcemia, severe hemorrhage or recurrent laryngeal nerve dysfunction. Preoperative and intraoperative methods decrease the incidence of mistakenly injuring the parathyroid glands and allow for the timely diagnosis of various abnormalities, including parathyroid adenomas. This article reviews 139 studies conducted between 1970 and 2020 (49 years). Studies that were reviewed focused on several techniques including application of carbon nanoparticles, carbon nanoparticles with technetium sestamibi (99m Tc-MIBI), Raman spectroscopy, near-infrared autofluorescence, dynamic optical contrast imaging, laser speckle contrast imaging, shear wave elastography, and indocyanine green to test their potential in providing proper parathyroid glands' localization. Apart from reviewing the aforementioned techniques, this study focused on the applications that helped in the detection of parathyroid adenomas. Results suggest that applying all the reviewed techniques significantly improves the possibility of providing proper localization of parathyroid glands, and the application of indocyanine green has proven to be the 'ideal' approach for the diagnosis of parathyroid adenomas.
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Affiliation(s)
- Jacek Baj
- Chair and Department of Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (R.S.); (A.F.); (A.M.)
| | - Robert Sitarz
- Chair and Department of Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (R.S.); (A.F.); (A.M.)
- Department of Surgery, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-090 Lublin, Poland;
| | - Marek Łokaj
- Department of Surgery, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-090 Lublin, Poland;
| | - Alicja Forma
- Chair and Department of Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (R.S.); (A.F.); (A.M.)
| | - Marcin Czeczelewski
- Chair and Department of Forensic Medicine, Medical University of Lublin, 20-950 Lublin, Poland;
| | - Amr Maani
- Chair and Department of Anatomy, Medical University of Lublin, 20-950 Lublin, Poland; (R.S.); (A.F.); (A.M.)
| | - Gabriella Garruti
- Section of Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantations, University of Bari “Aldo Moro” Medical School, 70124 Bari, Italy;
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Dallaire F, Picot F, Tremblay JP, Sheehy G, Lemoine É, Agarwal R, Kadoury S, Trudel D, Lesage F, Petrecca K, Leblond F. Quantitative spectral quality assessment technique validated using intraoperative in vivo Raman spectroscopy measurements. JOURNAL OF BIOMEDICAL OPTICS 2020; 25:1-8. [PMID: 32319263 PMCID: PMC7171512 DOI: 10.1117/1.jbo.25.4.040501] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 04/08/2020] [Indexed: 05/14/2023]
Abstract
SIGNIFICANCE Ensuring spectral quality is prerequisite to Raman spectroscopy applied to surgery. This is because the inclusion of poor-quality spectra in the training phase of Raman-based pathology detection models can compromise prediction robustness and generalizability to new data. Currently, there exists no quantitative spectral quality assessment technique that can be used to either reject low-quality data points in existing Raman datasets based on spectral morphology or, perhaps more importantly, to optimize the in vivo data acquisition process to ensure minimal spectral quality standards are met. AIM To develop a quantitative method evaluating Raman signal quality based on the variance associated with stochastic noise in important tissue bands, including C─C stretch, CH2 / CH3 deformation, and the amide bands. APPROACH A single-point hand-held Raman spectroscopy probe system was used to acquire 315 spectra from 44 brain cancer patients. All measurements were classified as either high or low quality based on visual assessment (qualitative) and using a quantitative quality factor (QF) metric. Receiver-operator-characteristic (ROC) analyses were performed to evaluate the performance of the quantitative metric to assess spectral quality and improve cancer detection accuracy. RESULTS The method can separate high- and low-quality spectra with a sensitivity of 89% and a specificity of 90% which is shown to increase cancer detection sensitivity and specificity by up to 20% and 12%, respectively. CONCLUSIONS The QF threshold is effective in stratifying spectra in terms of spectral quality and the observed false negatives and false positives can be linked to limitations of qualitative spectral quality assessment.
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Affiliation(s)
- Frédérick Dallaire
- Polytechnique Montréal, Department of Computer Engineering and Software Engineering, Montréal, Québec, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
| | - Fabien Picot
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
- Polytechnique Montréal, Department of Engineering Physics, Montréal, Québec, Canada
| | | | - Guillaume Sheehy
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
- Polytechnique Montréal, Department of Engineering Physics, Montréal, Québec, Canada
| | - Émile Lemoine
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
- Polytechnique Montréal, Department of Electrical Engineering Montréal, Québec, Canada
| | | | - Samuel Kadoury
- Polytechnique Montréal, Department of Computer Engineering and Software Engineering, Montréal, Québec, Canada
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
| | - Dominique Trudel
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
- Université de Montréal, Department of Pathology and Cellular Biology, Montréal, Québec, Canada
- Centre Hospitalier de l’Université de Montréal, Department of Pathology, Québec, Canada
| | - Frédéric Lesage
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
- Centre de Recherche de l’Institut de Cardiologie de Montréal, Montréal, Québec, Canada
| | - Kevin Petrecca
- McGill University, Montreal Neurological Institute and Hospital, Brain Tumour Research Center, Department of Neurology and Neurosurgery, Montréal, Québec, Canada
| | - Frédéric Leblond
- Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
- Polytechnique Montréal, Department of Engineering Physics, Montréal, Québec, Canada
- Address all correspondence to Frédéric Leblond, E-mail:
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Abstract
This is a review of relevant Raman spectroscopy (RS) techniques and their use in structural biology, biophysics, cells, and tissues imaging towards development of various medical diagnostic tools, drug design, and other medical applications. Classical and contemporary structural studies of different water-soluble and membrane proteins, DNA, RNA, and their interactions and behavior in different systems were analyzed in terms of applicability of RS techniques and their complementarity to other corresponding methods. We show that RS is a powerful method that links the fundamental structural biology and its medical applications in cancer, cardiovascular, neurodegenerative, atherosclerotic, and other diseases. In particular, the key roles of RS in modern technologies of structure-based drug design are the detection and imaging of membrane protein microcrystals with the help of coherent anti-Stokes Raman scattering (CARS), which would help to further the development of protein structural crystallography and would result in a number of novel high-resolution structures of membrane proteins—drug targets; and, structural studies of photoactive membrane proteins (rhodopsins, photoreceptors, etc.) for the development of new optogenetic tools. Physical background and biomedical applications of spontaneous, stimulated, resonant, and surface- and tip-enhanced RS are also discussed. All of these techniques have been extensively developed during recent several decades. A number of interesting applications of CARS, resonant, and surface-enhanced Raman spectroscopy methods are also discussed.
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Luther E, Matus A, Eichberg DG, Shah AH, Ivan M. Stimulated Raman Histology for Intraoperative Guidance in the Resection of a Recurrent Atypical Spheno-orbital Meningioma: A Case Report and Review of Literature. Cureus 2019; 11:e5905. [PMID: 31777692 PMCID: PMC6853273 DOI: 10.7759/cureus.5905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Meningiomas are the most common intracranial, extra-axial neoplasms and account for a significant proportion of all central nervous system (CNS) tumors. Regardless of the grade, treatment typically involves upfront surgical resection. However, in many instances, especially in meningiomas arising from the skull base, complete removal is often difficult given the close proximity to important anatomic structures. In this report, we discuss the use of stimulated Raman histology as a means to identify tissue boundaries during the resection of an extensive, recurrent, atypical spheno-orbital meningioma. We report a 75-year-old male with a history of a prior left frontotemporal craniotomy for a grade II meningioma three years prior, who presented with worsening left-sided visual loss and pronounced temporal bossing. Repeat magnetic resonance imaging (MRI) revealed a recurrent left spheno-orbital tumor suggestive of a meningioma extending into the middle cranial fossa, the lateral orbit, and the temporalis muscle. He underwent an extended orbito-pterional craniotomy, and intraoperative stimulated Raman histology aided in the identification of tumor margins within the orbit and the temporalis muscle in order to better preserve the normal orbital contents and muscle bulk of the infratemporal fossa. This case demonstrates the utility of stimulated Raman histology during the resection of invasive skull base tumors. The immediate intraoperative Raman histologic sections can clearly identify tissue boundaries and thus help preserve important anatomic structures. Continued development of this method can potentially improve the accuracy of intraoperative diagnoses and guide surgeons during tumor resections near eloquent anatomical regions or important normal structures.
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Affiliation(s)
- Evan Luther
- Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA
| | - Alejandro Matus
- Neurological Surgery, Florida International University, Herbert Wertheim College of Medicine, Miami, USA
| | - Daniel G Eichberg
- Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA
| | - Ashish H Shah
- Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA
| | - Michael Ivan
- Neurological Surgery, University of Miami Miller School of Medicine, Miami, USA
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Zhai XH, Xiao J, Yu JK, Sun H, Zheng S. Novel sphingomyelin biomarkers for brain glioma and associated regulation research on the PI3K/Akt signaling pathway. Oncol Lett 2019; 18:6207-6213. [PMID: 31788096 DOI: 10.3892/ol.2019.10946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 07/09/2019] [Indexed: 11/06/2022] Open
Abstract
Glioma is one of the most common malignant tumor types of the central nervous system. It is necessary to identify biomarkers and novel therapeutic targets for glioma. The purpose of the present study was to distinguish lipid biomarkers with differential expression patterns in glioma tissues and normal brain tissues by matrix assisted laser desorption/ionization (MALDI)-imaging and MALDI-time of flight (TOF)-mass spectrometry (MS). Additionally, identification of lipid biomarkers was performed to describe novel therapeutic targets for glioma treatment. A total of six tissues from three patients with glioma and three control patients with traumatic brain injury were analyzed using UltrafleXtreme MALDI-TOF/TOF. The expression levels of 15 lipid peaks were higher in the TBT samples compared with in the GBT samples. The expression levels of another 16 lipid peaks were higher in the GBT samples compared with in the TBT samples. 14 peaks were identified as sphingomyelins using MS/MS. Additional results were also obtained from experiments using the glioma cell line U373-MG. These results indicated that treatment with the drug desipramine (Desi) inhibited the accumulation of ceramide on the cell membranes of glioma U373-MG cells. Treatment with Desi inhibited the activation of insulin-like growth factor-1 receptor and inhibited the activation of proteins in the PI3K/Akt signaling pathway.
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Affiliation(s)
- Xiao-Hui Zhai
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510655, P.R. China.,Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Jian Xiao
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Jie-Kai Yu
- Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
| | - Hong Sun
- Department of Chemistry and Biochemistry, University of Nevada, Las Vegas, NV 89135, USA
| | - Shu Zheng
- Cancer Institute, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China
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Juarez-Chambi RM, Kut C, Rico-Jimenez JJ, Chaichana KL, Xi J, Campos-Delgado DU, Rodriguez FJ, Quinones-Hinojosa A, Li X, Jo JA. AI-Assisted In Situ Detection of Human Glioma Infiltration Using a Novel Computational Method for Optical Coherence Tomography. Clin Cancer Res 2019; 25:6329-6338. [PMID: 31315883 DOI: 10.1158/1078-0432.ccr-19-0854] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 05/24/2019] [Accepted: 07/12/2019] [Indexed: 12/28/2022]
Abstract
PURPOSE In glioma surgery, it is critical to maximize tumor resection without compromising adjacent noncancerous brain tissue. Optical coherence tomography (OCT) is a noninvasive, label-free, real-time, high-resolution imaging modality that has been explored for glioma infiltration detection. Here, we report a novel artificial intelligence (AI)-assisted method for automated, real-time, in situ detection of glioma infiltration at high spatial resolution.Experimental Design: Volumetric OCT datasets were intraoperatively obtained from resected brain tissue specimens of 21 patients with glioma tumors of different stages and labeled as either noncancerous or glioma-infiltrated on the basis of histopathology evaluation of the tissue specimens (gold standard). Labeled OCT images from 12 patients were used as the training dataset to develop the AI-assisted OCT-based method for automated detection of glioma-infiltrated brain tissue. Unlabeled OCT images from the other 9 patients were used as the validation dataset to quantify the method detection performance. RESULTS Our method achieved excellent levels of sensitivity (∼100%) and specificity (∼85%) for detecting glioma-infiltrated tissue with high spatial resolution (16 μm laterally) and processing speed (∼100,020 OCT A-lines/second). CONCLUSIONS Previous methods for OCT-based detection of glioma-infiltrated brain tissue rely on estimating the tissue optical attenuation coefficient from the OCT signal, which requires sacrificing spatial resolution to increase signal quality, and performing systematic calibration procedures using tissue phantoms. By overcoming these major challenges, our AI-assisted method will enable implementing practical OCT-guided surgical tools for continuous, real-time, and accurate intraoperative detection of glioma-infiltrated brain tissue, facilitating maximal glioma resection and superior surgical outcomes for patients with glioma.
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Affiliation(s)
| | - Carmen Kut
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland
| | - Jose J Rico-Jimenez
- Department of Biomedical Engineering, Texas A&M University, College Station, Texas
| | | | - Jiefeng Xi
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland
| | - Daniel U Campos-Delgado
- Facultad de Ciencias, Universidad Autónoma de San Luis de Potosí, San Luis de Potosí, Mexico
| | - Fausto J Rodriguez
- Division of Neuropathology, Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland
| | | | - Xingde Li
- Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland
| | - Javier A Jo
- School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma.
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Brozek-Pluska B, Miazek K, Musiał J, Kordek R. Label-free diagnostics and cancer surgery Raman spectra guidance for the human colon at different excitation wavelengths. RSC Adv 2019; 9:40445-40454. [PMID: 35542639 PMCID: PMC9076283 DOI: 10.1039/c9ra06831g] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 11/30/2019] [Indexed: 01/27/2023] Open
Abstract
Raman spectroscopy and imaging are highly structure-sensitive methods that allow the characterization of biological samples with minimal impact. In this paper, Raman spectra and imaging of noncancerous and cancerous human colon tissue samples were measured at different excitation wavelengths: 355, 532, and 785 nm. Intra-patient variability in the analyzed spectra showed colon sample heterogeneity for both noncancerous and cancerous human sample types. The lowest inter-patient variability of Raman spectra was observed for the fingerprint region of noncancerous samples for the 532 nm excitation laser line. The bands of principal biochemical constituents (proteins, lipids, nucleic acids) predominate in VIS and NIR-Raman spectra (excitation: 532, 785 nm), with the special role of the bands of intrinsic tissue chromophores—carotenoids for VIS excitation due to resonance enhancement. At 355 nm excitation, high autofluorescence of colon tissues were observed. Our studies proved high potential of Raman spectroscopy and Raman imaging in differentiation of noncancerous and cancerous human colon tissues and that the wavelengths 532 and 785 nm offer wide possibilities for the detection of human colon tissue pathology for ex vivo and in vivo measurements and prevail over 355 nm excitation. Raman spectroscopy and imaging are highly structure-sensitive methods that allow the characterization of biological samples with minimal impact.![]()
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Affiliation(s)
- Beata Brozek-Pluska
- Laboratory of Laser Molecular Spectroscopy
- Institute of Applied Radiation Chemistry
- Lodz University of Technology
- 93-590 Lodz
- Poland
| | - Krystian Miazek
- Laboratory of Laser Molecular Spectroscopy
- Institute of Applied Radiation Chemistry
- Lodz University of Technology
- 93-590 Lodz
- Poland
| | - Jacek Musiał
- Department of Pathology
- Chair of Oncology
- Medical University of Lodz
- 92-213 Lodz
- Poland
| | - Radzislaw Kordek
- Department of Pathology
- Chair of Oncology
- Medical University of Lodz
- 92-213 Lodz
- Poland
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38
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Del Bene M, Perin A, Casali C, Legnani F, Saladino A, Mattei L, Vetrano IG, Saini M, DiMeco F, Prada F. Advanced Ultrasound Imaging in Glioma Surgery: Beyond Gray-Scale B-mode. Front Oncol 2018; 8:576. [PMID: 30560090 PMCID: PMC6287020 DOI: 10.3389/fonc.2018.00576] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Accepted: 11/16/2018] [Indexed: 12/20/2022] Open
Abstract
Introduction: Glioma surgery is aimed at obtaining maximal safe tumor resection while preserving or improving patient's neurological status. For this reason, there is growing interest for intra-operative imaging in neuro-oncological surgery. Intra-operative ultrasound (ioUS) provides the surgeon with real-time, anatomical and functional information. Despite this, in neurosurgery ioUS mainly relies only on gray-scale brightness mode (B-mode). Many other ultrasound imaging modalities, such as Fusion Imaging with pre-operative acquired magnetic resonance imaging (MRI), Doppler modes, Contrast Enhanced Ultrasound (CEUS), and elastosonography have been developed and have been extensively used in other organs. Although these modalities offer valuable real-time intra-operative information, so far their usage during neurosurgical procedures is still limited. Purpose: To present an US-based multimodal approach for image-guidance in glioma surgery, highlighting the different features of advanced US modalities: fusion imaging with pre-operative acquired MRI for Virtual Navigation, B-mode, Doppler (power-, color-, spectral-), CEUS, and elastosonography. Methods: We describe, in a step-by-step fashion, the applications of the most relevant advanced US modalities during different stages of surgery and their implications for surgical decision-making. Each US modality is illustrated from a technical standpoint and its application during glioma surgery is discussed. Results: B-mode offers dynamic morphological information, which can be further implemented with fusion imaging to improve image understanding and orientation. Doppler imaging permits to evaluate anatomy and function of the vascular tree. CEUS allows to perform a real-time angiosonography, providing valuable information in regards of parenchyma and tumor vascularization and perfusion. This facilitates tumor detection and surgical strategy, also allowing to characterize tumor grade and to identify residual tumor. Elastosonography is a promising tool able to better define tumor margins, parenchymal infiltration, tumor consistency and permitting differentiation of high grade and low grade lesions. Conclusions: Multimodal ioUS represents a valuable tool for glioma surgery being highly informative, rapid, repeatable, and real-time. It is able to differentiate low grade from high grade tumors and to provide the surgeon with relevant information for surgical decision-making. ioUS could be integrated with other intra-operative imaging and functional approaches in a synergistic manner to offer the best image guidance for each patient.
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Affiliation(s)
- Massimiliano Del Bene
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.,Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Alessandro Perin
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Cecilia Casali
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Federico Legnani
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Andrea Saladino
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Luca Mattei
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | | | - Marco Saini
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy
| | - Francesco DiMeco
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.,Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.,Department of Neurological Surgery, Johns Hopkins Medical School, Baltimore, MD, United States
| | - Francesco Prada
- Department of Neurosurgery, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.,Department of Neurological Surgery, University of Virginia, Charlottesville, VA, United States.,Focused Ultrasound Foundation, Charlottesville, VA, United States
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Ikeda H, Ito H, Hikita M, Yamaguchi N, Uragami N, Yokoyama N, Hirota Y, Kushima M, Ajioka Y, Inoue H. Raman spectroscopy for the diagnosis of unlabeled and unstained histopathological tissue specimens. World J Gastrointest Oncol 2018; 10:439-448. [PMID: 30487955 PMCID: PMC6247109 DOI: 10.4251/wjgo.v10.i11.439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 09/06/2018] [Accepted: 10/17/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the possibility of diagnosing gastric cancer from an unstained pathological tissue using Raman spectroscopy, and to compare the findings to those obtained with conventional histopathology.
METHODS We produced two consecutive tissue specimens from areas with and without cancer lesions in the surgically resected stomach of a patient with gastric cancer. One of the two tissue specimens was stained with hematoxylin and eosin and used as a reference for laser irradiation positioning by the spectroscopic method. The other specimen was left unstained and used for Raman spectroscopy analysis.
RESULTS A significant Raman scattering spectrum could be obtained at all measurement points. Raman scattering spectrum intensities of 725 cm-1 and 782 cm-1, are associated with the nucleotides adenine and cytosine, respectively. The Raman scattering spectrum intensity ratios of 782 cm-1/620 cm-1, 782 cm-1/756 cm-1, 782 cm-1/1250 cm-1, and 782 cm-1/1263 cm-1 in the gastric adenocarcinoma tissue were significantly higher than those in the normal stomach tissue.
CONCLUSION The results of this preliminary experiment suggest the feasibility of our spectroscopic method as a diagnostic tool for gastric cancer using unstained pathological specimens.
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Affiliation(s)
- Haruo Ikeda
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Hiroaki Ito
- Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Muneaki Hikita
- Stem Cell Business Development Department, Nikon Corporation, Sakae-ku, Yokohama, Kanagawa 2448533, Japan
| | - Noriko Yamaguchi
- Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Naoyuki Uragami
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Noboru Yokoyama
- Department of Surgery, Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Yuko Hirota
- Department of Pathology, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Miki Kushima
- Department of Pathology, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
| | - Yoichi Ajioka
- Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata City, Niigata 9518510, Japan
| | - Haruhiro Inoue
- Digestive Disease Center, Showa University Koto Toyosu Hospital, Koto-ku, Tokyo 1358577, Japan
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40
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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: 114] [Impact Index Per Article: 16.3] [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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