Towards disease diagnosis through spectrochemical imaging of tissue architecture.
Lead Research Organisation:
University of Manchester
Department Name: Chem Eng and Analytical Science
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Bassan P
(2014)
Transmission FT-IR chemical imaging on glass substrates: applications in infrared spectral histopathology.
in Analytical chemistry
Bassan P
(2014)
Large scale infrared imaging of tissue micro arrays (TMAs) using a tunable Quantum Cascade Laser (QCL) based microscope.
in The Analyst
Ingham J
(2018)
An evaluation of the application of the aperture infrared SNOM technique to biomedical imaging
in Biomedical Physics & Engineering Express
Pilling M
(2016)
Fundamental developments in infrared spectroscopic imaging for biomedical applications.
in Chemical Society reviews
Pilling MJ
(2015)
Comparison of transmission and transflectance mode FTIR imaging of biological tissue.
in The Analyst
Pilling MJ
(2016)
High-throughput quantum cascade laser (QCL) spectral histopathology: a practical approach towards clinical translation.
in Faraday discussions
Pilling MJ
(2017)
Quantum Cascade Laser Spectral Histopathology: Breast Cancer Diagnostics Using High Throughput Chemical Imaging.
in Analytical chemistry
Description | We have discovered that infrared spectroscopy can be used as an objective method to diagnose cancer in biopsy tissue samples. We have used a range of infrared sampling methodologies at various spatial resolutions and have seen that a basic cancer vs cancer classifier can be made at low resolution with a standard instrumentation. For more detailed analysis and sub-classification finer details are required. As part of this project a new method of data analysis related to tissue has been developed |
Exploitation Route | We hope that infrared imaging will be commercialized so that it will be used routinely in the clinic. In addition the university of Manchester has provided ~450K of funding for a high resolution optical photothermal IR microscope to continue with the high resolution tissue imaging work. |
Sectors | Healthcare |
Description | It is part due to this work that we have set up the international society for clinical spectroscopy |
Sector | Healthcare |
Impact Types | Societal |
Description | Integrating Clinical Infrared and Raman Spectroscopy with digital pathology and AI: CLIRPath-AI |
Amount | £799,226 (GBP) |
Funding ID | EP/W00058X/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2021 |
End | 08/2025 |
Title | Quantum Cascade Laser Spectral Histopathology: Breast Cancer Diagnostics Using High Throughput Chemical Imaging |
Description | Fourier transform infrared (FT-IR) microscopy, coupled with machine learning approaches, has been demonstrated to be a powerful technique for identifying abnormalities in human tissue. The ability to objectively identify the prediseased state, and diagnose cancer with high levels of accuracy, has the potential to revolutionise current histopathological practice. Despite recent technological advances in FT-IR microscopy, sample throughput and speed of acquisition are key barriers to clinical translation. Wide-field quantum cascade laser (QCL) infrared imaging systems with large focal plane array detectors utilising discrete frequency imaging, have demonstrated that large tissue microarrays (TMA) can be imaged in a matter of minutes. However this ground breaking technology is still in its infancy and its applicability for routine disease diagnosis is, as yet, unproven. In light of this we report on a large study utilising a breast cancer TMA comprised of 207 different patients. We show that by using QCL imaging with continuous spectra acquired between 912 and 1800 cm -1, we can accurately differentiate between 4 different histological classes. We demonstrate that we can discriminate between malignant and non-malignant stroma spectra with high sensitivity (93.56%) and specificity (85.64%) for an independent test set. Finally, we classify each core in the TMA and achieve high diagnostic accuracy on a patient basis with 100% sensitivity and 86.67% specificity. The absence of false negatives reported here opens up the possibility of utilising high throughput chemical imaging for cancer screening, thereby reducing pathologist workload and improving patient care. |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
Description | Agilent |
Organisation | Agilent Technologies |
Country | United States |
Sector | Private |
PI Contribution | We have been working with Agilent on a number of projects to speed up data collection. We have provided know-how in data analysis |
Collaborator Contribution | Agilent have provided many hours of consultation regarding the software. |
Impact | This paper was ca direct result of our EPSRC Impact Acceleration award. P. Bassan, A. Sachdeva, J. H. Shanks, M. D. Brown, N. W. Clarke, P. Gardner, Automated high-throughput assessment of prostate biopsy tissue using infrared spectroscopic chemical imaging, Proc. SPIE 9041, Medical Imaging 2014: Digital Pathology, 90410D We have also presented at numerous conferences and workshops. High-throughput assessment of biopsy tissue using infrared spectroscopic chemical imaging, Agilent FTIR imaging workshop, Montreal, Canada, 26 June 2016 Rapid assessment of breast and prostate biopsy tissue using infrared spectroscopic chemical imaging. Agilent FTIR imaging workshop, Krakow, Poland 17th August 2014 The use of infrared imaging in urological pathology. Agilent International Imaging Workshop 2012, 11th November, Chiang Mai, Thailand |
Start Year | 2010 |
Description | Noel Clarke |
Organisation | The Christie NHS Foundation Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | We have had a number of joint projects and joint studentship over the last 18 years. We have provided access to state of the art infrared imaging systems. |
Collaborator Contribution | Noel's group have provided access to tissue samples, and numerous consultations regarding our work. We have regular project meeting at the Christie. |
Impact | This has been a very successful collaboration resulting in 34 peer reviewed publications and numerous presentations at international conferences. Publications 1. M. J Pilling, A. Henderson, J. H. Shanks, M. D. Brown, N. W. Clarke and P. Gardner, Infrared Spectral Histopathology Using Haematoxylin and Eosin (H&E) Stained Glass Slides: A major step forward towards clinical translation. Analyst on line 2. M. Jimenez-Hernandez, M. D. Brown , C. Hughes, N. W. Clarke, P. Gardner, Characterising cytotoxic agent action as a function of the cell cycle using Fourier Transform Infrared Mircospectroscopy, Analyst, 2015, 140, 4453 - 4464 3. C. Hughes, A. Henderson, M. Kansiz, K. M. Dorling, M. Jimenez-Hernandez, M. D. Brown, N. W. Clarkeb, and P. Gardner, Enhanced FTIR benchtop imaging of single biological cells, Analyst, 2015, 140, 2080 - 2085. DOI: 10.1039/C4AN02053G 4. P. Bassan, A. Sachdeva, J. H. Shanks, M. D. Brown, N. W. Clarke, P. Gardner, Automated high-throughput assessment of prostate biopsy tissue using infrared spectroscopic chemical imaging, Proc. SPIE 9041, Medical Imaging 2014: Digital Pathology, 90410D 5. C. Hughes, M. Brown, G. Clemens, A. Henderson, G. Monjardez, N.W. Clarke, P. Gardner, Assessing the challenges of Fourier transform infrared spectroscopic analysis of blood serum, J Biophotonics 2014 7(3-4) 180-188 6. C. Hughes, L. Gaunt, M. Brown, N.W. Clarke, P. Gardner, Assessment of Paraffin Removal from prostate FFPE Sections using transmission mode FTIR-FPA Imaging, Analytical Methods. 2014, 6 (4), 1028 - 1035 7. P. Bassan, A. Sachdeva, J. Shanks, Mick D. Brown, N.W. Clarke, P.Gardner, Whole organ cross-section chemical imaging using label-free mega-mosaic FTIR microscopy, Analyst 2013, 138(23), 7066-7069 8. M. Jimenez-Hernandez, C. Hughes, P. Bassan, F. Ball, M.D. Brown, N.W Clarke, P. Gardner. Exploring the spectroscopic differences of Caki-2 cells progressing through the cell cycle while proliferating in-vitro. Analyst 2013, 138(14), 3957-3966 9. C. Hughes, M. Brown, J. H Shanks J. Iqbal-Wahid, A. Eustac, H. Denley, P. J Hoskin, C. West, N. W Clarke, P. Gardner, FTIR microspectroscopy of diverse sub-variants of carcinoma of the urinary bladder: a pilot study. J Biophotonics, 6(1) (2013) 73-87 10. C. Hughes , M. D. Brown , F. Ball , G. Monjardez, P. Dumas, N. W. Clarke, K. R. Flower and P Gardner, Highlighting a Need to Distinguish Cell Cycle Signatures from Cellular Responses to Chemotherapeutics in SR-FTIR Spectroscopy, Analyst 137 (24),(2012), 5736 - 5742 11. C. Hughes , M. D. Brown , P. Dumas, N. W. Clarke, K. R. Flower and P Gardner, Tracking Cellular Responses to Chemotherapeutics in Renal Cell Carcinoma using Synchrotron and Benchtop FTIR Spectroscopy, Analyst, 137 (20), (2012), 4720 - 4726 12. P. Bassan, A. Sachdeva, A. Kohler, C. Hughes, A. Henderson, J. Boyle, J. H. Shanks, M. Brown, N. W. Clarke P.Gardner, FTIR Microscopy of biological cells and tissue: data analysis using resonant Mie scattering (RMieS) EMSC algorithm, Analyst 137, (2012) 1370-1377 13. C. Hughes, M. Liew, M. D. Brown, A. Sachdeva, P. Bassan, P. Dumas, C.Hart, N. W. Clarke, P.Gardner, SR-FTIR Spectroscopy of Renal Epithelial Carcinoma Cells Displaying Stem Cell Characteristics, Analyst, 135, (2010) 3133-3141 14. P. Bassan, A. Kohler, H. Martens, J. Lee, E. Jackson, N. Lockyer, P. Dumas, M. Brown, N. Clarke, P. Gardner RMieS-EMSC correction for infrared spectra of biological cells: Extension using full Mie theory and GPU computing, J. Biophotonics, 3 (2010) 609-620 15. M.J. Baker, C. Clarke, D. Démoulin, J. Nicholson, F. Lyng, H.J. Byrne, C.A. Hart, M.D. Brown, N.W. Clarke, P. Gardner, An Investigation of the RWPE Prostate Derived Family of Cell Lines Using FTIR Spectroscopy, Analyst, 135, (2010) 887- 894 16. P. Bassan, A. Kohler, H. Martens, J. Lee, H. J. Byrne, P. Dumas, E. Gazi, M. Brown, N. Clarke, P. Gardner, Resonant Mie Scattering (RMieS) Correction of Infrared Spectra from Highly Scattering Biological Samples, Analyst, 135 (2010) 268-277 (Front Cover) 17. M. Brown, C. Hart, E. Gazi, P. Gardner, N. Lockyer, N. Clarke, The influence of the omega 6 PUFA arachidonic acid and bone marrow adipocytes on the metastatic spread of prostate cancer, British Journal of Cancer, 102 (2010) 403-413 18. P. Bassan, H. J. Byrne, J. Lee, F. Bonnier, C. Clarke, P. Dumas, E. Gazi, M. D. Brown, N. W. Clarke, P. Gardner., Reflection contributions to dispersion artefact in FTIR spectra of cellular samples, Analyst, 134, (2009), 1171-1175 19. T. J. Harvey, E. Gazi, A. Henderson, R. D Snook, N. W. Clarke, M. Brown, P Gardner. Factors Influencing the Discrimination and Classification of Prostate Cancer Cells Lines by FTIR Microspectroscopy, Analyst 134, (2009) 1083-1091 20. M.J. Baker, E.Gazi, M.D. Brown, J.H. Shanks, N.W. Clarke, P. Gardner, Investigating FTIR Based Histopathology for the Diagnosis of Prostate Cancer, J. Biophotonics, 2 (2009) 104-113 21. T J Harvey, C Hughes, A D Ward, E Correia Faria, A Henderson, N W Clarke, M D Brown, R D Snook P. Gardner, Classification of Fixed Urological Cells using Raman Tweezers, J. Biophotonics, 2 (2009) 47-69 22. E. Gazi, T.J. Harvey, M.D.Brown, N.W. Clarke, N.P. Lockyer, P. Gardner, A FTIR Microspectroscopic Study of the Uptake and Metabolism of Isotopically Labelled Fatty Acids by Metastatic Prostate Cancer, Vibrational Spectroscopy, 50 (2009) 99-105 23. T. J. Harvey, E Correia Faria, E Gazi, A D Ward, N W Clarke, M D Brown, R.D. Snook, P Gardner, The Spectral Discrimination of Live Prostate and Bladder Cancer Cell Lines Using Raman Optical Tweezers, Journal of Biomedical Optics, 13 (2008) 064004 24. 76. M.J. Baker, E.Gazi, M.D. Brown, J.H. Shanks, P. Gardner, N.W. Clarke, FTIR Based Spectroscopic Analysis in the Identification of Clinically Aggressive Prostate Cancer, British Journal of Cancer, 99 (2008) 1859-1866 25. 74. E. Gazi, P. Gardner, N.P Lockyer, C.A Hart, N.W. Clarke, M.D Brown, Probing Lipid Translocation Between Adipocytes and Prostate Cancer Cells with Imaging FTIR Microspectroscopy, J. Lipid Research 48 (2007) 1846 26. 73. J. Lee, E Gazi, J Dwyer, M. D. Brown, N. W. Clarke, P. Gardner, Optical artefacts in transflection mode FTIR microspectroscopic images of single cells on a biological support: the effect of back-scattering into collection optics. Analyst 132 (2007) 750-755 27. T. J. Harvey, A. Henderson, E. Gazi, N. W. Clarke, M. Brown, E Correia Faria, R. D. Snook P. Gardner, Discrimination of prostate cancer cells by reflection mode FTIR photo-acoustic spectroscopy, Analyst 132 (2007) 292-295 28. E. Gazi, J. Dwyer, N.P Lockyer, P. Gardner, J.H Shanks, Jo-An Roulson, C.A Hart, N.W Clarke, M.D Brown, Biomolecular Profiling of Metastatic Prostate Cancer Cells in Bone Marrow Tissue Using FTIR Microspectroscopy: A Pilot Study, Analytical and Bioanalytical Chemistry, 387 (2007) 1621-1631. 29. E. Gazi, M. Baker, J. Dwyer, N. P. Lockyer, P. Gardner, J.H. Shanks, R. S. Reeve, C. Hart, N.W. Clarke M. Brown, A Correlation of FTIR Spectra Derived from Prostate Cancer Tissue with Gleason Grade, and Tumour Stage, 30. E. Gazi, J. Dwyer, N. P. Lockyer. J. Miyan, P. Gardner, C.A Hart, M.D Brown, N.W. Clarke, A Study of Cytokinetic and Motile Prostate Cancer Cells Using Synchrotron Based FTIR - Microspectroscopic Imaging, Vibrational Spectroscopy 38 (2005) 193 - 201 31. E. Gazi, J. Dwyer, J. Miyan, P. Gardner, C. Hart, M. Brown, N.W. Clarke, Fixation Protocols for Sub-cellular Imaging by Synchrotron Based FTIR Microspectroscopy, Biopolymers 77 (2005) 18-30 32. E. Gazi, N. P. Lockyer, J. C. Vickerman, P. Gardner, J. Dwyer, C. A. Hart, M. B. Brown, N. W. Clarke J. Miyan, Imaging ToF-SIMS and synchrotron based FTIR-microspectroscopic studies of prostate cancer cell lines, Applied Surface Science 231 - 232 (2004) 452 - 456 33. E. Gazi, J. Dwyer, N. Lockyer, P. Gardner, J.C. Vickerman, J. Miyan, C. Hart, M. Brown and N. Clarke, Application of FTIR Microspectroscopy and ToF-SIMS Imaging in the Study of Prostate Cancer, Faraday Discussions 126 (2004) 41 - 59 34. E. Gazi, J. Dwyer, P. Gardner, A. Ghanbari-Siakhali, A. P. Wade. J. Myan. N.P.Lockyer, J. C. Vickerman, N. W. Clarke, J. H. Shanks, C. Hart, M.Brown, Applications of Fourier Transform Infrared Microspectroscopy in Studies of Benign Prostate & Prostate Cancer. A pilot Study, J. Pathology 201 (2003) 99-108 |