Towards disease diagnosis through spectrochemical imaging of tissue architecture.

Lead Research Organisation: University of Liverpool
Department Name: Physics

Abstract

This proposal brings together a critical mass of scientists from the Universities of Cardiff, Lancaster, Liverpool and Manchester and clinicians from the Christie, Lancaster and Liverpool NHS Hospital Trusts with the complementary experience and expertise to advance the understanding, diagnosis and treatment of cervical, oesophageal and prostate cancers. Cervical and prostate cancer are very common and the incidence of oesophageal is rising rapidly. There are cytology, biopsy and endoscopy techniques for extracting tissue from individuals who are at risk of developing these diseases. However the analysis of tissue by the standard techniques is problematic and subjective. There is clearly a national and international need to develop more accurate diagnostics for these diseases and that is a primary aim of this proposal.
Experiments will be conducted on specimens from all three diseases using four different infrared based techniques which have complementary strengths and weaknesses: hyperspectral imaging, Raman spectroscopy, a new instrument to be developed by combining atomic force microscopy with infrared spectroscopy and a scanning near field microscope recently installed on the free electron laser on the ALICE accelerator at Daresbury. The latter instrument has recently been shown to have considerable potential for the study of oesophageal cancer yielding images which show the chemical composition with unprecedented spatial resolution (0.1 microns) while hyperspectral imaging and Raman spectroscopy have been shown by members of the team to provide high resolution spectra that provide insight into the nature of cervical and prostate cancers. The new instrument will be installed on the free electron laser at Daresbury and will yield images on the nanoscale. This combination of techniques will allow the team to probe the physical and chemical structure of these three cancers with unprecedented accuracy and this should reveal important information about their character and the chemical processes that underlie their malignant behavior. The results of the research will be of interest to the study of cancer generally particularly if it reveals feature common to all three cancers.
The infrared techniques have considerable medical potential and to differing extents are on the verge of finding practical applications. Newer terahertz techniques also have significant potential in this field and may be cheaper to implement. Unfortunately the development of cheap portable terahertz diagnositic instruments is being impeded by the weakness of existing sources of terahertz radiation. By exploiting the terahertz radiation from the ALICE accelerator, which is seven orders of magnitude more intense that conventional sources, the team will advance the design of two different terahertz instruments and assess their performance against the more developed infrared techniques in cancer diagnosis. However before any of these techniques can be used by medical professionals it is essential that their strengths and limitations of are fully understood. This is one of the objectives of the proposal and it will be realised by comparing the results of each technique in studies of specimens from the three cancers that are the primary focus of the research. This will be accompanied by developing data basis and algorithms for the automated analysis of spectral and imaging data thus removing subjectivity from the diagnostic procedure.
Finally the team will explore a new approach to monitoring the interactions between pathogens, pharmaceuticals and relevant cells or tissues at the cellular and subcellular level using the instruments deployed on the free electron laser at Daresbury together with Raman microscopy. If this is successful, it will be important in the longer term in developing new treatments for cancer and other diseases.

Planned Impact

The research programme will benefit the UK and world wide human population through improvements in health care, specifically through the development of new approaches to the diagnosis, and fundamental understanding of oesophageal, cervical and prostate cancers and more generally by the development of new techniques for fundamental research into the interactions between pathogens exploited as vectors or novel pharmaceutical-directed therapeutic approaches with healthy and diseased tissue.

More immediately the beneficiaries include all health care professionals; physicians, surgeons, pathologists, radiologists, scientists, nurses and dieticians working with these cancers and instrument manufacturers developing innovative technology for patient benefit.

All three cancers at the focus of the research programme have either a very high incidence or a rapidly increasing incidence in the UK and world population and the key to treating them is to obtain an early diagnosis. Considerable effort and resources have been invested in identifying individuals who are at risk of developing these diseases and there are cytology, biopsy and endoscopy techniques for extracting tissue for analysis. However such screening programmes are expensive. Some £ 200 million a year is needed in the UK alone to maintain the infrastructure to screen for cervical cancer so it is critical to optimize and simplify the technologies involved. Unfortunately the analysis of tissues by standard cytology and histology techniques remains significantly limited for these diseases. Typically for prostate cancer two histologists will only agree on the classification of excised tissue based on the Gleeson scale 50% of the time or less and false positives can lead to serious but unnecessary costly treatment and false negatives can be fatal. There is clearly a need to develop more accurate diagnostics for these diseases and that is a primary aim of this proposal.

One result of this proposal is that the UK will benefit from more informed policy making in the health section and the clinical members of the team are well placed to facilitate this though their membership of appropriate national policy bodies.

There is a UK and world-wide market for instruments that will deliver improved and more cost effective health care. UK companies are well placed to exploit this market and will benefit from the critical assessment of the potential of infrared (IR) and terahertz (THz) techniques for medical applications, one of the objectives of the proposal. The research programme will advance the development of several low cost portable IR and THz instruments which are expected to be used first as auxiliary instruments in medical practice. Combined with biospectral database for these cancers, and linked with refined data processing algorithms, they will be used by the developers of the instrumentation and medical professionals in clinical trials and if successful will augment, and may eventually replace, existing diagnostic procedures.

The understanding of pathogen-cell and drug-cell interactions and the exploration of a novel means for their direct study have considerable potential for use in the pharmaceutical industry, a sector where the UK is strong, in high-throughput screening in drug development.

Improved IR and THz instruments will find applications across a wide range of fields including security, plasma diagnostics, forensics, quality control, pharmaceutical, medical, automotive and cultural heritage. The industrial exploitation of these technological advances will be facilitated by patent protection of the resulting IPR and the close links between the applicants and instrument companies notably Anasys Instruments, QMC Instruments and TeraView. It is anticipated that this will bring licensing revenue to the collaborating Universities in addition to improving the commercial success of UK industry.

Publications

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Al Jedani S (2020) A de-waxing methodology for scanning probe microscopy. in Analytical methods : advancing methods and applications

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Dhillon S (2017) The 2017 terahertz science and technology roadmap in Journal of Physics D: Applied Physics

 
Description We have now constructed and commissioned a scanning near field optical microscope (SNOM) for use on the infrared free electron laser on the ALICE accelerator at Daresbury fitted with an inverted optical microscope.

Five papers have been published on studies of cancer as of February 20i9 and another has just been submitted for publication.
Our collaborators ion the award have submitted a significant number of papers on terahertz studies.

Cancer Research UK (Early Detection Committee) has funded a Project Award for the "Early detection of oral cancer using infrared imaging" C7738/A26196 (£ 430 k)

We have filed a patent on a machine learning algorithm for the characterisation of cancer. James Ingham, Steve Barrett and Peter Weightman 'A method of selecting discriminating wavelengths of radiation for use in absorption spectroscopy' GB Patent Application Number: 1806002.0, Filed: 11 Apr 2018 'Methods of spectroscopic analysis' WIPO Patent Application: PCT/GB2019/050998, Filed: 5 Apr 2019
Exploitation Route There is considerable scope for using the methodologies that we are developing for cancer diagnosis.

A tabletop instrument for cancer diagnosis has been designed and Cancer Research UK has fudned the instrument.

A patent has been filed: James Ingham, Steve Barrett and Peter Weightman 'A method of selecting discriminating wavelengths of radiation for use in absorption spectroscopy' GB Patent Application Number: 1806002.0, Filed: 11 Apr 2018 'Methods of spectroscopic analysis' WIPO Patent Application: PCT/GB2019/050998, Filed: 5 Apr 2019
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://iopscience.iop.org/article/10.1088/2057-1976/aaa0de/meta
 
Description Discussions with clinicians A presentation to a patient support group at a local hospital Numerous presentations at conferences including SPEC 2018 (Glasgow) June 2018 "An evaluation of the infrared aperture SNOM technique." Invited talks 6th July 2018 Quantum Leap Conference (Liverpool" Probing the secret of life with accelerator driven light sources. 9th July 2018 De Beers Diamond Conference (Warwick) Access to Free Electron Laser Light Sources for UK Scientists. 12th July 2018 THz Imaging of Cancer IOP Conference (London) Characteristics of cancerous tissue in the THz region of the electromagnetic spectrum. 2nd Feb 2019 "Recent advances in the application of infrared techniques to the study of cancer." Physics Dept. University of Sheffield A patent has been filed and the methodology has been sued to analysis oral cancer tissue in the research programme funded by Cancer Research UK. Patent is James Ingham, Steve Barrett and Peter Weightman 'A method of selecting discriminating wavelengths of radiation for use in absorption spectroscopy' GB Patent Application Number: 1806002.0, Filed: 11 Apr 2018 'Methods of spectroscopic analysis' WIPO Patent Application: PCT/GB2019/050998, Filed: 5 Apr 2019 An ICURe award from Innovate UK/Cancer Research UK to commercialise a design for a probe to be used in the early diagnosis of cancer. Initially the probe would be used in combination with the histological analysis of biopsies but it also has potential for in situ diagnosis of cancer and for use in surgery.
First Year Of Impact 2020
Sector Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural,Societal

 
Description Cancer Research Uk Early Detection Committee - Project Award
Amount £430,601 (GBP)
Funding ID C7738/A26196 
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2018 
End 06/2021
 
Description High performance Wide spectral range Nanoprobe (HiWiN)
Amount £745,943 (GBP)
Funding ID EP/V00767X/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 07/2020 
End 01/2023
 
Description MRC Proximity to Discovery Award
Amount £45,500 (GBP)
Funding ID P2D Scheme 
Organisation University of Liverpool 
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 02/2017
 
Description Response Mode National Research Facility
Amount £634,631 (GBP)
Funding ID EP/R007926/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2017 
End 04/2022
 
Description Conference for school children 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact A talk for school children on "Probing the secret of life with accelerator driven light sources."
Year(s) Of Engagement Activity 2018
 
Description Discussion meeting with hospital support group of patients with esophageal cancer 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I met with a group of cancer patients to describe the research programme aimed at developing a more accurate diagnostic for esophagael cancer.
Year(s) Of Engagement Activity 2015
 
Description FLUENCE workshop in Nijmegen 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a workshop to intrude a group of UK scientists to the use of the FELIX free electron lasers in Nijmegen
Year(s) Of Engagement Activity 2018
 
Description HFML-FELIX User Meeting 2019, FELIX, Nijmegen, The Netherlands, (8-9 July 2019) Invited talk by Michele Siggel-King 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a working group to design a scientific instrument.
Year(s) Of Engagement Activity 2019
 
Description Invited Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited Talk by Dr Michele Siggel-King
Year(s) Of Engagement Activity 2018
 
Description Invited Talk at Community Meeting: FELIX: Free Electron lasers for the Catalysis Community (18 July 2019) Research Complex at Harwell 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was a collaboration meeting of scientists interested in using the FELIX free electron lasers in Nijmegen.
Year(s) Of Engagement Activity 2019
 
Description Invited seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact 2nd Feb 2019 "Recent advances in the application of infrared techniques to the study of cancer." Physics Dept. University of Sheffield
Year(s) Of Engagement Activity 2019
 
Description Invited talk at "the University of the 3rd Age" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Supporters
Results and Impact Invited talk by Dy Michele Siggel-King on scents advances in the study of cancer
Year(s) Of Engagement Activity 2018
 
Description Invited talk at DeBeers Diamond Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Advice on "Access to Free Electron Laser Light Sources for UK Scientists."
Year(s) Of Engagement Activity 2018
 
Description Invited talk at TERANEW network meeting, National Physics Laboratory (4 Dec 2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was an invited talk at an EPSRC Network TERANET at the National Physical Laboratory.
Year(s) Of Engagement Activity 2019
 
Description Invited talk by Dr Michele Siggel-King in Finland 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Invited talk at Physics against cancer meeting in Finland
Year(s) Of Engagement Activity 2018
 
Description National Conference on the application of terahertz radiation to the study of cancer 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact An invited talk on "Characteristics of cancerous tissue in the THz region of the electromagnetic spectrum."
Year(s) Of Engagement Activity 2018
 
Description National meeting on terahertz radiation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact National conference on The radiation
Year(s) Of Engagement Activity 2018
 
Description Presentation at the SPEC2018 Conference June 2018 Glasgow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation on a new approach to cancer diagnosis
Year(s) Of Engagement Activity 2016
 
Description THz Imaging of Cancer, London (12 July 2019) Invited Talk (PW) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was an invited talk at a conference on application of Terahertz radiation in health care
Year(s) Of Engagement Activity 2019
 
Description The Fundamentals of Late Stage Cancer Meeting, NorthWest Cancer Research Centre, University of Liverpool (19-20 Sept 2019) Poster Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a conference on problems in the treatment of late stage cancer.
Year(s) Of Engagement Activity 2019
 
Description University of Sheffield Physics Department Seminar (6 Feb 2019) Invited Talk (PW) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact This was a dempartmental seminar
Year(s) Of Engagement Activity 2019
 
Description Workshop to coordinate the development of a proposal for an imaging system on the FELIX free electron lasers 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The meeting agreed vin a plan to develop a poroposall for an imaging instrument to be established on the FEKLIX free electron lasers in Nijmegen.
Year(s) Of Engagement Activity 2018
 
Description national Conference on THz radiation Chester 21 5 18 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact National conference on Thz radiation Chester 21 5 18
Year(s) Of Engagement Activity 2018