There is wide interest in developing optical tools to study and diagnose disease in humans since optical approaches can potentially offer minimally invasive molecular contrast at relatively low cost, which is increasingly important as healthcare costs continue to grow. However, this is challenging because optical accessibility is much more limited than is the case for cell biology or even preclinical studies and the use of exogenous labels to improve molecular contrast is not desirable and usually not permissible. In this clinical context, the benefits of label-free techniques are self-evident and we are particularly interested in the opportunities afforded by imaging and/or metrology of autofluorescence, for which we are developing and testing new technology to obtain quantitative readouts of changes in tissue properties associated with disease. This includes our programmes in endoscopy and clinical microscopy.

The following are some specific topics or projects that we have addressed in clinical studies as part of our mission to detect or study the progression of disease:

Clinical Studies

Development of endoscopy and clinical microscopy

High-speed wide-field time-gated endoscopic fluorescence lifetime imaging, J. Requejo-Isidro, J. McGinty, I. Munro, D.S. Elson, N. Galletly, M.J. Lever, M.A.A. Neil, G.W.H. Stamp and P.M.W. French, Opt Lett, 29 (2004) 2249

Towards the clinical application of time-domain fluorescence lifetime imaging, I. Munro, J. McGinty, N. Galletly, J. Requejo-Isidro, P.M.P. Lanigan, D. S. Elson, C. Dunsby, M.A.A. Neil, M. J. Lever, G.W.H. Stamp and P.M.W. French, J Biomed Opt. 10 (2005) 051403

A hyperspectral fluorescence lifetime probe for skin cancer diagnosis, P. A. A. De Beule, C. Dunsby, N. P. Galletly, G. W. Stamp, A. Chu, U. Anand, P. Anand, C. D. Benham, A. Naylor and P. M. W. French, Rev. Sci. Instr. 78 (2007) 123101

A Fluorescence Lifetime Imaging Scanning Confocal Endomicroscope, G.T. Kennedy, H.B. Manning, D.S. Elson, M. A. A. Neil, G.W. Stamp, B. Viellerobe, F. Lacombe, C. Dunsby and P.M.W. French, Journal of Biophotonics, 3 (2010) 103-107

Adaptive phase compensation for ultracompact laser scanning endomicroscopy, A. J. Thompson, C. Paterson, M. A. A. Neil, C. Dunsby and P. M. W. French, Opt. Lett. 36 (2011) 1707-1709

A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue, Hugh Sparks, Sean Warren, Joana Guedes, Nagisa Yoshida , Nadia Guerra, Taran Tatla, Chris Dunsby, Paul French, J Biophotonics 8 (2015) 168–178 / DOI 10.1002/jbio.201300203

Fibre-coupled handheld multiphoton microscope with active motion compensation, B. Sherlock, S. Warren, J. Stone, M. Neil, C. Paterson, J. Knight, P. French and C. Dunsby, Biomed. Opt. Exp. 6 (2015) 1876-1884

Adaptive multiphoton endomicroscope incorporating a polarization-maintaining multicore optical fibre, Y. Kim, S. C. Warren, J. M. Stone, J. C. Knight, M. A. A. Neil1, C. Paterson, C. Dunsby and P. M. W. French, IEEE J Selected Topics in QE, 22 (2015) Article #: 6800708, DOI: 10.1109/JSTQE.2015.2488283

Ex vivo clinical studies

Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer
P. J. Tadrous, J. Siegel, P. M.W. French, Dr S. Shousha, El-Nasir Lalani and G. W.H. Stamp
J Pathol 199 (2003): 309–317

Fluorescence Lifetime Imaging Distinguishes Basal Cell Carcinoma from Surrounding Uninvolved Skin, N. P. Galletly, J. McGinty, C. Dunsby, F. Teixeira, J. Requejo-Isidro, I. Munro, D. S. Elson, M. A. A Neil, A. C. Chu, P. M. W. French and G. W. Stamp, British Journal of Dermatology 159, (2008) 152–161

Wide-field fluorescence lifetime imaging of cancer, J. McGinty, N. P Galletly, C. Dunsby, I. Munro, D. S Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A Forsyth, A. V Thillainayagam, M. A. A. Neil, P. M W French and G.W Stamp, Biomedical Optics Express, 1 (2010) 627-640

Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fibre-optic probe, S. Coda, A. J. Thompson, G. T. Kennedy, K. L. Roche, L. Ayaru, D. S. Bansi, G. W. Stamp, A. V. Thillainayagam, P. M. W. French and C. Dunsby, Biomedical Optics Express 5 (2014) 515-538, http://dx.doi.org/10.1364/BOE.5.000515

Quantification of cellular autofluorescence of human skin using multiphoton tomography and fluorescence lifetime imaging in two spectral detection channels,
Rakesh Patalay, Clifford Talbot, Yuriy Alexandrov, Ian Munro, Mark A. A. Neil, Karsten König, Paul M. W. French, Anthony Chu, Gordon W. Stamp and Chris Dunsby
Biomedical Optics Express 2 (2012) 3295-3308

High-resolution imaging of basal cell carcinoma: a comparison between multiphoton microscopy with fluorescence lifetime imaging and reflectance confocal microscopy, M. Manfredini, F. Arginelli, C. Dunsby, P. French, C. Talbot, K. König, G. Pellacani, G. Ponti and S. Seidenari, Skin Res Technol. (2013) 19(1):e433-43. doi: 10.1111/j.1600-0846.2012.00661.x.

Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: Morphologic Features for Non-Invasive Diagnostics, S. Seidenari, F. Arginelli, C. Dunsby, P. M. W. French, K. König, C. Magnoni, M. Manfredini, C. Talbot and G. Ponti, Experimental Dermatology 21 (11), pp. 831–836, 2012, http://dx.doi.org/10.1111/j.1600-0625.2012.01554.x

High resolution diagnosis of common nevi by multiphoton laser tomography and fluorescence lifetime imaging, F. Arginelli, M. Manfredini, S. Bassoli, C. Dunsby, P. French, K. König, C. Magnoni, G. Ponti, C. Talbot and S. Seidenari, Skin Res Technol 19(2), pp. 194-204, 2012, http://dx.doi.org/10.1111/srt.12035

Multiphoton laser tomography and fluorescence lifetime imaging of melanoma: Morphologic Features and quantitative data for sensitive and specific non-invasive diagnostics, S. Seidenari, F. Arginelli, C. Dunsby, P. French, K. König, C. Magnoni, C. Talbot, G. Ponti, PLoS ONE 8(7), e70682, 2013, DOI: 10.1371/journal.pone.0070682

In vivo clinical studies

Quantitative evaluation of healthy epidermis by means of multiphoton microscopy and fluorescence lifetime imaging microscopy, E. Benati, V. Bellini, S. Borsari, C. Dunsby, C. Ferrari, P. French, M. Guanti, D. Guardoli, K. Koenig, G. Pellacani, G. Ponti, S. Schianchi, C. Talbot and S. Seidenari, Skin Research and Technology, 17 (2011) 295–303; doi: 10.1111/j.1600-0846.2011.00496.x,

In vivo measurements of diffuse reflectance and time-resolved autofluorescence emission spectra of basal cell carcinomas, Alex J. Thompson, Sergio Coda, Mikkel Brydegaard Sørensen, Gordon Kennedy, Rakesh Patalay; Ulrika Waitong-Brämming, Pieter A. A. De Beule, Mark A. A. Neil, Stefan Andersson-Engels, Niels Bendsøe, Paul M. W. French, Katarina Svanberg, and Chris Dunsby, J. Biophotonics 5 (2012) 240-254; DOI 10.1002/jbio.201100126

Multiphoton laser microscopy and fluorescence lifetime imaging for the evaluation of the skin, Stefania Seidenari, Federica Arginelli, Sara Bassoli, Jennifer Cautela, Paul M. W. French, Mario Guanti, Davide Guardoli, Karsten Koenig, Clifford Talbot and Chris Dunsby, Dermatology Research and Practice, Volume 2012, Article ID 810749, 8 pages, doi:10.1155/2012/810749

Multiphoton Multispectral Fluorescence Lifetime Tomography for the Evaluation of Basal Cell Carcinomas, R. Patalay, C. Talbot, Y. Alexandrov, M. O. Lenz, S. Kumar, S. Warren, I. Munro, M. A. A. Neil, K. König, P. M. W. French, A. Chu, G. W. H. Stamp and C. Dunsby, PLoS ONE 7 (9) e43460-, 2012, http://dx.doi.org/10.1371/journal.pone.0043460