Imperial College London

ProfessorPaulFrench

Faculty of Natural SciencesDepartment of Physics

Professor of Physics and Vice Dean (Research) - FoNS
 
 
 
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Contact

 

+44 (0)20 7594 7706paul.french Website

 
 
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Assistant

 

Ms Judith Baylis +44 (0)20 7594 7713

 
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Location

 

609Blackett LaboratorySouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

494 results found

Lagarto J, Dyer BT, Talbot C, Sikkel MB, Peters NS, French PMW, Lyon AR, Dunsby Cet al., 2015, Application of time-resolved autofluorescence to label-free in vivo optical mapping of changes in tissue matrix and metabolism associated with myocardial infarction and heart failure, Biomedical Optics Express, Vol: 6, Pages: 324-346, ISSN: 2156-7085

We investigate the potential of an instrument combining timeresolvedspectrofluorometry and diffuse reflectance spectroscopy tomeasure structural and metabolic changes in cardiac tissue in vivo in a 16week post-myocardial infarction heart failure model in rats. In the scarregion, we observed changes in the fluorescence signal that can beexplained by increased collagen content, which is in good agreement withhistology. In areas remote from the scar tissue, we measured changes in thefluorescence signal (p < 0.001) that cannot be explained by differences incollagen content and we attribute this to altered metabolism within themyocardium. A linear discriminant analysis algorithm was applied to themeasurements to predict the tissue disease state. When we combine allmeasurements, our results reveal high diagnostic accuracy in the infarctedarea (100%) and border zone (94.44%) as well as in remote regions fromthe scar (> 77%). Overall, our results demonstrate the potential of ourinstrument to characterize structural and metabolic changes in a failing heartin vivo without using exogenous labels.

Journal article

Kelly DJ, Warren SC, Alibhai D, Kumar S, Alexandrov Y, Munro I, Margineanu A, McCormack J, Welsh NJ, Serwa RA, Thinon E, Kongsema M, McGinty J, Talbot C, Murray EJ, Stuhmeier F, Neil MAA, Tate EW, Braga VMM, Lam EW-F, Dunsby C, French PMWet al., 2015, Automated multiwell fluorescence lifetime imaging for Forster resonance energy transfer assays and high content analysis, ANALYTICAL METHODS, Vol: 7, Pages: 4071-4089, ISSN: 1759-9660

Journal article

Nolte DD, Jeong K, Turek J, French PMWet al., 2015, Holographic optical coherence imaging, Optical Coherence Tomography: Technology and Applications, Second Edition, Pages: 941-964, ISBN: 9783319064185

© Springer-Verlag Berlin Heidelberg 2008 and Springer International Publishing Switzerland 2015. This chapter gives an overview of the principles of holographic OCI. It begins with a description of off-axis holography as spatial heterodyne detection and continues with the origin and role of speckle in multichannel illumination of tissue. Image-domain holography (IDH) and Fourier–domain holography (FDH) are described. Holography in the Fourier domain has the capability for phase–contrast imaging that can acquire small sub–wavelength displacements despite long coherence length. The trade–offs between photorefractive and digital holography are discussed. The chief biological target is multicellular spheroids, specifically rat osteogenic sarcomas that are grown in vitro. After describing the physiological and optical properties of these spheroids, results from holographic OCI are presented using both photorefractive and digital holography.

Book chapter

Tatla T, Sparks H, Charn T, Nigar E, Elson DS, Dunsby C, French PMWet al., Development of endoscopic fluorescence lifetime imaging microscopy (FLIM) for head and neck squamous cell cancer (HNSCC) screening: sub-site ex vivo data analysis, Head and Neck Optical Diagnostic Society Annual Meeting

Conference paper

McGinty J, Chen L, Kumar S, Alexandrov Y, Andrews N, Kelly D, Dallman MJ, French PMWet al., 2015, Techniques to improve the spatial and temporal resolution in optical projection tomography: Remote focal scanning and time-lapse cell tracking

© OSA 2015. Optical projection tomography is a 3-D imaging approach applicable to transparent samples and model organisms like zebrafish embryos. We present methods to improve the spatial resolution and realize 3-D cell tracking in OPT.

Conference paper

Kone M, Sun G, Ibberson M, Martinez-Sanchez A, Sayers S, Marie-Sophie N-T, Kantor C, Swisa A, Dor Y, Gorman T, Ferrer J, Thorens B, Reimann F, Gribble F, McGinty JA, Chen L, French PM, Birzele F, Hildebrandt T, Uphues I, Rutter GAet al., 2014, LKB1 and AMPK differentially regulate pancreatic beta-cell identity, Faseb Journal, Vol: 28, Pages: 4972-4985, ISSN: 1530-6860

Fully differentiated pancreatic b cellsare essential for normal glucose homeostasis in mammals.Dedifferentiation of these cells has been suggestedto occur in type 2 diabetes, impairing insulinproduction. Since chronic fuel excess (“glucotoxicity”)is implicated in this process, we sought here to identifythe potential roles in b-cell identity of the tumor suppressorliver kinase B1 (LKB1/STK11) and the downstreamfuel-sensitive kinase, AMP-activated proteinkinase (AMPK). Highly b-cell-restricted deletion ofeach kinase in mice, using an Ins1-controlled Cre, wastherefore followed by physiological, morphometric,and massive parallel sequencing analysis. Loss of LKB1strikingly (2.0–12-fold, E<0.01) increased the expressionof subsets of hepatic (Alb, Iyd, Elovl2) and neuronal(Nptx2, Dlgap2, Cartpt, Pdyn) genes, enhancing glutamatesignaling. These changes were partially recapitulatedby the loss of AMPK, which also up-regulated b-cell“disallowed” genes (Slc16a1, Ldha, Mgst1, Pdgfra) 1.8- to3.4-fold (E<0.01). Correspondingly, targeted promoterswere enriched for neuronal (Zfp206; P51.3310233)and hypoxia-regulated (HIF1; P52.5310216) transcriptionfactors. In summary, LKB1 and AMPK, through onlypartly overlapping mechanisms, maintain b-cell identityby suppressing alternate pathways leading to neuronal,hepatic, and other characteristics. Selective targetingof these enzymes may provide a new approach tomaintaining b-cell function in some forms of diabetes.—Kone,M., Pullen, T. J., Sun, G., Ibberson, M.,Martinez-Sanchez, A., Sayers, S., Nguyen-Tu, M.-S.,Kantor, C., Swisa, A., Dor, Y., Gorman, T., Ferrer, J.,Thorens, B., Reimann, F., Gribble, F., McGinty, J. A.,Chen, L., French, P. M., Birzele, F., Hildebrandt, T.,Uphues, I., Rutter, G. A. LKB1 and AMPK differentiallyregulate pancreatic b-cell identity.

Journal article

Robinson T, Valluri P, Kennedy G, Sardini A, Dunsby C, Neil MAA, Baldwin GS, French PMW, de Mello AJet al., 2014, Analysis of DNA Binding and Nucleotide Flipping Kinetics Using Two-Color Two-Photon Fluorescence Lifetime Imaging Microscopy, Analytical Chemistry, Vol: 86, Pages: 10732-10740, ISSN: 0003-2700

Uracil DNA glycosylase plays a key role in DNA maintenance via base excision repair. Its role is to bind to DNA, locate unwanted uracil, and remove it using a base flipping mechanism. To date, kinetic analysis of this complex process has been achieved using stopped-flow analysis but, due to limitations in instrumental dead-times, discrimination of the “binding” and “base flipping” steps is compromised. Herein we present a novel approach for analyzing base flipping using a microfluidic mixer and two-color two-photon (2c2p) fluorescence lifetime imaging microscopy (FLIM). We demonstrate that 2c2p FLIM can simultaneously monitor binding and base flipping kinetics within the continuous flow microfluidic mixer, with results showing good agreement with computational fluid dynamics simulations.

Journal article

Chen L, Kumar S, Kelly D, Andrews N, Dallman MJ, French PMW, McGinty Jet al., 2014, Remote focal scanning optical projection tomography with an electrically tunable lens, BIOMEDICAL OPTICS EXPRESS, Vol: 5, Pages: 3367-3375, ISSN: 2156-7085

Journal article

Kelly DJ, Warren SC, Kumar S, Lagarto JL, Dyer BT, Margineanu A, Lam EW-F, Dunsby C, French PMWet al., 2014, An automated multiwell plate reading film microscope for live cell autofluorescence lifetime assays, JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES, Vol: 7, ISSN: 1793-5458

Journal article

Sonnefraud Y, Sinclair HG, Sivan Y, Foreman MR, Dunsby CW, Neil MAA, French PM, Maier SAet al., 2014, Experimental Proof of Concept of Nanoparticle-Assisted STED, NANO LETTERS, Vol: 14, Pages: 4449-4453, ISSN: 1530-6984

Journal article

Watson TJ, Andrews N, Harry E, Bugeon L, Dallman MJ, French PMW, McGinty Jet al., 2014, Remote focal scanning and sub-volume optical projection tomography

© OSA 2016. We present a platform for sub-volume optical projection tomography utilising an electrically tunable lens and tracking technology. Applied to 3D fluorescent bead phantoms and zebrafish embryos, we demonstrate an improvement in resolution and light collection efficiency with respect to conventional optical projection tomography.

Conference paper

Kumar S, Lockwood N, Ramel MC, Correia T, Ellis M, Alexandrov Y, Andrews N, Patel R, Bugeon L, Dallman MJ, Brandner S, Arridge S, Katan M, McGinty J, Frankel P, French PMWet al., 2014, In vivo multiplexed OPT and FLIM OPT of an adult zebrafish cancer disease model

© OSA 2016. We report angular multiplexed OPT and FLIM OPT applied to in vivo imaging of cancer and FRET biosensors in adult zebrafish. Multiple-spectral 3-D datasets of entire adult zebrafish can be acquired in 3 minutes.

Conference paper

Marcu L, French PMW, Elson DS, 2014, Preface, Publisher: CRC Press

The text introduces these techniques within the wider context of fluorescence spectroscopy and describes basic principles underlying current instrumentation for fluorescence lifetime imaging and metrology (FLIM).

Other

Marcu L, French P, Elson DS, 2014, Chapter 1: Introduction, Fluorescence Lifetime Spectroscopy and Imaging Principles and Applications in Biomedical Diagnostics, Publisher: CRC Press, ISBN: 9781439861677

The text introduces these techniques within the wider context of fluorescence spectroscopy and describes basic principles underlying current instrumentation for fluorescence lifetime imaging and metrology (FLIM).

Book chapter

Dyer B, Lagarto J, Sikkel M, French P, Dunsby C, Peters N, Lyon Aet al., 2014, THE APPLICATION OF AUTOFLUORESCENCE LIFETIME METROLOGY AS A NOVEL LABEL-FREE TECHNIQUE FOR THE ASSESSMENT OF CARDIAC DISEASE, HEART, Vol: 100, Pages: A104-A104, ISSN: 1355-6037

Journal article

Gore DM, Margineanu A, French P, O'Brart D, Dunsby C, Allan BDet al., 2014, Two-Photon Fluorescence Microscopy of Corneal Riboflavin Absorption, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol: 55, Pages: 2476-2481, ISSN: 0146-0404

Journal article

Gore DM, Margineanu A, French P, O'Brart D, Dunsby C, Allan BDSet al., 2014, Two-photon fluorescence (TPF) microscopy of corneal riboflavin absorption, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404

Conference paper

sparks H, warren S, Guedes J, Yoshida N, Charn TC, Guerra N, Tatla T, dunsby C, french Pet al., A flexible wide-field FLIM endoscope utilising blue excitation light for label-free contrast of tissue., Journal of Biophotonics, Vol: 8, Pages: 168-178, ISSN: 1864-0648

Journal article

Coda S, Thompson AJ, Kennedy GT, Roche KL, Ayaru L, Bansi DS, Stamp GW, Thillainayagam AV, French PMW, Dunsby Cet al., 2014, Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe, Biomedical Optics Express, Vol: 5, Pages: 515-538

We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime −570 ± 740 ps (p = 0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue in a small number of specimens.

Journal article

Campagnola P, French PMW, Georgakoudi I, Mycek M-Aet al., 2014, Introduction: feature issue on optical molecular probes, imaging, and drug delivery, BIOMEDICAL OPTICS EXPRESS, Vol: 5, Pages: 643-644, ISSN: 2156-7085

Journal article

Coda S, French PMW, Dunsby C, 2014, Oncology applications: Gastrointestinal cancer, Fluorescence Lifetime Spectroscopy and Imaging: Principles and Applications in Biomedical Diagnostics, Pages: 379-386, ISBN: 9781439861677

© 2015 by Taylor & Francis Group, LLC. Cancers of esophagus, stomach, and colon are among the most common cancers worldwide, accounting for a total of 2.2 million new cases each year (Boyle and Levin 2008). Prevention of these conditions is currently based on early detection of early-stage cancers or premalignant conditions during conventional white-light endoscopy (WLE). Today, there is a range of more sophisticated biophotonics techniques under development that aim to enhance the contrast of areas of concern beyond what is possible with conventional WLE. Commercially available techniques include high-definition endoscopy (HDE; Adler et al. 2009; Buchner 2010; Rex and Helbig 2007), narrow band imaging (NBI; Gono et al. 2004), magnifying chromoendoscopy (MCE; Kudo et al. 1996), autofluorescence (AF) imaging (AFI; Nakaniwa et al. 2005), and confocal laser endomicroscopy (CLE; Kiesslich et al. 2004; Wang et al. 2007).

Book chapter

Elson DS, Marcu L, French PMW, 2014, Overview of fluorescence lifetime imaging and metrology, ISBN: 9781439861677

© 2015 by Taylor & Francis Group, LLC. This chapter aims to present an overview of fluorescence lifetime imaging (FLIM) and metrology in the context of their biomedical applications, introducing the main approaches that are discussed in detail in subsequent chapters of this book. Before discussing fluorescence lifetime measurements, however, it is important to understand the phenomenon of fluorescence, of which a brief discussion is provided here, and the reader is directed to the classic textbook by Lakowicz (1999) for further details.

Book

French PMW, 2014, Fluorescence lifetime imaging for biomedicine

I will review our development and application of fluorescence lifetime imaging implemented in microscopy, tomography and endoscopy to provide molecular readouts across the scales from super-resolved microscopy through imaging of disease models to clinical applications. © 2014 OSA.

Conference paper

Nickdel MB, Lagarto JL, Kelly DJ, Manning HB, Yamamoto K, Talbot CB, Dunsby C, French P, Itoh Yet al., 2014, Autofluorescence lifetime metrology for label-free detection of cartilage matrix degradation, Conference on Optical Biopsy XII, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X

Conference paper

Sonnefraud Y, Sivan Y, Sinclair HG, Dunsby CW, Neil MA, French PM, Maier SAet al., 2014, Nanoparticle-assisted STED, theory, and experimental demonstration, Conference on Nanoimaging and Nanospectroscopy II, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X

Conference paper

Marcu L, French PMW, Elson DS, 2014, Preface, ISBN: 9781439861677

© 2015 by Taylor & Francis Group, LLC. Wide-field time-gated fluorescence lifetime imaging (FLIM) essentially entails illuminating a sample with an ultrashort pulse of excitation radiation and sampling the resulting time varying fluorescence “image” following excitation by acquiring a series of gated fluorescence intensity images recorded at different relative delays with respect to the excitation pulse. This is represented schematically in Figure 8.1. In the simplest case, a map of the mean fluorescence decay times across the field of view is obtained. If the sampling of the fluorescence decay profiles is appropriately detailed, then the entire fluorescence decay profile for each image pixel can be acquired, and the resulting data set can be fitted to complex temporal decay models. For example, a double exponential decay model is frequently used to analyze data from Förster resonant energy transfer (FRET) experiments. The acquisition of time-gated fluorescence intensity images requires a 2-D detector, normally a charge-coupled device (CCD) camera, and some kind of fast “shutter” able to sample fluorescence decay profiles on subnanosecond timescales. Such a “shutter” function cannot be provided by mechanical means or yet by electronic circuitry and is typically provided by optical image intensifiers whose gain can be modulated by varying the applied voltage.

Book

French PMW, 2014, Overview of fluorescence imaging for biophotonics, 181st International School of Physics Enrico Fermi on Microscopy Applied to Biophotonics, Publisher: IOS PRESS, Pages: 1-27, ISSN: 0074-784X

Conference paper

Dunsby C, McGinty J, French P, 2014, Multidimensional fluorescence imaging of biological tissue, Biomedical Photonics Handbook, Second Edition: Fundamentals, Devices, and Techniques, Pages: 531-560, ISBN: 9781420085129

© 2015 by Taylor & Francis Group, LLC. This chapter aims to review multidimensional fluorescence imaging (MDFI) technology and its application to biological tissue, with a particular emphasis on fluorescence lifetime imaging (FLIM) of biological tissue with examples from our work at Imperial College London. Fluorescence imaging is flourishing tremendously, partly driven by advances in laser and detector technology, partly by advances in labeling technologies such as genetically expressed fluorescent proteins, and partly by advances in computational analysis techniques. Increasingly, fluorescence instrumentation is developed to provide more information than just the localization or distribution of specific fluorescent molecules. Often, fluorescence signals are analyzed to provide information on the local fluorophore environment or to contrast different fluorophores in complex mixtures-as often occur in biological tissue. This trend to higher-content fluorescence imaging increasingly exploits MDFI and measurement capabilities with instrumentation that resolves fluorescence lifetime together with other spectroscopic parameters such as excitation and emission wavelength and polarization, providing image information in two or three spatial dimensions as well as with respect to elapsed time (Figure 18.1). However, caution should be exercised when acquiring such MDFI since photobleaching or experimental considerations usually impose a limited photon budget and/or a maximum image acquisition time and also present significant challenges with respect to data analysis and data management. These considerations are particularly important for real-time clinical diagnostic applications, for higher-throughput assays, and for the investigation of dynamic biological systems (Figure 18.1).

Book chapter

Lenz MO, Sinclair HG, Savell A, Clegg JH, Brown ACN, Davis DM, Dunsby C, Neil MAA, French PMWet al., 2014, 3-D stimulated emission depletion microscopy with programmable aberration correction, JOURNAL OF BIOPHOTONICS, Vol: 7, Pages: 29-36, ISSN: 1864-063X

Journal article

French PMW, 2014, Fluorescence Lifetime Imaging for Biomedicine, 2014 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO), ISSN: 2160-9020

Journal article

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