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

481 results found

Seidenari S, Arginelli F, Dunsby C, French PMW, Koenig K, Magnoni C, Talbot C, Ponti Get al., 2013, Multiphoton Laser Tomography and Fluorescence Lifetime Imaging of Melanoma: Morphologic Features and Quantitative Data for Sensitive and Specific Non-Invasive Diagnostics, PLOS ONE, Vol: 8, ISSN: 1932-6203

Journal article

Arginelli F, Manfredini M, Bassoli S, Dunsby C, French P, Koenig K, Magnoni C, Ponti G, Talbot C, Seidenari Set al., 2013, High resolution diagnosis of common nevi by multiphoton laser tomography and fluorescence lifetime imaging, SKIN RESEARCH AND TECHNOLOGY, Vol: 19, Pages: 194-204, ISSN: 0909-752X

Journal article

Alibhai D, Kelly DJ, Warren S, Kumar S, Margineau A, Serwa RA, Thinon E, Alexandrov Y, Murray EJ, Stuhmeier F, Tate EW, Neil MAA, Dunsby C, French PMWet al., 2013, Automated fluorescence lifetime imaging plate reader and its application to Forster resonant energy transfer readout of Gag protein aggregation, Journal of Biophotonics, Vol: 6, Pages: 398-408, ISSN: 1864-0648

Fluorescence lifetime measurements can provide quantitativereadouts of local fluorophore environment andcan be applied to biomolecular interactions via Fo¨ rsterresonant energy transfer (FRET). Fluorescence lifetimeimaging (FLIM) can therefore provide a high contentanalysis (HCA) modality to map protein-protein interactions(PPIs) with applications in drug discovery, systemsbiology and basic research. We present here an automatedmultiwell plate reader able to perform rapid unsupervisedoptically sectioned FLIM of fixed and livebiological samples and illustrate its potential to assayPPIs through application to Gag protein aggregationduring the HIV life cycle. We demonstrate both heteroFRETand homo-FRET readouts of protein aggregationand report the first quantitative evaluation of a FLIMHCA assay by generating dose response curves throughaddition of an inhibitor of Gag myristoylation. Z0 factorsexceeding 0.6 are realised for this FLIM FRET assay.Fluorescence lifetime plate map with representativeimages of high and low FRET cells and correspondingdose response plot.

Journal article

Chen L, Andrews N, Kumar S, Frankel P, McGinty J, French PMWet al., 2013, Simultaneous angular multiplexing optical projection tomography at shifted focal planes, OPTICS LETTERS, Vol: 38, Pages: 851-853, ISSN: 0146-9592

Journal article

Manfredini M, Arginelli F, Dunsby C, French P, Talbot C, Koenig K, Pellacani G, Ponti G, Seidenari Set al., 2013, High-resolution imaging of basal cell carcinoma: a comparison between multiphoton microscopy with fluorescence lifetime imaging and reflectance confocal microscopy, SKIN RESEARCH AND TECHNOLOGY, Vol: 19, Pages: E433-E443, ISSN: 0909-752X

Journal article

Manning HB, Nickdel MB, Yamamoto K, Lagarto JL, Kelly DJ, Talbot CB, Kennedy G, Dudhia J, Lever J, Dunsby C, French P, Itoh Yet al., 2013, Detection of cartilage matrix degradation by autofluorescence lifetime, MATRIX BIOLOGY, Vol: 32, Pages: 32-38, ISSN: 0945-053X

Journal article

Roper JC, Yerolatsitis S, Birks TA, Mangan BJ, Dunsby C, French PMW, Knight JCet al., 2013, Minimising group index variations in a multicore endoscope fibre, Conference on Lasers and Electro-Optics (CLEO), Publisher: IEEE, ISSN: 2160-9020

Conference paper

Martins M, Warren S, Kimberley C, Margineanu A, Peschard P, McCarthy A, Yeo M, Marshall CJ, Dunsby C, French PMW, Katan Met al., 2012, Activity of PLC epsilon contributes to chemotaxis of fibroblasts towards PDGF, JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 5758-5769, ISSN: 0021-9533

Journal article

Chen L, McGinty J, Taylor HB, Bugeon L, Lamb JR, Dallman MJ, French Pet al., 2012, Improved OPT reconstructions based on the MTF and extension to FLIM-OPT

We demonstrate the improved reconstruction of OPT datasets by incorporating the measured MTF in the reconstruction process. We also extend OPT to FLIM-OPT and demonstrate its use for imaging live zebrafish embryos displaying autofluorescence. © 2012 OSA.

Conference paper

Laine R, Stuckey DW, Manning H, Warren SC, Kennedy G, Carling D, Dunsby C, Sardini A, French PMWet al., 2012, Fluorescence Lifetime Readouts of Troponin-C-Based Calcium FRET Sensors: A Quantitative Comparison of CFP and mTFP1 as Donor Fluorophores, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

Seidenari S, Arginelli F, Dunsby C, French P, Koenig K, Magnoni C, Manfredini M, Talbot C, Ponti Get al., 2012, Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: morphologic features for non-invasive diagnostics, EXPERIMENTAL DERMATOLOGY, Vol: 21, Pages: 831-836, ISSN: 0906-6705

Journal article

Xavier GDS, Mondragon A, Sun G, Chen L, McGinty JA, French PM, Rutter GAet al., 2012, Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice, DIABETOLOGIA, Vol: 55, Pages: 2667-2676, ISSN: 0012-186X

Journal article

Patalay R, Talbot C, Alexandrov Y, Lenz MO, Kumar S, Warren S, Munro I, Neil MAA, Koenig K, French PMW, Chu A, Stamp GWH, Dunsby Cet al., 2012, Multiphoton Multispectral Fluorescence Lifetime Tomography for the Evaluation of Basal Cell Carcinomas, PLOS One, Vol: 7, ISSN: 1932-6203

We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples of normal skin (in & ex vivo). Features from fluorescence lifetime images were used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively. A mosaic of BCC fluorescence lifetime images covering >1 mm2 is also presented, demonstrating the potential for tumour margin delineation.Using 10,462 manually segmented cells from the image data, we quantify the cellular morphology and spectroscopic differences between BCCs and normal skin for the first time. Statistically significant increases were found in the fluorescence lifetimes of cells from BCCs in all spectral channels, ranging from 19.9% (425–515 nm spectral emission) to 39.8% (620–655 nm emission). A discriminant analysis based diagnostic algorithm allowed the fraction of cells classified as malignant to be calculated for each patient. This yielded a receiver operator characteristic area under the curve for the detection of BCC of 0.83.We have used both morphological and spectroscopic parameters to discriminate BCC from normal skin, and provide a comprehensive base for how this technique could be used for BCC assessment in clinical practice.

Journal article

Brown AC, Oddos S, Dobbie IM, Alakoskela JM, Parton RM, Eissmann P, Neil MA, Dunsby C, French PM, Davis I, Davis DMet al., 2012, Correction: Remodelling of Cortical Actin Where Lytic Granules Dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy., PLoS Biol, Vol: 10

[This corrects the article on p. e1001152 in vol. 9.].

Journal article

Patalay R, Chu A, Dunsby C, Talbot C, Konig K, French P, Alexandrov Yet al., 2012, A noninvasive imaging study of skin using two photon microscopy of cellular autofluorescence, 70th Annual Meeting of the American-Academy-of-Dermatology (AAD), Publisher: MOSBY-ELSEVIER, Pages: AB83-AB83, ISSN: 0190-9622

Conference paper

Chen L, McGinty J, Taylor HB, Bugeon L, Lamb JR, Dallman MJ, French PMWet al., 2012, Incorporation of an experimentally determined MTF for spatial frequency filtering and deconvolution during optical projection tomography reconstruction, OPTICS EXPRESS, Vol: 20, Pages: 7323-7337, ISSN: 1094-4087

Journal article

Thompson AJ, Coda S, Sorensen MB, Kennedy G, Patalay R, Waitong-Bramming U, De Beule PAA, Neil MAA, Andersson-Engels S, Bendsoe N, French PMW, Svanberg K, Dunsby Cet al., 2012, In vivo measurements of diffuse reflectance and time-resolved autofluorescence emission spectra of basal cell carcinomas, JOURNAL OF BIOPHOTONICS, Vol: 5, Pages: 240-254, ISSN: 1864-063X

Journal article

Sardini A, Stuckey DW, McGinty J, Laine R, Soloviev VY, Arridge SR, Wells DJ, French PMW, Hajnal JVet al., 2012, In Vivo Investigation of Calpain Activity by Lifetime Imaging of Genetically Encoded FRET Sensors, BIOPHYSICAL JOURNAL, Vol: 102, Pages: 159A-159A, ISSN: 0006-3495

Journal article

Esseling M, Kemper B, Antkowiak M, Stevenson DJ, Chaudet L, Neil MAA, French PW, von Bally G, Dholakia K, Denz Cet al., 2012, Multimodal biophotonic workstation for live cell analysis, JOURNAL OF BIOPHOTONICS, Vol: 5, Pages: 9-13, ISSN: 1864-063X

Journal article

Antkowiak M, Torres-Mapa ML, McGinty J, Chahine M, Bugeon L, Rose A, Finn A, Moleirinho S, Okuse K, Dallman M, French P, Harding SE, Reynolds P, Gunn-Moore F, Dholakia Ket al., 2012, Towards gene therapy based on femtosecond optical transfection, BIOPHOTONICS: PHOTONIC SOLUTIONS FOR BETTER HEALTH CARE III, Vol: 8427, ISSN: 0277-786X

Journal article

Seidenari S, Arginelli F, Bassoli S, Cautela J, French PMW, Guanti M, Guardoli D, König K, Talbot C, Dunsby Cet al., 2012, Multiphoton laser microscopy and fluorescence lifetime imaging for the evaluation of the skin., Dermatol Res Pract, Vol: 2012

Multiphoton laser microscopy is a new, non-invasive technique providing access to the skin at a cellular and subcellular level, which is based both on autofluorescence and fluorescence lifetime imaging. Whereas the former considers fluorescence intensity emitted by epidermal and dermal fluorophores and by the extra-cellular matrix, fluorescence lifetime imaging (FLIM), is generated by the fluorescence decay rate. This innovative technique can be applied to the study of living skin, cell cultures and ex vivo samples. Although still limited to the clinical research field, the development of multiphoton laser microscopy is thought to become suitable for a practical application in the next few years: in this paper, we performed an accurate review of the studies published so far, considering the possible fields of application of this imaging method and providing high quality images acquired in the Department of Dermatology of the University of Modena.

Journal article

Soloviev VY, McGinty J, Stuckey DW, Laine R, Wylezinska-Arridge M, Wells DJ, Sardini A, Hajnal JV, French PMW, Arridge SRet al., 2011, Förster resonance energy transfer imaging in vivo with approximated radiative transfer equation, Applied Optics, Vol: 50, Pages: 6583-6590

We describe a new light transport model, which was applied to three-dimensional lifetime imaging of Förster resonance energy transfer in mice in vivo. The model is an approximation to the radiative transfer equation and combines light diffusion and ray optics. This approximation is well adopted to wide-field time-gated intensity-based data acquisition. Reconstructed image data are presented and compared with results obtained by using the telegraph equation approximation. The new approach provides improved recovery of absorption and scattering parameters while returning similar values for the fluorescence parameters.

Journal article

Patalay R, Talbot C, Alexandrov Y, Munro I, Breunig HG, König K, Warren S, Neil MAA, French PMW, Chu A, Stamp GW, Dunsby Cet al., 2011, Non-invasive imaging of skin cancer with fluorescence lifetime imaging using two photon tomography, Optics InfoBase Conference Papers

Multispectral fluorescence lifetime imaging (FLIM) using two photon microscopy as a non-invasive technique for the diagnosis of skin lesions is described. Skin contains fluorophores including elastin, keratin, collagen, FAD and NADH. This endogenous contrast allows tissue to be imaged without the addition of exogenous agents and allows the in vivo state of cells and tissues to be studied. A modified DermaInspect® multiphoton tomography system was used to excite autofluorescence at 760 nm in vivo and on freshly excised ex vivo tissue. This instrument simultaneously acquires fluorescence lifetime images in four spectral channels between 360-655 nm using time-correlated single photon counting and can also provide hyperspectral images. The multispectral fluorescence lifetime images were spatially segmented and binned to determine lifetimes for each cell by fitting to a double exponential lifetime model. A comparative analysis between the cellular lifetimes from different diagnoses demonstrates significant diagnostic potential. © 2011 SPIE-OSA.

Journal article

Patalay R, Talbot C, Alexandrov Y, Munro I, Neil MAA, Koenig K, French PMW, Chu A, Stamp GW, Dunsby Cet al., 2011, Quantification of cellular autofluorescence of human skin using multiphoton tomography and fluorescence lifetime imaging in two spectral detection channels, BIOMEDICAL OPTICS EXPRESS, Vol: 2, Pages: 3295-3308, ISSN: 2156-7085

Journal article

Brown ACN, Oddos S, Dobbie IM, Alakoskela J-M, Parton RM, Eissmann P, Neil MAA, Dunsby C, French PMW, Davis I, Davis DMet al., 2011, Remodelling of Cortical Actin Where Lytic Granules Dock at Natural Killer Cell Immune Synapses Revealed by Super-Resolution Microscopy, PLOS BIOLOGY, Vol: 9, ISSN: 1544-9173

Journal article

Benati E, Bellini V, Borsari S, Dunsby C, Ferrari C, French P, Guanti M, Guardoli D, Koenig K, Pellacani G, Ponti G, Schianchi S, Talbot C, Seidenari Set al., 2011, Quantitative evaluation of healthy epidermis by means of multiphoton microscopy and fluorescence lifetime imaging microscopy, SKIN RESEARCH AND TECHNOLOGY, Vol: 17, Pages: 295-303, ISSN: 0909-752X

Journal article

Talbot CB, Patalay R, Munro I, Warren S, Ratto F, Matteini P, Pini R, Breunig HG, König K, Chu AC, Stamp GW, Neil MAA, French PMW, Dunsby Cet al., 2011, Application of ultrafast gold luminescence to measuring the instrument response function for multispectral multiphoton fluorescence lifetime imaging., Opt Express, Vol: 19, Pages: 13848-13861

When performing multiphoton fluorescence lifetime imaging in multiple spectral emission channels, an instrument response function must be acquired in each channel if accurate measurements of complex fluorescence decays are to be performed. Although this can be achieved using the reference reconvolution technique, it is difficult to identify suitable fluorophores with a mono-exponential fluorescence decay across a broad emission spectrum. We present a solution to this problem by measuring the IRF using the ultrafast luminescence from gold nanorods. We show that ultrafast gold nanorod luminescence allows the IRF to be directly obtained in multiple spectral channels simultaneously across a wide spectral range. We validate this approach by presenting an analysis of multispectral autofluorescence FLIM data obtained from human skin ex vivo.

Journal article

Talbot CB, Patalay R, Munro I, Warren S, Ratto F, Matteini P, Pini R, Breunig HG, Koenig K, Chu AC, Stamp GW, Neil MAA, French PMW, Dunsby Cet al., 2011, Application of ultrafast gold luminescence to measuring the instrument response function for multispectral multiphoton fluorescence lifetime imaging, OPTICS EXPRESS, Vol: 19, Pages: 13848-13861, ISSN: 1094-4087

Journal article

Coda S, Kennedy GT, Thompson A, Talbot CB, Alexandrov Y, Munro I, Neil MA, Stamp GW, Elson DS, Dunsby C, French PM, Thillainayagam AVet al., 2011, FLUORESCENCE LIFETIME IMAGING FOR LABEL-FREE CONTRAST OF GASTROINTESTINAL DISEASES, International School of Physics "Enrico Fermi", Course CLXXXI "Microscopy Applied to Biophotonics"

INTRODUCTION: Autofluorescence (AF) has been used to distinguish between normal and diseased tissue, but its molecular basis is still unclear and making quantitative intensity measurements is challenging. Fluorescence lifetime imaging (FLIM) measures the decay rate of the autofluorescent signal from tissue, providing quantitative AF contrast. FLIM has been recently implemented by our group in three endoscopic instruments consisting of a confocal laser endomicroscope, a wide-field fibre-optic endoscope and a single point fibre-optic probe. FLIM has the potential to report on tissue structure and function in real-time during endoscopy, providing a label-free means to detect the early onset of diseases that cause changes in tissue AF. We are developing these 3 modalities for in vivo clinical application, supported by ex vivo studies on freshly-biopsied/resected GI tissues.AIMS & METHODS: The aim of this work is to translate our FLIM instrumentation from the optical bench to in vivo clinical application. AF from 43 endoscopic samples from different GI sites was excited using a conventional confocal FLIM microscope in the range 405-420nm, which is compatible with our FLIM endoscopes, and which is the range needed to excite a number of important endogenous GI tissue fluorophores such as porphyrins, flavins, collagen and elastin. The samples were collected from patients undergoing endoscopy, transported to the FLIM laboratory to be imaged and then submitted for histopathology. The following disorders were investigated: Barrett’s oesophagus, gastric cancer, ulcerative colitis, Crohn’s disease, adenomatous polyps and colon cancer. The accuracy of FLIM in discriminating dysplastic/cancerous samples from normal tissue has been tested by measuring the Area Under the Curve (AUC).RESULTS: Our preliminary data show that premalignant or neoplastic samples display either shorter or longer fluorescence lifetime than that of normal tissue. Increased lifetime val

Conference paper

McGinty J, Stuckey DW, Soloviev VY, Laine R, Wylezinska-Arridge M, Wells DJ, Arridge SR, French PMW, Hajnal JV, Sardini Aet al., 2011, In vivo fluorescence lifetime tomography of a FRET probe expressed in mouse, Biomedical Optics Express, Vol: 2, Pages: 1907-1917, ISSN: 2156-7085

Förster resonance energy transfer (FRET) is a powerful biological tool for reading out cell signaling processes. In vivo use of FRET is challenging because of the scattering properties of bulk tissue. By combining diffuse fluorescence tomography with fluorescence lifetime imaging (FLIM), implemented using wide-field time-gated detection of fluorescence excited by ultrashort laser pulses in a tomographic imaging system and applying inverse scattering algorithms, we can reconstruct the three dimensional spatial localization of fluorescence quantum efficiency and lifetime. We demonstrate in vivo spatial mapping of FRET between genetically expressed fluorescent proteins in live mice read out using FLIM. Following transfection by electroporation, mouse hind leg muscles were imaged in vivo and the emission of free donor (eGFP) in the presence of free acceptor (mCherry) could be clearly distinguished from the fluorescence of the donor when directly linked to the acceptor in a tandem (eGFP-mCherry) FRET construct.

Journal article

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