title: From morphology to biochemical state - intravital multiphoton fluorescence lifetime imaging of inflamed human skin.
abstract: The application of multiphoton microscopy in the field of biomedical research and advanced diagnostics promises unique insights into the pathophysiology of inflammatory skin diseases. In the present study, we combined multiphoton-based intravital tomography (MPT) and fluorescence lifetime imaging (MPT-FLIM) within the scope of a clinical trial of atopic dermatitis with the aim of providing personalised data on the aetiopathology of inflammation in a non-invasive manner at patients' bedsides. These 'optical biopsies' generated via MPT were morphologically analysed and aligned with classical skin histology. Because of its subcellular resolution, MPT provided evidence of a redistribution of mitochondria in keratinocytes, indicating an altered cellular metabolism. Two independent morphometric algorithms reliably showed an even distribution in healthy skin and a perinuclear accumulation in inflamed skin. Moreover, using MPT-FLIM, detection of the onset and progression of inflammatory processes could be achieved. In conclusion, the change in the distribution of mitochondria upon inflammation and the verification of an altered cellular metabolism facilitate a better understanding of inflammatory skin diseases and may permit early diagnosis and therapy.
authors.affiliation: Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Huck
authors.affiliation: Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gorzelanny
authors.affiliation: University of Münster, Department of Dermatology, Von-Esmarch-Str. 58, 48149 Münster, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Thomas
authors.affiliation: University of Münster, Department of Dermatology, Von-Esmarch-Str. 58, 48149 Münster, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Getova
authors.affiliation: Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Niemeyer
authors.affiliation: Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Zens
authors.affiliation: University of Münster, Department of Dermatology, Von-Esmarch-Str. 58, 48149 Münster, Germany.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Unnerstall
authors.affiliation: Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Feger
authors.affiliation: University of Konstanz, Department of Biophysical Chemistry, Universitätsstr. 10, 78457 Konstanz, Germany.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Fallah
authors.affiliation: University of Münster, Department of Dermatology, Von-Esmarch-Str. 58, 48149 Münster, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Metze
authors.affiliation: University of Münster, Department of Dermatology, Von-Esmarch-Str. 58, 48149 Münster, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Ständer
authors.affiliation: University of Münster, Department of Dermatology, Von-Esmarch-Str. 58, 48149 Münster, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Luger
authors.affiliation: Saarland University, Mechatronics &Physics, Campus A5 1, 66123 Saarbrücken, Germany.|JenLab GmbH, Schillerstr. 1, 07745 Jena, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Koenig
authors.affiliation: Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.|University of Münster, Department of Dermatology, Von-Esmarch-Str. 58, 48149 Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Mess
authors.affiliation: Heidelberg University, Medical Faculty Mannheim, Experimental Dermatology, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
mesh_terms: D000465:Algorithms; D001706:Biopsy; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods*; D008928:Mitochondria / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D041622:Tomography, Optical / Q000379:methods*