Abstract
.Two-photon microscopes have been successfully translated into clinical imaging tools to obtain high-resolution optical biopsies for in vivo histology. We report on clinical multiphoton coherent anti-Stokes Raman spectroscopy (CARS) tomography based on two tunable ultrashort near-infrared laser beams for label-free in vivo multimodal skin imaging. The multiphoton biopsies were obtained with the compact tomograph “MPTflex-CARS” using a photonic crystal fiber, an optomechanical articulated arm, and a four-detector-360 deg measurement head. The multiphoton tomograph has been employed to patients in a hospital with diseased skin. The clinical study involved 16 subjects, 8 patients with atopic dermatitis, 4 patients with psoriasis vulgaris, and 4 volunteers served as control. Two-photon cellular autofluorescence lifetime, second harmonic generation (SHG) of collagen, and CARS of intratissue lipids/proteins have been detected with single-photon sensitivity, submicron spatial resolution, and picosecond temporal resolution. The most important signal was the autofluorescence from nicotinamide adenine dinucleotide [NAD(P)H]. The SHG signal from collagen was mainly used to detect the epidermal–dermal junction and to calculate the ratio elastin/collagen. The CARS/Raman signal provided add-on information. Based on this view on the disease-affected skin on a subcellular level, skin areas affected by dermatitis and by psoriasis could be clearly identified. Multimodal multiphoton tomographs may become important label-free clinical high-resolution imaging tools for in vivo skin histology to realize rapid early diagnosis as well as treatment control.
Highlights
Two-photon effects were predicted by the German PhD student Maria Göppert more than 90 years ago
The fluorescence lifetime imaging (FLIM) images generally reaffirm the morphology of the fluorescence intensity images and indicate, in addition, the fluorescence lifetimes, which are characteristics for the involved molecules
The two-beam multiphoton/coherent anti-Stokes Raman spectroscopy (CARS) tomograph has been successfully tested in a clinical trial involving patients suffering from Atopic dermatitis (AD) and psoriasis vulgaris” (PV)
Summary
Two-photon effects were predicted by the German PhD student Maria Göppert more than 90 years ago. The first paper was submitted on October 28, 1928, with the title “Über die Wahrscheinlichkeit des Zusammenwirkens zweier Lichtquanten in einem Elementarakt” (“On the probability of two light quantum working together in an elementary act”), and was published in 1929.1 Her PhD thesis, supervised by Max Born, was published in 1931.2 In 1930, she married the American Joseph Edward Mayer, who worked in Göttingen and moved to the United States. In 1960, Maria Goeppert-Mayer was appointed to a position as a full professor of physics at the University of California at San Diego (UCSD). It was the year the laser was invented. The simultaneous absorption by two photons, where the nonlinear absorption process scales with the square of the light intensity. The unit GM for the characterization of two-photon absorption cross-sections (1 GM 1⁄4 1 × 1050 cm[4] s photon) refers to her
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