Review: history of multiphoton tomography

Abstract

Two decades ago, the very first prototype of a multiphoton tomograph was built and delivered as a high-resolution skin imaging device to the cosmetic company Beiersdorf AG on November 2, 2001. The tomograph was based on a tunable 80 MHz NIR femtosecond laser system and able to detect two-photon excited autofluorescence intensity and fluorescence lifetime based on time-correlated single photon counting (TCSPC) as well as second harmonic generation (SHG) with 300 nm lateral resolution and 250 ps temporal resolution. Two-photon fluorescence lifetime imaging (FLIM) was performed based in a biexponential decay and false-color coding. The first clinical in vivo study on melanocytic lesions with the DermaInspect started at the Department of Dermatology of the University Jena on September 5, 2003. The study was performed on 53 patients and resulted in optical biopsies based on 2108 optical sections. The tomograph worked under clinical conditions without any problem. Finally, the CE0118 certificate for the multiphoton tomograph DermaInspect as medical device was granted by the European Certified Body Thuringian State Authority of Metrology and Verification (LMET) on December 22, 2004. The DermaInspect became the world’s first femtosecond laser medical device for clinical imaging. The CE0118 certificate for the 2nd generation of multiphoton tomographs, the portable medical device with a tunable titanium:sapphire laser, an optical arm and a 360° measurement head mounted on a mechanical arm, the “MPTflex”, was granted on Nov 8, 2010. The third generation, the multimodal multiphoton tomograph MPTcompact, is based on a chiller-free ultracompact femtosecond fiber laser and miniaturized detectors to measure autofluorescence, SHG, FLIM, and confocal reflectance. The first two MPTcompact prototypes were delivered to hospitals in Heidelberg and Gera in 2018 to realize a multicenter clinical study on the detection of malignant melanoma. JenLab’s multiphoton tomographs have been used to realize the word’s first clinical in vivo two-photon imaging of patients, including (i) the first two-photon fluorescence lifetime imaging, (ii) the first microendoscopy, the first (iii) diseased skin imaging, (iv) brain imaging, and (v) the first CARS studies.