Two-photon retinal theranostics by adaptive compact laser source
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S.I. : CURRENT STATE-OF-THE-ART IN LASER ABLATION
Two‑photon retinal theranostics by adaptive compact laser source Rok Podlipec1,2 · Jaka Mur3 · Jaka Petelin3 · Janez Štrancar2 · Rok Petkovšek3 Received: 14 October 2019 / Accepted: 27 April 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract To avoid a devastating effect of eye vision impairment on the information flow from the eye to our brain, enormous effort is being put during the last decades into the development of more sensitive diagnostics and more efficient therapies of retinal tissue. While morphology can be impressively imaged by optical coherence tomography, molecular-associated pathology information can be provided almost exclusively by auto-fluorescence-based methods. Among the latter, the recently developed fluorescence lifetime imaging ophthalmoscopy (FLIO) has the potential to provide both structural information and interacting pictures at the same time. The requirements for FLIO laser sources are almost orthogonal to the laser sources used in phototherapy that is expected to follow up the FLIO diagnostics. To make theranostics more effective and cheaper, the complete system would need to couple at least the modalities of low-power high-repetition-rate FLIO and precision highpulse energy-adjustable repetition rate phototherapy. In addition, the intermediate-power high repetition rate for two-photon excitation would also be desired to increase the depth resolution. In our work, compact fiber-laser based on high-speed gainswitched laser diode has been shown to achieve adaptable/independently tunable repetition rate and energy per pulse allowing coupled fluorescence lifetime diagnostics via two-photon excitation and phototherapy via laser-induced photodisruption on a local molecular environment in a complex ex vivo retinal tissue. Keywords Adaptable fiber laser · Retinal tissue · Theranostics · Multimodal imaging · Fluorescence lifetime imaging
1 Introduction
* Rok Petkovšek [email protected]‑lj.si Rok Podlipec [email protected] Jaka Mur [email protected]‑lj.si Jaka Petelin [email protected]‑lj.si Janez Štrancar [email protected] 1
Ion Beam Center, Helmholz Zentrum Dresden Rossendorf (HZDR), Bautzner Landstraße 400, 01328 Dresden, Germany
2
Jožef Stefan Institute, Jamova cesta 39, 1000 Ljubljana, Slovenia
3
Faculty of Mechanical Engineering, University of Ljubljana, Aškerčeva 6, 1000 Ljubljana, Slovenia
Remarkable progress in the development of advanced retinal diagnostics and therapies has been done in the last decade to provide better sensitivity and specificity for detecting retinal pathologies and to minimize the potential risks for damaging the targeted tissue. Two large families of diagnostic methods evolved, the first based on detecting retinal fluorescence in the visual part of the spectrum called fundus autofluorescence (FAF) [1, 2] and the second based on the interferometric imaging of retinal layers with NIR light called optical coherence tomography (OCT) [3]. Although, OCT has been devel
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