Forschung

Die Arbeitsgruppe um Robert Huber forscht in den Bereichen der optischen Kohärenztomographie (OCT), der nichtlinearen Bildgebung und der Laserphysik. Hierbei wird vor allem an neuartigen Pikosekundenlaser und an Fourier domain modengekoppelten (FDML) Lasern gearbeitet. Dieses Laserkonzept wurde von Robert Huber entwickelt und erlaubt, besonders schnell durchstimmbare Laserlichtquellen zu realisieren. Die Forschungsschwerpunkte liegen hier in der technologischen Weiterentwicklung, dem Verständnis der physikalischen Vorgänge und auch in der Implementierung von FDML Lasern für OCT. Neben der OCT werden FDML Laser auch für die nichtlineare Bildgebung und Spektroskopie verwendet.

Ein weiterer Schwerpunkt liegt in der optischen Kohärenztomographie mit durchstimmbaren Lichtquellen (swept source OCT, SS-OCT). Hier werden unter anderem die selbst entwickelten FDML Laser für die ultraschnelle Bildgebung eingesetzt, um Schnittbilder von biologischen Gewebe wie Haut oder Auge zu erzeugen. Aufgrund der hohen Durchstimmrate sind Anwendungen wie die VR-OCT, die in einer virtuellen Umgebung ganze Volumina mit Video-Wiederholraten in Echtzeit darstellt, möglich.

Mit der nichtlinearen optischen Bildgebung verfolgt die Arbeitsgruppe weitere Bildgebungsverfahren. Die Forschungsgebiete liegen in der zeitcodierten (TICO) Ramanspektroskopie und -mikroskopie, der Zweiphotonen-Fluoreszenzmikroskopie (TPEF) und der Zweiphotonen-Einzelpuls-Fluoreszenzlebenszeitbildgebung (SP-FLIM). Für diese Verfahren kommen neuartige Pikosekunden zum Einsatz die ebenfalls in der Arbeitsgruppe erforscht und entwickelt werden.

Unsere Forschungsschwerpunkte:

Publikationen

2019

2018

Josef Maertz, Jan Philip Kolb, Thomas Klein, Kathrin J. Mohler, Matthias Eibl, Wolfgang Wieser, Robert Huber, Siegfried Priglinger, and Armin Wolf,
Combined in-depth, 3D, en face imaging of the optic disc, optic disc pits and optic disc pit maculopathy using swept-source megahertz OCT at 1050 nm, Graefes Arch Clin Exp Ophthalmol , vol. 256, no. 2, pp. 289-298, Dez. 2018.
DOI:10.1007/s00417-017-3857-9
Bibtex: BibTeX
@article{Maertz2018,
   author = {Maertz, J; Kolb, J P; Klein, T; Mohler, K J; Eibl, M; Wieser, W; Huber, R; Priglinger, S and Wolf, A},
   title = {Combined in-depth, 3D, en face imaging of the optic disc, optic disc pits and optic disc pit maculopathy using swept-source megahertz OCT at 1050 nm},
   journal = {Graefe's Archive for Clinical and Experimental Ophthalmology},
   number = {2},
   pages = {289-298},
   DOI = {10.1007/s00417-017-3857-9},
   url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032262413&doi=10.1007%2fs00417-017-3857-9&partnerID=40&md5=a46c315f12cf5e633ea0f7e644116eb3},
   year = {2018},
   Keywords= {En face imaging, Optical coherence tomography, Swept-source OCT, Megahertz OCT, 3D rendering, Optic disc, Optic disc pit, Optic disc pit maculopathy, AG-Huber_OCT},
   type = {Journal Article}
}
Matthias Eibl, Daniel Weng, Hubertus Hakert, Jan Philip Kolb, Tom Pfeiffer, Jennifer Hundt, Robert Huber, and Sebastian Karpf,
Wavelength agile multi-photon microscopy with a fiber amplified diode laser, Biomedical Optics Express , vol. 9, no. 12, pp. 6273-6282, Nov. 2018. The Optical Society.
DOI:10.1364/BOE.9.006273
Bibtex: BibTeX
@article{Eibl2018,
  doi = {10.1364/boe.9.006273},
  url = {https://doi.org/10.1364/boe.9.006273},
  year = {2018},
  month = nov,
  publisher = {The Optical Society},
  volume = {9},
  number = {12},
  pages = {6273},
  author = {Matthias Eibl and Daniel Weng and Hubertus Hakert and Jan Philip Kolb and Tom Pfeiffer and Jennifer E. Hundt and Robert Huber and Sebastian Karpf},
  title = {Wavelength agile multi-photon microscopy with a fiber amplified diode laser},
  journal = {Biomedical Optics Express}
}
Hinnerk Schulz-Hildebrandt, Tom Pfeiffer, Tim Eixmann, Sabrina Lohmann, Martin Ahrens, Josua Rehra, Wolfgang Draxinger, Peter König, Robert Huber, and Gereon Hüttmann,
High-speed fiber scanning endoscope for volumetric multi-megahertz optical coherence tomography, Opt. Lett. , vol. 43, no. 18, pp. 4386-4389, 09 2018. Optica Publishing Group.
DOI:10.1364/OL.43.004386
Bibtex: BibTeX
@article{Schulz-Hildebrandt:18,
author = {Hinnerk Schulz-Hildebrandt and Tom Pfeiffer and Tim Eixmann and Sabrina Lohmann and Martin Ahrens and Joshua Rehra and Wolfgang Draxinger and Peter K\"{o}nig and Robert Huber and Gereon H\"{u}ttmann},
journal = {Opt. Lett.},
keywords = {Fiber optics imaging; Endoscopic imaging; Medical and biological imaging; Optical coherence tomography; Fourier domain mode locking; Image quality; Optical coherence tomography; Single mode fibers; Step index fibers; Three dimensional imaging},
number = {18},
pages = {4386--4389},
publisher = {Optica Publishing Group},
title = {High-speed fiber scanning endoscope for volumetric multi-megahertz optical coherence tomography},
volume = {43},
month = {Sep},
year = {2018},
url = {https://opg.optica.org/ol/abstract.cfm?URI=ol-43-18-4386},
doi = {10.1364/OL.43.004386},
abstract = {We present a forward-viewing fiber scanning endoscope (FSE) for high-speed volumetric optical coherence tomography (OCT). The reduction in size of the probe was achieved by substituting the focusing optics by an all-fiber-based imaging system which consists of a combination of scanning single-mode fibers, a glass spacer, made from a step-index multi-mode fiber, and a gradient-index fiber. A lateral resolution of 11 $\mu$m was achieved at a working distance of 1.2 mm. The newly designed piezo-based FSE has an outer diameter of 1.6 mm and a rigid length of 13.5 mm. By moving the whole imaging optic in spirals for scanning the sample, the beam quality remains constant over the entire field of view with a diameter of 0.8 mm. The scanning frequency was adjusted to 1.22 kHz for use with a 3.28 MHz Fourier domain mode locked OCT system. Densely sampled volumes have been imaged at a rate of 6 volumes per second.},
}
Tom Pfeiffer, Markus Petermann, Wolfgang Draxinger, Christian Jirauschek, and Robert Huber,
Ultra low noise Fourier domain mode locked laser for high quality magahertz optical coherence tomography, Biomed. Opt. Express , vol. 9, no. 9, pp. 4130-4148, 09 2018. Optica Publishing Group.
DOI:10.1364/BOE.9.004130
Bibtex: BibTeX
@article{Pfeiffer:18,
author = {Tom Pfeiffer and Markus Petermann and Wolfgang Draxinger and Christian Jirauschek and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Fiber optics imaging; Lasers, fiber; Optical coherence tomography; Laser stabilization ; Lasers, frequency modulated ; Analog to digital converters; Dark solitons; Image quality; Laser modes; Mode locking; Optical coherence tomography},
number = {9},
pages = {4130--4148},
publisher = {Optica Publishing Group},
title = {Ultra low noise Fourier domain mode locked laser for high quality megahertz optical coherence tomography},
volume = {9},
month = {Sep},
year = {2018},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-9-9-4130},
doi = {10.1364/BOE.9.004130},
abstract = {We investigate the origin of high frequency noise in Fourier domain mode locked (FDML) lasers and present an extremely well dispersion compensated setup which virtually eliminates intensity noise and dramatically improves coherence properties. We show optical coherence tomography (OCT) imaging at 3.2 MHz A-scan rate and demonstrate the positive impact of the described improvements on the image quality. Especially in highly scattering samples, at specular reflections and for strong signals at large depth, the noise in optical coherence tomography images is significantly reduced. We also describe a simple model that suggests a passive physical stabilizing mechanism that leads to an automatic compensation of remaining cavity dispersion in FDML lasers.},
}
Mark Schmidt, Tom Pfeiffer, Christin Grill, Robert Huber, and Christian Jirauschek,
Self-Stabilization Mechanism in Fourier Domain Mode-Locked (FDML) Lasers, OSA Continuum , vol. 3, no. 6, pp. 1589--1607, 06 2018. Optica Publishing Group.
DOI:10.1364/OSAC.389972
Bibtex: BibTeX
@article{Schmidt:20,
author = {Mark Schmidt and Tom Pfeiffer and Christin Grill and Robert Huber and Christian Jirauschek},
journal = {OSA Continuum},
keywords = {Doppler effect; Laser modes; Laser sources; Nonlinear effects; Stimulated Raman scattering; Vertical cavity surface emitting lasers},
number = {6},
pages = {1589--1607},
publisher = {Optica Publishing Group},
title = {Self-stabilization mechanism in ultra-stable Fourier domain mode-locked (FDML) lasers},
volume = {3},
month = {Jun},
year = {2020},
url = {https://opg.optica.org/osac/abstract.cfm?URI=osac-3-6-1589},
doi = {10.1364/OSAC.389972},
abstract = {Understanding the dynamics of Fourier domain mode-locked (FDML) lasers is crucial for determining physical coherence limits, and for finding new superior methods for experimental realization. In addition, the rich interplay of linear and nonlinear effects in a laser ring system is of great theoretical interest. Here we investigate the dynamics of a highly dispersion-compensated setup, where over a bandwidth of more than 100\&\#x2009;nm, a highly coherent output with nearly shot-noise-limited intensity fluctuations was experimentally demonstrated. This output is called the sweet-spot. We show by numerical simulation that a finite amount of residual dispersion in the fiber delay cavity of FDML lasers can be compensated by the group delay dispersion in the swept bandpass filter, such that the intensity trace exhibits no dips or high-frequency distortions, which are the main source of noise in the laser. In the same way, a small detuning from the ideal sweep filter frequency can be tolerated. Furthermore, we find that the filter\&\#x2019;s group delay dispersion improves the coherence properties of the laser, and acts as a self-stabilizing element in the cavity. Our theoretical model is validated against experimental data, showing that all relevant physical effects for the sweet-spot operating regime are included.},
}
Jan Philip Kolb, Tom Pfeiffer, Matthias Eibl, Hubertus Hakert, and Robert Huber,
High-resolution retinal swept source optical coherence tomography with an ultra-wideband Fourier-domain mode-locked laser at MHz A-scan rates, Biomed. Opt. Express , vol. 9, no. 1, pp. 120-130, 01 2018. Optica Publishing Group.
DOI:10.1364/BOE.9.000120
Bibtex: BibTeX
@article{Kolb:18,
author = {Jan Philip Kolb and Tom Pfeiffer and Matthias Eibl and Hubertus Hakert and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Medical optics instrumentation; Lasers, fiber; Medical and biological imaging; Ophthalmic optics and devices ; Optical coherence tomography; Adaptive optics; Image quality; In vivo imaging; Mode locking; Ophthalmic imaging; Three dimensional imaging},
number = {1},
pages = {120--130},
publisher = {Optica Publishing Group},
title = {High-resolution retinal swept source optical coherence tomography with an ultra-wideband Fourier-domain mode-locked laser at MHz A-scan rates},
volume = {9},
month = {Jan},
year = {2018},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-9-1-120},
doi = {10.1364/BOE.9.000120},
abstract = {We present a new 1060 nm Fourier domain mode locked laser (FDML laser) with a record 143 nm sweep bandwidth at 2\&\#x2219;\&\#x202F;417 kHz\&\#x202F; $=$ \&\#x202F;834 kHz and 120 nm at 1.67 MHz, respectively. We show that not only the bandwidth alone, but also the shape of the spectrum is critical for the resulting axial resolution, because of the specific wavelength-dependent absorption of the vitreous. The theoretical limit of our setup lies at 5.9 \&\#x00B5;m axial resolution. In vivo MHz-OCT imaging of human retina is performed and the image quality is compared to the previous results acquired with 70 nm sweep range, as well as to existing spectral domain OCT data with 2.1 \&\#x00B5;m axial resolution from literature. We identify benefits of the higher resolution, for example the improved visualization of small blood vessels in the retina besides several others.},
}

2017

Matthias Eibl, Sebastian Karpf, Hubertus Hakert, Torben Blömker, Jan Philip Kolb, Christian Jirauschek, and Robert Huber,
Pulse-to-pulse wavelength switching of a nanosecond fiber laser by four-wave mixing seeded stimulated Raman amplification, Opt. Lett. , vol. 42, no. 21, pp. 4406-4409, Nov. 2017. Optica Publishing Group.
DOI:10.1364/OL.42.004406
Bibtex: BibTeX
@article{Eibl:17,
author = {Matthias Eibl and Sebastian Karpf and Hubertus Hakert and Torben Bl\"{o}mker and Jan Philip Kolb and Christian Jirauschek and Robert Huber},
journal = {Opt. Lett.},
keywords = {Lasers, fiber; Lasers, Raman; Nonlinear optics, four-wave mixing; Scattering, stimulated Raman; Lasers, ytterbium ; Fiber lasers; Master oscillator power amplifiers; Nanosecond pulses; Raman scattering; Stimulated Brillouin scattering; Wavelength conversion},
number = {21},
pages = {4406--4409},
publisher = {Optica Publishing Group},
title = {Pulse-to-pulse wavelength switching of a nanosecond fiber laser by four-wave mixing seeded stimulated Raman amplification},
volume = {42},
month = {Nov},
year = {2017},
url = {https://opg.optica.org/ol/abstract.cfm?URI=ol-42-21-4406},
doi = {10.1364/OL.42.004406},
abstract = {We report on a multi-color fiber laser based on four-wave mixing (FWM) and stimulated Raman scattering (SRS), delivering rapidly wavelength switchable narrowband output at 1064, 1122, and 1186\&\#x00A0;nm. High-power pulses from a nanosecond pulsed fiber master oscillator power amplifier at 1064\&\#x00A0;nm are combined with 1122\&\#x00A0;nm of seed light for Raman amplification at the first Stokes order in a standard single-mode fiber. With increasing power, we observe a narrowband spectral component at 1186\&\#x00A0;nm, without any additional seed or resonator at this wavelength. We analyze this occurrence of a narrowband second Stokes order both experimentally and theoretically and suggest it is a result of FWM seeding of the SRS amplification in the fiber. We demonstrate that the wavelength shifting can be controlled electronically within microseconds for very rapid and even pulse-to-pulse wavelength changes. This wavelength conversion method can extend the spectral coverage of single-wavelength fiber lasers for biomedical imaging.},
}
Tianshi Wang, Tom Pfeiffer, Min Wu, Wolfgang Wieser, Gaetano Amenta, Wolfgang Draxinger, Antonius F. W. van der Steen, Robert Huber, and Gijs van Soest,
Thermo-elastic optical coherence tomography, Optica Publishing Group, 092017. pp. 3466-3469.
DOI:10.1364/OL.42.003466
Bibtex: BibTeX
@article{Wang:17,
author = {Tianshi Wang and Tom Pfeiffer and Min Wu and Wolfgang Wieser and Gaetano Amenta and Wolfgang Draxinger and Antonius F. W. van der Steen and Robert Huber and Gijs van Soest},
journal = {Opt. Lett.},
keywords = {Imaging systems; Medical and biological imaging; Optical coherence tomography; Lasers, pulsed ; Fourier domain mode locking; Functional imaging; Laser beams; Nanosecond pulses; Optical coherence tomography; Phantom studies},
number = {17},
pages = {3466--3469},
publisher = {Optica Publishing Group},
title = {Thermo-elastic optical coherence tomography},
volume = {42},
month = {Sep},
year = {2017},
url = {https://opg.optica.org/ol/abstract.cfm?URI=ol-42-17-3466},
doi = {10.1364/OL.42.003466},
abstract = {The absorption of nanosecond laser pulses induces rapid thermo-elastic deformation in tissue. A sub-micrometer scale displacement occurs within a few microseconds after the pulse arrival. In this Letter, we investigate the laser-induced thermo-elastic deformation using a 1.5 MHz phase-sensitive optical coherence tomography (OCT) system. A displacement image can be reconstructed, which enables a new modality of phase-sensitive OCT, called thermo-elastic OCT. An analysis of the results shows that the optical absorption is a dominating factor for the displacement. Thermo-elastic OCT is capable of visualizing inclusions that do not appear on the structural OCT image, providing additional tissue type information.},
}
Jan Philip Kolb, Julian Klee, Tom Pfeiffer, and Robert Huber,
1060nm FDML laser with centimeter coherence length and 1.67 MHz sweep rate for full eye length and retinal ultra-widefield OCT, in Optical Coherence Imaging Techniques and Imaging in Scattering Media II , Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh, Eds. SPIE, 082017. pp. 104160J.
DOI:10.1117/12.2286854
Bibtex: BibTeX
@inproceedings{10.1117/12.2286854,
author = {Jan Philip Kolb and Julian Klee and Tom Pfeiffer and Robert Huber},
title = {{1060nm FDML laser with centimeter coherence length and 1.67 MHz sweep rate for full eye length and retinal ultra-widefield OCT}},
volume = {10416},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media II},
editor = {Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {104160J},
abstract = {We present a new design of a 1060nm Fourier Domain Mode Locked-Laser (FDML-Laser) that combines 1.67 MHz A-scan rate with a centimeter scale coherence length. The extended coherence length is achieved by synchronizing the cavity roundtrip time over the 75 nm sweep with a relative accuracy of 10<sup>-7</sup>. We will show that this requires careful combination of multiple fiber types in the cavity with a gradient heated chirped Fiber Bragg grating.},
keywords = {optical coherence tomograhy, OCT, tunable laser, Fourier domain mode locking, FDML, MHz OCT},
year = {2017},
doi = {10.1117/12.2286854},
URL = {https://doi.org/10.1117/12.2286854}
}
Tom Pfeiffer, Wolfgang Draxinger, Christin Grill, and Robert Huber,
Long-range live 3D-OCT at different spectral zoom levels, in Optical Coherence Imaging Techniques and Imaging in Scattering Media II , Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh, Eds. SPIE, 082017. pp. 104160L.
DOI:10.1117/12.2287484
Bibtex: BibTeX
@inproceedings{10.1117/12.2287484,
author = {Tom Pfeiffer and Wolfgang Draxinger and Christin Grill and Robert Huber},
title = {{Long-range live 3D-OCT at different spectral zoom levels}},
volume = {10416},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media II},
editor = {Maciej Wojtkowski and Stephen A. Boppart and Wang-Yuhl Oh},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {104160L},
abstract = {We demonstrate that the 3.2 MHz a-scan rate and the improved coherence of our new low noise FDML laser enables live 3D-OCT with different spectral zooms and up to 10 cm of imaging range.},
keywords = {Optical coherence tomography, Fourier Domain Mode Locking, FDML, OCT},
year = {2017},
doi = {10.1117/12.2287484},
URL = {https://doi.org/10.1117/12.2287484}
}
Matthias Eibl, Sebastian Karpf, Hubertus Hakert, Daniel Weng, Tom Pfeiffer, Jan Philip Kolb, and Robert Huber,
Single pulse two-photon fluorescence lifetime imaging (SP-FLIM) with MHz pixel rate and an all fiber based setup, in Advances in Microscopic Imaging , Emmanuel Beaurepaire and Francesco Saverio Pavone and Peter T. C. So, Eds. SPIE, 072017. pp. 1041403.
DOI:10.1117/12.2286035
Bibtex: BibTeX
@inproceedings{10.1117/12.2286035,
author = {Matthias Eibl and Sebastian Karpf and Hubertus Hakert and Daniel Weng and Tom Pfeiffer and Jan Philip Kolb and Robert Huber},
title = {{Single pulse two-photon fluorescence lifetime imaging (SP-FLIM) with MHz pixel rate and an all fiber based setup }},
volume = {10414},
booktitle = {Advances in Microscopic Imaging},
editor = {Emmanuel Beaurepaire and Francesco Saverio Pavone and Peter T. C. So},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1041403},
abstract = {Newly developed microscopy methods have the goal to give researches in bio-molecular science a better understanding of processes ongoing on a cellular level. Especially two-photon excited fluorescence (TPEF) microscopy is a readily applied and widespread modality. Compared to one photon fluorescence imaging, it is possible to image not only the surface but also deeper lying structures. Together with fluorescence lifetime imaging (FLIM), which provides information on the chemical composition of a specimen, deeper insights on a molecular level can be gained. However, the need for elaborate light sources for TPEF and speed limitations for FLIM hinder an even wider application. In this contribution, we present a way to overcome this limitations by combining a robust and inexpensive fiber laser for nonlinear excitation with a fast analog digitization method for rapid FLIM imaging. The applied sub nanosecond pulsed laser source is perfectly suited for fiber delivery as typically limiting non-linear effects like self-phase or cross-phase modulation (SPM, XPM) are negligible. Furthermore, compared to the typically applied femtosecond pulses, our longer pulses produce much more fluorescence photons per single shot. In this paper, we show that this higher number of fluorescence photons per pulse combined with a high analog bandwidth detection makes it possible to not only use a single pulse per pixel for TPEF imaging but also to resolve the exponential time decay for FLIM. To evaluate our system, we acquired FLIM images of a dye solution with single exponential behavior to assess the accuracy of our lifetime determination and also FLIM images of a plant stem at a pixel rate of 1 MHz to show the speed performance of our single pulse two-photon FLIM (SP-FLIM) system.},
keywords = {Nonlinear microscopy, Fluorescence microscopy, Fiber optics imaging, Lifetime-based sensing, Lasers, fiber, Nonlinear optics, fibers},
year = {2017},
doi = {10.1117/12.2286035},
URL = {https://doi.org/10.1117/12.2286035}
}
Hubertus Hakert, Matthias Eibl, Sebastian Karpf, and Robert Huber,
Sparse-sampling with time-encoded (TICO) stimulated Raman scattering for fast image acquisition, in Advances in Microscopic Imaging , Emmanuel Beaurepaire and Francesco Saverio Pavone and Peter T. C. So, Eds. SPIE, 072017. pp. 1041408.
DOI:10.1117/12.2287947
Bibtex: BibTeX
@inproceedings{10.1117/12.2287947,
author = {Hubertus Hakert and Matthias Eibl and Sebastian Karpf and Robert Huber},
title = {{Sparse-sampling with time-encoded (TICO) stimulated Raman scattering for fast image acquisition}},
volume = {10414},
booktitle = {Advances in Microscopic Imaging},
editor = {Emmanuel Beaurepaire and Francesco Saverio Pavone and Peter T. C. So},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1041408},
abstract = {Modern biomedical imaging modalities aim to provide researchers a multimodal contrast for a deeper insight into a
specimen under investigation. A very promising technique is stimulated Raman scattering (SRS) microscopy, which can
unveil the chemical composition of a sample with a very high specificity. Although the signal intensities are enhanced
manifold to achieve a faster acquisition of images if compared to standard Raman microscopy, there is a trade-off between
specificity and acquisition speed. Commonly used SRS concepts either probe only very few Raman transitions as the
tuning of the applied laser sources is complicated or record whole spectra with a spectrometer based setup. While the first
approach is fast, it reduces the specificity and the spectrometer approach records whole spectra -with energy differences
where no Raman information is present-, which limits the acquisition speed. Therefore, we present a new approach based
on the TICO-Raman concept, which we call sparse-sampling. The TICO-sparse-sampling setup is fully electronically
controllable and allows probing of only the characteristic peaks of a Raman spectrum instead of always acquiring a whole
spectrum. By reducing the spectral points to the relevant peaks, the acquisition time can be greatly reduced compared to a
uniformly, equidistantly sampled Raman spectrum while the specificity and the signal to noise ratio (SNR) are maintained.
Furthermore, all laser sources are completely fiber based. The synchronized detection enables a full resolution of the
Raman signal, whereas the analogue and digital balancing allows shot noise limited detection. First imaging results with
polystyrene (PS) and polymethylmethacrylate (PMMA) beads confirm the advantages of TICO sparse-sampling. We
achieved a pixel dwell time as low as 35 μs for an image differentiating both species. The mechanical properties of the
applied voice coil stage for scanning the sample currently limits even faster acquisition.},
keywords = {nonlinear microscopy, fiber optics imaging, stimulated raman scattering microscopy, time encoded, sparse sampling, Raman spectroscopy , Fourier Domain Mode Locked Laser, FDML, Lasers, fiber},
year = {2017},
doi = {10.1117/12.2287947},
URL = {https://doi.org/10.1117/12.2287947}
}
Josef Maertz, Kathrin J. Mohler, Jan Philip Kolb, Thomas Klein, Aljoscha Neubauer, Anselm Kampik, Siegfried Priglinger, Wolfgang Wieser, Robert Huber, and Armin Wolf,
INTRAPAPILLARY PROLIFERATION IN OPTIC DISK PITS: Clinical Findings and Time-Related Changes, Retina , vol. 37, no. 5, pp. 906-914, 05 2017.
DOI:10.1097/iae.0000000000001260
Bibtex: BibTeX
@article{Maertz2017,
   author = {Maertz, J. and Mohler, K. J. and Kolb, J. P. and Klein, T. and Neubauer, A. and Kampik, A. and Priglinger, S. and Wieser, W. and Huber, R. and Wolf, A.},
   title = {INTRAPAPILLARY PROLIFERATION IN OPTIC DISK PITS: Clinical Findings and Time-Related Changes},
   journal = {Retina},
   volume = {37},
   number = {5},
   pages = {906-914},
   DOI = {10.1097/iae.0000000000001260},
   year = {2017},
keywords = {AG-Huber_OCT},
   type = {Journal Article}
}
Sebastian Karpf, Matthias Eibl, Wolfgang Wieser, Thomas Klein, and Robert Huber,
Shot-Noise Limited Time-Encoded Raman Spectroscopy, Journal of Spectroscopy , vol. 2017, pp. 1-6, 03 2017. Hindawi.
DOI:10.1155/2017/9253475
Bibtex: BibTeX
@article{Karpf2017,
   author = {Karpf, Sebastian and Eibl, Matthias and Wieser, Wolfgang and Klein, Thomas and Huber, Robert},
   title = {Shot-Noise Limited Time-Encoded Raman Spectroscopy},
   journal = {Journal of Spectroscopy},
   volume = {2017},
   pages = {1-6},
   url = {https://doi.org/10.1155/2017/9253475},
   year = {2017},
keywords = {AG-Huber_NL},
   type = {Journal Article}
}
Matthias Eibl, Sebastian Karpf, Hubertus Hakert, Daniel Weng, Torben Blömker, and Robert Huber,
Pulse-to-pulse wavelength switching of diode based fiber laser for multi-color multi-photon imaging, in Fiber Lasers XIV: Technology and Systems , Craig A. Robin and Ingmar Hartl, Eds. SPIE, 032017. pp. 100831C.
DOI:10.1117/12.2251965
Bibtex: BibTeX
@inproceedings{10.1117/12.2251965,
author = {Matthias Eibl and Sebastian Karpf and Hubertus Hakert and Daniel Weng and Torben Bl{\"o}mker and Robert Huber},
title = {{Pulse-to-pulse wavelength switching of diode based fiber laser for multi-color multi-photon imaging}},
volume = {10083},
booktitle = {Fiber Lasers XIV: Technology and Systems},
editor = {Craig A. Robin and Ingmar Hartl},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {100831C},
abstract = {We present an entirely fiber based laser source for non-linear imaging with a novel approach for multi-color excitation. The high power output of an actively modulated and amplified picosecond fiber laser at 1064 nm is shifted to longer wavelengths by a combination of four-wave mixing and stimulated Raman scattering. By combining different fiber types and lengths, we control the non-linear wavelength conversion in the delivery fiber itself and can switch between 1064 nm, 1122 nm, and 1186 nm on-the-fly by tuning the pump power of the fiber amplifier and modulate the seed diodes. This is a promising way to enhance the applicability of short pulsed laser diodes for bio-molecular non-linear imaging by reducing the spectral limitations of such sources. In comparison to our previous work [1, 2], we show for the first time two-photon imaging with the shifted wavelengths and we demonstrate pulse-to-pulse switching between the different wavelengths without changing the configuration.},
keywords = {stimulated raman scattering, two-photon imaging, fiber amplifier, four-wave-mixing, wavelength conversion, non-linear imaging},
year = {2017},
doi = {10.1117/12.2251965},
URL = {https://doi.org/10.1117/12.2251965}
}
Max-Heinrich Laves, Andreas Schoob, Lüder A. Kahrs, Tom Pfeiffer, Robert Huber, and Tobias Ortmaier,
Feature tracking for automated volume of interest stabilization on 4D-OCT images, in Medical Imaging 2017: Image-Guided Procedures, Robotic Interventions, and Modeling , Robert J. Webster III and Baowei Fei, Eds. SPIE, 032017. pp. 101350W.
DOI:10.1117/12.2255090
Bibtex: BibTeX
@inproceedings{10.1117/12.2255090,
author = {Max-Heinrich Laves and Andreas Schoob and L{\"u}der A. Kahrs and Tom Pfeiffer and Robert Huber and Tobias Ortmaier},
title = {{Feature tracking for automated volume of interest stabilization on 4D-OCT images}},
volume = {10135},
booktitle = {Medical Imaging 2017: Image-Guided Procedures, Robotic Interventions, and Modeling},
editor = {Robert J. Webster III and Baowei Fei},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {101350W},
abstract = {A common representation of volumetric medical image data is the triplanar view (TV), in which the surgeon manually selects slices showing the anatomical structure of interest. In addition to common medical imaging such as MRI or computed tomography, recent advances in the field of optical coherence tomography (OCT) have enabled live processing and volumetric rendering of four-dimensional images of the human body. Due to the region of interest undergoing motion, it is challenging for the surgeon to simultaneously keep track of an object by continuously adjusting the TV to desired slices. To select these slices in subsequent frames automatically, it is necessary to track movements of the volume of interest (VOI). This has not been addressed with respect to 4DOCT images yet. Therefore, this paper evaluates motion tracking by applying state-of-the-art tracking schemes on maximum intensity projections (MIP) of 4D-OCT images. Estimated VOI location is used to conveniently show corresponding slices and to improve the MIPs by calculating thin-slab MIPs. Tracking performances are evaluated on an in-vivo sequence of human skin, captured at 26 volumes per second. Among investigated tracking schemes, our recently presented tracking scheme for soft tissue motion provides highest accuracy with an error of under 2.2 voxels for the first 80 volumes. Object tracking on 4D-OCT images enables its use for sub-epithelial tracking of microvessels for image-guidance.},
keywords = {4D imaging, maximum intensity projection, optical coherence tomography, feature tracking},
year = {2017},
doi = {10.1117/12.2255090},
URL = {https://doi.org/10.1117/12.2255090}
}
Matthias Eibl, Sebastian Karpf, Hubertus Hakert, Daniel Weng, and Robert Huber,
Two-photon-excited fluorescence (TPEF) and fluorescence lifetime imaging (FLIM) with sub-nanosecond pulses and a high analog bandwidth signal detection, in Multiphoton Microscopy in the Biomedical Sciences XVII , Ammasi Periasamy and Peter T. C. So and Karsten König and Xiaoliang S. Xie, Eds. SPIE, 022017. pp. 100691F.
DOI:10.1117/12.2250831
Bibtex: BibTeX
@inproceedings{10.1117/12.2250831,
author = {Matthias Eibl and Sebastian Karpf and Hubertus Hakert and Daniel Weng and Robert Huber},
title = {{Two-photon-excited fluorescence (TPEF) and fluorescence lifetime imaging (FLIM) with sub-nanosecond pulses and a high analog bandwidth signal detection}},
volume = {10069},
booktitle = {Multiphoton Microscopy in the Biomedical Sciences XVII},
editor = {Ammasi Periasamy and Peter T. C. So and Karsten K{\"o}nig and Xiaoliang S. Xie},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {100691F},
abstract = {Two-photon excited fluorescence (TPEF) microscopy and fluorescence lifetime imaging (FLIM) are powerful imaging techniques in bio-molecular science. The need for elaborate light sources for TPEF and speed limitations for FLIM, however, hinder an even wider application. We present a way to overcome this limitations by combining a robust and inexpensive fiber laser for nonlinear excitation with a fast analog digitization method for rapid FLIM imaging. The applied sub nanosecond pulsed laser source is synchronized to a high analog bandwidth signal detection for single shot TPEF- and single shot FLIM imaging. The actively modulated pulses at 1064nm from the fiber laser are adjustable from 50ps to 5ns with kW of peak power. At a typically applied pulse lengths and repetition rates, the duty cycle is comparable to typically used femtosecond pulses and thus the peak power is also comparable at same cw-power. Hence, both types of excitation should yield the same number of fluorescence photons per time on average when used for TPEF imaging. However, in the 100ps configuration, a thousand times more fluorescence photons are generated per pulse. In this paper, we now show that the higher number of fluorescence photons per pulse combined with a high analog bandwidth detection makes it possible to not only use a single pulse per pixel for TPEF imaging but also to resolve the exponential time decay for FLIM. To evaluate the performance of our system, we acquired FLIM images of a Convallaria sample with pixel rates of 1 MHz where the lifetime information is directly measured with a fast real time digitizer. With the presented results, we show that longer pulses in the many-10ps to nanosecond regime can be readily applied for TPEF imaging and enable new imaging modalities like single pulse FLIM.},
keywords = {FLIM, TPEF, fiber laser, endoscope, MOPA, Nonlinear microscopy, Fluorescence microscopy, Lifetime-based sensing},
year = {2017},
doi = {10.1117/12.2250831},
URL = {https://doi.org/10.1117/12.2250831}
}
Tianshi Wang, Tom Pfeiffer, Min Wu, Wolfgang Wieser, Wolfgang Draxinger, Antonius F. W. van der Steen, Robert Huber, and Gijs van Soest,
Short pulse laser induced thermo-elastic deformation imaging, in Optical Interactions with Tissue and Cells XXVIII , E. Duco Jansen and Hope Thomas Beier, Eds. SPIE, 022017. pp. 100620C.
DOI:10.1117/12.2251502
Bibtex: BibTeX
@inproceedings{10.1117/12.2251502,
author = {Tianshi Wang and Tom Pfeiffer and Min Wu and Wolfgang Wieser and Wolfgang Draxinger and Antonius F. W. van der Steen and Robert Huber and Gijs van Soest},
title = {{Short pulse laser induced thermo-elastic deformation imaging}},
volume = {10062},
booktitle = {Optical Interactions with Tissue and Cells XXVIII},
editor = {E. Duco Jansen and Hope Thomas Beier},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {100620C},
abstract = {Absorption of nanosecond laser pulses induces rapid thermo-elastic deformation in tissue, i.e. a sub-micrometer scale displacement happens within a couple of microseconds. In this study, we initially investigate the depth-resolved deformation using a 1.5 MHz phase-sensitive optical coherence tomography (OCT) system. Functional images can be reconstructed based on the detected deformation, which enables a new imaging modality called thermo-elastic deformation imaging (TDI). Our results show that the associated displacement is related to the optical absorption of the short laser pulses. The TDI images can provide tissue type information in addition to the conventional OCT images.},
keywords = {thermal-elastic deformation, optical coherence tomography},
year = {2017},
doi = {10.1117/12.2251502},
URL = {https://doi.org/10.1117/12.2251502}
}
Thomas Klein, and Robert Huber,
High-speed OCT light sources and systems [Invited], Biomed. Opt. Express , vol. 8, no. 2, pp. 828-859, 02 2017. Optica Publishing Group.
DOI:10.1364/BOE.8.000828
Bibtex: BibTeX
@article{Klein:17,
author = {Thomas Klein and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Imaging systems; Optical coherence tomography; Lasers and laser optics; Lasers, tunable; Optical coherence tomography; Full field optical coherence tomography; High speed imaging; Image quality; Imaging systems; Light wavelength; X ray imaging},
number = {2},
pages = {828--859},
publisher = {Optica Publishing Group},
title = {High-speed OCT light sources and systems \[Invited\]},
volume = {8},
month = {Feb},
year = {2017},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-8-2-828},
doi = {10.1364/BOE.8.000828},
abstract = {Imaging speed is one of the most important parameters that define the performance of optical coherence tomography (OCT) systems. During the last two decades, OCT speed has increased by over three orders of magnitude. New developments in wavelength-swept lasers have repeatedly been crucial for this development. In this review, we discuss the historical evolution and current state of the art of high-speed OCT systems, with focus on wavelength swept light sources and swept source OCT systems.},
}
Matthias Eibl, Sebastian Karpf, Daniel Weng, Hubertus Hakert, Tom Pfeiffer, Jan Philip Kolb, and Robert Huber,
Single pulse two photon fluorescence lifetime imaging (SP-FLIM) with MHz pixel rate, Biomed. Opt. Express , vol. 8, no. 7, pp. 3132-3142, 2017. Optica Publishing Group.
DOI:10.1364/BOE.8.003132
Bibtex: BibTeX
@article{Eibl:17,
author = {Matthias Eibl and Sebastian Karpf and Daniel Weng and Hubertus Hakert and Tom Pfeiffer and Jan Philip Kolb and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Fiber optics imaging; Nonlinear optics, fibers; Lasers, fiber; Lifetime-based sensing; Fluorescence microscopy; Nonlinear microscopy; Fourier domain mode locking; Image quality; Imaging techniques; Laser sources; Pulsed fiber lasers; Three dimensional sensing},
number = {7},
pages = {3132--3142},
publisher = {Optica Publishing Group},
title = {Single pulse two photon fluorescence lifetime imaging (SP-FLIM) with MHz pixel rate},
volume = {8},
month = {Jul},
year = {2017},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-8-7-3132},
doi = {10.1364/BOE.8.003132},
abstract = {Two-photon-excited fluorescence lifetime imaging microscopy (FLIM) is a chemically specific 3-D sensing modality providing valuable information about the microstructure, composition and function of a sample. However, a more widespread application of this technique is hindered by the need for a sophisticated ultra-short pulse laser source and by speed limitations of current FLIM detection systems. To overcome these limitations, we combined a robust sub-nanosecond fiber laser as the excitation source with high analog bandwidth detection. Due to the long pulse length in our configuration, more fluorescence photons are generated per pulse, which allows us to derive the lifetime with a single excitation pulse only. In this paper, we show high quality FLIM images acquired at a pixel rate of 1 MHz. This approach is a promising candidate for an easy-to-use and benchtop FLIM system to make this technique available to a wider research community.},
}
Tom Pfeiffer, Wolfgang Draxinger, Wolfgang Wieser, Thomas Klein, Markus Petermann, and Robert Huber,
Analysis of FDML lasers with meter range coherence, in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXI , James G. Fujimoto and Joseph A. Izatt and Valery V. Tuchin, Eds. SPIE, 2017. pp. 100531T.
DOI:10.1117/12.2254792
Bibtex: BibTeX
@inproceedings{10.1117/12.2254792,
author = {Tom Pfeiffer and Wolfgang Draxinger and Wolfgang Wieser and Thomas Klein and Markus Petermann and Robert Huber},
title = {{Analysis of FDML lasers with meter range coherence}},
volume = {10053},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXI},
editor = {James G. Fujimoto and Joseph A. Izatt and Valery V. Tuchin},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {100531T},
abstract = {FDML lasers provide sweep rates in the MHz range at wide optical bandwidths, making them ideal sources for high
speed OCT. Recently, at lower speed, ultralong-range swept-source OCT has been demonstrated using a tunable
vertical cavity surface emitting laser (VCSEL) and also using a Vernier-tunable laser. These sources provide relatively
high sweep rates and meter range coherence lengths. In order to achieve similar coherence, we developed an extremely
well dispersion compensated Fourier Domain Mode Locked (FDML) laser, running at 3.2 MHz sweep rate and 120 nm
spectral bandwidth. We demonstrate that this laser offers meter range coherence and enables volumetric long range OCT
of moving objects.},
keywords = {Optical coherence tomography, OCT, tunable laser, Fourier domain mode locking, FDML, MHz OCT},
year = {2017},
doi = {10.1117/12.2254792},
URL = {https://doi.org/10.1117/12.2254792}
}

2016

Sebastian Karpf, Matthias Eibl, Benjamin Sauer, Fred Reinholz, Gereon Hüttmann, and Robert Huber,
Two-photon microscopy using fiber-based nanosecond excitation, Biomed. Opt. Express , vol. 7, no. 7, pp. 2432-2440, 07 2016. Optica Publishing Group.
DOI:10.1364/BOE.7.002432
Bibtex: BibTeX
@article{Karpf:16,
author = {Sebastian Karpf and Matthias Eibl and Benjamin Sauer and Fred Reinholz and Gereon H\"{u}ttmann and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Fiber optics imaging; Nonlinear optics, fibers; Lasers, fiber; Fluorescence microscopy; Nonlinear microscopy; Femtosecond pulses; In vivo imaging; Laser sources; Nanosecond pulses; Optical systems; Ultrafast lasers},
number = {7},
pages = {2432--2440},
publisher = {Optica Publishing Group},
title = {Two-photon microscopy using fiber-based nanosecond excitation},
volume = {7},
month = {Jul},
year = {2016},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-7-7-2432},
doi = {10.1364/BOE.7.002432},
abstract = {Two-photon excitation fluorescence (TPEF) microscopy is a powerful technique for sensitive tissue imaging at depths of up to 1000 micrometers. However, due to the shallow penetration, for in vivo imaging of internal organs in patients beam delivery by an endoscope is crucial. Until today, this is hindered by linear and non-linear pulse broadening of the femtosecond pulses in the optical fibers of the endoscopes. Here we present an endoscope-ready, fiber-based TPEF microscope, using nanosecond pulses at low repetition rates instead of femtosecond pulses. These nanosecond pulses lack most of the problems connected with femtosecond pulses but are equally suited for TPEF imaging. We derive and demonstrate that at given cw-power the TPEF signal only depends on the duty cycle of the laser source. Due to the higher pulse energy at the same peak power we can also demonstrate single shot two-photon fluorescence lifetime measurements.},
}
Robert Huber, Lars Dworak, Jacques E. Moser, Michael Grätzel, and Josef Wachtveitl,
Beyond Vibrationally Mediated Electron Transfer: Coherent Phenomena Induced by Ultrafast Charge Separation, The Journal of Physical Chemistry C , vol. 120, no. 16, pp. 8534-8539, 04 2016.
DOI:10.1021/acs.jpcc.6b02012
Bibtex: BibTeX
@article{doi:10.1021/acs.jpcc.6b02012,
author = {Huber, Robert and Dworak, Lars and Moser, Jacques E. and Grätzel, Michael and Wachtveitl, Josef},
title = {Beyond Vibrationally Mediated Electron Transfer: Coherent Phenomena Induced by Ultrafast Charge Separation},
journal = {The Journal of Physical Chemistry C},
volume = {120},
number = {16},
pages = {8534-8539},
year = {2016},
doi = {10.1021/acs.jpcc.6b02012},

URL = { 
        https://doi.org/10.1021/acs.jpcc.6b02012
    
},
eprint = { 
        https://doi.org/10.1021/acs.jpcc.6b02012
    
}
,
    abstract = { Wave packet propagation succeeding electron transfer (ET) from alizarin dye molecules into the nanocrystalline TiO2 semiconductor has been studied by ultrafast transient absorption spectroscopy. Because of the ultrafast time scale of the ET reaction of about 6 fs, the system shows substantial differences to molecular ET systems. We show that the ET process is not mediated by molecular vibrations, and therefore classical ET theories lose their applicability. Here the ET reaction itself prepares a vibrational wave packet and not the electromagnetic excitation by the laser pulse. Furthermore, the generation of phonons during polaron formation in the TiO2 lattice is observed in real time for this system. The presented investigations enable an unambiguous assignment of the involved photoinduced mechanisms and can contribute to a corresponding extension of molecular ET theories to ultrafast ET systems like alizarin/TiO2. }
}
Tianshi Wang, Tom Pfeiffer, Evelyn Regar, Wolfgang Wieser, Heleen van Beusekom, Charles T. Lancee, Geert Springeling, Ilona Krabbendam-Peters, Antonius F. W. van der Steen, Robert Huber, and Gijs van Soest,
Heartbeat OCT and Motion-Free 3D In Vivo Coronary Artery Microscopy, JACC: Cardiovascular Imaging , vol. 9, no. 5, pp. 622-623, 2016.
DOI:10.1016/j.jcmg.2015.08.010
Bibtex: BibTeX
@article{WANG2016622,
title = {Heartbeat OCT and Motion-Free 3D In Vivo Coronary Artery Microscopy},
journal = {JACC: Cardiovascular Imaging},
volume = {9},
number = {5},
pages = {622-623},
year = {2016},
issn = {1936-878X},
doi = {https://doi.org/10.1016/j.jcmg.2015.08.010},
url = {https://www.sciencedirect.com/science/article/pii/S1936878X15006713},
author = {Tianshi Wang and Tom Pfeiffer and Evelyn Regar and Wolfgang Wieser and Heleen {van Beusekom} and Charles T. Lancee and Geert Springeling and Ilona Krabbendam-Peters and Antonius F.W. {van der Steen} and Robert Huber and Gijs {van Soest}}
}

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