The research group led by Robert Huber conducts research in the fields of optical coherence tomography (OCT), non-linear imaging and laser physics. Here, work is mainly done on novel pico second lasers and on Fourier domain mode-locked (FDML) lasers. This laser concept was developed by Robert Huber and enables the realization of particularly fast tunable laser light sources. The research focus here is on further technological development, understanding of the physical processes and also on the implementation of FDML lasers for OCT applications. Besides OCT, FDML lasers are also used for nonlinear imaging and spectroscopy.
Another focus is on optical coherence tomography with tunable light sources (swept source OCT, SS-OCT). Here, among other applications, the in-house developed FDML lasers are used for ultrafast imaging to generate cross-sectional images of biological tissues such as skin or eye. Due to the high tuning rate, applications like VR-OCT, which displays entire volumes in a virtual environment with real-time video repetition rates, are possible.
With non-linear optical imaging, the group is pursuing further imaging techniques. Research areas are in time-encoded (TICO) Raman spectroscopy and microscopy, two-photon fluorescence microscopy (TPEF), and two-photon single-pulse fluorescence lifetime imaging (SP-FLIM). These techniques use novel pico second lasers that are also being researched and developed in the group.
Our main research topics:
- Fourier Domain Mode Locked (FDML) lasers - laser physics, technology and application.
- Optical Coherence Tomography (OCT) - applications of MHz-OCT on skin and eye
- Non-linear microscopy and spectroscopy
- Pico second lasers
Publications
2019
Live video rate volumetric OCT imaging of the retina with multi-MHz A-scan rates, PLOS ONE , vol. 14, no. 7, pp. e0213144, 03 2019.
DOI: | 10.1371/journal.pone.0213144 |
Bibtex: | @article{Kolb2019, author = {Kolb, J P;Draxinger, W;Klee, J;Pfeiffer, T;Eibl, M;Klein, T;Wieser, W and Huber, R}, title = {Live video rate volumetric OCT imaging of the retina with multi-MHz A-scan rates}, journal = {J pone}, keywords = {AG-Huber_OCT}, url = {https://doi.org/10.1371/journal.pone.0213144}, pages = {e0213144}, ISSN = {1932-6203}, year = {2019}, type = {Journal Article} } |
Virtual HE histology by fiber-based picosecond two-photon microscopy, in Multiphoton Microscopy in the Biomedical Sciences XIX , Ammasi Periasamy; Peter T. C. So; Karsten König, Eds. International Society for Optics and Photonics, 022019. pp. 108822F.
DOI: | 10.1117/12.2507866 |
Bibtex: | @inproceedings{10.1117/12.2507866, author = {Jan Philip Kolb and Daniel Weng and Hubertus Hakert and Matthias Eibl and Wolfgang Draxinger and Tobias Meyer and Thomas Gottschall and Ralf Brinkmann and Reginald Birngruber and J{\"u}rgen Popp and Jens Limpert and Sebastian Nino Karpf and Robert Huber}, title = {{Virtual HE histology by fiber-based picosecond two-photon microscopy}}, volume = {10882}, booktitle = {Multiphoton Microscopy in the Biomedical Sciences XIX}, editor = {Ammasi Periasamy and Peter T. C. So and Karsten K{\"o}nig}, organization = {International Society for Optics and Photonics}, publisher = {SPIE}, pages = {108822F}, abstract = {Two-Photon Microscopy (TPM) can provide three-dimensional morphological and functional contrast in vivo. Through proper staining, TPM can be utilized to create virtual, HE equivalent images and thus can improve throughput in histology-based applications. We previously reported on a new light source for TPM that employs a compact and robust fiber-amplified, directly modulated laser. This laser is pulse-to-pulse wavelength switchable between 1064 nm, 1122 nm, and 1186 nm with an adjustable pulse duration from 50ps to 5ns and arbitrary repetition rates up to 1MHz at kW-peak powers. Despite the longer pulse duration, it can achieve similar average signal levels compared to fs-setups by lowering the repetition rate to achieve similar cw and peak power levels. The longer pulses lead to a larger number of photons per pulse, which yields single shot fluorescence lifetime measurements (FLIM) by applying a fast 4 GSamples/s digitizer. In the previous setup, the wavelengths were limited to 1064 nm and longer. Here, we use four wave mixing in a non-linear photonic crystal fiber to expand the wavelength range down to 940 nm. This wavelength is highly suitable for imaging green fluorescent proteins in neurosciences and stains such as acridine orange (AO), eosin yellow (EY) and sulforhodamine 101 (SR101) used for histology applications. In a more compact setup, we also show virtual HE histological imaging using a direct 1030 nm fiber MOPA.}, keywords = {Multiphoton Microscopy, Four Wave Mixing, FWM, Histology, Laser, Non Linear Microscopy, Two Photon Microscopy, JenLab Young Investigator Award}, year = {2019}, doi = {10.1117/12.2507866}, URL = {https://doi.org/10.1117/12.2507866} } |
Sectioning-Free Virtual H&E Imaging of Tissue Samples with Two-Photon Microscopy, in 31st Congress of the ESP , 2019.
DOI: | 10.1007/s00428-019-02631-8 |
Bibtex: | @InProceedings{Strauch2019, author = {Strauch, Matthias and Kolb, Jan Philip and Weng, Daniel and Wacker, Melanie and Draxinger, Wolfgang and Karpf, Sebastian and Huber, Robert}, booktitle = {31st Congress of the ESP}, title = {Sectioning-Free Virtual H&E Imaging of Tissue Samples with Two-Photon Microscopy}, year = {2019}, keywords = {AG-Huber_NL}, } |
Measurement of Inter-Sweep Phase Stability of an FDML Laser with a 10 kHz Tunable Ring Laser, in 2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference , Optical Society of America, 2019. pp. 1-1.
DOI: | 10.1109/CLEOE-EQEC.2019.8872860 |
Bibtex: | @inproceedings{Kastner:19, author = {Kastner, D; Bl\"{o}mker, T; Pfeiffer, T; Grill, C; Schmidt, M; Jirauschek, C and Huber, R}, booktitle = {2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference}, journal = {2019 Conference on Lasers and Electro-Optics Europe and European Quantum Electronics Conference}, keywords = {Fourier domain mode locking; Image quality; Optical coherence tomography; Phase noise; Ring lasers; Tunable lasers}, pages = {cj_7_5}, publisher = {Optical Society of America}, title = {Measurement of Inter-Sweep Phase Stability of an FDML Laser with a 10 kHz Tunable Ring Laser}, year = {2019}, keywords = {AG-Huber_FDML, AG-Huber_OCT}, doi = { 10.1109/CLEOE-EQEC.2019.8872860}, abstract = {Fourier Domain Mode Locking (FDML) lasers are light sources that generate a sequence of narrowband optical frequency sweeps at the fundamental or harmonic of the cavity repetition rate \[1\]. This frequency swept output can also be considered as a sequence of strongly chirped, long pulses. FDML lasers are mainly used in swept source optical coherence tomography (SS-OCT), a medical imaging technique. The coherence length of the source, i.e. the intra-sweep phase stability of an FDML sweep, is decisive for the image quality and performance of OCT imaging \[2\].}, } |
Coexistence of Intensity Pattern Types in Broadband Fourier Domain Mode Locked (FDML) Lasers, in 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) , 2019. pp. 1--1.
DOI: | 10.1109/CLEOE-EQEC.2019.8872381 |
Bibtex: | @inproceedings{schmidt2019coexistence, title={Coexistence of Intensity Pattern Types in Broadband Fourier Domain Mode Locked (FDML) Lasers}, author={Schmidt, M; Pfeiffer, T; Grill, C; Huber, R and Jirauschek, C}, booktitle={2019 Conference on Lasers and Electro-Optics Europe \& European Quantum Electronics Conference (CLEO/Europe-EQEC)}, pages={1--1}, year={2019}, organization={IEEE}, keywords= { AG-Huber_FDML}, url={ https://ieeexplore.ieee.org/document/8872381} } |
2018
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, Dec. 2018.
DOI: | 10.1007/s00417-017-3857-9 |
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} } |
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: | @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} } |
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: | @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.}, } |
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: | @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.}, } |
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: | @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.}, } |
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: | @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
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: | @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.}, } |
Thermo-elastic optical coherence tomography, Optica Publishing Group, 092017. pp. 3466-3469.
DOI: | 10.1364/OL.42.003466 |
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.}, } |
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: | @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} } |
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: | @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} } |
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: | @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} } |
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: | @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} } |
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: | @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} } |
Shot-Noise Limited Time-Encoded Raman Spectroscopy, Journal of Spectroscopy , vol. 2017, pp. 1-6, 03 2017. Hindawi.
DOI: | 10.1155/2017/9253475 |
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} } |
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: | @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} } |
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: | @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} } |
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: | @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} } |
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: | @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} } |
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: | @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.}, } |
Text