Research

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:

Publications

2023

Philipp Lamminger, Hubertus Hakert, Simon Lotz, Jan Philip Kolb, Tonio Kutscher, Sebastian Karpf, and Robert Huber,
Four-wave mixing seeded by a rapid wavelength-sweeping FDML laser for nonlinear imaging at 900 nm and 1300 nm, Opt. Lett. , vol. 48, no. 14, pp. 3713-3716, Jul. 2023. Optica Publishing Group.
DOI:10.1364/OL.488181
Bibtex: BibTeX
@article{Lamminger:23,
author = {Philipp Lamminger and Hubertus Hakert and Simon Lotz and Jan Philip Kolb and Tonio Kutscher and Sebastian Karpf and Robert Huber},
journal = {Opt. Lett.},
keywords = {Green fluorescent protein; Laser beam combining; Laser crystals; Laser imaging; Optical amplifiers; Photonic crystal lasers},
number = {14},
pages = {3713--3716},
publisher = {Optica Publishing Group},
title = {Four-wave mixing seeded by a rapid wavelength-sweeping FDML laser for nonlinear imaging at 900 nm and 1300 nm},
volume = {48},
month = {Jul},
year = {2023},
url = {https://opg.optica.org/ol/abstract.cfm?URI=ol-48-14-3713},
doi = {10.1364/OL.488181},
abstract = {Four-wave mixing (FWM) enables the generation and amplification of light in spectral regions where suitable fiber gain media are unavailable. The 1300 nm and 900 nm regions are of especially high interest for time-encoded (TICO) stimulated Raman scattering microscopy and spectro-temporal laser imaging by diffracted excitation (SLIDE) two-photon microscopy. We present a new, to the best of our knowledge, FWM setup where we shift the power of a home-built fully fiber-based master oscillator power amplifier (MOPA) at 1064 nm to the 1300-nm region of a rapidly wavelength-sweeping Fourier domain mode-locked (FDML) laser in a photonic crystal fiber (PCF) creating pulses in the 900-nm region. The resulting 900-nm light can be wavelength swept over 54 nm and has up to 2.5 kW (0.2 {\textmu}J) peak power and a narrow instantaneous spectral linewidth of 70 pm. The arbitrary pulse patterns of the MOPA and the fast wavelength tuning of the FDML laser (419 kHz) allow it to rapidly tune the FWM light enabling new and faster TICO-Raman microscopy, SLIDE imaging, and other applications.},
}
Wolfgang Draxinger, Dirk Theisen-Kunde, Lion Schützeck, Nicolas Detrez, Paul Strenge, Veit Danicke, Jessica Kren, Patrick Kuppler, Sonja Spahr-Hess, Matteo Mario Bonsanto, Ralf Brinkmann, and Robert Huber,
High speed 4D in-vivo OCT imaging of the human brain: creating high density datasets for machine learning toward identification of malign tissue in real time, in High-Speed Biomedical Imaging and Spectroscopy VIII , Kevin K. Tsia and Keisuke Goda, Eds. SPIE, Mar.2023. pp. 123900D.
DOI:10.1117/12.2648505
Bibtex: BibTeX
@inproceedings{10.1117/12.2648505,
author = {Wolfgang Draxinger and Dirk Theisen-Kunde and Lion Sch{\"u}tzeck and Nicolas Detrez and Paul Strenge and Veit Danicke and Jessica Kren and Patrick Kuppler and Sonja Spahr-Hess and Matteo Mario Bonsanto and Ralf Brinkmann and Robert Huber},
title = {{High speed 4D in-vivo OCT imaging of the human brain: creating high density datasets for machine learning toward identification of malign tissue in real time}},
volume = {12390},
booktitle = {High-Speed Biomedical Imaging and Spectroscopy VIII},
editor = {Kevin K. Tsia and Keisuke Goda},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {123900D},
abstract = {Neuro-surgery is challenged by the difficulties of determining brain tumor boundaries during excisions. Optical coherence tomography is investigated as an imaging modality for providing a viable contrast channel. Our MHz-OCT technology enables rapid volumetric imaging, suitable for surgical workflows. We present a surgical microscope integrated MHz-OCT imaging system, which is used for the collection of in-vivo images of human brains, with the purpose of being used in machine learning systems that shall be trained to identify and classify tumorous tissue.},
keywords = {optical coherence tomography, brain tumor, neurosurgery, machine learning, contrast augmentation, histology dataset, clinical study, in-vivo imaging},
year = {2023},
doi = {10.1117/12.2648505},
URL = {https://doi.org/10.1117/12.2648505}
}
Muhammad Asim Bashir, Simon Lotz, Marie Klufts, Igor Krestnikov, Christian Jirauschek, and Robert Huber,
1190 nm Fourier domain mode locked (FDML) laser for optical coherence tomography (OCT), in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII , Joseph A. Izatt and James G. Fujimoto, Eds. SPIE, Mar.2023. pp. 1236707.
DOI:10.1117/12.2652884
Bibtex: BibTeX
@inproceedings{10.1117/12.2652884,
author = {M. A. Bashir and S. Lotz and M. Klufts and I. Krestnikov and C. Jirauschek and R. Huber},
title = {{1190 nm Fourier domain mode locked (FDML) laser for optical coherence tomography (OCT)}},
volume = {12367},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1236707},
abstract = {We demonstrate a Fourier domain mode locked (FDML) laser centered at 1190 nm with 2×410 kHz sweep repetition rate, a sweeping range of 100 nm and 2.5 mW output power. The laser is based on a quantum dot-semiconductor optical amplifier with small linewidth enhancement factor. The laser could be used as a probe laser in stimulated Raman scattering microscopy and it may be attractive for optical coherence tomography due to low water absorption and the spectral signature of lipids around 1200nm. Moreover, it is ideal to close the gap between FDML lasers at 1064 nm and 1300 nm. Combining these three lasers can enable ultrawideband sweeping to improve the axial OCT resolution down to 2 μm. },
keywords = {FDML, Swept source, laser, SS-OCT, OCT, Tunable lasers},
year = {2023},
doi = {10.1117/12.2652884},
URL = {https://doi.org/10.1117/12.2652884}
}
Marie Klufts, Simon Lotz, Muhammad Asim Bashir, Tom Pfeiffer, Alexander Mlynek, Wolfgang Wieser, Alexander Chamorovskiy, Vladimir Shidlovski, and Robert Huber,
850 nm FDML: performance and challenges, in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII , Joseph A. Izatt and James G. Fujimoto, Eds. SPIE, Mar.2023. pp. 1236705.
DOI:10.1117/12.2649646
Bibtex: BibTeX
@inproceedings{10.1117/12.2649646,
author = {M. Klufts and S. Lotz and M. A. Bashir and T. Pfeiffer and A. Mlynek and W. Wieser and A. Chamorovskiy and V. Shidlovski and R. Huber},
title = {{850 nm FDML: performance and challenges}},
volume = {12367},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1236705},
abstract = {We demonstrate a Fourier domain mode locked (FDML) laser centered around 850 nm with a sweeping range of 50 nm, a fundamental repetition rate of 2×416 kHz and an output power of 2 mW. A new cavity design using three chirped Fiber Bragg gratings is required to overcome sweeping limitations caused by high dispersion. Other solutions to address challenges such as high loss and high polarization mode dispersion will be discussed along with performance. A main application of this laser will be retinal imaging, but it might also be applicable for TiCo-Raman and SLIDE microscopy. },
keywords = {Swept source, FDML, Laser, Ophthalmic imaging, OCT, 800 nm, retinal imaging, light sources},
year = {2023},
doi = {10.1117/12.2649646},
URL = {https://doi.org/10.1117/12.2649646}
}
Philipp Lamminger, Hubertus Hakert, Simon Lotz, Jan Philip Kolb, Tonio Kutscher, Sebastian Karpf, and Robert Huber,
900 nm swept source FDML laser with kW peak power, in Fiber Lasers XX: Technology and Systems , V. R. Supradeepa, Eds. SPIE, Mar.2023. pp. 124001I.
DOI:10.1117/12.2649663
Bibtex: BibTeX
@inproceedings{10.1117/12.2649663,
author = {Philipp Lamminger and Hubertus Hakert and Simon Lotz and Jan Philip Kolb and Tonio Kutscher and Sebastian Karpf and Robert Huber},
title = {{900 nm swept source FDML laser with kW peak power}},
volume = {12400},
booktitle = {Fiber Lasers XX: Technology and Systems},
editor = {V.  R. Supradeepa},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {124001I},
abstract = {A wavelength agile 900 nm 2.5 kW peak power fiber laser is created by four-wave mixing (FWM) in a photonic crystal fiber (PCF), while amplifying a 1300 nm Fourier-domain mode-locked (FDML) laser. The FWM process is pumped by a home-built 1064 nm master oscillator power amplifier (MOPA) laser and seeded by a home-built 1300 nm FDML laser, generating high power pulses at wavelengths, where amplification by active fiber media is difficult. The 900 nm pulses have a spectral linewidth of 70 pm, are tunable over 54 nm and have electronic pulse-to-pulse tuning capability. These pulses can be used for nonlinear imaging like two-photon or coherent anti-Stokes Raman microscopy (CARS) microscopy including spectro-temporal laser imaging by diffracted excitation (SLIDE) and time-encoded (Tico) stimulated Raman microscopy.},
keywords = {Fourier domain mode locking,  FDML, Raman, two photon microscopy, SLIDE, 900 nm, fiber laser, photonic crystal fiber, swept source},
year = {2023},
doi = {10.1117/12.2649663},
URL = {https://doi.org/10.1117/12.2649663}
}
Sazgar Burhan, Nicolas Detrez, Katharina Rewerts, Madita Göb, Christian Hagel, Matteo M. Bonsanto, Dirk Theisen-Kunde, Robert Huber, and Ralf Brinkmann,
Characterization of brain tumor tissue by time-resolved, phase-sensitive optical coherence elastography at 3.2 MHz line rate, in Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XXI , Caroline Boudoux and James W. Tunnell, Eds. SPIE, Mar.2023. pp. 123680F.
DOI:10.1117/12.2648301
Bibtex: BibTeX
@inproceedings{10.1117/12.2648301,
author = {Sazgar Burhan and Nicolas Detrez and Katharina Rewerts and Madita G{\"o}b and Christian Hagel and Matteo Mario Bonsanto and Dirk Theisen-Kunde and Robert Huber and Ralf Brinkmann},
title = {{Characterization of brain tumor tissue by time-resolved, phase-sensitive optical coherence elastography at 3.2 MHz line rate}},
volume = {12368},
booktitle = {Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XXI},
editor = {Caroline Boudoux and James W. Tunnell},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {123680F},
abstract = {Optical coherence elastography (OCE) offers the possibility of obtaining the mechanical behavior of a tissue. When also  using a non-contact mechanical excitation, it mimics palpation without interobserver variability. One of the most frequently  used techniques is phase-sensitive OCE. Depending on the system, depth-resolved changes in the sub-µm to nm range can  be detected and visualized volumetrically. Such an approach is used in this work to investigate and detect transitions  between healthy and tumorous brain tissue as well as inhomogeneities in the tumor itself to assist the operating surgeon  during tumor resection in the future. We present time-resolved, phase-sensitive OCE measurements on various ex vivo brain tumor samples using an ultra-fast 3.2 MHz swept-source optical coherence tomography (SS-OCT) system with a frame rate of 2.45 kHz. 4 mm line scans are acquired which, in combination with the high imaging speed, allow monitoring and investigation of the sample's behavior in response to the mechanical load. Therefore, an air-jet system applies a 200 ms  short air pulse to the sample, whose non-contact property facilitates the possibility for future in vivo measurements. Since we can temporally resolve the response of the sample over the entire acquisition time, the mechanical properties are evaluated at different time points with depth resolution. This is done by unwrapping the phase data and performing subsequent assessment. Systematic ex vivo brain tumor measurements were conducted and visualized as distribution maps.  The study outcomes are supported by histological analyses and examined in detail.},
keywords = { Optical Coherence Tomography, Optical Coherence Elastography, Phase-sensitive OCT, Fourier Domain Mode Locking, Brain Tumor, Phase Unwrapping, Tissue Characterization, Biomechanics},
year = {2023},
doi = {10.1117/12.2648301},
URL = {https://doi.org/10.1117/12.2648301}
}
Madita Göb, Simon Lotz, Linh Ha-Wissel, Sazgar Burhan, Sven Böttger, Floris Ernst, Jennifer Hundt, and Robert Huber,
Large area robotically assisted optical coherence tomography (LARA-OCT) for skin imaging with MHz-OCT surface tracking, in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII , Joseph A. Izatt and James G. Fujimoto, Eds. SPIE, Mar.2023. pp. 123670C.
DOI:10.1117/12.2652616
Bibtex: BibTeX
@inproceedings{10.1117/12.2652616,
author = {Madita G{\"o}b and Simon Lotz and Linh Ha-Wissel and Sazgar Burhan and Sven B{\"o}ttger and Floris Ernst and Jennifer Hundt and Robert Huber},
title = {{Large area robotically assisted optical coherence tomography (LARA-OCT) for skin imaging with MHz-OCT surface tracking}},
volume = {12367},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {123670C},
abstract = {Optical coherence tomography (OCT) is a powerful imaging technique to non-invasively differentiate between healthy skin and pathological conditions. Unfortunately, commercially available OCT-systems are typically slow and not capable of scanning large areas at reasonable speed. Since skin lesions may extend over several square centimeters, potential inflammatory infiltrates remain undetected. Here, we present large area robotically assisted OCT (LARA-OCT) for skin imaging. Therefor a collaborative robot is combined with an existing, home-built 3.3 MHz-OCT-system and for surface tracking an online probe-to-surface control is implemented which is solely based on the OCT surface signal. It features a combined surface-distance and surface-orientation closed-loop control algorithm, which enables automatic positioning and alignment of the probe across the target while imaging. This allows to acquire coherent OCT images of skin areas beyond 10 cm<sup>2</sup>. },
keywords = {Optical Coherence Tomography, Fourier Domain Mode Locking, Robotically Assisted Imaging Systems, Three-dimensional image acquisition, Large Area Scanning, Skin Imaging , OCT, FDML},
year = {2023},
doi = {10.1117/12.2652616},
URL = {https://doi.org/10.1117/12.2652616}
}
Awanish P. Singh, Madita Göb, Martin Ahrens, Tim Eixmann, Hinnerk Schulz-Hildebrandt, Gereon Hüttmann, Robert Huber, and Maik Rahlves,
Synchronous high-speed OCT imaging with sensor less brushless DC motor and FDML laser in a phase-locked loop, in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII , Joseph A. Izatt and James G. Fujimoto, Eds. SPIE, Mar.2023. pp. 1236703.
DOI:10.1117/12.2652955
Bibtex: BibTeX
@inproceedings{10.1117/12.2652955,
author = {Awanish Pratap Singh and Madita G{\"o}b and Martin Ahrens and Tim Eixmann and Hinnerk Schulz-Hildebrandt and Gereon H{\"u}ttmann and Robert Huber and Maik Rahlves},
title = {{Synchronous high-speed OCT imaging with sensor less brushless DC motor and FDML laser in a phase-locked loop}},
volume = {12367},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1236703},
abstract = {High-speed endoscopic optical coherence tomography (OCT) imaging in the MHz range has shown great potential in various medical applications ranging from cancer screening to vascular disease monitoring. High-speed imaging always suffers from non-uniform rotational distortion (NURD) due to asynchronous motor rotation with the OCT system. Several research groups have previously attempted to solve this problem, using either an expensive motor with a sensor or numerical correction after data acquisition. However, both techniques pose challenges for practical use. Therefore, in this study, we use an inexpensive sensorless brushless DC motor with a Fourier domain mode-locked (FDML) laser-based MHz OCT system and try to resolve the problem of synchronization using three different modalities, (i) Slave-mode: The FDML frequency serves as a master frequency for the motor, which is phase-locked to the FDML frequency, (ii) Master-mode: The revolution trigger obtained from the motor’s back electromotive force (BEMF) signal serves as a trigger signal for the OCT imaging system, (iii) Both: Fully synchronized setup, where the motor rotation is synchronized with the laser and the imaging system is synchronized with the motor to achieve phase-stable OCT imaging. The first case slightly fluctuates in live preview and imaging due to the absence of a revolution trigger, while the second has varying motor speeds. Therefore, we use the third case to phase-lock the motor with FDML and get a distortion-free live preview and image acquisition. Finally, we demonstrate high-speed SS-OCT structural imaging (at 3.3 MHz A-scan rates) of a finger with a 16 mm diameter probe (at 40,000 rpm).},
keywords = {Optical Coherence Tomography, Endoscopy, FDML , Closed Loop Motor Control, NURD compensation, Brushless DC Motor, Back Electromotive Force},
year = {2023},
doi = {10.1117/12.2652955},
URL = {https://doi.org/10.1117/12.2652955}
}
Paul Strenge, Birgit Lange, Wolfgang Draxinger, Christian Hagel, Christin Grill, Veit Danicke, Dirk Theisen-Kunde, Sonja Spahr-Hess, Matteo M. Bonsanto, Robert Huber, Heinz Handels, and Ralf Brinkmann,
Dual wavelength analysis and classification of brain tumor tissue with optical coherence tomography, in Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XXI , Caroline Boudoux and James W. Tunnell, Eds. SPIE, Mar.2023. pp. 1236805.
DOI:10.1117/12.2649963
Bibtex: BibTeX
@inproceedings{10.1117/12.2649963,
author = {Paul Strenge and Birgit Lange and Wolfgang Draxinger and Christian Hagel and Christin Grill and Veit Danicke and Dirk Theisen-Kunde and Sonja Spahr-Hess and Matteo M. Bonsanto and Robert Huber and Heinz Handels and Ralf Brinkmann},
title = {{Dual wavelength analysis and classification of brain tumor tissue with optical coherence tomography}},
volume = {12368},
booktitle = {Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XXI},
editor = {Caroline Boudoux and James W. Tunnell},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1236805},
abstract = {The ill-defined tumor borders of glioblastoma multiforme pose a major challenge for the surgeon during tumor resection,  since the goal of the tumor resection is the complete removal, while saving as much healthy brain tissue as possible. In  recent years, optical coherence tomography (OCT) was successfully used to classify white matter from tumor infiltrated  white matter by several research groups. Motivated by these results, a dataset was created, which consisted of sets of  corresponding ex vivo OCT images, which were acquired by two OCT-systems with different properties (e.g. wavelength  and resolution). Each image was annotated with semantic labels. The labels differentiate between white and gray matter  and three different stages of tumor infiltration. The data from both systems not only allowed a comparison of the ability of  a system to identify the different tissue types present during the tumor resection, but also enable a multimodal tissue  analysis evaluating corresponding OCT images of the two systems simultaneously. A convolutional neural network with  dirichlet prior was trained, which allowed to capture the uncertainty of a prediction. The approach increased the sensitivity  of identifying tumor infiltration from 58 % to 78 % for data with a low prediction uncertainty compared to a previous  monomodal approach. },
keywords = {optical coherence tomography, oct, brain, classification, tumor, dual wavelength, glioblastoma multiforme, tissue analysis},
year = {2023},
doi = {10.1117/12.2649963},
URL = {https://doi.org/10.1117/12.2649963}
}
Matthias Strauch, Jan Philip Kolb, Christian Rose, Nadine Merg, Jennifer Hundt, Christiane Kümpers, Sven Perner, Sebastian Karpf, and Robert Huber,
Accelerating intraoperative tumor histology with sectioning-free multiphoton microscopy, European Journal of Surgical Oncology , vol. 49, no. 2, pp. e210, Feb. 2023.
DOI:https://doi.org/10.1016/j.ejso.2022.11.575
File: S0748798322013245
Bibtex: BibTeX
@article{STRAUCH2023e210,
title = {Accelerating intraoperative tumor histology with sectioning-free multiphoton microscopy},
journal = {European Journal of Surgical Oncology},
volume = {49},
number = {2},
pages = {e210},
year = {2023},
issn = {0748-7983},
doi = {https://doi.org/10.1016/j.ejso.2022.11.575},
url = {https://www.sciencedirect.com/science/article/pii/S0748798322013245},
author = {Matthias Strauch and Jan Philip Kolb and Christian Rose and Nadine Merg and Jennifer Hundt and Christiane Kümpers and Sven Perner and Sebastian Karpf and Robert Huber}
}
Sazgar Burhan, Nicolas Detrez, Katharina Rewerts, Madita Göb, Steffen Buschschlüter, Christian Hagel, Matteo M. Bonsanto, Dirk Theisen-Kunde, Robert Huber, and Ralf Brinkmann,
Phase analysis strategies for MHz OCE in the large displacement regime, in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII , Joseph A. Izatt and James G. Fujimoto, Eds. SPIE, 2023. pp. 123670Q.
DOI:10.1117/12.2652847
Bibtex: BibTeX
@inproceedings{10.1117/12.2652847,
author = {Sazgar Burhan and Nicolas Detrez and Katharina Rewerts and Madita G{\"o}b and Steffen Buschschl{\"u}ter and Christian Hagel and Matteo Mario Bonsanto M.D. and Dirk Theisen-Kunde and Robert Huber and Ralf Brinkmann},
title = {{Phase analysis strategies for MHz OCE in the large displacement regime}},
volume = {12367},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVII},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {123670Q},
abstract = {In neurosurgical tumor operations on the central nervous system, intraoperative haptic information often assists for discrimination between healthy and diseased tissue. Thus, it can provide the neurosurgeon with additional intraoperative source of information during resection, next to the visual information by the light microscope, fluorescent dyes and neuronavigation. One approach to obtain elastic and viscoelastic tissue characteristics non-subjectively is phase-sensitive optical coherence elastography (OCE), which is based on the principle of optical coherence tomography (OCT). While phase-sensitive OCE offers significantly higher displacement sensitivity inside a sample than commonly used intensity-based correlation methods, it requires a reliable algorithm to recover the phase signal, which is mathematically restricted in the -&pi; to &pi; range. This problem of phase wrapping is especially critical for inter-frame phase analysis since the time intervals between two referenced voxels is long. Here, we demonstrate a one-dimensional unwrapping algorithm capable of removing up to 4&pi;-ambiguities between two frames in the complex phase data obtained from a 3.2 MHz-OCT system. The high sampling rate allows us to resolve large sample displacements induced by a 200 ms air pulse and acquires pixel-precise detail information. The deformation behavior of the tissue can be monitored over the entire acquisition time, offering various subsequent mechanical analysis procedures. The reliability of the algorithm and imaging concept was initially evaluated using different brain tumor mimicking phantoms. Additionally, results from human ex vivo brain tumor samples are presented and correlated with histological findings supporting the robustness of the algorithm.},
keywords = {Optical Coherence Tomography, Megahertz OCT, Fourier Domain Mode Locking, Optical Coherence Elastography, Phase-sensitive OCT, Phase Unwrapping, Brain tumor, Biomechanics},
year = {2023},
doi = {10.1117/12.2652847},
URL = {https://doi.org/10.1117/12.2652847}
}

2022

Linh Ha-Wissel, Handan Yasak, Robert Huber, Detlef Zillikens, Ralf J. Ludwig, Diamant Thaci, and Jennifer E. Hundt,
Case report: Optical coherence tomography for monitoring biologic therapy in psoriasis and atopic dermatitis, Frontiers in Medicine , vol. 9, Sep. 2022.
DOI:10.3389/fmed.2022.995883
File: fmed.2022.995883
Bibtex: BibTeX
@article{RN5359,
   author = {Ha-Wissel, L.;Yasak, H.;Huber, R.;Zillikens, D.;Ludwig, R. J.;Thaçi, D. and Hundt, J. E.},
   title = {Case report: Optical coherence tomography for monitoring biologic therapy in psoriasis and atopic dermatitis},
   journal = {Front Med (Lausanne)},
   volume = {9},
   pages = {995883},
   ISSN = {2296-858X (Print)
2296-858x},
   DOI = {10.3389/fmed.2022.995883},
   year = {2022},
   type = {Journal Article}
}
Paul Strenge, Birgit Lange, Wolfgang Draxinger, Christin Grill, Veit Danicke, Dirk Theisen-Kunde, Christian Hagel, Sonja Spahr-Hess, Matteo M. Bonsanto, Heinz Handels, Ralf Brinkmann, and Robert Huber,
Differentiation of different stages of brain tumor infiltration using optical coherence tomography: Comparison of two systems and histology, Frontiers in Oncology , Aug. 2022.
DOI:10.3389/fonc.2022.896060
Bibtex: BibTeX
@article{Strenge-2022,
   author = {Strenge, P.;Lange, B.;Grill,C.;Danicke,V.;Theisen-Kunde, D.;Hagel, C.;Spahr-Hess, S.;;Bonsanto, Matteo M.;Handels, H.; and Huber, R.;Brinkmann, R.},
   title = {Differentiation of different stages of brain tumor infiltration using optical coherence tomography: Comparison of two systems and histology},
   journal = {Frontiers in Oncology},
Keywords = {AG-Huber_FDML, AG-Huber_OCT, brain, tumor, glioblastoma multiforme, OCT, neural network, attenuation (absorption)
coefficient, optical coherence tomography},
   DOI = {https://doi.org/10.3389/fonc.2022.896060},
   url = {https://www.frontiersin.org/articles/10.3389/fonc.2022.896060/full},
   year = {2022},
   type = {Journal Article}
}
Christin Grill, Torben Blömker, Mark Schmidt, Dominic Kastner, Tom Pfeiffer, Jan Philip Kolb, Wolfgang Draxinger, Sebastian Karpf, Christian Jirauschek, and Robert Huber,
Towards phase-stabilized Fourier domain mode-locked frequency combs, Communications Physics , vol. 5, no. 1, Aug. 2022. Springer Science and Business Media LLC.
DOI:10.1038/s42005-022-00960-w
Bibtex: BibTeX
@article{Grill2022,
  doi = {10.1038/s42005-022-00960-w},
  year = {2022},
  publisher = {Springer Science and Business Media {LLC}},
  volume = {{5}},
  number = {{1}},
  author = {C. Grill, T. Bl\"{o}mker, M. Schmidt, D. Kastner, T. Pfeiffer, J.P. Kolb, W. Draxinger, S. Karpf, C. Jirauschek and R. Huber},
  title = {Towards phase-stabilized Fourier domain mode-locked frequency combs},
  journal = {{Communications Physics}},
keywords={AG-Huber_FDML, FDML, Fourier domain mode locking, phase, frequency comb, coherence, beating}
}
Paul Strenge, Birgit Lange, Christin Grill, Wolfgang Draxinger, Veit Danicke, Dirk Theisen-Kunde, Christian Hagel, Sonja Spahr-Hess, Matteo M. Bonsanto, Robert Huber, Heinz Handels, and Ralf Brinkmann,
Registration of histological brain images onto optical coherence tomography images based on shape information, Physics in Medicine & Biology , Jun. 2022.
DOI:10.1088/1361-6560/ac6d9d
Bibtex: BibTeX
@article{Strenge2022,
   author = {Strenge, P;Lange, B;Grill, C;Draxinger, W;Danicke, V;Theisen-Kunde, D;Hagel, C;Spahr-Hess, S;Bonsanto, Matteo M.;Huber, R;Handels, H and Brinkmann, R},
   title = {Registration of histological brain images onto optical coherence tomography images based on shape information},
keywords = {brain, glioblastoma multiforme, shape, OCT, optical coherence tomography, AG-Huber_OCT,},
   journal = {Physics in Medicine & Biology},
   ISSN = {0031-9155},
   url = {http://iopscience.iop.org/article/10.1088/1361-6560/ac6d9d},
   year = {2022},
   type = {Journal Article}
}
Madita Göb, Sazgar Burhan, Simon Lotz, and Robert Huber,
Towards ultra-large area vascular contrast skin imaging using multi-MHz-OCT, in Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVI , Joseph A. Izatt and James G. Fujimoto, Eds. SPIE, Mar.2022. pp. 27 -- 31.
DOI:10.1117/12.2612171
Bibtex: BibTeX
@inproceedings{10.1117/12.2612171,
author = {Madita G{\"o}b and Sazgar Burhan and Simon Lotz and Robert Huber},
title = {{Towards ultra-large area vascular contrast skin imaging using multi-MHz-OCT}},
volume = {11948},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXVI},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1194807},
abstract = {We demonstrate ultra-large field of view OCT scanning using standard optics, a X-Y-galvanometer scanner and a synchronously driven motorized XYZ-positioning stage. The integration of a movable stage into our self-built 3.3 MHz- OCT system allows acquiring coherent ultra-large area images, fully leveraging the high speed potential of our system. For fast OCT-angiography, one galvanometer axis scanner is driven in a repetitive sawtooth pattern, fully synchronized to the movement of the linear stage, to obtain multiple measurements at each position. This technique requires exact synchronization, precise repositioning, and uniform movements with low tolerances to ensure a minimum revisitation error. We analyze error and performance of our setup and demonstrate angiographic imaging.},
keywords = {Optical Coherence Tomography, Fourier Domain Mode Locking, FDML, Optical Coherence Angiography, OCTA, Medical optics and biotechnology, Medical imaging, Three-dimensional image acquisition, Scanners, Microscopy},
year = {2022},
doi = {10.1117/12.2612171},
URL = {https://doi.org/10.1117/12.2612171}
}
Marie Klufts, Simon Lotz, Muhammad Asim Bashir, Sebastian Karpf, and Robert Huber,
Ultra-high-accuracy chromatic dispersion measurement in optical fibers, in Optical Components and Materials XIX , Shibin Jiang and Michel J. F. Digonnet, Eds. SPIE, Mar.2022. pp. 119970L.
DOI:10.1117/12.2608773
Bibtex: BibTeX
@inproceedings{10.1117/12.2608773,
author = {M. Klufts and S. Lotz and M. Bashir and S. Karpf and R. Huber},
title = {{Ultra-high-accuracy chromatic dispersion measurement in optical fibers}},
volume = {11997},
booktitle = {Optical Components and Materials XIX},
editor = {Shibin Jiang and Michel J. F. Digonnet},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {119970L},
abstract = {The chromatic dispersion in optical fibers is a key property for applications where a broadband light source is used and the timing of each individual wavelength is crucial. Counteracting the timing offset introduced by the fiber is a challenge in many applications especially in mode locked lasers. The dispersion parameters need to be measured with high precision. The length of the fiber, the temperature, and the used wavelength will highly impact the amount of dispersion and the accuracy of the measurement. We developed an ultra-high-accuracy dispersion measurement setup at 1080 &plusmn; 50 nm considering all the parameters that may influence the measurement. It is based on a home-built wavelength tunable laser where the output is modulated by an electro-optical modulator connected to a 24 GSamples/s arbitrary waveform generator to a complex pattern consisting of pulses and a 4 GHz sine wave. After passing through the fiber the signal is measured with an 80 GSamples/s real time oscilloscope. The fiber’s temperature is controlled to allow for reproducible measurements over several days and we achieve timing measurement accuracies down to ~200 fs. We also present the performance of the setup at ~850 nm. We will discuss and quantify all effects which can negatively impact the system accuracy and we will report on more cost-effective options using lower performance equipment.},
keywords = {Dispersion measurement, Chromatic dispersion, fiber dispersion measurement, optical component characterization, tunable laser, FDML},
year = {2022},
doi = {10.1117/12.2608773},
URL = {https://doi.org/10.1117/12.2608773}
}
Aaron Doug Deen, Heleen van Beusekom, Tom Pfeiffer, Mathijs Stam, Dominique de Kleijn, Jolanda Wentzel, Robert Huber, Antonius F. W. van der Steen, Gijs van Soest, and Tianshi Wang,
Spectroscopic thermo-elastic optical coherence tomography for tissue characterization, Biomedical Optics Express , vol. 13(3), pp. 1430-1446, Feb. 2022.
DOI:10.1364/BOE.447911
Bibtex: BibTeX
@article{Deen2022,
   author = {Deen, A D;Van Beusekom, H M. M.;Pfeiffer, T;Stam, M;Kleijn, D De;Wentzel, J;Huber, R;Van Der Steen, A F. W.;Soest, G Van and Wang, T},
   title = {Spectroscopic thermo-elastic optical coherence tomography for tissue characterization},
   journal = {BioOptExpr},
keywords = {AG-Huber, Endoscopic imaging, Image processing, Image quality, Imaging techniques, Optical imaging, Tissue characterization},
   volume = {13(3)},
   pages = {1430-1446},
   DOI = {10.1364/BOE.447911},
    year = {2022},
   type = {Journal Article}
}
Madita Göb, Tom Pfeiffer, Wolfgang Draxinger, Simon Lotz, Jan Philip Kolb, and Robert Huber,
Continuous spectral zooming for in vivo live 4D-OCT with MHz A-scan rates and long coherence, Biomed. Opt. Express , vol. 13, no. 2, pp. 713--727, Feb. 2022. OSA.
DOI:10.1364/BOE.448353
Bibtex: BibTeX
@article{Gob:22,
author = {Madita G\"{o}b and Tom Pfeiffer and Wolfgang Draxinger and Simon Lotz and Jan Philip Kolb and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {High speed imaging; Image processing; Image quality; In vivo imaging; Range imaging; Vertical cavity surface emitting lasers},
number = {2},
pages = {713--727},
publisher = {Optica Publishing Group},
title = {Continuous spectral zooming for in vivo live 4D-OCT with MHz A-scan rates and long coherence},
volume = {13},
month = {Feb},
year = {2022},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-13-2-713},
doi = {10.1364/BOE.448353},
abstract = {We present continuous three-dimensional spectral zooming in live 4D-OCT using a home-built FDML based OCT system with 3.28 MHz A-scan rate. Improved coherence characteristics of the FDML laser allow for imaging ranges up to 10 cm. For the axial spectral zoom feature, we switch between high resolution and long imaging range by adjusting the sweep range of our laser. We present a new imaging setup allowing for synchronized adjustments of the imaging range and lateral field of view during live OCT imaging. For this, a novel inline recalibration algorithm was implemented that enables numerical k-linearization of the raw OCT fringes for every frame instead of every volume. This is realized by acquiring recalibration data within the dead time of the raster scan at the turning points of the fast axis scanner. We demonstrate in vivo OCT images of fingers and hands at different resolution modes and show real three-dimensional zooming during live 4D-OCT. A three-dimensional spectral zooming feature for live 4D-OCT is expected to be a useful tool for a wide range of biomedical, scientific and research applications, especially in OCT guided surgery.},
}
Konstantin Yashin, Matteo Mario Bonsanto, Ksenia Achkasova, Anna Zolotova, Al-Madhaji Wael, Elena Kiseleva, Alexander Moiseev, Igor Medyanik, Leonid Kravets, Robert Huber, Ralf Brinkmann, and Natalia Gladkova,
OCT-Guided Surgery for Gliomas: Current Concept and Future Perspectives, Diagnostics , vol. 12, no. 2, pp. 335, Jan. 2022.
DOI:10.3390/diagnostics12020335
File: 335
Bibtex: BibTeX
@article{Yashin-2022,
   author = {Yashin, K;Bonsanto, M M;Achkasova, K;Zolotova, A;Wael, Al-M;Kiseleva, E;Moiseev, A;Medyanik, I;Kravets, L;Huber, R;Brinkmann, R and Gladkova, N},
   title = {OCT-Guided Surgery for Gliomas: Current Concept and Future Perspectives},
   journal = {Diagnostics},
   volume = {12},
   number = {2},
   pages = {335},
   ISSN = {2075-4418},
keywords = {AG-Huber; optical coherence tomography; brain imaging; neurosurgical guidance; brain tumor; minimally invasive theranostics; intraoperative imaging},
   url = {https://www.mdpi.com/2075-4418/12/2/335},
   year = {2022},
   type = {Journal Article}
}

2021

Paul Strenge, Birgit Lange, Christin Grill, Wolfgang Draxinger, Veit Danicke, Dirk Theisen-Kunde, Heinz Handels, Matteo M. Bonsanto, Christian Hagel, Robert Huber, and Ralf Brinkmann,
Comparison of two optical coherence tomography systems to identify human brain tumor, Optical Society of America, Dec.2021. pp. EW1C.7.
DOI:10.1117/12.2616044
Bibtex: BibTeX
@inproceedings{Strenge:21,
author = {P. Strenge, B. Lange, C. Grill, W. Draxinger, V. Danicke, D. Theisen-Kunde, H. Handels, M. M. Bonsanto, C. Hagel, R. Huber and R. Brinkmann},
journal = {European Conferences on Biomedical Optics 2021 (ECBO)},
keywords = {AG-Huber_OCT; Absorption coefficient; Attenuation coefficient; Fourier domain mode locking; Multiple scattering; Optical coherence tomography; Spectral domain optical coherence tomography},
pages = {EW1C.7},
publisher = {Optical Society of America},
title = {Comparison of two optical coherence tomography systems to identify human brain tumor},
year = {2021},
url = {https://doi.org/10.1117/12.2616044},
abstract = {The identification of ex vivo brain tumor tissue was investigated with two different optical coherence tomography systems exploiting two optical parameters. The optical parameters were calculated from semantically labelled OCT B-scans.},
}
Madita Göb, Sazgar Burhan, Wolfgang Draxinger, Jan Philip Kolb, and Robert Huber,
Towards densely sampled ultra-large area multi-MHz-OCT for in vivo skin measurements beyond 1 cm2/sec, in European Conferences on Biomedical Optics 2021 (ECBO) , Optical Society of America, Dec.2021. pp. EW3C.4.
DOI:10.1117/12.2616054
Bibtex: BibTeX
@inproceedings{Gob:21,
author = {Madita G\"{o}b and Sazgar Burhan and Wolfgang Draxinger and Jan Philip Kolb and Robert Huber},
booktitle = {European Conferences on Biomedical Optics 2021 (ECBO)},
journal = {European Conferences on Biomedical Optics 2021 (ECBO)},
keywords = {AG-Huber_OCT;Fourier domain mode locking; Image processing; Image quality; Optical coherence tomography; Temporal resolution; Three dimensional imaging},
pages = {EW3C.4},
publisher = {Optical Society of America},
title = {Towards densely sampled ultra-large area multi-MHz-OCT for in vivo skin measurements beyond 1 cm$^2$/sec},
year = {2021},
url = {http://www.osapublishing.org/abstract.cfm?URI=ECBO-2021-EW3C.4},
abstract = {We demonstrate a 3.3 MHz A-scan rate OCT for rapid scanning of large areas of human skin. The mosaicking performance and different OCT imaging modalities including intervolume speckle contrast are evaluated.},
}
Nicolas Detrez, Katharina Rewerts, Moritz Matthiae, Steffen Buschschlüter, Matteo M. Bonsanto, Dirk Theisen-Kunde, and Ralf Brinkmann,
Flow Controlled Air Puff Generator Towards In Situ Brain Tumor Detection Based on MHz Optical Coherence Elastography, in ECBO , Optical Society of America, Dec.2021. pp. EW4A.10.
Weblink: https://opg.optica.org/abstract.cfm?uri=ECBO-2021-EW4A.10
Bibtex: BibTeX
@inproceedings{Detrez:21,
author = {N. Detrez, K. Rewerts, M. Matthiae, S. Buschschlueter, M.M. Bonsanto, D. Theisen-Kunde and R. Brinkmann},
journal = {European Conferences on Biomedical Optics 2021 (ECBO)},
keywords = {AG-Huber_OCT},
pages = {EW4A.10},
publisher = {Optical Society of America},
title = {Flow Controlled Air Puff Generator Towards In Situ Brain Tumor Detection Based on MHz Optical Coherence Elastography},
year = {2021},
url = {https://doi.org/10.1117/12.2615022},
abstract = {A precision air puff excitation system for MHz Optical Coherence Elastography in neurosurgery was developed. It enables non-contact soft-tissue excitation down to {\textmu}N, with direct, noncontact force determination via gas flow measurement.},
}
Katharina Rewerts, Moritz Matthiae, Nicolas Detrez, Steffen Buschschlüter, Matteo M. Bonsanto, Robert Huber, and Ralf Brinkmann,
Phase-Sensitive Optical Coherence Elastography with a 3.2 MHz FDML-Laser Using Focused Air-Puff Tissue Indentation, in ECBO , Optical Society of America, Dec.2021. pp. ETh3A.3.
Weblink: https://opg.optica.org/abstract.cfm?URI=ECBO-2021-ETh3A.3
Bibtex: BibTeX
@inproceedings{Rewerts2021ECBO,
author = {K. Rewerts, M. Matthiae, N. Detrez, S. Buschschlueter, M.M. Bonsanto, R. Huber and R. Brinkmann},
journal = {European Conferences on Biomedical Optics 2021 (ECBO)},
keywords = {AG-Huber_OCT},
pages = {ETh3A.3},
publisher = {Optical Society of America},
title = {Phase-Sensitive Optical Coherence Elastography with a 3.2 MHz FDML-Laser Using Focused Air-Puff Tissue Indentation},
year = {2021},
url = {http://www.osapublishing.org/abstract.cfm?URI=ECBO-2021-ETh3A.3},
abstract = {Tumor discrimination from healthy tissue is often performed by haptically probing tissue elasticity. We demonstrate non-contact elastography using air-puff excitation and tissue indentation measurement by phase-sensitive OCT with a 3.2 MHz FDML-laser.},
}
Hubertus Hakert, Matthias Eibl, Marie Tillich, Ralph Pries, Gereon Hüttmann, Ralf Brinkmann, Barbara Wollenberg, Ludwig Bruchhage, Sebastian Karpf, and Robert Huber,
Time-encoded stimulated Raman scattering microscopy of tumorous human pharynx tissue in the fingerprint region from 1500–1800  cm-1, Optics Letters , vol. 46(14), no. 14, pp. 3456-3459, Jul. 2021.
DOI:10.1364/OL.424726
Bibtex: BibTeX
@article{Hakert2021,
   author = {H. Hakert, M. Eibl, M. Tillich, R.Pries, G. Hüttmann, R. Brinkmann, B. Wollenberg, K-L. Bruchhage, S. Karpf and R. Huber},
   title = {Time-encoded stimulated Raman scattering microscopy of tumorous human pharynx tissue in the fingerprint region from 1500–1800  cm-1},
   journal = {Optics Letters},
   volume = {46(14)},
   number = {14},
   pages = {3456-3459},
keywords = {AG-Huber_NL, Clinical applications, Master oscillator power amplifiers, Optical coherence tomography, Raman scattering, Stimulated Raman scattering, Stimulated scattering},
   DOI = {https://doi.org/10.1364/OL.424726},
   year = {2021},
   type = {Journal Article}
}

Text