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

2024

Wolfgang Draxinger, Nicolas Detrez, Paul Strenge, Veit Danicke, Dirk Theisen-Kunde, Lion Schützeck, Sonja Spahr-Hess, Patrick Kuppler, Jessica Kren, Wolfgang Wieser, Matteo Mario Bonsanto, Ralf Brinkmann, and Robert Huber,
Microscope integrated MHz optical coherence tomography system for neurosurgery: development and clinical in-vivo imaging, Biomed. Opt. Express , vol. 15, no. 10, pp. 5960--5979, Oct. 2024. Optica Publishing Group.
DOI:10.1364/BOE.530976
Bibtex: BibTeX
@article{Draxinger:24,
author = {Wolfgang Draxinger and Nicolas Detrez and Paul Strenge and Veit Danicke and Dirk Theisen-Kunde and Lion Sch\"{u}tzeck and Sonja Spahr-Hess and Patrick Kuppler and Jessica Kren and Wolfgang Wieser and Matteo Mario Bonsanto and Ralf Brinkmann and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Brain imaging; Imaging systems; In vivo imaging; Magnetic resonance imaging; Speckle imaging; Spectral domain optical coherence tomography},
number = {10},
pages = {5960--5979},
publisher = {Optica Publishing Group},
title = {Microscope integrated MHz optical coherence tomography system for neurosurgery: development and clinical in-vivo imaging},
volume = {15},
month = {Oct},
year = {2024},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-15-10-5960},
doi = {10.1364/BOE.530976},
abstract = {Neurosurgical interventions on the brain are impeded by the requirement to keep damages to healthy tissue at a minimum. A new contrast channel enhancing the visual separation of malign tissue should be created. A commercially available surgical microscope was modified with adaptation optics adapting the MHz speed optical coherence tomography (OCT) imaging system developed in our group. This required the design of a scanner optics and beam delivery system overcoming constraints posed by the mechanical and optical parameters of the microscope. High quality volumetric OCT C-scans with dense sample spacing can be acquired in-vivo as part of surgical procedures within seconds and are immediately available for post-processing.},
}
Sebastian Karpf, Nina Glöckner Burmeister, Laurence Dubreil, Shayantani Ghosh, Reka Hollandi, Julien Pichon, Isabelle Leroux, Alessandra Henkel, Valerie Lutz, Jonas Jurkevičius, Alexandra Latshaw, Vasyl Kilin, Tonio Kutscher, Moritz Wiggert, Oscar Saavedra-Villanueva, Alfred Vogel, Robert Huber, Peter Horvath, Karl Rouger, and Luigi Bonacina,
Harmonic Imaging of Stem Cells in Whole Blood at GHz Pixel Rate, Small , pp. 2401472, 06 2024.
DOI:https://doi.org/10.1002/smll.202401472
Bibtex: BibTeX
@article{https://doi.org/10.1002/smll.202401472,
author = {Karpf, Sebastian and Glöckner Burmeister, Nina and Dubreil, Laurence and Ghosh, Shayantani and Hollandi, Reka and Pichon, Julien and Leroux, Isabelle and Henkel, Alessandra and Lutz, Valerie and Jurkevičius, Jonas and Latshaw, Alexandra and Kilin, Vasyl and Kutscher, Tonio and Wiggert, Moritz and Saavedra-Villanueva, Oscar and Vogel, Alfred and Huber, Robert A. and Horvath, Peter and Rouger, Karl and Bonacina, Luigi},
title = {Harmonic Imaging of Stem Cells in Whole Blood at GHz Pixel Rate},
journal = {Small},
volume = {n/a},
number = {n/a},
pages = {2401472},
keywords = {fiber lasers, harmonic imaging, multiphoton microscopy, nanoparticles, regenerative medicine, SHG, SLIDE},
doi = {https://doi.org/10.1002/smll.202401472},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.202401472},
eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/smll.202401472},
abstract = {Abstract The pre-clinical validation of cell therapies requires monitoring the biodistribution of transplanted cells in tissues of host organisms. Real-time detection of these cells in the circulatory system and identification of their aggregation state is a crucial piece of information, but necessitates deep penetration and fast imaging with high selectivity, subcellular resolution, and high throughput. In this study, multiphoton-based in-flow detection of human stem cells in whole, unfiltered blood is demonstrated in a microfluidic channel. The approach relies on a multiphoton microscope with diffractive scanning in the direction perpendicular to the flow via a rapidly wavelength-swept laser. Stem cells are labeled with metal oxide harmonic nanoparticles. Thanks to their strong and quasi-instantaneous second harmonic generation (SHG), an imaging rate in excess of 10 000 frames per second is achieved with pixel dwell times of 1 ns, a duration shorter than typical fluorescence lifetimes yet compatible with SHG. Through automated cell identification and segmentation, morphological features of each individual detected event are extracted and cell aggregates are distinguished from isolated cells. This combination of high-speed multiphoton microscopy and high-sensitivity SHG nanoparticle labeling in turbid media promises the detection of rare cells in the bloodstream for assessing novel cell-based therapies.}
}
Simon Lotz, Madita Göb, Sven Böttger, Linh Ha-Wissel, Jennifer Hundt, Floris Ernst, and Robert Huber,
Large area robotically assisted optical coherence tomography (LARA-OCT), Biomed. Opt. Express , vol. 15, no. 6, pp. 3993-4009, 06 2024. Optica Publishing Group.
DOI:10.1364/BOE.525524
Bibtex: BibTeX
@article{Lotz:24,
author = {Simon Lotz and Madita G\"{o}b and Sven B\"{o}ttger and Linh Ha-Wissel and Jennifer Hundt and Floris Ernst and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Angiography; Biomedical imaging; In vivo imaging; Machine vision; Point clouds; Spectral domain optical coherence tomography},
number = {6},
pages = {3993--4009},
publisher = {Optica Publishing Group},
title = {Large area robotically assisted optical coherence tomography (LARA-OCT)},
volume = {15},
month = {Jun},
year = {2024},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-15-6-3993},
doi = {10.1364/BOE.525524},
abstract = {We demonstrate large-area robotically assisted optical coherence tomography (LARA-OCT), utilizing a seven-degree-of-freedom robotic arm in conjunction with a 3.3\&\#x2005;MHz swept-source OCT to raster scan samples of arbitrary shape. By combining multiple fields of view (FOV), LARA-OCT can probe a much larger area than conventional OCT. Also, nonplanar and curved surfaces like skin on arms and legs can be probed. The lenses in the LARA-OCT scanner with their normal FOV can have fewer aberrations and less complex optics compared to a single wide field design. This may be especially critical for high resolution scans. We directly use our fast MHz-OCT for tracking and stitching, making additional machine vision systems like cameras, positioning, tracking or navigation devices obsolete. This also eliminates the need for complex coordinate system registration between OCT and the machine vision system. We implemented a real time probe-to-surface control that maintains the probe alignment orthogonal to the sample by only using surface information from the OCT images. We present OCT data sets with volume sizes of 140\&\#x2009;\&\#x00D7;\&\#x2009;170\&\#x2009;\&\#x00D7;\&\#x2009;20 mm3, captured in 2.5 minutes.},
}
Linh Ha-Wissel, Hanna Graßhoff, Madita Göb, Bayan Mustafa, Robert Huber, Henner Zirpel, Hadan Yasak, Diamant Thaci, and Jennifer E. Hundt,
Optical coherence tomography-based imaging biomarkers for disease activity monitoring in plaque psoriasis, Journal of the European Academy of Dermatology and Venereology , 05 2024.
DOI:https://doi.org/10.1111/jdv.20097
Bibtex: BibTeX
@article{https://doi.org/10.1111/jdv.20097,
author = {Ha-Wissel, L. and Graßhoff, H. and Göb, M. and Mustafa, B. and Huber, R. and Zirpel, H. and Yasak, H. and Thaçi, D. and Hundt, J. E.},
title = {Optical coherence tomography-based imaging biomarkers for disease activity monitoring in plaque psoriasis},
journal = {Journal of the European Academy of Dermatology and Venereology},
volume = {n/a},
number = {n/a},
pages = {},
doi = {https://doi.org/10.1111/jdv.20097},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/jdv.20097},
eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdv.20097}
}
Rene Riha, Alejandro Martinez Jimenez, Gopika Venugopal, Marie Klufts, Robert Huber, and Adrian Podoleanu,
Dispersion-Tuned Mode-Locked Laser for Swept Source OCT At 850 Nm Using a cFBG and the Pulse Modulation Technique, IEEE Photonics Journal , pp. 1-6, May 2024.
DOI:10.1109/JPHOT.2024.3417829
Bibtex: BibTeX
@ARTICLE{10568460,
  author={Riha, Rene and Jimenez, Alejandro Martinez and Venugopal, Gopika and Klufts, Marie and Huber, Robert and Podoleanu, Adrian},
  journal={IEEE Photonics Journal}, 
  title={Dispersion-Tuned Mode-Locked Laser for Swept Source OCT At 850 Nm Using a cFBG and the Pulse Modulation Technique}, 
  year={2024},
  volume={},
  number={},
  pages={1-6},
  keywords={Modulation;Dispersion;Semiconductor optical amplifiers;Optical interferometry;Optical pulses;Frequency modulation;Optical fiber amplifiers;OCT;dispersion tuning;cFBG;intensity modulator},
  doi={10.1109/JPHOT.2024.3417829}}
Mark Ellrichmann, Berenice Schulte, Claudio C Conrad, Stephan Schoch, Johannes Bethge, Marcus Seeger, Robert Huber, Madita Göb, Alexander Arlt, Susanna Nikolaus, Christoph Röcken, and Stefan Schreiber,
Contrast enhanced endoscopic ultrasound detects early therapy response following anti-TNF-therapy in patients with ulcerative colitis, Journal of Crohn's and Colitis , pp. jjae034, 03 2024.
DOI:10.1093/ecco-jcc/jjae034
Bibtex: BibTeX
@article{10.1093/ecco-jcc/jjae034,
    author = {Ellrichmann, Mark and Schulte, Berenice and Conrad, Claudio C and Schoch, Stephan and Bethge, Johannes and Seeger, Marcus and Huber, Robert and Goeb, Madita and Arlt, Alexander and Nikolaus, Susanna and Röcken, Christoph and Schreiber, Stefan},
    title = "{Contrast enhanced endoscopic ultrasound detects early therapy response following anti-TNF-therapy in patients with ulcerative colitis}",
    journal = {Journal of Crohn's and Colitis},
    pages = {jjae034},
    year = {2024},
    month = {03},
    abstract = "{Though colonoscopy plays a crucial role in assessing active ulcerative colitis (aUC), its scope is limited to the mucosal surface. Endoscopic ultrasound (EUS) coupled with contrast-enhancement (dCEUS) can precisely quantify bowel wall thickness and microvascular circulation, potentially enabling the quantitative evaluation of inflammation.We conducted a prospective, longitudinal study to assess therapy response using dCEUS in aUC patients undergoing treatment with adalimumab (ADA) or infliximab (IFX).30 ADA- and 15 IFX-treated aUC patients were examined at baseline and at 2, 6, 14 weeks of therapy and 48 weeks of follow-up. Bowel wall thickness (BWT) was measured by EUS in the rectum. Vascularity was quantified by dCEUS using Rise Time (RT) and Time To Peak (TTP). Therapy response was defined after 14 weeks using the Mayo Score.Patients with aUC displayed a mean BWT of 3.9±0.9 mm. In case of response to ADA/IFX a significant reduction in BWT was observed after 2 weeks (p=0.04), whereas non-responders displayed no significant changes. The TTP was notably accelerated at baseline and significantly normalised by week 2 in responders (p=0.001), while non-responders exhibited no significant alterations (p=0.9). At week 2, the endoscopic Mayo score did not exhibit any changes, thus failing to predict treatment responses.dCEUS enables the early detection of therapy response in patients with aUC, which serves as a predictive marker for long term clinical success. Therefore, dCEUS serves as a diagnostic tool for assessing the probability of future therapy success.}",
    issn = {1873-9946},
    doi = {10.1093/ecco-jcc/jjae034},
    url = {https://doi.org/10.1093/ecco-jcc/jjae034},
    eprint = {https://academic.oup.com/ecco-jcc/advance-article-pdf/doi/10.1093/ecco-jcc/jjae034/56911128/jjae034.pdf},
}
Berenice Schulte, Madita Göb, Awanish Pratap Singh, Simon Lotz, Wolfgang Draxinger, Marvin Heimke, Mario Pieper, Tillmann Heinze, Thilo Wedel, Maik Rahlves, Robert Huber, and Mark Ellrichmann,
High-resolution rectoscopy using MHz optical coherence tomography: a step towards real time 3D endoscopy, Scientific Reports , vol. 14, no. 1, pp. 4672, 02 2024.
DOI:10.1038/s41598-024-55338-5
Bibtex: BibTeX
@article{RN5474,
   author = {Schulte, Berenice;Göb, Madita;Singh, Awanish Pratap;Lotz, Simon;Draxinger, Wolfgang;Heimke, Marvin;pieper, Mario;Heinze, Tillmann;Wedel, Thilo;Rahlves, Maik;Huber, Robert and Ellrichmann, Mark},
   title = {High-resolution rectoscopy using MHz optical coherence tomography: a step towards real time 3D endoscopy},
   journal = {Scientific Reports},
   volume = {14},
   number = {1},
   pages = {4672},
   ISSN = {2045-2322},
   DOI = {10.1038/s41598-024-55338-5},
   url = {https://doi.org/10.1038/s41598-024-55338-5},
   year = {2024},
   type = {Journal Article}
}
Jessica Kren, Patrick Kuppler, Steffen Buschschlüter, Nicolas Detrez, Sazgar Burhan, Robert Huber, Ralf Brinkmann, and Matteo Mario Bonsanto,
Mechanical characteristics of glioblastoma and peritumoral tumor-free human brain tissue, Acta Neurochirurgica , vol. 166, no. 1, pp. 102, 02 2024.
DOI:10.1007/s00701-024-06009-x
Bibtex: BibTeX
@article{RN5472,
   author = {Kren, Jessica;Skambath, Isabelle;Kuppler, Patrick;Buschschlüter, Steffen;Detrez, Nicolas;Burhan, Sazgar;Huber, Robert;Brinkmann, Ralf and Bonsanto, Matteo Mario},
   title = {Mechanical characteristics of glioblastoma and peritumoral tumor-free human brain tissue},
   journal = {Acta Neurochirurgica},
   volume = {166},
   number = {1},
   pages = {102},
   ISSN = {0942-0940},
   DOI = {10.1007/s00701-024-06009-x},
   url = {https://doi.org/10.1007/s00701-024-06009-x},
   year = {2024},
   type = {Journal Article}
}
[DE] Berenice Schulte, Sazgar Burhan, Awanish Pratap Singh, Wolfgang Draxinger, Simon Lotz, Marvin Heimke, Tillmann Heinze, Thilo Wedel, Maik Rahlves, Robert Huber, and Mark Ellrichmann,
Hochauflösende Rektoskopie mittels dual-mode MHz optischer Kohärenztomographie - ein Schritt zur real time 3D Endoskopie, Z Gastroenterol , vol. 62, no. 09, pp. KV 355, 2024. Georg Thieme Verlag KG.
DOI:10.1055/s-0044-1790019
Bibtex: BibTeX
@Article{Schulte2024,
author={Schulte, B.; Burhan, S.; Singh, A. P.; Draxinger, W.; Lotz, S.; Heimke, M.; Heinze, T.; Wedel, T.; Rahlves, M.; Huber, R.; Ellrichmann, M.},
title={Hochaufl{\"o}sende Rektoskopie mittels dual-mode MHz optischer Koh{\"a}renztomographie -- ein Schritt zur real time 3D Endoskopie},
journal={Z Gastroenterol},
year={2024},
month={Sep},
day={26},
publisher={Georg Thieme Verlag KG},
volume={62},
number={09},
pages={KV 355},
issn={0044-2771},
doi={10.1055/s-0044-1790019},
url={http://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0044-1790019},
url={https://doi.org/10.1055/s-0044-1790019},
language={DE}
}
Patrick Kuppler, Paul Strenge, Birgit Lange, Sonja Spahr-Hess, Wolfgang Draxinger, Christian Hagel, Dirk Theisen-Kunde, Ralf Brinkmann, Robert Huber, Volker Tronnier, and Matteo Mario Bonsanto,
Microscope-integrated optical coherence tomography for in vivo human brain tumor detection with artificial intelligence, Journal of Neurosurgery , pp. 1 - 9, 2024. American Association of Neurological Surgeons.
DOI:10.3171/2024.1.JNS231511
Bibtex: BibTeX
@article { Microscopeintegratedopticalcoherencetomographyforinvivohumanbraintumordetectionwithartificialintelligence,
      author = "Patrick Kuppler and Paul Strenge and Birgit Lange and Sonja Spahr-Hess and Wolfgang Draxinger and Christian Hagel and Dirk Theisen-Kunde and Ralf Brinkmann and Robert Huber and Volker Tronnier and Matteo Mario Bonsanto",
      title = "Microscope-integrated optical coherence tomography for in vivo human brain tumor detection with artificial intelligence",
      journal = "Journal of Neurosurgery",
      year = "2024",
      publisher = "American Association of Neurological Surgeons",
      doi = "10.3171/2024.1.JNS231511",
      pages=      "1 - 9",
      url = "https://thejns.org/view/journals/j-neurosurg/aop/article-10.3171-2024.1.JNS231511/article-10.3171-2024.1.JNS231511.xml"
}
Sazgar Burhan, Nicolas Detrez, Katharina Rewerts, Paul Strenge, Steffen Buschschlüter, Jessica Kren, Christian Hagel, Matteo Mario Bonsanto, Ralf Brinkmann, and Robert Huber,
Phase unwrapping for MHz optical coherence elastography and application to brain tumor tissue, Biomed. Opt. Express , vol. 15, no. 2, pp. 1038--1058, 2024. Optica Publishing Group.
DOI:10.1364/BOE.510020
Bibtex: BibTeX
@article{Burhan:24,
author = {Sazgar Burhan and Nicolas Detrez and Katharina Rewerts and Paul Strenge and Steffen Buschschl\"{u}ter and Jessica Kren and Christian Hagel and Matteo Mario Bonsanto and Ralf Brinkmann and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {High speed imaging; Imaging systems; In vivo imaging; Magnetic resonance imaging; Phase noise; Phase shift},
number = {2},
pages = {1038--1058},
publisher = {Optica Publishing Group},
title = {Phase unwrapping for MHz optical coherence elastography and application to brain tumor tissue},
volume = {15},
month = {Feb},
year = {2024},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-15-2-1038},
doi = {10.1364/BOE.510020},
abstract = {During neuro-oncologic surgery, phase-sensitive optical coherence elastography (OCE) can be valuable for distinguishing between healthy and diseased tissue. However, the phase unwrapping process required to retrieve the original phase signal is a challenging and critical task. To address this issue, we demonstrate a one-dimensional unwrapping algorithm that recovers the phase signal from a 3.2\&\#x2005;MHz OCE system. With a processing time of approximately 0.11 s per frame on the GPU, multiple 2\&\#x03C0; wraps are detected and corrected. By utilizing this approach, exact and reproducible information on tissue deformation can be obtained with pixel accuracy over the entire acquisition time. Measurements of brain tumor-mimicking phantoms and human ex vivo brain tumor samples verified the algorithm\&\#x0027;s reliability. The tissue samples were subjected to a 200\&\#x2005;ms short air pulse. A correlation with histological findings confirmed the algorithm\&\#x0027;s dependability.},
}
Awanish Pratap Singh, Madita Göb, Martin Ahrens, Tim Eixmann, Berenice Schulte, Hinnerk Schulz-Hildebrandt, Gereon Hüttmann, Mark Ellrichmann, Robert Huber, and Maik Rahlves,
Virtual Hall sensor triggered multi-MHz endoscopic OCT imaging for stable real-time visualization, Opt. Express , vol. 32, no. 4, pp. 5809--5825, 2024. Optica Publishing Group.
DOI:10.1364/OE.514636
Bibtex: BibTeX
@article{Singh:24,
author = {Awanish Pratap Singh and Madita G\"{o}b and Martin Ahrens and Tim Eixmann and Berenice Schulte and Hinnerk Schulz-Hildebrandt and Gereon H\"{u}ttmann and Mark Ellrichmann and Robert Huber and Maik Rahlves},
journal = {Opt. Express},
keywords = {Biomedical imaging; Endoscopic imaging; Imaging systems; Optical coherence tomography; Real time imaging; Vertical cavity surface emitting lasers},
number = {4},
pages = {5809--5825},
publisher = {Optica Publishing Group},
title = {Virtual Hall sensor triggered multi-MHz endoscopic OCT imaging for stable real-time visualization},
volume = {32},
month = {Feb},
year = {2024},
url = {https://opg.optica.org/oe/abstract.cfm?URI=oe-32-4-5809},
doi = {10.1364/OE.514636},
abstract = {Circumferential scanning in endoscopic imaging is crucial across various disciplines, and optical coherence tomography (OCT) is often the preferred choice due to its high-speed, high-resolution, and micron-scale imaging capabilities. Moreover, real-time and high-speed 3D endoscopy is a pivotal technology for medical screening and precise surgical guidance, among other applications. However, challenges such as image jitter and non-uniform rotational distortion (NURD) are persistent obstacles that hinder real-time visualization during high-speed OCT procedures. To address this issue, we developed an innovative, low-cost endoscope that employs a brushless DC motor for scanning, and a sensorless technique for triggering and synchronizing OCT imaging with the scanning motor. This sensorless approach uses the motor\&\#x2019;s electrical feedback (back electromotive force, BEMF) as a virtual Hall sensor to initiate OCT image acquisition and synchronize it with a Fourier Domain Mode-Locked (FDML)-based Megahertz OCT system. Notably, the implementation of BEMF-triggered OCT has led to a substantial reduction in image jitter and NURD (\<4 mrad), thereby opening up a new window for real-time visualization capabilities. This approach suggests potential benefits across various applications, aiming to provide a more accurate, deployable, and cost-effective solution. Subsequent studies can explore the adaptability of this system to specific clinical scenarios and its performance under practical endoscopic conditions.},
}

2023

Marie Klufts, A. Martínez Jiménez, Simon Lotz, Muhammad Asim Bashir, Tom Pfeiffer, Alexander Mlynek, Wolfgang Wieser, Alexander Chamorovskiy, Adrian Bradu, Adrian Podoleanu, and Robert Huber,
828 kHz retinal imaging with an 840 nm Fourier domain mode locked laser, Biomed. Opt. Express , vol. 14, no. 12, pp. 6493-6508, Nov. 2023. Optica Publishing Group.
DOI:10.1364/BOE.504302
Bibtex: BibTeX
@article{Klufts:23,
author = {Marie Klufts and Alejandro Martinez Jimenez and Simon Lotz and Muhammad Asim Bashir and Tom Pfeiffer and Alexander Mlynek and Wolfgang Wieser and Alexander Chamorovskiy and Adrian Bradu and Adrian Podoleanu and Robert Huber},
journal = {Biomed. Opt. Express},
keywords = {Analog to digital converters; Laser beams; Laser imaging; Laser modes; Point spread function; Vertical cavity surface emitting lasers},
number = {12},
pages = {6493--6508},
publisher = {Optica Publishing Group},
title = {828 kHz retinal imaging with an 840\&\#x2005;nm Fourier domain mode locked laser},
volume = {14},
month = {Dec},
year = {2023},
url = {https://opg.optica.org/boe/abstract.cfm?URI=boe-14-12-6493},
abstract = {This paper presents a Fourier domain mode locked (FDML) laser centered around 840 nm. It features a bidirectional sweep repetition rate of 828 kHz and a spectral bandwidth of 40 nm. An axial resolution of ∼9.9 µm in water and a 1.4 cm sensitivity roll-off are achieved. Utilizing a complex master-slave (CMS) recalibration method and due to a sufficiently high sensitivity of 84.6 dB, retinal layers of the human eye in-vivo can be resolved during optical coherence tomography (OCT) examination. The developed FDML laser enables acquisition rates of 3D-volumes with a size of 200 × 100 × 256 voxels in under 100 milliseconds. Detailed information on the FDML implementation, its challenging design tasks, and OCT images obtained with the laser are presented in this paper.},
}
Sazgar Burhan, Nicolas Detrez, Madita Göb, Matteo Mario Bonsanto, Ralf Brinkmann, and Robert Huber,
Advanced FFT-based contrast approach for MHz optical coherence elastography, in Optical Coherence Imaging Techniques and Imaging in Scattering Media V , Benjamin J. Vakoc and Maciej Wojtkowski and Yoshiaki Yasuno, Eds. SPIE, 082023. pp. 1263215.
DOI:10.1117/12.2670957
Bibtex: BibTeX
@inproceedings{10.1117/12.2670957,
author = {Sazgar Burhan and Nicolas Detrez and Madita G{\"o}b and Matteo Mario Bonsanto and Ralf Brinkmann and Robert Huber},
title = {{Advanced FFT-based contrast approach for MHz optical coherence elastography}},
volume = {12632},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media V},
editor = {Benjamin J. Vakoc and Maciej Wojtkowski and Yoshiaki Yasuno},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1263215},
abstract = {Optical coherence elastography represents mechanical characteristics of biological tissue in so-called mechanical contrast maps. In addition to the standard intensity image, the contrast map illustrates numerous mechanical tissue features that would otherwise be undetectable. This is of great interest as abnormal physiological changes influence the mechanical behavior of the tissue. We demonstrate an advanced mechanical contrast approach based on the phase signal of our 3.2 MHz optical coherence tomography system. The robustness and performance of this contrast approach is evaluated and discussed based on preliminary results. },
keywords = {Optical Coherence Tomography, OCT, Megahertz OCT, Fourier Domain Mode Locking, Optical Coherence Elastography, OCE, Phase-sensitive OCT, Biomechanics},
year = {2023},
doi = {10.1117/12.2670957},
URL = {https://doi.org/10.1117/12.2670957}
}
Wolfgang Draxinger, Dirk Theisen-Kunde, Lion Schuetz, Nicolas Detrez, Paul Strenge, Maximilian Rixius, Veit Danicke, Wolfgang Wieser, Jessica Kren, Patrick Kuppler, Sonja Spar-Hess, Matteo M. Bonsanto, Ralf Brinkmann, and Robert Huber,
Microscope integrated realtime high density 4D MHz-OCT in neurosurgery: a depth and tissue resolving visual contrast channel and the challenge of fused presentation, in Translational Biophotonics: Diagnostics and Therapeutics III , Zhiwei Huang and Lothar D. Lilge, Eds. SPIE, 082023. pp. 126270W.
DOI:10.1117/12.2670953
Bibtex: BibTeX
@inproceedings{10.1117/12.2670953,
author = {Wolfgang Draxinger and Dirk Theisen-Kunde and Lion Schuetz and Nicolas Detrez and Paul Strenge and Maximilian Rixius and Veit Danicke and Wolfgang Wieser and Jessica Kren and Patrick Kuppler and Sonja Spar-Hess and Matteo Mario Bonsanto M.D. and Ralf Brinkmann and Robert Huber},
title = {{Microscope integrated realtime high density 4D MHz-OCT in neurosurgery: a depth and tissue resolving visual contrast channel and the challenge of fused presentation}},
volume = {12627},
booktitle = {Translational Biophotonics: Diagnostics and Therapeutics III},
editor = {Zhiwei Huang and Lothar D. Lilge},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {126270W},
abstract = {Microscope integrated realtime 4D MHz-OCT operating at high scanning densities are capable of capturing additional visual contrast resolving depth and tissue. Even within a plain C-scan en-face projection structures are recognizable, that are not visible in a white light camera image. With advanced post processing methods, such as absorbtion coefficient mapping, and morphological classifiers more information is extraced. Presentation to the user in an intuitive way poses practical challenges that go beyond the implementation of a mere overlay display. We present our microscope integrated high speed 4D OCT imaging system, its clinical study use for in-vivo brain tissue imaging, and user feedback on the presentation methods we developed.},
keywords = {optical coherence tomography, neurosurgery, tissue contrast, image fusion, surgical guidance, theranostics},
year = {2023},
doi = {10.1117/12.2670953},
URL = {https://doi.org/10.1117/12.2670953}
}
Madita Göb, Simon Lotz, Linh Ha-Wissel, Sazgar Burhan, Sven Böttger, Floris Ernst, Jennifer Hundt, and Robert Huber,
Advances in large area robotically assisted OCT (LARA-OCT): towards drive-by continuous motion imaging, in Optical Coherence Imaging Techniques and Imaging in Scattering Media V , Benjamin J. Vakoc and Maciej Wojtkowski and Yoshiaki Yasuno, Eds. SPIE, 082023. pp. 126321N.
DOI:10.1117/12.2670950
Bibtex: BibTeX
@inproceedings{10.1117/12.2670950,
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 = {{Advances in large area robotically assisted OCT (LARA-OCT): towards drive-by continuous motion imaging}},
volume = {12632},
booktitle = {Optical Coherence Imaging Techniques and Imaging in Scattering Media V},
editor = {Benjamin J. Vakoc and Maciej Wojtkowski and Yoshiaki Yasuno},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {126321N},
abstract = {Optical coherence tomography is a powerful imaging technique to visualize and localize depth-dependent tissue structure to differentiate between healthy and pathological conditions. However, conventional OCT systems are only capable of detecting small areas. To overcome this limitation, we have developed a large area robotically assisted OCT (LARA-OCT) system for automatic acquisition of large OCT images. Using mosaic pattern acquisition and subsequent stitching, we previously demonstrated initial in vivo OCT skin images beyond 10 cm². To improve acquisition speed and reduce dead times, we here demonstrate and analyze LARA-OCT with a new drive-by continuous motion imaging protocol.},
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 = {10.1117/12.2670950},
URL = {https://doi.org/10.1117/12.2670950}
}
Philipp Lamminger, Hubertus Hakert, Simon Lotz, Jan Philip Kolb, Tonio Kutscher, Sebastian Karpf, and Robert Huber,
Four-Wave Mixing Fast Wavelength Sweeping FDML Laser with kW Peak Power at 900 nm and 1300 nm, in 2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) , 072023. pp. 1.
DOI:10.1109/CLEO/Europe-EQEC57999.2023.10232141
Bibtex: BibTeX
@INPROCEEDINGS{10232141,
  author={Lamminger, Philipp and Hakert, Hubertus and Lotz, Simon and Kolb, Jan Philip and Kutscher, Tonio and Karpf, Sebastian and Huber, Robert},
  booktitle={2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC)}, 
  title={Four-Wave Mixing Fast Wavelength Sweeping FDML Laser with kW Peak Power at 900 nm and 1300 nm}, 
  year={2023},
  volume={},
  number={},
  pages={1-1},
  doi={10.1109/CLEO/Europe-EQEC57999.2023.10232141}}
Simon Lotz, Madita Göb, Wolfgang Draxinger, Anneli Dick, and Robert Huber,
13.4 MHz FDML Laser for Intra-Surgical Optical Coherence Tomography, in 2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) , 072023. pp. 1.
DOI:10.1109/CLEO/Europe-EQEC57999.2023.10231419
Bibtex: BibTeX
@INPROCEEDINGS{10231419,
  author={Lotz, Simon and Göb, Madita and Draxinger, Wolfgang and Dick, Anneli and Huber, Robert},
  booktitle={2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC)}, 
  title={13.4 MHz FDML Laser for Intra-Surgical Optical Coherence Tomography}, 
  year={2023},
  volume={},
  number={},
  pages={1-1},
  doi={10.1109/CLEO/Europe-EQEC57999.2023.10231419}}
Marie Klufts, Simon Lotz, Muhammad Asim Bashir, Tom Pfeiffer, Alexander Mlynek, Wolfgang Wieser, Alexander Chamorovskiy, Vladimir Shidlovski, Adrian Podoleanu, and Robert Huber,
Dual Amplification 850 nm FDML Laser, in 2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) , 072023. pp. 1.
DOI:10.1109/CLEO/Europe-EQEC57999.2023.10232019
Bibtex: BibTeX
@INPROCEEDINGS{10232019,
  author={Klufts, M. and Lotz, S. and Bashir, M. A. and Pfeiffer, T. and Mlynek, A. and Wieser, W. and Chamorovskiy, A. and Shidlovski, V. and Podoleanu, A. and Huber, R.},
  booktitle={2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC)}, 
  title={Dual Amplification 850 nm FDML Laser}, 
  year={2023},
  volume={},
  number={},
  pages={1-1},
  doi={10.1109/CLEO/Europe-EQEC57999.2023.10232019}}
Muhammad Asim Bashir, Simon Lotz, Marie Klufts, Christian Jirauschek, and Robert Huber,
1190 nm FDML laser: Challenges and Strategies, in 2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) , 072023. pp. 1.
DOI:10.1109/CLEO/Europe-EQEC57999.2023.10232661
Bibtex: BibTeX
@INPROCEEDINGS{10232661,
  author={Bashir, M. A. and Lotz, S. and Kluftsa, M. and Jirauschek, C. and Huberab, R.},
  booktitle={2023 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC)}, 
  title={1190 nm FDML laser: Challenges and Strategies}, 
  year={2023},
  volume={},
  number={},
  pages={1-1},
  doi={10.1109/CLEO/Europe-EQEC57999.2023.10232661}}
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, 07 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, 032023. 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}
}
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, 032023. 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, 032023. 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}
}
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, 032023. 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}
}

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