@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}
}

@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}
}

@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}
}

@inproceedings{10.1117/12.2649835,
author = {Nicolas Detrez and Sazgar Burhan and Katharina Rewerts and Jessica Kren and Christian Hagel and Matteo Mario Bonsanto and Dirk Theisen-Kunde and Robert Huber and Ralf Brinkmann},
title = {{Air-Jet based optical coherence elastography: processing and mechanical interpretation of brain tumor data}},
volume = {12381},
booktitle = {Optical Elastography and Tissue Biomechanics X},
editor = {Kirill V. Larin and Giuliano Scarcelli and Fr{\'e}d{\'e}rique Vanholsbeeck},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {1238105},
keywords = {Optical Coherence Elastography, Air-Jet, Air-Puff, biomechanics, viscoelasticity, rheology, brain tissue, brain tumor},
year = {2023},
doi = {10.1117/12.2649835},
URL = {https://doi.org/10.1117/12.2649835}
}

@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 -π to π 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 4π-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}
}

@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}
}

@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}
}

@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}
}

@article{Lange2022,
   author = {Lange, B;Ozimek, T;Wießmeyer, J R;Kramer, M W.;Merseburger, A S. and Brinkmann, R},
   title = {Theoretical and experimental evaluation of the distance dependence of fiber-based fluorescence and reflection measurements for laser lithotripsy},
   journal = {Biomedical Physics & Engineering Express},
   volume = {8},
   number = {5},
abstract = {Objectives. In laser lithotripsy, a green aiming beam overlying the infrared (IR) treatment radiation gives rise to reflection and fluorescence signals that can be measured via the treatment fiber. While stone autofluorescence is used for target detection, the condition of the fiber can be assessed based on its Fresnel reflection. For good applicability, fluorescence detection of stones should work even when the stone and fiber are not in direct contact. Fiber breakage detection, on the other hand, can be falsified if surfaces located in front of the fiber reflect light from the aiming laser back into it. For both applications, therefore, a fundamental investigation of the dependence of the signal amplitude on the distance between fiber and surface is important. Methods. Calculations of the signal drop of fluorescence or diffuse and specular reflection with increasing fiber distance were performed using ray tracing based on a simple geometric model for different fiber core diameters. Reflection signals from a mirror, diffuse reflector, human calculi, and porcine renal tissue placed in water were measured at varying distances (0–5 mm). For human calculi, fluorescence signals were recorded simultaneously. Results. The calculations showed a linear signal decrease down to ∼60% of the maximum signal (fiber in contact). The distance z at which the signal drops to for example 50% depends linearly on the diameter of the fiber core. For fibers used in lithotripsy and positioned in water, z50% ranges from 0.55 mm (200 μm core diameter) to 2.73 mm, (1 mm core diameter). The calculations were in good agreement with the experimental results. Conclusions. The autofluorescence signals of stones can be measured in non-contact mode. Evaluating the Fresnel signal of the end face of the fiber to detect breakage is possible unless the fiber is situated less than some millimeters to reflecting surfaces.},
keywords = {urolithiasis, laser lithotripsy, fluorescence, reflectance},
   pages = {055023},
   ISSN = {2057-1976},
   DOI = {10.1088/2057-1976/ac82c7},
   
   year = {2022},
   type = {Journal Article}
}

@article{Miura2022,
   author = {Miura, Y;Inagaki, K;Hutfilz, A;Seifert, E;Schmarbeck, B;Murakami, A;Ohkoshi, K and Brinkmann, R},
   title = {Temperature Increase and Damage Extent at Retinal Pigment Epithelium Compared between Continuous Wave and Micropulse Laser Application},
   journal = {Life},
   volume = {12(9)},
  
   pages = {1313},
   ISSN = {2075-1729},
   url = {https://www.mdpi.com/2075-1729/12/9/1313},
   year = {2022},
   type = {Journal Article}
}

@article{Schaller2022,
   author = {Schaller, M.;Kleyman, K.;Mordmüller, M.;Schmidt, C.;Wilson, M.;Brinkmann, R.;Müller, M.A. and Worthmann, K.},
   title = {Model predictive control for retinal laser treatment at 1 kHz},
   journal = {at - Automatisierungstechnik},
   volume = {70(11)},
   keywords = {model predictive control; real-time control;retinal photocoagulation},
   pages = {992-1002},
  
   url = {https://doi.org/10.1515/auto-2022-0030},
   year = {2022},
   type = {Journal Article}
}

@article{Schaller2022,
   author = {Schaller, M;Wilson, M;Kleyman, V;Mordmüller, M;Brinkmann, R;Müller, M. A. and Worthmann, K},
   title = {Parameter estimation and model reduction for model predictive control in retinal laser treatment},
   journal = {Control Engineering Practice},
   volume = {128},
   pages = {105320},
   ISSN = {0967-0661},
   DOI = {https://doi.org/10.1016/j.conengprac.2022.105320},

   year = {2022},
   type = {Journal Article}
}

@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.},
}

@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.},
}

@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.},
}

@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}
}

@inproceedings{Strenge2021A,
author = {P. Strenge, B. Lange, C. Grill, W. Draxinger, V. Danicke, D. Theisen-Kunde, H. Handels, M. Bonsanto, C. Hagel, R. Huber and R. Brinkmann},
title = {{Characterization of brain tumor tissue with 1310 nm optical coherence tomography}},
volume = {11630},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXV},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {74 -- 80},
abstract = {The separation of tumorous brain tissue and healthy brain tissue is still a big challenge in the field of neurosurgery, especially when it comes to the detection of different infiltration grades of glioblastoma multiforme at the tumor border. On the basis of a recently created labelled OCT dataset of ex vivo glioblastoma multiforme tumor samples the detection of brain tumor tissue and the identification of zones with varying degrees of infiltration of tumor cells was investigated. The identification was based on the optical properties, which were extracted by an exponential fit function. The results showed that a separation of tumorous tissue and healthy white matter based on these optical properties is possible. A support vector machine was trained on the optical properties to separate tumor from healthy white matter tissue, which achieved a sensitivity of 91% and a specificity of 76% on an independent training dataset.},
keywords = {AG-Huber_OCT, optical coherence tomography, OCT, glioblastoma multiforme, MHz-OCT, brain imaging, tumor, neurosurgery},
year = {2021},
URL = {hhttps://doi.org/10.1117/12.2578409}
}

@inproceedings{Strenge2021,
author = {P. Strenge, B. Lange, C. Grill, W. Draxinger, V. Danicke, D. Theisen-Kunde, H. Handels, C. Hagel, M. Bonsanto, R. Huber and R. Brinkmann},
title = {{Creating a depth-resolved OCT-dataset for supervised classification based on ex vivo human brain samples}},
volume = {11630},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXV},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {66 -- 73},
abstract = {Optical coherence tomography (OCT) has the potential to become an additional imaging modality for surgical guidance in the field of neurosurgery, especially when it comes to the detection of different infiltration grades of glioblastoma multiforme at the tumor border. Interpretation of the images, however, is still a big challenge. A method to create a labeled OCT dataset based on ex vivo brain samples is introduced. The tissue samples were embedded in an agarose mold giving them a distinctive shape before images were acquired with two OCT systems (spectral domain (SD) and swept source (SS) OCT) and histological sections were created and segmented by a neuropathologist. Based on the given shape, the corresponding OCT images for each histological image can be determined. The transfer of the labels from the histological images onto the OCT images was done with a non-affine image registration approach based on the tissue shape. It was demonstrated that finding OCT images of a tissue sample corresponding to segmented histological images without any color or laser marking is possible. It was also shown that the set labels can be transferred onto OCT images. The accuracy of method is 26 ± 11 pixel, which translates to 192 ± 75 μm for the SS-OCT and 94 ± 43 μm for the SD-OCT. The dataset consists of several hundred labeled OCT images, which can be used to train a classification algorithm.},
keywords = {AG-Huber_OCT, optical coherence tomography, OCT, image registration, glioblastoma multiforme, MHz-OCT, brain imaging, tumor, neurosurgery},
year = {2021},
URL = {https://doi.org/10.1117/12.2578391}
}

@article{Mordmüller-2021,
   author = {Mordmüller, M;Kleyman, V;Schaller, M;Wilson, M;Theisen-Kunde, D;Worthmann, K;Müller, M.A and Brinkmann, R},
   title = {Towards temperature controlled retinal laser treatment with a single laser at 10 kHz repetition rate},
   journal = {Advanced Optical Technologies},
Keywords = {extended Kalman filter; laser-coagulation; model predictive control; ophthalmology; photo-acoustics},
  
   url = {https://doi.org/10.1515/aot-2021-0041},
   year = {2021},
   type = {Journal Article}
}

@article{Kleyman2021,
   author = {Kleyman, V;Schaller, M;Wilson, M;Mordmüller, M;Brinkmann, R;Worthmann, K and Müller, M.A.},
   title = {State and parameter estimation for model-based retinal laser treatment⁎⁎The collaborative project ”Temperature controlled retinal laser treatment” is funded by the German Research Foundation (DFG) under the project number 430154635 (MU 3929/3-1, WO 2056/7-1, BR 1349/6-1). MS was also funded by the DFG (grant WO 2056/2-1, project number 289034702). KW gratefully acknowledges funding by the German Research Foundation (DFG; grant WO 2056/6-1, project number 406141926)},
   journal = {IFAC-PapersOnLine},
   volume = {54(6)},
 
   pages = {244-250},
   ISSN = {2405-8963},
   DOI = {https://doi.org/10.1016/j.ifacol.2021.08.552},
   url = {https://www.sciencedirect.com/science/article/pii/S2405896321013276},
   year = {2021},
   type = {Journal Article}
}

@article{Richert2021,
   title        = {Selective retina therapy and thermal stimulation of the retina: different regenerative properties - implications for AMD therapy},
   author       = {Richert, E;Papenkort, J;von der Burchard, C;Klettner, A;Arnold, P;Lucius, R;Brinkmann, R;Framme, C;Roider, J and Tode, J},
   year         = 2021,
   journal      = {BMC Ophthalmology},
   volume       = {21(1)},
   pages        = 412,
   issn         = {1471-2415},
   url          = {https://doi.org/10.1186/s12886-021-02188-8},
   keywords     = {Selective retina therapy (SRT), Thermal stimulation of the retina (TSR),  Age- related macular  degeneration (AMD), Regeneration, Rejuvenation},
   type         = {Journal Article}
}

@inproceedings{Mordmüller2021,
   author = {Mordmüller, M;Kleymann, V;Schaller, M;Wilson, M;Wothmann, K;Müller, M A and Brinkman, R},
   title = { Towards Model-based Control Techniques for Retinal Laser
Treatment Using Only One Laser},
   booktitle = {ECBO},
url = {https://doi.org/10.1117/12.2615851},
year = {2021},
   type = {Conference Proceedings}
}

@article{Seifert2021,
   author = {Seifert, E;Sonntag, S R;Kleingarn, P;Theisen-Kunde, D;Grisanti, S;Birngruber, R;Miura, Y and Brinkmann, R},
   title = {Investigations on Retinal Pigment Epithelial Damage at Laser Irradiation in the Lower Microsecond Time Regime},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {62(3)},
  
   pages = {32-32},
   ISSN = {1552-5783},
   DOI = {10.1167/iovs.62.3.32},
   url = {https://doi.org/10.1167/iovs.62.3.32},
   year = {2021},
   type = {Journal Article}
}

@article{Miura2021-2,
   author = {Sonntag, S R;Seifert, E;Hamann, M;Lewke, B;Theisen-Kunde, D;Grisanti, S;Brinkmann, R and Miura, Y},
   title = {Fluorescence Lifetime Changes Induced by Laser Irradiation: A Preclinical Study towards the Evaluation of Retinal Metabolic States},
   journal = {Life},
   volume = {11(6)},
  keywords = {retinal laser treatment; metabolic change; fluorescence lifetime imaging ophthalmoscopy},
   pages = {555},
   ISSN = {2075-1729},
   url = {https://www.mdpi.com/2075-1729/11/6/555},
   year = {2021},
   type = {Journal Article}
}

@article{Kyo-2021,
   author = {Kyo, A.;Yamamoto, M.;Hirayama, K.;Kohno, T.;Theisen-Kunde, D.;Brinkmann, R.;Miura, Y. and Honda, S.},
   title = {Factors affecting resolution of subretinal fluid after selective retina therapy for central serous chorioretinopathy},
   journal = {Sci Rep},
   volume = {11(1)},
  
   pages = {8973},
   ISSN = {2045-2322},
   DOI = {10.1038/s41598-021-88372-8},
   year = {2021},
   type = {Journal Article}
}

@article{Burri2021,
   author = {Burri, C;Hutfilz, A;Grimm, L;Salzmann, S;Arnold, P;Považay, B;Meier, C;Ebneter, A;Theisen-Kunde, D and Brinkmann, R},
   title = {Dynamic OCT Signal Loss for Determining RPE Radiant Exposure Damage Thresholds in Microsecond Laser Microsurgery},
   journal = {Applied Sciences},
   volume = {11(12)},
   
   pages = {5535},
   ISSN = {2076-3417},
   DOI = { https://doi.org/10.3390/app11125535},
   url = {https://www.mdpi.com/2076-3417/11/12/5535},
   year = {2021},
keywords = {selective retina therapy; viability assay; photocoagulation; microbubble formation;
thermomechanical damage; fringe washout; coherence-loss},
   type = {Journal Article}
}

@article{Seifert2021,
   author = {Seifert, E;Tode, J;Pielen, A;Theisen-Kunde, D;Framme, C;Roider, J;Miura, Y;Birngruber, R and Brinkmann, R},
   title = {Algorithms for optoacoustically controlled selective retina therapy (SRT)},
   journal = {Photoacoustics},
Keywords = {SRT; Lasers in medicine; Ophthalmology; RPE; Selectivity; Algorithm; Retina therapy; Optoacoustics; Feedback},
   volume = {25},
   pages = {100316},
   ISSN = {2213-5979},
   url = {https://www.sciencedirect.com/science/article/pii/S2213597921000756},
   year = {2021},
   type = {Journal Article}
}

@article{RN5351,
   author = {Richert, E;von der Burchard, C;Klettner, A;Arnold, P;Lucius, R;Brinkmann, R;Roider, J and Tode, J},
   title = {Modulation of inflammatory processes by thermal stimulating and RPE regenerative laser therapies in age related macular degeneration mouse models},
   journal = {Cytokine: X},
   volume = {2},
   number = {3},
   pages = {100031},
   ISSN = {2590-1532},
   DOI = {https://doi.org/10.1016/j.cytox.2020.100031},
   url = {https://www.sciencedirect.com/science/article/pii/S2590153220300112},
   year = {2020},
   type = {Journal Article}
}

@inproceedings{Strenge2020,
author = {P. Strenge and B. Lange and C. Grill and W. Draxinger and M. M. Bonsanto and C. Hagel and R. Huber and R. Brinkmann},
title = {{Segmented OCT data set for depth resolved brain tumor detection validated by histological analysis}},
volume = {11228},
booktitle = {Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIV},
editor = {Joseph A. Izatt and James G. Fujimoto},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {82 -- 89},
keywords = {AG-Huber_OCT, Optical coherence tomography, OCT, FDML Laser, MHz-OCT, brain tumor, brain imaging, neurosurgery},
year = {2020},

URL = {  https://www.spiedigitallibrary.org/conference-proceedings-of-spie/11228/112282O/Segmented-OCT-data-set-for-depth-resolved-brain-tumor-detection/10.1117/12.2545659.short}
}

@article{Brinkmann2020,
   author = {Richert, E;Bartsch, S;Hillenkamp, J;Treumer, F;Tode, J;von der Burchard, C;Brinkmann, R;Klettner, A K and Roider, J},
   title = {Einfluss der Selektiven Retinatherapie (SRT) auf inflammatorische Zellmediatoren des subretinalen Raums},
   journal = {Klin Monatsbl Augenheilkd},
   volume = {237(02)},
   
   pages = {192-201},
   ISSN = {0023-2165},
   DOI = {10.1055/a-0838-5633},
   year = {2020},
   type = {Journal Article}
}

@article{Kleymann2020,
   author = {Kleymann, V;Gernandt, H;Worthmann, K;Hossam, S.A;Brinkmann, R and Müller, A.M},
   title = {Modeling parameter for temperature controlled retinal laser therapies },
   journal = {DeGruyter-at-Automatisierungstechnik},
   volume = {68(11)},
keywords = {retinal photocoagulation, parametric model order
reduction, identification},
   pages = {953-966},
  URL = {https://www.degruyter.com/view/journals/auto/68/11/article-p953.xml},
   year = {2020},
   type = {Journal Article}
}

@article{Miura2020-2,
   author = {Yamamoto, M;Miura, Y;Hirayama, K;;Kohno, T;Kabata, D;Theisen-Kunde, D;Brinkmann, R and Honda, S;},
   title = {Predictive factors of outcome of selective retina therapy for diabetic macular edema},
   journal = {International Ophthalmology},
   ISSN = {1573-2630},
   
   url = {https://doi.org/10.1007/s10792-020-01288-6},
   year = {2020},
   type = {Journal Article}
}

@article{Richert2020,
   author = {Richert, E;Papenkort, J;Klettner, A;Tode, J;Koinzer, S;Brinkmann, R;Fink, C;Roeder, T;Lucius, R. and Roider, J},
   title = {Response of Retinal Pigment Epithelium (RPE)‐Choroid Explants to Thermal Stimulation Therapy of the RPE (TSR)},
   journal = {Lasers in Surgery and Medicine},
Keywords = {age‐related macular degeneration; thermal stimulation therapy of the retinal pigment epithelium;
matrix metalloproteases; pigment epithelium derived factor; retinal pigment epithelium; vascular endothelial
growth factor; transforming growth factor‐β},
   DOI = {DOI 10.1002/lsm.23288},
   year = {2020},
   type = {Journal Article}
}

@article{Hirayama2020,
   author = {Hirayama, K.;Yamamoto, M.;Kohno, T.;Kyo, A.;Theisen-Kunde, D.;Brinkmann, R.;Miura, Y. and Honda, S.},
   title = {Selective retina therapy (SRT) for macular serous retinal detachment associated with tilted disc syndrome},
   journal = {Graefes Arch Clin Exp Ophthalmol},
   ISSN = {0721-832x},
 volume = {259},
   pages = {387-393},
   DOI = {10.1007/s00417-020-04931-1},
   year = {2020},
   type = {Journal Article}
}

@article{yamamoto2020,
   author = {Yamamoto, M;Miura, Y;Kyo, A;Hirayama, K;Kohno, T;Theisen-Kunde, D;Brinkmann, R and Honda, S},
   title = {Selective retina therapy for subretinal fluid associated with choroidal nevus},
   journal = {Amer J Ophthalm Case Rep},
   volume = {19},
   pages = {100794},
   ISSN = {2451-9936},
keywords = {Laser therapy, Choroidal tumor, Retinal pigment epithelium, Retinal disorder},
   DOI = {https://doi.org/10.1016/j.ajoc.2020.100794},
   
   year = {2020},
   type = {Journal Article}
}

@article{brinkmann2020-2,
   author = {Luecking, M;Brinkmann, R;Ramos, Sc;Stork, W and Heussner, N},
   title = {Capabilities and limitations of a new thermal finite volume model for the evaluation of laser-induced thermo-mechanical retinal damage},
   journal = {CompBioMed},
   volume = {122},
   pages = {103835},
   ISSN = {0010-4825},
   DOI = {https://doi.org/10.1016/j.compbiomed.2020.103835},
 
   year = {2020},
   type = {Journal Article}
}

@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}
}

@article{Miura2019/4,
   author = {Miura, Y;Seifert, E;Rehra, J;Kern, K;Theisen-Kunde, D;Denton, M and Brinkmann, R},
   title = {Real-time optoacoustic temperature determination on cell cultures during heat exposure: a feasibility study},
   journal = {Int J Hyperth},
   pages = {1-7},
   ISSN = {0265-6736},
  
   url = {https://doi.org/10.1080/02656736.2019.1590653},
   year = {2019},
   type = {Journal Article}
}

@inbook{Brinkmann2019,
   author = {Považay, Boris;Brinkmann, Ralf;Stoller, Markus and Kessler, Ralf},
   title = {Selective Retina Therapy},
   booktitle = {High Resolution Imaging in Microscopy and Ophthalmology: New Frontiers in Biomedical Optics},
   editor = {Bille, Josef F.},
   publisher = {Springer International Publishing},
   address = {Cham},
   pages = {237-259},
   ISBN = {978-3-030-16638-0},
  
   url = {https://doi.org/10.1007/978-3-030-16638-0_11},
   year = {2019},
   type = {Book Section}
}

@article{Miura2019,
   author = {Hirayama, K;Manabu Yamamoto, M; Takeya Kohno, T; Miura, Y; Brinkmann, R;  Shiraki,K;Theisen-Kunde, D; and Honda, S;},
   title = {Change in the Thickness of Retinal Layers after Selective Retina
Therapy (SRT) in Patients with Central Serous Chorioretinopathy},
   journal = {Osaka City Med.},
   volume = {65},
   pages = {55-63},
   url = {http://dlisv03.media.osaka-cu.ac.jp/il/meta_pub/G0000438repository_00306096-65-1-55},
   year = {2019},
   type = {Journal Article}
}

@article{Brinkmann2020,
   author = {Strittmatter, F;Eisel, M; Brinkmann, R; Cordes, J;Lange, B and Sroka, R},
   title = {Laser-induced lithotripsy: a review, insight into laboratory work, and lessons learned},
   journal = {Translational Biophotonics},
   volume = {n/a},
   number = {n/a},
   pages = {e201900029},
   ISSN = {2627-1850},
   DOI = {10.1002/tbio.201900029},
   url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/tbio.201900029},
   year = {2019},
   type = {Journal Article}
}

@inproceedings{Detrez2019,
   author = {Detrez, N;Miura, Y;Seifert, E;Theisen-Kunde, D and Brinkmann, R},
   title = {Heating and optoacoustic temperature determination of cell cultures},
   publisher = {SPIE},
   volume = {11079},
   series = {European Conferences on Biomedical Optics},
booktitle =    {Proc. SPIE 11079, Medical Laser Applications
and Laser-Tissue Interactions IX},
   url = {https://doi.org/10.1117/12.2527024},
keywords = {Laser, Noninvasive thermometry, hyperthermia, temperature measurement, photoacoustics}, optoacoustics,
   year = {2019},
   type = {Conference Proceeding}
}

@article{Hutfilz2019,
   author = {Hutfilz, A;Sonntag, S;Lewke, B;Theisen-Kunde, D;Grisanti, S;Brinkmann, R and Miura, Y},
   title = {Fluorescence Lifetime Imaging Ophthalmoscopy of the Retinal Pigment Epithelium During Wound Healing After Laser Irradiation},
   journal = {Translational Vision Science & Technology},
   volume = {8(5)},
 
   ISSN = {2164-2591},
   DOI = {10.1167/tvst.8.5.12},
   year = {2019},
   type = {Journal Article}
}

@article{Miura2019/3,
   
   author = {Miura, Y;Lewke, B;Hutfilz, A and Brinkmann, R},
   title = {Change in fluorescence lifetime of retinal pigment epithelium under oxidative stress},
   journal = {Nippon Ganka Gakkai Zasshi },
  
   pages = {105-114},
   url = {http://journal.nichigan.or.jp/Disp?style=abst&vol=123&year=2019&mag=0&number=2&start=105},
   year = {2019},
   type = {Journal Article}
}

@article{seifert2018,
   author = {Seifert, E; Tode, J; Pielen, A; Theisen-Kunde, D; Framme, C; Roider, J; Miura, Y; Birngruber, R and Brinkmann, R},
   title = {Selective retina therapy: toward an optically controlled automatic dosing},
   journal = {J Biomed Opt},
   
   pages = {1-12},
   ISSN = {1560-2281 (Electronic)
1083-3668 (Linking)},
   DOI = {10.1117/1.JBO.23.11.115002},   
keywords = {algorithm, lasers in medicine, ophthalmology, retinal pigment epithelium, selective retina therapy, selectivity},
   year = {2018},
   type = {Journal Article}
}

@article{Brinkmann2018,
   author = {Han, J W; Choi, J; Kim, Y S, Kim, J; Brinkmann, R; Lyu, J and Park, T K},
   title = {Comparison of the neuroinflammatory responses to selective retina therapy and continuous-wave laser photocoagulation in mouse eyes},
   journal = {Graefe's Archive for Clinical and Experimental Ophthalmology},
   
   pages = {341-353},
 
URL= {https://doi.org/10.1007/s00417-017-3883-7},
   year = {2018},
   type = {Journal Article}
}

@article{Miura2018,
   author = {Kern, K; Mertineit, C L; Brinkmann, R and Miura, Y},
   title = {Expression of heat shock protein 70 and cell death kinetics after different thermal impacts on cultured retinal pigment epithelial cells},
   journal = {Exp Eye Res},
  
   pages = {117-126},
   ISSN = {1096-0007 (Electronic)
0014-4835 (Linking)},
   DOI = {10.1016/j.exer.2018.02.013},
   year = {2018},
   type = {Journal Article}
}

@article{Brinkmann2018,
   author = {Richert, E; Koinzer, S; Tode, J; Schlott, K; Brinkmann, R; Hillenkamp, J; Klettner, A and Roider, J},
   title = {Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy},
   journal = {Investigative Ophthalmology & Visual Science},
   
   pages = {1323-1331},
   ISSN = {1552-5783},
  
   url = {http://dx.doi.org/10.1167/iovs.17-23163},
   year = {2018},
   type = {Journal Article}
}

   @book{Brinkmann2018/2,
   author = {Herzog, C;Thompson, O; Schmarbeck, B; Siebert, M and Brinkmann, R},
   title = {Temperature-controlled laser therapy of the retina via robust adaptive Ɦ∞-control},
   publisher = {De Gruyter},
   
   journal = {at-Automatisierungstechnik},
   pages = {1051-1063},   
   year = {2018},
   type = {Book},
  URL = {https://doi.org/10.1515/auto-2018-0066},
   
  
keywords = {Laser therapy; robust control; parameter estimation; photoacoustics; real-time temperature determination},
   abstract = {Recent studies demonstrate therapeutic benefits in retinal laser therapy even for non-visible effects of the irradiation. However, in practice, ophthalmologists often rely on the visual inspection of irradiation sites to manually set the laser power for subsequent ones. Since absorption properties vary strongly between sites, this procedure can lead to under- or over-treatment. To achieve safe automatic retinal laser therapy, this article proposes a robust control scheme based on photoacoustic feedback of the retinal temperature increase. The control scheme is further extended to adapt to real-time parameter estimates and associated bounds on the uncertainty of each irradiation site. Both approaches are successfully validated in ex vivo experiments on pigs’ eyes, achieving consistent irradiation durations of 55 ms despite the uncertainty in absorption properties.}
}

@article{Baade2017,
   author = {Baade, A; von der Burchard, C; Lawin, M; Koinzer, S; Schmarbeck, B; Schlott, K; Miura, Y; Roider, J; Birngruber, R and Brinkmann, R},
   title = {Power-controlled temperature guided retinal laser therapy},
   journal = {J Biomed Opt},
   
   pages = {1-11},
   ISSN = {1083-3668},
   DOI = {10.1117/1.jbo.22.11.118001},
   year = {2017},
   type = {Journal Article}
}

@article{Lange2017,
   author = {Lange, Birgit and Jocham, Dieter and Brinkmann, Ralf and Cordes, Jens},
   title = {Stone/tissue differentiation for Holmium laser lithotripsy using autofluorescence: Clinical proof of concept study},
   journal = {Lasers in Surgery and Medicine},
   volume = {49},
   number = {4},
   pages = {361-365},
   ISSN = {1096-9101},
   DOI = {10.1002/lsm.22611},
   year = {2017},
   type = {Journal Article}
}

@article{Brinkmann2017,
   author = {Tode, J;Richert, E;von der Burchard, C;Koinzer, S;Klettner, A;Brinkmann, R and Roider, J},
   title = {Schonende retinale Lasertherapien als Behandlungsoption der trockenen AMD },
   journal = {Spitzenforschung in der Ophthalmologie},
   pages = {170-173},
   ISSN = {1861-4620},
   url = {https://www.dog.org/wp-content/uploads/2009/12/DOG_Sonderband_WEB-min.pdf#page=1&zoom=auto,-57,877},
   year = {2017},
   type = {Journal Article}
}

@inbook{Kepp2017,
   author = {Kepp, Timo and Koinzer, Stefan and Handels, Heinz and Brinkmann, Ralf},
   title = {Registrierung von nicht sichtbaren Laserbehandlungsarealen der Retina in Live-Aufnahmen des Fundus},
   booktitle = {Bildverarbeitung für die Medizin 2017: Algorithmen - Systeme - Anwendungen. Proceedings des Workshops vom 12. bis 14. März 2017 in Heidelberg},
   editor = {Maier-Hein, geb Fritzsche Klaus Hermann and Deserno, geb Lehmann Thomas Martin and Handels, Heinz and Tolxdorff, Thomas},
   publisher = {Springer Berlin Heidelberg},
   address = {Berlin, Heidelberg},
   pages = {331-336},
   ISBN = {978-3-662-54345-0},
   url = {http://dx.doi.org/10.1007/978-3-662-54345-0_74},
   year = {2017},
   type = {Book Section}
}

@article{Miura2017,
   author = {Miura, Y; Pruessner, J; Mertineit, C L; Kern, K; Muenter, M; Moltmann, M; Danicke, V and Brinkmann, R},
   title = {Continuous-wave Thulium Laser for Heating Cultured Cells to Investigate Cellular Thermal Effects},
   journal = {J Vis Exp},
   
   ISSN = {1940-087x},
   DOI = {10.3791/54326},
   year = {2017},
   type = {Journal Article}
  } 

@article{Verbytskyi2017,
   author = {Verbytskyi, Ievgen and Münter, Michael and Buj, Christian and Brinkmann, Ralf},
   title = {A Problem of a Displacement Calculation of Tissue Surface in Non-Contact Photoacoustic Tomography},
   journal = {Naukovi Visti NTUU KPI},
   number = {2},
   pages = {58-64},
   ISSN = {2519-8890},
   url = {http://dx.doi.org/10.20535/1810-0546.2017.2.98021},
   year = {2017},
   type = {Journal Article}
}

@article{Schlott2016,
   author = {Schlott, Kerstin and Koinzer, Stefan and Baade, Alexander and Birngruber, Reginald and Roider, Johann and Brinkmann, Ralf},
   title = {Lesion strength control by automatic temperature guided retinal photocoagulation},
   journal = {Journal of Biomedical Optics},
   volume = {21},
   number = {9},
   pages = {098001-098001},
   note = {10.1117/1.JBO.21.9.098001},
   abstract = {Abstract.  Laser photocoagulation is an established treatment for a variety of retinal diseases. However, when using the same irradiation parameter, the size and strength of the lesions are unpredictable due to unknown inter- and intraindividual optical properties of the fundus layers. The aim of this work is to investigate a feedback system to generate desired lesions of preselectable strengths by automatically controlling the irradiation time. Optoacoustics were used for retinal temperature monitoring. A 532-nm continuous wave Nd:YAG laser was used for photocoagulation. A 75-ns/523-nm Q-switched Nd:YLF laser simultaneously excited temperature-dependent pressure transients, which were detected at the cornea by an ultrasonic transducer embedded in a contact lens. The temperature data were analyzed during the irradiation by a LabVIEW routine. The treatment laser was switched off automatically when the required lesion strength was achieved. Five different feedback control algorithms for different lesion sizes were developed and tested on rabbits in vivo. With a laser spot diameter of 133  μm, five different lesion types with ophthalmoscopically visible diameters ranging mostly between 100 and 200  μm, and different appearances were achieved by automatic exposure time control. The automatically controlled lesions were widely independent of the treatment laser power and the retinal pigmentation.},
   ISSN = {1083-3668},
   DOI = {10.1117/1.JBO.21.9.098001},
   year = {2016},
   type = {Journal Article}
}

@article{Yasui2016,
   author = {Yasui, Ayako and Yamamoto, Manabu and Hirayama, Kumiko and Shiraki, Kunihiko and Theisen-Kunde, Dirk and Brinkmann, Ralf and Miura, Yoko and Kohno, Takeya},
   title = {Retinal sensitivity after selective retina therapy (SRT) on patients with central serous chorioretinopathy},
   journal = {Graefe's Archive for Clinical and Experimental Ophthalmology},
   pages = {1-12},
   abstract = {To assess retinal sensitivity after selective retina therapy (SRT) in patients with central serous chorioretinopathy (CSCR).},
   ISSN = {1435-702X},
   url = {http://dx.doi.org/10.1007/s00417-016-3441-8},
   year = {2016},
   type = {Journal Article}
}

@inproceedings{Bliedtner2016,
   author = {Bliedtner, Katharina and Seifert, Eric and Stockmann, Leoni and Effe, Lisa and Brinkmann, Ralf},
   title = {Towards real time speckle controlled retinal photocoagulation},
   volume = {9693},
   pages = {96931A-96931A-6},
   note = {10.1117/12.2212703},
   abstract = {Photocoagulation is a laser treatment widely used for the therapy of several retinal diseases. Intra- and inter-individual variations of the ocular transmission, light scattering and the retinal absorption makes it impossible to achieve a uniform effective exposure and hence a uniform damage throughout the therapy. A real-time monitoring and control of the induced damage is highly requested. Here, an approach to realize a real time optical feedback using dynamic speckle analysis is presented. A 532 nm continuous wave Nd:YAG laser is used for coagulation. During coagulation, speckle dynamics are monitored by a coherent object illumination using a 633nm HeNe laser and analyzed by a CMOS camera with a frame rate up to 1 kHz. It is obvious that a control system needs to determine whether the desired damage is achieved to shut down the system in a fraction of the exposure time. Here we use a fast and simple adaption of the generalized difference algorithm to analyze the speckle movements. This algorithm runs on a FPGA and is able to calculate a feedback value which is correlated to the thermal and coagulation induced tissue motion and thus the achieved damage. For different spot sizes (50-200 μm) and different exposure times (50-500 ms) the algorithm shows the ability to discriminate between different categories of retinal pigment epithelial damage ex-vivo in enucleated porcine eyes. Furthermore in-vivo experiments in rabbits show the ability of the system to determine tissue changes in living tissue during coagulation.},
   url = {http://dx.doi.org/10.1117/12.2212703},
   type = {Conference Proceedings},
year = { 2016}
}

@article{Hüttmann2016,
   author = {Huttmann, Gereon and Moltmann, Moritz and Spahr, Hendrik and Tode, Jan and de Roeck, Anna and Theisen-Kunde, Dirk and Birngruber, Reginald and Koinzer, Stefan and Brinkmann, Ralf},
   title = {Retinal lesion formation during photocoagulation investigated by high-speed 1060 nm Doppler-OCT: first clinical results},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {57},
   number = {12},
   pages = {5852-5852},
   abstract = {Abstract Purpose : The molecular processes during heating with a photocoagulation laser, particularly in sub-visible or mere thermal stimulation treatment, have only partly been understood, and different theories exist that try to explain its clinical efficacy. Optical coherence tomography (OCT) was successfully used to grade lesions with high accuracy 1 hour after the treatments and beyond. During the irradiation, changes in tissue scattering and, by use of the Doppler signal, tissue motion caused by thermal expansion and coagulation-induced tissue contraction were shown to correlate ex-vivo and in rabbits with the strength of photocoagulation lesions. Aim of this study was to validate feasibility and reproducibility of these results in humans. Methods : In an ongoing study more than 100 lesions of three patients have been imaged with a slitlamp-based OCT (1060 nm, 90,000 A-scans/s) with varying irradiance during laser exposure. Durations of the exposure were 50 ms and 200 ms; spot size was 300 µm. Eye movements and heart beat were corrected by cross-correlation of the images. Increased tissue scattering and movement of the neuronal retina due to thermal expansion were determined from the image sequences with 3 ms temporal resolution. Results : In the first treatments with this prototype device, we received acceptable image quality in 1/3 of the lesions. Changes in the neuronal retina were successful visualized during and after the laser irradiation, demonstrating the feasibility of a real-time assessment of initial effects of photocoagulation in humans. Lesion visibility in standard, reflection-based OCT was much weaker during treatment compared to 1 hour afterwards. Increased tissue scattering was observed in stronger lesions already during the laser irradiation. At reduced irradiance, scattering increase was only observed after the end of irradiation. However, tissue motion towards the vitreous was still observed in these cases. Conclusions : In conclusion, high-speed OCT recording during photocoagulation measures initial tissue changes during photocoagulation in humans. It may enhance our understanding of the tissue dynamics right after laser irradiation. It may provide useful information for a real-time dosage control as well. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.},
   ISSN = {1552-5783},
   url = {http://dx.doi.org/},
   year = {2016},
   type = {Journal Article}
}

@article{Park2015,
   author = {Park, Young Gun and Kang, Seungbum and Brinkmann, Ralf and Roh, Young-Jung},
   title = {A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation},
   journal = {Journal of Ophthalmology},
   volume = {2015},
   pages = {8},
   DOI = {10.1155/2015/247259},
   url = {http://dx.doi.org/10.1155/2015/247259},
   year = {2015},
   type = {Journal Article}
}

@article{Hüttmann2015,
   author = {Huttmann, Gereon and Koinzer, Stefan Otto Johannes and Müller, Heike and Ellerkamp, Iris and Baade, Alex and Moltmann, Moritz and Theisen-Kunde, Dirk and Lange, Birgit and Brinkmann, Ralf and Birngruber, Reginald},
   title = {Predicting ophthalmoscopic visibility of retinal photocoagulation lesions byhigh-speedOCT: an animal studyinrabbits},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {56},
   number = {7},
   pages = {5980-5980},
   ISSN = {1552-5783},
   year = {2015},
   type = {Journal Article}
}

@article{Steiner2015,
   author = {Steiner, Patrick and Ebneter, Andreas and Berger, Lieselotte Erika and Zinkernagel, Martin and Považay, Boris and Meier, Christoph and Kowal, Jens H. and Framme, Carsten and Brinkmann, Ralf and Wolf, Sebastian and Sznitman, Raphael},
   title = {Time-Resolved Ultra–High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina TherapyTime-Resolved Ultra–High Resolution OCT During SRT},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {56},
   number = {11},
   pages = {6654-6662},
   note = {10.1167/iovs.15-17151},
   abstract = {Abstract Purpose: Selective retina therapy (SRT) is a novel treatment for retinal pathologies, solely targeting the RPE. During SRT, the detection of an immediate tissue reaction is challenging, as tissue effects remain limited to intracellular RPE photodisruption. Time-resolved ultra-high axial resolution optical coherence tomography (OCT) is thus evaluated for the monitoring of dynamic optical changes at and around the RPE during SRT. Methods: An experimental OCT system with an ultra-high axial resolution of 1.78 μm was combined with an SRT system and time-resolved OCT M-scans of the target area were recorded from four patients undergoing SRT. Optical coherence tomography scans were analyzed and OCT morphology was correlated with findings in fluorescein angiography, fundus photography, and cross-sectional OCT. Results: In cases in which the irradiation caused RPE damage proven by fluorescein angiography, the lesions were well discernible in time-resolved OCT images but remained invisible in fundus photography and cross-sectional OCT acquired after treatment. If RPE damage was introduced, all applied SRT pulses led to detectable signal changes in the time-resolved OCT images. The extent of optical signal variation seen in the OCT data appeared to scale with the applied SRT pulse energy. Conclusions: The first clinical results proved that successful SRT irradiation induces detectable changes in the OCT M-scan signal while it remains invisible in conventional ophthalmoscopic imaging. Thus, real-time high-resolution OCT is a promising modality to monitor and analyze tissue effects introduced by selective retina therapy and may be used to guide SRT in an automatic feedback mode (www.swissmedic.ch number, 2011-MD-0006).},
   ISSN = {1552-5783},
   DOI = {10.1167/iovs.15-17151},
   year = {2015},
   type = {Journal Article}
}

@article{Iwami2014,
   author = {Iwami, H. and Pruessner, J. and Shiraki, K. and Brinkmann, R. and Miura, Y.},
   title = {Protective effect of a laser-induced sub-lethal temperature rise on RPE cells from oxidative stress},
   journal = {Exp Eye Res},
   volume = {124c},
   pages = {37-47},
   note = {1096-0007
Iwami, Hisashi
Pruessner, Joachim
Shiraki, Kunihiko
Brinkmann, Ralf
Miura, Yoko
Journal article
Exp Eye Res. 2014 May 5;124C:37-47. doi: 10.1016/j.exer.2014.04.014.},
   abstract = {Recently introduced new technologies that enable temperature-controlled laser irradiation on the RPE allowed us to investigate temperature-resolved RPE cell responses. In this study we aimed primarily to establish an experimental setup that can realize laser irradiation on RPE cell culture with the similar temperature distribution as in the clinical application, with a precise time/temperature history. With this setup, we conducted investigations to elucidate the temperature-dependent RPE cell biochemical responses and the effect of transient hyperthermia on the responses of RPE cells to the secondary-exposed oxidative stress. Porcine RPE cells cultivated in a culture dish (inner diameter = 30 mm) with culture medium were used, on which laser radiation (lambda = 1940 nm, spot diameter = 30 mm) over 10 s was applied as a heat source. The irradiation provides a radially decreasing temperature profile which is close to a Gaussian shape with the highest temperature in the center. Power setting for irradiation was determined such that the peak temperature (Tmax) in the center of the laser spot at the cells reaches from 40 degrees C to 58 degrees C (40, 43, 46, 50, 58 degrees C). Cell viability was investigated with ethidium homodimer III staining at the time points of 3 and 24 h following laser irradiation. Twenty four hours after laser irradiation the cells were exposed to hydrogen peroxide (H2O2) for 5 h, followed by the measurement of intracellular glutathione, intracellular 4-hydroxynonenal (HNE) protein adducts, and secreted vascular endothelial growth factor (VEGF). The mean temperature threshold for RPE cell death after 3 h was found to be around 52 degrees C, and for 24 h around 50 degrees C with the current irradiation setting. A sub-lethal preconditioning on Tmax = 43 degrees C significantly induced the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, and decreased H2O2-induced increase of intracellular 4-HNE protein adducts. Although sub-lethal hyperthermia (Tmax = 40 degrees C, 43 degrees C, and 46 degrees C) caused a slight increase of VEGF secretion in 6 h directly following irradiation, secondary exposed H2O2-induced VEGF secretion was significantly reduced in the sub-lethally preheated groups, where the largest effect was seen following the irradiation with Tmax = 43 degrees C. In summary, the current results suggest that sub-lethal thermal laser irradiation on the RPE at Tmax = 43 degrees C for 10 s enhances cell defense system against oxidative stress, with increasing the GSH/GSSG ratio. Together with the results that the decreased amount of H2O2-induced 4-HNE in sub-lethally preheated RPE cells was accompanied by the lower secretion of VEGF, it is also strongly suggested that the sub-lethal hyperthermia may modify RPE cell functionality to protect RPE cells from oxidative stress and associated functional decrease, which are considered to play a significant role in the pathogenesis of age-related macular degeneration and other chorioretinal degenerative diseases.},
   ISSN = {0014-4835},
   DOI = {10.1016/j.exer.2014.04.014},
   year = {2014},
   type = {Journal Article}
}

@article{Koinzer2014,
   title        = {Comprehensive detection, grading, and growth behavior evaluation of subthreshold and low intensity photocoagulation lesions by optical coherence tomographic and infrared image analysis},
   author       = {Koinzer, S. and Caliebe, A. and Portz, L. and Saeger, M. and Miura, Y. and Schlott, K. and Brinkmann, R. and Roider, J.},
   year         = 2014,
   journal      = {Biomed Res Int},
   volume       = 2014,
   pages        = 492679,
   doi          = {10.1155/2014/492679},
   url          = {http://dx.doi.org/10.1155/2014/492679},
   note         = {2314-6141 Koinzer, Stefan Caliebe, Amke Portz, Lea Saeger, Mark Miura, Yoko Schlott, Kerstin Brinkmann, Ralf Roider, Johann Journal Article Research Support, Non-U.S. Gov't United States Biomed Res Int. 2014;2014:492679. doi: 10.1155/2014/492679. Epub 2014 May 12.},
   abstract     = {PURPOSE: To correlate the long-term clinical effect of photocoagulation lesions after 6 months, as measured by their retinal damage size, to exposure parameters. We used optical coherence tomographic (OCT)-based lesion classes in order to detect and assess clinically invisible and mild lesions. METHODS: In this prospective study, 488 photocoagulation lesions were imaged in 20 patients. We varied irradiation diameters (100/300 microm), exposure-times (20-200 ms), and power. Intensities were classified in OCT images after one hour, and we evaluated OCT and infrared (IR) images over six months after exposure. RESULTS: For six consecutive OCT-based lesion classes, the following parameters increased with the class: ophthalmoscopic, OCT and IR visibility rate, fundus and OCT diameter, and IR area, but not irradiation power. OCT diameters correlated with exposure-time, irradiation diameter, and OCT class. OCT classes discriminated the largest bandwidth of OCT diameters. CONCLUSION: OCT classes represent objective and valid endpoints of photocoagulation intensity even for "subthreshold" intensities. They are suitable to calculate the treated retinal area. As the area is critical for treatment efficacy, OCT classes are useful to define treatment intensity, calculate necessary lesion numbers, and universally categorize lesions in clinical studies.},
   type         = {Journal Article}
}

@article{Rohde2014,
   author = {Rohde, Ingo and Brinkmann, Ralf},
   title = {Gain broadening and mode-locking in overcoupled second harmonic Q-switched microsecond pulses},
   journal = {Journal of Optics},
   volume = {16},
   number = {10},
   pages = {105209},
   abstract = {An intracavity frequency doubled, Q-switched Nd:YLF emitting at a wavelength of 527 nm was designed with the goal to temporally stretch the Q-switched pulses up to some microseconds at pulse energies of several millijoules. With different resonator configurations pulse durations between 12 μ s and 3 μ s with energies of 1 mJ–4.5 mJ have been achieved, which is demanded for an application in ophthalmology. For tighter intracavity foci and high pump power, however, strong power modulations by trains of picosecond pulses on the rear flank of the microsecond pulses were observed, indicating the occurrence of cascading nonlinearities and mode-locking. Simultaneously a significant increase of the fundamental spectrum up to 5 nm was found. A similar effect, which is referred to as gain broadening, has previously been observed by using ppKTP for intracavity second harmonic generation. This is, to the best of our knowledge, the first observation of this effect with unpoled second harmonic media.},
   ISSN = {2040-8986},
   url = {http://stacks.iop.org/2040-8986/16/i=10/a=105209},
   year = {2014},
   type = {Journal Article}
}

@inproceedings{Bliedtner2013,
   author = {Bliedtner, Kathrin and Seifert, Eric and Brinkmann, Ralf},
   title = {Temperature induced tissue deformation monitored
by dynamic speckle interferometry},
   booktitle = {Studierendentagung},
   publisher = {Universität zu Lübeck},
   type = {Conference Proceedings},
year = { 2013},
url = { http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.714.8862&rep=rep1&type=pdf}
}

@inproceedings{Baade2013,
   author = {Baade, Alexander and Schlott, Kerstin and Birngruber, Reginald and Brinkmann, Ralf},
   title = {A numerical model for heat and pressure propagation for temperature controlled retinal photocoagulation},
   volume = {8803},
   pages = {88030O-88030O-9},
   note = {10.1117/12.2033590},
   abstract = {Retinal photocoagulation is an established treatment for various retinal diseases. The temperature development during a treatment can be monitored by applying short laser pulses in addition to the treatment laser light. The laser pulses induce thermoelastic pressure waves that can be detected at the cornea. We present a numerical model to examine the temperature development during the treatment as well as the formation and propagation of the ultrasonic waves. Using the model, it is possible to determine the peak temperature during retinal photocoagulation from the measured signal, and investigate the behaviour of the temperature profile and the accuracy of the temperature determination under varying conditions such as inhomogeneous pigmentation or change in irradiation parameters. It was shown that there is an uncertainty of 2.5 -9% in the determination of the peak temperature when the absorption coefficient between the absorbing layers is varied by a factor of 2. Furthermore the model was extended in order to incorporate the photoacoustic pressure generation and wave propagation. It was shown that for an irradiation pulse duration of 75 ns the resulting pressure wave energy is attenuated by 76 % due to frequency dependent attenuation in water.},
   url = {http://dx.doi.org/10.1117/12.2033590},
   type = {Conference Proceedings}, 
year = { 2013}
}

@inproceedings{Rohde2013,
   author = {Rohde, Ingo and Masch, Jennifer- M. and Theisen-Kunde, Dirk and Marczynski-Bühlow, Martin and Lutter, Georg and Brinkmann, Ralf},
   title = {Cardiovascular damage after cw and Q-switched 2μm laser irradiation},
   volume = {8803},
   pages = {88030I-88030I-6},
   note = {10.1117/12.2033550},
   abstract = {Aiming for laser-assisted resection of calcified aortic valve structures for Transcatheter Aortic Valve Implantation (TAVI), a Q-switched Tm:YAG laser emitting at a wavelength of 2.01 μm was used to evaluate the cutting efficiency on highly calcified human aortic leaflets in-vitro. The calcified aortic leaflets were examined regarding ablation rates and debris generation, using a pulse energy of 4.3 mJ, a pulse duration of 0.8-1 μs and a repetition rate of 1 kHz. The radiation was transmitted via a 200 μm core diameter quartz fiber. Resection was performed in a fiber-tissue contact mode on water-covered samples in a dish. The remnant particles were analyzed with respect to quantity and size by light microscopy. Additionally, soft tissue of porcine aortic vessels was examined for histologically detectable thermo-mechanical damage after continuous wave and Q-switched 2μm laser irradiation. An ablation rate of 36.7 ± 25.3 mg/min could be realised on highly calcified aortic leaflets, with 85.4% of the remnant particles being <6 μm in diameter. The maximum damaged area of the soft tissue was < 1 mm for both, cw and pulsed laser irradiation. This limits the expected collateral damage of healthy tissue during the medical procedure. Overall, the Q-switched Tm:YAG laser system showed promising results in cutting calcified aortic valves, transmitting sufficient energy through a small flexible fibre.},
   url = {http://dx.doi.org/10.1117/12.2033550},
   type = {Conference Proceedings},
year = { 2013}
}

@inproceedings{Horstmann2013,
   author = {Horstmann, Jens and Brinkmann, Ralf},
   title = {Non-contact photoacoustic tomography using holographic full field detection},
   publisher = {Proc. SPIE},
   volume = {8800},
   pages = {880007-880007-6},
   note = {10.1117/12.2033599},
   abstract = {An innovative very fast non-contact imaging technique for Photoacoustic Tomography is introduced. It is based on holographic optical speckle detection of a transiently altering surface topography for the reconstruction of absorbing targets. The surface movement is obtained by parallel recording of speckle phase changes known as Electronic Speckle Pattern Interferometry. Due to parallelized 2-D camera detection and repetitive excitation with variable delay with respect to the image acquisition, data recording of whole volumes for Photoacoustic Imaging can be completed in times far below one second. The size of the detected area is scalable by optical magnification. As a proof of concept, an interferometric setup is realized, capable of surface displacement detection with an axial resolution of less than 3 nm. The potential of the proposed method for in vivo Photoacoustic Imaging is discussed.},
   url = {http://dx.doi.org/10.1117/12.2033599},
   type = {Conference Proceedings},
year = { 2013}
}

@article{Koinzer2013,
   author = {Koinzer, Stefan and Saeger, Mark and Hesse, Carola and Portz, Lea and Kleemann, Susanne and Schlott, Kerstin and Brinkmann, Ralf and Roider, Johann},
   title = {Correlation with OCT and histology of photocoagulation lesions in patients and rabbits},
   journal = {Acta Ophthalmologica},
   pages = {no-no},
   abstract = {Purpose:  To examine spectral domain optical coherence tomographic (OCT) and histological images from comparable retinal photocoagulation lesions in rabbits, and to correlate these images with comparable OCT images from patients. Methods:  508 rabbit lesions were examined by HE-stained paraffin histology. 1019 rabbit lesions versus 236 patient lesions were examined by OCT, all at the time-points 1 hr, 1 week and 4 weeks after photocoagulation. We analysed 100 μm lesions (in humans) and 133 μm lesions (in rabbits) of 200 ms exposures at powers titrated from the histological threshold up to intense damage. Lesions were matched according to morphological criteria. Results:  Dome-shaped layer alterations, retinal infiltration by round, pigmented cells, outer nuclear layer interruption, and eventually full thickness retinal coagulation are detectable in histology and OCT. Horizontal damage extensions are found 1½ times larger in OCT. More intense irradiation was necessary to induce comparable layer affection in rabbit OCT as in histology. Restoration of the inner retinal layers is only shown in the OCT images. Comparable primary lesions caused more pronounced OCT changes in patients than in rabbits during healing. Conclusions:  Optical coherence tomographic images indicate different tissue changes than histologic images. After photocoagulation, they show wider horizontal damage diameters, but underestimate axial damage particularly during healing. Conclusions on retinal restoration should not be drawn from OCT findings alone. Retinal recovery after comparable initial lesions appears to be more complete in rabbit than in patient OCTs.},
   keywords = {histology
laser
optical coherence tomography
photocoagulation
retina
retinal healing},
   year = {2013}
}

@article{Miura2013,
   author = {Miura, Y. and Huettmann, G. and Orzekowsky-Schroeder, R. and Steven, P. and Szaszak, M. and Koop, N. and Brinkmann, R.},
   title = {Two-Photon Microscopy and Fluorescence Lifetime Imaging of Retinal Pigment Epithelial Cells under Oxidative Stress},
   journal = {Invest Ophthalmol Vis Sci},
   note = {Miura, Yoko
Huettmann, Gereon
Orzekowsky-Schroeder, Regina
Steven, Philipp
Szaszak, Marta
Koop, Norbert
Brinkmann, Ralf
ENG
2013/04/06 06:00
Invest Ophthalmol Vis Sci. 2013 Apr 4. pii: iovs.13-11808v1. doi: 10.1167/iovs.13-11808.},
   abstract = {PURPOSE: The aim of this study was to investigate the autofluorescence (AF) of the RPE with two-photon microscopy (TPM) and fluorescence lifetime imaging (FLIM) under normal and oxidative stress conditions. METHODS: Porcine RPE-choroid explants were used for investigation. The RPE-choroid tissue was preserved in a perfusion organ culture system. Oxidative stress was induced by laser photocoagulation with frequency-doubled Nd:YAG laser (532 nm) and by exposure to different concentrations (0, 1, 10 mM) of ferrous sulfate (FeSO4) for 1 hr. At indicated time points after exposure, the tissue was examined with TPM and FLIM. Intracellular reactive oxygen species around the photocoagulation lesion were detected with chloromethyl-2'7'-dichlorofluorescein diacetate (CM-H2DCFDA). Melanosomes were isolated from RPE cells and its fluorescence properties were investigated under normal and oxidized conditions. RESULTS: Under normal condition, AF in RPE cells with TPM is mostly originated from melanosomes, which has a very short fluorescence lifetime (FLT) (mean=117 ps). Under oxidative stress induced by laser irradiation and FeSO4 exposure, bright granular AF appears inside and around RPE cells, whose FLT is significantly longer (mean=1388 ps) than the FLT of the melanosome-AF. Excitation and emission peaks are found at 710-750 nm and 450-500 nm, respectively. Oxidative stress increases the fluorescence intensity of the melanosomes but does not change their FLT. CONCLUSION: TPM reveals acute oxidative stress-induced bright AF granules inside and around RPE cells which can be clearly discriminated from melanosomes by FLIM. TPM combined with FLIM is a useful tool of live-cell analysis to investigate functional alterations of the RPE.},
   year = {2013}
}

@misc{Miura2013,
   author = {Miura, Y and Huettmann, G and Orzekowsky-Schroeder, R and Steven, P and Szaszák, M and Koop, N and Brinkmann, R },
   title = {Two-photon Microscopy and Fluorescence Lifetime Analysis of Lipid Peroxidation Product in Photoreceptor Outer Segment and in Retinal Pigment Epithelial Cell},
   publisher = {ARVO Meeting Abstracts},
   month = {March 26, 2012 },
   url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=57630548-893d-4e45-9ddc-b6f547dd4ff0&cKey=d08a30bc-fe98-40a2-8a1c-1b171e4becd3&mKey=f0fce029-9bf8-4e7c-b48e-9ff7711d4a0e},
   year = {2013},
   type = {Poster}
}

@article{Brinkmann2013,
   author = {Brinkmann, Ralf and Iwami, Hisashi and Pruessner, Joachim and Danicke, Veit and Miura, Yoko},
   title = {Temperature-dependent response of retinal pigment epithelial cells to laser irradiation},
   journal = {Invest. Ophthalmol. Vis. Sci.},
   volume = {54},
   number = {6},
   pages = {1809-},
   abstract = {PurposeSublethal thermal therapy of the retinal pigment epithelium (RPE) is discussed as a new prophylactic therapy for age-related macular degeneration. However, temperature-dependent RPE cell effects have not been well elucidated. We investigated the biochemical responses of RPE cells following sublethal to lethal thermal laser irradiation. MethodsPorcine RPE cells cultured in a dish (33mm) were heated with a Thulium laser (1.92{micro}m, 1-20W, 10s) over a spot of 3mm. Temperatures during irradiation were measured with thermocouples. Cell viability was examined using annexin-V, ethidium homodimer III and Hoechst 33342 for detecting apoptotic, necrotic and living cell, respectively, by using fluorescence microscopy for localization and flow cytometry for quantification. Secretion of vascular endothelial growth factor (VEGF) for 6h following irradiation on different temperatures was assessed with Elisa assay. In order to examine a protective effect of sublethal hyperthremia, the cells were heated up to 45C 24h prior to the exposure of 2 mM hydroxyl peroxide (H2O2) for 5 h. The involvement of TRPV (Transient Receptor Potential Vanilloid)-1 receptor, which is activated with temperatures > 43C, was investigated by adding capsazepin, a TRPV-1 inhibitor, before irradiation. ResultsCell apoptosis and necrosis was observed 24 h after irradiation with a central peak temperature [&ge;]52C. Fluorescence microscopy revealed apoptotic cells around the central necrotic area. VEGF secretion for 6h after irradiation was significantly increased at peak temperatures between 40 and 52C in a temperature dependent manner (max. 110%, p<0.05), whereas the total secretion decreases with temperatures > 52C. Pre-irradiation onto 45C significantly reduced H2O2-induced cell death after 5h compared to non-heated cells (total cell death: 15.6% to 10.2%, necrosis: 6% to 4 %, early apoptosis: 5.1% to 3.6%; p<0.01). These effects were not observed in the existence of capsazepin during laser irradiation. ConclusionsThe number of apoptotic and necrotic RPE cells increase at least over 24h following thermal laser irradiation. Sublethal temperatures between 40 and 52C seem to induce various cellular responses as VEGF secretion, which might be related to the protective effect against oxidative stress. Results with capsazepin suggest that TRPV-1 channel activation by hyperthermia is essential to exert this protective effect.},
   url = {http://abstracts.iovs.org/cgi/content/abstract/54/6/1809},
   year = {2013},
   type = {Journal Article}
}

@article{Cordes2013,
   author = {Cordes, Jens and Nguyen, Felix and Lange, Birgit and Brinkmann, Ralf and Jocham, Dieter},
   title = {Damage of Stone Baskets by Endourologic Lithotripters: A Laboratory Study of 5 Lithotripters and 4 Basket Types},
   journal = {Advances in Urology},
   volume = {2013},
   pages = {6},
   DOI = {10.1155/2013/632790},
   url = {http://dx.doi.org/10.1155/2013/632790},
   year = {2013},
   type = {Journal Article}
}

@inproceedings{Seifert2013,
   author = {Seifert, Eric and Roh, Young-Jung and Fritz, Andreas and Park, Young Gun and Kang, Seungbum and Theisen-Kunde, Dirk and Brinkmann, Ralf},
   title = {Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model},
   volume = {8803},
   pages = {880303-880303-6},
year = {2013},
   note = {10.1117/12.2033560},
   abstract = {Selective Retina Therapy (SRT) targets the Retinal Pigment Epithelium (RPE) without effecting neighboring layers as the photoreceptors or the choroid. SRT related RPE defects are ophthalmoscopically invisible. Owing to this invisibility and the variation of the threshold radiant exposure for RPE damage the treating physician does not know whether the treatment was successful or not. Thus measurement techniques enabling a correct dosing are a demanded element in SRT devices. The acquired signal can be used for monitoring or automatic irradiation control. Existing monitoring techniques are based on the detection of micro-bubbles. These bubbles are the origin of RPE cell damage for pulse durations in the ns and μs time regime 5μs. The detection can be performed by optical or acoustical approaches. Monitoring based on an acoustical approach has already been used to study the beneficial effects of SRT on diabetic macula edema and central serous retinopathy. We have developed a first real time feedback technique able to detect micro-bubble induced characteristics in the backscattered laser light fast enough to cease the laser irradiation within a burst. Therefore the laser energy within a burst of at most 30 pulses is increased linearly with every pulse. The laser irradiation is ceased as soon as micro-bubbles are detected. With this automatic approach it was possible to observe invisible lesions, an intact photoreceptor layer and a reconstruction of the RPE within one week.},
   url = {http://dx.doi.org/10.1117/12.2033560},
   type = {Conference Proceedings}
}

@inproceedings{Oepen2013,
   author = {van Oepen, Alexander and Horstmann, Jens and Brinkmann, Ralf},
   title = {Characterization of an Electronic Speckle Pattern Detection System},
   booktitle = {Studierendentagung},
   type = {Conference Proceedings}
}

@article{Rohde2012,
   author = {Rohde, Ingo and Brinkmann, Ralf and Theisen-Kunde, Dirk},
   title = {Temporally stretched Q-switched pulses in the 2 µm spectral range},
   journal = {Laser Physics Letters},
   volume = {9},
   number = {11},
   pages = {808-813},
   year = {2012}
}

@article{Treumer2012,
   author = {Treumer, F. and Klettner, A. and Baltz, J. and Hussain, A. A. and Miura, Y. and Brinkmann, R. and Roider, J. and Hillenkamp, J.},
   title = {Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): towards slowing the macular ageing process},
   journal = {Exp Eye Res},
   volume = {97},
   number = {1},
   pages = {63-72},
   note = {1096-0007
Treumer, F
Klettner, A
Baltz, J
Hussain, A A
Miura, Y
Brinkmann, R
Roider, J
Hillenkamp, J
Journal Article
England
Exp Eye Res. 2012 Apr;97(1):63-72. doi: 10.1016/j.exer.2012.02.011. Epub 2012 Feb 22.},
   abstract = {The purpose of this study was to investigate release of matrix metalloproteinases (MMP) 2 and 9 during retinal pigment epithelium (RPE) wound healing after Selective Retina Therapy (SRT) with laser energy levels below and above the threshold of RPE cell death. Following exposure to SRT using a prototype pulsed Nd:YLF laser with energies of 80-180 mJ/cm(2) fresh porcine RPE-monolayers with Bruch's membrane and choroid were cultured in modified Ussing chambers which separate the apical (RPE-facing) and basal (choroid facing) sides of the RPE monolayer. Threshold energy for RPE cell death and wound healing were determined with calcein-AM viability test. Inactive and active forms of MMP 2 and 9 were quantified within tissue samples and in the culture medium of the apical and basal compartments of the Ussing chamber using gelatine zymography. Laser energies of 160-180 mJ/cm(2) resulted in cell death within 1 h while 120-140 mJ/cm(2) resulted in delayed death of exposed RPE cells. All cells survived 80 and 100 mJ/cm(2). Laser spots healed within 6 days after SRT accompanied by a transient vectorial increase of MMPs. SRT with 180 mJ/cm(2) increased active MMP 2 by 1.9 (p < 0.05) and 1.6 (p < 0.05) fold in tissue and basal compartments, respectively, without alterations in the apical compartment. Pro-MMP 2 levels were also significantly increased in all compartments (p < 0.05). Release of MMP 9 was not altered. Laser energy below the threshold of RPE cell death did not alter the release of MMP 2 or 9. The findings suggest that the release of active MMP 2 on the basal side of the RPE during wound healing following SRT may address age-related pathological changes of Bruch's membrane with a potential to slow degenerative macular ageing processes before irreversible functional loss has occurred.},
   keywords = {Animals
Cell Death
Cell Survival
Choroid/*enzymology/pathology
Diffusion Chambers, Culture
Fluoresceins/metabolism
*Laser Therapy
Lasers, Solid-State
Macular Degeneration/enzymology/pathology/*surgery
Matrix Metalloproteinase 2/*metabolism
Matrix Metalloproteinase 9/*metabolism
Organ Culture Techniques
Retinal Pigment Epithelium/*enzymology/pathology
Sensory Thresholds
Swine
Wound Healing/*physiology},
   ISSN = {0014-4835},
   DOI = {10.1016/j.exer.2012.02.011},
   year = {2012},
   type = {Journal Article}
}

@article{Koinzer2012,
   author = {Koinzer, S. and Schlott, K. and Ptaszynski, L. and Bever, M. and Kleemann, S. and Saeger, M. and Baade, A. and Caliebe, A. and Miura, Y. and Birngruber, R. and Brinkmann, R. and Roider, J.},
   title = {Temperature-controlled retinal photocoagulation - a step toward automated laser treatment},
   journal = {Invest Ophthalmol Vis Sci},
   volume = {53},
   number = {7},
   pages = {3605-14},
   note = {Using Smart Source Parsing
Jun 14; Print 2012 Jul},
   abstract = {Purpose. Retinal laser photocoagulation carries the risk of overtreatment due to effect variation of identically applied lesions. The degree of coagulation depends on the induced temperature increase and on exposure time. We introduce temperature controlled photocoagulation (TCP), which uses optoacoustics to determine individually exposure times necessary to create reproducible lesions. Methods. Optoacoustic temperature measurement relies on pressure waves that are excited in the retinal tissue by repetitive low-energy laser pulses. Signal amplitudes correlate with tissue temperature and are detected by a transducer in the laser contact lens. We used a continuous wave (CW) photocoagulator for treatment irradiation and superimposed probe laser pulses for simultaneous temperature measurement. Optoacoustic data of 1500 lesions (rabbit) were evaluated to develop an algorithm that controls exposure times automatically in TCP. Lesion diameters of 156 TCP lesions were compared to 156 non-controlled lesions. Histology was performed after 1 hour, and 1 and 4 weeks. Results. TCP resulted in exposure times from 4 to 800 ms depending on laser power chosen. Ophthalmoscopic and histologic lesion diameters were independent of power between 14 and 200 mW. TCP lesions barely were visible with a mean diameter equal to the treatment beam (130 mum). In contrast, standard lesion diameters increased linearly and statistically significantly with power. Histology confirmed sparing of the ganglion and nerve fiber layers in TCP. Conclusions. TCP facilitates uniform retinal lesions over a wide power range. In a clinical setting, it should generate soft and reproducible lesions independently of local tissue variation and improve safety, particularly at short exposure times.},
   year = {2012}
}

@article{Yoshimoto,
   author = {Yoshimoto, Kumiko and Yamamoto, Manabu and Kohno, Takeya and Yoneda, Tasuku and Yoshida, Yusaku and Fritz, Andreas and Theisen-Kunde, Dirk and Miura, Yoko and Brinkmann, Ralf and Shiraki, Kunihiko},
   title = {Detection Of Sub-threshold Laser Irradiation Spots With Various Fundus Imaging Methods And Its Correlation With Irradiation Energy And Optoacoustic Values In Selective Retina Therapy },
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {53},
   pages = {5198},
   year = {2012}
}

@article{Iwami2012,
   author = {Iwami, Hisashi and Ptaszynski, Lars and Danicke, Veit and Brinkmann, Ralf and Miura, Yoko},
   title = {Sublethal Hyperthermia-induced Vascular Endothelial Growth Factor Secretion And Its Contribution To Adoptive Response Of Retinal Pigment Epithelial Cell},
   journal = {Invest. Ophthalmol. Vis. Sci.},
   volume = {53},
   number = {6},
   pages = {4782-},
   abstract = {PurposeTo investigate temperature increase-induced secretion of vascular endothelial growth factor (VEGF) from retinal pigment epithelial (RPE) cells and its contribution to adoptive response relating to cell defence system against oxidative stress. MethodsPorcine RPE cells on 35 mm culture dish were used in the study. Thulium laser ({lambda}=1940 nm, spot size 33 mm was utilized as a heat source. Temperature increase during irradiation for different power and time setting at cell level was measured with thermocouple, and power and time setting of the experiment was determined based on this calibration. Culture medium was replaced by 1.2 ml phosphate buffer saline and then laser was irradiated with different power settings for 10 seconds, so that the peak temperature reaches from 40{degrees}C to 65{degrees}C. Cellular viability after laser irradiation was examined with MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay immediately after irradiation. VEGF secretion was investigated with enzyme-linked immunosorbent assay (ELISA) at 2 and 24 hrs after irradiation. Contribution of a temperature-dependent calcium channel, TRPV (transient receptor potential vanilloid) channels in laser-induced VEGF secretion was investigated using TRPV channel blocker, ruthenium red (20 {micro}M). TRPV channel blocker-containing medium was replaced by the normal medium soon after laser irradiation. Hydrogen peroxide (H2O2) or advanced glycation endproduct (AGE)-was exposed after 6 hrs of laser irradiation and cell viability was examined with MTT assay. ResultsPeak temperature threshold for immediate RPE cell death was found around 55 {degrees}C with our irradiation setting. VEGF secretion was increased after sub-lethal irradiation in power-dependent manner, which was partially suppressed by TRPV channel blocker. Sublethal laser irradiation reduced H2O2 and AGE-induced cell death and this effect was smaller in the cells treated with TRPV channel inhibitor during laser irradiation. ConclusionsSublethal temperature increase-induced VEGF production might contribute to the enhancement of RPE cell defence system against oxidative stress.},
   url = {http://abstracts.iovs.org/cgi/content/abstract/53/6/4782},
   year = {2012},
   type = {Journal Article}
}

@article{Schlott2012,
   author = {Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Bever, Marco and Baade, Alex and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Automatic temperature controlled retinal photocoagulation},
   journal = {Journal of Biomedical Optics},
   volume = {17},
   number = {6},
   pages = {061223},
   keywords = {AutoPhoN},
   year = {2012}
}

@article{Koinzer,
   author = {Koinzer, Stefan and Schlott, Kerstin and Portz, Lea and Ptaszynski, Lars and Baade, Alexander and Bever, Marco and Saeger, Mark and Caliebe, Amke and Denner, Renè and Birngruber, Reginald and Brinkmann, Ralf and Roider, Johann},
   title = {Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation},
   journal = {Journal of Biophotonics},
   pages = {n/a-n/a},
   abstract = {We conducted a study to correlate the retinal temperature rise during photocoagulation to the afterward detected tissue effect in optical coherence tomography (OCT). 504 photocoagulation lesions were examined in 20 patients. The retinal temperature increase was determined in real-time during treatment based on thermoelastic tissue expansion which was probed by repetitively applied ns laser pulses. The tissue effect was examined on fundus images and OCT images of individualized lesions. We discerned seven characteristic morphological OCT lesion classes. Their validity was confirmed by increasing visibility and diameters. Mean peak temperatures at the end of irradiation ranged from approx. 60 °C to beyond 100 °C, depending on burn intensity. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)},
   keywords = {laser photocoagulation
optoacoustics
photocoagulation
retinal temperature
spectral domain optical coherence tomography
OCT
subthreshold
classification},
   year = {2012}
}

@article{Yamamoto,
   author = {Yamamoto, Manabu and Kohno, Takeya and Yoshida, Yusaku and Yoneda, Tasuku and Iwami, Hisashi and Fritz, Andreas and Theisen-Kunde, Dirk and Miura, Yoko and Brinkmann, Ralf and Shiraki, Kunihiko},
   title = {Selective Retina Therapy for Patients with Central Serous Chorioretinopathy in Japan },
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {53},
   pages = {5222},
   year = {2012}
}

@article{Brinkmann2012,
   author = {Brinkmann, Ralf and Koinzer, Stefan and Schlott, Kerstin and Ptaszynski, Lars and Bever, Marco and Baade, Alexander and Luft, Susanne and Miura, Yoko and Roider, Johann and Birngruber, Reginald},
   title = {Real-time temperature determination during retinal photocoagulation on patients},
   journal = {Journal of Biomedical Optics},
   volume = {17},
   number = {6},
   pages = {061219},
   note = {Journal Article},
   year = { 2012}
}

@book{RN5360,
   author = {Brinkmann, Ralf;Koinzer, Stefan;Schlott, Kerstin;Ptaszynski, Lars;Bever, Marco;Baade, Alex;Miura, Yoko;Birngruber, Reginald and Roider, Johann},
   title = {Realtime temperature determination during retinal photocoagulation on patients},
   publisher = {SPIE},
   volume = {7885},
   series = {SPIE BiOS},
   url = {https://doi.org/10.1117/12.875276},
   year = {2011},
   type = {Book}
}

@inproceedings{Horstmann2011,
   author = {Horstmann, Jens and Baade, Alexander and Brinkmann, Ralf},
   title = {Photoacoustic blood vessel detection during surgical laser interventions},
   publisher = {SPIE ECBO},
   volume = {8092},
   pages = {80920Z-80920Z-6},
   note = {10.1117/12.889635},
   abstract = {This paper presents a discussion about the potential of photoacoustics with regard to its application in surgical assistance during minimally invasive, laser assisted interventions. Aim of the work is the detection of obscured large blood vessels in order to prevent unintentional dissection. Based on spectroscopic investigations of the target tissue (liver), a wavelength for the photoacoustic excitation laser was chosen with respect to a high absorption contrast between the vessel and the surrounding liver tissue. An experimental setup featuring a simple liver model is created. Preliminary results show, that vessels with a diameter of 2 mm can be detected up to a distance of 1 mm from the treatment fibre. It is shown, that detection of acoustic waves induced inside liver is feasible over distances higher than 10 cm.},
   url = {http://dx.doi.org/10.1117/12.889635},
   type = {Conference Proceedings},
year = { 2011}
}

@inproceedings{Schlott2011,
   author = {Schlott, Kerstin and Koinzer, Stefan and Ptaszynski, Lars and Luft, Susanne and Baade, Alex and Bever, Marco and Roider, Johann and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Optoacoustic temperature determination and automatic coagulation control in rabbits},
   booktitle = {Ophthalmic Technologies XXI },
   editor = {Ho, Fabrice Manns; Per G. Söderberg; Arthur},
   publisher = {Proc. SPIE},
   volume = {7885},
   note = {10.1117/12.875104},
   abstract = {Retinal laser photocoagulation is an established treatment method for many retinal diseases like macula edema or diabetic retinopathy. The selection of the laser parameters is so far based on post treatment evaluation of the lesion size and strength. Due to local pigment variations in the fundus and individual transmission the same laser parameters often lead to an overtreatment. Optoacoustic allows a non invasive monitoring of the retinal temperature increase during retinal laser irradiation by measuring the temperature dependent pressure amplitudes, which are induced by short probe laser pulses. A 75 ns/ 523 nm Nd:YLF was used as a probe laser at a repetition rate of 1 kHz, and a cw / 532 nm treatment laser for heating. A contact lens was modified with a ring-shaped ultrasonic transducer to detect the pressure waves at the cornea. Temperatures were collected for irradiations leading to soft or invisible lesions. Based on this data the threshold for denaturation was found. By analyzing the initial temperature increase, the further temperature development during irradiation could be predicted. An algorithm was found to calculate the irradiation time, which is needed for a soft lesion formation, from the temperature curve. By this it was possible to provide a real-time dosimetry by automatically switching off the treatment laser after the calculated irradiation time. Automatically controlled coagulations appear softer and more uniformly.},
   keywords = {AutoPhoN},
   url = {http://dx.doi.org/10.1117/12.875104},
   type = {Conference Proceedings},
year = { 2011}
}

@inproceedings{Müller-2011-2,
   author = {Muller, Heike H. and Ptaszynski, Lars and Schlott, Kerstin and Bonin, Tim and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf and Huttmann, Gereon},
   title = {Imaging of temperature distribution and retinal tissue changes during photocoagulation by high speed OCT},
   editor = {James, G. Fujimoto and Joseph, A. Izatt and Valery, V. Tuchin},
   publisher = {SPIE},
   volume = {7889},
   pages = {78890E},
URL = { https://doi.org/10.1117/12.874788},
year = { 2011}

}

@inproceedings{Fritz2011,
   author = {Fritz, Andreas and Zegelin, Andrea and Ptaszynski, Lars and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Dynamics of laser induced micro bubble clusters on tissue phantoms},
   volume = {7885},
   pages = {78850S-78850S-6},
   note = {10.1117/12.875031},
   abstract = {Selective retina treatment (SRT) is a laser based method to treat retinal diseases associated with disorders of the retinal pigment epithelium (RPE) while preserving photoreceptors and choroid. Applying microsecond laser pulses to the 100- 200 strongly absorbing melanin granules inside the RPE cells induces transient micro bubbles which disrupt the cells. Aim of this work is to understand bubble dynamics in clusters with respect to the influence of the adjacent retina. Bubble dynamics were investigated in vitro on porcine RPE. An about 200 μm thick layer of agarose gel was applied to the RPE layer in order to simulate the mechanical properties of retina. Different laser pulse durations from 1 ns (532 nm, Nd:YAG) to 1.7 μs (527 nm, Nd:YLF) were used. The bubbles were investigated interferometrically (fiber interferometer @ 830 nm) and with fast flash photography (25 ns flash duration). Bubble lifetimes were measured. The results show that with retina phantoms the bubble formation threshold was reached at 2.5 times higher irradiation than without retina phantom for 1.7 μs laser pulses. The microbubbles generated with 1 ns laser pulses were almost not influenced by the agarose layer. Irradiation twofold over bubble formation threshold resulted in 3.5 times longer bubble lifetimes for μs and 2 times longer for ns pulse durations, respectively.},
   url = {https://www.spiedigitallibrary.org/conference-proceedings-of-spie/7885/1/Dynamics-of-laser-induced-micro-bubble-clusters-on-tissue-phantoms/10.1117/12.875031.short},
   type = {Conference Proceedings},
year = { 2011}
}

@article{Obana,
   title        = {A Case of Retinal Injury By A Violet Light-Emitting Diode},
   author       = {Obana, Akira and Brinkmann, Ralf and Gohto, Yuko and Nishimura, Kasumi},
   year         = 2011,
   journal      = {Retinal Cases and Brief Reports},
   volume       = 5,
   number       = 3,
   pages        = {223--226 10.1097/ICB.0b013e3181e180d5},
   abstract     = {Purpose: To describe the first case of retinal injury by a misuse of a toy using light-emitting diode. Methods: A 15-year-old male Japanese student received irradiation on his right eye by a 5 mW light-emitting diode of 410 nm wavelength for 20 seconds in 2 days. He noticed decreased vision and central scotoma approximately 2 weeks later from these events. The mechanism of injury was evaluated from the estimated irradiance on the retina by comparison with experimental threshold data published. Results: Chorioretinal atrophy with visual loss and central scotoma has remained on the fovea. The patient received an estimated dose of 1.58 J/cm2 2 times, which was close to the experimentally determined radiant exposure for photochemical injury of rat retina. Conclusion: The violet light from light-emitting diodes is a potential hazard for the retina, and thus, direct viewing into the beam should be avoided. Children, especially, should not be allowed to play with such toys without being carefully instructed about their proper use and fully supervised.},
   keywords     = {black light light-emitting diode photochemical damage retinal injury visual disturbance. 01271216-201100530-00011}
}

@article{Obana,
   author = {Obana, Akira and Brinkmann, Ralf and Gohto, Yuko and Nishimura, Kasumi},
   title = {A Case of Retinal Injury By A Violet Light-Emitting Diode},
   journal = {Retinal Cases and Brief Reports},
   volume = {5},
   number = {3},
   pages = {223-226 10.1097/ICB.0b013e3181e180d5},
   abstract = {Purpose: To describe the first case of retinal injury by a misuse of a toy using light-emitting diode. Methods: A 15-year-old male Japanese student received irradiation on his right eye by a 5 mW light-emitting diode of 410 nm wavelength for 20 seconds in 2 days. He noticed decreased vision and central scotoma approximately 2 weeks later from these events. The mechanism of injury was evaluated from the estimated irradiance on the retina by comparison with experimental threshold data published. Results: Chorioretinal atrophy with visual loss and central scotoma has remained on the fovea. The patient received an estimated dose of 1.58 J/cm2 2 times, which was close to the experimentally determined radiant exposure for photochemical injury of rat retina. Conclusion: The violet light from light-emitting diodes is a potential hazard for the retina, and thus, direct viewing into the beam should be avoided. Children, especially, should not be allowed to play with such toys without being carefully instructed about their proper use and fully supervised.},
   keywords = {black light
light-emitting diode
photochemical damage
retinal injury
visual disturbance.
01271216-201100530-00011},
   year = {2011}
}

@inproceedings{Miura2010,
   author = {Miura, Y and Huettmann, G and Orzekowsky-Schroeder, R and Steven, P and Szaszák, M and Koop, N and Brinkmann, R},
   title = {Appearance of autofluorescence in RPE cells at the rim of photocoagulation},
   booktitle = {FLIM 2010 - Symposium "Fluorescence Lifetime Imaging of the Human Retina"},
   type = {Conference Proceedings},
Year = { 2010}
}

@inproceedings{Schlott2009,
   author = {Schlott, Kerstin and Langejürgen, Jens and Bever, Marco and Koinzer, Stefan and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Time resolved detection of tissue denaturation during retinal photocoagulation},
   editor = {7373, Proc. SPIE},
   pages = {73730E-73730E},
   note = {10.1117/12.831877},
   abstract = {The retinal photocoagulation is an established treatment method for different retinal diseases. The extent of the thermal coagulations depends strongly on the generated temperature increase. Until now the dosage is based on a pool of experience of the treating physicians as well as the appearance of the whitish lesions on the retina. The temperature course during photocoagulation can be measured in real-time by optoacoustics. A frequency-doubled Q-switched Nd:YLF laser (523nm, 75 ns) is used for optoacoustic excitation and a continuous-wave Nd:YAG laser (532nm) with adjustable irradiation time and power for heating of the fundus tissue. The onset of coagulation is determined by a photodiode that is placed directly behind enucleated porcine eyes, which served as a model. The onset of coagulation is observed clearly when scattering sets in. The required power for coagulation increases exponentially with decreasing irradiation time. The first results on rabbit eyes in vivo indicate that the onset of coagulation defined by just barely visibile lesions at a slit lamp sets in at an ED50 threshold temperature of 63°C for an irradiation time of 400 ms. In conclusion, optoacoustics can be used to determine temperatures during retinal laser treatments in real-time. This allows evaluating the time-temperature-dependence of retinal coagulation in vivo.},
   keywords = {AutoPhoN},
   url = {http://dx.doi.org/10.1117/12.831877},
   type = {Conference Proceedings},
year = { 2009},
url = { https://doi.org/10.1117/12.168030}
}

@inproceedings{Fritz2007,
   author = {Fritz, Andreas and Ptaszynski, Lars and Stoehr, Hardo and Brinkmann, Ralf},
   title = {Dynamics and detection of laser induced microbubbles in the retinal pigment epithelium (RPE)},
   volume = {6632},
   pages = {66321C-66321C-11},
   note = {10.1117/12.728344},
   abstract = {Selective Retina Treatment (SRT) is a new method to treat eye diseases associated with disorders of the RPE. Selective RPE cell damage is achieved by applying a train of 1.7 μs laser pulses at 527 nm. The treatment of retinal diseases as e.g. diabetic maculopathy (DMP), is currently investigated within clinical studies, however 200 ns pulse durations are under investigation. Transient micro bubbles in the retinal pigment epithelium (RPE) are expected to be the origin of cell damage due to irradiation with laser pulses shorter than 50 μs. The bubbles emerge at the strongly absorbing RPE melanosomes. Cell membrane disruption caused by the transient associated volume increase is expected to be the origin of the angiographically observed RPE leakage. We investigate micro bubble formation and dynamics in porcine RPE using pulse durations of 150 ns. A laser interferometry system at 830 nm with the aim of an online dosimetry control for SRT was developed. Bubble formation was detected interferometrically and by fast flash photography. A correlation to cell damage observed with a vitality stain is found. A bubble detection algorithm is presented.},
   url = {http://dx.doi.org/10.1117/12.728344},
   type = {Conference Proceedings}
}

@inproceedings{Herrmann2007,
   author = {Herrmann, Katharina and Flöhr, Christian and Stalljohann, Jens and Apiou-Sbirlea, Gabriela and Kandulla, Jochen and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Influence of choroidal perfusion on retinal temperature increase during retinal laser treatments},
   volume = {6632},
   pages = {66321D-66321D-7},
   note = {10.1117/12.728222},
   abstract = {In most retinal laser treatments the therapeutic effect is initiated by a transient temperature increase at and around the retinal pigment epithelium (RPE). Especially in long exposure time treatments like Transpupillary Thermotherapy (TTT) choroidal perfusion has a strong influence on the realized temperature at the fundus. The fundus blood circulation and therefore the heat dissipation is influenced by the intraocular pressure (IOP), which is investigated in the study presented here. In order to reduce the choroidal perfusion, the IOP is increased by injection of physiological saline solution into the eye of anaesthetized rabbits. The fundus is irradiated with 3.64 W/cm2 by means of a TTT-laser (λ = 810 nm) for t = 20 s causing a retinal temperature increase. Realtime temperature determination at the irradiated spot is achieved by a non invasive optoacoustic technique. Perfusion can be reduced by increasing IOP, which leads to different temperature increases when irradiating the retina. This should be considered for long time laser treatments.},
   url = {http://dx.doi.org/10.1117/12.728222},
   type = {Conference Proceedings},
year = { 2007}
}

@inproceedings{Stoehr2007-1,
   author = {Stoehr, Hardo and Ptaszynski, Lars and Fritz, Andreas and Brinkmann, Ralf},
   title = {Interferometric optical online dosimetry for selective retina treatment (SRT)},
   volume = {6426},
   pages = {642619-642619-7},
   note = {10.1117/12.708521},
   abstract = {In selective retina treatment (SRT) spatial confined tissue damage in the absorbing retinal pigment epithelium (RPE) is obtained by applying microsecond laser pulses. The damage in the RPE is caused by transient microbubbles forming around the laser heated melanin granules inside the cells. For treatment of RPE related diseases, SRT is thought to share the therapeutic benefits of conventional photocoagulation but without affecting the photoreceptors. A drawback for effective clinical SRT is that the laser-induced lesions are ophthalmoscopically invisible. Therefore, a real-time feedback system for dosimetry is demanded in order to avoid undertreatment or unwanted collateral damage to the adjacent tissue. We develop a dosimetry system which uses optical interferometry for the detection of the transient microbubbles. The system is based on an optical fiber interferometer which is operated with a laser diode at 830nm. We present current results obtained with porcine RPE explants in vitro and complete porcine eye globes ex vivo.},
   url = {http://dx.doi.org/10.1117/12.708521},
   type = {Conference Proceedings},
Year = { 2007}
}

@inproceedings{Schlott2007,
   author = {Schlott, Kerstin and Stalljohann, Jens and Weber, Benjamin and Kandulla, Jochen and Herrmann, Katharina and Birngruber, Reginald and Brinkmann, Ralf},
   title = {Optoacoustic online temperature determination during retinal laser photocoagulation},
   volume = {6632},
   pages = {66321B-66321B-8},
   note = {10.1117/12.728291},
   abstract = {Retinal photocoagulation is an established treatment of different retinal diseases. The treatment relies on a short, local heating of the tissue which induces a denaturation. The resulting scar formation may for example prevent the further detachment of the retina. The extent of the coagulation is besides other parameters mostly dependent on the induced temperature increase. However, until today a temperature based dosimetry for photocoagulation does not exist. The dosage is rather based on the experience of the treating physicians to achieve visible whitish lesions on the retina. In this work a technique is presented, which allows an online temperature monitoring during photocoagulation. If an absorbing material is irradiated with short laser pulses, a thermoelastic expansion of the absorber induces an acoustic wave. Its amplitude is dependent on the temperature of the absorber. For analyzing the applicability of the optoacoustic temperature determination for dosimetry, measurements were performed on enucleated porcine eye globes. The pressure transients are detected by an ultrasonic transducer, which is embedded in an ophthalmologic contact lens. As long as no strong lesions occur, the determined temperatures are almost proportional to the power of the treatment laser. Using a spot diameter of 200 μm and different laser powers, the temperature rise at the end of the 400 ms irradiation was found to be approximately 0.16 °C/mW. The onset of the denaturation was observed around 50°C. The far aim of this project is an automatic regulation of the treatment laser onto a desired temperature course.},
   url = {http://dx.doi.org/10.1117/12.728291},
   type = {Conference Proceedings},
year = { 2007}
}