@article{Wang2015,
   author = {Wang, S. and Huttmann, G. and Zhang, Z. and Vogel, A. and Birngruber, R. and Tangutoori, S. and Hasan, T. and Rahmanzadeh, R.},
   title = {Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67},
   journal = {Mol Pharm},
   note = {1543-8392
Wang, Sijia
Huttmann, Gereon
Zhang, Zhenxi
Vogel, Alfred
Birngruber, Reginald
Tangutoori, Shifalika
Hasan, Tayyaba
Rahmanzadeh, Ramtin
Journal article
Mol Pharm. 2015 Aug 13.},
   abstract = {The selective inhibition of intracellular and nuclear molecules such as Ki-67 holds great promise for the treatment of cancer and other diseases. However, the choice of the target protein and the intracellular delivery of the functional agent remain crucial challenges. Main hurdles are (a) an effective delivery into cells, (b) endosomal escape of the delivered agents, and (c) an effective, externally triggered destruction of cells. Here we show a light-controlled two-step approach for selective cellular delivery and cell elimination of proliferating cells. Three different cell-penetrating nano constructs, including liposomes, conjugates with the nuclear localization sequence (NLS), and conjugates with the cell penetrating peptide Pep-1, delivered the light activatable antibody conjugate TuBB-9-FITC, which targets the proliferation associated protein Ki-67. HeLa cells were treated with the photosensitizer benzoporphyrin monoacid derivative (BPD) and the antibody constructs. In the first optically controlled step, activation of BPD at 690 nm triggered a controlled endosomal escape of the TuBB-9-FITC constructs. In more than 75% of Ki-67 positive, irradiated cells TuBB-9-FITC antibodies relocated within 24 h from cytoplasmic organelles to the cell nucleus and bound to Ki-67. After a second light irradiation at 490 nm, which activated FITC, cell viability decreased to approximately 13%. Our study shows an effective targeting strategy, which uses light-controlled endosomal escape and the light inactivation of Ki-67 for cell elimination. The fact that liposomal or peptide-assisted delivery give similar results leads to the additional conclusion that an effective mechanism for endosomal escape leaves greater variability for the choice of the delivery agent.},
   keywords = {endosomal entrapment
liposome
nanotechnology
nuclear localization sequence (NLS)
photodynamic therapy},
   ISSN = {1543-8384},
   DOI = {10.1021/acs.molpharmaceut.5b00260},
   year = {2015},
   type = {Journal Article}
}

@article{Ansari2015,
   author = {Ansari, R. and Buj, C. and Pieper, M. and Konig, P. and Schweikard, A. and Huttmann, G.},
   title = {Micro-anatomical and functional assessment of ciliated epithelium in mouse trachea using optical coherence phase microscopy},
   journal = {Opt Express},
   volume = {23},
   number = {18},
   pages = {23217-24},
   note = {1094-4087
Ansari, Rehman
Buj, Christian
Pieper, Mario
Konig, Peter
Schweikard, Achim
Huttmann, Gereon
Journal Article
United States
Opt Express. 2015 Sep 7;23(18):23217-24. doi: 10.1364/OE.23.023217.},
   abstract = {Motile cilia perform a range of important mechanosensory and chemosensory functions, along with expulsion of mucus and inhaled pathogens from the lungs. Here we demonstrate that spectral domain optical coherence phase microscopy (SD-OCPM), which combines the principles of optical coherence tomography (OCT) and confocal microscopy, is particularly well-suited for characterization of both morphology and the ciliary dynamics of mouse trachea. We present micro-anatomical images of mouse trachea, where different cell types can be clearly visualized. The phase contrast, which measures the sub-nanometer changes in axial optical pathlength is used to determine the frequency and direction of cilia beatings.},
   ISSN = {1094-4087},
   DOI = {10.1364/oe.23.023217},
   year = {2015},
   type = {Journal Article}
}

title = {Non-Invasive Multi-Dimensional Two-Photon Microscopy enables optical fingerprinting (TPOF) of immune cells},
journal = {Journal of Biophotonics},
volume = {8},
number = {6},
pages = {466-479},
keywords = {ocular surface, intravital two-photon microscopy, antigen presenting cells, in vivo, non invasive},
doi = {https://doi.org/10.1002/jbio.201400036},
url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/jbio.201400036},
eprint = {https://onlinelibrary.wiley.com/doi/pdf/10.1002/jbio.201400036},
abstract = {Mucosal surfaces are constantly exposed to pathogens and show high immunological activity. In a broad variety of ocular surface disorders inflammation is common, but underlying mechanisms are often not fully understood. However, the main clinical problem is that inflammatory processes are difficult to characterize and quantify due to the impossibility of repeated tissue probing of the delicate ocular surface. Therefore non-invasive optical methods are thought to have the potential for intravital investigation of ocular surface inflammation. This study demonstrates the general potential of two-photon microscopy to non-invasively detect and discriminate key players of inflammation in the ocular surface by using intrinsic fluorescence-based features without the necessity of tissue probing or the use of dyes. The use of wavelength dependent measurements of fluorescence lifetime, in addition to autofluorescence intensity enables a functional differentiation of isolated immune cells in vitro at excitation wavelengths between 710 to 830 nm. Mixed cell cultures and first in vivo results indicate the use of excitation wavelength of 710 to 750 nm for further experiments and future use in patients. Two photon based autofluorescence features of immune cells enables non-invasive differentiation.},
year = {2015}
}

@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{Guder2014,
   author = {Guder, Ellen and Lankenau, Eva and Fleischhauer, F. and Schulz-Hildebrandt, H. and Hüttmann, G. and Pau, H. W. and Just, Tino},
   title = {Microanatomy of the tympanic membrane in chronic myringitis obtained with optical coherence tomography},
   journal = {European Archives of Oto-Rhino-Laryngology},
   pages = {1-7},
   keywords = {Optical coherence tomography
Tympanic membrane
Chronic myringitis},
   ISSN = {0937-4477},
   DOI = {10.1007/s00405-014-3373-z},
   url = {http://dx.doi.org/10.1007/s00405-014-3373-z},
   year = {2014},
   type = {Journal Article}
}

@article {Steven900,
	author = {Philipp Steven and Carolin Le Blanc and Eva Lankenau and Marc Krug and Stefan Oelckers and Ludwig M Heindl and Uta Gehlsen and Gereon Huettmann and Claus Cursiefen},
	title = {Optimising deep anterior lamellar keratoplasty (DALK) using intraoperative online optical coherence tomography (iOCT)},
	volume = {98},
	number = {7},
	pages = {900--904},
	year = {2014},
	doi = {10.1136/bjophthalmol-2013-304585},
	publisher = {BMJ Publishing Group Ltd},
	abstract = {Background/aims To describe the use of intraoperative online optical coherence tomography (iOCT) for improving deep anterior lamellar keratoplasty (DALK) surgery. Methods Retrospective case series of 6 eyes of 6 male patients with keratokonus, corneal dystrophy or herpetic stromal scars undergoing DALK were investigated using intraoperative optical coherence tomography and postsurgical image/video analysis. Main outcome measures were: visibility of surgical steps, especially, assessment of placement depth of injection needle, preparation of bare Descemet{\textquoteright}s membrane and drainage of interface fluid. Results iOCT enables real-time visualisation of all surgical steps of DALK procedure in all patients. Placement of air injection needle above Descemet{\textquoteright}s membrane was reliably monitored as was presence of bare Descemet{\textquoteright}s membrane and potential interface fluid. Conclusions iOCT assists with visualisation of injection needle placement and with assessment of bare Descemet{\textquoteright}s membrane as well as interface fluid during the DALK procedure. Overall iOCT may be a helpful device that supports surgeons in all steps of DALK procedure.},
	issn = {0007-1161},
	URL = {https://bjo.bmj.com/content/98/7/900},
	eprint = {https://bjo.bmj.com/content/98/7/900.full.pdf},
	journal = {British Journal of Ophthalmology}
}

@article{Ansari2014,
   author = {Ansari, Rehman and Myrtus, Christian and Aherrahrou, Redouane and Erdmann, Jeanette and Schweikard, Achim and Hüttmann, Gereon},
   title = {Ultrahigh-resolution, high-speed spectral domain optical coherence phase microscopy},
   journal = {Optics Letters},
   volume = {39},
   number = {1},
   pages = {45-47},
   abstract = {We present an ultrahigh-resolution, high-speed spectral domain optical coherence phase microscopy (SD-OCPM) system that combines submicrometer transverse spatial resolution and subnanometer optical path length sensitivity, with an acquisition speed of over 217,000  voxels/s. The proposed SD-OCPM system overcomes two significant drawbacks of traditional common-path interferometers—limited transverse spatial resolution and suboptimal detection sensitivity—while maintaining phase stability that is comparable with common-path interferometer setups. The transverse and axial spatial resolution of the setup is measured to be 0.6 and 1.9 μm, respectively, with a phase sensitivity of 0.0027 rad (corresponds to optical path length sensitivity of 110 pm). High-speed acquisition allows for phase-sensitive 4D imaging of biological samples with subcellular resolution.},
   keywords = {Microscopy
Coherence imaging
Three-dimensional microscopy},
   DOI = {10.1364/OL.39.000045},
   url = {http://ol.osa.org/abstract.cfm?URI=ol-39-1-45},
   year = {2014},
   type = {Journal Article}
}

@article{10.1001/jamaophthalmol.2013.4672,
    author = {Steven, Philipp and Le Blanc, Carolin and Velten, Kai and Lankenau, Eva and Krug, Marc and Oelckers, Stefan and Heindl, Ludwig M. and Gehlsen, Uta and Hüttmann, Gereon and Cursiefen, Claus},
    title = "{Optimizing Descemet Membrane Endothelial Keratoplasty Using Intraoperative Optical Coherence Tomography}",
    journal = {JAMA Ophthalmology},
    volume = {131},
    number = {9},
    pages = {1135-1142},
    year = {2013},
    month = {09},
    abstract = "{Descemet membrane endothelial keratoplasty (DMEK) is a challenging procedure for the surgeon, particularly because of deficient visibility of the delicate tissue due to the natural en face view through the operating microscope. A cross-sectional view would greatly enhance intraoperative overview and enable the surgeon to better control the procedure.  To retrospectively analyze the use of intraoperative optical coherence tomography (iOCT) for improving the safety of DMEK.Intraoperative OCT during DMEK was performed in 26 eyes of 26 patients. We retrospectively analyzed imaging and video data. Department of Ophthalmology, University of Cologne.Seven men and 19 women aged 39 to 93 years with corneal endothelial dysfunction undergoing DMEK.Descemet membrane endothelial keratoplasty.Visibility of surgical steps, overall duration of DMEK, overall time for complete intraoperative air filling of the anterior chamber, and correlation between donor age and Descemet rolling behavior.Intraoperative OCT enables visualization of all steps of the DMEK procedure. Overall mean (SD) duration of the DMEK procedure was 25.7 (6.9) minutes when using iOCT. Overall mean (SD) complete intraoperative anterior chamber air-filling time was 236 (108) seconds in contrast to 60 to 90 minutes for standard air-filling time. Descemet membrane rolling behavior showed significant inverse correlation between donor age (range, 39-93 years) and the extent of rolling (R2 = 0.5 [P = .006]).Intraoperative OCT enhances the visibility of graft orientation and unfolding, thereby improving safety of the DMEK procedure. Overall, iOCT is a helpful device that may support surgeons in all steps of DMEK procedures.}",
    issn = {2168-6165},
    doi = {10.1001/jamaophthalmol.2013.4672},
    url = {https://doi.org/10.1001/jamaophthalmol.2013.4672},
    eprint = {https://jamanetwork.com/journals/jamaophthalmology/articlepdf/1708786/eoi130143.pdf},
}

@inproceedings{10.1117/12.2033174,
author = {B. Olzowy and N. Starke and T. Schuldt and G. H{\"u}ttmann and E. Lankenau and T. Just},
title = {{Optical coherence tomography and confocal endomicroscopy for rhinologic pathologies: a pilot study}},
volume = {8805},
booktitle = {Head and Neck Optical Diagnostics},
editor = {Christian Betz and Brian J. F. Wong M.D.},
organization = {International Society for Optics and Photonics},
publisher = {SPIE},
pages = {880505},
keywords = {optical coherence tomography, confocal microscopy, inverted papilloma , chronic rhinosinusitis, nasal polyps, mucociliary function, ciliated epithelium},
year = {2013},
doi = {10.1117/12.2033174},
URL = {https://doi.org/10.1117/12.2033174}
}

@article{LankenauKrugOelckersSchrageJustHüttmann+2013+233+239,
url = {https://doi.org/10.1515/aot-2013-0011},
title = {iOCT with surgical microscopes: a new imaging during microsurgery},
title = {},
author = {Eva Maria Lankenau and Marc Krug and Stefan Oelckers and Norbert Schrage and Tino Just and Gereon Hüttmann},
pages = {233--239},
volume = {2},
number = {3},
journal = {Advanced Optical Technologies},
doi = {doi:10.1515/aot-2013-0011},
year = {2013},
lastchecked = {2023-04-13}
}

@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{Xie_2013,
doi = {10.1088/0031-9155/58/3/555},
url = {https://dx.doi.org/10.1088/0031-9155/58/3/555},
year = {2013},
month = {jan},
publisher = {IOP Publishing},
volume = {58},
number = {3},
pages = {555},
author = {Yijing Xie and Tim Bonin and Susanne Löffler and Gereon Hüttmann and Volker Tronnier and Ulrich G Hofmann},
title = {Coronal in vivo forward-imaging of rat brain morphology with an ultra-small optical coherence tomography fiber probe},
journal = {Physics in Medicine & Biology},
abstract = {A well-established navigation method is one of the key conditions for successful brain surgery: it should be accurate, safe and online operable. Recent research shows that optical coherence tomography (OCT) is a potential solution for this application by providing a high resolution and small probe dimension. In this study a fiber-based spectral-domain OCT system utilizing a super-luminescent-diode with the center wavelength of 840 nm providing 14.5 μm axial resolution was used. A composite 125 μm diameter detecting probe with a gradient index (GRIN) fiber fused to a single mode fiber was employed. Signals were reconstructed into grayscale images by horizontally aligning A-scans from the same trajectory with different depths. The reconstructed images can display brain morphology along the entire trajectory. For scans of typical white matter, the signals showed a higher reflection of light intensity with lower penetration depth as well as a steeper attenuation rate compared to the scans typical for gray matter. Micro-structures such as axon bundles (70 μm) in the caudate nucleus are visible in the reconstructed images. This study explores the potential of OCT to be a navigation modality in brain surgery.}
}

@inproceedings{Sudkamp2013,
   author = {Sudkamp, Helge and Lee, H Y and Hüttmann, Gereon and Kellerbee, A K},
   title = {An approach to increase the speed of Optical Coherence Tomography using a Virtually Imaged Phased Array},
   booktitle = {Studierendentagung},
   publisher = {Universität zu Lübeck},
   type = {Conference Proceedings},
year= { 2013}
}

@article{Hillmann2013,
   author = {Hillmann, Dierck and Franke, Gesa and Hinkel, Laura and Bonin, Tim and Koch, Peter and Hüttmann, Gereon},
   title = {Off-axis full-field swept-source optical coherence tomography using holographic refocusing},
   pages = {857104-857104},
   note = {10.1117/12.2006436},
   abstract = {We demonstrate a full-field swept-source OCT using an off-axis geometry of the reference illumination. By using holographic refocusing techniques, a uniform lateral resolution is achieved over the measurement depth of approximately 80 Rayleigh lengths. Compared to a standard on-axis setup, artifacts and autocorrelation signals are suppressed and the measurement depth is doubled by resolving the complex conjugate ambiguity. Holographic refocusing was done efficiently by Fourier-domain resampling as demonstrated before in inverse scattering and holoscopy. It allowed to reconstruct a complete volume with about 10μm resolution over the complete measurement depth of more than 10mm. Off-axis full-field swept-source OCT enables high measurement depths, spanning many Rayleigh lengths with reduced artifacts.},
   DOI = {10.1117/12.2006436},
   url = {http://dx.doi.org/10.1117/12.2006436},
   year = {2013},
   type = {Journal Article}
}

@inproceedings{Fleischhauer2013,
   author = {Fleischhauer, Felix and Schulz-Hildebrandt, Hinnerk and Bonin, Tim and Hüttmann, Gereon},
   title = {Polarization-sensitive optical coherence tomography on different tissues samples for tumor discrimination},
   booktitle = {Studierendentagung},
   publisher = {Universität zu Lübeck},
   type = {Conference Proceedings},
url = { https://pdfs.semanticscholar.org/a581/a18366acff021e12dcc090b40890ea70dcb8.pdf},
 year = { 2013}
}

@article{Franke2013,
   author = {Franke, Gesa Lilith and Hillmann, Dierck and Lührs, Christian and Koch, Peter and Wollenzin, Jörn and Hüttmann, Gereon},
   title = {Towards microscopic resolution in holoscopy},
   pages = {85711O-85711O},
   note = {10.1117/12.2006806},
   abstract = {Holoscopy is a new imaging approach combining digital holography and full-field Fourier-domain optical coherence tomography. The interference pattern between light scattered by a sample and a defined reference wave is recorded and processed numerically. During reconstruction numerical refocusing is applied, overcoming the limitation of the focal depth and thus a uniform, diffraction limited lateral resolution over the whole measurement depth can be obtained. The advantage of numerical refocusing becomes especially significant for imaging at high numerical apertures (NAs). We use a high-resolution setup based on a Mach-Zehnder interferometer with an high-resolution microscope objective (NA = 0.75). For reliable reconstruction of a sample volume the Rayleigh length of the microscope objective and the axial resolution, given by the spectral range of the light source, need to be matched. For a 0.75 NA objective a tunable light source with a sweeping range of ! 300nm is required. Here we present as a first step a tunable Ti:sapphire laser with a tuning range of 187 nm. By characterizing the spectral properties of the Ti:sapphire laser and determining the axial point spread function we demonstrate the feasibility of this light source for high-resolution holoscopy.},
   DOI = {10.1117/12.2006806},
   url = {http://dx.doi.org/10.1117/12.2006806},
   year = {2013},
   type = {Journal Article}
}

@article{Müller2012,
   author = {Mueller, H. H. and Ptaszynski, L. and Schlott, K. and Debbeler, C. and Bever, M. and Koinzer, S. and Birngruber, R. and Brinkmann, R. and Huettmann, G.},
   title = {Imaging thermal expansion and retinal tissue changes during photocoagulation by high speed OCT},
   journal = {Biomedical Optics Express},
   volume = {3},
   number = {5},
   pages = {1025-1046},
   note = {935RH
Times Cited:8
Cited References Count:37},
   abstract = {Visualizing retinal photocoagulation by real-time OCT measurements may considerably improve the understanding of thermally induced tissue changes and might enable a better reproducibility of the ocular laser treatment. High speed Doppler OCT with 860 frames per second imaged tissue changes in the fundus of enucleated porcine eyes during laser irradiation. Tissue motion, measured by Doppler OCT with nanometer resolution, was correlated with the temperature increase, which was measured non-invasively by optoacoustics. In enucleated eyes, the increase of the OCT signal near the retinal pigment epithelium (RPE) corresponded well to the macroscopically visible whitening of the tissue. At low irradiance, Doppler OCT revealed additionally a reversible thermal expansion of the retina. At higher irradiance additional movement due to irreversible tissue changes was observed. Measurements of the tissue expansion were also possible in vivo in a rabbit with submicrometer resolution when global tissue motion was compensated. Doppler OCT may be used for spatially resolved measurements of retinal temperature increases and thermally induced tissue changes. It can play an important role in understanding the mechanisms of photocoagulation and, eventually, lead to new strategies for retinal laser treatments. (c) 2012 Optical Society of America},
   keywords = {optical coherence tomography
laser photocoagulation
vein occlusion
management
diseases
fundus
blood},
   ISSN = {2156-7085},
   url = {<Go to ISI>://WOS:000303537400018},
   year = {2012},
   type = {Journal Article}
}

@article{Gehlsen,
   author = {Gehlsen, U. and Oetke, A. and Szaszak, M. and Koop, N. and Paulsen, F. and Gebert, A. and Huettmann, G. and Steven, P.},
   title = {Two-photon fluorescence lifetime imaging monitors metabolic changes during wound healing of corneal epithelial cells in vitro},
   journal = {Graefes Arch Clin Exp Ophthalmol},
   volume = {6},
   pages = {6},
   note = {Using Smart Source Parsing
May},
   abstract = {BACKGROUND: Early and correct diagnosis of delayed or absent corneal epithelial wound healing is a key factor in the prevention of infection and consecutive destruction of the corneal stroma with impending irreversible visual loss. Two-photon microscopy (TPM) is a novel technology that has potential to depict epithelial cells and to evaluate cellular function by measuring autofluorescence properties such as fluorescence intensity and fluorescence lifetimes of metabolic co-factors such as NAD(P)H. METHODS: Using non-invasive TPM in a tissue-culture scratch model and an organ-culture erosion model, fluorescence intensity and fluorescence lifetimes of NAD(P)H were measured before and during closure of the epithelial wounds. Influence of temperature and selective inhibition of metabolism on intensity and lifetimes were tested additionally. RESULTS: Decrease of temperature resulted in significant increase of fluorescence lifetimes and decrease of the relative amount of free NAD(P)H due to decreased global metabolism. Increase in temperature and upregulation of glycolysis through blocking the mitochondrial electron transport chain by rotenone resulted in increased intensity, decreased lifetimes and increase in the relative amount of free NAD(P)H. Changes of lifetimes and free:protein-bound NAD(P)H ratios were similar to changes measured during wound healing in both scratch and erosion models. CONCLUSIONS: Fluorescence lifetime measurements (FLIM) detected enhancement of cellular metabolism following epithelial damage in both models. The prospective detection of cellular autofluorescence in vivo, in particular FLIM of metabolic cofactor NAD(P)H, has the potential to become an indispensible tool in clinical use to differentiate healing from non-healing epithelial cells and to evaluate effects of newly developed substances on cellular metabolism in preclinical and clinical trials.},
   year = {2012}
}

@inproceedings{Xie,
   author = {Xie, Y. and Bonin, T. and Loeffler, S. and Huettmann, G. and Tronnier, V. and Hofmann, U. G.},
   title = {Fiber spectral domain optical coherence tomography for in vivo rat brain imaging},
   editor = {Jurgen, Popp and Wolfgang, Drexler and Valery, V. Tuchin and Dennis, L. Matthews},
   publisher = {SPIE},
   volume = {7715},
   pages = {77152F},
year = { 2010},
URL = { https://doi.org/10.1117/12.854798}

}

@article{Müller-2010,
   author = {Mueller, M. and Schulz-Wackerbarth, C. and Steven, P. and Lankenau, E. and Bonin, T. and Mueller, H. and Brueggemann, A. and Birngruber, R. and Grisanti, S. and Huettmann, G.},
   title = {Slit-lamp-adapted fourier-domain OCT for anterior and posterior segments: preliminary results and comparison to time-domain OCT},
   journal = {Curr Eye Res},
   volume = {35(8)},
 DOI = { 10.3109/02713683.2010.481069},
year = { 2010},
   pages = {722-32},
   note = {Using Smart Source Parsing
Aug},
   abstract = {PURPOSE: To evaluate the diagnostic potential of a slit-lamp (SL)-adapted Fourier-domain (= spectral radar, SR) optical coherence tomography (OCT)-SL-SR-OCT-instrument as an in vivo imaging device for use in examinations of the anterior and posterior segments. MATERIALS AND METHODS: In a pilot study, 88 eyes from 70 healthy volunteers and patients were examined using a prototype Fourier-domain SL-SR-OCT system. Results were compared to those from the following commercially available systems: the 1310-nm SL-OCT (Heidelberg Engineering, Heidelberg, Germany) for anterior segment and the Stratus OCT (Zeiss Meditec, Jena, Germany) for posterior segment imaging. Our SL-SR-OCT provides 1025 axial scans, 5000 Hz line-scan frequency, scan length of up to 8 mm, axial depth in air of 3.5 mm, and resolution of 9 mum. For posterior visualization, a hand-held 78-diopter ophthalmoscopic lens was used. RESULTS: Our SL-SR-OCT system allowed simultaneous scanning with direct biomicroscopic and SL imaging of anterior and posterior segment structures. Anatomical structures and pathological changes were displayed with high resolution and excellent contrast. Measurements of corneal and retinal thickness were possible. In comparison to images obtained by the SL-OCT, our SL-SR-OCT boasted a higher resolution, thus providing more clinically relevant details of the corneal epithelium, internal structure of filtering blebs, etc. Complete imaging of the chamber angle was limited, however, due to the backscattering properties of the sclera at 830 nm. For posterior segment imaging, excellent delineation of the macula and optic nerve head details, with a distinct portrayal of macular pathology and retinal edema, was possible with SL-SR-OCT. CONCLUSION: SL-SR-OCT enables detailed imaging of physiological and pathological anterior and posterior segment structures. As a multi-purpose device, it offers a wide spectrum of applications, with high-quality OCT-imaging, in a comfortable setting without the need to move the patient.},
  
}

@article{Gasca,
   author = {Gasca, F. and Ramrath, L. and Huettmann, G. and Schweikard, A.},
   title = {Automated segmentation of tissue structures in optical coherence tomography data},
   journal = {J Biomed Opt},
   volume = {14},
   number = {3},
   pages = {034046},
   note = {Using Smart Source Parsing
May-Jun},
   abstract = {Segmentation of optical coherence tomography (OCT) images provides useful information, especially in medical imaging applications. Because OCT images are subject to speckle noise, the identification of structures is complicated. Addressing this issue, two methods for the automated segmentation of arbitrary structures in OCT images are proposed. The methods perform a seeded region growing, applying a model-based analysis of OCT A-scans for the seed's acquisition. The segmentation therefore avoids any user-intervention dependency. The first region-growing algorithm uses an adaptive neighborhood homogeneity criterion based on a model of an OCT intensity course in tissue and a model of speckle noise corruption. It can be applied to an unfiltered OCT image. The second performs region growing on a filtered OCT image applying the local median as a measure for homogeneity in the region. Performance is compared through the quantitative evaluation of artificial data, showing the capabilities of both in terms of structures detected and leakage. The proposed methods were tested on real OCT data in different scenarios and showed promising results for their application in OCT imaging.},
   year = {2009}
}

@article{Yao,
   author = {Yao, C and Qu, X. and Zhang, Z. and B., Yao and Hüttmann, G and Rahmanzadeh, R.},
   title = {Influence of Laser Parameters on Membrane Permeability with Nanoparticles and Targeted Antibody Transfection},
   journal = {J Biomed Opt},
   volume = {14},
   pages = {054034},
   note = {Journal article},
   year = {2009}
}

@misc{Qu,
   author = {Qu, X. and Wang, J. and Zhang, Z. and Koop, N. and Rahmanzadeh, R. and Huttmann, G.},
   title = {Imaging of cancer cells by multiphoton microscopy using gold nanoparticles and fluorescent dyes},
   volume = {13},
   number = {3},
   pages = {031217},
   note = {Using Smart Source Parsing
May-Jun},
   abstract = {Due to their unique optical properties, optical probes, including metal nanoparticles (NPs) and fluorescent dyes, are increasingly used as labeling tools in biological imaging. Using multiphoton microscopy and fluorescence lifetime imaging (FLIM) at 750-nm excitation, we recorded intensity and FLIM images from gold NPs (30 nm) and the fluorescent dye Alexa 488 (A488) conjugated with monoclonal ACT-1 antibodies as well as Hoechst 33258 (H258) after incubation with the lymphoma cell line (Karpas-299). From the FLIM images, we can easily discriminate the imaging difference between cells and optical probes according to their distinct fluorescence lifetimes (cellular autofluorescence: 1 to 2 ns; gold NPs: <0.02 ns; A488: 3.5 ns; H258: 2.5 ns). The NP-ACT-1 and A488-ACT-1 conjugates were bound homogeneously on the surface of cells, whereas H258 stained the cell nucleus. We demonstrate that the emission intensity of gold NPs is about ten times stronger than that of the autofluorescence of Karpas-299 cells at the same excitation power. Compared with fluorescent dyes, stronger emission is also observed from gold NPs. Together with their high photostability, these observations suggest that gold NPs are a viable alternative to fluorescent dyes for cellular imaging and cancer diagnosis.},
   ISBN = {1083-3668 (Print)
1083-3668 (Linking)},
   year = {2008}
}

@article{Yao,
   author = {Yao, C. P. and Zhang, Z. X. and Rahmanzadeh, R. and Huettmann, G.},
   title = {Laser-based gene transfection and gene therapy},
   journal = {IEEE Trans Nanobioscience},
   volume = {7},
   number = {2},
   pages = {111-9},
   note = {Yao, C P
Zhang, Z X
Rahmanzadeh, R
Huettmann, G
Research Support, Non-U.S. Gov't
Review
United States
IEEE Trans Nanobioscience. 2008 Jun;7(2):111-9.},
   abstract = {The plasma membrane of mammalian cells can be transiently permeablized by optical means and exogenous materials or genes can be introduced into the cytoplasm of living cells. Until now, few mechanisms were exploited for the manipulation: laser is directly and tightly focused on the cells for optoinjection, laser-induced stress waves, photochemical internalization, and irradiation of selective cell targeting with light-absorbing particles. During the past few years, extensive progress and numerous breakthroughs have been made in this area of research. This review covers four different laser-assisted transfection techniques and their advantages and disadvantages. Universality towards various cell lines is possibly the main advantage of laser-assisted optoporation in comparison with presently existing methods of cell transfection.},
   keywords = {Cell Membrane/ radiation effects
DNA/ administration & dosage/ pharmacokinetics
Gene Therapy/ methods
Lasers
Transfection/ methods},
   year = {2008}
}

@article{Mueller2008,
   author = {Mueller, M. and Huettmann, G. and Koop, N. and Steven, P.},
   title = {Minimal-Invasive Imaging of Ocular Surface Pathologies - Confocal vs. Two-Photon Microscopy},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {49},
   number = {13},
   pages = {2258-2258},
   ISSN = {1552-5783},
   url = {http://dx.doi.org/},
   year = {2008},
   type = {Journal Article}
}

@article{Ramrath,
   author = {Ramrath, L. and Moreno, G. and Mueller, H. and Bonin, T. and Huettmann, G. and Schweikard, A.},
   title = {Towards multi-directional OCT for speckle noise reduction},
   journal = {Med Image Comput Comput Assist Interv},
   volume = {11},
   number = {Pt 1},
   pages = {815-23},
   note = {Using Smart Source Parsing},
   abstract = {Multi-directional optical coherence tomography (MD-OCT) applies and extends the concept of angular compounding for speckle noise reduction to the area of OCT imaging. OCT images are acquired from a wide range of angles of view. Averaging of the rotated images therefore requires compensation of the parallax which is achieved by simple image registration for image reconstruction. Test measurements of a sample structure in a low and highly scattering environment show that the method improves the signal-to-noise ratio by a factor of 4 and hence reduces speckle noise significantly. Experimental results also show that the proposed averaging increases the performance of common edge-detection algorithms.},
   year = {2008}
}

@inproceedings{Just-2008,
   author = {Just, T. and Lankenau, E. and Huettmann, G. and Pau, H.W.},
   title = {Optical coherence tomography as a guide for cochlear implant surgery},
   booktitle = {Progress in Biomedical Optics and Imaging},
   editor = {Nikiforos, K. and Bernard, C. and Haishan, Z.},
   publisher = {SPIE 6842},
   pages = {F1-F6},
url = { https://doi.org/10.1117/12.771446},
year = { 2008}

}

@article{Rahmanzadeh,
   author = {Rahmanzadeh, R. and Huttmann, G. and Gerdes, J. and Scholzen, T.},
   title = {Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis},
   journal = {Cell Prolif},
   volume = {40},
   number = {3},
   pages = {422-30},
   note = {Rahmanzadeh, R
Huttmann, G
Gerdes, J
Scholzen, T
England
Cell Prolif. 2007 Jun;40(3):422-30.},
   abstract = {OBJECTIVES: Expression of the nuclear Ki-67 protein (pKi-67) is strongly associated with cell proliferation. For this reason, antibodies against this protein are widely used as prognostic tools for the assessment of cell proliferation in biopsies from cancer patients. Despite this broad application in histopathology, functional evidence for the physiological role of pKi-67 is still missing. Recently, we proposed a function of pKi-67 in the early steps of ribosomal RNA (rRNA) synthesis. Here, we have examined the involvement of pKi-67 in this process by photochemical inhibition using chromophore-assisted light inactivation (CALI). MATERIALS AND METHODS: Anti-pKi-67 antibodies were labelled with the fluorochrome fluorescein 5(6)-isothiocyanate and were irradiated after binding to their target protein. RESULTS: Performing CALI in vitro on cell lysates led to specific cross-linking of pKi-67. Moreover, the upstream binding factor (UBF) necessary for rRNA transcription was also partly subjected to cross-link formation, indicating a close spatial proximity of UBF and pKi-67. CALI in living cells, using micro-injected antibody, caused a striking relocalization of UBF from foci within the nucleoli to spots located at the nucleolar rim or within the nucleoplasm. pKi-67-CALI resulted in dramatic inhibition of RNA polymerase I-dependent nucleolar rRNA synthesis, whereas RNA polymerase II-dependent nucleoplasmic RNA synthesis remained almost unaltered. CONCLUSIONS: Our data presented here argue for a crucial role of pKi-67 in RNA polymerase I-dependent nucleolar rRNA synthesis.},
   keywords = {Antibodies, Antinuclear
Antibodies, Monoclonal
Cell Division/physiology
Cell Nucleolus/physiology
Fluorescein-5-isothiocyanate
Fluorescent Dyes
HeLa Cells
Humans
Ki-67 Antigen/*genetics/*metabolism
Photochemistry
RNA Polymerase I/metabolism
RNA, Ribosomal/*biosynthesis},
   year = {2007}
}

@article{Steven2007,
   author = {Steven, P. and Rupp, J. and Huettmann, G. and Koop, N. and Laqua, H.},
   title = {Two-Photon Real-Time Imaging of Conjunctiva-Associated Lymphoid Tissue (CALT)},
   journal = {Investigative Ophthalmology & Visual Science},
   volume = {48},
   number = {13},
   pages = {201-201},
   abstract = {AbstractPurpose:: Immunological real-time analysis of conjunctiva-associated lymphoid tissue (CALT) is challenging at state. For the first time, two-photon microscopy, a new optical method, is evaluated in its use to analyze morphology and function of CALT. Methods:: Conjunctiva of female Balb/c mice is challenged with Chlamydia trachomatis serovar C (ChtC) or ovalbumin and choleratoxin subunit B (OVA/CTB) for CALT induction. A two-photon microscope equipped with a near infrared femtosecond-laser and a fluorescence-lifetime detector is used for ex-vivo analysis of unfixed and unstained ocular tissue with additional application of fluorescent microspheres to demonstrate transepithelial particle transport. Results:: Challenge with ChtC or OVA/CTB induce all CALT components (lymphoepithelium, follicles, blood and lymphatic vessels), that are demonstrated in cellular and subcellular resolution by means of autofluorescence imaging. Wavelength adaptation allows specific differentiation of cellular and acellular components. Fluorescence-lifetime detection permits differentiation of cellular subsets (e.g. lymphocytes and macrophages). Application of fluorescent microspheres demonstrates transepithelial particle transport and detection within intracellular vesicles. Conclusions:: Two-photonmicroscopy is an innovative optical technique to analyse morphological and functional features of CALT. Detection of transepithelial particle transport and its impact on conjunctival immunological processes can be visualized in real-time. Future in-vivo experiments with suitable animal models would allow detailed analysis of CALT in a clinical context e.g. corneal transplant rejection, keratoconjunctivitis sicca and follicular conjunctivitis.},
   ISSN = {1552-5783},
   url = {http://dx.doi.org/},
   year = {2007},
   type = {Journal Article}
}

@article{Yao,
   author = {Yao, C. and Rahmanzadeh, R. and Endl, E. and Zhang, Z. and Gerdes, J. and Huttmann, G.},
   title = {Elevation of plasma membrane permeability by laser irradiation of selectively bound nanoparticles},
   journal = {J Biomed Opt},
   volume = {10},
   number = {6},
   pages = {064012},
   note = {Yao, Cuiping
Rahmanzadeh, Ramtin
Endl, Elmar
Zhang, Zhenxi
Gerdes, Johannes
Huttmann, Gereon
Research Support, Non-U.S. Gov't
United States
J Biomed Opt. 2005 Nov-Dec;10(6):064012.},
   abstract = {Irradiation of nanoabsorbers with pico- and nanosecond laser pulses could result in thermal effects with a spatial confinement of less than 50 nm. Therefore absorbing nanoparticles could be used to create controlled cellular effects. We describe a combination of laser irradiation with nanoparticles, which changes the plasma membrane permeability. We demonstrate that the system enables molecules to penetrate impermeable cell membranes. Laser light at 532 nm is used to irradiate conjugates of colloidal gold, which are delivered by antibodies to the plasma membrane of the Hodgkin's disease cell line L428 and/or the human large-cell anaplastic lymphoma cell line Karpas 299. After irradiation, membrane permeability is evaluated by fluorescence microscopy and flow cytometry using propidium iodide (PI) and fluorescein isothiocyanate (FITC) dextran. The fraction of transiently permeabilized and then resealed cells is affected by the laser parameter, the gold concentration, and the membrane protein of the different cell lines to which the nanoparticles are bound. Furthermore, a dependence on particle size is found for these interactions in the different cell lines. The results suggest that after optimization, this method could be used for gene transfection and gene therapy.},
   keywords = {Biopolymers/pharmacokinetics
Cell Line, Tumor
Cell Membrane Permeability/ physiology/ radiation effects
Drug Delivery Systems/ methods
Fluoresceins/ pharmacokinetics
Humans
Lasers
Lymphoma/ metabolism
Nanostructures},
   year = {2005}
}