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Ex vivo nonlinear microscopy imaging of Ehlers-Danlos syndrome-affected skin by Norbert Kiss, Dóra Haluszka, Kende Lőrincz, Enikő Kuroli, Judit Hársing, Balázs Mayer, Sarolta Kárpáti, György Fekete, Róbert Szipőcs, Norbert Wikonkál, Márta Medvecz || 2018

Abstract: Ehlers–Danlos syndrome (EDS) is the name for a heterogenous group of rare genetic connective tissue disorders with an overall incidence of 1 in 5000. The histological characteristics of EDS have been previously described in detail in the late 1970s and early 1980s. Since that time, the classification of EDS has undergone significant changes, yet the description of the histological features of collagen morphology in different EDS subtypes has endured the test of time. Nonlinear microscopy techniques can be utilized for non-invasive in vivo label-free imaging of the skin. Among these techniques, two-photon absorption fluorescence (TPF) microscopy can visualize endogenous fluorophores, such as elastin, while the morphology of collagen fibers can be assessed by second-harmonic generation (SHG) microscopy. In our present work, we performed TPF and SHG microscopy imaging on ex vivo skin samples of one patient with classical EDS and two patients with vascular EDS and two healthy controls. We detected irregular, loosely dispersed collagen fibers in a non-parallel arrangement in the dermis of the EDS patients, while as expected, there was no noticeable impairment in the elastin content. Based on further studies on a larger number of patients, in vivo nonlinear microscopic imaging could be utilized for the assessment of the skin status of EDS patients in the future.

Quantitative Analysis on Ex Vivo Nonlinear Microscopy Images of Basal Cell Carcinoma Samples in Comparison to Healthy Skin by Norbert Kiss, Dóra Haluszka, Kende Lőrincz, Nóra Gyöngyösi, Szabolcs Bozsányi, András Bánvölgyi, Róbert Szipőcs, Norbert Wikonkál || 2018

Abstract: Basal cell carcinoma (BCC) is the most frequent malignant neoplasm in the Caucasian population. There are several therapeutic options for BCC, but surgical excision is considered gold standard treatment. As BCCs often have poorly defined borders, the clinical assessment of the tumor margins can be challenging. Therefore, there is an increasing demand for efficient in vivo imaging techniques for the evaluation of tumor borders prior to and during surgeries. In the near future, nonlinear microscopy techniques might meet this demand.We measured the two-photon excitation fluorescence (TPEF) signal of nicotinamide adenine dinucleotide hydride (NADH) and elastin and second harmonic generation (SHG) signal of collagen on 10 ex vivo healthy control and BCC skin samples and compared the images by different quantitative image analysis methods. These included integrated optical density (IOD) measurements on TPEF and SHG images and application of fast Fourier transform (FFT), CT-FIRE and CurveAlign algorithms on SHG images to evaluate the collagen structure. In the BCC samples, we found significantly lower IOD of both the TPEF and SHG signals and higher collagen orientation index utilizing FFT. CT-FIRE algorithm revealed increased collagen fiber length and decreased fiber angle while CurveAlign detected higher fiber alignment of collagen fibers in BCC. These results are in line with previous findings which describe pronounced changes in the collagen structure of BCC. In the future, these novel image analysis methods could be integrated in handheld nonlinear microscope systems, for sensitive and specific identification of BCC.

Quantitative analysis of lipid debris accumulation caused by cuprizone induced myelin degradation in different CNS areas by Attila Ozsvár, Róbert Szipőcs, Zoltán Ozsvár, Judith Baka, Pál Barzó, Gábor Tamás, Gábor Molnár || 2018

Abstract: Degradation of myelin sheath is thought to be the cause of neurodegenerative diseases, such as multiple sclerosis (MS), but definitive agreement on the mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS has been recently questioned by proposing that the immune response is a consequence of oligodendrocyte degeneration. To study the process of myelin breakdown, we induced demyelination with cuprizone and applied coherent anti-Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to image lipid structures in living tissue. We confirmed earlier results showing a brain region dependent myelin destructive effect of cuprizone. In addition, high resolution in situ CARS imaging revealed myelin debris forming lipid droplets alongwith myelinated axon fibers. Quantification of lipid debris with custom-made software for segmentation and three dimensional reconstruction revealed brain region dependent accumulation of lipid drops inversely correlated with the thickness of myelin sheaths. Finally, we confirmed that in situ CARS imaging is applicable to living human brain tissue in brain slices derived from a patient. Thus, CARS microscopy is potent tool for quantitative monitoring of myelin degradation in unprecedented spatiotemporal resolution during oligodendrocyte damage. We think that the accumulation of lipid drops around degrading myelin might be instrumental in triggering subsequent inflammatory processes.

Stain-free Histopathology of Basal Cell Carcinoma by Dual Vibration Resonance Frequency CARS Microscopy by Norbert Kiss, Ádám Krolopp, Kende Lőrincz, András Bánvölgyi, Róbert Szipőcs, Norbert Wikonkál || 2017

Abstract: Basal cell carcinoma (BCC) is the most common malignancy in Caucasians. Nonlinear microscopy has been previously utilized for the imaging of BCC, but the captured images do not correlate with H&E staining. Recently, Freudiger et al. introduced a novel method to visualize tissue morphology analogous to H&E staining, using coherent anti- Stokes Raman scattering (CARS) technique. In our present work, we introduce a novel algorithm to post-process images obtained from dual vibration resonance frequency (DVRF) CARS measurements to acquire high-quality pseudo H&E images of BCC samples. We adapted our CARS setup to utilize the distinct vibrational properties of CH3 (mainly in proteins) and CH2 bonds (primarily in lipids). In a narrowband setup, the central wavelength of the pump laser is set to 791 nm and 796 nm to obtain optimal excitation. Due to the partial overlap of the excitation spectra and the 5–10 nm FWHM spectral bandwidth of our lasers, we set the wavelengths to 790 nm (proteins) and 800 nm (lipids). Nonresonant background from water molecules also reduces the chemical selectivity which can be significantly improved if we subtract the DVRF images from each other. As a result, we acquired two images: one for Blipids^ and one for^ proteins^ when we properly set a multiplication factor to minimize the non-specific background. By merging these images, we obtained high contrast H&E Bstained^ images of BBC’s.

Voluntary exercise improves murine dermal connective tissue status in high-fat diet-induced obesity by Kende Lőrincz, Dóra Haluszka, Norbert Kiss, Nóra Gyöngyösi, András Bánvölgyi, Róbert Szipőcs, Norbert M. Wikonkál || 2017

Abstract: Obesity is a risk factor for several cardiovascular and metabolic diseases. Its influence on the skin is less obvious, yet certain negative effects of adipose tissue inflammation on the dermis have been suggested. Excess weight is closely associated with sedentary behavior, so any increase in physical activity is considered beneficial against obesity. To investigate the effects of obesity and physical exercise on the skin, we established a mouse model in which mice were kept either on a high-fat diet or received standard chow. After the two groups achieved a significant weight difference, physical exercise was introduced to both. Animals were given the opportunity to perform voluntary exercise for 40 min daily in a hamster wheel for a period of 8 weeks. We evaluated the status of the dermis at the beginning and at the end of the exercise period by in vivo nonlinear microscopy. Obese mice kept on high-fat diet lost weight steadily after they started to exercise. In the high-fat diet group, we could detect significantly larger adipocytes and a thicker layer of subcutaneous tissue; both changes started to normalize after exercise. Nonlinear microscopy revealed an impaired collagen structure in obese mice that improved considerably after physical activity was introduced. With the ability to detect damage on collagen structure, we set out to address the question whether this process is reversible. With the use of a novel imaging method, we were able to show the reversibility of connective tissue deterioration as a benefit of physical exercise.

Diet-induced obesity skin changes monitored by in vivo SHG and ex vivo CARS microscopy by Dóra Haluszka, Kende Lőrincz, Norbert Kiss, Róbert Szipőcs, Enikő Kuroli, Nóra Gyöngyösi, and Norbert M. Wikonkál || 2016

Abstract: Obesity related metabolic syndrome and type 2 diabetes have severe consequences on our skin. Latest developments in nonlinear microscopy allow the use of noninvasive, label free imaging methods, such as second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS), for early diagnosis of metabolic syndrome-related skin complications by 3D imaging of the skin and the connective tissue. Our aim was to study effects of various types of diet-induced obesity in mice using these methods. We examined mice on different diets for 32 weeks. The collagen morphology was evaluated four times in vivo by SHG microscopy, and adipocytes were examined once at the end of experiment by ex vivo CARS method. A strong correlation was found between the body weight and the adipocyte size, while we found that the SHG intensity of dermal collagen reduces considerably with increasing body weight. Obese mice on high-fat diet showed worse results than those on high-fat - high-fructose diet. Animals on high-fructose diet did not gain more weight than those on ordinary diet despite of the increased calorie intake, but their collagen damage was nonetheless significant. Obesity and high sugar intake damages the skin, mainly the dermal connective tissue and subcutaneous adipose tissue, which efficiently can be monitored by in vivo SHG and ex vivo CARS microscopy.

Handheld nonlinear microscope system comprising a 2 MHz repetition rate, modelocked Yb-fiber laser for in vivo biomedical imaging by Ádám Krolopp, Attila Csákányi, Dóra Haluszka, Dániel Csáti, Lajos Vass, Attila Kolonics, Norbert Wikonkál, Róbert Szipőcs || 2016

Abstract: A novel, Yb-fiber laser based, handheld 2PEF/SHG microscope imaging system is introduced. It is suitable for in vivo imaging of murine skin at an average power level as low as 5 mW at 200 kHz sampling rate. Amplified and compressed laser pulses having a spectral bandwidth of 8 to 12 nm at around 1030 nm excite the biological samples at a ~1.89 MHz repetition rate, which explains how the high quality two-photon excitation fluorescence (2PEF) and second harmonic generation (SHG) images are obtained at the average power level of a laser pointer. The scanning, imaging and detection head, which comprises a conventional microscope objective for beam focusing, has a physical length of ~180 mm owing to the custom designed imaging telescope system between the laser scanner mirrors and the entrance aperture of the microscope objective. Operation of the all-fiber, all-normal dispersion Yb-fiber ring laser oscillator is electronically controlled by a two-channel polarization controller for Q-switching free mode-locked operation. The whole nonlinear microscope imaging system has the main advantages of the low price of the fs laser applied, fiber optics flexibility, a relatively small, light-weight scanning and detection head, and a very low risk of thermal or photochemical damage of the skin samples.

In vivo second-harmonic generation and ex vivo coherent anti-Stokes Raman scattering microscopy to study the effect of obesity to fibroplast cell function using an Yb-fiber laser based CARS extension unit by Haluszka Dóra, Lőrincz Kende, Molnár Gábor, Tamás Gábor, Kolonics Attila, Szipőcs Róbert, Kárpáti Sarolta, Wikonkál Norbert || 2015

Abstract: Nonlinear microscopy techniques are being increasingly used to perform in vivo studies in dermatology. These methods enable us to investigate the morphology and monitor the physiological process in the skin by the use of femtosecond lasers operating in the red, nearinfrared spectral range (680-1300 nm). In this work we used two different techniques that require no labeling: second harmonic generation (SHG) for collagen detection and coherent anti-Stokes Raman scattering (CARS) to assess lipid distribution in genetically obese murine skin. Obesity is one of the most serious public health problems due to its high and increasing prevalence and the associated risk of type 2 diabetes and cardiovascular diseases. Other than these diseases, nearly half of patients with diabetes mellitus suffer from dermatological complications such as delayed wound healing, foot ulcers and several other skin changes. In our experiment we investigated and followed the effects of obesity on dermal collagen alterations and adipocyte enlargement using a technique not reported in the literature so far. Our results indicate that the in vivo SHG and ex vivo CARS imaging technique might be an important tool for diagnosis of diabetes-related skin disorders in the near future.

Hosszú távú PUVA kezelés bôröregítô hatásának vizsgálata egereken (Analysis of skin aging during long term PUVA treatment on mice) by Lőrincz Kende Dr, Bánvölgyi András Dr, Haluszka Dóra, Keszeg András, Márton Dalma, Kuroli Enikő Dr, Szipőcs Róbert Dr, Karin Scharfetter-Kohsanek Dr, Meinhard Wlaschek Dr, Kárpáti Sarolta Dr, Wikonkál Norbert Dr. || 2015

Abstract: PUVA therapy is a frequently used treatment option in a variety of dermatological diseases for decades. However there is no comprehensive consensus in its short and longterm risks, according to the literature. Many animal experiments proved the carcinogenic and photoaging potential of narrow band UVB radiation. Such effects of PUVA therapy are not well documented in similar experimental settings. Epidemiological studies, on the other hand indicate the formerly mentioned long-term adverse effects of PUVA therapy. For this reason we set out to investigate and demonstrate the effects of chronic PUVA therapy with using a mouse model.

Nemlineáris mikroszkópia alapjai és alkalmazási lehetôségei a dermatológiában (Principles of nonlinear microscopy and application possibilities in dermatology) by Haluszka Dóra, Lőrincz Kende Dr, Csákányi Attila, Vass Lajos, Krolopp Ádám, Kolonics Attila Dr, Szipőcs Róbert Dr, Kárpáti Sarolta Dr, Wikonkál Norbert Dr. || 2015

Abstract: Nonlinear optical imaging techniques have become increasingly popular over the past decade both in the field of basic research and clinical practice. The excitation of skin chromophores in the near infrared spectral range (700-1300 nm) allows safe, label-free imaging with high spatial and temporal resolution. In the first part of our article we discuss the main principles of various nonlinear optical techniques, then we show the application possibilities of them in dermatology. In the second part of our review we report the main investigations and results of our group.

Monitoring the dominance of higher-order chromatic dispersion with spectral interferometry using the stationary phase point method by Tímea Grósz, Attila P.Kovács, Katalin Mecseki, Lénárd Gulyás, Róbert Szipőcs || 2015

Abstract: Simulations were performed in order to investigate whether the stationary phase point method can be used to estimate the dominance of higher-order dispersion of the optical element under study. It was shown that different higher-order dispersion terms may result in the appearance of more than one stationary phase point on the interferogram in contrast to common glasses having group-delay dispersion as the highest decisive term in their spectral phase. The results obtained by simulations were demonstrated experimentally with spectral interferometric measurements conducted on a photonic bandgap ?ber sample and a prism pair. We concluded that from the shape, movement and number of the stationary phase points it is generally possible to predict which dispersion terms are the most signi?cant, however, in some cases the retrieval of the coef?cients is also necessary in order to rule out any ambiguity. The method can offer a dispersion monitoring possibility which is useful in quality testing of specialty ?bers and when adjusting stretcher-compressor systems, for example.

Stored Energy, Transmission Group Delay and Mode Field Distorsion in Optical Fibers by Zoltán Várallyay and Róbert Szipőcs || 2014

Abstract: The relationship between transmission group delay and stored energy in optical fibers is discussed. We show by numerical computations that the group delay of an optical pulse of finite bandwidth transmitted through a piece of a low loss optical fiber of unit length is proportional to the energy stored by the standing wave electromagnetic field. The stored energy-group delay ratio typically approaches unity as the confinement loss converges to zero. In case of a dispersion tailored Bragg fiber, we found that the stored energy-group delay ratio decreased while the confinement loss increased compared to those of the standard quarter-wave Bragg fiber configuration. Furthermore, a rapid variation in the group delay versus wavelength function due to mode-crossing events (in hollow core photonic bandgap fibers for instance) or resonances originating from slightly coupled cavities, surface or leaking modes in index guiding, photonic bandgap, or photonic crystal fibers always results in a rapid change in the mode-field distribution, which seriously affects splicing losses and focusability of the transmitted laser beam. All of these factors must be taken into consideration during the design of dispersion tailored fibers for different applications.

In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy by Attila Kolonics, Zsolt Csiszovszki, Enikő R.Tőke Orsolya Lőrincz, Dóra Haluszka and Szipőcs Róbert || 2014

Abstract: 333 Epidermal Langerhans cells (LCs) function as professional antigen-presenting cells of the skin. We investigated the LC-targeting properties of a special mannose–moiety-coated pathogen-like synthetic nanomedicine DermaVir (DV), which is capable to express antigens to induce immune responses and kill HIV-infected cells. Our aim was to use multiphoton laser microscopy (MLM) in vivo in order to visualize the uptake of Alexa-labelled DV (AF546-DV) by LCs. Knock-in mice expressing enhanced green fluorescent protein (eGFP) under the control of the langerin gene (CD207) were used to visualize LCs. After 1 h, AF546-DV penetrated the epidermis and entered the eGFP-LCs. The AF546-DV signal was equally distributed inside the LCs. After 9 h, we observed AF546-DV signal accumulation that occurred mainly at the cell body. We demonstrated in live animals that LCs picked up and accumulated the nanoparticles in the cell body.

Exploitition of Langerhans cells for in vivo DNA vaccine delivery into the lymph nodes by ER Tőke, O Lőrincz, Z Csiszovszki, E Somogyi, G Felföldi, L Molnár, R Szipőcs, A Kolonics, B Malisson, F Lori, J Trocio, N Bakare, F Horkay, N Romani, CH Tripp P Stoizner and J Lisziewicz. || 2014

Abstract: There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic ‘pathogen-like’nanoparticles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the native skin poorly penetrated and poorly induced LC motility. The combination of nanoparticle administration and skin treatment was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph nodes. Preclinical toxicity of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin treatment. This novel, clinically proven LC-targeting DNA vaccine platform technology broadens the options on DC-targeting vaccines to generate therapeutic immunity against cancer.

Measurement of higher order chromatic dispersion in a photonic bandgap filter: comparative study of spectral interferometric methods by T.Grósz, A.P.Kovács, M.Kiss and R.Szipőcs || 2014

Abstract: Chromatic dispersion of a 37 cm long, solid-core photonic bandgap (PBG) fiber was studied in the wavelength range of 740–840 nm with spectral interferometry employing a Mach–Zehnder interferometer and a high resolution spectrometer. The interferometer was illuminated by a Ti:sapphire laser providing 20 fs pulses. A comparative study has been carried out to find the most accurate spectral phase retrieval method that is suitable for measuring higher order chromatic dispersion. The stationary phase point, the minima–maxima, the cosine function fit, the Fourier transform, and the windowed Fourier transform methods were tested. It was shown that out of these five techniques, the Fourier-transform method provided the dispersion coefficients with the highest accuracy, and it could also detect rapid phase changes in the vicinity of leaking mode frequencies within the transmission band of the PBG fiber. © 2014 Optical Society of America

Pre-excitation studies for rubidium-plasma generation by Márk Aladi, József Bakos, I.F. Barna, Aladár Czitrovszky, Gagik Djotyan, Péter Dombi, David Dzsotjan, István Földes, Gergő Hamar, Péter Ignácz, Miklós Kedves, Attila Kerekes, Péter Lévai, István Márton, Attila Nagy, Dániel Oszetzky, Mihály Pocsai, Péter Rácz, Béla Ráczkevi, János Szigeti, Zsuzsa Sörlei, Róbert Szipöcs, Dezső Varga, Károly Varga-Umbrich, Sándor Varró, Lénárd Vámos, György Vesztergombi || 2014

Abstract: The key element in the Proton-Driven-Plasma-Wake-Field-Accelerator (PWFA) project is the generation of highly uniform plasma from Rubidium vapor. A scientifically straightforward, yet highly challenging way to achieve full ionization is to use high power laser which can assure the barrier suppression ionization (BSI) along the 10 m long active region. The Wigner-team in Budapest is investigating an alternative way of uniform plasma generation. The proposed Resonance Enhanced Multi-Photon Ionization (REMPI) scheme can be probably realized by much less laser power. In the following we plan to investigate the resonant pre-excitations of the Rb atoms, both theoretically and experimentally. In the following our theoretical framework is presented together with the status report about the preparatory work of the planned experiments.

Reduced Inflammatory Threshold Indicates Skin Barrier Defect in Transglutaminase 3 Knockout Mice by Peter Bognár, Ilona Nemeth, Dora Haluszka, Norbert Wikonkál, Eszter Ostorhazi, Susan John, Mats Paulsson, Neil Smyth, Maria Pasztoi, Edit Buzas, Robert Szipocs, Attila Kolonics, Erzsebet Temesvari and Sarolta Karpati || 2013

Abstract: Recently, a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired hair development, but no gross defects in the epidermal barrier, although increased fragility of isolated corneocytes was demonstrated. Here we investigated the functionality of skin barrier in vivo by percutaneous sensitization to FITC in TGM3/KO (n = 64) and C57BL/6 wild-type (WT) mice (n = 36). Cutaneous inflammation was evaluated by mouse ear swelling test (MEST), histology, serum IgE levels, and by flow cytometry from draining lymph nodes. Inflammation-induced significant MEST difference (P < 0.0001) was detected between KO and WT mice and was supported also by histopathology. A significant increase of CD4+ CD25+ -activated T cells (P < 0.01) and elevated serum IgE levels (P < 0.05) in KO mice indicated more the development of FITC sensitization than an irritative reaction. Propionibacter acnes–induced intracutaneous inflammation showed no difference (P = 0.2254) between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous penetration in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired barrier function and higher susceptibility to FITC sensitization indicating that TGM3 has a significant contribution to the functionally intact cutaneous barrier.

Relation among group delay, energy storage and loss in dispersive dielectric mirrors by P.G. Antal, R. Szipocs || 2012

Abstract: We show that absorbed and stored electromagnetic energy are proportional to the reflection group delay in highly reflective dispersive dielectric mirrors over the high-reflectivity band. Our theoretical considerations are verified by numerical simulations performed on different dielectric mirror structures. The revealed proportionality between group delay and absorbed energy sets constraint on the application of ultrabroadband and/or dispersive dielectric mirrors in broadband or widely tunable, high power laser systems.

Tunable, low-repetition-rate, cost efficient femtosecond Ti:sapphire laser for nonlinear microscopy by P.G. Antal, R. Szipocs || 2011

Abstract: We report on a broadly tunable, long-cavity Ti:sapphire laser oscillator being mode-locked in the net negative intracavity dispersion regime by Kerr-lens mode-locking, delivering τFWHM < 300 fs pulses at 22 MHz repetion rate. The wavelength of the laser can be tuned over a 170 nm wide range between 712 nm and 882 nm. Having a typical pump power of 2.6 W, the maximum pulse peak power is 60 kW. Comparison of the reported laser with a standard, 76 MHz Ti:sapphire oscillator regarding two-photon excitation efficiency in a laser scanning microscope shows that the 22 MHz laser generates the same fluorescence signal at considerably, 1.82 times lower average power, which is expected to result in a reduced photothermal damage probability of biological samples. This fact along with the broad tunabiéity and a low pump power requirement makes this cost-effective laser and ideal light source for nonlinear microscopy.

Photonic bandgap fibers with resonant structures for tailoring the dispersion by Z. Varallyay, K. Saitoh, A. Szabo, and R. Szipocs || 2009

Abstract: Numerical simulations on different kinds of realistic photonic bandgap fibers exhibiting reversed dispersion slope for the propagating fundamental mode are reported. We show that reversed or flat dispersion functions in a wide wavelength range using hollow-core, air-silica photonic bandgap fibers and solid core Bragg fibers with step-index profile can be obtained by introducing resonant structures in the fiber cladding. We evaluate the dispersion and confinement loss profiles of these fibers from the Helmholtz eigenvalue equation and the calculated fiber properties are used to investigate the propagation of chirped femtosecond pulses through serially connected hollow core fiber compressors

All-fiber, all-normal dispersion ytterbium ring oscillator by J. Fekete, A. Cserteg, and R. Szipocs || 2008

Abstract: Experimental results on an all-fiber, all-normal dispersion ytterbium ring laser are reported. It produces stable mode-locking of ~10 ps pulses that can be externally compressed to as short as ~200 fs.

Reversed dispersion slope photonic bandgap fibers for broadband dispersion control in femtosecond fiber lasers by Z. Varallyay, K. Saitoh, J. Fekete, K. Kakihara, M. Koshiba, and R. Szipocs || 2008

Abstract: Higher-order-mode solid and hollow core photonic bandgap fibers exhibiting reversed or zero dispersion slope over tens or hundreds of nanometer bandwidths within the bandgap are presented. This attractive feature makes them well suited for broadband dispersion control in femtosecond pulse fiber lasers, amplifiers and optical parametric oscillators. The canonical form of the dispersion profile in photonic bandgap fibers is modified by a partial reflector layer/interface placed around the core forming a 2D cylindrical Gires-Tournois type interferometer. This small perturbation in the index profile induces a frequency dependent electric field distribution of the preferred propagating higher-order-mode resulting in a zero or reversed dispersion slope.

Design of high-bandwidth one- and two-dimensional photonic bandgap dielectric structures at grazing incidence of light by J. Fekete, Z. Varallyay, and R. Szipocs || 2008

Abstract: We propose one-dimensional photonic bandgap (PB) dielectric structures to be used at grazing incidence in order to obtain an extended bandgap exhibiting considerably reduced reflection loss and dispersion compared to similar structures used at a normal incidence of light. The well-known quarter-wave condition is applied for the design in this specific case, resulting in resonance-free reflection bands without drops in reflection versus wavelength function and a monotonous variation of the group delay dispersion versus wavelength function, which are important issues in femtosecond pulse laser applications. Based on these results we extend our studies to two-dimensional PB structures and provide guidelines to the design of leaking mode-free hollow-core Bragg PB fibers providing anomalous dispersion over most of the bandgap.

Chirped-pulse supercontinuum generation with a long-cavity Ti:sapphire oscillator by P. Dombi, P. Antal, J. Fekete, R. Szipőcs, Z. Várallyay || 2007

Abstract: We demonstrate chirped-pulse supercontinuum generation in a conventional fibre with a relatively narrowband, long-cavity, chirped-pulse Ti:sapphire oscillator delivering 200 nJ pulses. The inherent chirp of the outcoupled pulses were overcompensated by a 4-prism compressor to overcome damage threshold problems at the fibre entrance. The resulting fibre output spectrum corresponds to a pulse length of 7 fs in the transform-limit. The experimentally observed highly efficient spectral broadening process of negatively chirped pulses in the fibre is supported by simulation data.

Optimizing input and output chirps up to the third-order for sub-nanojoule, ultra-short pulse compression in small core area PCF by Z. Várallyay, J. Fekete, Á. Bányász, R. Szipőcs || 2006

Abstract: Compression of sub-nanojoule laser pulses using a commercially available photonic crystal fiber (PCF)with zero dispersion wavelength of 860 nm is discussed. A twofold pulse compression starting from 24 fs transform limited seed pulses around 800 nm is experimentally demonstrated as a verification of our simulations. Theory shows that by the optimization of input and output chirp parameters up to the third order, high quality, 5.7 fs pulses can be generated from a cost efficient experimental setup. Further calculations show that 1 ps pulses with central wavelength of 800 nm can be compressed down to 50 fs in the normal dispersion regime of the fiber with proper dispersion compensation. Calculations also show that dispersion flattened fibers can improve both the quality and the duration of compressed pulses.

Random access three-dimensional two-photon microscopy by Balázs Rózsa, Gergely Katona, E. Sylvester Vizi, Zoltán Várallyay, Attila Sághy, László Valenta, Pál Maák, Júlia Fekete, Ákos Bányász, and Róbert Szipőcs || 2006

Abstract: We propose a two-photon microscope scheme capable of real-time, three-dimensional investigation of the electric activity pattern of neural networks or signal summation rules of individual neurons in a 0.6 mm x 0.6 mm x 0.2 mm volume of the sample. The points of measurement are chosen according to a conventional scanning two-photon image, and they are addressed by separately adjustable optical fibers. This allows scanning at kilohertz repetition rates of as many as 100 data points. Submicrometer spatial resolution is maintained during the measurement similarly to conventional two-photon microscopy.

Trends in Optics and Photonics Series || TOPS Vol 98, Series editor Alexander A. Sawchuck || 2005, Optical Society of America

Sub-nanojoulepulse compression in small core area photonic crystal fibers below the zero dispersion wavelength by Z. Várallyay, J. Fekete, Á.Bányász, R. Szipőcs || p. 571-576

Low reflection loss ion-beam sputtered negative dispersion mirrors with MCGTl structure for low pump threshold, compact femtosecond pulse lasers by B. Császár, A. Koházi- Kis, F. Szipőcs & R. Szipőcs || p 674-679

Cubic phase distortion of single attosecond pulses being reflected on narrowband Mo/Si filtering mirrors by András Lukács, Zoltán Várallyay, Róbert Szipőcs || p. 806-810

Real time 3D nonlinear microscopy by B. Rozsa, E. S. Vizi, G.Katona, A. Lukács, Z. Várallyay, A. Sághy, L. Valenta, P. Maák, J. Fekete, Á. Bányász, R. Szipőcs || p. 858-863


Broad tunability from a compact, low-threshold Cr:LiSAF laser incorporating an improved birefringent filter and multiple-cavity Gires-Tournois interferometer mirrors by Barry Stormont, Alan J. Kemp, Iain G. Cormack, Ben Agate, C. Tom A. Brown, and Wilson Sibbett and Róbert Szipőcs || 2005

Abstract: We demonstrate prismless tuning of a compact femtosecond Cr:LiSAF laser. The employed technique, which uses a specially designed birefringent filter in combination with dispersion compensation from a pair of multiple-cavity Gires-Tournois interferometer mirrors, provides tuning over 20 nm. We give the results of theoretical modeling of the tuning velocity and the spectral width of the central passband. We show, both experimentally and theoretically, that a single birefringent plate can be used to control the oscillating bandwidth of the laser. The effect this has on the output-pulse duration has also been investigated.


2005 Conference on Lasers and Electro-Optics, Quantum Electronics and Laser Science, May22-27, Baltimore, MD, USA || The four articles presented at the CLEO 2005 conference are now available online.


Nonlinear refraction and absorption of Mg doped stoichiometric and congruent LiNbO3 by L. Pálfalvi, G. Almási, Á. Péter, K. Polgár, K. Lengyel, and R. Szipőcs || February 2004

Abstract: The light induced change of refraction is studied in pure and Mg doped LiNbO3 with congruent and stoichiometric compositions by the Z-scan method using all-lines visible argonion laser, up to MW/cm intensity level. In Mg-doped congruent and stoichiometric crystals with Mg concentrations above threshold a positive change in the refractive index was found, in contrast to all other cases where beam fanning and negative change of the refractive index were observed.


Pulse compression of nanojoule pulses in the visible using microstructure optical fiber and dispersion compensation by S. Lakó, J. Seres, P. Apai, J. Balázs, R.S. Windeler, and R. Szipőcs || June 2002

Abstract: Experimental results on the pulse compression of 1-nJ, 150-fs pulses from a tunable, 76-MHz Ti:sapphire laser oscillator operating at around 750 nm are reported. The length of the pulses can be compressed to nearly one tenth by applying a high-delta, single-mode microstructured optical fiber exhibiting zero group-delay dispersion at 767 nm, and by a prismpair/ chirped-mirror compressor. The experimental results are verified by theoretical investigations modeling the pulse propagation taking into account non-linear self-phase modulation and fiber dispersion. PACS 42.65; 42.81


Spectral filtering of femtosecond laser pulses by interference filters by R. Szipőcs, A.Köházi-Kis, P. Apai, E. Finger, A. Euteneuer M.Hofmann || October 1999

Abstract: Phase properties of optical thin film interference filters are discussed from the aspect of their usage for phaseerror free wavelength separation of broadband femtosecond laser pulses. It is shown that both transmissive or reflective interference filters with high contrast ratios exhibit high cubic phase shifts on transmission or reflection, respectively, causing intolerable distortion in the temporal pulse shape. We show, however, that high efficiency wavelength separation of broadband femtosecond laser pulses can be achieved by using low contrast, properly designed reflective optical interference filters directly built into the cavity of the broad spectrum, femtosecond pulse lasers or parametric oscillators. For demonstrative purposes, we implemented the idea for a Kerrlens mode-locked Ti:sapphire laser, and obtained two-color, inherently synchronized, unchirped, femtosecond pulse outputs from a single laser oscillator.


Negative dispersion mirrors for dispersion control in femtosecond lasers: chirped dielectric mirrors and multi-cavity Gires-Tournois interferometers by R. Szipőcs, A.Köházi-Kis, S. Lakó, P. Apai, A.P.Kovács, G. DeBell, L.Mott, A.W. Louderback, A.V. Tikhonravov, M.K. Trubetskov || October 1999

Abstract. Chirped dielectric laser mirrors have been known for years as useful devices for broadband feedback and dispersion control in femtosecond pulse lasers. First we present a novel design technique referred to as frequency domain synthesis of chirped mirrors. These mirrors exhibit high reflectivity and nearly constant group delay over 150 THz supporting generation of sub-5-fs pulses in the visible...


Measurement of dispersive properties of optical materials and mirrors using spectrally resolved white- light interferometry by Zsolt Bor, Attila P Kovács, Károly Osvary and Róbert Szipőcs || April 1998

Abstract: We present a simple, accurate and inexpensive interferometric technique based on spectrally resolved white-light iterferometry to determine the group-delay dispersion of optical elements, such as layer crystals and multilayer mirrors. Due to the different dispersion of these elements, different evaluation methis of interference fringes are used for the mirrors and crystals.

A Compact All-Solid-State Sub-5fsec Laser by Andrius Baltuka, Maxim S Pschenichnikov, Róbert Szipőcs, Douwe A. Wiersma || December 1997

Abstract: n/a


Sub-20 fs pulse generation from the mirror dispersion controlled Cr:LiSGaFandCr:LiSAFlasers by I.T. Sorokina, E. Sorokin, E.Wintner, A. Cassanho, H.P. Jenssen and R. Szipőcs || May 1997


Abstract: We describe the state of the art of mirror-dispersioncontrolled (MDC) Kerr-lens mode-locked (KLM) Cr:LiSGaF and Cr:LiSAF lasers. Such lasers, in comparison to their prism-controlled forerunners, are distinguished by high reproducibility, stability, and quality of the pulses, as well as compactness of the cavity. The shortest pulses of ~18 fs duration and nearly bandwidth-limited quality (delta = 0.33) have been produced in Cr:LiSGaF lasers, which have an average output power of 100mW. In both lasers, krypton-laser was used as an ideal pump source. The effect of a red-shift of the operating wavelength (from 850 to 880 nm) when shortening of the pulse width (from ~ 50 fs to ~ 20 fs) has been observed and discussed.


Theory and design of chirped dielectric laser mirrors by A.Kõházi-Kis and R. Szipőcs || April 1997

Abstract: Chirped dielectric laser mirrors offer a general solution for broadband feedback and dispersion control in femtosecond laser systems. Chirped mirrors developed for modelocked solid-state lasers, femtosecond parametric oscillators, chirped pulse amplification systems and pulse compressors are introduced. Basic theoretical and design considerations are also presented.


All-solid-state cavity-dumped sub-5-fs laser by A. Baltuka1, Z.Wei, M.S. Pshenichnikov, D.A. Wiersma, Róbert Szipőcs || March 1997

Abstract. We discuss in detail a compact all-solid-state laser delivering sub-5-fs, 2-MW pulses at repetition rates up to 1MHz. The shortest pulse generated thus far measures only 4:6 fs. The laser system employed is based on a cavitydumped Ti:sapphire oscillator whose output is chirped in a single-mode fiber. The resulting white-light continuum is compressed in a novel high-throughput prism chirped-mirror Gires-Tournois interferometer pulse compressor. The temporal and spectral phase of the sub-5-fs pulses are deduced from the collinear fringe-resolved autocorrelation and optical spectrum. The derived pulse shape agrees well with the one retrieved from the measured group delay of the continuum and calculated characteristics of the pulse compressor.


Ultrabroadband chirped mirrors for femtosecond lasers by E. J. Mayer, J. Möbius, A. Euteneuer, and W. W. Rühle and R. Szipőcs || November 1996

Abstract: We report on the performance of widely tunable femtosecond and continuous-wave Ti:sapphire lasers that use a newly developed ultrabroadband mirror set. The mirrors exhibit high ref lectivity (R > 99%) and smooth variation of group delay versus frequency over a wavelength range from 660 to 1060 nm. Mode-locked operation with pulse durations of 85 fs was achieved from 693 to 978 nm with only one set of ultrabroadband mirrors.


Compression of high-energy laser pulses below 5 fs by M. Nisoli, S. De Silvestri and O. Svelto; R. Szipőcs and K. Ferencz; Ch. Spielmann, S. Sartania, and F. Krausz; || February 1996

Abstract: High-energy 20-fs pulses generated by a Ti:sapphire laser system were spectrally broadened to more than 250 nm by self-phase modulation in a hollow fiber filled with noble gases and subsequently compressed in a broadband high-throughput dispersive system. Pulses as short as 4.5 fs with energy up to 20-mJ were obtained with krypton, while pulses as short as 5 fs with energy up to 70 mJ were obtained with argon. These pulses are, to our knowledge, the shortest generated to date at multigigawatt peak powers.


Prismless passively mode-locked femtosecond Cr:LiSGaF laser by I. T. Sorokina, E. Sorokin, and E. Wintner, A. Cassanho, H. P. Jenssen and R. Szipőcs || February 1996

Abstract: A Kerr-lens mode-locked Cr:LiSrGaF laser containing no intracavity prisms has been demonstrated for the first time to the authors' knowledge. The laser produced stable near-transform-limited 44-fs pulses with an output power of 200 mW, tunable between 833 and 857 nm. Low-loss Gires-Tournois structured dielectric mirrors were used for dispersion control. The measured group-delay dispersion of the active medium as well as of the mirrors permitted to minimize the number of ref lections, permitting higher output power.


Ultrabroadband ring oscillator for sub-10-fs pulse generation by Lin Xu, Christian Spielmann, Ferenc Krausz and R. Szipőcs || January 1996

Abstract: A four-mirror ring cavity formed by chirped dielectric mirrors is proposed for self-mode-locked solid-state lasers. It offers, for the first time to our knowledge, the potential for approaching the gain-bandwidth limit in Ti:sapphire and related broadband lasers. Using this concept, we produced nearly bandwidth-limited 7.5-fs pulses from a feedback-initiated, self-mode-locked Ti:sapphire ring oscillator. Our experiments provide new insight into the physics and limitations of sub-10-fs oscillators.


Chirped dielectric mirrors improve Ti:sapphire lasers by Ch. Spielmann, M. Lenzner, R. Szipőcs and F. Krausz || December 1995

Abstract: High quality seed pulses from mirror dispersion-controlled Ti:sapphire system allow chirped pulse amplification without a pulse strectcher.


Compact, high-throughput expansion-compression scheme for chirped pulse amplification in the 10 fs range by Ch. Spielmanna, M. Lenzner, F. Krausz, R.Szipőcs || July 1995

Abstract: A novel pulse stretching-compression system suitable for kHz-rate chirped-pulse amplification of ~10 fs pulses in Ti:sapphire systems is demonstrated. The material dispersion of the system components used for pulse selection and isolation broadens the wide-band seed pulses by a factor of -300, allowing amplification up to the submillijoule energy range. The compressor consists of a pair of prisms and newly-developed chirped multilayer dielectric mirrors for compensating high order dispersion. Using this simple scheme a recompression of unamplified pulses down to 15 fs with a throughput as high as 80% is demonstrated.


Pushing the limits of Femtosecond Technology: Chirped Dielectric Mirrors by Róbert Szipőcs, Andreas Sitingl, Christian Spielmann and Ferenc Krausz || June 1995

Abstract: The authors explain the theory behind the ultrashort pulses and offer a new method - chirped dielectric mirrors - for achieving.


Measurement of the group delay of laser mirrors by a Fabry-Perot interferometer by K. Osvay, G. Kurdi, J. Hebling, A. P. Kovács, Z. Bor and R.Szipőcs || June 1995

Abstract: The group delay of multilayer laser mirrors was measured by determining the spectral position of transmission maxima of a Fabry–Perot interferometer formed by the mirrors to be characterized. By optimizing the spacer thickness, we obtained an accuracy of the group-delay measurement of better than 0.23 fs. To our knowledge, this is the most precise direct measuring method reported.


Chirped-mirror dispersion-compensated femtosecond optical parametric oscillator by J. Hebling, E. J. Mayer, J. Kuhl, R. Szipőcs || January 1995

Abstract: We describe the operating characteristics of a femtosecond optical parametric oscillator employing chirped mirrors for intracavity group-velocity dispersion compensation. Pumped by 760 mW of power from a self-mode-locked Ti:sapphire laser, this device provides 100-fs near-transform-limited pulses continuously tunable from 1.18 to 1.32 mm with an average power of 100-180 mW. The limitations of the present setup and strategies for further pulse shortening are discussed.


Group-delay easurement on laser mirrors by spectrally resolved white-light interferometry by A. P. Kovács, K. Osvay, Zs. Bor and R. Szipőcs || October 1994

Abstract: The frequency-dependent group delay of dielectric mirrors was measured by spectrally resolved white-light interferometry. Chirped mirrors and thin-film Gires-Tournois interferometers designed for dispersion control in a femtosecond Ti:sapphire laser oscillator-amplifier system were tested with a group-delay resolution of 60.2 fs and a spectral resolution of ,1 nm over the spectral range of 670-870 nm.


Sub-10-fs mirror-dispersion-controlled Ti:sapphire laser by A. Stingl, M. Lenzner, Ch. Spielmann, and F. Krausz and R. Szipőcs || October 1994

Abstract: We demonstrate the generation of nearly bandwidth-limited 8-fs optical pulses near 0.8 mm from a self-modelocked Ti:sapphire laser oscillator, using chirped dielectric mirrors for dispersion control. The mode-locking performance is described, and limitations are discussed.


Design of dielectric high reflectors for dispersion in femtosecond lasers by Róbert Szipőcs, Ambrus Kõházi-Kis || June 1994

Abstract: Chirped dielectric rugate mirrors were constructed for broadband dispersion control in femtosecond laser oscillators by Fouries transform. Dispersive properties of the mirrors are tailored and explained on the basis of the time shifting theorem of Fourier analysis. Depending on their construction parameters, these chirped gradientüindex structures exhibit high reflectivity amd neary constamt negative, i.e. anomalous, group delay dispersion over frequency ranges well beyond the currently available fluorescence bandwidth of broadbanc laser-active materials. As a consequence, practical implementation of these novel dispersive devices would permit the full utilisation of the bandwidth offered by these broadband gain media, and allow the construction of small, compat femtosecond solid state laser oscillators generating optical pulses shorter than those achieved so far, directly from the laser oscillator.


Tunneling of Optical Pulses through Photonic Band Gaps by and Ch. Spielmann, F. Krausz, A. Stingl and R. Szipőcs || April 1994

Abstract: Propagation of electromagnetic wave packed through ID photonic band gap materials has been studies using 12 fs optical pulses. The measured transit time is found to be paradoxically short (implying superluminal tunneling) and independent of the barriers thickness for opaque barriers, in analogy to the behavior of electrons tunneling through potential barriers. Shortening of Fourier-limited incident wave packets is observed upon transmission through these linear systems. Although in apparent conflict with causality and the uncertainty principle, neither of these general principles is violated because of the strong attenuation suffered by the transmitted signals.


Generation of 11-fs pulses from a Ti:sapphire laser without the use of prisms by Andreas Stingl, Christian Spielmann, Ferenc Krausz and Róbert Szipőcs || September 1993

Abstract: The generation of highly stable optical pulses as short as 11 fs from a Kerr-lens mode-locked Ti:sapphire laser containing no intracavity prisms is demonstrated. In the femtosecond oscillator design reported, novel dielectric mirrors provide broadband dispersion control for solitonlike pulse formation.


Chirped multilayer coatings for broadband dispersion control in femtosecond lasers by Robert Szipőcs, Kárpát Ferencz, Christian Spielmann and Ferenc Krausz || August 1993

Abstract: Optical thin-film structures exhibiting high reflectivity and a nearly constant negative group-delay dispersion over frequency ranges as broad as 80 THz are presented. This attractive combination makes these coatings well suited for intracavity dispersion control in broadband femtosecond solid-state lasers. We address design issues and the principle of operation of these novel devices...


Recent Developements of Laser Optical Coatings in Hungary by Kárpát Ferencz and Robert Szipőcs || October 1993

Abstract: Optical coating suppliers specialized to meet pecial needs of laser developers often have to face challenges to help them in building high-performance, high-efficiency lasers. Some aspects of laser optical coating design and manufacturing are discussed.