Lars Kirsten

Optical coherence tomography in biomedical research.

Optical coherence tomography (OCT) is a noninvasive, high-resolution, interferometric imaging modality using near-infrared light to acquire cross-sections and three-dimensional images of the subsurface microstructure of biological specimens. Because of rapid improvement of the acquisition speed and axial resolution of OCT over recent years, OCT is becoming increasingly attractive for applications in biomedical research. Therefore, OCT is no longer used solely for structural investigations of biological samples but also for functional examination, making it potentially useful in bioanalytical science. The combination of in vivo structural and functional findings makes it possible to obtain thorough knowledge on basic physiological and pathological processes. Advanced applications, for example, optical biopsy in visceral cavities, have been enabled by combining OCT with established imaging modalities. This report gives an outline of the state of the art and novel trends of innovative OCT approaches in biomedical research in which the main focus is on applications in fundamental research and pre-clinical utilization.

Investigation of the human tympanic membrane oscillation ex vivo by Doppler optical coherence tomography.

Investigations of the tympanic membrane (TM) can have an important impact on understanding the sound conduction in the ear and can therefore support the diagnosis and treatment of diseases in the middle ear. High-speed Doppler optical coherence tomography (OCT) has the potential to describe the oscillatory behaviour of the TM surface in a phase-sensitive manner and additionally allows acquiring a three-dimensional image of the underlying structure. With repeated sound stimuli from 0.4 kHz to 6.4 kHz, the whole TM can be set in vibration and the spatially resolved frequency response functions (FRFs) of the tympanic membrane can be recorded. Typical points, such as the umbo or the manubrium of malleus, can be studied separately as well as the TM surface with all stationary and wave-like vibrations. Thus, the OCT methodology can be a promising technique to distinguish between normal and pathological TMs and support the differentiation between ossicular and membrane diseases.

Four‐dimensional imaging of murine subpleural alveoli using high‐speed optical coherence tomography

The investigation of lung dynamics on alveolar scale is crucial for the understanding and treatment of lung diseases, such as acute lung injury and ventilator induced lung injury, and to promote the development of protective ventilation strategies. One approach to this is the establishment of numerical simulations of lung tissue mechanics where detailed knowledge about three-dimensional alveolar structure changes during the ventilation cycle is required. We suggest four-dimensional optical coherence tomography (OCT) imaging as a promising modality for visualizing the structural dynamics of single alveoli in subpleural lung tissue with high temporal resolution using a mouse model. A high-speed OCT setup based on Fourier domain mode locked laser technology facilitated the acquisition of alveolar structures without noticeable motion artifacts at a rate of 17 three-dimensional stacks per ventilation cycle. The four-dimensional information, acquired in one single ventilation cycle, allowed calculating the volume-pressure curve and the alveolar compliance for single alveoli.

Improved non-invasive Optical Coherence Tomography detection of different engineered nanoparticles in food-mimicking matrices

Food industry and regulators require fast and reliable analytical methods for quality control. This especially counts for the detection of engineered nanomaterials (ENMs) in food products. Respective EU regulation is in force, but the development of appropriate methods is still underway. This paper updates the scope of Optical Coherence Tomography (OCT) for ENM/food matrix analysis. A range of nanomaterials and composites - Au@SiO2, Ag, Ag@SiO2 and SiO2 - in a simplified food matrix was investigated. The earlier finding of linear dependencies between concentration in the dispersion and light responses could be reproduced. Being able to analyse non-invasively for a relevant industrial compound such as SiO2, makes OCT an excellent candidate for screening purposes.

Feasibility of non-invasive detection of engineered nanoparticles in food mimicking matrices by Optical Coherence Tomography

The study was dedicated towards the detection of Engineered Nanoparticles (ENPs) by means of Optical Coherence Tomography (OCT). Polymeric films were produced to mimic complex food matrices whereas gold nanorods (AuNRs) were embedded to act as ENPs. The straightforward coating application resulted in a sufficient film wetting, adhesion and homogenous AuNR distribution. Compared to food samples, these films are simpler and better defined. Such artefacts are therefore promising candidate materials for quality assurance and regulatory matters. The OCT investigations revealed a dependency of the measured signal intensity on the AuNR concentration in the film. The limit of detection for the setup and material was estimated to be -8 dB. This value corresponds to a ppm nanoparticle concentration being well below the concentration used in food additive applications. Thus, the findings indicate the potential of OCT to screen food/feed products for a number of ENPs.

Total liquid ventilation: a new approach to improve 3D OCT image quality of alveolar structures in lung tissue

Little is known about mechanical processes of alveolar tissue during mechanical ventilation. Optical coherence tomography (OCT) as a three-dimensional and high-resolution imaging modality can be used to visualize subpleural alveoli during artificial ventilation. The quality of OCT images can be increased by matching the refractive index inside the alveoli to the one of tissue via liquid-filling. Thereby, scattering loss can be decreased and higher penetration depth and tissue contrast can be achieved. We show the liquid-filling of alveolar structures verified by optical coherence tomography and intravital microscopy (IVM) and the advantages of index matching for OCT imaging of subpleural alveoli in a mouse model using a custom-made liquid ventilator.

Advanced analysis of domain walls in Mg doped LiNbO 3 crystals with high resolution OCT

The structure of domain walls (DW) in ferroelectric media is of great interest as this material is used for frequency doublers and other applications. We show that the structure of the DWs can nicely be visualized by high resolution optical coherence tomography (OCT). While the high group refractive index of lithium niobate allows a resolution much better than 1 µm, the large dispersion can blur the image and has to be compensated. Therefore, we developed an adaptive dispersion compensation algorithm based on maximizing the intensity of the DWs. By measuring a group of DWs, the mean period of the DWs could be measured with an accuracy of less than 10 nm differentiating samples with only 30 nm distinct periods. By analyzing the peak position, amplitude and phase shift within a DW, we were able to determine steps in the DW of only 50 nm. Furthermore, the inclined course of the DWs in a fan-shaped frequency doubler could be displayed. Therefore, we conclude that OCT is able to provide valuable information about the structure of domain walls in periodically poled lithium niobate (PPLN).

Imaging the tympanic membrane oscillation ex vivo with Doppler optical coherence tomography during simulated Eustachian catarrh

Recently, optical coherence tomography (OCT) was utilized in multiple studies for structural and functional imaging of the middle ear and the tympanic membrane. Since Doppler OCT allows both, the spatially resolved measurement of the tympanic membrane oscillation and high-resolution imaging, it is regarded as a promising tool for future in vivo applications. In this study, Doppler OCT is utilized for the visualization of the tympanic membrane oscillation in temporal bones with simulated Eustachian catarrh, which was realized by generating a depression in the tympanic cavity. The transfer function, meaning the oscillation amplitude normalized to the applied sound pressure, is measured frequency resolved in the range from 0.5 kHz to 6 kHz and with a lateral spatial resolution of 0.4 mm. Typical oscillation patterns could be observed in case of ambient pressure in the tympanic cavity. Under depression the characteristic oscillation patterns were observed with widely congruent appearance but at higher frequencies.

Optical coherence tomography for imaging of subpleural alveolar structure using a Fourier domain mode locked laser

Optical coherence tomography (OCT) is a noninvasive imaging modality generating cross sectional and volumetric images of translucent samples. In Fourier domain OCT (FD OCT), the depth profile is calculated by a fast Fourier transformation of the interference spectrum, providing speed and SNR advantage and thus making FD OCT well suitable in biomedical applications. The interference spectrum can be acquired spectrally resolved in spectral domain OCT or time-resolved in optical frequency domain imaging (OFDI). Since OCT images still suffer from motion artifacts, especially under in vivo conditions, increased depth scan rates are required. Therefor, the principle of Fourier domain mode locking has been presented by R. Huber et al. circumventing the speed limitations of conventional FD OCT systems. In FDML lasers, a long single mode fiber is inserted in the ring resonator of the laser resulting in an optical round trip time of a few microseconds. Sweeping the wavelength synchronously by a tunable Fabry-Perot filter can provide wavelength sweeps with repetition rates up to a few MHz used for OFDI. Imaging of subpleural lung tissue for investigation of lung dynamics and its elastic properties is a further biomedical application demanding high-speed OCT imaging techniques. For the first time, the visualization of subpleural alveolar structures of a rabbit lung is presented by the use of an FDML-based OCT system enabling repetition rates of 49.5 kHz and 122.6 kHz, respectively.

Doppler optical coherence tomography as a promising tool for detecting fluid in the human middle ear

Abstract The treatment of otitis media requires classifying the effusion in the tympanic cavity for choosing appropriate therapeutic strategies. Otoscopic examination of the middle ear depends on the expertise of the physician and is often hampered in case of inflammatory alterations of the tympanic membrane. In otologic research, optical coherence tomography is an innovative non-invasive imaging technique utilized for visualizing the tympanic membrane. This ex vivo study presents the possibility of OCT and Doppler-OCT for the detection of effusions in the tympanic cavity. Structural OCT imaging allows the direct visualization of scattering fluids behind the tympanic membrane. In addition, the measurement of the reduced oscillation amplitude by means of Doppler-OCT permits the indirect detection of scattering and transparent fluids.