Christian Schnabel

Three-dimensional Fourier domain optical coherence tomography in vivo imaging of alveolar tissue in the intact thorax using the parietal pleura as a window

In vivo determination of 3-D and dynamic geometries of alveolar structures with adequate resolution is essential for developing numerical models of the lung. A thorax window is prepared in anesthetized rabbits by removal of muscle tissue between the third and fourth rib without harming the parietal pleura. The transparent parietal pleura allows contact-free imaging by intravital microscopy (IVM) and 3-D optical coherence tomography (3-D OCT). We demonstrate that dislocation of the lung surface is small enough to observe identical regions in the expiratory and inspiratory plateau phase, and that OCT in this animal model is suitable for generating 3-D geometry of in vivo lung parenchyma. To our knowledge, we present a novel thorax window preparation technique for 3-D imaging of alveolar dynamics for the first time. The 3-D datasets of the fine structure of the lung beneath the pleura could provide a basis for the development of 3-D numerical models of the lung.

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.

Highly sensitive time-resolved thermography and multivariate image analysis of the cerebral cortex for intrasurgical diagnostics

Time-resolved thermography is a novel method to assess thermal variations and heterogeneities in tissue and blood. The recent generation of thermal cameras provides a sensitivity of less than mK. This high sensitivity in conjunction with non-invasive, label-free and radiation-free monitoring makes thermography a promising tool for intrasurgical diagnostics. In brain surgery, time-resolved thermography can be employed to distinguish between normal and anomalous tissue. In this study, we investigated and discussed the potential of time-resolved thermography in neurosurgery for the intraoperative detection and demarcation of tumor borders. Algorithms for segmentation, reduction of movement artifacts and image fusion were developed. The preprocessed image stacks were subjected to discrete wavelet transform to examine individual frequency components. K-means clustering was used for image evaluation to reveal similarities within the image sequence. The image evaluation shows significant differences for both types of tissue. Tumor and normal tissues have different time characteristics in heat production and transfer. Furthermore, tumor could be highlighted. These results demonstrate that time-resolved thermography is able to support the detection of tumors in a contactless manner without any side effects for the tissue. The intraoperative usage of time-resolved thermography improves the accuracy of tumor resections to prevent irreversible brain damage during surgery.

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.

Experimental methods for flow and aerosol measurements in human airways and their replicas

Abstract Recent developments in the prediction of local aerosol deposition in human lungs are driven by the fast development of computational simulations. Although such simulations provide results in unbeatable resolution, significant differences among distinct methods of calculation emphasize the need for highly precise experimental data in order to specify boundary conditions and for validation purposes. This paper reviews and critically evaluates available methods for the measurement of single and disperse two‐phase flows for the study of respiratory airflow and deposition of inhaled particles, performed both in vivo and in replicas of airways. Limitations and possibilities associated with the experimental methods are discussed and aspects of the computational calculations that can be validated are indicated. The review classifies the methods into following categories: 1) point‐wise and planar methods for velocimetry in the airways, 2) classic methods for the measurement of the regional distribution of inhaled particles, 3) standard medical imaging methods applicable to the measurement of the regional aerosol distribution and 4) emerging and nonconventional methods. All methods are described, applications in human airways studies are illustrated, and recommendations for the most useful applications of each method are given. Graphical abstract Figure. No caption available.

Wavelet Subspace Analysis of Intraoperative Thermal Imaging for Motion Filtering

Intraoperative thermography allows fast capturing of small temperature variations during neurosurgical operations. External influences induce periodic vibrational motion to the whole camera system superimposing signals of high-frequent neuronal activity, heart rate activity and injected perfusion tracers by motion artifacts. In this work, we propose a robust method to eliminate the effects induced by the vibrational motion allowing further inference of clinical information. For this purpose, an efficient wavelet shrinkage scheme is developed based on subspace analysis in 1D wavelet domain to recognize and remove motion related patterns. The approach does not require any specific motion modeling or image warping, making it fast and preventing image deformations. Promising results of a simulation study and by intraoperative measurements make this method a reliable and efficient method improving subsequent perfusion and neuronal activity analysis.

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).

Heart valve stenosis in laser spotlights: insights into a complex disease.

Degenerative heart valve disease is a life-threatening disease affecting about 3% of the population over 65 years. Up to date, cardiac surgery with heart valve replacement is the only available therapy. The disease is characterized by degenerative disorganization of the heart valve structure and alterations in the residing cell populations. Causes and mechanisms of disease genesis are still not fully understood and until now pharmacological therapies are not available. Thus there is enormous interest in new technologies that enable a better characterization of structure and composition of diseased valves. Currently most research techniques demand for extensive processing of extracted valve material. We present a novel approach combining coherent anti-Stokes Raman scattering, endogenous two-photon excited fluorescence and second harmonic generation. Cusp constituents can be examined simultaneously, three-dimensionally and without extensive manipulation of the sample enabling impressive insights into a complex disease.

Ex vivo 4D visualization of aortic valve dynamics in a murine model with optical coherence tomography

The heart and its mechanical components, especially the heart valves and leaflets, are under enormous strain and undergo fatigue, which impinge upon cardiac output. The knowledge about changes of the dynamic behavior and the possibility of early stage diagnosis could lead to the development of new treatment strategies. Animal models are suited for the development and evaluation of new experimental approaches and therefor innovative imaging techniques are necessary. In this study, we present the time resolved visualization of healthy and calcified aortic valves in an ex vivo artificially stimulated heart model with 4D optical coherence tomography and high-speed video microscopy.

Improved OCT imaging of lung tissue using a prototype for total liquid ventilation

Optical coherence tomography (OCT) is used for imaging subpleural alveoli in animal models to gain information about dynamic and morphological changes of lung tissue during mechanical ventilation. The quality of OCT images can be increased if the refraction index inside the alveoli is matched to the one of tissue via liquid-filling. Thereby, scattering loss can be decreased and higher penetration depth and tissue contrast can be achieved. Until now, images of liquid-filled lungs were acquired in isolated and fixated lungs only, so that an in vivo measurement situation is not present. To use the advantages of liquid-filling for in vivo imaging of small rodent lungs, it was necessary to develop a liquid ventilator. Perfluorodecalin, a perfluorocarbon, was selected as breathing fluid because of its refraction index being similar to the one of water and the high transport capacity for carbon dioxide and oxygen. The setup is characterized by two independent syringe pumps to insert and withdraw the fluid into and from the lung and a custom-made control program for volume- or pressure-controlled ventilation modes. The presented results demonstrate the liquid-filling verified by optical coherence tomography and intravital microscopy (IVM) and the advantages of liquid-filling to OCT imaging of subpleural alveoli.