Beyond backscattering: Optical neuroimaging by BRAD

Optical coherence tomography (OCT) is a powerful technology for rapid volumetric imaging in biomedicine. The bright field imaging approach of conventional OCT systems is based on the detection of directly backscattered light, thereby waiving the wealth of information contained in the angular scattering distribution. Here we demonstrate that the unique features of few-mode fibers (FMF) enable simultaneous bright and dark field (BRAD) imaging for OCT. As backscattered light is picked up by the different modes of a FMF depending upon the angular scattering pattern, we obtain access to the directional scattering signatures of different tissues by decoupling illumination and detection paths. We exploit the distinct modal propagation properties of the FMF in concert with the long coherence lengths provided by modern wavelength-swept lasers to achieve multiplexing of the different modal responses into a combined OCT tomogram. We demonstrate BRAD sensing for distinguishing differently sized microparticles and showcase the performance of BRAD-OCT imaging with enhanced contrast for ex vivo tumorous tissue in glioblastoma and neuritic plaques in Alzheimer's disease

Label-free intratissue activity imaging of alveolar organoids with dynamic optical coherence tomography

An organoid is a three-dimensional (3D) in vitro cell culture emulating human organs. We applied 3D dynamic optical coherence tomography (DOCT) to visualize the intratissue and intracellular activities of human induced pluripotent stem cells (hiPSCs)-derived alveolar organoids in normal and fibrosis models. 3D DOCT data were acquired with an 840-nm spectral domain optical coherence tomography with axial and lateral resolutions of 3.8 {\mu}m (in tissue) and 4.9 {\mu}m, respectively. The DOCT images were obtained by the logarithmic-intensity-variance (LIV) algorithm, which is sensitive to the signal fluctuation magnitude. The LIV images revealed cystic structures surrounded by high-LIV borders and mesh-like structures with low LIV. The former may be alveoli with a highly dynamics epithelium, while the latter may be fibroblasts. The LIV images also demonstrated the abnormal repair of the alveolar epithelium

Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography

Label-free metabolic imaging of non-alcoholic fatty liver disease (NAFLD) mouse liver is demonstrated ex vivo by dynamic optical coherence tomography (OCT). The NAFLD mouse is a methionine choline-deficient (MCD)-diet model, and two mice fed MCD diet for 1 and 2 weeks are involved in addition to a normal-diet mouse. The dynamic OCT is based on repeating raster scan and logarithmic intensity variance (LIV) analysis which enables volumetric metabolic imaging with a standard-speed (50,000 A-lines/s) OCT system. Metabolic domains associated with lipid droplet accumulation and inflammation are clearly visualized three-dimensionally. Particularly, the normal-diet liver exhibits highly metabolic vessel-like structures of peri-vascular hepatic zones. The 1-week MCD-diet liver shows ring-shaped highly metabolic structures formed with lipid droplets. The 2-week MCD-diet liver exhibits fragmented vessel-like structures associated with inflammation. These results imply that volumetric LIV imaging is useful for visualizing and assessing NAFLD abnormalities

Theoretical model for en face optical coherence tomography imaging and its application to volumetric differential contrast imaging

A new formulation of lateral imaging process of point-scanning optical coherence tomography (OCT) and a new differential contrast method designed by using this formulation are presented. The formulation is based on a mathematical sample model called the dispersed scatterer model (DSM), in which the sample is represented as a material with a spatially slowly varying refractive index and randomly distributed scatterers embedded in the material. It is shown that the formulation represents a meaningful OCT image and speckle as two independent mathematical quantities. The new differential contrast method is based on complex signal processing of OCT images, and the physical and numerical imaging processes of this method are jointly formulated using the same theoretical strategy as in the case of OCT. The formula shows that the method provides a spatially differential image of the sample structure. This differential imaging method is validated by measuring in vivo and in vitro samples

Modeling and simulation of the cervical spine : mechanical stress in injuries

Zsfassung in dt. SpracheInjuries to the human neck are most of time very dangerous and in numerous cases they lead to severe damages to the human body. Due to the fact that the number of serious injuries to the human neck has risen in our modern society, the research in this field is gaining more and more importance. Reasons are among others high-speed transportation as well as increasing leisure-time activities. Hence, main objective is the individual safety and, thus, the identification of the most relevant improvement potentials. A very critical part of the human neck is the upper cervical spine. The spinal cord is the main nerve fiber that runs through it. This nerve fiber controls nearly every essential function. Therefore, its protection has highest priority. In the human body this protection function is performed, amongst others, by the vertebrae of the backbone. The vertebral column, especially the upper cervical spine, is because of its high range of movability a common place for dangerous injuries. To be more precise, fractures occurring in the vertebrae of the upper cervical spine are responsible for many life-threatening injuries. Due to this fact, the goal of this thesis was to get a deeper inside into the upper cervical spine and investigate fractures in the vertebrae of this part of the human body. At the division of Neuronic Engineering, KTH, a Finite Element Model of the human cervical spine has been developed and used extensively since 1996. One main question was if it is possible to use the vertebrae in the existing level of detail in order to predict vertebral fractures. To investigate this question, the second vertebrae, also called axis or shorter C2, is picked out, as this axis is the most common place for fractures in the upper cervical spine. A new finite element model for the C2 vertebrae was established and compared to the behavior with the already existing one from the KTH neck model. Based on computer tomography data of the vertebrae, a three dimensional model of the axis was created and a Finite Element meshing is done with the help of the software ICEM CDF. After that, material properties and boundary conditions were added with the help of the software LS-DYNA. In order to compare the models, two test case sets were defined. Firstly, the vertebrae was directly loaded with various forces at different places. Secondly, a whole fall scenario using the neck model was simulated to apply forces to the vertebrae. The results from the test case set 1 indicate that with the new axis model it is possible to simulate a similar behavior as with the existing KTH model. Further, with a mesh convergence analysis it could be shown that the new C2 Finite Element model has a slightly better convergence rate. Regarding the results of test case 2, it was concluded that both models could deliver the expected and reasonable Von Mises stress distributions. In the context of fracture modeling it can be said that with both models typical fracture patterns can be obtained. All results are in good agreement with experimental data and literature data of already accomplished models. To summarize, the basis for further investigations in the area of fracture prediction in the human vertebrae was elaborated with this thesis. It was shown that most important elements for the creation and application of an appropriate model are a proper geometry definition, a good choice of the finite element mesh and the selection of realistic test cases.8

Blood Flow Simulation in Arterial Networks with 1D FEM

Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in engl. SpracheKardiovaskuläre Krankheiten sind die häufigste Todesursache in unserer Gesellschaft.Um die Diagnose und in weiterer Folge die Behandlung dieser Krankheiten zu verbessern, wird vermehrt auf dynamische Modelle des Herzkreislaufsystems zurückgegriffen. Bei der Modellauswahl sind Genauigkeit, Rechenaufwand und Identifizierbarkeit der Modellparameter entscheidende Faktoren. Modelle mit einer Raumdimension rücken auf Grund ihrer hohen Effizienz dabei immer mehr in den Fokus der Forschung. Ziel dieser Diplomarbeit ist es, mit Hilfe der Finiten Elementen Methode den Blutfluss durch diverse Netzwerke von Arterien in einer Dimension zu simulieren. Ausgangspunkt dafür sind die allgemeinen Navier-Stokes Gleichungen, welche die Grundlage der Strömungsmechanik bilden. Aus diesen Gleichungen wird unter zusätzlichen Annahmen ein eindimensionales Modell hergeleitet. Ein Arterienstück wird dafür durch ein axialsymmetrisches Rohr abstrahiert, welches zusätzlich bestimmte druck- und geschwindigkeitsabhängige Eigenschaften aufweist. Das führt zu einem eindimensionalen hyperbolischen Differentialgleichungssystem für die Zustandsgrößen Querschnittfläche, Fluss, Geschwindigkeit und Druck. Dieses System wird im Folgenden in Erhaltungsform gebracht und es wird eine charakteristische Analyse des Systems durchgeführt. Die geeignete Wahl der Randbedingungen im Modell ist von entscheidender Wichtigkeit, um einerseits eine eindeutige Lösung des Problems zu erhalten und andererseits die physiologischen Vorgänge im kardiovaskulären System optimal modellieren zu können. Dabei dient der Blutdruck aus dem Herzen als Eingangsfunktion für das Modell. Der Ausfluss aus dem Arteriensystem muss ebenfalls geeignet modelliert werden. In dieser Arbeit kommt ein drei-elementiges Windkesselmodell zum Einsatz, da man mit diesem die Dehnbarkeit und den im System vorherrschenden Widerstand realistisch abbilden kann. Die Randwerte werden dabei über die charakteristischen Variablen berechnet. Ein zentrales Thema dieser Arbeit ist die Modellierung der Bifurkationen, also die Verzweigung einer Arterie in zwei Folgende. Mit Hilfe dieser werden diverse abstrahierte arterielle Bäume simuliert. Dazu müssen an einer Bifurkation die Stetigkeit des Druckes und die Aufteilung des Flusses auf die folgenden Arterien gewährleistet sein. Das führt zu einem nichtlinearen Gleichungssystem, welches gelöst werden muss. Da es sich bei dem eindimensionalen Modell um ein nicht analytisch lösbares System handelt, wird eine numerische Methode zur Lösung benötigt. In dieser Arbeit kommt dabei eine Finite Elemente Methode zum Einsatz, um das partielle Differentialgleichungssystem zu lösen. Dazu wird eine Diskretisierung der Gleichungen in Raum und Zeit durchgeführt. Die Diskretisierung erfolgt mit einem Taylor-Galerkin Verfahren zweiter Ordnung, wobei Basisfunktionen erster Ordnung verwendet werden. Da man bei diesem rasch an Stabilitäts- und Effizienzgrenzen stößt, wird in dieser Arbeit überdies ein Discontinuous Galerkin Verfahren mit Legendre Polynomen höherer Ordnung als Basisfunktionen, füdie Diskretisierung verwendet. Die Umsetzung der Implementierung der beiden Methoden erfolgt mit Hilfe der mathematischen Software Matlab. Um das Modell zu validieren, werden diverse Simulationen durchgeführt. Dabei werden unterschiedlich große arterielle Netzwerke betrachtet: ein Arterienstück; eine Bifurkation (drei Arterienstücke); ein abstrahierter arterieller Arterienbaum bestehend aus dreizehn zentral liegenden Arterien. Bei allen Versuchen werden mit Hilfe der zu wählenden Windkesselparameter und der die Arterien betreffenden Parameter, welche einerseits durch Versuche bestimmt und andererseits an die Physiologie angelehnt sind, physiologisch passende Resultate berechnet. Die Berechnungen werden mit bereits vorhandenen Ergebnissen von aus der Literatur stammenden Simulationen verglichen und somit validiert. Dabei können gute Übereinstimmungen festgestellt werden. Außerdem werden die zwei numerischen Verfahren, also das Taylor-Galerkin und das Discontinuous Galerkin Verfahren, anhand der Simulation eines Arterienstückes verglichen. Beide Methoden liefern die gleichen Ergebnisse, allerdings stellt sich das Discontinuous Galerkin Verfahren im Vergleich als recheneffizienter heraus. Es zeigt sich, dass die eindimensionalen Finite Elemente Methode in der vorliegenden Implementierung die Vorgänge im Arteriensystem realistisch und recheneffizient abbilden kann. Ein Anwendungsgebiet für das Modell ist die Früherkennung von Krankheiten des arteriellen Systems des Menschen. Mit Hilfe von Messdaten gesunder Menschen kann das Modell parametrisiert werden. Die somit erhaltenen Modellergebnisse können dann mit Messdaten von Patienten mit kardiovaskulären Krankheiten verglichen werden, um Rückschlüsse auf krankhafte Veränderungen im System ziehen zu können.Cardiovascular diseases are the most common causes of death in the modern society. To improve the diagnosis and further the therapy of such diseases, dynamic models for the heart circulation system are used more and more often. In these models, the main factors which must be considered are accurateness, computing time and identifiability of the parameters. Therefore, one dimensional models, which have in fact a high efficiency, come to the center of attention. The aim of this master thesis is to simulate the bloodstream through networks of blood vessels with the Finite Element Method in one dimension. The starting points are the general Navier-Stokes equations which build the basis for fluid mechanics. Based on these very complex equations a one dimensional model is derived using additional assumptions. In this context, it is not only very important to understand the biological behavior of human blood vessels, but also to have a profound knowledge about blood pressure, wave propagation and other factors which will have an influence on the simulation. The precedent model condition is that an artery can be represented by an axisymmetric cylinder in which certain flow and pressure conditions exist. As result a one dimensional system of partial differential equations is derived. This system can be written in hyperbolic conservation form with the state variables crosssectional area, the flow, the velocity and the pressure. To solve the system of partial differential equations, numerically correct boundary conditions have to be considered. To be more precise, the main questions are on the one hand, how to simulate the input from the heart, and on the other hand, how to simulate the load downstream and compliance in a physiological way. For the input, a pressure function is used. To simulate the load downstream and the compliance of the arteries, a Windkessel model consisting of three elements is used. The literature has shown that this model can simulate the physiological effects which appear in a system of arteries in a realistic way. Furthermore, a main part of this thesis is to describe bifurcations, the branching of the arteries. By using bifurcations the considered abstract vascular networks can be simulated. In this context two conditions have to be fulfilled. Firstly, same pressure in all branches and, secondly, mass conservation at the junction. With these two conditions, a nonlinear system of equations is set up and solved to simulate bifurcations. The partial differential equation system cannot be solved analytically. Hence, to solve it in this thesis a numerical Finite Element Method is used. To set up a Finite Element Method a discretization in space and time has to be done. In this context, a Taylor Galerkin method of second order with basic functions of first order is used. With this method, efficiency and stability limitations are reached and therefore a second method, the Discontinuous Galerkin method with high order Legendre polynomial as basic functions is considered. The model is implemented by using the mathematical software Matlab. To verify the model, several simulations are done, using one artery, one bifurcation consisting of three arteries and an abstract arterial tree built up by thirteen central arteries. In all simulations, the parameters of the Windkessel model and the parameters of the arteries are based on experiments and on physiological values. In all tests, physiologically realistic results are obtained. After that, the calculations are verified with published results of already accomplished models. The comparison shows very good agreements. Furthermore, the two numerical methods, namely the Taylor-Galerkin and the Discontinuous Galerkin method, are compared by the simulation of one arterial segment. The same results are obtained with both methods. However, it can be seen that the Discontinuous Galerkin method has a higher computational efficiency than the Taylor-Galerkin method. It can be concluded that the application of a one dimensional Finite Element Method approach along with the particular implementation presented can describe the effects in a system of human arteries in a realistic way and, on top of that, has a shorter computing time. A field of application for this model is the early diagnosis of cardiovascular diseases. With measurements gained from healthy patients, the model can be parameterized. The calculations from this model can be compared with measurements from patients with cardiovascular diseases in order to conclude about abnormal changes in the cardiovascular system.11

Optical Coherence Tomography Is a Promising Tool for Zebrafish-Based Research—A Review

The zebrafish is an established vertebrae model in the field of biomedical research. With its small size, rapid maturation time and semi-transparency at early development stages, it has proven to be an important animal model, especially for high-throughput studies. Three-dimensional, high-resolution, non-destructive and label-free imaging techniques are perfectly suited to investigate these animals over various development stages. Optical coherence tomography (OCT) is an interferometric-based optical imaging technique that has revolutionized the diagnostic possibilities in the field of ophthalmology and has proven to be a powerful tool for many microscopic applications. Recently, OCT found its way into state-of-the-art zebrafish-based research. This review article gives an overview and a discussion of the relevant literature and an outlook for this emerging field

Polymer-derived Ni/SiOC materials structured by vat-based photopolymerization with catalytic activity in CO2 methanation

A new concept for the additive manufacturing of nickel-modified polymer-derived ceramics via vat-based photopolymerization is presented. A photoactive polysiloxane resin system modified by nickel nitrate via methacrylic acid complexation was developed and modified to facilitate vat-based photopolymerization. Through pyrolysis of the Ni-modified preceramic polymer at temperatures between 600 and 800 °C, amorphous SiOC components with well-dispersed Ni nanoparticles can be obtained. The modified polymer and the fabricated structures were characterized by photorheology, thermal analysis, scanning and transmission electron microscopy, optical coherence tomography, and powder X-ray diffraction. In addition, the effect of pyrolysis temperature on specific surface area, crystallinity, and shrinkage was investigated. The developed material systems enable additive manufacturing of porous SiOC structures containing crystalline, uniformly distributed, and bimodally sized Ni nanoparticles, exhibiting catalytic activity suitable for CO2 methanation. The developed printable SiOC/Ni materials represent a promising approach for combining metal-modified polymer-derived ceramic systems and additive manufacturing for prospective catalysis applications

Attenuation coefficient as a quantitative parameter for analyzing cataracts with optical coherence tomography

Crystalline lenses of mice were imaged in vivo with a custom-made swept-source optical coherence tomography system. The use of the attenuation coefficient as a quantitative parameter for investigating the lens opacities magnitude is proposed, demonstrating a significant difference between the values retrieved from cataractous and normal mouse lenses