There has so far been no shared understanding of validity in agent-based simulation. We here conceptualise validation as systematically substantiating the premises on which conclusions from simulation analysis for a particular modelling context are built. Given such a systematic perspective, validity of agent-based models cannot be ensured if validation is merely understood as an isolated step in the modelling process. Rather, valid conclusions from simulation analysis require context-adequate method choices at all steps of the simulation analysis including model construction, model and parameter inference, uncertainty analysis and simulation. We present a twelve-step protocol to highlight the (often hidden) premises for methodological choices and their link to the modelling context. It is designed to aid modelers in understanding their context and in choosing and documenting context-adequate and mutually consistent methods throughout the modelling process. Its purpose is to assist reviewers and the community as a whole in assessing and discussing context-adequacy.@en

Optical imaging techniques that provide free space, label free imaging are powerful tools in obtaining structural and biochemical information in biological samples. To date, most of the optical imaging technologies create images with a specific contrast and require multimodality integration to add additional contrast. In this study, we demonstrate spectroscopic Thermo-elastic Optical Coherence Tomography (TE-OCT) as a potential tool in tissue identification. TE-OCT creates images based on two different forms of contrast: optical reflectance and thermo-elastic deformation. TE-OCT uses short laser pulses to induce thermo-elastic tissue deformation and measures the resulting surface displacement using phase-sensitive OCT. In this work we characterized the relation between thermo-elastic displacement and optical absorption, excitation, fluence and illumination area. The experimental results were validated with a 2-dimensional analytical model. Using spectroscopic TE-OCT, the thermo-elastic spectra of elastic phantoms and tissue components in coronary arteries were extracted. Specific tissue components, particularly lipid, an important biomarker for identifying atherosclerotic lesions, can be identified in the TE-OCT spectral response. As a label-free, free-space, dual-contrast, all-optical imaging technique, spectroscopic TE-OCT holds promise for biomedical research and clinical pathology diagnosis.

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Optical coherence elastography (OCE), a functional extension of optical coherence tomography (OCT), visualizes tissue strain to deduce the tissue’s biomechanical properties. In this study, we demonstrate intravascular OCE using a 1.1 mm motorized catheter and a 1.6 MHz Fourier domain mode-locked OCT system. We induced an intraluminal pressure change by varying the infusion rate from the proximal end of the catheter. We analysed the pixel-matched phase change between two different frames to yield the radial strain. Imaging experiments were carried out in a phantom and in human coronary arteries in vitro. At an imaging speed of 3019 frames/s, we were able to capture the dynamic strain. Stiff inclusions in the phantom and calcification in atherosclerotic plaques are associated with low strain values and can be distinguished from the surrounding soft material, which exhibits elevated strain. For the first time, circumferential intravascular OCE images are provided side by side with conventional OCT images, simultaneously mapping both the tissue structure and stiffness.

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We exploit the thermoelastic effect to acquire spectroscopic information which is based on the inherent tissue optical absorption properties. We support the acquired data with a 2D model along with system characterisation.

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In this study, we demonstrate a 12x36 mm motorized capsule for OCT imaging of the esophagus. The capsule produces unobstructed images by using a distal reflector design, thus avoiding shadow caused by the motor wires. The motor synchronous control enables three working modes: circumferential imaging, angular sector imaging and accurate beam positioning. Distortion artifacts shown in the sector imaging were found to be induced by velocity changes of the motor. We specifically characterized the motor speed and found a symmetric and repeatable behavior during sector scanning. Resampling of the sector images A-lines was carried out to achieve uniform angular spacing according to the measured speed profile. Also, distortion between consecutive sector frames was corrected using image registration to achieve stable imaging.

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The absorption of laser pulses by tissue leads not only to the generation of acoustic waves, but also to nanometer to sub-micrometer scale displacement. After the initial expansion, a quasi-steady state is achieved in a few microseconds. Previously we introduced the concept of thermo-elastic optical coherence tomography (TE-OCT) to "visualise" the rapid thermo-elastic expansion by measuring the Doppler phase shift rather than istening" to the acoustic wave as in photoacoustic imaging. In this study, we built a microscopic setup for high-speed 3D TE-OCT imaging, by means of thermo-elastic optical coherence microscopy (TE-OCM). The repetition rate of pulsed laser was set to 100 Hz and the line rate of the OCT system is 1.5 MHz. The OCT beam and the laser pulse were focused upon the same location on the sample FWHM spot sizes of 300 μm for the pulsed laser and 40 μm FWHM for the OCT beam. For each laser pulse, an M-mode OCT image consisting of 90 A-lines was acquired. The Doppler phase shift was extracted by comparing the phase signal before and after the pulse arrival. Within 6 minutes, a 3D TE-OCM image (10 × 10 × 4 mm³) can be acquired and processed. Imaging experiments were carried out in swine meat using 1210 nm excitation wavelength to highlight lipid in tissue. The results show that no significant displacement was detected in swine muscle while strong displacement was observed in lipid, owing to the optical absorption features. Furthermore, fatty tissue is easily identified in the 3D TE-OCM image while the conventional OCT images provides the structural information.

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We demonstrate megahertz intravascular Doppler Optical Coherence Tomography (OCT). The OCT system relies on a 1.1 mm diameter motorized catheter and a 1.5 MHz Fourier Domain Mode Locked (FDML) laser. By resolving the phase shift between adjoint A-lines, the flow pattern image can be reconstructed. Imaging experiments were carried out in swine coronary artery in vitro at a speed of 600 frames/s. The MHz sweep rate not only allows us to investigate flow velocity of up to 37.5 cm/s without phase-unwrapping, but also enables dynamic flow imaging at high frame rate.

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We demonstrate a tethered motorized capsule for unobstructed optical coherence tomography (OCT) imaging of the esophagus. By using a distal reflector design, we avoided the common shadow artifact induced by the motor wires. A synchronous driving technique features three types of beam-scanning modes of the capsule, i.e., circumferential beam scanning, localized beam scanning, and accurate beam positioning. We characterized these three modes and carried out ex vivo imaging experiments using the capsule. The results show that the capsule can potentially be a useful tool for diagnostic OCT imaging and OCT-guided biopsy and therapy of the esophagus.

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The absorption of nanosecond laser pulses induces rapid thermo-elastic deformation in tissue. A sub-micrometer scale displacement occurs within a few microseconds after the pulse arrival. In this Letter, we investigate the laser-induced thermo-elastic deformation using a 1.5 MHz phase-sensitive optical coherence tomography (OCT) system. A displacement image can be reconstructed, which enables a new modality of phase-sensitive OCT, called thermo-elastic OCT. An analysis of the results shows that the optical absorption is a dominating factor for the displacement. Thermo-elastic OCT is capable of visualizing inclusions that do not appear on the structural OCT image, providing additional tissue type information.

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