Virtual Tissues Research Articles

Integration mapping of cardiac fibroblast single-cell transcriptomes elucidates cellular principles of fibrosis in diverse pathologies.

Single-cell technology has allowed researchers to probe tissue complexity and dynamics at unprecedented depth in health and disease. However, the generation of high-dimensionality single-cell atlases and virtual three-dimensional tissues requires integrated reference maps that harmonize disparate experimental designs, analytical pipelines, and taxonomies. Here, we present a comprehensive single-cell transcriptome integration map of cardiac fibrosis, which underpins pathophysiology in most cardiovascular diseases. Our findings reveal similarity between cardiac fibroblast (CF) identities and dynamics in ischemic versus pressure overload models of cardiomyopathy. We also describe timelines for commitment of activated CFs to proliferation and myofibrogenesis, profibrotic and antifibrotic polarization of myofibroblasts and matrifibrocytes, and CF conservation across mouse and human healthy and diseased hearts. These insights have the potential to inform knowledge-based therapies.

Using machine learning to parametrize large scale tumor simulations.

While clinical imaging of tissues focuses on macroscopic tumors, many experiments investigate only small clusters of cells. We aim on providing a scale-bridging link by performing large scale tissue simulations. We employ highly parallelized code in an HPC setting to simulate mm-sized virtual tissues such as embryogenetic zebrafish tissue or breastcancer tumors with more than a million µm-resolved individual cells. We deploy Cells in Silico (CiS), which combines a cellular potts model with an agent based layer and is thus capable of accurately representing many physical and biological properties, such as individual cell shapes, cell division, cell motility etc. Using a model with such a strong representational capacity poses the task of adjusting a large number of parameters to reproduce experimental findings. Prior work has attempted to characterize the similarity between experimental and simulated data by extracting different features and using statistical tests to establish a distance measure. This work highlights how this difficult task can be circumvented by training neural networks to distinguish between experimental and simulated data while simultaneously optimizing the model parameters to maximize the error rate of the network.

Development of Haptic Interface for Neurosurgical Simulators with Micro Scissors Module for Displaying the Cutting Force

Introduction of surgical simulators, which enable repeated learning of new surgical techniques, is advancing and they are desired in the field of neurosurgery. This study aims to make a two-fold contribution. First is the development of a haptic interface, which can be used while changing the operative tools necessary for training the cerebral fissure opening technique while using both the hands. Second is to develop a module for the haptic interface, which can display the cutting force when using micro scissors. To realize the operation with both the hands, the haptic interfaces for the right and left hands are designed so that they do not interfere. In addition, surgical tools, such as retractors, micro dissectors, and micro scissors, can be exchanged. In the cutting experiment carried out prior to the development of the haptic interface, it was clarified that the force when the dura mater was cut using micro scissors was 0.5 N. For comparison, the cutting forces required to cut two and three sheets of paper were measured to be 0.4 N and 0.6 N, respectively. The developed micro scissors module was designed using one motor and planetary gear mechanism. The gear mechanism is designed such that the right and left handles rotate in reverse directions around the rotation axis of the micro scissors using only one motor. This mechanism enables the micro scissors to cut the virtual tissues in the middle of the blade. The developed module could display a force of 0.4 N.

8.2: Anatomy Education Method using Autostereoscopic 3D Image Overlay and Mid‐Air Augmented Reality Interaction

The augmented reality (AR) medical education systems offer unique advantages for an interactive and hands‐on integration with the student in surgical skill training. However, there are still major differences in visualization and interaction between real surgical environments and AR‐based medical education systems. In this paper, we propose an anatomy education method using an autostereoscopic 3D image overlay and mid‐air augmented reality interaction with soft tissue deformation. To achieve good depth perception and intuitive interaction, we introduce a model‐based occlusion handling for accurate occlusion processing in real time and a position‐based dynamics (PBD) simulation method for virtual soft tissue deformation in real time. The experimental results showed that our approach could provide 3D visualization and interaction of virtual soft tissues and handle the mutual occlusion automatically in real time. Our proposed medical education system will provide users with a visualization and interaction experience close to real surgical environments.

Haptically enhanced VR surgical training system

Abstract This paper proposes a cost-effective VR surgical training system which computes haptic feedback forces when a VR surgical tool interacts with virtual tissues. A 3 degrees of freedom (DoF) reverse linear Delta mechanism is used to render computed force feedback data which are then received by the fingertip of the operator. Additionally, the moving plate allows rendering of surface properties and lateral forces occurring due to a tumor with different stiffness parameters below the skin surface. Controllers are designed and implemented to regulate the haptic feedback device’s end-effector position and applied force. The virtual surgical instruments are controlled by a 7DoF serial link manipulator which captures the operator’s movement by the utilization of various sensors. The controllers to regulate forces as well as the positions are evaluated with the proposed haptic feedback device. The mean RMSE of the force and mean error of the angular displacement are 0.0707 N and 1.95°, respectively. The presented system can provide multisensory feedback including visual, auditory and haptic feedback interactively depending on the operator’s input in the presented VR surgical training system.

Usability, acceptance, and educational usefulness study of a new haptic operative dentistry virtual reality simulator

BackgroundDental preclinical training has been traditionally centered onverbal instructions and subsequent execution on phantom heads and plastic training models. However, these present present limitations. Virtual Reality (VR) and haptic simulators have been proposed with promising results and advantages and have showed usefullness in the preclinical training environment. We designed DENTIFY, a multimodal immersive simulator to assist Operative Dentistry learning, which exposes the user to different virtual clinical scenarios while operating a haptic pen to simulate dental drilling. ObjectiveThe main objective is to assess DENTIFY’s usability, acceptance, and educational usefulness to dentists, in order to make the proper changes and, subsequently, to test DENTIFY with undergraduate preclinical dental students. MethodsDENTIFY combines an immersive head mounted VR display, a haptic pen in which the pen itself has been replaced by a 3D printed model of a dental turbine and a controller with buttons to adjust and select the scenario of the simulation, along with 3D sounds of real dental drilling. The user’s dominant hand operated the virtual turbine on the VR-created scenario, while the non-dominant hand is used to activate the simulator and case selection. The simulation sessions occurred in a controlled virtual environment. We evaluated DENTIFY’s usability and acceptance over the course of 13 training sessions with dental professionals, after the users performed a drilling task in virtual dental tissues. ResultsThe conducted user acceptance indicates that DENTIFY shows potencial enhancing learning in operative dentistry as it promotes self-evaluation and multimodal immersion on the dental drilling experience. ConclusionsDENTIFY presented significant usability and acceptance from trained dentists. This tool showed to have teaching and learning (hence, pedagogical) potential in operative dentistry.

Application of computer-generated images to train pattern recognition used in semiquantitative immunohistochemistry scoring.

This study aimed to clarify whether the pattern recognition involved in scoring proliferation fractions can be trained by abstract computerized images of virtual tissues. Twenty computer-generated images with randomly distributed blue or red dots were scored by 12 probands (all co-workers or collaborators of the Institute of Pathology, University of Bonn). Afterward, the probands underwent a training phase during which they received an immediate feedback on the actual rate of positivity after each image. Finally, the initial testing series was rescored. In a second round with 15 different probands, 20 Ki-67 immunohistochemistry images of tonsil tissue were scored, followed by the same training phase with computer-generated images, before the immunohistochemistry slides were scored again. Paired t-tests were used to compare the differences in mean rates pre- and post-training. Concerning computerized images, untrained probands scored the percentages of positive dots with a mean deviation from the true rates of 8.2%. Following training, the same testing series was scored significantly better with a mean deviation of 4.9% (mean improvement 3.3%, p < 0.001). Scoring real immunohistochemistry slides, the training with computerized images also improved correct estimations, albeit to a lesser degree (mean improvement 1%, p = 0.03). Abstract computerized images of virtual tissues may be a useful tool to train and improve the accuracy of pattern recognition involved in semiquantitative scoring of immunohistochemistry slides. As a side results, this study highlights the value of computer-generated images to verify the performance of image-analysis software.

Analysis of the response of human iPSC-derived cardiomyocyte tissue to ICaL block. A combined in vitro and in silico approach

The high incidence of cardiac arrythmias underlines the need for the assessment of pharmacological therapies. In this field of drug efficacy, as in the field of drug safety highlighted by the Comprehensive in Vitro Proarrhythmia Assay initiative, new pillars for research have become crucial: firstly, the integration of in-silico experiments, and secondly the evaluation of fully integrated biological systems, such as human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In this study, we therefore aimed to combine in-vitro experiments and in-silico simulations to evaluate the antiarrhythmic effect of L-type calcium current (ICaL) block in hiPSC-CMs. For this, hiPSC-CM preparations were cultured and an equivalent virtual tissue was modeled. Re-entry patterns of electrical activation were induced and several biomarkers were obtained before and after ICaL block. The virtual hiPSC-CM simulations were also reproduced using a tissue composed of adult ventricular cardiomyocytes (hAdultV-CMs). The analysis of phases, currents and safety factor for propagation showed an increased size of the re-entry core when ICaL was blocked as a result of depressed cellular excitability. The bigger wavefront curvature yielded reductions of 12.2%, 6.9%, and 4.2% in the frequency of the re-entry for hiPSC-CM cultures, virtual hiPSC-CM, and hAdultV-CM tissues, respectively. Furthermore, ICaL block led to a 47.8% shortening of the vulnerable window for re-entry in the virtual hiPSC-CM tissue and to re-entry vanishment in hAdultV-CM tissue. The consistent behavior between in-vitro and in-silico hiPSC-CMs and between in-silico hiPSC-CMs and hAdultV-CMs evidences that virtual hiPSC-CM tissues are suitable for assessing cardiac efficacy, as done in the present study through the analysis of ICaL block.

Proposal for computer-aided diagnosis based on ultrasound images of the kidney: is it possible to compare shades of gray among such images?

ObjectiveTo compare ultrasound images of the kidney obtained, randomly or in a controlled manner (standardizing the physical aspects of the ultrasound system), by various professionals and with different devices.Materials and MethodsWe evaluated a total of 919 images of kidneys, obtained by five professionals using two types of ultrasound systems, in 24 patients. The images were categorized into four types, by how they were acquired and processed. We compared the gray-scale median and different gray-scale ranges representative of virtual histological tissues.ResultsThere were statistically significant differences among the five professionals, regardless of the type of ultrasound system employed, in terms of the gray-scale medians for the images obtained (p < 2.2e-16). Analyzing the four categories of images-a totally random image (without any standardization); a standardized image (with fixed values for gain, time gain control, and dynamic range); a normalized version of the random image; and a normalized version of the standardized image-we determined that the random image, even after normalization, differed quite significantly among the professionals (p = 0.006098). The analysis of the normalized version of the standardized image did not differ significantly among the professionals (p = 0.7319).ConclusionOur findings indicate that a gray-scale analysis of ultrasound images of the kidney performs better when the image acquisition process is standardized and the images undergo a process of normalization.

Populations of in silico myocytes and tissues reveal synergy of multiatrial-predominant K+ -current block in atrial fibrillation.

Pharmacotherapy of atrial fibrillation (AF), the most common cardiac arrhythmia, remains unsatisfactory due to low efficacy and safety concerns. New therapeutic strategies target atrial-predominant ion-channels and involve multichannel block (poly)therapy. As AF is characterized by rapid and irregular atrial activations, compounds displaying potent antiarrhythmic effects at fast and minimal effects at slow rates are desirable. We present a novel systems pharmacology framework to quantitatively evaluate synergistic anti-AF effects of combined block of multiple atrial-predominant K+ currents (ultra-rapid delayed rectifier K+ current, IKur , small conductance Ca2+ -activated K+ current, IKCa , K2P 3.1 2-pore-domain K+ current, IK2P ) in AF. We constructed experimentally calibrated populations of virtual atrial myocyte models in normal sinus rhythm and AF-remodelled conditions using two distinct, well-established atrial models. Sensitivity analyses on our atrial populations was used to investigate the rate dependence of action potential duration (APD) changes due to blocking IKur , IK2P or IKCa and interactions caused by blocking of these currents in modulating APD. Block was simulated in both single myocytes and one-dimensional tissue strands to confirm insights from the sensitivity analyses and examine anti-arrhythmic effects of multi-atrial-predominant K+ current block in single cells and coupled tissue. In both virtual atrial myocytes and tissues, multiple atrial-predominant K+ -current block promoted favourable positive rate-dependent APD prolongation and displayed positive rate-dependent synergy, that is, increasing synergistic antiarrhythmic effects at fast pacing versus slow rates. Simultaneous block of multiple atrial-predominant K+ currents may be a valuable antiarrhythmic pharmacotherapeutic strategy for AF.

A High-Fidelity Hybrid Virtual Reality Simulator of Aneurysm Clipping Repair With Brain Sylvian Fissure Exploration for Vascular Neurosurgery Training.

Microsurgery clipping is one of the most challenging surgical interventions in neurosurgery. The opportunities to train residents are scarce, but the need for accumulating practice is mandatory. New simulating tools are needed for skill learning. The design, implementation, and assessment of a new hybrid aneurysm clipping simulator are presented. It consists of an ergonomic workstation with a patient head mannequin and a physics-based virtual reality simulation with bimanual haptic feedback. The simulator recreates scenarios of microsurgery from the patient fixation and the exploration of the brain lobes through Sylvian fissure and vascular structures to the aneurysm clipping. Skill metrics were introduced, including monitoring of gestures movements, exerted forces, tissue displacements, and precision in clipping. Two experimental conditions were tested: (1) simple clipping without brain tissue exploration and (2) clipping the aneurysm with brain Sylvian fissure exploration. Differences in the bimanual gestures were observed between both conditions. The quantitative measurements of tissue displacement of the brain lobes exhibited more tissue retrieval for the surgical gestures of neurosurgeons. Appraisal with questionnaires showed positive scores by neurosurgeons in all items evaluating the usability and realism of the simulator. The simulator was well accepted and feasible for training purposes. The analysis of the interactions with virtual tissues offers information to establish differential and common patterns between tested groups and thus useful metrics for skill evaluation of practitioners. Future work can lead to other tasks during the intervention and the inclusion of more clinical cases.

A Review of Cell-Based Computational Modeling in Cancer Biology.

Cancer biology involves complex, dynamic interactions between cancer cells and their tissue microenvironments. Single-cell effects are critical drivers of clinical progression. Chemical and mechanical communication between tumor and stromal cells can co-opt normal physiologic processes to promote growth and invasion. Cancer cell heterogeneity increases cancer’s ability to test strategies to adapt to microenvironmental stresses. Hypoxia and treatment can select for cancer stem cells and drive invasion and resistance. Cell-based computational models (also known as discrete models, agent-based models, or individual-based models) simulate individual cells as they interact in virtual tissues, which allows us to explore how single-cell behaviors lead to the dynamics we observe and work to control in cancer systems. In this review, we introduce the broad range of techniques available for cell-based computational modeling. The approaches can range from highly detailed models of just a few cells and their morphologies to millions of simpler cells in three-dimensional tissues. Modeling individual cells allows us to directly translate biologic observations into simulation rules. In many cases, individual cell agents include molecular-scale models. Most models also simulate the transport of oxygen, drugs, and growth factors, which allow us to link cancer development to microenvironmental conditions. We illustrate these methods with examples drawn from cancer hypoxia, angiogenesis, invasion, stem cells, and immunosurveillance. An ecosystem of interoperable cell-based simulation tools is emerging at a time when cloud computing resources make software easier to access and supercomputing resources make large-scale simulation studies possible. As the field develops, we anticipate that high-throughput simulation studies will allow us to rapidly explore the space of biologic possibilities, prescreen new therapeutic strategies, and even re-engineer tumor and stromal cells to bring cancer systems under control.

Regulation of plant cell wall stiffness by mechanical stress: a mesoscale physical model.

A crucial question in developmental biology is how cell growth is coordinated in living tissue to generate complex and reproducible shapes. We address this issue here in plants, where stiff extracellular walls prevent cell migration and morphogenesis mostly results from growth driven by turgor pressure. How cells grow in response to pressure partly depends on the mechanical properties of their walls, which are generally heterogeneous, anisotropic and dynamic. The active control of these properties is therefore a cornerstone of plant morphogenesis. Here, we focus on wall stiffness, which is under the control of both molecular and mechanical signaling. Indeed, in plant tissues, the balance between turgor and cell wall elasticity generates a tissue-wide stress field. Within cells, mechano-sensitive structures, such as cortical microtubules, adapt their behavior accordingly and locally influence cell wall remodeling dynamics. To fully apprehend the properties of this feedback loop, modeling approaches are indispensable. To that end, several modeling tools in the form of virtual tissues have been developed. However, these models often relate mechanical stress and cell wall stiffness in relatively abstract manners, where the molecular specificities of the various actors are not fully captured. In this paper, we propose to refine this approach by including parsimonious biochemical and biomechanical properties of the main molecular actors involved. Through a coarse-grained approach and through finite element simulations, we study the role of stress-sensing microtubules on organ-scale mechanics.

Measuring the sensitivity of total knee replacement kinematics and laxity to soft tissue imbalances

Ligament balancing during total knee replacement (TKR) is receiving increased attention due to its influence on resulting joint kinematics and laxity. We employed a novel in vitro technique to measure the kinematics and laxity of TKR implants during gait, and measured how these characteristics are influenced by implant shape and soft tissue balancing, simulated using virtual ligaments. Compared with virtual ligaments that were equally balanced in flexion and extension, the largest changes in stance-phase tibiofemoral AP and IE kinematics occurred when the virtual ligaments were simulated to be tighter in extension (tibia offset 1.0 ± 0.1 mm posterior and 3.6 ± 0.1° externally rotated). Virtual ligaments which were tight in flexion caused the largest swing-phase changes in AP kinematics (tibia offset 2.3 ± 0.2 mm), whereas ligaments which were tight in extension caused the largest swing-phase changes in IE kinematics (4.2 ± 0.1° externally rotated). When AP and IE loads were superimposed upon normal gait loads, incremental changes in AP and IE kinematics occurred (similar to laxity testing); and these incremental changes were smallest for joints with virtual ligaments that were tight in extension (in both the stance and swing phases). Two different implant designs (symmetric versus medially congruent) exhibited different kinematics and sensitivities to superimposed loads, but demonstrated similar responses to changes in ligament balancing. Our results demonstrate the potential for pre-clinical testing of implants using joint motion simulators with virtual soft tissues to better understand how ligament balancing affects implant motion.

Real-time cutting simulation in virtual reality systems based on the measurement of porcine organs

A virtual soft tissues cutting model consistent with the organ specificity of real soft tissues was established in this paper, which was applied to the virtual operation training system. A measurement platform of soft tissue organ was designed and built, and the stress–strain and stress–relaxation data of pig liver and kidney were experimentally measured. Then, using the viscoelasticity mathematical formula, an improved virtual cutting model of the meshless classified balls-filling was constructed through VC++ and OpenGL. The cutting performance of the virtual soft tissues was further increased by leveraging the improved cutting classification algorithm. Finally, the extrusion and cutting simulation was enabled through the force feedback device, and the accuracy and effectiveness of this cutting model were validated by a comparative study of the virtual soft tissues cutting model and the stress–strain and stress–relaxation data of pig liver and kidney.

Virtual Reality simulator for dental anesthesia training in the inferior alveolar nerve block.

Objectives This study shows the development and validation of a dental anesthesia-training simulator, specifically for the inferior alveolar nerve block (IANB). The system developed provides the tactile sensation of inserting a real needle in a human patient, using Virtual Reality (VR) techniques and a haptic device that can provide a perceived force feedback in the needle insertion task during the anesthesia procedure.Material and Methods To simulate a realistic anesthesia procedure, a Carpule syringe was coupled to a haptic device. The Volere method was used to elicit requirements from users in the Dentistry area; Repeated Measures Two-Way ANOVA (Analysis of Variance), Tukey post-hoc test and averages for the results’ analysis. A questionnaire-based subjective evaluation method was applied to collect information about the simulator, and 26 people participated in the experiments (12 beginners, 12 at intermediate level, and 2 experts). The questionnaire included profile, preferences (number of viewpoints, texture of the objects, and haptic device handler), as well as visual (appearance, scale, and position of objects) and haptic aspects (motion space, tactile sensation, and motion reproduction).Results The visual aspect was considered appropriate and the haptic feedback must be improved, which the users can do by calibrating the virtual tissues’ resistance. The evaluation of visual aspects was influenced by the participants’ experience, according to ANOVA test (F=15.6, p=0.0002, with p<0.01). The user preferences were the simulator with two viewpoints, objects with texture based on images and the device with a syringe coupled to it.Conclusion The simulation was considered thoroughly satisfactory for the anesthesia training, considering the needle insertion task, which includes the correct insertion point and depth, as well as the perception of tissues resistances during the insertion.

A passivity criterion for real-time haptic simulation of viscoelastic soft tissues

Passivity analysis provides a convenient measure to assess the stability of haptic systems interacting with virtual environments. Passivity analysis of haptic sampled-data systems coupled with virtual environments requires knowledge of parameters of the employed environment model. Kelvin–Voigt models have been popularly used to describe viscoelastic behavior of soft tissues being simulated in a virtual environment. This paper employs a standard linear solid model that has been recently shown to be better suited to represent the behavior of the actual soft tissues, and provides passivity analysis of the haptic systems interacting with virtual viscoelastic soft tissues based on the standard linear solid model. The analysis results in a new criterion for design and control of passive haptic interfaces. The effect of the employed discretization method on passivity is also discussed. Experimental results show that the new passivity criterion is less conservative. This criterion increases the domain of soft-tissue environments that can be interacted with passively by the haptic interface.

Measuring tactile cues at the fingerpad for object compliances harder and softer than the skin.

Distinguishing an object's compliance, into percepts of "softness" and "hardness," is crucial to our ability to grasp and manipulate it. Biomechanical cues at the skin's surface such as contact area and force rate have been thought to help encode compliance. However, no one has directly measured contact area with compliant materials, and few studies have considered compliances softer than the fingerpad. Herein, we developed a novel method to precisely measure the area in contact between compliant stimuli and the fingerpad, at given levels of force and displacement. To determine the method's robustness, we conducted psychophysical and biomechanical experiments with human subjects. The results indicate that cues including contact area at stimulus peak force of 3 Newtons, force rate over stimulus movement and at peak force, displacement and/or time to reach peak force may help in discriminating compliances while the directional spread of contact area is less important. Between softer and harder compliances, some cues were slightly more evident, though not yet definitively. Based upon the method's utility, the next step is to conduct broader experiments to distill the mixture of cues that encode compliance. The importance of such work lies in building haptic displays, for example, to render virtual tissues.

Virtual microstructural leaf tissue generation based on cell growth modeling

A cell growth algorithm for virtual leaf tissue generation is presented based on the biomechanics of plant cells in tissues. The algorithm can account for typical differences in epidermal layers, palisade mesophyll layer and spongy mesophyll layer which have characteristic differences in the shape of cells, arrangement of cells and void fractions present in each layer. The cell is considered as a closed thin walled structure, maintained in tension by turgor pressure. The cell walls are modelled as linear elastic elements which obey Hooke's law. A Voronoi tessellation was used to generate the initial topology of the cells in the spongy mesophyll layer. Then two layers of brick structured cells are added to the top of it to represent the palisade mesophyll and upper epidermis and a single layer is added at bottom of the Voronoi tessellation to represent the lower epidermal layer. Intercellular air spaces are generated by separating the Voronoi cells along the edges starting from where three Voronoi cells are in contact (schizogenous origin) and/or by deleting some of the Voronoi cells (lysigenous origin). Cell expansion then results from turgor pressure acting on the yielding cell wall material. To find the sequence of positions of each vertex and thus the shape of the tissue with time, a system of differential equations for the positions and velocities of each vertex is established and solved using the ordinary differential equation solver in MatLab. Statistical comparison of the cellular characteristics with 2D cross-sectional slices of real leaf tissue of tomato is excellent. The virtual tissues can be used to systematically study effects of leaf structure on water and gas exchange.

Two applications of solid phantoms in performance assessment of optical coherence tomography systems

Virtual tissues (phantoms) are widely used for performance evaluation of imaging systems. Specific design of the phantom is necessary for the correct assessment of a system's parameters. In an effort to reduce the amount of time and energy spent making application-oriented phantoms, we describe procedures to make epoxy-resin solid phantoms based on Mie scattering theory, with two different scatterers: polystyrene and gold microspheres. The phantoms are specifically designed to be used in two applications: (a)the gold microspheres solid phantoms are used to estimate the point-spread function (PSF) of an optical coherence tomography (OCT) system, and (b)the polystyrene solid phantom are used to evaluate the performance of an OCT-images optical properties extraction (OPE) algorithm. Phantoms with differing combination of materials have been tested to achieve the most suitable combination for producing an accurate PSF for application (a) and a valid evaluation/parameter optimization of the algorithm in application (b). An en face time-domain dynamic focus OCT is used for imaging.