Method for the biomechanical analysis of aqueous veins and perilimbal sclera by three-dimensional photoacoustic imaging and strain field calculation.
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ABSTRACT:
SUBMITTER: Ni L
PROVIDER: S-EPMC8585983 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The collagen fiber architecture of the peripapillary sclera (PPS), which surrounds the scleral canal, is a critical factor in determining the mechanical response of the optic nerve head (ONH) to variations in intraocular pressure (IOP). Experimental and clinical evidence point to IOP-induced deformations within the scleral canal as important contributing factors of glaucomatous neural tissue damage and consequent vision loss. Hence, it is imperative to understand PPS architecture and biomechanics. Current consensus is that the fibers of the PPS form a closed ring around the canal to support the delicate neural tissues within. We propose an alternative fiber architecture for the PPS, in which the scleral canal is supported primarily by long-running fibers oriented tangentially to the canal. We present evidence that this tangential model is consistent with histological observations in multiple species, and with quantitative measurements of fiber orientation obtained from small angle light scattering and wide-angle X-ray scattering. Using finite element models, we investigated the biomechanical implications of a tangential fiber PPS architecture. We found that the tangential arrangement of fibers afforded better mechanical support to the tissues within the scleral canal as compared to a simple circumferential ring of fibers or a combination of fibers oriented radially and circumferentially. We also found that subtle variations from a tangential orientation could reproduce clinically observed ONH behavior which has yet to be explained using current theories of PPS architecture and simulation, namely, the contraction of the scleral canal under elevated IOP.Statement of significanceIt is hypothesized that vision loss in glaucoma is due to excessive mechanical deformation within the neural tissue inside the scleral canal. This study proposes a new model for how the collagen of the peripapillary sclera surrounding the canal is organized to support the delicate neural tissue inside. Previous low-resolution studies of the peripapillary sclera suggested that the collagen fibers are arranged in a ring around the canal. Instead, we provide microscopic evidence suggesting that the canal is also supported by long-running interwoven fibers oriented tangentially to the canal. We demonstrate that this arrangement has multiple biomechanical advantages over a circular collagen arrangement and can explain previously unexplained experimental findings including contraction of the scleral canal under elevated intraocular pressure.
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Project description:By providing complementary functional information, photoacoustic (PA) breast imaging based on the handheld ultrasound (US) probe has demonstrated promising potential for breast cancer diagnosis. However, the quantitative PA imaging primarily relies on the knowledge of the optical fluence distribution in the three-dimensional (3D) heterogeneous breast tissue. Previous studies based on the handheld system generally provided two-dimensional (2D) B-scan results, which contains limited anatomical information of the tissue and the lesion. This study proposed a method to perform 3D modeling of the photon transportation for dual-modality PA/US system based on the local 3D breast anatomical information by scanning US probe. Then the calculated optical fluence distribution can be used for PA imaging. Our phantom and clinical pilot study results demonstrated that this method has potential to improve the accuracy of the quantitative PA breast imaging, and it can also be used in other clinical implementations.
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Project description:PurposeThis study tested the hypothesis that intraocular pressure (IOP) elevations, induced by controlled increase of intraocular volume, are correlated with the biomechanical responses of the posterior sclera.MethodsPorcine globes were tested within 48 hours postmortem. The first group of globes (n = 11) was infused with 15 ?L of phosphate-buffered saline at three different rates to investigate rate-dependent IOP elevations. The second group (n = 16) was first infused at the fast rate and then underwent inflation tests to investigate the relationship between IOP elevations (?IOP) and scleral strains. The strains in the superotemporal region of the posterior sclera were measured by ultrasound speckle tracking. Linear regression was used to examine the association between ?IOP due to micro-volumetric infusion and the scleral strains at a specific inflation pressure.ResultsThe average ?IOP was 14.9 ± 4.3 mm Hg for the infusion of 15 ?L in 1 second. The ?IOP was greater for the faster infusion rates but highly correlated across different rates (P < 0.001). A significant negative association was found between the ?IOP and the tangential strains in both the circumferential (R(2) = 0.54, P = 0.003) and meridian (R(2) = 0.53, P = 0.002) directions in the posterior sclera.ConclusionsThis study showed a substantial increase in IOP, with a large intersubject variance during micro-volumetric change. A stiffer response of the sclera was associated with larger IOP spikes, providing experimental evidence linking corneoscleral biomechanics to IOP fluctuation. In vivo measurement of corneoscleral biomechanics may help better predict the dynamic profile of IOP.
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Project description:In glaucoma, lowered intraocular pressure (IOP) confers neuroprotection. Elevated IOP characterizes glaucoma and arises from impaired aqueous humor (AH) outflow. Increased resistance in the trabecular meshwork (TM), a filter-like structure essential to regulate AH outflow, may result in the impaired outflow. Flow through the 360° circumference of TM structures may be non-uniform, divided into high and low flow regions, termed as segmental. After flowing through the TM, AH enters Schlemm's canal (SC), which expresses both blood and lymphatic markers; AH then passes into collector channel entrances (CCE) along the SC external well. From the CCE, AH enters a deep scleral plexus (DSP) of vessels that typically run parallel to SC. From the DSP, intrascleral collector vessels run radially to the scleral surface to connect with AH containing vessels called aqueous veins to discharge AH to blood-containing episcleral veins. However, the molecular mechanisms that maintain homeostatic properties of endothelial cells along the pathways are not well understood. How these molecular events change during aging and in glaucoma pathology remain unresolved. In this review, we propose mechanistic possibilities to explain the continuum of AH outflow control, which originates at the TM and extends through collector channels to the episcleral veins.
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Project description:Clinical 2D photoacoustic (PA) imaging can be easily implemented in a traditional ultrasound (US) system. However, 3D PA imaging is still preferable because 2D B-mode PA/US imaging suffers from low reproducibility and high-operator dependency. Here, we demonstrate a compact clinical handheld 3D PA/US scanner using an 1D linear array US transducer combined with a mechanical scanning stage working via a Scotch yoke mechanism. The entire scanner measures just 100 × 80 × 100 mm3 and weighs only 950 g, so it can easily be operated by hand. Blood vessels and hemoglobin oxygen saturation images of different parts of the human body (e.g., neck, wrist, thigh, and instep) have been successfully acquired. The system can potentially be used for clinical applications in fields such as oncology, dermatology, nephrology, and internal medicine.
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Project description:We developed JVirGel, a collection of tools for the simulation and analysis of proteomics data. The software creates and visualizes virtual two-dimensional (2D) protein gels based on the migration behaviour of proteins in dependence of their theoretical molecular weights in combination with their calculated isoelectric points. The utilization of all proteins of an organism of interest deduced from genes of the corresponding genome project in combination with the elimination of obvious membrane proteins permits the creation of an optimized calculated proteome map. The electrophoretic separation behaviour of single proteins is accessible interactively in a Java(TM) applet (small application in a web browser) by selecting a pI/MW range and an electrophoretic timescale of interest. The calculated pattern of protein spots helps to identify unknown proteins and to localize known proteins during experimental proteomics approaches. Differences between the experimentally observed and the calculated migration behaviour of certain proteins provide first indications for potential protein modification events. When possible, the protein spots are directly linked via a mouse click to the public databases SWISS-PROT and PRODORIC. Additionally, we provide tools for the serial calculation and visualization of specific protein properties like pH dependent charge curves and hydrophobicity profiles. These values are helpful for the rational establishment of protein purification procedures. The proteomics tools are available on the World Wide Web at http://prodoric.tu-bs.de/proteomics.php.
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Project description:BackgroundThe inflation of falsely rejected hypotheses associated with multiple hypothesis testing is seen as a threat to the knowledge base in the scientific literature. One of the most recently developed statistical constructs to deal with this problem is the false discovery rate (FDR), which aims to control the proportion of the falsely rejected null hypotheses among those that are rejected. FDR has been applied to a variety of problems, especially for the analysis of 3-D brain images in the field of Neuroimaging, where the predominant form of statistical inference involves the more conventional control of false positives, through Gaussian random field theory (RFT). In this study we considered FDR and RFT as alternative methods for handling multiple testing in the analysis of 1-D continuum data. The field of biomechanics has recently adopted RFT, but to our knowledge FDR has not previously been used to analyze 1-D biomechanical data, nor has there been a consideration of how FDR vs. RFT can affect biomechanical interpretations.MethodsWe reanalyzed a variety of publicly available experimental datasets to understand the characteristics which contribute to the convergence and divergence of RFT and FDR results. We also ran a variety of numerical simulations involving smooth, random Gaussian 1-D data, with and without true signal, to provide complementary explanations for the experimental results.ResultsOur results suggest that RFT and FDR thresholds (the critical test statistic value used to judge statistical significance) were qualitatively identical for many experimental datasets, but were highly dissimilar for others, involving non-trivial changes in data interpretation. Simulation results clarified that RFT and FDR thresholds converge as the true signal weakens and diverge when the signal is broad in terms of the proportion of the continuum size it occupies. Results also showed that, while sample size affected the relation between RFT and FDR results for small sample sizes (<15), this relation was stable for larger sample sizes, wherein only the nature of the true signal was important.DiscussionRFT and FDR thresholds are both computationally efficient because both are parametric, but only FDR has the ability to adapt to the signal features of particular datasets, wherein the threshold lowers with signal strength for a gain in sensitivity. Additional advantages and limitations of these two techniques as discussed further. This article is accompanied by freely available software for implementing FDR analyses involving 1-D data and scripts to replicate our results.
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Project description:We report photoacoustic and ultrasonic endoscopic images of two intact rabbit esophagi. To investigate the esophageal lumen structure and microvasculature, we performed in vivo and ex vivo imaging studies using a 3.8-mm diameter photoacoustic endoscope and correlated the images with histology. Several interesting anatomic structures were newly found in both the in vivo and ex vivo images, which demonstrates the potential clinical utility of this endoscopic imaging modality. In the ex vivo imaging experiment, we acquired high-resolution motion-artifact-free three-dimensional photoacoustic images of the vasculatures distributed in the walls of the esophagi and extending to the neighboring mediastinal regions. Blood vessels with apparent diameters as small as 190 ?m were resolved. Moreover, by taking advantage of the dual-mode high-resolution photoacoustic and ultrasound endoscopy, we could better identify and characterize the anatomic structures of the esophageal lumen, such as the mucosal and submucosal layers in the esophageal wall, and an esophageal branch of the thoracic aorta. In this paper, we present the first photoacoustic images showing the vasculature of a vertebrate esophagus and discuss the potential clinical applications and future development of photoacoustic endoscopy.
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Project description:Although strongly correlated with elevated intraocular pressure, primary open-angle glaucoma (POAG) occurs in normotensive eyes. Mechanical properties of the sclera around the optic nerve head (ONH) may play a role in this disparity. The purpose of this study is to present an automated inverse mechanics based approach to determine the distribution of heterogeneous mechanical properties of the human sclera as derived from its surface deformations arising from pressure inflation experiments. The scleral shell of a 78 year old European Descent male donor eye was utilized to demonstrate the method; the sclera was coated with a speckle pattern on the outer surface and was subjected to inflation pressures of 5, 15, 30, and 45 mmHg. The speckle pattern was imaged at each pressure, and a displacement field was calculated for each pressure step using a previously described sequential digital image correlation (S-DIC) technique. The fiber splay and fiber orientation of the sclera collagen were determined experimentally, and the thickness across the scleral globe was determined using micro CT images. The displacement field from the inflation test was used to calculate the strain and also used as an input for inverse mechanics to determine the heterogeneity of material properties. The scleral geometry was divided into subdomains using the first principal strain. The Holzapfel anisotropic material parameters of matrix and fiber stiffness were estimated within each individual subdomain using an inverse mechanics approach by minimizing the sum of the square of the residuals between the computational and experimental displacement fields. The mean and maximum error in displacement across all subdomains were 8.9 ± 3.0 ?m and 13.2 ?m, respectively. The full pressure-inflation forward mechanics experiment was done using subdomain-specific mechanical properties on the entire scleral surface. The proposed approach is effective in determining the distribution of heterogeneous mechanical properties of the human sclera in a user-independent manner. Our research group is currently utilizing this approach to better elucidate how scleral stiffness influences those at high risk for POAG.
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Project description:This study aimed to characterize the mechanical responses of the sclera, the white outer coat of the eye, under equal-biaxial loading with unrestricted shear. An ultrasound speckle tracking technique was used to measure tissue deformation through sample thickness, expanding the capabilities of surface strain techniques. Eight porcine scleral samples were tested within 72 h postmortem. High resolution ultrasound scans of scleral cross-sections along the two loading axes were acquired at 25 consecutive biaxial load levels. An additional repeat of the biaxial loading cycle was performed to measure a third normal strain emulating a strain gage rosette for calculating the in-plane shear. The repeatability of the strain measurements during identical biaxial ramps was evaluated. A correlation-based ultrasound speckle tracking algorithm was used to compute the displacement field and determine the distributive strains in the sample cross-sections. A Fung type constitutive model including a shear term was used to determine the material constants of each individual specimen by fitting the model parameters to the experimental stress-strain data. A non-linear stress-strain response was observed in all samples. The meridian direction had significantly larger strains than that of the circumferential direction during equal-biaxial loadings (P's<0.05). The stiffness along the two directions was also significantly different (P=0.02) but highly correlated (R(2)=0.8). These results showed that the mechanical properties of the porcine sclera were nonlinear and anisotropic under biaxial loading. This work has also demonstrated the feasibility of using ultrasound speckle tracking for strain measurements during mechanical testing.
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