The iris plays an important role in certain types of glaucoma, including primary angle-closure glaucoma and pigmentary glaucoma. Iris mechanics are also important in influencing trabecular meshwork deformation in response to intraocular pressure changes in some animal species. Although mice are widely used to study ocular disease, including glaucoma, the in vivo biomechanical properties of the murine iris are unknown. Thus, the primary objective of this study was to estimate murine iris biomechanical stiffness. We used optical coherence tomography (OCT) images of the anterior segment of living mice (n = 13, age = 7.3 ± 3.2 [mean ± SD] months) at sequentially increasing IOP levels, observing IOP-dependent iris deformations. We then used an inverse finite element model to predict iris deformations under the same conditions, estimating iris stiffness by maximizing agreement between OCT data and numerical simulations. Our results show an in vivo murine iris stiffness of 96.1 ± 54.7 kPa (mean ± SD), which did not correlate with age but was dependent on gender. Our results further showed strong evidence of reverse pupillary block, with mean posterior chamber pressure remaining at approximately 12 mmHg even as anterior chamber pressure was set to much higher levels. Our approach to monitoring iris stiffness in vivo is applicable to study potential changes of iris stiffness in various pathophysiological conditions and thus has significant potential for clinical care of ocular disease involving iris biomechanics.
Assessment and prediction of vulnerable plaque progression and rupture risk are of utmost importance for diagnosis, management and treatment of cardiovascular diseases and possible prevention of acute cardiovascular events such as heart attack and stroke. However, accurate assessment of plaque vulnerability assessment and prediction of its future changes require accurate plaque cap thickness, tissue component and structure quantifications and mechanical stress/strain calculations. Multi-modality intravascular ultrasound (IVUS), optical coherence tomography (OCT) and angiography image data with follow-up were acquired from ten patients to obtain accurate and reliable plaque morphology for model construction. Three-dimensional thin-slice finite element models were constructed for 228 matched IVUS + OCT slices to obtain plaque stress/strain data for analysis. Quantitative plaque cap thickness and stress/strain indices were introduced as substitute quantitative plaque vulnerability indices (PVIs) and a machine learning method (random forest) was employed to predict PVI changes with actual patient IVUS + OCT follow-up data as the gold standard. Our prediction results showed that optimal prediction accuracies for changes in cap-PVI (C-PVI), mean cap stress PVI (meanS-PVI) and mean cap strain PVI (meanSn-PVI) were 90.3% (AUC = 0.877), 85.6% (AUC = 0.867) and 83.3% (AUC = 0.809), respectively. The improvements in prediction accuracy by the best combination predictor over the best single predictor were 6.6% for C-PVI, 10.0% for mean S-PVI and 8.0% for mean Sn-PVI. Our results demonstrated the potential using multi-modality IVUS + OCT image to accurately and efficiently predict plaque cap thickness and stress/strain index changes. Combining mechanical and morphological predictors may lead to better prediction accuracies.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Recent evidence suggests that grammatical aspect can bias how individuals perceive criminal intentionality during discourse comprehension. Given that criminal intentionality is a common criterion for legal definitions (e.g., first-degree murder), the present study explored whether grammatical aspect may also impact legal judgments. In a series of four experiments participants were provided with a legal definition and a description of a crime in which the grammatical aspect of provocation and murder events were manipulated. Participants were asked to make a decision (first- vs. second-degree murder) and then indicate factors that impacted their decision. Findings suggest that legal judgments can be affected by grammatical aspect but the most robust effects were limited to temporal dynamics (i.e., imperfective aspect results in more murder actions than perfective aspect), which may in turn influence other representational systems (i.e., number of murder actions positively predicts perceived intentionality). In addition, findings demonstrate that the influence of grammatical aspect on situation model construction and evaluation is dependent upon the larger linguistic and semantic context. Together, the results suggest grammatical aspect has indirect influences on legal judgments to the extent that variability in aspect changes the features of the situation model that align with criteria for making legal judgments.
BACKGROUND: The structure of trauma memories impacts mental health, but questions remain about how structure changes with time and may shape coping with trauma. This study considered the structure of trauma narratives collected during an emergency department (ED) visit and at one-year follow-up. We addressed change in narrative structure over time, the extent structure predicted twelve-month psychological symptoms, and possible mechanisms in coping responses. METHODS: Sixty-eight community adults (age range 18-67; 41% women) recruited from a trauma center ED provided narratives of the traumatic event that brought them to the ED. Participants provided multiple follow-up reports on psychological symptoms and coping strategies, and another narrative of the traumatic event at twelve months. RESULTS: Narrative structure improved over time. Baseline narrative structure was negatively associated with twelve-month depressive and posttraumatic symptoms. Two measures of trauma narrative structure-interpretive elaboration and coherence-predicted change in coping strategies. Interpretive elaboration (rich details of the subjective experience) promoted early gains in endorsed engagement and later declines in endorsed disengagement. Coherence (the overall thematic structure of the narrative) buffered participant endorsement of disengagement at earlier follow-ups. Engagement was tied with fewer reported symptoms, whereas disengagement was associated with higher reported symptoms. Coping served as a mediator between baseline narrative structure and later mental health. LIMITATIONS: The study sample was relatively small and depended on self-reports for symptoms. CONCLUSIONS: Findings suggest there is meaningful variability in trauma memory structure, and early recollections of traumatic experiences may improve targeting of individuals in need of active interventions.
Introduction: Coronary stenosis due to atherosclerosis restricts blood flow. Stenosis progression would lead to increased clinical risk such as heart attack. Although many risk factors were found to contribute to atherosclerosis progression, factors associated with fatigue is underemphasized. Our goal is to investigate the relationship between fatigue and stenosis progression based on in vivo intravascular ultrasound (IVUS) images and finite element models.
Methods: Baseline and follow-up in vivo IVUS and angiography data were acquired from seven patients using Institutional Review Board approved protocols with informed consent obtained. Three hundred and five paired slices at baseline and follow-up were matched and used for plaque modeling and analysis. IVUS-based thin-slice models were constructed to obtain the coronary biomechanics and stress/strain amplitudes (stress/strain variations in one cardiac cycle) were used as the measurement of fatigue. The change of lumen area (DLA) from baseline to follow-up were calculated to measure stenosis progression. Nineteen morphological and biomechanical factors were extracted from 305 slices at baseline. Correlation analyses of these factors with DLA were performed. Random forest (RF) method was used to fit morphological and biomechanical factors at baseline to predict stenosis progression during follow-up.
Results: Significant correlations were found between stenosis progression and maximum stress amplitude, average stress amplitude and average strain amplitude (p < 0.05). After factors selection implemented by random forest (RF) method, eight morphological and biomechanical factors were selected for classification prediction of stenosis progression. Using eight factors including fatigue, the overall classification accuracy, sensitivity and specificity of stenosis progression prediction with RF method were 83.61%, 86.25% and 80.69%, respectively.
Glaucoma is the leading cause of irreversible blindness worldwide, and women represent roughly 60% of the affected population. Early menopause and estrogen signaling defects are risk factors for glaucoma. Recently, we found that surgical menopause exacerbated visual dysfunction in an ocular hypertension model of glaucoma. Here, we investigated if surgical menopause exacerbated visual dysfunction in a model of direct retinal ganglion cell (RGC) damage via optic nerve crush (ONC). Female Long Evans rats (n = 12) underwent ovariectomy (OVX) to induce surgical menopause or Sham surgery. Eight weeks post-surgery, baseline visual function was assessed via optomotor response. Afterwards, rats underwent monocular ONC. Visual function was assessed at 4, 8, and 12 weeks post-ONC. At 12 weeks, retinal function via electroretinography and retinal nerve fiber layer (RNFL) thickness via optical coherence tomography were measured. Visual acuity was reduced after ONC (p < 0.001), with surgical menopausal animals having 31.7% lower visual acuity than Sham animals at 12 weeks (p = 0.01). RNFL thinning (p < 0.0001) and decreased RGC function (p = 0.0016) occurred at 12 weeks in ONC groups. Surgical menopause worsens visual acuity after direct RGC damage using an ONC model. This demonstrates that surgical menopause plays a role in visual function after injury.
Accurate plaque cap thickness quantification and cap stress/strain calculations are of fundamental importance for vulnerable plaque research. To overcome uncertainties due to intravascular ultrasound (IVUS) resolution limitation, IVUS and optical coherence tomography (OCT) coronary plaque image data were combined together to obtain accurate and reliable cap thickness data, stress/strain calculations, and reliable plaque progression predictions. IVUS, OCT, and angiography baseline and follow-up data were collected from nine patients (mean age: 69; m: 5) at Cardiovascular Research Foundation with informed consent obtained. IVUS and OCT slices were coregistered and merged to form IVUS + OCT (IO) slices. A total of 114 matched slices (IVUS and OCT, baseline and follow-up) were obtained, and 3D thin-layer models were constructed to obtain stress and strain values. A generalized linear mixed model (GLMM) and least squares support vector machine (LSSVM) method were used to predict cap thickness change using nine morphological and mechanical risk factors. Prediction accuracies by all combinations (511) of those predictors with both IVUS and IO data were compared to identify optimal predictor(s) with their best accuracies. For the nine patients, the average of minimum cap thickness from IVUS was 0.17 mm, which was 26.08% lower than that from IO data (average = 0.23 mm). Patient variations of the individual errors ranged from ‒58.11 to 20.37%. For maximum cap stress between IO and IVUS, patient variations of the individual errors ranged from ‒30.40 to 46.17%. Patient variations of the individual errors of maximum cap strain values ranged from ‒19.90 to 17.65%. For the GLMM method, the optimal combination predictor using IO data had AUC (area under the ROC curve) = 0.926 and highest accuracy = 90.8%, vs. AUC = 0.783 and accuracy = 74.6% using IVUS data. For the LSSVM method, the best combination predictor using IO data had AUC = 0.838 and accuracy = 75.7%, vs. AUC = 0.780 and accuracy = 69.6% using IVUS data. This preliminary study demonstrated improved plaque cap progression prediction accuracy using accurate cap thickness data from IO slices and the differences in cap thickness, stress/strain values, and prediction results between IVUS and IO data. Large-scale studies are needed to verify our findings.
In recent years, there has been a growing interest for using mouse models in refractive development and myopia research. The crystalline lens is a critical optical component of the mouse eye that occupies greater than 50% of the ocular space, and significant increases in thickness with age. However, changes in refractive index of the mouse crystalline lens are less known. In this study, we examined the changes in thickness and refractive index of the mouse crystalline lens for two different strains, wild-type (WT) and a nyx mutant (nob) over the course of normal visual development or after form deprivation. Refractive index and lens thickness measurements were made on exvivo lenses using spectral domain optical coherence tomography (SD-OCT). Comparison of refractive index measurements on 5 standard ball lenses using the SD-OCT and their known refractive indices (manufacturer provided) indicated good precision (intra-class correlation coefficient, 0.998 and Bland-Altman coefficient of repeatability, 0.116) of the SD-OCT to calculate mouse lens refractive index exvivo. During normal visual development, lens thickness increased significantly with age for three different cohorts of mice, aged 4 (average thickness from both eyes; WT: 1.78±0.03, nob: 1.79±0.08mm), 10 (WT: 2.02±0.05, nob: 2.01±0.04mm) and 16 weeks (WT: 2.12±0.06, nob: 2.09±0.06mm, p<0.001). Lens thickness was not significantly different between the two strains at any age (p=0.557). For mice with normal vision, refractive index for isolated crystalline lenses in nob mice was significantly greater than WT mice (mean for all ages; WT: 1.42±0.01, nob: 1.44±0.001, p<0.001). After 4 weeks of form deprivation to the right eye using a skull-mounted goggling apparatus, a thinning of the crystalline lens was observed in both right and left eyes of goggled animals compared to their naïve controls (average from both the right and the left eye) for both strains (p=0.052). In form deprived mice, lens refractive index was significantly different between the goggled animals and non-goggled naïve controls in nob mice, but not in WT mice (p=0.009). Both eyes of goggled nob mice had significantly greater lens refractive index (goggled, 1.49±0.01; opposite, 1.47±0.03) compared to their naïve controls (1.45±0.02, p<0.05). The results presented here suggest that there are genetic differences in the crystalline lens refractive index of the mouse eye, and that the lens refractive index in mice significantly increase with form deprivation. Research applications requiring precise optical measurements of the mouse eye should take these lens refractive indices into account when interpreting SD-OCT data.
by
Nan Zhang;
Xian Zhang;
Preston E Girardot;
Micah A Chrenek;
Jana T Sellers;
Ying Li;
Yong-Kyu Kim;
Vivian R Summers;
Salma Ferdous;
Debresha A Shelton;
Jeffrey Boatright;
John Nickerson
Purpose: We aimed to explore differences in the NaIO3-elicited responses of retinal pigment epithelium (RPE) and other retinal cells associated with mouse strains and dosing regimens. Methods: One dose of NaIO3 at 10 or 15 mg/kg was given intravenously to adult male C57BL/6J and 129/SV-E mice. Control animals were injected with PBS. Morphologic and functional changes were characterized by spectral domain optical coherence tomography, electroretinography, histologic, and immunofluorescence techniques. Results: Injection with 10 mg/kg of NaIO3 did not cause consistent RPE or retinal changes in either strain. Administration of 15 mg/kg of NaIO3 initially induced a large transient increase in scotopic electroretinography a-, b-, and c-wave amplitudes within 12 hours of injection, followed by progressive structural and functional degradation at 3 days after injection in C57BL/6J mice and at 1 week after injection in 129/SV-E mice. RPE cell loss occurred in a large posterior-central lesion with a ring-like transition zone of abnormally shaped cells starting 12 hours after NaIO3 treatment. Conclusions: NaIO3 effects depended on the timing, dosage, and mouse strain. The RPE in the periphery was spared from damage compared with the central RPE. The large transient increase in the electroretinography was remarkable. Translational Relevance: This study is a phase T1 translational research study focusing on the development and validation of a mouse model of RPE damage. It provides a detailed foundation for future research, informing choices of mouse strain, dosage, and time points to establish NaIO3-induced RPE damage.
PURPOSE. Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with a thickened choroid at the optic nerve head (ONH). Here, we use computational modeling to better understand how choroidal expansion and choroidal geometry influence tissue deformation within the ONH relative to intraocular pressure (IOP) and intracranial pressure (ICP) effects. METHODS. Using a model of the posterior eye that included the sclera, peripapillary sclera, annular ring, pia mater, dura mater, neural tissues, Bruch’s membrane, choroid, and lamina cribrosa, we examined how varying material properties of ocular tissues influenced ONH deformations under physiological and supra-physiological, or “pathological,” conditions. We considered choroidal expansion (c. 35 μL of expansion), elevated IOP (30 mm Hg), and elevated ICP (20 mm Hg), and calculated peak strains in the ONH relative to a baseline condition representing an individual in the upright position. RESULTS. Supra-physiological choroidal expansion had the largest impact on strains in the prelaminar neural tissue. In addition, compared to a tapered choroid, a “blunt” choroid insertion at the ONH resulted in higher strains. Elevated IOP and ICP caused the highest strains within the lamina cribrosa and retrolaminar neural tissue, respectively. CONCLUSIONS. Acute choroidal expansion caused large deformations of the ONH and these deformations were impacted by choroid geometry. These results are consistent with the concept that compartment syndrome due to the choroid geometry and/or expansion at the ONH contributes to NAION. Prolonged deformations due to supra-physiological loading may induce a mechanobiological response or ischemia, highlighting the potential impact of choroidal expansion on biomechanical strains in the ONH.