Characterizaton of the vessel geometry, flow mechanics and wall shear stress in the great arteries of wildtype prenatal mouse

Introduction: Abnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5). Methods: Ultrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics. Results: In normal mouse fetuses between E14.5-18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus ), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here. Conclusion: Our EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels. © 2014 Yap et al

A survey, review, and future trends of skin lesion segmentation and classification

The Computer-aided Diagnosis or Detection (CAD) approach for skin lesion analysis is an emerging field of research that has the potential to alleviate the burden and cost of skin cancer screening. Researchers have recently indicated increasing interest in developing such CAD systems, with the intention of providing a user-friendly tool to dermatologists to reduce the challenges encountered or associated with manual inspection. This article aims to provide a comprehensive literature survey and review of a total of 594 publications (356 for skin lesion segmentation and 238 for skin lesion classification) published between 2011 and 2022. These articles are analyzed and summarized in a number of different ways to contribute vital information regarding the methods for the development of CAD systems. These ways include: relevant and essential definitions and theories, input data (dataset utilization, preprocessing, augmentations, and fixing imbalance problems), method configuration (techniques, architectures, module frameworks, and losses), training tactics (hyperparameter settings), and evaluation criteria. We intend to investigate a variety of performance-enhancing approaches, including ensemble and post-processing. We also discuss these dimensions to reveal their current trends based on utilization frequencies. In addition, we highlight the primary difficulties associated with evaluating skin lesion segmentation and classification systems using minimal datasets, as well as the potential solutions to these difficulties. Findings, recommendations, and trends are disclosed to inform future research on developing an automated and robust CAD system for skin lesion analysis

Synthesising facial macro-and micro-expressions using reference guided style transfer

Long video datasets of facial macro-and micro-expressions remains in strong demand with the current dominance of data-hungry deep learning methods. There are limited methods of generating long videos which contain micro-expressions. Moreover, there is a lack of performance metrics to quantify the generated data. To address the research gaps, we introduce a new approach to generate synthetic long videos and recommend assessment methods to inspect dataset quality. For synthetic long video generation, we use the state-of-the-art generative adversarial network style transfer method—StarGANv2. Using StarGANv2 pre-trained on the CelebA dataset, we transfer the style of a reference image from SAMM long videos (a facial micro-and macro-expression long video dataset) onto a source image of the FFHQ dataset to generate a synthetic dataset (SAMM-SYNTH). We evaluate SAMM-SYNTH by conducting an analysis based on the facial action units detected by OpenFace. For quantitative measurement, our findings show high correlation on two Action Units (AUs), i.e., AU12 and AU6, of the original and synthetic data with a Pearson’s correlation of 0.74 and 0.72, respectively. This is further supported by evaluation method proposed by OpenFace on those AUs, which also have high scores of 0.85 and 0.59. Additionally, optical flow is used to visually compare the original facial movements and the transferred facial movements. With this article, we publish our dataset to enable future research and to increase the data pool of micro-expressions research, especially in the spotting task

Fluid mechanics of the zebrafish embryonic heart trabeculation

Embryonic heart development is a mechanosensitive process, where specific fluid forces are needed for the correct development, and abnormal mechanical stimuli can lead to malformations. It is thus important to understand the nature of embryonic heart fluid forces. However, the fluid dynamical behaviour close to the embryonic endocardial surface is very sensitive to the geometry and motion dynamics of fine-scale cardiac trabecular surface structures. Here, we conducted image-based computational fluid dynamics (CFD) simulations to quantify the fluid mechanics associated with the zebrafish embryonic heart trabeculae. To capture trabecular geometric and motion details, we used a fish line that expresses fluorescence at the endocardial cell membrane, and high resolution 3D confocal microscopy. Our endocardial wall shear stress (WSS) results were found to exceed those reported in existing literature, which were estimated using myocardial rather than endocardial boundaries. By conducting simulations of single intra-trabecular spaces under varied scenarios, where the translational or deformational motions (caused by contraction) were removed, we found that a squeeze flow effect was responsible for most of the WSS magnitude in the intra-trabecular spaces, rather than the shear interaction with the flow in the main ventricular chamber. We found that trabecular structures were responsible for the high spatial variability of the magnitude and oscillatory nature of WSS, and for reducing the endocardial deformational burden. We further found cells attached to the endocardium within the intra-trabecular spaces, which were likely embryonic hemogenic cells, whose presence increased endocardial WSS. Overall, our results suggested that a complex multi-component consideration of both anatomic features and motion dynamics were needed to quantify the trabeculated embryonic heart fluid mechanics

Myocardial biomechanics and the consequent differentially expressed genes of the left atrial ligation chick embryonic model of hypoplastic left heart syndrome

Left atrial ligation (LAL) of the chick embryonic heart is a model of the hypoplastic left heart syndrome (HLHS) where a purely mechanical intervention without genetic or pharmacological manipulation is employed to initiate cardiac malformation. It is thus a key model for understanding the biomechanical origins of HLHS. However, its myocardial mechanics and subsequent gene expressions are not well-understood. We performed finite element (FE) modeling and single-cell RNA sequencing to address this. 4D high-frequency ultrasound imaging of chick embryonic hearts at HH25 (ED 4.5) were obtained for both LAL and control. Motion tracking was performed to quantify strains. Image-based FE modeling was conducted, using the direction of the smallest strain eigenvector as the orientations of contractions, the Guccione active tension model and a Fung-type transversely isotropic passive stiffness model that was determined via micro-pipette aspiration. Single-cell RNA sequencing of left ventricle (LV) heart tissues was performed for normal and LAL embryos at HH30 (ED 6.5) and differentially expressed genes (DEG) were identified.After LAL, LV thickness increased by 33%, strains in the myofiber direction increased by 42%, while stresses in the myofiber direction decreased by 50%. These were likely related to the reduction in ventricular preload and underloading of the LV due to LAL. RNA-seq data revealed potentially related DEG in myocytes, including mechano-sensing genes (Cadherins, NOTCH1, etc.), myosin contractility genes (MLCK, MLCP, etc.), calcium signaling genes (PI3K, PMCA, etc.), and genes related to fibrosis and fibroelastosis (TGF-β, BMP, etc.). We elucidated the changes to the myocardial biomechanics brought by LAL and the corresponding changes to myocyte gene expressions. These data may be useful in identifying the mechanobiological pathways of HLHS

Cardiac motion estimation from medical images: a regularisation framework applied on pairwise image registration displacement fields

Accurate cardiac motion estimation from medical images such as ultrasound is important for clinical evaluation. We present a novel regularisation layer for cardiac motion estimation that will be applied after image registration and demonstrate its effectiveness. The regularisation utilises a spatio-temporal model of motion, b-splines of Fourier, to fit to displacement fields from pairwise image registration. In the process, it enforces spatial and temporal smoothness and consistency, cyclic nature of cardiac motion, and better adherence to the stroke volume of the heart. Flexibility is further given for inclusion of any set of registration displacement fields. The approach gave high accuracy. When applied to human adult Ultrasound data from a Cardiac Motion Analysis Challenge (CMAC), the proposed method is found to have 10% lower tracking error over CMAC participants. Satisfactory cardiac motion estimation is also demonstrated on other data sets, including human fetal echocardiography, chick embryonic heart ultrasound images, and zebrafish embryonic microscope images, with the average Dice coefficient between estimation motion and manual segmentation at 0.82–0.87. The approach of performing regularisation as an add-on layer after the completion of image registration is thus a viable option for cardiac motion estimation that can still have good accuracy. Since motion estimation algorithms are complex, dividing up regularisation and registration can simplify the process and provide flexibility. Further, owing to a large variety of existing registration algorithms, such an approach that is usable on any algorithm may be useful

Effects of myocardial sheetlet sliding on left ventricular function

Left ventricle myocardium has a complex micro-architecture, which was revealed to consist of myocyte bundles arranged in a series of laminar sheetlets. Recent imaging studies demonstrated that these sheetlets re-orientated and likely slided over each other during the deformations between systole and diastole, and that sheetlet dynamics were altered during cardiomyopathy. However, the biomechanical effect of sheetlet sliding is not well-understood, which is the focus here. We conducted finite element simulations of the left ventricle (LV) coupled with a windkessel lumped parameter model to study sheetlet sliding, based on cardiac MRI of a healthy human subject, and modifications to account for hypertrophic and dilated geometric changes during cardiomyopathy remodeling. We modeled sheetlet sliding as a reduced shear stiffness in the sheet-normal direction and observed that (1) the diastolic sheetlet orientations must depart from alignment with the LV wall plane in order for sheetlet sliding to have an effect on cardiac function, that (2) sheetlet sliding modestly aided cardiac function of the healthy and dilated hearts, in terms of ejection fraction, stroke volume, and systolic pressure generation, but its effects were amplified during hypertrophic cardiomyopathy and diminished during dilated cardiomyopathy due to both sheetlet angle configuration and geometry, and that (3) where sheetlet sliding aided cardiac function, it increased tissue stresses, particularly in the myofibre direction. We speculate that sheetlet sliding is a tissue architectural adaptation to allow easier deformations of the LV walls so that LV wall stiffness will not hinder function, and to provide a balance between function and tissue stresses. A limitation here is that sheetlet sliding is modeled as a simple reduction in shear stiffness, without consideration of micro-scale sheetlet mechanics and dynamics

Betel nut chewing and incidence of newly diagnosed type 2 diabetes mellitus in Taiwan.

<p>Abstract</p> <p>Background</p> <p>Betel nut chewing is associated with type 2 diabetes mellitus (T2DM) in a recent prevalence study in Taiwan. The present study further investigated its link with the incidence of newly diagnosed T2DM during the years 1992-1996.</p> <p>Methods</p> <p>Population-based datasets of a sample of 93,484 out of 256,036 diabetic patients from 66 medical settings using the National Health Insurance scheme covering > 96% of the population, published population prevalence of betel nut chewing and the governmental census of national population were used for calculation of odds ratios, incidence rates and incidence rate ratios between chewers and never-chewers in the male population for the year 1992 to 1996.</p> <p>Results</p> <p>Ever chewers among the diabetic patients were younger, more obese and had higher prevalence of parental diabetes than never-chewers (all <it>p </it>values < 0.001). Odds ratios for T2DM for ever chewers vs. never-chewers in the age of < 40, 40-49, 50-59, 60-69 and ≥70 years were 1.06 (0.92-1.23), 1.60 (1.45-1.76), 2.12 (1.88-2.39), 3.58 (3.10-4.13) and 7.14 (5.47-9.31), respectively. In 1996, incidence rates (per 100,000 population) in the respective age groups were 19.1, 251.5, 567.3, 721.7 and 971.4 for never-chewers; and were 30.2, 520.9, 2566.9, 11672.8 and 630.3 for ever chewers. The respective incidence rate ratios were 1.58, 2.07, 4.52, 16.17 and 0.65. The age-specific incidence rates and rate ratios were relatively consistent from 1992 to 1996. The differences in obesity and parental diabetes between ever chewers and never-chewers were mostly not statistically significant after age stratification, suggesting the link could not be attributed to these two factors.</p> <p>Conclusions</p> <p>Chewing betel nut is associated with newly diagnosed T2DM, supporting the suggestion that the habit is diabetogenic.</p

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations