Cheminformatics-based identification of phosphorylated RET tyrosine kinase inhibitors for human cancer.

Background: Rearranged during transfection (RET), an oncogenic protein, is associated with various cancers, including non-small-cell lung cancer (NSCLC), papillary thyroid cancer (PTC), pancreatic cancer, medullary thyroid cancer (MTC), breast cancer, and colorectal cancer. Dysregulation of RET contributes to cancer development, highlighting the importance of identifying lead compounds targeting this protein due to its pivotal role in cancer progression. Therefore, this study aims to discover effective lead compounds targeting RET across different cancer types and evaluate their potential to inhibit cancer progression. Methods: This study used a range of computational techniques, including Phase database creation, high-throughput virtual screening (HTVS), molecular docking, molecular mechanics with generalized Born surface area (MM-GBSA) solvation, assessment of pharmacokinetic (PK) properties, and molecular dynamics (MD) simulations, to identify potential lead compounds targeting RET. Results: Initially, a high-throughput virtual screening of the ZINC database identified 2,550 compounds from a pool of 170,269. Subsequent molecular docking studies revealed 10 compounds with promising negative binding scores ranging from -8.458 to -7.791 kcal/mol. MM-GBSA analysis further confirmed the potential of four compounds to exhibit negative binding scores. MD simulations demonstrated the stability of CID 95842900, CID 137030374, CID 124958150, and CID 110126793 with the target receptors. Conclusion: These findings suggest that these selected four compounds have the potential to inhibit phosphorylated RET (pRET) tyrosine kinase activity and may represent promising candidates for the treatment of various cancers.

Targeting endocytosis to sensitize cancer cells to programmed cell death.

Evading programmed cell death (PCD) is a hallmark of cancer that allows tumor cells to survive and proliferate unchecked. Endocytosis, the process by which cells internalize extracellular materials, has emerged as a key regulator of cell death pathways in cancer. Many tumor types exhibit dysregulated endocytic dynamics that fuel their metabolic demands, promote resistance to cytotoxic therapies, and facilitate immune evasion. This review examines the roles of endocytosis in apoptotic resistance and immune escape mechanisms utilized by cancer cells. We highlight how inhibiting endocytosis can sensitize malignant cells to therapeutic agents and restore susceptibility to PCD. Strategies to modulate endocytosis for enhanced cancer treatment are discussed, including targeting endocytic regulatory proteins, altering membrane biophysical properties, and inhibiting Rho-associated kinases. While promising, challenges remain regarding the specificity and selectivity of endocytosis-targeting agents. Nonetheless, harnessing endocytic pathways represents an attractive approach to overcome apoptotic resistance and could yield more effective therapies by rendering cancer cells vulnerable to PCD. Understanding the interplay between endocytosis and PCD regulation is crucial for developing novel anticancer strategies that selectively induce tumor cell death.

Longitudinal Changes in Maximal Forced Inspiratory Flow and Clinical Outcomes in COPD Patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) primarily impairs expiratory flow due to progressive airflow obstruction and reduced lung elasticity. Increasing evidence underlines the importance of inspiratory flow as a biomarker for selecting inhaler devices and providing ancillary aerodynamic information. RESEARCH QUESTION: Does the longitudinal changes in maximum forced inspiratory flow (FIFmax) influence acute exacerbations and lung function decline in COPD patients? STUDY DESIGN AND METHODS: This longitudinal study observed FIFmax in COPD patients over a 7-year period from 2004 to 2020. Eligible patients were categorized into two groups based on FIFmax trajectory: the increased FIFmax group and the decreased FIFmax group. Our study assessed the annual rate of acute exacerbations and the annual decline rate of forced expiratory volume in 1 second (FEV1). Subgroup analyses were conducted based on treatment status, with a focus on inhaled therapy and inhaler device usage. RESULTS: Among the eligible 956 COPD patients, 56.5% belonged to the increased FIFmax group. After propensity score matching, the increased FIFmax group experienced lower rates of severe exacerbations (0.16/yr vs. 0.25/yr, P-value=0.017) and a slower decline in FEV1 (0 [interquartile range (IQR), -51-71] vs. -43 [IQR, -119-6] ml/yr, P-value<0.001) compared to the decreased FIFmax group. These associations were particularly prominent in patients using specific inhaler therapies, such as DPI therapies. INTERPRETATION: Our study revealed that the longitudinal changes in FIFmax are associated with clinical outcomes in COPD patients. Patients with increased FIFmax experienced a lower rate of severe exacerbations and a slower decline in lung function. These findings suggest the potential benefits of optimizing inspiratory flow in COPD management, though further studies are needed to confirm these observations due to potential confounding factors.

Intrinsic Skeletal Muscle Function and Contraction-stimulated Glucose Uptake Do Not Vary by Time-of-day in Mice.

A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at four times-of-day (zeitgeber times 1, 7, 13, 19). Significantly, though both muscles demonstrated circadian-related changes in gene expression, there were no differences between the four time points in intrinsic contractile function, endurance, and contraction-stimulated glucose uptake, regardless of sex. Overall, these results suggest that time-of-day variation in exercise performance and the glycemia-reducing benefits of exercise are not due to chronobiological effects on intrinsic muscle function or contraction-stimulated glucose uptake.

Innovative Treatment Approach: Multiple Variability (MV) Loop Intervention for Angle Class I Malocclusion with Dewey's Type 2 Modification: A Case Report.

Proclination of anteriors is significantly found in developing malocclusions and affecting both aesthetics and function. In patients with protrusions or crowding, extraction therapy is often necessary. Orthodontic treatment is initiated with the extraction of maxillary first premolars to address the protrusions or crowding and achieve a harmonious occlusion. There are two ways to retract anteriors during extraction space closure: friction or frictionless. The present case report explains the innovative treatment approach for the correction of anterior protrusion using multiple variability (MV) loops. Even with the good efficiency of the MV loop, meticulous wire bending is one of the disadvantages of the loop, and it requires clinician skills. Smaller loop fabrication will be the future scope of the appliance to increase patient compliance toward the treatment using MV loop as it will cause less hindrance in the vestibular region.

Influence of Lead Knee Extension on Ball Velocity and Elbow Varus Torque in Professional and High School Baseball Pitchers.

Background: When the lead leg of a pitcher contacts the ground, the knee braces and then rapidly extends, initiating energy transfer to begin pelvis and trunk rotation. Purpose: To investigate the relationship of lead knee extension during the pitching delivery with peak lead knee extension velocity, ball velocity, and elbow varus torque in high school and professional pitchers. Study Design: Descriptive laboratory study. Methods: Data from 50 professional (PRO) and 50 high school (HS) pitcher groups were retrospectively analyzed. Pitchers threw 8 to 12 fastballs under 3-dimensional motion analysis (480 Hz). The groups were divided according to high or low lead knee extension: PRO-high (n = 18), PRO-low (n = 16), HS-high (n = 16), and HS-low (n = 17). Lead knee flexion, lead knee extension velocity, ball velocity, and elbow varus torque were analyzed between groups. Regression analyses were performed to quantify associations between lead knee extension and ball velocity and elbow varus torque for all pitchers. Results: At foot contact, all pitchers landed with similar knee flexion. PRO-high and HS-high pitchers had significantly greater lead knee extension through remaining pitching time points compared with the PRO-low and HS-low pitchers. PRO-high pitchers had faster ball velocity than PRO-low pitchers (39.8 ± 1.1 vs 39.3 ± 1.3 m/s, respectively), and HS-high pitchers had faster ball velocity than HS-low pitchers (34.1 ± 2.6 vs 31.2 ± 1.8 m/s, respectively) (P < .05). PRO-high pitchers had decreased elbow varus torque compared with PRO-low pitchers (85.3 ± 10.7 vs 95.4 ± 13.3 N·m, respectively); conversely, HS-high pitchers had greater elbow varus torque than HS-low pitchers (64.2 ± 14.7 vs 56.3 ± 12.2 N·m, respectively). For every 1° increase in lead knee extension, ball velocity increased by 0.47 m/s (P < .001) and elbow varus torque increased by 0.27 N·m (P = .025). Conclusion: Proper lead knee extension allowed efficient energy transfer through the kinetic chain to produce optimal ball velocity and minimize elbow varus torque in professional pitchers. Conversely, while proper lead knee extension improved ball velocity among high school pitchers, this did not minimize elbow varus torque. Clinical Relevance: Professional pitchers can extend their lead knee with minimal impact at the elbow. In high school pitchers, cognizance of proper full-body pitching mechanics remains a priority over increased velocity.

Hemodynamic influence of mild stenosis morphology in different coronary arteries: a computational fluid dynamic modelling study.

Introduction: Mild stenosis [degree of stenosis (DS) < 50%] is commonly labeled as nonobstructive lesion. Some lesions remain stable for several years, while others precipitate acute coronary syndromes (ACS) rapidly. The causes of ACS and the factors leading to diverse clinical outcomes remain unclear. Method: This study aimed to investigate the hemodynamic influence of mild stenosis morphologies in different coronary arteries. The stenoses were modeled with different morphologies based on a healthy individual data. Computational fluid dynamics analysis was used to obtain hemodynamic characteristics, including flow waveforms, fractional flow reserve (FFR), flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI). Results: Numerical simulation indicated significant hemodynamic differences among different DS and locations. In the 20%-30% range, significant large, low-velocity vortexes resulted in low TAWSS (<4 dyne/cm2) around stenoses. In the 30%-50% range, high flow velocity due to lumen area reduction resulted in high TAWSS (>40 dyne/cm2), rapidly expanding the high TAWSS area (averagely increased by 0.46 cm2) in left main artery and left anterior descending artery (LAD), where high OSI areas remained extensive (>0.19 cm2). Discussion: While mild stenosis does not pose any immediate ischemic risk due to a FFR > 0.95, 20%-50% stenosis requires attention and further subdivision based on location is essential. Rapid progression is a danger for lesions with 20%-30% DS near the stenoses and in the proximal LAD, while lesions with 30%-50% DS can cause plaque injury and rupture. These findings support clinical practice in early assessment, monitoring, and preventive treatment.

Postprandial cardiac hypertrophy is sustained by mechanics, epigenetic, and metabolic reprogramming in pythons.

Constricting pythons, known for their ability to consume infrequent, massive meals, exhibit rapid and reversible cardiac hypertrophy following feeding. Our primary goal was to investigate how python hearts achieve this adaptive response after feeding. Isolated myofibrils increased force after feeding without changes in sarcomere ultrastructure and without increasing energy cost. Ca2+ transients were prolonged after feeding with no changes in myofibril Ca2+ sensitivity. Feeding reduced titin-based tension, resulting in decreased cardiac tissue stiffness. Feeding also reduced the activity of sirtuins, a metabolically linked class of histone deacetylases, and increased chromatin accessibility. Transcription factor enrichment analysis on transposase-accessible chromatin with sequencing revealed the prominent role of transcription factors Yin Yang1 and NRF1 in postfeeding cardiac adaptation. Gene expression also changed with the enrichment of translation and metabolism. Finally, metabolomics analysis and adenosine triphosphate production demonstrated that cardiac adaptation after feeding not only increased energy demand but also energy production. These findings have broad implications for our understanding of cardiac adaptation across species and hold promise for the development of innovative approaches to address cardiovascular diseases.

Physics-informed neural networks for high-resolution weather reconstruction from sparse weather stations.

Background: The accurate provision of weather information holds immense significance to many disciplines. One example corresponds to the field of air traffic management, in which one basis for weather detection is set upon recordings from sparse weather stations on ground. The scarcity of data and their lack of precision poses significant challenges to achieve a detailed description of the atmosphere state at a certain moment in time. Methods: In this article, we foster the use of physics-informed neural networks (PINNs), a type of machine learning (ML) architecture which embeds mathematically accurate physics models, to generate high-quality weather information subject to the regularization provided by the Navier-Stokes equations. Results: The application of PINNs is oriented to the reconstruction of dense and precise wind and pressure fields in areas where only a few local measurements provided by weather stations are available. Our model does not only disclose and regularize such data, which are potentially corrupted by noise, but is also able to precisely compute wind and pressure in target areas. Conclusions: The effect of time and spatial resolution over the capability of the PINN to accurately reconstruct fluid phenomena is thoroughly discussed through a parametric study, concluding that a proper tuning of the neural network's loss function during training is of utmost importance.

There is currently a great interest in the many uses of artificial intelligence (AI) and how it is affecting our daily lives. From the robotics field to the use of language recognition to interact with different users, we are experiencing how machine intelligence is increasing day by day. In this article, we delve into one of the many applications of artificial intelligence: weather reconstruction. The ability to accurately determine weather conditions is believed to have an impact on various disciplines, e.g. reducing costs at airports due to delays, cancellations and associated compensations. In this particular example, a precise description of the status of the atmosphere is therefore necessary if countermeasures are to be executed. However, conventional weather recording with on-ground stations is often limited to a few sparse locations. Following that line of thought, it is not only necessary to estimate the weather in areas surrounding stations, but also on other target areas which may be subject to lack of weather information. Our strategy is based on the application of neural networks, a type of AI architecture, to infer data based on the underlying physics that drive the measured weather phenomena. For that purpose, we make use of neural networks which are consistent with physics laws, the so-called physics-informed neural networks (PINNs). This article deals with their adoption to weather pattern reconstruction, with the objective of further increasing the precision and availability of information given scarce reference measurements.

Nanoscale mesh acts as anti-adhesive surface against particulate contamination in eyes of whiteflies.

In many insects the surface of the eye is nanostructured by arrays of protuberances termed ommatidial gratings which provide the cuticle with anti-reflective, anti-wetting and self-cleaning properties. The hypothesised anti-contamination role of the gratings against dust and pollen results from theoretical predictions on grating geometry and experiments on synthetic replicas of ommatidia surfaces but has not yet been proven in an animal. Whiteflies are biological test beds for anti-contamination surfaces because they deliberately distribute wax particles extruded from abdominal plates over their entire bodies. The numerous particles protect the animal against water evaporation and radiation, but may severely impair vision. Using scanning electron microscopy (SEM) and CryoSEM, we here show that the cornea of whiteflies exhibits ~ 220 nm wide mesh-like structures forming hexagonal gratings with thin ~ 40 nm connecting walls. Quantitative measurements of wax particles on the eye show that the nanostructures reduce particle contamination by more than ~ 96% compared to other areas of the cuticle. Altogether, our study is the first description of a predicted optimized grating geometry for anti-contamination in an arthropod. The findings serve as evidence of the high effectiveness of nanostructured surfaces for reducing contact area and thus adhesion forces between biological surfaces and contaminating particles.

On the generation of force required for actin-based motility.

The fundamental question of how forces are generated in a motile cell, a lamellipodium, and a comet tail is the subject of this note. It is now well established that cellular motility results from the polymerization of actin, the most abundant protein in eukaryotic cells, into an interconnected set of filaments. We portray this process in a continuum mechanics framework, claiming that polymerization promotes a mechanical swelling in a narrow zone around the nucleation loci, which ultimately results in cellular or bacterial motility. To this aim, a new paradigm in continuum multi-physics has been designed, departing from the well-known theory of Larché-Cahn chemo-transport-mechanics. In this note, we set up the theory of network growth and compare the outcomes of numerical simulations with experimental evidence.

ECG and Atrial Appendage Doppler Discordance Is Common in Patients Undergoing Cardiac Surgery: Prospective Study.

Background: Patients with atrial fibrillation (AF) remain at increased risk of thromboembolism despite apparent maintenance of sinus rhythm with the cause often attributed to periods of asymptomatic AF. Atrial mechanical discordance, with the body of the left atrium (LA) in sinus rhythm and the left atrial appendage (LAA) in AF may also be a contributor. Objectives: The purpose of this study was to assess the frequency of electrocardiogram (ECG) rhythm and LAA and/right atrial appendage (RAA) Doppler ejection phenotype (transesophageal echocardiography [TEE]) discordance in patients undergoing cardiac surgery. Methods: A total of 124 patients undergoing coronary artery bypass graft (CABG), CABG and valve surgery, or isolated valve repair or replacement (valve ± CABG) were prospectively studied. Intraoperative surface ECG rhythm strip and TEE were performed before cardiopulmonary bypass. The ECG and TEE LAA/RAA Doppler spectrum were independently classified as sinus or AF. Results: Of 107 patients (age 65 ± 12 years; 31% female; 65% CABG, 31% valve ± CABG) without a history of AF, 39 (36%) had ECG and LAA and/or RAA discordance (ECG/LAA Doppler discordance, n = 12 [11%]; ECG/RAA Doppler discordance, n = 35 [33%]). There was no significant difference between concordant and discordant groups with regard to age, gender, history of hypertension, diabetes, heart failure, or stroke (all P > 0.05). Conclusions: A large minority of patients without a history of AF undergoing cardiac surgery have ECG/atrial appendage Doppler discordance, a setting that may promote thromboembolism in non-anticoagulated patients. Clinical parameters do not identify patients at increased risk for discordance.

The deflection of fatigued neck.

The human neck is a unique mechanical structure, highly flexible but fatigue prone. The rising prevalence of neck pain and chronic injuries has been attributed to increasing exposure to fatigue loading in activities such as prolonged sedentary work and overuse of electronic devices. However, a causal relationship between fatigue and musculoskeletal mechanical changes remains elusive. This work aimed to establish this relationship through a unique experiment design, inspired by a cantilever beam mechanical model of the neck, and an orchestrated deployment of advanced motion-force measurement technologies including dynamic stereo-radiographic imaging. As a group of 24 subjects performed sustained-till-exhaustion neck exertions in varied positions-neutral, extended, and flexed, their cervical spine musculoskeletal responses were measured. Data verified the occurrence of fatigue and revealed fatigue-induced neck deflection which increased cervical lordosis or kyphosis by 4-5° to 11°, depending on the neck position. This finding and its interpretations render a renewed understanding of muscle fatigue from a more unified motor control perspective as well as profound implications on neck pain and injury prevention.

Analysis of stress response distribution in patients with lateral ankle ligament injuries: a study of neural control strategies utilizing predictive computing models.

Background: Ankle sprains are prevalent in sports, often causing complex injuries to the lateral ligaments. Among these, anterior talofibular ligament (ATFL) injuries constitute 85%, and calcaneofibular ligament (CFL) injuries comprise 35%. Despite conservative treatment, some ankle sprain patients develop chronic lateral ankle instability (CLAI). Thus, this study aimed to investigate stress response and neural control alterations during landing in lateral ankle ligament injury patients. Method: This study recruited twenty individuals from a Healthy group and twenty CLAI patients performed a landing task using relevant instruments to collect biomechanical data. The study constructed a finite element (FE) foot model to examine stress responses in the presence of laxity of the lateral ankle ligaments. The lateral ankle ligament was modeled as a hyperelastic composite structure with a refined representation of collagen bundles and ligament laxity was simulated by adjusting material parameters. Finally, the validity of the finite element model is verified by a high-speed dual fluoroscopic imaging system (DFIS). Result: CLAI patients exhibited earlier Vastus medialis (p < 0.001) and tibialis anterior (p < 0.001) muscle activation during landing. The FE analysis revealed that with laxity in the ATFL, the peak von Mises stress in the fifth metatarsal was 20.74 MPa, while with laxity in the CFL, it was 17.52 MPa. However, when both ligaments were relaxed simultaneously, the peak von Mises stress surged to 21.93 MPa. When the ATFL exhibits laxity, the CFL is subjected to a higher stress of 3.84 MPa. Conversely, when the CFL displays laxity, the ATFL experiences a peak von Mises stress of 2.34 MPa. Conclusion: This study found that changes in the laxity of the ATFL and the CFL are linked to shifts in metatarsal stress levels, potentially affecting ankle joint stability. These alterations may contribute to the progression towards CLAI in individuals with posterolateral ankle ligament injuries. Additionally, significant muscle activation pattern changes were observed in CLAI patients, suggesting altered neural control strategies post-ankle ligament injury.

Modeling biological growth of human keratoconus: On the effect of tissue degradation, location and size.

Keratoconus is a non-inflammatory bilateral disease, that usually occurs in the inferior-temporal region, where the cornea bulges out and becomes thinner, due to the gradual loss of structural organization in corneal tissue. Degenerated extracellular matrix and fibers breakage have been observed in keratoconic corneas, that may promote the progression of the pathology. While keratoconus histopathology has been widely described in literature, its etiology is still not clear. Being able to fully understand keratoconus growing process could be crucial to detect its development and improve prevention strategies. This work proposes a novel continuum-based keratoconus growth model. The proposed framework accounts for the structural changes occurring in the underlying tissue during the progression of the disease, as indicated in experiments. The developed formulation is able to replicate the typical bulging and thinning of keratoconic corneas, as well as different forms in terms of shape, as they are commonly classified in clinics (nipple, oval and globus cones). The cone that is obtained constitutes a permanent deformed state, not pressure dependent. The resulting model may help to better understand the etiology of the behavior of this disease with the aim of improving the diagnosis and the treatment of the pathology.

Relation between soft tissue energy dissipation and leg stiffness in running at different step frequencies.

This study aims to investigate the relationship between soft tissue energy dissipation and leg stiffness during running. Eight recreational healthy male runners (age: 22.2 ± 1.0 years; height: 1.84 ± 0.03 m; mass: 73.7 ± 5.7 kg) were asked to run at different speeds and step frequencies. Their soft tissue energy dissipation was estimated by the difference between the total mechanical work of the body, measured as the work done to move the body centre of mass relative to the surroundings plus the work to move the limbs relative to the body centre of mass, and lower-limb joint work. A mass-spring model with an actuator was used to analyse the force-length curve of the bouncing mechanism of running. In this way, the stiffness and damping coefficient were assessed at each speed and step frequency. Pearson's correlations were used to describe the relationship between the deviation from the spring-mass model and soft tissue energy fluctuations. The soft tissue dissipation was found to be significantly influenced by step frequency, with both positive and negative work phases decreasing when step frequency increases. Moreover, deviation from a spring-mass model was positively associated with the amount of soft tissue dissipation (r > 0.6). The findings emphasize the substantial role of soft tissues in dissipating or returning energy during running, behaving in a damped-elastic manner. Also, we introduce a novel approach for evaluating the elastic rebound of the body during running. The insights gained may have broad implications for assessing running mechanics, with potential applications in various contexts.

Soliton structures of fractional coupled Drinfel'd-Sokolov-Wilson equation arising in water wave mechanics.

This article delves into the dynamic constructions of distinctive traveling wave solutions for wave circulation in shallow water mechanics, specifically addressing the time-fractional couple Drinfel'd-Sokolov-Wilson (DSW) equation. Introducing the previously untapped e x p ( - ϕ ( ξ ) ) -expansion method, we successfully generate a diverse set of analytic solutions expressed in hyperbolic, trigonometric, and rational functions, each with permitted parameters. Visualization through three-dimensional (3D) as well two-dimensional (2D) plots, including contour plots, reveals inherent wave phenomena in the DSW equation. These newly obtained wave solutions serve as a catalyst for refining theories in applied science, offering a means to validate mathematical simulations for the proliferation of waves in shallow water as well as other nonlinear scenarios. Obtained wave solutions demonstrate the bright soliton, periodic, multiple soliton, and kink soliton shape. The simplicity and efficacy of the implemented methods are demonstrated, providing a valuable tool for approximating the considered equation. All figures are devoted to demonstrate the complete wave futures of the attained solutions to the studied equation with the collaboration of specific selections of the chosen parameters. Moreover, it may have summarized that the attained wave solutions and their physical phenomena might be useful to comprehend the various kind of wave propagation in mathematical physics and engineering.

Ultracoherent Gigahertz Diamond Spin-Mechanical Lamb Wave Resonators.

We report the development of an all-optical approach that excites the fundamental compression mode in a diamond Lamb wave resonator with an optical gradient force and detects the induced vibrations via strain coupling to a silicon vacancy center, specifically, via phonon sidebands in the optical excitation spectrum of the silicon vacancy. Sideband optical interferometry has also been used for the detection of in-plane mechanical vibrations, for which conventional optical interferometry is not effective. These experiments demonstrate a gigahertz fundamental compression mode with a Q factor of >107 at temperatures near 7 K, providing a promising platform for reaching the quantum regime of spin mechanics, especially phononic cavity quantum electrodynamics of electron spins.

Patient-specific arterial wall generation for intracranial aneurysms with a variable and a near realistic vessel wall thickness for FSI studies.

BACKGROUND AND OBJECTIVE: Imaging methodologies such as, computed tomography (CT) aid in three-dimensional (3D) reconstruction of patient-specific aneurysms. The radiological data is useful in understanding their location, shape, size, and disease progression. However, there are serious impediments in discerning the blood vessel wall thickness due to limitations in the current imaging modalities. This further restricts the ability to perform high-fidelity fluid structure interaction (FSI) studies for an accurate assessment of rupture risk. FSI studies would require the arterial wall mesh to be generated to determine realistic maximum allowable wall stresses by performing coupled calculations for the hemodynamic forces with the arterial walls. METHODS: In the present study, a novel methodology is developed to geometrically model variable vessel wall thickness for the lumen isosurface extracted from CT scan slices of patient-specific aneurysms based on clinical and histopathological inputs. FSI simulations are carried out with the reconstructed models to assess the importance of near realistic wall thickness model on rupture risk predictions. RESULTS: During surgery, clinicians often observe translucent vessel walls, indicating the presence of thin regions. The need to generate variable vessel wall thickness model, that embodies the wall thickness gradation, is closer to such clinical observations. Hence, corresponding FSI simulations performed can improve clinical outcomes. Considerable differences in the magnitude of instantaneous wall shear stresses and von Mises stresses in the walls of the aneurysm was observed between a uniform wall thickness and a variable wall thickness model. CONCLUSION: In the present study, a variable vessel wall thickness generation algorithm is implemented. It was shown that, a realistic wall thickness modeling is necessary for an accurate prediction of the shear stresses on the wall as well as von Mises stresses in the wall. FSI simulations are performed to demonstrate the utility of variable wall thickness modeling.