In this paper, we discuss some well-known experimental observations on self-organization in dissipative systems. The examples range from pure fluid flow, pattern selection in fluid–solid systems to chemical-reaction-induced flocking and aggregation in fluid systems. In each case, self-organization can be seen to be a function of a persistent internal gradient. One goal of this article is to hint at a common theory to explain such phenomena, which often takes the form of the extremum of some thermodynamic quantity, for instance the rate of entropy production. Such variational theories are not new; they have been in existence for decades and gained popularity through the Nobel Prize-winning work of theorists such as Lars Onsager and Ilya Prigogine. The arguments have evolved since then to include systems of higher complexity and for nonlinear systems, though a comprehensive theory remains elusive. The overall attempt is to bring out examples from physics, chemistry, engineering, and biology that reveal deep connections between variational principles in physics and biological, or living systems. There is sufficient evidence to at least raise suspicion that there exists an organization principle common to both living and non-living systems, which deserves deep attention.

This study aims to computationally identify the detailed mechanisms of the adhesion process of mucin and foreign bodies in the human tear film subject to the blinking motion of eyelid. The results give us a clue about the role of mucus as a protective agent for the ocular surface and its role in diseases such as dry eye syndrome (DES). We propose a multi-phase model which models the tear film as an inhomogeneous fluid comprising of a mixture of an aqueous layer in which mucin particles are exponentially distributed in the direction normal to corneal surface. We model the mucin adherence to any immersed foreign object, and its overall clearance through the blinking motion of the eyelid. The motions of mucin in the flow are solved by a force balance equation which accounts for the macroscopic interactions between the fluid and the body. The clearance rates of the foreign particle are explored under various conditions with different varying mechanical properties of mucin such as its adhesion force, distribution profile, as well as its viscosity. Our parametric study shows that a condition for higher clearance rate requires (i) greater mucin population in the entire region of tear film, i.e., larger viscosity, (ii) an optimal mucin distribution profile, and (iii) normal physiologic adhesion force between mucin and immersed particles.

The autorotation and energy harvesting potential of bladeless turbine models are tested in a confined water stream with Reynolds numbers from 20 K to 40 K. Mini bladeless turbine models of various geometrical shapes are 3D-printed using plastic material with low printing density. Experiments were performed using a commercial closed-loop water tank capable of delivering fine incremental speed up to a maximum of 60 cm/s. The cross-cylinder models with low density appear to demonstrate autorotation at high Reynolds numbers. Other turbine models demonstrate either stagnation or oscillation for a wide range of Reynolds numbers. For the cross-cylinder models, the autorotation phenomenon appears to be promoted at lower average flow speed when an upstream asymmetrical obstacle is introduced in the stream. The rotation per minute and energy potential (voltage and current) of the autorotating model are increased with the Reynolds number.

While previous studies have identified many risk factors for the progression and rupture of cerebral aneurysms, the changes in aneurysm flow characteristics during its evolution are not fully understood. This work analyzes the changes in the aneurysm hemodynamic environment from its initial development to later stages when the aneurysm has substantially enlarged. A total of 88 aneurysms at four locations were studied with image based computational fluid dynamics (CFD). Two synthetic sequences representing the aneurysm geometry at three earlier stages were generated by shrinking the aneurysm sac while keeping the neck fixed or shrinking the neck simultaneously. The flow conditions were then quantitatively compared between these two modes of evolution. As aneurysms enlarged, the inflow rate increased in growing neck sequences, but decreased in fixed neck sequences. The inflow jet became more concentrated in both sequences. The mean aneurysm flow velocity and wall shear stress decreased in both sequences, but they decreased faster in enlarging aneurysms if the neck was fixed. Additionally, the intra-aneurysmal flows became more complex and more unstable, wall shear stress distribution became more oscillatory, and the area under low wall shear stress increased for both sequences. The evolution of flow characteristics of aneurysms with fixed and growing necks are different. The observed trends suggest that fixed neck aneurysms may evolve towards a flow environment characteristic of stable aneurysms faster than aneurysms with growing necks, which could also evolve towards a more disfavorable environment.

The paper by Kuchling et al. [9] presents cellular morphogenesis as a self-organizing process in light of the min-imization of the free energy of the system. The FEP principle has been gaining in popularity and is handling quite complex issues in biology as evidenced by the numerous other publications cited in this review paper alone. The FEP sits on a rigorous mathematical foundation and the computations are quite impressive. The comments presented here are focused, however on its connections to physics, including existing theories of non-equilibrium thermodynamics which have proven to be successful as well as some underlying philosophical issues.

Background Although it is generally believed that blebs represent weaker spots in the walls of intracranial aneurysms (IAs), it is largely unknown which aneurysm characteristics favor their development. Objective To investigate possible associations between aneurysm hemodynamic and geometric characteristics and the development of blebs in intracranial aneurysms. Methods A total of 270 IAs in 199 patients selected for surgical clipping were studied. Blebs were visually identified and interactively marked on patient-specific vascular models constructed from presurgical images. Blebs were then deleted from the vascular reconstruction to approximate the aneurysm before bleb formation. Computational fluid dynamics studies were performed in these models and in cases without blebs. Hemodynamic and geometric characteristics of aneurysms with and without blebs were compared. Results A total of 173 aneurysms had no blebs, while 97 aneurysms had a total of 122 blebs. Aneurysms favoring bleb formation had stronger (p<0.0001) and more concentrated inflow jets (p<0.0001), higher flow velocity (p=0.0061), more complex (p<0.0001) and unstable (p=0.0157) flow patterns, larger maximum wall shear stress (WSS; p<0.0001), more concentrated (p=0.0005) and oscillatory (p=0.0004) WSS distribution, and a more heterogeneous WSS field (p<0.0001), than aneurysms without blebs. They were also larger (p<0.0001), more elongated (p<0.0001), had wider necks (p=0.0002), and more distorted and irregular shapes (p<0.0001). Conclusions Strong and concentrated inflow jets, high-speed, complex, and unstable flow patterns, and concentrated, oscillatory, and heterogeneous WSS patterns favor the formation of blebs in IAs. Blebs are more likely to form in large, elongated, and irregularly shaped aneurysms. These adverse characteristics could be considered signs of aneurysm instability when evaluating aneurysms for conservative observation or treatment.

BACKGROUND:Blebs are rupture risk factors in intracranial aneurysms (IAs), but their prevalence, distribution, and associations with clinical factors as well as their causes and effects on aneurysm vulnerability remain unclear. METHODS:A total of 122 blebs in 270 IAs selected for surgery were studied using patient-specific vascular reconstructions from 3D angiographic images. Bleb geometry, location on the aneurysm, and frequency of occurrence in aneurysms at different locations were analyzed. Associations between gender, age, smoking, hypertension, hormone therapy, dental infection, and presence of blebs were investigated. RESULTS:Of all aneurysms with blebs, 77% had a single bleb and 23% had multiple blebs. Only 6% of blebs were at the neck, while 46% were in the body and 48% in the dome. Aneurysms with blebs were larger (p<0.0001), more elongated (p=0.0002), and with wider necks than aneurysms without blebs. Bleb presence was associated with dental infection (p=0.0426) and negatively associated with hormone therapy (p=0.0426) in women. Anterior and posterior communicating arteries had larger percentages of aneurysms with blebs than internal carotid arteries. Patients with a history of hypertension tended to have a larger percentage of aneurysms with blebs. However, these trends did not reach significance in this sample. CONCLUSIONS:Blebs are common in IAs, and most aneurysms harboring blebs have a single bleb. Blebs in the aneurysm neck are rare, but they are equally common in the body and dome. The presence of blebs in IAs was associated with dental infection, and negatively associated with hormone replacement therapy.

OBJECTIVE Incidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors’ goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data. METHODS Patient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm’s shape and hemodynamics. Next, the previously developed model’s discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data. RESULTS The US model’s AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10. CONCLUSIONS Developing an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

OBJECTIVE:Although the clinical and biological importance of calcification is well recognized for the extracerebral vasculature, its role in cerebral vascular disease, particularly, intracranial aneurysms (IAs), remains poorly understood. Extracerebrally, 2 distinct mechanisms drive calcification, a nonatherosclerotic, rapid mineralization in the media and a slower, inflammation driven, atherosclerotic mechanism in the intima. This study aims to determine the prevalence, distribution, and type (atherosclerotic, nonatherosclerotic) of calcification in IAs and assess differences in occurrence between ruptured and unruptured IAs. Approach and Results: Sixty-five 65 IA specimens (48 unruptured, 17 ruptured) were resected perioperatively. Calcification and lipid pools were analyzed nondestructively in intact samples using high resolution (0.35 μm) microcomputed tomography. Calcification is highly prevalent (78%) appearing as micro (<500 µm), meso (500 µm-1 mm), and macro (>1 mm) calcifications. Calcification manifests in IAs as both nonatherosclerotic (calcification distinct from lipid pools) and atherosclerotic (calcification in the presence of lipid pools) with 3 wall types: Type I-only calcification, no lipid pools (20/51, 39%), Type II-calcification and lipid pools, not colocalized (19/51, 37%), Type III-calcification colocalized with lipid pools (12/51, 24%). Ruptured IAs either had no calcifications or had nonatherosclerotic micro- or meso-calcifications (Type I or II), without macro-calcifications. CONCLUSIONS:Calcification in IAs is substantially more prevalent than previously reported and presents as both nonatherosclerotic and atherosclerotic types. Notably, ruptured aneurysms had only nonatherosclerotic calcification, had significantly lower calcification fraction, and did not contain macrocalcifications. Improved understanding of the role of calcification in IA pathology should lead to new therapeutic targets.

Modeling the flow dynamics in cerebral aneurysms after the implantation of intrasaccular devices is important for understanding the relationship between flow conditions created immediately posttreatment and the subsequent outcomes. This information, ideally available a priori based on computational modeling prior to implantation, is valuable to identify which aneurysms will occlude immediately and which aneurysms will likely remain patent and would benefit from a different procedure or device. In this report, a methodology for modeling the hemodynamics in intracranial aneurysms treated with intrasaccular flow diverting devices is described. This approach combines an image-guided, virtual device deployment within patient-specific vascular models with an immersed boundary method on adaptive unstructured grids. A partial mesh refinement strategy that reduces the number of mesh elements near the aneurysm dome where the flow conditions are largely stagnant was compared with the full refinement strategy that refines the mesh everywhere around the device wires. The results indicate that using the partial mesh refinement approach is adequate for analyzing the posttreatment hemodynamics, at a reduced computational cost. The results obtained on a series of four cerebral aneurysms treated with different intrasaccular devices were in good qualitative agreement with angiographic observations. Promising results were obtained relating posttreatment flow conditions and outcomes of treatments with intrasaccular devices, which need to be confirmed on larger series.

This study is devoted to the investigation of optimal conditions for flow-induced autorotation of a hinged cylinder in a direction perpendicular to the flow in a water tunnel. Previous studies of hinged, immersed cylinders inflow have shown autorotation to be dependent upon the geometric aspects of the body and flow speed when the speed is beyond a critical threshold. Our experiments indicate that introducing a blockage of the appropriate width and at the right distance, upstream of the cylinder, can help induce autorotation, even at much lower flow speeds. Additionally, the percentage of the cylinder?s area blocked (i.e. the blockage ratio), is a significant control parameter, which can be used to manipulate the rotational speed of the cylinder. This phenomenon can be used to generate power which is demonstrated here by a suitable modification of our setup. Our mechanism deviates from traditional wind and hydro-power generators which use blade turbines by considering a cylinder and its modifications as a turbine. Such a design is easy to manufacture and control as is demonstrated in our experiments. Induced autorotation by the introduction of a control body upstream of the turbine is shown to increase power generation in our setup up to 400%.

PURPOSE:The mechanisms of cerebral aneurysm rupture are not fully understood. We analyzed the associations of hemodynamics, morphology, and patient age and gender with aneurysm rupture stratifying by location.METHODS:Using image-based models, 20 hemodynamic and 17 morphological parameters were compared in 1931 ruptured and unruptured aneurysms with univariate logistic regression. Rupture rates were compared between males and females as well as younger and older patients and bifurcation versus sidewall aneurysms for different aneurysm locations. Subsequently, associations between hemodynamics and morphology and patient as well as aneurysm characteristics were analyzed for aneurysms at five locations.RESULTS:Compared to unruptured aneurysms, ruptured aneurysms were characterized by a more irregular shape and were exposed to a more adverse hemodynamic environment described by faster flow, higher wall shear stress, more oscillatory shear, and more unstable and complex flows. These associations with rupture status were consistent for different aneurysm locations. Rupture rates were significantly higher in males at the internal carotid artery (ICA) bifurcation, ophthalmic ICA, and the middle cerebral artery (MCA) bifurcation. At the anterior communicating artery (ACOM) and MCA bifurcation, they were significantly higher for younger patients. Bifurcation aneurysms had significantly larger rupture rates at the MCA and posterior communicating artery (PCOM). In these groups with higher rupture rates, aneurysms were characterized by adverse hemodynamics and more complex shapes.CONCLUSION:Hemodynamic and morphological differences between ruptured and unruptured aneurysms are consistent across locations. Adverse morphology and hemodynamics are related to rupture as well as younger age, male gender, and bifurcation aneurysms.

Background Intracranial aneurysms at the posterior communicating artery (PCOM) are known to have high rupture rates compared to other locations. We developed and internally validated a statistical model discriminating between ruptured and unruptured PCOM aneurysms based on hemodynamic and geometric parameters, angio-architectures, and patient age with the objective of its future use for aneurysm risk assessment. Methods A total of 289 PCOM aneurysms in 272 patients modeled with image-based computational fluid dynamics (CFD) were used to construct statistical models using logistic group lasso regression. These models were evaluated with respect to discrimination power and goodness of fit using tenfold nested cross-validation and a split-sample approach to mimic external validation. Results The final model retained maximum and minimum wall shear stress (WSS), mean parent artery WSS, maximum and minimum oscillatory shear index, shear concentration index, and aneurysm peak flow velocity, along with aneurysm height and width, bulge location, non-sphericity index, mean Gaussian curvature, angio-architecture type, and patient age. The corresponding area under the curve (AUC) was 0.8359. When omitting data from each of the three largest contributing hospitals in turn, and applying the corresponding model on the left-out data, the AUCs were 0.7507, 0.7081, and 0.5842, respectively. Conclusions Statistical models based on a combination of patient age, angio-architecture, hemodynamics, and geometric characteristics can discriminate between ruptured and unruptured PCOM aneurysms with an AUC of 84%. It is important to include data from different hospitals to create models of aneurysm rupture that are valid across hospital populations.

Purpose Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. Methods To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. Results Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. Conclusions MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

PURPOSE:Unruptured cerebral aneurysms pose a dilemma for physicians who need to weigh the risk of a devastating subarachnoid hemorrhage against the risk of surgery or endovascular treatment and their complications when deciding on a treatment strategy. A prediction model could potentially support such treatment decisions. The aim of this study was to develop and internally validate a model for aneurysm rupture based on hemodynamic and geometric parameters, aneurysm location, and patient gender and age.METHODS:Cross-sectional data from 1061 patients were used for image-based computational fluid dynamics and shape characterization of 1631 aneurysms for training an aneurysm rupture probability model using logistic group Lasso regression. The model's discrimination and calibration were internally validated based on the area under the curve (AUC) of the receiver operating characteristic and calibration plots.RESULTS:The final model retained 11 hemodynamic and 12 morphological variables, aneurysm location, as well as patient age and gender. An adverse hemodynamic environment characterized by a higher maximum oscillatory shear index, higher kinetic energy and smaller low shear area as well as a more complex aneurysm shape, male gender and younger age were associated with an increased rupture risk. The corresponding AUC of the model was 0.86 (95% CI [0.85, 0.86], after correction for optimism 0.84).CONCLUSION:The model combining variables from various domains was able to discriminate between ruptured and unruptured aneurysms with an AUC of 86%. Internal validation indicated potential for the application of this model in clinical practice after evaluation with longitudinal data.

The terminal orientation of a rigid body in a moving fluid is an example of a dissipative system, out of thermodynamic equilibrium and therefore a perfect testing ground for the validity of the maximum entropy production principle (MaxEP). Thus far, dynamical equations alone have been employed in studying the equilibrium states in fluid-solid interactions, but these are far too complex and become analytically intractable when inertial effects come into play. At that stage, our only recourse is to rely on numerical techniques which can be computationally expensive. In our past work, we have shown that the MaxEP is a reliable tool to help predict orientational equilibrium states of highly symmetric bodies such as cylinders, spheroids and toroidal bodies. The MaxEP correctly helps choose the stable equilibrium in these cases when the system is slightly out of thermodynamic equilibrium. In the current paper, we expand our analysis to examine i) bodies with fewer symmetries than previously reported, for instance, a half-ellipse and ii) when the system is far from thermodynamic equilibrium. Using two-dimensional numerical studies at Reynolds numbers ranging between 0 and 14, we examine the validity of the MaxEP. Our analysis of flow past a half-ellipse shows that overall the MaxEP is a good predictor of the equilibrium states but, in the special case of the half-ellipse with aspect ratio much greater than unity, the MaxEP is replaced by the Min-MaxEP, at higher Reynolds numbers when inertial effects come into play. Experiments in sedimentation tanks and with hinged bodies in a flow tank confirm these calculations.

This paper investigates the mechanics of clearance of an embedded particle in a lubrication layer of viscoelastic fluid. We show theoretically that in a slider bearing domain containing a viscoelastic fluid, the oscillating shearing motion of a wall aids in transporting away any embedded particle towards the moving boundary. The impact of geometry and material properties of the fluid layer are explored by coupling theoretical and numerical methods. Our approach suggests a possible mechanism by which the human eye could clear out any debris beneath the eyelid, under responsive blinking. Our simplified analysis brings to bear interesting approaches from physics and engineering upon a very complex biological problem and could provide essential clues about the physiological design of the tear film.

Symmetric bodies such as cylinders and spheroidal bodies, in their terminal stable states, are long known to have their long axis align themselves perpendicular to the direction of the flow. This property has been confirmed in primarily sedimentation based theoretical, experimental and numerical techniques and the transition to a terminal stable state is believed to coincide with the onset of significant inertial effects in the flow. However, the threshold at which this transition occurs is yet unknown. We conduct modified experiments with hinged bodies and a CFD study to examine the nature of the transition of prolate spheroids and cylinders of various aspect ratios, from initial to their terminal stable equilibrium. Our experiments and numerics, both reveal the presence of intermediate metastable states which are sensitive to the flow Reynolds number and physical attributes of the immersed body and gradually lead to the stable state.

The evolution of intracranial aneurysms (IAs) is thought to be driven by progressive wall degradation in response to abnormal hemodynamics. Previous studies focused on the relationship between global hemodynamics and wall properties. However, hemodynamics, wall structure and mechanical properties of cerebral aneurysms can be non-uniform across the aneurysm wall. Therefore, the aim of this work is to introduce a methodology for mapping local hemodynamics to local wall structure in resected aneurysm specimens. This methodology combines image-based computational fluid dynamics, tissue resection, micro-CT imaging of resected specimens mounted on 3D-printed aneurysm models, alignment to 3D vascular models, multi-photon microscopy of the wall, and regional mapping of hemodynamics and wall properties. This approach employs a new 3D virtual marking tool for surgeons to delineate the location of the resected specimen directly on the 3D model, while in the surgical suite. The case of a middle cerebral artery aneurysm is used to illustrate the application of this methodology to the assessment of the relationship between local wall shear stress and local wall properties including collagen fiber organization and wall geometry. This methodology can similarly be used to study the relationship between local intramural stresses and local wall structure.