Load-sharing characteristics of stenting and post-dilation in heavily calcified coronary artery.

In this work, stenting in non-calcified and heavily calcified coronary arteries was quantified in terms of diameter-pressure relationships and load transfer from the balloon to the artery. The efficacy of post-dilation in non-calcified and heavily calcified coronary arteries was also characterized in terms of load sharing and the changes in tissue mechanics. Our results have shown that stent expansion exhibits a cylindrical shape in non-calcified lesions, while it exhibits a dog bone shape in heavily calcified lesions. Load-sharing analysis has shown that only a small portion of the pressure load (1.4 N, 0.8% of total pressure load) was transferred to the non-calcified lesion, while a large amount of the pressure load (19 N, 12%) was transferred to the heavily calcified lesion. In addition, the increasing inflation pressure (from 10 to 20 atm) can effectively increase the minimal lumen diameter (from 1.48 to 2.82 mm) of the heavily calcified lesion, the stress (from 1.5 to 8.4 MPa) and the strain energy in the calcification (1.77 mJ to 26.5 mJ), which are associated with the potential of calcification fracture. Results indicated that increasing inflation pressure can be an effective way to improve the stent expansion if a dog bone shape of the stenting profile is observed. Considering the risk of a balloon burst, our results support the design and application of the high-pressure balloon for post-dilation. This work also sheds some light on the stent design and choice of stent materials for improving the stent expansion at the dog bone region and mitigating stresses on arterial tissues.

Prediction of stent under-expansion in calcified coronary arteries using machine learning on intravascular optical coherence tomography images.

It can be difficult/impossible to fully expand a coronary artery stent in a heavily calcified coronary artery lesion. Under-expanded stents are linked to later complications. Here we used machine/deep learning to analyze calcifications in pre-stent intravascular optical coherence tomography (IVOCT) images and predicted the success of vessel expansion. Pre- and post-stent IVOCT image data were obtained from 110 coronary lesions. Lumen and calcifications in pre-stent images were segmented using deep learning, and lesion features were extracted. We analyzed stent expansion along the lesion, enabling frame, segmental, and whole-lesion analyses. We trained regression models to predict the post-stent lumen area and then computed the stent expansion index (SEI). Best performance (root-mean-square-error = 0.04 ± 0.02 mm2, r = 0.94 ± 0.04, p < 0.0001) was achieved when we used features from both lumen and calcification to train a Gaussian regression model for segmental analysis of 31 frames in length. Stents with minimum SEI > 80% were classified as "well-expanded;" others were "under-expanded." Under-expansion classification results (e.g., AUC = 0.85 ± 0.02) were significantly improved over a previous, simple calculation, as well as other machine learning solutions. Promising results suggest that such methods can identify lesions at risk of under-expansion that would be candidates for intervention lesion preparation (e.g., atherectomy).

The role of intrapartum fetal head compression in neonatal retinal hemorrhage.

PURPOSE: Neonatal retinal hemorrhage is a common finding in newborns, but the underlying mechanisms are not fully understood. A computational simulation was designed to study the events taking place in the eye and orbit when the head is compressed as the neonate passes through the birth canal. METHODS: A finite element model of the eye, optic nerve sheath, and orbit was simulated and subjected to forces mimicking rises in intracranial pressure (ICP) associated with maternal contractions during normal vaginal delivery. Resulting changes in intraocular pressure (IOP), pressure in the optic nerve sheath, and stress within the sclera and retina were measured. RESULTS: During contractions, increased ICP was transmitted to the orbit, globe, and optic nerve sheath. IOP rose by 2.71 kPa near the posterior pole. Pressure at the center of the optic nerve sheath rose by 7.31 kPa and up to 9.30 kPa at its interface with the sclera. Stress in the retina was highest near the optic disk and reached 10.93, 10.99, and 13.28 kPa in the preretinal, intraretinal, and subretinal layers, respectively. Stress in the sclera peaked at 12.76 kPa. CONCLUSIONS: Increasing ICP associated with natural vaginal delivery increases intraorbital pressure, which applies stress to the retina. Associated retinal deformation may cause tearing of the retinal vasculature. Increased pressure within the optic nerve sheath may occlude the central retinal vein, resulting in outflow obstruction and subsequent rupture. Forces accumulated near the optic disk, likely accounting for the tendency of neonatal retinal hemorrhage to occur posteriorly.

Load-sharing characteristics of stenting and post-dilation in heavily calcified coronary artery.

In this work, stenting in non-calcified and heavily calcified coronary arteries was quantified in terms of diameter-pressure relationships and load transfer from the balloon to the artery. The efficacy of post-dilation in non-calcified and heavily calcified coronary arteries was also characterized in terms of load sharing and the changes in tissue mechanics. Our results have shown that stent expansion exhibits a cylindrical shape in non-calcified lesions, while it exhibits a dog bone shape in heavily calcified lesions. Load-sharing analysis has shown that only a small portion of the pressure load (1.4 N, 0.8% of total pressure load) was transferred to the non-calcified lesion, while a large amount of the pressure load (19 N, 12%) was transferred to the heavily calcified lesion. In addition, the increasing inflation pressure (from 10 to 20 atm) can effectively increase the minimal lumen diameter (from 1.48 mm to 2.82 mm) of the heavily calcified lesion, the stress (from 1.5 MPa to 8.4 MPa) the strain energy in the calcification (1.77 mJ to 26.5 mJ), which associated with the potential of calcification fracture. Results indicated that increasing inflation pressure can be an effective way to improve the stent expansion if a dog bone shape of the stenting profile is observed. Considering the risk of a balloon burst, our results support the design and application of the high-pressure balloon for post-dilation.

Quantifying the efficacy of protective eyewear in pediatric soccer-induced retinal injury.

BACKGROUND: Ocular injury is common in children playing sports. Sports-related eye injuries, if severe enough, can lead to permanent vision impairment. Soccer, the most popular sport in the world, is a sport in which players rarely use protective eyewear. The purpose of this study was to determine how eye injuries are induced by a soccer ball impact and to evaluate whether eye protection influences the effects of impact. METHODS: A finite element (FE) computer simulation was used to simulate soccer ball trauma on a model of the eye with and without eye protection. Protective eyewear of different materials (polycarbonate and acrylic) was modeled to investigate the optimal medium for eye protection. Stress and strain experienced by the eyeball was quantified by the FE computer simulation in each model. RESULTS: Protective eyewear was found to be effective in lowering ocular stress and strain by absorbing and redirecting energy from the ball. Compared to the unprotected eye model, polycarbonate eyewear reduced the average stress the retina experienced by 61%, whereas the acrylic model reduced the average stress by 40%. Polycarbonate and acrylic eyewear also reduced the maximum strain experienced by the retina by 69% and 47%, respectively, reducing the severity of deformations of the eye on impact. CONCLUSIONS: These findings suggest that wearing protective eyewear, especially when made of polycarbonate, can be an effective means of reducing injury-inducing retinal stress. The use of eye protection is thus recommended for pediatric patients participating in soccer.

Finite Element Analysis of Soccer Ball-Related Ocular and Retinal Trauma and Comparison with Abusive Head Trauma.

Purpose: Trauma to the eye resulting from a soccer ball is a common sports-related injury. Although the types of ocular pathologic features that result from impact have been documented, the underlying pathophysiologic mechanics are not as well studied. The purpose of this study was to evaluate the biomechanical events after the collision of a soccer ball with the eye to better understand the pathophysiology of observed ocular and retinal injuries and to compare them with those observed in abusive head trauma (AHT). Design: Computer simulation study. Participants: None. Methods: A finite element model of the eye was used to investigate the effects of a collision of a soccer ball on the eye. Main Outcome Measures: Intraocular pressure and stress. Results: Impact of the soccer ball with the eye generated a pressure wave that traveled through the vitreous, creating transient pockets of high and negative pressure. During the high-frequency phase, pressure in the vitreous near the posterior pole ranged from 39.6 to -30.9 kPa. Stress in ocular tissue was greatest near the point of contact, with a peak of 66.6 kPa. The retina experienced the greatest stress at the vasculature, especially at distal branches, where stress rose to 15.4 kPa. On average, retinal stress was greatest in the subretinal layer, but was highest in the preretinal layer when considering only vascular tissue. Conclusions: The high intraocular pressure and stress in ocular tissue near the point of soccer ball impact suggest that injuries to the anterior segment of the eye can be attributed to direct transmission of force from the ball. The subsequent propagation of a pressure wave may cause injuries to the posterior segment as the positive and negative pressures exert compressive and tractional forces on the retina. The linear movement of the pressure wave likely accounts for localization of retinal lesions to the posterior pole or superior temporal quadrant. The primarily linear force in soccer ball trauma is the probable cause for the more localized injury profile and lower retinal hemorrhage incidence compared with AHT, in which repetitive angular force is also at play.

Connecting Aortic Stiffness to Vascular Contraction: Does Sex Matter?

This study was designed to connect aortic stiffness to vascular contraction in young male and female Wistar rats. We hypothesized that female animals display reduced intrinsic media-layer stiffness, which associates with improved vascular function. Atomic force microscopy (AFM)-based nanoindentation analysis was used to derive stiffness (Young's modulus) in biaxially (i.e., longitudinal and circumferential) unloaded aortic rings. Reactivity studies compatible with uniaxial loading (i.e., circumferential) were used to assess vascular responses to a selective α1 adrenergic receptor agonist in the presence or absence of extracellular calcium. Elastin and collagen levels were indirectly evaluated with fluorescence microscopy and a picrosirius red staining kit, respectively. We report that male and female Wistar rats display similar AFM-derived aortic media-layer stiffness, even though female animals withstand higher aortic intima-media thickness-to-diameter ratio than males. Female animals also present reduced phenylephrine-induced aortic force development in concentration-response and time-force curves. Specifically, we observed impaired force displacement in both parts of the contraction curve (Aphasic and Atonic) in experiments conducted with and without extracellular calcium. Additionally, collagen levels were lower in female animals without significant elastin content and fragmentation changes. In summary, sex-related functional differences in isolated aortas appear to be related to dissimilarities in the dynamics of vascular reactivity and extracellular matrix composition rather than a direct response to a shift in intrinsic media-layer stiffness.

Fractional Flow Reserve (FFR) Estimation from OCT-Based CFD Simulations: Role of Side Branches.

The computational fluid dynamic method has been widely used to quantify the hemodynamic alterations in a diseased artery and investigate surgery outcomes. The artery model reconstructed based on optical coherence tomography (OCT) images generally does not include the side branches. However, the side branches may significantly affect the hemodynamic assessment in a clinical setting, i.e., the fractional flow reserve (FFR), defined as the ratio of mean distal coronary pressure to mean aortic pressure. In this work, the effect of the side branches on FFR estimation was inspected with both idealized and optical coherence tomography (OCT)-reconstructed coronary artery models. The electrical analogy of blood flow was further used to understand the impact of the side branches (diameter and location) on FFR estimation. Results have shown that the side branches decrease the total resistance of the vessel tree, resulting in a higher inlet flowrate. The side branches located at the downstream of the stenosis led to a lower FFR value, while the ones at the upstream had a minimal impact on the FFR estimation. Side branches with a diameter larger than one third of the main vessel diameter are suggested to be considered for a proper FFR estimation. The findings in this study could be extended to other coronary artery imaging modalities and facilitate treatment planning.

An asynchronous artifact-enhanced electroencephalogram based control paradigm assisted by slight facial expression.

In this study, an asynchronous artifact-enhanced electroencephalogram (EEG)-based control paradigm assisted by slight-facial expressions (sFE-paradigm) was developed. The brain connectivity analysis was conducted to reveal the dynamic directional interactions among brain regions under sFE-paradigm. The component analysis was applied to estimate the dominant components of sFE-EEG and guide the signal processing. Enhanced by the artifact within the detected electroencephalogram (EEG), the sFE-paradigm focused on the mainstream defect as the insufficiency of real-time capability, asynchronous logic, and robustness. The core algorithm contained four steps, including "obvious non-sFE-EEGs exclusion," "interface 'ON' detection," "sFE-EEGs real-time decoding," and "validity judgment." It provided the asynchronous function, decoded eight instructions from the latest 100 ms signal, and greatly reduced the frequent misoperation. In the offline assessment, the sFE-paradigm achieved 96.46% ± 1.07 accuracy for interface "ON" detection and 92.68% ± 1.21 for sFE-EEGs real-time decoding, with the theoretical output timespan less than 200 ms. This sFE-paradigm was applied to two online manipulations for evaluating stability and agility. In "object-moving with a robotic arm," the averaged intersection-over-union was 60.03 ± 11.53%. In "water-pouring with a prosthetic hand," the average water volume was 202.5 ± 7.0 ml. During online, the sFE-paradigm performed no significant difference (P = 0.6521 and P = 0.7931) with commercial control methods (i.e., FlexPendant and Joystick), indicating a similar level of controllability and agility. This study demonstrated the capability of sFE-paradigm, enabling a novel solution to the non-invasive EEG-based control in real-world challenges.

Upper Airway Flow Dynamics in Obstructive Sleep Apnea Patients with Various Apnea-Hypopnea Index.

BACKGROUND AND AIM: This study evaluates the upper airway flow characteristics, anatomical features and analyzes their correlations with AHI in patients with varied degrees of OSA severity seeking for discernments of the underlying pathophysiological profile. MATERIALS AND METHODS: Patient-specific computational fluid dynamics models were reconstructed from high-resolution cone-beam computed tomography images for 4 OSA patients classified as minimal, mild, moderate, and severe according to AHI. RESULTS: The parameters, minimal cross-sectional area (MCA), and the pharyngeal airway volume did not show clear correlations with the OSA severity defined according to AHI. No correlations were found between the classically defined resistance of the airway in terms of pressure drop and AHI. The flow analysis further showed that the fluid mechanisms likely to cause airway collapse are associated with the degree of narrowing in the pharyngeal airway rather than AHI. Results also suggested that some patients classified as severe OSA according to the AHI can show less susceptibility to airway collapse than patients with relatively lower AHI values and vice versa. CONCLUSIONS: The relative contribution of anatomical and non-anatomical causes to the OSA severity can significantly vary between patients. AHI alone is inadequate to be used as a marker of the pathophysiological profile of OSA. Combining airflow analysis with AHI in diagnosing OSA severity may provide additional details about the underlying pathophysiology, subsequently improving the individualized clinical outcomes.

Rapid Prediction of Retina Stress and Strain Patterns in Soccer-Related Ocular Injury: Integrating Finite Element Analysis with Machine Learning Approach.

Soccer-related ocular injuries, especially retinal injuries, have attracted increasing attention. The mechanics of a flying soccer ball have induced abnormally higher retinal stresses and strains, and their correlation with retinal injuries has been characterized using the finite element (FE) method. However, FE simulations demand solid mechanical expertise and extensive computational time, both of which are difficult to adopt in clinical settings. This study proposes a framework that combines FE analysis with a machine learning (ML) approach for the fast prediction of retina mechanics. Different impact scenarios were simulated using the FE method to obtain the von Mises stress map and the maximum principal strain map in the posterior retina. These stress and strain patterns, along with their input parameters, were used to train and test a partial least squares regression (PLSR) model to predict the soccer-induced retina stress and strain in terms of distributions and peak magnitudes. The peak von Mises stress and maximum principal strain prediction errors were 3.03% and 9.94% for the frontal impact and were 9.08% and 16.40% for the diagonal impact, respectively. The average prediction error of von Mises stress and the maximum principal strain were 15.62% and 21.15% for frontal impacts and were 10.77% and 21.78% for diagonal impacts, respectively. This work provides a surrogate model of FE analysis for the fast prediction of the dynamic mechanics of the retina in response to the soccer impact, which could be further utilized for developing a diagnostic tool for soccer-related ocular trauma.

Serum Homocysteine Level Predictive Capability for Severity of Restenosis Post Percutaneous Coronary Intervention.

Background: In stent restenosis (ISR) is one of the major complications after stent implantation. Thus, there is a growing interest in identifying a biomarker for the onset of ISR. High levels of serum homocysteine (Hcy) have been associated with the progression of cardiovascular disease. Therefore, the study was carried out to quantify the correlation between serum Hcy and ISR severity. Compared with coronary angiography (CAG), Hcy levels provided a significantly better clinical detection of ISR severity after PCI. Methods: A total of 155 patients were recruited from Shanxi Bethune hospital, from 6 months to 2 years post PCI. Serum Hcy levels and postoperative angiography results were used to differentiate the patients into two experimental groups: ISR (>50% diametrical stenosis), and non-ISR. The non-ISR included two subgroups: intimal hyperplasia (10-50% diametrical stenosis), and recovery (<10% diametrical stenosis). In addition, a group of 80 healthy individuals was used as a negative control. The correlation between homocysteine level and ISR severity t was analyzed for all groups. In addition, the correlation between serum Hcy level and the severity of ISR in the experimental group was analyzed by the Pearson correlation test. Results: The serum Hcy level in the experimental group and control group was determined to be (20.21 ± 11.42) µmol/L and (15.11 ± 10.25) µmol/L respectively. The level of serum Hcy in the experimental group was significantly higher than in the control group (t-value of 2.385; p-value of 0.019). The serum Hcy level in the restenosis and the intimal hyperplasia group was (25.72 ± 13.71) µmol/L and (17.35 ± 7.70) µmol/L respectively. The serum Hcy level in the restenosis group was significantly higher than in the intimal hyperplasia group (t-value of 2.215; p-value of 0.033). The level of serum Hcy in the group without a plaque in the stent was (16.30 ± 6.08) µmol/L, whereas in the control group was (15.11 ± 10.25) µmol/L. The no plaque group had a slightly higher serum Hcy level than the control group (t-value of 0.634; p-value of 0.528). All included patients were divided into four quartiles based on the serum Hcy concentration: quartile 1 (8.90-13.20 µmol/L), quartile 2 (13.30-16.45 µmol/L), quartile 3 (16.60-24.25 µmol/L) and quartile 4 (24.30-65.30 µ mol/L). The incidence of ISR was 5, 6.25, 7.5 and 15%, in the 1,2,3 and four quartiles respectively. The serum Hcy level in the experimental group was (20.21 ± 11.42) µmol/L, the severity of in-stent restenosis was (0.25 ± 0.31), (R-value was 0.234; p-value was 0.037), indicating a correlation between serum Hcy and the severity of restenosis (p < 0.05). Taking coronary angiography as the gold standard, a ROC curve analysis was performed on the serum Hcy levels for the experimental group. The area under the curve (AUC) was 0.718 (95% CI 0.585-0.854, p < 0.001), indicating that the serum Hcy concentration could predict ISR. On the ROC curve, the best critical value of serum Hcy concentration for predicting ISR was 20.05 µmol/L, with a sensitivity of 45% and specificity of 88.1%. Conclusion: A positive correlation was observed between homocysteine and the severity of restenosis after PCI, The level of Hcy could serve as a predictive biomarker for the severity of ISR.

Exploring the Vitreoretinal Interface: A Key Instigator of Unique Retinal Hemorrhage Patterns in Pediatric Head Trauma.

PURPOSE: Various types of trauma can cause retinal hemorrhages in children, including accidental and nonaccidental head trauma. We used animal eyes and a finite element model of the eye to examine stress patterns produced during purely linear and angular accelerations, along with stresses attained during simulated repetitive shaking of an infant. METHODS: Using sheep and primate eyes, sclerotomy windows were created by removing the sclera, choroid, and retinal pigment epithelium to expose the retina. A nanofiber square was glued to a 5 mm2 area of retina. The square was pulled and separated from vitreous while force was measured. A finite element model of the pediatric eye was used to computationally measure tension stresses during shaking. RESULTS: In both sheep and primate eyes, tension stress required for separation of retina from vitreous range from 1 to 5 kPa. Tension stress generated at the vitreoretinal interface predicted by the computer simulation ranged from 3 to 16 kPa during a cycle of shaking. Linear acceleration generated lower tension stress than angular acceleration. Angular acceleration generated maximal tension stress along the retinal vasculature. Linear acceleration produced more diffuse force distribution centered at the poster pole. CONCLUSIONS: The finite element model predicted that tension stress attained at the retina during forcible shaking of an eye can exceed the minimum threshold needed to produce vitreoretinal separation as measured in animal eyes. Furthermore, the results show that movements that involve significant angular acceleration produce strong stresses localized along the vasculature, whereas linear acceleration produces weaker, more diffuse stress centered towards the posterior pole of the eye.

Assessment of Post-Dilatation Strategies for Optimal Stent Expansion in Calcified Coronary Lesions: Ex Vivo Analysis With Optical Coherence Tomography.

INTRODUCTION: Interventional cardiologists make adjustments in the presence of coronary calcifications known to limit stent expansion, but proper balloon sizing, plaque-modification approaches, and high-pressure regimens are not well established. Intravascular optical coherence tomography (IVOCT) provides high-resolution images of coronary tissues, including detailed imaging of calcifications, and accurate measurements of stent deployment, providing a means for detailed study of stent deployment. OBJECTIVE: Evaluate stent expansion in an ex vivo model of calcified coronary arteries as a function of balloon size and high-pressure, post-dilatation strategies. METHODS: We conducted experiments on cadaver hearts with calcified coronary lesions. We assessed stent expansion as a function of size and pressure of non-compliant (NC) balloons (i.e., nominal, 0.5, 1.0, and 1.5 mm balloons at 10, 20 and 30 atm). IVOCT images were acquired pre-stent, post-stent, and at all post-dilatations. Stent expansion was calculated using minimum expansion index (MEI). RESULTS: We analyzed 134 IVOCT pullbacks from ten ex-vivo experiments. The mean distal and proximal reference lumen diameters were 2.2 ± 0.5 mm and 2.5 ± 0.7 mm, respectively, 80% of times using a 3.0 mm diameter stent. Overall, based on stent sizing, a good expansion (MEI ≥ 80%) was reached using the 1:1 NC balloon at 20 atm, and expansion > 100% was reached using the 1:1 NC balloon at 30 atm. In the subgroup analysis, comparing low-calcified and high-calcified lesions, good expansion (MEI ≥ 80%) was reached using the 1:1 NC balloon at nominal pressure (10 atm) versus using 1:1 NC balloon at 30 atm, respectively. Significant vessel rupture was identified in all the vessels mainly upon post-dilatation with larger balloons, and 60% of the experiments (6 vessels, 3 in each calcium subgroup) presented rupture with the +1.0 mm NC balloon at 20 atm. CONCLUSION: When treating calcified lesions, good stent expansion was reached using smaller balloons at higher pressures without coronary injuries, whereas bigger balloons yielded unpredictable expansion even at lower pressures and demonstrated potential harmful damages to the vessels. As these findings could help physicians with appropriate planning of stent post-dilatation for calcified lesions, it will be important to clinically evaluate the recommended protocol.

Effects of Acute Intracranial Pressure Changes on Optic Nerve Head Morphology in Humans and Pig Model.

PURPOSE: The lamina cribrosa (LC) is a layer of fenestrated connective tissue tethered to the posterior sclera across the scleral canal in the optic nerve head (ONH). It is located at the interface of intracranial and intraocular compartments and is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) or Cerebrospinal fluid (CSF) pressure (CSFP) posteriorly. We hypothesize that the pressure difference across LC will determine LC position and meridional diameter of scleral canal (also called Bruch's membrane opening diameter; BMOD). METHODS: We enrolled 19 human subjects undergoing a medically necessary lumbar puncture (LP) to lower CSFP and 6 anesthetized pigs, whose ICP was increased in 5 mm Hg increments using a lumbar catheter. We imaged ONH using optical coherence tomography and measured IOP and CSFP/ICP at baseline and after each intervention. Radial tomographic ONH scans were analyzed by two independent graders using ImageJ, an open-source software. The following ONH morphological parameters were obtained: BMOD, anterior LC depth and retinal thickness. We modeled effects of acute CSFP/ICP changes on ONH morphological parameters using ANOVA (human study) and generalized linear model (pig study). RESULTS: For 19 human subjects, CSFP ranged from 5 to 42 mm Hg before LP and 2 to 19.4 mm Hg after LP. For the six pigs, baseline ICP ranged from 1.5 to 9 mm Hg and maximum stable ICP ranged from 18 to 40 mm Hg. Our models showed that acute CSFP/ICP changes had no significant effect on ONH morphological parameters in both humans and pigs. CONCLUSION: We conclude that ONH does not show measurable morphological changes in response to acute changes of CSFP/ICP. Proposed mechanisms include compensatory and opposing changes in IOP and CSFP/ICP and nonlinear or nonmonotonic effects of IOP and CSFP/ICP across LC.

Optimization of Freeze-FRESH Methodology for 3D Printing of Microporous Collagen Constructs.

Freeform reversible embedding of suspended hydrogels (FRESH) is a layer-by-layer extrusion-based technique to enable three-dimensional (3D) printing of soft tissue constructs by using a thermo-reversible gelatin support bath. Suboptimal resolution of extrusion-based printing limits its use for the creation of microscopic features in the 3D construct. These microscopic features (e.g., pore size) are known to have a profound effect on cell migration, cell-cell interaction, proliferation, and differentiation. In a recent study, FRESH-based 3D printing was combined with freeze-casting in the Freeze-FRESH (FF) method, which yielded alginate constructs with hierarchical porosity. However, use of the FF approach allowed little control of micropore size in the printed alginate constructs. Herein, the FF methodology was optimized for 3D printing of collagen constructs with greater control of microporosity. Modifications to the FF method entailed melting of the FRESH bath before freezing to allow more efficient heat transport, achieve greater control on microporosity, and permit polymerization of collagen molecules to enable 3D printing of stable microporous collagen constructs. The effects of different freezing temperatures on microporosity and physical properties of the 3D-printed collagen constructs were assessed. In addition, finite element (FE) models were generated to predict the mechanical properties of the microporous constructs. Further, the impact of different micropore sizes on cellular response was evaluated. Results showed that the microporosity of 3D-printed collagen constructs can be tailored by customizing the FF approach. Compressive modulus of microporous constructs was significantly lower than the non-porous control, and the FE model verified these findings. Constructs with larger micropore size were more stable and showed significantly greater cell infiltration and metabolic activity. Together, these results suggest that the FF method can be customized to guide the design of 3D-printed microporous collagen constructs.

Plasma D-Dimer Level Correlates with Age, Metastasis, Recurrence, Tumor-Node-Metastasis Classification (TNM), and Treatment of Non-Small-Cell Lung Cancer (NSCLC) Patients.

OBJECTIVE: This study is aimed at teasing out the correlation of plasma D-dimer (D-D) levels to age, metastasis, TNM stage (tumor-node-metastasis classification), and treatment in non-small-cell lung cancer (NSCLC) patients of different ages, to facilitate early diagnosis of hypercoagulable state, choose appropriate treatment, and use appropriate anticoagulants. Hence, thrombosis and complications caused by excessive anticoagulants can be prevented; thrombus or disseminated intravascular coagulation (DIC) and other complications in elderly patients with NSCLC can be reduced or avoided. By monitoring the level of plasma D-D in patients with NSCLC, recurrence and metastasis can be predicted in the early stage and the TNM stage can be evaluated. METHODS: A total of 670 patients with NSCLC were selected in Shanxi Bethune Hospital from March 2014 to October 2020 as the experimental group, and 950 healthy people were selected from the physical examination center of the same hospital as the control group. The data of patients with NSCLC diagnosed for the first time without any treatment were collected and grouped based on metastasis, TNM stage, treatment, and pathological type, and the correlation with plasma D-D level was analyzed. Plasma D-D levels were measured by immunoturbidimetry on an ACL TOP 700 Automatic Coagulation Analyzer. The patients were further divided into two groups according to different treatment methods, and the differences in plasma D-D levels between patients receiving chemotherapy and those receiving targeted therapy in different treatment cycles were analyzed. The correlation between D-D levels and age in healthy controls was analyzed. The difference in D-D levels between NSCLC patients and healthy controls of the same age was analyzed. RESULTS: All data of both the experimental group and the control group were normally distributed. The average age of the experimental group was 61.31 ± 6.23 (range: 36-92) years. The average age of the control group was 61.14 ± 11.12 (range: 35-85) years. There was no significant difference in gender between the experimental group and the control group (p > 0.05). The plasma D-D level of NSCLC patients was significantly higher than that of the healthy controls (p < 0.05). No significant difference in plasma D-D level was found between NSCLC patients of different genders, and the finding was similar between healthy controls of different genders (p > 0.05). Significant difference in the D-D level was found between the groups of 30-59 years and 60-69 years (p < 0.05), between groups of 60-69 years and 70-79 years (p < 0.05), and between 70-79 years and ≥80 years (p < 0.05). The plasma D-D level of patients ≤ 79 years old increased with age, but it decreased in those over 80 years old. According to Pearson correlation analysis, there was a positive correlation between the D-D level and the age of NSCLC patients under 79 years old (p < 0.05). The differences in D-D levels between the four age groups were statistically significant (p < 0.05), showing an upward trend of the D-D level in healthy controls with the increase of age. There were statistically significant differences in D-D levels between NSCLC patients and healthy controls of the matching age group (p < 0.05), suggesting that NSCLC patients had significantly higher D-D levels than healthy people of the same age group. The differences in D-D levels between NSCLC patients without metastasis, NSCLC patients with metastasis, and healthy people were statistically significant (p < 0.05). The patients with metastasis had the highest D-D level, and healthy people had the lowest D-D level. The difference in plasma D-D levels between patients of different TNM stages was statistically significant (p < 0.05). Patients with an advanced TNM stage tended to have higher D-D levels. The TNM stage and D-D level of NSCLC patients changed significantly before and after treatment. An earlier stage was related to a more obvious change in D-D levels after treatment with a statistically significant difference (p < 0.05). A more advanced stage was associated with a smaller change in the D-D level after treatment, with no statistically significant difference (p > 0.05). The plasma D-D levels before and after four cycles of chemotherapy or targeted therapy were higher than those of the healthy control group, and the differences were statistically significant (p < 0.05). The D-D level of patients after chemotherapy was significantly lower than that before chemotherapy (p < 0.05), but there was no significant difference before and after targeted therapy (p > 0.05). The D-D level after the first cycle of chemotherapy was higher than that before chemotherapy. The level of D-D after the third and fourth cycles was significantly lower than that before chemotherapy (p < 0.05). No significant difference was found between the D-D level before treatment and that after four cycles of chemotherapy (p > 0.05). CONCLUSION: It is suggested that coagulation test indexes should be included to evaluate the treatment regimen for NSCLC patients. Most patients with NSCLC are in a hypercoagulable state, which is related to age, tumor invasion and metastasis, recurrence, and treatment. Regular monitoring of plasma D-D levels can facilitate early diagnosis of a hypercoagulable state and timely and appropriate use of anticoagulants, to avoid or reduce complications such as venous thromboembolism in NSCLC patients and to prevent the risk of bleeding caused by excessive anticoagulants. Clinicians can choose the treatment with less harm and maximum benefit for NSCLC patients based on the plasma D-D level. When in a hypercoagulable state, the body's blood viscosity increases, making it more conducive to the growth and infiltration of tumor cells. Our study shows that the recurrence and metastasis of NSCLC are related to coagulation indexes, which provides a theoretical basis for the early diagnosis and treatment of recurrent and metastatic NSCLC.

Hemodynamic alternations following stent deployment and post-dilation in a heavily calcified coronary artery: In silico and ex-vivo approaches.

In this work, hemodynamic alterations in a patient-specific, heavily calcified coronary artery following stent deployment and post-dilations are quantified using in silico and ex-vivo approaches. Three-dimensional artery models were reconstructed from OCT images. Stent deployment and post-dilation with various inflation pressures were performed through both the finite element method (FEM) and ex vivo experiments. Results from FEM agreed very well with the ex-vivo measurements, interms of lumen areas, stent underexpansion, and strut malapposition. In addition, computational fluid dynamics (CFD) simulations were performed to delineate the hemodynamic alterations after stent deployment and post-dilations. A pressure time history at the inlet and a lumped parameter model (LPM) at the outlet were adopted to mimic the aortic pressure and the distal arterial tree, respectively. The pressure drop across the lesion, pertaining to the clinical measure of instantaneous wave-free flow ratio (iFR), was investigated. Results have shown that post-dilations are necessary for the lumen gain as well as the hemodynamic restoration towards hemostasis. Malapposed struts induced much higher shear rate, flow disturbances and lower time-averaged wall shear stress (TAWSS) around struts. Post-dilations mitigated the strut malapposition, and thus the shear rate. Moreover, stenting induced larger area of low TAWSS (<0.4 Pa) and lager volume of high shear rate (>2000 s-1), indicating higher risks of in-stent restenosis (ISR) and stent thrombosis (ST), respectively. Oscillatory shear index (OSI) and relative residence time (RRT) indicated the wall regions more prone to ISR are located near the malapposed stent struts.

Mechanical performances of balloon post-dilation for improving stent expansion in calcified coronary artery: Computational and experimental investigations.

Stent deployment in a calcified coronary artery is often associated with suboptimal outcomes such as stent underexpansion and malapposition. Post-dilation after stent deployment is commonly used for optimal stent implantation. There is no guideline for choosing the post-dilation balloon diameter and inflation pressure. In this work, ex-vivo/in-silico experiments were performed to investigate the efficacy of post-dilation balloon diameter and inflation pressure in improving the stent expansion in a calcified lesion. Post-dilations with three balloon diameters (3 mm, 3.5 mm, and 4 mm) were performed. For each balloon diameter, three inflation pressures (10 atm, 20 atm, and 30 atm) were sequentially applied. In ex-vivo experiments, optical coherence tomography images were acquired during the stenting procedure, i.e., pre- and post-deployment of 3 mm diameter stent, as well as after each post-dilation. The results from in-silico experiments were compared with ex-vivo experiments in terms of lumen area. In addition, stretch ratio analysis was developed to predict the stent-induced lumen area, along with the strain analysis and the in-silico experiments. Results have shown that target lumen area could be achieved with an oversized nominal balloon diameter of +0.5 mm (i.e., 0.5 mm greater than reference lumen diameter) at an inflation pressure of 20 atm. After each post-dilation, fibrotic tissue demonstrated a larger strain, contributing to improved lumen gain. However, minimal changes were observed in calcification. Moreover, a strong correlation (R2 = 0.95) between the stretch ratio of fibrotic tissue and lumen area after each post-dilation was observed. This indicated that the morphology of the fibrotic tissue could be a potential marker to predict the lumen gain. The detailed mechanistic quantifications of a single lesion cannot be generalized to all clinical cases. However, this work could be used to provide a fundamental understanding of the post-dilations, to develop experimental protocols for producing generalized guidelines, and to exploit their potential for optimal pre- and post-stent strategies.

Design and Evaluation of an In Vitro Mild Traumatic Brain Injury Modeling System Using 3D Printed Mini Impact Device on the 3D Cultured Human iPSC Derived Neural Progenitor Cells.

Despite significant progress in understanding the disease mechanism of traumatic brain injury (TBI), promising preclinical therapeutics have seldom been translated into successful clinical outcomes, partially because the model animals have physiological and functional differences in the central nervous system (CNS) compared to humans. Human relevant models are thus urgently required. Here, an in vitro mild TBI (mTBI) modeling system is reported based on 3D cultured human induced pluripotent stem cells (iPSC) derived neural progenitor cells (iPSC-NPCs) to evaluate consequences of single and repetitive mTBI using a 3D printed mini weight-drop impact device. Computational simulation is performed to understand the single/cumulative effects of weight-drop impact on the NPC differentiated neurospheres. Experimental results reveal that neurospheres show reactive astrogliosis and glial scar formation after repetitive (10 hits) mild impacts, while no astrocyte activation is found after one or two mild impacts. A 3D co-culture model of human microglia cells with neurospheres is further developed. It is found that astrocyte response is promoted even after two mild impacts, possibly caused by the chronic neuroinflammation after microglia activation. The in vitro mTBI modeling system recapitulates several hallmarks of the brain impact injury and might serve as a good platform for future drug screening.