Volume Fraction Of Tissue Research Articles

Modeling the biomechanics of the lamina cribrosa microstructure in the human eye

Glaucoma is among the leading causes of blindness worldwide that is characterized by irreversible damage to the retinal ganglion cell axons in the lamina cribrosa (LC) region of the optic nerve head (ONH), most often associated with elevated intraocular pressure (IOP). The LC is a porous, connective tissue structure that provides mechanical support to the axons as they exit the eye and the biomechanics of the LC microstructure likely play a crucial role in protecting the axons passing through it. There is a limited knowledge of the IOP-driven biomechanics of the LC microstructure, primarily due to its small size and the difficulty with imaging the LC both in vitro and in vivo. We present finite element (FE) models of three human eye posterior poles that include the LC microstructure and interspersed neural tissues (NT) composed of retinal axons that are constructed directly from segmented, binary images of the LC. These models were used to estimate the stresses and strains in the LC and NT for an acute IOP elevation from 0 to 45 mmHg and compared with identical models except that the LC was represented as a homogenized continuum material with either homogeneous isotropic neo-Hookean properties or heterogeneous properties derived from local connective tissue volume fraction (CTVF) and predominant LC beam orientation. Stresses and strains in the LC and NT microstructure were investigated, and results were compared against those from the models wherein the LC was represented as a homogenized continuum. The regionalized volumetric average stresses and strains showed that the microstructural model yielded similar patterns to our prior approach using an LC continuum representation with mapped LC CTVF/anisotropy, but the microstructural modeling approach allows analysis of the stresses and strains in the LC and NT separately. As expected, the LC beams carried most of the IOP load in the microstructural models but exhibited less strain, while the encapsulated NT exhibited lower stresses and much higher strains. Results also revealed that the continuum models underestimate the maximum strains in the LC beams and NT by a factor of 2-3. Microstructural modeling should provide greater insight into the biomechanical factors driving damage to the axons (NT) and LC connective tissue remodeling that occur in glaucoma. The methods presented are ideal for modeling any structure with a complex microstructure composed of different materials, such as trabecular bone, lung, and tissue engineering scaffolds such as decellularized LC. Matlab code for mesh generation from a segmented image stack of the microstructure is included as Supplemental Material. Statement of significanceGlaucoma is among the leading causes of blindness worldwide that is characterized by axon damage in the lamina cribrosa (LC) region of the eye. We present a new approach for finite element modeling the entire eye-specific 3D LC microstructure and the interspersed neural tissues, incorporated into an eye-specific posterior eye model that provides appropriate boundary and loading conditions. Results are presented for three human donor eyes, showing that prior modeling approaches underestimate the stresses and strains in the laminar microstructure. We constructed models from image stacks of the segmented microstructure (Matlab code included) using an approach that is ideal for modeling any structure with a complex microstructure composed of different materials, such as trabecular bone, lung, and tissue engineering scaffolds.

Heterogeneity and Development of Fine Astrocyte Morphology Captured by Diffraction-Limited Microscopy.

The fine processes of single astrocytes can contact many thousands of synapses whose function they can modulate through bi-directional signaling. The spatial arrangement of astrocytic processes and neuronal structures is relevant for such interactions and for the support of neuronal signaling by astrocytes. At the same time, the geometry of perisynaptic astrocyte processes is variable and dynamically regulated. Studying these fine astrocyte processes represents a technical challenge, because many of them cannot be fully resolved by diffraction-limited microscopy. Therefore, we have established two indirect parameters of astrocyte morphology, which, while not fully resolving local geometry by design, provide statistical measures of astrocyte morphology: the fraction of tissue volume that astrocytes occupy and the density of resolvable astrocytic processes. Both are straightforward to obtain using widely available microscopy techniques. We here present the approach and demonstrate its robustness across various experimental conditions using mainly two-photon excitation fluorescence microscopy in acute slices and in vivo as well as modeling. Using these indirect measures allowed us to analyze the morphology of relatively large populations of astrocytes. Doing so we captured the heterogeneity of astrocytes within and between the layers of the hippocampal CA1 region and the developmental profile of astrocyte morphology. This demonstrates that volume fraction (VF) and segment density are useful parameters for describing the structure of astrocytes. They are also suitable for online monitoring of astrocyte morphology with widely available microscopy techniques.

Can quantitative analysis of multi-parametric MRI independently predict failure of focal salvage HIFU therapy in men with radio-recurrent prostate cancer?

ObjectivesFocal salvage HIFU is a feasible therapeutic option in some men who have recurrence after primary radiotherapy for prostate cancer. We aimed to determine if multi-parametric quantitative parameters, in addition to clinical factors, might have a role in independently predicting focal salvage HIFU outcomes. MethodsA retrospective registry analysis included 150 consecutive men who underwent focal salvage HIFU (Sonablate500) (2006-2015); 89 had mpMRI available. Metastatic disease was excluded by nodal assessment on pelvic MRI, a radioisotope bone-scan and/or choline or FDG PET/CT scan. All men had mpMRI and either transperineal template prostate mapping biopsy or targeted and systematic TRUS-biopsy. mpMRI included T2‐weighted, diffusion‐weighted and dynamic contrast‐enhancement. Pre-HIFU quantitative mpMRI data was obtained using Horos DICOM Viewer v3.3.5 for general MRI parameters and IB DCE v2.0 plug-in. Progression-free survival (PFS) was defined by biochemical failure and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer‐specific death. Potential predictors of PFS were analyzed by univariable and multivariable Cox-regression. ResultsMedian age at focal salvage HIFU was 71 years (interquartile range [IQR] 65–74.5) and median PSA pre-focal salvage treatment was 5.8ng/ml (3.8-8). Median follow-up was 35 months (23-47) and median time to failure was 15 months (7.8–24.3). D-Amico low, intermediate and high-risk disease was present in 1% (1/89), 40% (36/89) and 43% (38/89) prior to focal salvage HIFU (16% missing data). 56% (50/89) failed by the composite outcome. A total of 22 factors were evaluated on univariable and 8 factors on multivariable analysis. The following quantitative parameters were included: Ktrans, Kep, Ve, Vp, IS, rTTP and TTP. On univariable analysis, PSA, prostate volume at time of radiotherapy failure and Ve (median) value were predictors for failure. Ve represents extracellular fraction of the whole tissue volume. On multivariable analysis, only Ve (median) value remained as an independent predictor. ConclusionsOne pharmacokinetic quantitative parameter based on DCE sequences seems to independently predict failure following focal salvage HIFU for radio-recurrent prostate cancer. This likely relates to the tumor microenvironment producing heat-sinks which counter the heating effect of HIFU. Further validation in larger datasets and evaluating mechanisms to reduce heat-sinks are required.

Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction.

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-β, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.

Effects of 16months of high intensity resistance training on thigh muscle fat infiltration in elderly men with osteosarcopenia.

Osteosarcopenia is characterized by a progressive decline in muscle function and bone strength and associated with muscle fat accumulation. This study aimed to determine the effect of long-term high intensity resistance training (HIRT) on thigh muscle fat infiltration in older men with osteosarcopenia. Forty-three community-dwelling men (72years and older) were randomly assigned to either an exercise group (EG, n = 21) or an inactive control group (CG, n = 22). EG participants performed a supervised single-set exercise training with high effort two times per week. Participants of both groups were individually provided with dietary protein to reach a cumulative intake of 1.5-1.6g/kg/day or 1.2-1.3g/kg/day (EG/CG), respectively, and Up to 10,000IE/week of Vitamin-D were supplemented in participants with 25 OH Vitamin-D 3 levels below 100nmol/l. Magnetic resonance (MR) imaging was performed to determine muscle and adipose tissue volume and fat fraction of the thigh. At baseline, there were no significant differences between the two groups. After 16month,, there were significant training effects of 15% (p = 0.004) on intermuscular adipose tissue (IMAT) volume, which increased in the CG (p = 0.012) and was stable in the EG. In parallel, fat fraction within the deep fascia of the thigh (Baseline, EG: 18.2 vs CG: 15.5, p = 0.16) significantly differed between the groups (Changes, EG: 0.77% vs. CG: 7.7%, p = 0.009). The study confirms the role of fat infiltration of the muscles as an advanced imaging marker in osteosarcopenia and the favorable effects of HIRT on adipose tissue volume of the thigh, in men with osteosarcopenia.

Prediction of the Inelastic Behaviour of Radius Segments: Damage-based Nonlinear Micro Finite Element Simulation vs Pistoia Criterion

The Pistoia criterion (PC) is widely used to estimate the failure load of distal radius segments based on linear micro Finite Element (μFE) analyses. The advantage of the PC is that a simple strain-threshold and a tissue volume fraction can be used to predict failure properties. In this study, the PC is compared to materially nonlinear μFE analyses, where the bone tissue is modelled as an elastic, damageable material. The goal was to investigate for which outcomes the PC is sufficient and when a nonlinear (NL) simulation is required. Three types of simulation results were compared: (1) prediction of the failure load, (2) load sharing of cortical and trabecular regions, and (3) distribution of local damaged/overstrained tissue at the maximum sustainable load. The failure load obtained experimentally could be predicted well with both the PC and the NL simulations using linear regression. Although the PC strongly overestimated the failure load, it was sufficient to predict adequately normalized apparent results. An optimised PC (oPC) was proposed which uses experimental data to calibrate the individual volume of overstrained tissue. The main areas of local over-straining predicted by the oPC were the same as estimated by the NL simulation, although the oPC predicted more diffuse regions. However, the oPC relied on an individual calibration requiring the experimental failure load while the NL simulation required no a priori knowledge of the experimental failure load.

Resveratrol Inhibits Myocardial Apoptosis by Regulating the Protein Kinase R-like Endoplasmic Reticulum Kinase Endoplasmic Reticulum Stress Pathway and Improves Myocardial Remodeling and Cardiac Function after Myocardial Infarction

To analyze the effect of resveratrol on myocardial remodeling and cardiac function after myocardial infarction by inhibiting myocardial cell apoptosis through regulating silent information regulator 1/protein kinase R-like endoplasmic reticulum kinase pathway. 32 healthy male sprague dawley rats were divided into control group (without any treatment), model group (ligation of left anterior descending branch to establish a model), sham operation group (ligation of left anterior descending branch without ligation) and resveratrol group (ligation of left anterior descending branch+resveratrol 8 mg/kg/d), 8 rats each. The changes of cardiac function, myocardial remodeling, myocardial apoptosis and silent information regulator 1/protein kinase R-like endoplasmic reticulum kinase pathway related proteins were observed 4 w after modeling. Left ventricular end-diastolic diameter and left ventricular end-systolic dimension levels in the model group were significantly higher than those in the control group, left ventricular ejection fraction and left ventricular short axis shortening rate levels were significantly lower than those in the control group (p<0.01), left ventricular end-diastolic diameter and left ventricular end-systolic dimension levels in the resveratrol group were significantly lower than those in the model group and left ventricular ejection fraction and left ventricular short axis shortening rate levels were significantly higher than those in the model group (p<0.01). In the model group, the myocardial cells were arranged in a disordered manner and fibrogenic hyperplasia occurred, while the pathological changes of the myocardial cells in the resveratrol group were reduced compared with the model group. The collagen volume fraction of myocardial tissue in the model group was significantly higher than that in the control group (p<0.05) and the collagen volume fraction in the resveratrol group was significantly lower than that in the model group (p<0.05). The apoptosis rate of myocardial cells in the model group was significantly higher than that in the control group (p<0.01) and the apoptosis rate of myocardial cells in the resveratrol group was significantly lower than that in the model group (p<0.01). The expression levels of Phosphate-protein kinase R like endoplasmic reticulum kinase, Phosphate eukaryotic initiation factor 2 and Activating transcription factor 4 in the model group were significantly higher than those of the control group and the expression levels of Silent Information Regulator 1 were significantly lower than those of the control group (p<0.01). The expression levels of Phosphate-protein kinase R like endoplasmic reticulum kinase, Phosphate eukaryotic initiation factor 2 and Activating transcription factor 4 in the resveratrol group were significantly lower than those of the model group and the expression levels of silent information regulator 1 were significantly higher than those of the model group (p<0.01). Resveratrol can reduce apoptosis of myocardial cells after myocardial infarction by regulating the silent information regulator 1/protein kinase R-like endoplasmic reticulum kinase pathway endoplasmic reticulum stress pathway and improve myocardial remodeling and cardiac function in rats, providing a new target for clinical treatment of myocardial infarction.

Modeling the Biomechanics of the Lamina Cribrosa Microstructure in the Human Eye

Glaucoma is among the leading causes of blindness worldwide that is characterized by irreversible damage to the retinal ganglion cell axons in the lamina cribrosa (LC) region of the optic nerve head (ONH), most often associated with elevated intraocular pressure (IOP). The LC is a porous, connective tissue structure that provides mechanical support to the axons as they exit the eye and the biomechanics of the LC microstructure likely play a crucial role in protecting the axons passing through it. There is a limited knowledge of the IOP-driven biomechanics of the LC microstructure, primarily due to its small size and the difficulty with imaging the LC both in vitro and in vivo. We present finite element (FE) models of three human eye posterior poles that include the LC microstructure and interspersed neural tissues (NT) composed of retinal axons that are constructed directly from segmented, binary images of the LC. These models were used to estimate the stresses and strains in the LC and NT for an acute IOP elevation from 0 to 45 mmHg and compared with identical models except that the LC was represented as a homogenized continuum material with either homogeneous isotropic neo-Hookean properties or heterogeneous properties derived from local connective tissue volume fraction (CTVF) and predominant LC beam orientation. Stresses and strains in the LC and NT microstructure were investigated, and results were compared against those from the models wherein the LC was represented as a homogenized continuum. The regionalized volumetric average stresses and strains showed that the microstructural model yielded similar patterns to our prior approach using an LC continuum representation with mapped LC CTVF/anisotropy, but the microstructural modeling approach allows analysis of the stresses and strains in the LC and NT separately. As expected, the LC beams carried most of the IOP load in the microstructural models but exhibited less strain, while the encapsulated NT exhibited lower stresses and much higher strains. Results also revealed that the continuum models underestimate the maximum strains in the LC beams and NT. Microstructural modeling should provide greater insight into the biomechanical factors driving damage to the axons (NT) and LC connective tissue remodeling that occur in glaucoma. The methods presented are ideal for modeling any structure with a complex microstructure composed of different materials, such as trabecular bone, lung, and tissue engineering scaffolds such as decellularized LC. Matlab code for mesh generation from a segmented image stack of the microstructure is included as Supplemental Material.

Preventive Moderate Continuous Running-Exercise Conditioning Improves the Healing of Non-Critical Size Bone Defects in Male Wistar Rats: A Pilot Study Using µCT.

Although physical exercise has unquestionable benefits on bone health, its effects on bone healing have been poorly investigated. This study evaluated the effects of preemptive moderate continuous running on the healing of non-critical sized bone defects in rats by µCT. We hypothesized that a preemptive running exercise would quicken bone healing. Twenty 5-week-old, male, Wistar rats were randomly allocated to one of the following groups (n = 10): sedentary control (SED) or continuous running (EX, 45 min/d, 5 d/week at moderate speed, for 8 consecutive weeks). A 2 mm diameter bone defect was then performed in the right tibia and femur. No exercise was performed during a 4 week-convalescence. Healing-tissue trabecular microarchitectural parameters were assessed once a week for 4 weeks using µCT and plasma bone turnover markers measured at the end of the study protocol (time point T12). At T12, bone volume fraction (BV/TV; BV: bone volume, TV: tissue volume) of the healing tissue in tibiae and femurs from EX rats was higher compared to that in SED rats (p = 0.001). BV/TV in EX rats was also higher in tibiae than in femurs (p < 0.01). The bone mineral density of the healing tissue in femurs from EX rats was higher compared to that in femurs from SED rats (p < 0.03). N-terminal telopeptide of collagen type I in EX rats was decreased compared to SED rats (p < 0.05), while no differences were observed for alkaline phosphatase and parathyroid hormone. The study provides evidence that preemptive moderate continuous running improves the healing of non-critical sized bone defects in male Wistar rats.

Xanthine oxidase inhibitor allopurinol improves atrial electrical remodeling in diabetic rats by inhibiting CaMKII/NCX signaling

AimsAtrial fibrillation (AF) is a common arrhythmia which is associated with higher risk of stroke, heart failure and all-cause mortality. Abnormal Ca2+ handling in diabetes mellitus (DM) can cause delayed depolarization involved with increased NCX activity. Complicated mechanisms are involved in atrial remodeling, of which CaMKII may be a key node signal. Therefore, we intend to explore whether CaMKII activation induces atrial electrical remodeling by regulating NCX expression in this study. Main methodsAdult male SD rats were used to establish a diabetic rat model, divided into three groups: the control group, DM group and allopurinol group. Hemodynamic and ECG indicators were recorded, after which electrophysiological studies were conducted. The protein expression of CaMKII, p-CaMKII, XO, MnSOD and NCX was measured by Western blot and immunohistochemistry. H&E and Masson staining were applied for observing myocardial fibrosis. HL-1 cells were cultured for the measurement of ROS generation. Key findingsThe arrangement of atrial myocytes was disordered and the collagen volume fraction of the atrium tissue was elevated in the DM group compared with the control group, and improved by allopurinol. Higher incidence of inducible AF, reduced conduction velocity and higher conduction inhomogeneity were observed in diabetic rats. These electrophysiological abnormalities were accompanied by higher oxidative stress and protein expression of p-CaMKII and NCX. Allopurinol prevented the development of these abnormal changes. SignificanceAllopurinol can improve atrial electrical remodeling by inhibiting CaMKII activity and protein expression of NCX. These data indicate xanthine oxidase inhibition can reduce oxidative stress and ameliorate atrial electrical remodeling.

Effects of Propranolol on Bone, White Adipose Tissue, and Bone Marrow Adipose Tissue in Mice Housed at Room Temperature or Thermoneutral Temperature.

Growing female mice housed at room temperature (22°C) weigh the same but differ in body composition compared to mice housed at thermoneutrality (32°C). Specifically, mice housed at room temperature have lower levels of white adipose tissue (WAT). Additionally, bone marrow adipose tissue (bMAT) and cancellous bone volume fraction in distal femur metaphysis are lower in room temperature-housed mice. The metabolic changes induced by sub-thermoneutral housing are associated with lower leptin levels in serum and higher levels of Ucp1 gene expression in brown adipose tissue. Although the precise mechanisms mediating adaptation to sub-thermoneutral temperature stress remain to be elucidated, there is evidence that increased sympathetic nervous system activity acting via β-adrenergic receptors plays an important role. We therefore evaluated the effect of the non-specific β-blocker propranolol (primarily β1 and β2 antagonist) on body composition, femur microarchitecture, and bMAT in growing female C57BL/6 mice housed at either room temperature or thermoneutral temperature. As anticipated, cancellous bone volume fraction, WAT and bMAT were lower in mice housed at room temperature. Propranolol had small but significant effects on bone microarchitecture (increased trabecular number and decreased trabecular spacing), but did not attenuate premature bone loss induced by room temperature housing. In contrast, propranolol treatment prevented housing temperature-associated differences in WAT and bMAT. To gain additional insight, we evaluated a panel of genes in tibia, using an adipogenesis PCR array. Housing temperature and treatment with propranolol had exclusive as well as shared effects on gene expression. Of particular interest was the finding that room temperature housing reduced, whereas propranolol increased, expression of the gene for acetyl-CoA carboxylase (Acacb), the rate-limiting step for fatty acid synthesis and a key regulator of β-oxidation. Taken together, these findings provide evidence that increased activation of β1 and/or β2 receptors contributes to reduced bMAT by regulating adipocyte metabolism, but that this pathway is unlikely to be responsible for premature cancellous bone loss in room temperature-housed mice.

Morphometric analysis of the efficiency of bone defect substitution with fabric equivalents of bone tissue on the basis of multipotent mesenchymal stromal cells in dentistry

Bone tissue is a rather dynamic tissue that has the ability to recover from injury without scarring. The differentiation of multipotent mesenchymal stromal cells (MМSC) into osteoblasts plays a crucial role in bone regeneration and remodeling. MМSC derived from adipose tissue are considered to be an adequate source for bone tissue engineering because of their capacity for osteogenic differentiation. The effectiveness of osteogenic differentiation of different human MMSC has been demonstrated in the settlement of biocompatible polymer matrices. It was found that MMSC derived from adipose tissue showed a high efficiency of differentiation into osteoblasts. These cells are typically transplanted into three-dimensional porous scaffolds that provide the necessary extracellular environment that contains physical and chemical signals for tissue development and regeneration.The aim of the study: to analyze the results of morphometric studies to determine the effectiveness of the use of tissue equivalents of bone tissue based on multipotent mesenchymal stromal fat cells in dental practice.Material and methods. The experiment was conducted on the Wistar line rats, weighing 200–250 grams, which were divided into VI groups. A bone defect model was formed in the parietal section of the skull of rats. The formed defect implanted the harvested material. Morphometric studies were performed in accordance with the principles of systematic quantitative analysis (Avtandilov GG, 2002). To do this, we used the automatic image processing system „Videotest-Morpho 3.0” (Russia), which contains a binocular research microscope „Biolam”, an analog-to-digital converter, a computer with a high-resolution color printer and software. In the regenerate, the volume particles (Vp, μm3/μm3) of connective tissue, vessels and bone beams, as well as the numerical density of cellular elements (1/μm3) were determined using morphometric methods. The obtained results are processed statistically.Results. After 3 months of observations, clear quantitative positive changes in the structure of the regenerates were observed in the skull defect area of the experimental animals. Thus, in animals of groups IV and VI the volume fraction of bone beams in regenerates increased to 43,90 ± 1,68%, p1 — p2 &lt;0,01 and to 45,10 ± 1,74%, p1, p2, p4 &lt;0,01, respectively, was equal to that in control rats. A decrease in the connective tissue volume fraction was observed in the bone tissue regenerators of the experimental rats, with the minimum values of this parameter in the IV and VI experimental groups: 12,45 ± 2,20% and 10,00 ± 2,15%, p1&lt;0,05, p4&lt; 0,01, respectively, p&gt;0.05. On the 90th day of observation there was a significant decrease in the volume fraction of vessels, which in the IV and VI groups with values 7,44 ± 0.82% and 6,15 ± 0,90%, p2&lt;0.01, respectively, was equal to the data in rats of the control group, p&gt;0,05. In animals of group VI, where the combination of MMSC-AT +PRP + Kolapan was used to repair the bone defect, the maximum increase was determined: the number of osteoblasts and osteocytes, the number of osteoclasts against the background of reduction of fibroblasts and fibrocytes. The normalization of cellular element cell density in group IV rats, where bone defect replacement occurred due to the combination of MMSC-AT +PRP, was quite significant. At the same time, in the animals of this group the number of osteoclasts, р1&lt;0,05 and fibroblasts and fibrocytes was equal to the data in intact animals of the first group, p&gt;0.05, with 1,2 times smaller number of osteoblasts and osteocytes, р&gt;0,05 р1 — р2&gt;0,01.Conclusions. Therefore, by the results of morphometric studies on the model defects of the skull bone of rats proved the suitability of the investigated implants for use, especially with the combination of MMSC-AT +PRP and MMSC-AT +PRP + Kolapan, which provided complete closure of the defect in 90 days.

Small airways pathology in idiopathic pulmonary fibrosis: a retrospective cohort study

The observation that patients with idiopathic pulmonary fibrosis (IPF) can have higher than normal expiratory flow rates at low lung volumes led to the conclusion that the airways are spared in IPF. This study aimed to re-examine the hypothesis that airways are spared in IPF using a multiresolution imaging protocol that combines multidetector CT (MDCT), with micro-CT and histology. This was a retrospective cohort study comparing explanted lungs from patients with severe IPF treated by lung transplantation with a cohort of unused donor (control) lungs. The donor control lungs had no known lung disease, comorbidities, or structural lung injury, and were deemed appropriate for transplantation on review of the clinical files. The diagnosis of IPF in the lungs from patients was established by a multidisciplinary consensus committee according to existing guidelines, and was confirmed by video-assisted thoracic surgical biopsy or by pathological examination of the contralateral lung. The control and IPF groups were matched for age, sex, height, and bodyweight. Samples of lung tissue were compared using the multiresolution imaging approach: a cascade of clinical MDCT, micro-CT, and histological imaging. We did two experiments: in experiment 1, all the lungs were randomly sampled; in experiment 2, samples were selected from regions of minimal and established fibrosis. The patients and donors were recruited from the Katholieke Universiteit Leuven (Leuven, Belgium) and the University of Pennsylvania Hospital (Philadelphia, PA, USA). The study took place at the Katholieke Universiteit Leuven, and the University of British Columbia (Vancouver, BC, Canada). Between Oct 5, 2009, and July 22, 2016, explanted lungs from patients with severe IPF (n=11), were compared with a cohort of unused donor (control) lungs (n=10), providing 240 samples of lung tissue for comparison using the multiresolution imaging approach. The MDCT specimen scans show that the number of visible airways located between the ninth generation (control 69 [SD 22] versus patients with IPF 105 [33], p=0·0023) and 14th generation (control 9 [6] versus patients with IPF 49 [28], p<0·0001) of airway branching are increased in patients with IPF, which we show by micro-CT is due to thickening of their walls and distortion of their lumens. The micro-CT analysis showed that compared with healthy (control) lung anatomy (mean 5·6 terminal bronchioles per mL [SD 1·6]), minimal fibrosis in IPF tissue was associated with a 57% loss of the terminal bronchioles (mean 2·4 terminal bronchioles per mL [SD 1·0]; p<0·0001), the appearance of fibroblastic foci, and infiltration of the tissue by inflammatory immune cells capable of forming lymphoid follicles. Established fibrosis in IPF tissue had a similar reduction (66%) in the number of terminal bronchioles (mean 1·9 terminal bronchioles per mL [SD 1·4]; p<0·0001) and was dominated by increased airspace size, Ashcroft fibrosis score, and volume fractions of tissue and collagen. Small airways disease is a feature of IPF, with significant loss of terminal bronchioles occuring within regions of minimal fibrosis. On the basis of these findings, we postulate that the small airways could become a potential therapeutic target in IPF. Katholieke Universiteit Leuven, US National Institutes of Health, BC Lung Association, and Genentech.

Mechanical behavior and microstructure evolution of TC4 alloy during high temperature plastic deformation

In this paper, the mechanical behaviour and microstructure evolution of TC4 titanium alloy during high temperature plastic deformation are studied. The compression experiment was carried out on the Gleeble-3800 thermal simulator at the deformation temperature ranging from 900℃~1100℃ and at the strain rate of 0.1/s~10/s. The experimental results show that the flow softening mechanism of TC4 titanium alloy is dynamic recrystallization under condition of high temperature deformation. As the deformation temperature increases, the volume fraction and size of the β-transformed tissue become larger, and more acicular martensite appears in the β-transformed tissue. With the increase of strain rate, the grain size is reduced. Moreover, under the condition of high-temperature deformation, TC4 titanium alloy has obvious discontinuous yield phenomenon, and the higher the deformation temperature is, the more obvious the discontinuous yield phenomenon is. At low strain rate, TC4 titanium alloy has a slight strain hardening in a small strain rage, then it exhibits the characteristic of continuous softening flow, and it eventually tends to steady state. At high strain rates, TC4 titanium alloy exhibits wave yielding phenomenon.

Ex vivo cardiovascular\xa0magnetic resonance diffusion weighted imaging in congenital heart disease, an insight into the microstructures of tetralogy of Fallot, biventricular and univentricular systemic right ventricle

PurposeCommon types of congenital heart disease exhibit a variety of structural and functional variations which may be accompanied by changes in the myocardial microstructure. We aimed to compare myocardial architecture from magnetic resonance diffusion tensor imaging (DTI) in preserved pathology specimens.Materials and methodsPathology specimens (n = 24) formalin-fixed for 40.8 ± 7.9 years comprised tetralogy of Fallot (TOF, n = 10), dextro-transposition of great arteries (D-TGA, n = 8) five with ventricular septal defect (VSD), systemic right ventricle (n = 4), situs inversus totalis (SIT, n = 1) and levo-TGA (L-TGA, n = 1). Specimens were imaged using a custom spin-echo sequence and segmented automatically according to tissue volume fraction. In each specimen T1, T2, fractional anisotropy, mean diffusivity, helix angle (HA) and sheet angle (E2A) were quantified. Pathologies were compared according to their HA gradient, HA asymmetry and E2A mean value in each myocardial segment (anterior, posterior, septal and lateral walls).ResultsTOF and D-TGA with VSD had decreased helix angle gradient by − 0.34°/% and remained symmetric in the septum in comparison to D-TGA without VSD. Helix angle range was decreased by 45°. It was associated with a decreased HA gradient in the right ventricular (RV) wall, i.e. predominant circumferential myocytes. The sheet angle in the septum of TOF was opposing those of the left ventricular (LV) free wall. Univentricular systemic RV had the lowest HA gradient (− 0.43°/%) and the highest HA asymmetry (75%). HA in SIT was linear, asymmetric, and reversed with a sign change at about 70% of the depth at mid-ventricle. In L-TGA with VSD, HA was asymmetric (90%) and its gradients were decreased in the septum, anterior and lateral wall.ConclusionThe organization of the myocytes as determined by DTI differs between TOF, D-TGA, L-TGA, systemic RV and SIT specimens. These differences in cardiac structure may further enlighten our understanding of cardiac function in these diverse congenital heart diseases.

Influence of Ibuprofen on Bone Healing After Colles' Fracture: A Randomized Controlled Clinical Trial.

Non-steroidal anti-inflammatory drugs (NSAIDs) may delay bone healing. [Therefore, it is important to establish whether NSAID preparations delay bone healing and what correlations, if any, exist between different bone studies-DEXA-scanning, bone markers, roentgenology controls, and histological examination of newly formed bone]. The purpose of this prospective controlled study was to investigate whether ibuprofen affects bone mineral density, turnover biomarkers, and histomorphometric characteristics of the callus after a Colles' fracture. This study was a single-center, triple-blinded, randomized clinical trial. Ninety-five patients (80 females) with displaced Colles' fracture, median age 65 (range 40-85) years were included in the study and operated on by external fixation from June 2012 through to June 2015. Eighty-nine patients received interventional medicine and 83 completed the 1-year follow-up. The 7-day ibuprofen group received 600 mg of ibuprofen three times a day (N = 29), the 3-day ibuprofen group received ibuprofen for 3 days (N = 30) and a placebo for the following 4 days, and finally, the placebo group received a placebo for 7 days (N = 30). The primary outcome was the difference in bone mineral density between the ultra-distal region of the injured and non-injured radius at 3 months after surgery. The histomorphometric outcomes included the assessment of callus tissue volume and surface fractions at 6 weeks postoperatively. The biomarkers Osteocalcin and CrossLaps were measured at baseline, 1 week, 2 weeks, 6 weeks, 3 months, and 1 year. We included the results of the dropped-out patients in the intention to treat analysis. There was no difference between treatment groups in bone mineral density, histomorphometric estimations, and changes in bone biomarkers. These findings may offer an indication of ibuprofen as a bone-safe analgesic treatment in an acute fracture-phase. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:545-554, 2020.

Dynamic single-slice CT estimates whole-lung dual-energy CT variables in pigs with and without experimental lung injury

BackgroundDynamic single-slice CT (dCT) is increasingly used to examine the intra-tidal, physiological variation in aeration and lung density in experimental lung injury. The ability of dCT to predict whole-lung values is unclear, especially for dual-energy CT (DECT) variables. Additionally, the effect of inspiration-related lung movement on CT variables has not yet been quantified.MethodsEight domestic pigs were studied under general anaesthesia, including four following saline-lavage surfactant depletion (lung injury model). DECT, dCT and whole-lung images were collected at 12 ventilatory settings. Whole-lung single energy scans images were collected during expiratory and inspiratory apnoeas at positive end-expiratory pressures from 0 to 20 cmH2O. Means and distributions of CT variables were calculated for both dCT and whole-lung images. The cranio-caudal displacement of the anatomical slice was measured from whole-lung images.ResultsMean CT density and volume fractions of soft tissue, gas, iodinated blood, atelectasis, poor aeration, normal aeration and overdistension correlated between dCT and the whole lung (r2 0.75–0.94) with agreement between CT density distributions (r 0.89–0.97). Inspiration increased the matching between dCT and whole-lung values and was associated with a movement of 32% (SD 15%) of the imaged slice out of the scanner field-of-view. This effect introduced an artefactual increase in dCT mean CT density during inspiration, opposite to that caused by the underlying physiology.ConclusionsOverall, dCT closely approximates whole-lung aeration and density. This approximation is improved by inspiration where a decrease in CT density and atelectasis can be interpreted as physiological rather than artefactual.

Experimental Investigation of the Relief Time for Fiberglass/Epoxy Composites with Volume Fraction 30% and 40%

This paper deals with an experimental study of a relaxation behaviour of fibreglass/epoxy composite material subjected to tensile stress. The small tensile testing machine including the heating chamber with the temperature controller is designed and manufactured to perform the stress relief testing at different operating conditions. The influence of the operating temperature onto both the relief time and the number of the loading cycles is considered. The test specimens having a different number of layers of fibreglass tissues are prepared in the laboratory. The effect of the fiberglass tissue volume fraction on the relief behaviour of the fibreglass/epoxy composite is investigated. The constant of the relief time is evaluated for various operating temperature. The obtained results showed that the relief time and the number of relaxation cycles are highly increased by increasing the fibreglass layers. The total number of relief cycles was increased by about 34% when increasing the volume fraction of the fibreglass tissue by about 15%. The relief time of the first cycle was increased by about 83% when increasing the volume fraction of the fibreglass tissue from 30% to 45 % at operating temperature equal to 〖60〗^o C. The time taken to fracture the specimens decreased significantly by increasing the operating temperature as it decreased by about 88% and 73% for volume fraction 30% and 40% respectively when raising the operating temperature by about〖30〗^o C. The material relief time constant is strongly affected by both the operating temperature and the volume fraction of the fibreglass tissue.

Fibrosis and Ventricular Arrhythmogenesis: Role of Cardiac MRI.

Cardiac fibrosis is a significant increase in collagen volume fraction of myocardial tissue. It plays an important role in the pathophysiology of many cardiovascular abnormalities. Electrophysiologically, myocardial fibrosis produces anisotropic conduction, inhomogeneity, and conduction delay. Several markers are available to detect myocardial fibrosis. CMRI is the most common imaging technique; late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) provides markers for tissue characterization, disease progression and arrhythmic events. LGE-CMR can be used as risk marker of occurrence of pathologic conditions. LGE-CMR demonstrates specific patterns related to different pathologic substrates. We discuss the role of CMRI in ventricular arrhythmogenesis.

Effect of paeoniflorin on cardiac remodeling in chronic heart failure rats through the transforming growth factor β1/Smad signaling pathway.

Cardiac remodeling is an important mechanism for the occurrence and development of chronic heart failure (CHF). Paeoniflorin (Pae) is the main active ingredient of Chinese herbaceous peony and has novel anti-inflammatory effect. This study was conducted to assess the effects and mechanisms of Pae on cardiac remodeling in CHF rats. A cardiac remodeling rat model was induced by isoprenaline (Iso). Pae (20 µg/kg/d) was administrated to CHF rats for six weeks. Cardiac ultrasound was used to assess the structure and function of CHF rats. Collagen volume fraction (CVF) and perivascular collagen volume area of myocardial tissues were calculated. With real-time polymerase chain reaction and Western blot, the protein and mRNA levels of transforming growth factor β1 (TGF-β1) and Smad3 were detected. Compared to Iso group, Pae can alleviate cardiac remodeling and improve cardiac function in CHF rats. The levels of CVF and perivascular collagen volume area reduced in Pae group (P<0.05). The expression of TGF-β1 and Smad3 protein decreased in Pae and Cap group (P<0.05). Further, the expression of TGF-β1 and Smad3 mRNA also decreased markedly in the Pae group (P<0.05). Pae could attenuate cardiac remodeling and improve cardiac function in CHF rats. The potential mechanism for the cardioprotective effect of Pae may be highly associated with the down-regulating of TGF-β1/Smad signaling pathway.