Increased Tissue Density Research Articles

Development of a cost-effective compact diode-laser-based photoacoustic sensing instrument for breast tissue diagnosis.

The photoacoustic (PA) technique, a noninvasive pump-probe technique, has found interesting applications in biomedical tissue diagnosis over the last decade. To take it a step further to clinical applications, the PA technique needs to be designed as an instrument focusing on a compact design, reducing the cost, and quickly providing a quantitative diagnosis. This work presents a design and characterization of a cost-effective, compact PA sensing instrument for biomedical tissue diagnosis. A compact laser diode case design is developed to house several laser diodes for PA excitation, and a pulsed current supply unit is also developed in-house to power the laser diodes to generate a 25ns current pulse at a frequency of 20kHz. After PA experimental data acquisition, the signal's frequency spectra were calculated to characterize the tissue quantitatively and correlated with their mechanobiological properties. The corresponding dominant frequency peak in the PA spectral response (PASR) study was low in the fibrofatty normal breast tissue , compared to the dominant frequency peak of in the fibrocystic disease tissue, which had increased glandular and stromal elements, thereby increased tissue density. The histopathological findings correlated with the PASR results, and the fibrocystic breast disease tissue exhibited a higher dominant frequency peak and energy compared to the normal breast tissue. We experimented with an in vitro PASR study of fibrocystic human breast tissues and successfully differentiated different tissue types using quantitative spectral parameters peak frequency, mean frequency, and spectral energy. This gives the potential to take this technique further for cost-effective and quick clinical applications.

The forming quality of Tungsten-Carbide coatings synthesized in situ by laser remelting

The work aimed to improve the forming quality of multi-pass coatings synthesized by laser remelting in situ. The influence-relation model of the overlap rate on surface flatness and dilution rate of coatings was constructed by the single-factor method. The functions of laser power, scanning speed, defocusing distance, and scanning mode on the surface flatness and pore area of remelted coatings were studied by mixed horizontal orthogonal test, and the influence law of process parameters on surface flatness and internal pore area was revealed. Flatness increased first and then decreased with the increased overlap rate. Energy acting on the substrate decreased, and the dilution rate decreased. When the dilution rate was satisfied, the overlap rate corresponding to the maximum value of the flatness fitting curve was 26.7%. The scanning speed and laser power of remelting significantly affected coating flatness and the signal-to-noise ratio of the pore area. The signal-to-noise ratio of flatness to the pore area was positively correlated with laser power and negatively correlated with the scanning speed. When the scanning speed of remelting decreased, the duration of the molten pool increased, and its solidification rate decreased. Therefore, bubbles in the molten pool had sufficient time to overflow, which increased coating flatness and decreased the internal pore area.The optimum process parameters under multi-index optimization of integrated flatness and pore area were as follows using grey relational analysis: the laser power of 1,600 W, scanning speed of 3 mm/s, a defocusing distance of 10 mm, and parallel cladding direction. Sticky powders in the coating disappeared under the optimal remelting process parameters, and flatness and the internal pore area were improved. Maximum hardness was increased from 1,281.7HV to 1,454.2 HV, with an increase of 13.46%. The grain size was small and hardness was improved due to the increased tissue density in the remelting area of the coating.

Relaxation differences using EIS through bronchoscopy of healthy and pathological lung tissue.

The use of electrical impedance spectroscopy for lung tissue differentiation is an opportunity for the improvement of clinical diagnosis. The aim of this work is to distinguish among different lung tissue states by evaluating the differences among impedance spectrum parameters between two separate frequencies (15 kHz and 307 kHz) in the beta dispersion region. In previous studies we have used single frequency measurements for tissue differentiation. Differences (P < 0.05) are found between those tissues that undergo an increase in tissue density (neoplasm and fibrosis) and those tissues that lead to tissue destruction (emphysema). Electrical impedance spectroscopy shows its utility for lung tissue differentiation for diagnosis improvement among pathologies with different tissue structure. Further studies are necessary for the differentiation among those tissue states that are more similar to each other.Clinical Relevance- Expand the diagnostic tools currently available in bronchoscopy by using minimally-invasive bioimpedance measurements to differentiate between lung patterns.

Positron Emission Tomography-Computed Tomography Imaging of Selective Lobar Delivery of Stem Cells in Ex Vivo Lung Model of Mechanical Ventilation.

Introduction: The delivery of cell therapies may be an important frontier to treat different respiratory diseases in the near future. However, the cell size, delivery conditions, cell viability, and effect in the pulmonary function are critical factors. We performed a proof-of-concept experiment using ex vivo lungs and novel subglottic airway device that allows for selective lobar isolation and administration of drugs and biologics in liquid solution deep into the lung tissues, while simultaneously ventilating the rest of the lung lobes. Methods: We used radiolabeled cells and positron emission tomography-computed tomography (PET-CT) imaging to demonstrate the feasibility of high-yield cell delivery to a specifically targeted lobe. This study proposes an alternative delivery method of live cells labeled with radioactive isotope into the lung parenchyma and tracks the cell delivery using PET-CT imaging. The technique combines selective lobar isolation and lobar infusion to carry large particles distal to the trachea, subtending bronchial segments and reaching alveoli in targeted regions. Results: The solution with cells and carrier achieved a complete and homogeneous lobar distribution. An increase in tissue density was shown on the computed tomography (CT) scan, and the PET-CT imaging demonstrated retention of the activity at central, peripheral lung parenchyma, and pleural surface. The increase in CT density and metabolic activity of the isotope was restricted to the desired lobe only without leak to other lobes. Conclusion: The selective lobe delivery is targeted and imaging-guided by bronchoscopy and CT to a specific diseased lobe during mechanical ventilation. The feasibility of high-yield cell delivery demonstrated in this study will lead to the development of potential novel therapies that contribute to lung health.

Correlation of Shear-Wave Elastography and Apparent Diffusion Coefficient Values in Breast Cancer and Their Relationship with the Prognostic Factors.

Diffusion-weighted imaging and elastography are widely accepted methods in the evaluation of breast masses, however, there is very limited data comparing the two methods. The apparent diffusion coefficient is a measure of the diffusion of water molecules obtained by diffusion-weighted imaging as a part of breast MRI. Breast elastography is an adjunct to conventional ultrasonography, which provides a noninvasive evaluation of the stiffness of the lesion. Theoretically, increased tissue density and stiffness are related to each other. The purpose of this study is to compare MRI ADC values of the breast masses with quantitative elastography based on ultrasound shear wave measurements and to investigate their possible relation with the prognostic factors and molecular subtypes. We retrospectively evaluated histopathologically proven 147 breast lesions. The molecular classification of malignant lesions was made according to the prognostic factors. Shear wave elastography was measured in kiloPascal (kPa) units which is a quantitative measure of tissue stiffness. DWI was obtained using a 1.5-T MRI system. ADC values were strongly inversely correlated with elasticity (r = -0.662, p &lt; 0.01) according to Pearson Correlation. In our study, the cut-off value of ADC was 1.00 × 10-3 cm2/s to achieve a sensitivity of 84.6% and specificity of 75.4%, and the cut-off value of elasticity was 105.5 kPa to achieve the sensitivity of 96.3% and specificity 76.9% to discriminate between the malignant and benign breast lesions. The status of prognostic factors was not correlated with the ADC values and elasticity. Elasticity and ADC values are correlated. Both cannot predict the status of prognostic factors and differentiate between molecular subtypes.

Effects of 5-alpha reductase inhibitors prior to Holmium Laser Enucleation of the prostate: Does increased adenoma density result in prolonged morcellation times?

IntroductionThe use of 5-alpha reductase inhibitors (5-ARIs) has been shown to improve lower urinary tract symptoms (LUTS) and decrease prostate size in men with benign prostate hyperplasia (BPH). 5-ARI therapy could increase prostate tissue density through increased collagen deposition and contraction of stromal/epithelial components. Increased tissue density could prolong morcellation times, but the effects of preoperative 5-ARI exposure on morcellation efficiency during Holmium Laser Enucleation of the Prostate (HoLEP) are not well described. Herein, we examine outcomes after HoLEP of patients on pre-operative 5-ARIs.MethodsA retrospective review of patients undergoing HoLEP by an expert surgeon from Jan – Oct 2021 was performed. Student t-tests and chi-square tests were performed for continuous and categorical variables, respectively. Matched-pair analysis was performed using SPSS v28 (IBM, 2022). A p-value &amp;lt;0.05 was determined statistically significant. All other statistical analyses were performed using SAS v9.4 (SAS, 2019).ResultsA total of 322 patients underwent HoLEP during the study period and 84 patients had pre-operative 5-ARI exposure. Patients in the 5-ARI group had larger preoperative prostate size (p = 0.016). Morcellation time was longer (p=0.01), specimen weight was higher (p=0.02), and morcellation efficiency (p=0.02) was lower in the 5-ARI group. After matching, there were 67 patients in each chort (total 134) and these associations for size, morcellation time, specimen weight, and morcellation efficiency were no longer seen (p=0.8, 0.6, 0.5, and 0.7, respectively). Furthermore, no associations between 5-ARI and post-operative admissions or ED visits were noted.ConclusionIn this retrospective study, preoperative use of 5-ARIs did not affect enucleation or morcellation efficiency. Thus, preoperative 5-ARI therapy does not appear to alter outcomes after HoLEP.

How Does Voluntary Medical Male Circumcision Reduce HIV Risk?

Voluntary medical male circumcision (VMMC) is a surgical procedure that reduces HIV acquisition risk by almost two-thirds. However, global implementation is lagging, in part due to VMMC hesitancy. A better understanding of the mechanism(s) by which this procedure protects against HIV may increase acceptance of VMMC as an HIV risk reduction approach among health care providers and their clients. HIV acquisition in the uncircumcised penis occurs preferentially across the inner foreskin tissues, due to increased susceptibility that is linked to elevated inflammatory cytokine levels in the sub-preputial space and an increased tissue density of HIV-susceptible CD4 + T cells. Inflammation can be caused by sexually transmitted infections, but is more commonly induced by specific anaerobic components of the penile microbiome. Circumcision protects by both directly removing the susceptible tissues of the inner foreskin, and by inducing a less inflammatory residual penile microbiome. VMMC reduces HIV susceptibility by removing susceptible penile tissues, and also through impacts on the penile immune and microbial milieu. Understanding these mechanisms may not only increase VMMC acceptability and reinvigorate global VMMC programs, but may also lead to non-surgical HIV prevention approaches focused on penile immunology and/or microbiota.

ENDOBRONCHIAL VALVES FOR TREATMENT OF PERSISTENT AIR LEAK AFTER SECONDARY SPONTANEOUS PNEUMOTHORAX IN PATIENTS WITH CYSTIC FIBROSIS

ENDOBRONCHIAL VALVES FOR TREATMENT OF PERSISTENT AIR LEAK AFTER SECONDARY SPONTANEOUS PNEUMOTHORAX IN PATIENTS WITH CYSTIC FIBROSIS

Carbon Monoxide Diffusing Capacity (DLCO) Correlates with CT Morphology after Chemo-Radio-Immunotherapy for Non-Small Cell Lung Cancer Stage III.

Introduction: Curatively intended chemo-radio-immunotherapy for non-small cell lung cancer (NSCLC) stage III may lead to post-therapeutic pulmonary function (PF) impairment. We hypothesized that the decrease in global PF corresponds to the increase in tissue density in follow-up CTs. Hence, the study aim was to correlate the dynamics in radiographic alterations to carbon monoxide diffusing capacity (DL) and FEV, which may contribute to a better understanding of radiation-induced lung disease. Methods: Eighty-five patients with NSCLC III were included. All of them received two cycles of platinum-based induction chemotherapy followed by high dose radiation. Thereafter, durvalumab was administered for one year in 63/85 patients (74%). Pulmonary function tests (PFTs) were performed three months and six months after completion of radiotherapy (RT) and compared to baseline. At the same time points, patients underwent diagnostic CT (dCT). These dCTs were matched to the planning CT (pCT) using RayStation® Model Based Segmentation and deformable image registration. Differential volumes defined by specific isodoses were generated to correlate them with the PFTs. Results: In general, significant correlations between PFTs and differential volumes were found in the mid-dose range, especially for the volume of the lungs receiving between 65% and 45% of the dose prescribed (V) and DL (). This volume range predicted DL after RT (p-value 0.03) as well. In multivariate analysis, DL (p-value 0.040) and FEV (p-value 0.014) predicted pneumonitis. Conclusions: The current analysis revealed a strong relation between the dynamics of DL and CT morphology changes in the mid-dose range, which convincingly indicates the importance of routinely used PFTs in the context of a curative treatment approach.

A Novel and Automated Approach to Classify Radiation Induced Lung Tissue Damage on CT Scans.

Simple SummaryRadiation-induced lung damage (RILD) is a common side effect of treating lung cancer with radiotherapy (RT). RILD is visible on CT imaging, and its radiological appearance can vary dramatically from patient to patient as well as across different sub-regions of the lung and treatment volumes. A classification system for RILD able to differentiate radiological damage on a local level would allow us to better understand the underlying patterns of RILD, see how they change over time post irradiation, and link it with clinical outcomes. In this work we propose a five-class morphological lung tissue classification system that can describe parenchymal tissue changes at the voxel level. The classifier was implemented in a fully automated manner using an optimised deep-learning method, then trained and tested using data acquired through a multi-centre clinical trial. The proposed method performed well on an unseen testing dataset. The automated segmentation achieved considerable overlap with manual segmentations (ranging between 26% and 98% for the five classes) and was graded as acceptable by a clinical expert in 88% of cases. This demonstrates it to be suitable for application on a large dataset to help uncover different patterns of changes in the population.Radiation-induced lung damage (RILD) is a common side effect of radiotherapy (RT). The ability to automatically segment, classify, and quantify different types of lung parenchymal change is essential to uncover underlying patterns of RILD and their evolution over time. A RILD dedicated tissue classification system was developed to describe lung parenchymal tissue changes on a voxel-wise level. The classification system was automated for segmentation of five lung tissue classes on computed tomography (CT) scans that described incrementally increasing tissue density, ranging from normal lung (Class 1) to consolidation (Class 5). For ground truth data generation, we employed a two-stage data annotation approach, akin to active learning. Manual segmentation was used to train a stage one auto-segmentation method. These results were manually refined and used to train the stage two auto-segmentation algorithm. The stage two auto-segmentation algorithm was an ensemble of six 2D Unets using different loss functions and numbers of input channels. The development dataset used in this study consisted of 40 cases, each with a pre-radiotherapy, 3-, 6-, 12-, and 24-month follow-up CT scans (n = 200 CT scans). The method was assessed on a hold-out test dataset of 6 cases (n = 30 CT scans). The global Dice score coefficients (DSC) achieved for each tissue class were: Class (1) 99% and 98%, Class (2) 71% and 44%, Class (3) 56% and 26%, Class (4) 79% and 47%, and Class (5) 96% and 92%, for development and test subsets, respectively. The lowest values for the test subsets were caused by imaging artefacts or reflected subgroups that occurred infrequently and with smaller overall parenchymal volumes. We performed qualitative evaluation on the test dataset presenting manual and auto-segmentation to a blinded independent radiologist to rate them as ‘acceptable’, ‘minor disagreement’ or ‘major disagreement’. The auto-segmentation ratings were similar to the manual segmentation, both having approximately 90% of cases rated as acceptable. The proposed framework for auto-segmentation of different lung tissue classes produces acceptable results in the majority of cases and has the potential to facilitate future large studies of RILD.

Engineering Modular 3D Liver Culture Microenvironments In Vitro to Parse the Interplay between Biophysical and Biochemical Microenvironment Cues on Hepatic Phenotypes.

In vitro models of human liver functions are used across a diverse range of applications in preclinical drug development and disease modeling, with particular increasing interest in models that capture facets of liver inflammatory status. This study investigates how the interplay between biophysical and biochemical microenvironment cues influence phenotypic responses, including inflammation signatures, of primary human hepatocytes (PHH) cultured in a commercially available perfused bioreactor. A 3D printing-based alginate microwell system was designed to form thousands of hepatic spheroids in a scalable manner as a comparator 3D culture modality to the bioreactor. Soft, synthetic extracellular matrix (ECM) hydrogel scaffolds with biophysical properties mimicking features of liver were engineered to replace polystyrene scaffolds, and the biochemical microenvironment was modulated with a defined set of growth factors and signaling modulators. The supplemented media significantly increased tissue density, albumin secretion, and CYP3A4 activity but also upregulated inflammatory markers. Basal inflammatory markers were lower for cells maintained in ECM hydrogel scaffolds or spheroid formats than polystyrene scaffolds, while hydrogel scaffolds exhibited the most sensitive response to inflammation as assessed by multiplexed cytokine and RNA-seq analyses. Together, these engineered 3D liver microenvironments provide insights for probing human liver functions and inflammatory response in vitro.

Electrochemical Therapy of In Vivo Rabbit Cutaneous Tissue.

To examine the acid-base and histological changes in in vivo rabbit cutaneous tissue after electrochemical therapy. In vivo rabbit tissue study. The shaved skin on the backs of female Oryctolagus cuniculi were assigned to treatments with or without tumescence with normal saline. Two platinum-needle electrodes were inserted into each treatment area and connected to a direct current (DC) power supply. Voltage (3-5 V) was varied and applied for 5 minutes. The wound-healing process was monitored via digital photography and ultrasonography until euthanasia at day 29. Treatment areas were biopsied, and specimens were sectioned through a sagittal midline across both electrode insertion sites. Samples were then evaluated utilizing light microscopy (hematoxylin and eosin, Masson's Trichrome, and Picrosirius red). Treatment sites developed mild inflammation that dissipated at lower voltages or became scabs at higher voltages. Ultrasonography demonstrated acoustic shadowing with spatial spread that increased with increasing voltage application. The 4- and 5-V sites treated with saline had localized areas of increased tissue density at day 29. Although specimens treated with 3 V did not look significantly different from control tissue, 4- and 5-V samples with and without saline tumescence had finer, less-organized collagen fibers and increased presence of fibrocytes and inflammatory infiltrates. Electrochemical therapy caused localized injury to in vivo rabbit cutaneous tissue, prompting regenerative wound repair. With future development, this technology may offer precise, low-cost rejuvenation to restore the functionality and appearance of dermal scars and keloids. NA Laryngoscope, 131:E2196-E2203, 2021.

T2-Pseudonormalization and Microstructural Characterization in Advanced Stages of Late-infantile Metachromatic Leukodystrophy

PurposeT2-weighted signal hyperintensities in white matter (WM) are a diagnostic finding in brain magnetic resonance imaging (MRI) of patients with metachromatic leukodystrophy (MLD). In our systematic investigation of the evolution of T2-hyperintensities in patients with the late-infantile form, we describe and characterize T2-pseudonormalization in the advanced stage of the natural disease course.MethodsThe volume of T2-hyperintensities was quantified in 34 MRIs of 27 children with late-infantile MLD (median age 2.25 years, range 0.5–5.2 years). In three children with the most advanced clinical course (age >4 years) and for whom the T2-pseudonormalization was the most pronounced, WM microstructure was investigated using a multimodal MRI protocol, including diffusion-weighted imaging, MR spectroscopy (MRS), myelin water fraction (MWF), magnetization transfer ratio (MTR), T1-mapping and quantitative susceptibility mapping.ResultsT2-hyperintensities in cerebral WM returned to normal in large areas of 3 patients in the advanced disease stage. Multimodal assessment of WM microstructure in areas with T2-pseudonormalization revealed highly decreased values for NAA, neurite density, isotropic water, mean and radial kurtosis, MWF and MTR, as well as increased radial diffusivity.ConclusionIn late-infantile MLD patients, we found T2-pseudonormalization in WM tissue with highly abnormal microstructure characterizing the most advanced disease stage. Pathological hallmarks might be a loss of myelin, but also neuronal loss as well as increased tissue density due to gliosis and accumulated storage material. These results suggest that a multimodal MRI protocol using more specific microstructural parameters than T2-weighted sequences should be used when evaluating the effect of treatment trials in MLD.

Positional Therapy and Regional Pulmonary Ventilation.

Prone ventilation redistributes lung inflation along the gravitational axis; however, localized, nongravitational effects of body position are less well characterized. The authors hypothesize that positional inflation improvements follow both gravitational and nongravitational distributions. This study is a nonoverlapping reanalysis of previously published large animal data. Five intubated, mechanically ventilated pigs were imaged before and after lung injury by tracheal injection of hydrochloric acid (2 ml/kg). Computed tomography scans were performed at 5 and 10 cm H2O positive end-expiratory pressure (PEEP) in both prone and supine positions. All paired prone-supine images were digitally aligned to each other. Each unit of lung tissue was assigned to three clusters (K-means) according to positional changes of its density and dimensions. The regional cluster distribution was analyzed. Units of tissue displaying lung recruitment were mapped. We characterized three tissue clusters on computed tomography: deflation (increased tissue density and contraction), limited response (stable density and volume), and reinflation (decreased density and expansion). The respective clusters occupied (mean ± SD including all studied conditions) 29.3 ± 12.9%, 47.6 ± 11.4%, and 23.1 ± 8.3% of total lung mass, with similar distributions before and after lung injury. Reinflation was slightly greater at higher PEEP after injury. Larger proportions of the reinflation cluster were contained in the dorsal versus ventral (86.4 ± 8.5% vs. 13.6 ± 8.5%, P < 0.001) and in the caudal versus cranial (63.4 ± 11.2% vs. 36.6 ± 11.2%, P < 0.001) regions of the lung. After injury, prone positioning recruited 64.5 ± 36.7 g of tissue (11.4 ± 6.7% of total lung mass) at lower PEEP, and 49.9 ± 12.9 g (8.9 ± 2.8% of total mass) at higher PEEP; more than 59.0% of this recruitment was caudal. During mechanical ventilation, lung reinflation and recruitment by the prone positioning were primarily localized in the dorso-caudal lung. The local effects of positioning in this lung region may determine its clinical efficacy.

P1782INFLUENCE OF IMMUNOSUPPRESSIVE REGIMEN ON OXYGENATION AND DIFFUSIVITY OF KIDNEY TRANSPLANTS - ANALYSIS OF FUNCTIONAL MRI DATA FROM THE RANDOMIZED ZEUS STUDY

Abstract Background and Aims The ZEUS study was a multi-center open-label randomized controlled trial designed to investigate the effect of an early conversion from a calcineurin-inhibitor-based immunosuppression to a mammalian-target-of-rapamycin inhibitor-based regimen on graft function twelve months post-transplantation. Persistent improvement of renal function up to five years together with albeit higher rejection rates were found in the intervention group. In the context of an investigator-initiated local sub-study, functional magnetic resonance imaging (fMRI) was prospectively performed in a subset of the study population in order to non-invasively assess differences in renal graft oxygenation, diffusion and perfusion between groups and time-points using blood-oxygen level-dependent (BOLD)- and diffusion-weighted (DWI) MRI respectively. Method In the ZEUS trial, 300 de novo kidney graft recipients were randomized to continue ciclosporin (CsA) or be converted to everolimus (EVE) at 4.5 months post-transplant. Concomitant immunosuppression contained enteric-coated mycophenolic acid, steroids and basiliximab. From the 36 subjects included in the ZEUS study at our study center, sixteen were enrolled in the MRI sub-study. FMRI including BOLD-MRI and DWI was prospectively performed at month 4.5 and 12 post-transplantation on a 3 Tesla and 1.5 Tesla (n=3) MR scanner. Blinded image analysis was done by placing up to 24 regions of interest in cortex and medulla. BOLD-MRI yielded the relaxation rate R2*, a parameter indirectly proportional to tissue oxygen content, DWI yielded the perfusion-cleared apparent diffusion coefficient ADCD, a marker of tissue diffusivity, and the perfusion fraction FP, a marker of microperfusion. All data were analyzed using in-house custom-scripts written in IDL® and MATLAB®. Results After exclusion of subjects due to image quality, outlier values or missing data, BOLD data was analyzed in eight, DWI in ten subjects. Mean absolute values and standard deviations corresponded to published values. A clear cortico-medullary gradient was shown for R2* and FP values, but not for ADCD, corresponding to previous results. For all fMRI parameters, there was no change for the whole population from 4.5 to 12 months post-transplantation in cortex and medulla. FMRI parameters did not differ significantly between both medication groups at month 4.5. In BOLD, R2* values increased (decreased tissue oxygen) over time in the CsA-treated and decreased in the EVE-treated group in cortex and medulla. Similarly, R2* values at month 12 were higher in the CsA- vs. EVE-treated group; the low number of subjects having completed BOLD-MRI at month 12 precluded formal statistical testing. In DWI, ADCD decreased in the CsA-group over time, whereas it increased in the EVE-group in cortex and medulla (p=0.046). Likewise, ADCD at month 12 was lower by trend in the CsA- vs. EVE-treated group in both medulla and cortex. The change in ADCD from month 4.5 to month 12 significantly differed in cortex (p=0.033) and medulla (p=0.019) between treatment groups. There was no significant difference for FP between medication groups nor over time. Baseline renal function and blood pressure were comparable in both groups. Conclusion The R2* values obtained by BOLD point to reduced graft oxygenation on CsA and ameliorated graft oxygenation on EVE, possibly due to the known vasoconstrictor effect of calcineurin inhibitors. The observed decreased diffusivity by DWI on CsA might be due to increased tissue density in the context of beginning calcineurin inhibitor-induced interstitial fibrosis. There was no clear trend for microperfusion as assessed by FP. Limitations of this study are the low number of subjects available for analysis. In conclusion, this prospective sub-study of the ZEUS trial suggests an impact of immunosuppressive regimen on fMRI parameters of the renal graft.

Plastic responses of fine root morphological traits of Castanopsis fabri and Castanopsis carlesii to short-term nitrogen addition

Nitrogen deposition will affect the morphology of fine roots and its absorption of nutrien-ts, resulting in changes nutrient cycling in terrestrial ecosystems. In order to understand the effects of nitrogen deposition on fine root morphological traits of Castanopsis fabri and C. carlesii, two ectomycorrhizas tree species, we carried out in situ experiment using the root bags method in an evergreen broadleaved forest in the subtropical zone. The results showed that the plastic responses of specific root length and specific root surface area of low-order roots (first to third order) to nitrogen addition was higher than that of high-order roots (fourth order). The plastic responses of root tissue density to nitrogen addition increased from the first-order to the fourth-order, while the average root diameter of each order had no significant plastic responses to nitrogen addition. There was a certain synergistic change between the plastic response of specific root length and specific surface area in the low order fine root and the plastic response of tissue density in the high order fine root. The specific root length, specific root surface area and root tissue density of the two species showed opposite plastic responses to nitrogen addition, indicating that different ectomycorrhizal tree species had different nutrient foraging strategies. C. fabri adopted rapid absorption strategy by increasing specific root length, specific root surface area, and proliferation rate of fine root length, while C. carlesii adopted a relatively conservative resource absorption strategy by increasing tissue density of fine roots.

Matrisome Properties of Scaffolds Direct Fibroblasts in Idiopathic Pulmonary Fibrosis.

In idiopathic pulmonary fibrosis (IPF) structural properties of the extracellular matrix (ECM) are altered and influence cellular responses through cell-matrix interactions. Scaffolds (decellularized tissue) derived from subpleural healthy and IPF lungs were examined regarding biomechanical properties and ECM composition of proteins (the matrisome). Scaffolds were repopulated with healthy fibroblasts cultured under static stretch with heavy isotope amino acids (SILAC), to examine newly synthesized proteins over time. IPF scaffolds were characterized by increased tissue density, stiffness, ultimate force, and differential expressions of matrisome proteins compared to healthy scaffolds. Collagens, proteoglycans, and ECM glycoproteins were increased in IPF scaffolds, however while specific basement membrane (BM) proteins such as laminins and collagen IV were decreased, nidogen-2 was also increased. Findings were confirmed with histology, clearly showing a disorganized BM. Fibroblasts produced scaffold-specific proteins mimicking preexisting scaffold composition, where 11 out of 20 BM proteins were differentially expressed, along with increased periostin and proteoglycans production. We demonstrate how matrisome changes affect fibroblast activity using novel approaches to study temporal differences, where IPF scaffolds support a disorganized BM and upregulation of disease-associated proteins. These matrix-directed cellular responses emphasize the IPF matrisome and specifically the BM components as important factors for disease progression.

Comparison between Mammography and Breast Ultrasound in the Detection of Breast Cancer in Dense Breast Tissue among a Sample of Iraqi Women

Background: Breast cancer is the most common cancer reported in women worldwide . In Iraq, it is the most common registered malignancy. Mammography plays a major role in the early detection of breast cancers. Dense breast parenchyma has been reported to be the most important inherent factor that limits depiction of breast cancer on mammogram, and often needs supplementary breast ultrasound for complete assessment. &#x0D; Objectives: To evaluate and compare the diagnostic performance of mammography and ultrasound in the&#x0D; detection of breast cancer in dense breast tissue.&#x0D; Patients and methods: A record review study was performed in the Oncology Teaching Hospital/ Medical&#x0D; City from April 2018 to December 2018. The study included forty five females, who attended the Main&#x0D; Referral Center for Early Detection of Breast Tumors during 2017 and 2018 were diagnosed with breast cancer histopathologically . They had dense breast tissues on mammography (either heterogeneously dense&#x0D; breast tissue i.e . category C or extremely dense breast tissue i.e. category D). All patients underwent subsequent breast ultrasound . Their information including the mammogram findings, breast ultrasound,&#x0D; fine needle aspiration (FNA) and biopsy results were reviewed analyzed and compared.&#x0D; Results:Twenty four patients (53.3%) had heterogeneously dense breast tissue (ACR category C) and 21&#x0D; patients (46.6%) had extremely dense breast tissue (ACR category D). The mammogram detected 36 from 45&#x0D; breast cancers (80%) while 9 (20%) were not detected by mammogram, so the mammogram had a detection&#x0D; rate of breast cancer of 80% in mammographically dense breast, while breast ultrasound had higher detection rate of about 97.7% .The sensitivity of mammography in extremely dense breast tissue was about 71% and in heterogeneously dense breast was about 87% while ultrasound had shown a higher sensitivity&#x0D; with increasing tissue density (98% vs. 100%).&#x0D; Conclusion: Breast cancer can be easily obscured and missed in mammographically dense breast tissue due&#x0D; to overlapping surrounding fibroglandular tissue and additional complementary breast ultrasound is highly&#x0D; recommended for a thorough evaluation and to depict mammographically occult breast carcinoma.

Comparison of Contrast-Enhanced Mammography With Conventional Digital Mammography in Breast Cancer Screening: A Pilot Study

PurposeTo perform a pilot evaluation of contrast-enhanced mammography (CEM) for screening to determine whether it can improve accuracy and reader confidence in diagnosis. Methods and MaterialsThis institutional review board–approved reader study was comprised of 64 de-identified CEM cases acquired from December 1, 2014, to June 7, 2016, including 48 negative, 5 biopsy-proven benign, and 11 biopsy-proven malignancies. Negative cases were followed for at least 2 years without evidence of cancer. Ten breast imagers of varying experience first rated the low-energy (LE) mammogram and then the CEM examination using BI-RADS categories and a 5-point Likert scale for confidence in diagnosis. ResultsThere were 635 out a total possible 640 complete reader interpretations included in this analysis. The remaining five incomplete interpretations were excluded. Median sensitivity and specificity improved with the addition of CEM (sensitivity: 0.86 [95% confidence interval {CI}: 0.74-0.95] versus 1 [95% CI: 0.83-1.00], specificity: 0.85 [95% CI: 0.64-0.94] versus 0.88 [95% CI: 0.80-0.92]). Individual receiver operating characteristic curves showed significant improvement with CEM (mean area under the curve increase = 0.056 [95% CI: 0.015-0.097], P = .002). The addition of CEM significantly improved average confidence in 5 of 10 readers when compared with LE (P < .0001) and improved pooled confidence across all tissue density categories, except the almost entirely fatty category. There was a trend toward improved confidence with increasing tissue density with CEM. Degree of background parenchymal enhancement did not affect readers’ level of improvement in confidence when interpreting CEM. SummaryCEM improved reader performance and confidence compared with viewing only LE, suggesting a role for CEM in breast cancer screening for which larger trials are warranted.

Mechanobiology of mice cervix: expression profile of mechano-related molecules during pregnancy.

There is a known reciprocation between the chronic exertion of force on tissue and both increased tissue density (e.g., bone) and hypertrophy (e.g., heart). This can also be seen in cervical tissue where the excessive gravitational forces associated with multiple fetal pregnancies promote preterm births. While there is a well-known regulation of cervical remodeling (CR) by sex steroid hormones and growth factors, the role of mechanical force is less appreciated. Using proteome-wide technology, we previously provided evidence for the presence of and alteration in mechano-related signaling molecules in the mouse cervix during pregnancy. Here, we profile the expression of select cytoskeletal factors (filamin-A, gelsolin, vimentin, actinin-1, caveolin-1, transgelin, keratin-8, profilin-1) and their associated signaling molecules [focal adhesion kinase (FAK) and the Rho GTPases CDC42, RHOA, and RHOB] in cervices of pregnant mice by real-time PCR and confocal immunofluorescence microscopy. Messenger RNA and protein levels increased for each of these 12 factors, except for 3 (keratin-8, profilin-1, RHOA) that decreased during the course of pregnancy and this corresponded with an increase in gravitational force exerted by the fetus on the cervix. We therefore conclude that size or weight of the growing fetus likely plays a key role in CR through mechanotransduction processes.