Biomedical Engineering

Novel biomaterials for medical device applications must be stable throughout all stages of preparation for surgery, including sterilization. There is a paucity of information on the effects of sterilization on sub-10 nm-thick polymeric surface coatings suitable for silicon-based bioartificial organs. This study explores the effect of five standard sterilization methods on three surface coatings applied to silicon: polyethylene glycol (PEG), poly(sulfobetaine methacrylate) (pSBMA), and poly (2-methacryloyloxyethyl phosphorylcholine) (pMPC). Autoclave, dry heat, hydrogen peroxide (HO) plasma, ethylene oxide gas (EtO), and electron beam (E-beam) treated coatings were analyzed to determine possible polymer degradation with sterilization. Poststerilization, there were significant alterations in contact angle, maximum change resulting from HO(Δ - 14°), autoclave (Δ + 15°), and dry heat (Δ + 23°) treatments for PEG, pSBMA, and pMPC, respectively. Less than 5% coating thickness change was f...

Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas-permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water-based bench-top set-up as well in a porcine in vivo model. It was determ...

Gas permeable membranes are a vital component of extracorporeal membrane oxygenation systems. Over more than half a century, membrane fabrication and packaging technology have progressed to enable safer and longer duration use of respiratory life support. Current research efforts seek to improve membrane efficiency and hemocompatibility, with the aim of producing smaller and more robust systems for ambulatory use. This review explores past and present innovations in oxygenator technology, suggesting possible applications of state-of-the-art membrane fabrication methods to address shortcomings of earlier concepts.

An implantable hemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3–8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5–8 nm × 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics models of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta ...

Silicon nanopore membranes (SNM) with compact geometry and uniform pore size distribution have demonstrated a remarkable capacity for hemofiltration. These advantages could potentially be used for hemodialysis. Here we present an initial evaluation of theSNM's mechanical robustness, diffusive clearance, and hemocompatibility in a parallel plate configuration. Mechanical robustness of the SNM was demonstrated by exposing membranes to high flows (200ml/min) and pressures (1,448mmHg). Diffusive clearance was performed in an albumin solution and whole blood with blood and dialysate flow rates of 25ml/min. Hemocompatibility was evaluated using scanning electron microscopy and immunohistochemistry after 4-hours in an extra-corporeal porcine model. The pressure drop across the flow cell was 4.6mmHg at 200ml/min. Mechanical testing showed that SNM could withstand up to 775.7mmHg without fracture. Urea clearance did not show an appreciable decline in blood versus albumin solution. Extra-...

Growth of human connective tissue progenitor cells (CTPs) was characterized on smooth and microtextured polydimethylsiloxane (PDMS) surfaces. Human bone marrow derived cells were cultured for nine days under conditions promoting osteoblastic differentiation on Smooth PDMS and PDMS Channel microtextures (11 µm high, 45 µm wide channels, and separated by 5 µm wide ridges). Glass tissue culture dish surfaces were used

In this preliminary study we used a goat model to quantify pressure at an interbody bone graft interface. Although the study was designed to assess fusion status, the concept behind the technology could lead to early detection of implant failure and potential hazardous complications related to motion-preservation devices. Th e purpose of this study was to investigate the feasibility of in vivo pressure monitoring as a strategy to determine fusion status. Telemetric pressure transducers were implanted, and pressure at the bone graft interfaces of cervical interbody fusion autografts placed into living goats (Groups A and B) was evaluated. Group A constituted the 4-month survival group and Group B the 6-month survival group. One goat served as the study control (Group C) and was not implanted with a pressure transducer. An additional six cadaveric goat cervical spines (Group D) were obtained from a local slaughterhouse and implanted with bone grafts and ventral plates and used for in vitro biomechanical comparison to the specimens from Groups A and B. All goats demonstrated an increase in interface pressure within the fi rst 10 days postoperatively, with the largest relative change in pressure occurring between the sixth and ninth days. Th e goats from Groups A and B had a 200% to 400% increase in relative pressure. Although this was a pilot study to assess pressure as an indicator for a fusion or pseudarthrosis, the preliminary data suggest that early bone healing is detectable by an increase in pressure. Th us, pressure may serve as an indicator of fusion status by detecting altered biomechanical parameters.

A spatially uniform magnetic energy density gradient (∇B2) distribution offers a controlled environment to separate magnetically tagged cells or biomolecules based on their magnetophoretic mobility [L. R. Moore et al., J. Biochem. Biophys. Methods 37, 11 (1998)]. A design to obtain a uniform ∇B2 distribution for a microelectromechanical-systems-based magnetic cell separator was developed. The design consists of an external magnetic circuit and a microfabricated channel (biochip) with embedded discrete pole pieces on the channel walls. The two-dimensional and three-dimensional magnetostatic simulation softwares utilizing boundary element methods were used to optimize the positions and the dimensions of the discrete pole pieces, as well as the external magnetic circuit—the combination of which would generate a uniform ∇B2 profile over the channel cross section. It was found that the discrete pole pieces required specific magnetic properties (saturation magnetization constant >1.55T...

Congenital pulmonary hypoplasia is a devastating condition affecting fetal and newborn pulmonary physiology, resulting in great morbidity and mortality. The fetal lung develops in a fluid-filled environment. In this paper, we describe a novel, implantable pressure sensing and recording device which we use to study the pressures present in the fetal pulmonary tree throughout gestation. The system achieves 0.18 cm H 2 O resolution and can record for 21 days continuously at 256 Hz. Sample tracings of in vivo fetal lamb recordings are shown.

Varying geometry and layout of microposts on a cell culture substrate provides an effective technique for applying mechanical stimuli to living cells. In the current study, the optimal geometry and arrangement of microposts on the polydimethylsiloxane (PDMS) surfaces to enhance cell growth behavior were investigated. Human bone marrow derived connective tissue progenitor cells were cultured on PDMS substrates comprising unpatterned smooth surfaces and cylindrical post microtextures that were 10 µm in diameter, 4 heights (5, 10, 20 and 40 µm) and 3 pitches (10, 20, and 40 µm). With the same 10 µm diameter, post heights ranging from 5 to 40 µm resulted in a more than 535000 fold range of rigidity from 0.011 nNµm -1 (40 µm height) up to 5888 nNµm -1 (5 µm height). Even though shorter microposts result in higher effective stiffness, decreasing post heights below the optimal value, 5 µm height micropost in this study decreased cell growth behavior. The maximum number of cells was observed on the post microtextures with 20 µm height and 10 µm inter-space, which exhibited a 675% increase relative to the smooth surfaces. The cells on all heights of post microtextures with 10 µm and 20 µm inter-spaces exhibited highly contoured morphology. Elucidating the cellular response to various external geometry cues enables us to better predict and control cellular behavior. In addition, knowledge of cell response to surface stimuli could lead to the incorporation of specific size post microtextures into surfaces of implants to achieve surface-textured scaffold materials for tissue engineering applications.

Microelectromechanical systems (MEMS) are used to machine miniaturized implantable medical devices. Our group has used MEMS technology to develop hemofiltration membranes for use in renal replacement therapy which possess enhanced selectivity and permeability. The use of silicon in blood-contacting environments may be limited, however, due to contact activation of the coagulation cascade by silicon which form the surface oxides in atmospheric conditions. As well, reports of long-term biocompatibility of blood-contacting silicon devices are lacking. The aims of this pilot study were: 1) to develop a model for investigating the effects of intravascular implants and 2) to characterize the degree of thrombosis and tissue inflammation incited by prolonged implantation of silicon materials. Silicon implants with and without polyethylene glycol (PEG) coatings were surgically implanted transluminally through rat femoral veins. Gore-Tex and stainless steel implants served as controls. Implants were left in vivo for four weeks. All femoral veins remained patent. Veins associated with silicon implants exhibited rare thrombi and occasional mild perivascular inflammation. In contrast, Gore-Tex and stainless steel controls caused moderate vein thrombosis and provoked a moderate to marked cellular infiltrate. Under scanning electron microscopy, bare silicon implants were found to have significant adherent microthrombi, while PEG-treated implants showed no evidence of thrombi. PEG-treated silicon appears to be biocompatible and holds potential as an excellent material with which to construct an implantable, miniaturized hemofiltration membrane.

Over 300,000 Americans are dependent on hemodialysis as treatment for renal failure, and kidney transplantation is limited by scarcity of donor organs. This shortage has prompted research into tissue engineering of renal replacement therapy. Existing bioartificial kidneys are large and their use labor intensive, but they have shown improved survival compared to conventional therapy in preclinical studies and an US Food and Drug Administration-approved phase 2 clinical trial. This hybrid technology will require miniaturization of hemofilters, cell culture substrates, sensors, and integration of control electronics. Using the same harvesting and isolation techniques used in preparing bioartificial kidneys for clinical use, we characterized human renal tubule cell growth on a variety of silicon and related thin-film material substrates commonly used in the construction of microelectromechanical systems (MEMS), as well as novel silicon nanopore membranes (SNMs). Human cortical tubular epithelial cells (HCTC) were seeded onto samples of single-crystal silicon, polycrystalline silicon, silicon dioxide, silicon nitride, SU-8 photoresist, SNMs, and polyester tissue culture inserts, and grown to confluence. The cells formed confluent monolayers with tight junctions and central cilia. Transepithelial resistances were similar between SNMs and polyester membranes. The differentiated growth of human tubular epithelial cells on MEMS materials strongly suggests that miniaturization of the existing bioartificial kidney will be feasible, paving the way for widespread application of this novel technology.

Proteoglycans, once thought to primarily serve as structural components of extracellular matrix, are now being focused on for their role in tissue and cell regulation, particularly angiogenesis. Many growth factors, notably the fibroblast growth family ͑FGF͒ which now numbers 19 members, bind to heparin and heparan sulfate proteoglycans and this binding has been shown to have a significant impact on the availability and activity of these growth factors. Proteoglycans can serve as both temporal and spatial regulators and effective inhibitor design may depend on disruption of these interactions. We have developed a simple assay for evaluating small inhibitors of proteoglycan-ligand binding. The assay is based on cell-free incubation of the reactants and filtration across a cationic membrane. Conditions were established that allow one to semiquantitatively determine binding constants for both direct proteoglycan as well as soluble inhibitor affinity. The assay has been demonstrated using a model heparan sulfate proteoglycan preparation ͑perlecan from cultured bovine endothelial cells͒ and FGF-2. Protamine sulfate, sucrose octasulfate, and heparin were analyzed as model inhibitor molecules. This type of assay may have wide application as a fast and easy screening tool for small potential agonists and antagonists of proteoglycan-protein interactions.

Transplantation of encapsulated pancreatic islets is a promising approach for the treatment of type 1 diabetes. Large-scale application of this technique, however, is hampered by insufficient biocompatibility of the capsules. In this study, we have evaluated the biocompatibility of a new synthetic material with six different chemical groups on their surface (amino, carboxy-sulfate, carboxylate, hydroxylate, sulfate, and PMMA) used for the fabrication of the microcapsules. Eight Lewis rats were inoculated with a suspension of empty capsules made for each candidate material in the retroperitoneal ileopsoas muscle and renal subcapsular space. Four weeks later kidney and muscle containing the capsules were explanted, paraffin embedded, sectioned and stained with Sirius Red and Masson's Trichrome for histological analysis. The amount of fibrosis was also ultrastruc-turally evaluated with scanning electron microscopy. The samples were then subjected to digitalized quantitative analysis using specific software to determine the degree of fibrotic overgrowth. The quantification of collagen deposition, calculated in proximity of the microcapsules, was expressed as a percentage of the total area and can be considered a good index for the biocompatibility, an essential prerequisite for functional pancreatic islet transplantation. The results show that subcapsular renal space is the best implantation site and the positive surface charge induces a more intense collagen synthesis.

Tissue spheroids formed from fibroblasts using a micromolded non adhesive hydrogel were located using a three dimensional (3D) bioprinter on the surface of a nanofibrous polyurethane matrix produced by electrospinning. It was shown that the tissue spheroids attach to the matrix surface within a few hours and completely flatten after several days, indicating high biocompatibility of the matrix used. Tissue structures formed by the attachment and spreading of tissue spheroids on an electrospun matrix are a new technological platform for biofabrication and 3D bioprinting of tissues and organs.

Collagen is one of the most promising materials for 3D bioprinting because of its distinguished biocompatibility. Cell-laden constructs made of pure collagen with or without incorporated growth supplements support engineered constructs persistence in culture and are perfectly suitable for grafting. The limiting factor for direct 3D collagen printing was poor printability of collagen solutions, especially admixed with cells or tissue spheroids. In our study, we showed that concentrated solutions of native collagen branded Viscoll were effective as bioinks with high fidelity performance. Viscoll containing 20, 30, or 40 mg/ml collagen were used for direct extrusion 3D bioprinting to form scaffolds appropriate to support spatial arrangement of tissue spheroids into rigid patterns with resolution of 0.5 mm in details. Incorporated cells demonstrated sufficient viability. Associated rheological study showed that good printability of the collagen solutions correlates with their increased storage modulus value, notably exceeding the loss modulus value. The proper combination of these physical parameters could become technological criteria for manufacturing various collagen bioinks for 3D bioprinting.

In this work, we adapt a method based on multiple hypothesis tracking (MHT) that has been shown to give state-of-the-art vessel segmentation results in interactive settings, for the purpose of extracting trees. Methods: Regularly spaced tubular templates are fit to image data forming local hypotheses. These local hypotheses are then used to construct the MHT tree, which is then traversed to make segmentation decisions. Some critical parameters in the method, we base ours on, are scale-dependent and have an adverse effect when tracking structures of varying dimensions. We propose to use statistical ranking of local hypotheses in constructing the MHT tree which yields a probabilistic interpretation of scores across scales and helps alleviate the scale-dependence of MHT parameters. This enables our method to track trees starting from a single seed point. Results: The proposed method is evaluated on chest CT data to extract airway trees and coronary arteries and compared to relevant baselines. In both cases, we show that our method performs significantly better than the Original MHT method in semi-automatic setting. Conclusions: The statistical ranking of local hypotheses introduced allows the MHT method to be used in non-interactive settings yielding competitive results for segmenting tree-structures.

Accurate segmentation of the pulmonary arteries and aorta is important due to the association of the diameter and the shape of these vessels with several cardiovascular diseases and with the risk of exacerbations and death in patients with chronic obstructive pulmonary disease. We propose a fully automatic method based on an optimal surface graph-cut algorithm to quantify the full 3D shape and the diameters of the pulmonary arteries and aorta in noncontrast computed tomography (CT) scans. Methods: The proposed algorithm first extracts seed points in the right and left pulmonary arteries, the pulmonary trunk, and the ascending and descending aorta by using multi-atlas registration. Subsequently, the centerlines of the pulmonary arteries and aorta are extracted by a minimum cost path tracking between the extracted seed points, with a cost based on a combination of lumen intensity similarity and multiscale medialness in three planes. The centerlines are refined by applying the path tracking algorithm to curved multiplanar reformatted scans and are then smoothed and dilated nonuniformly according to the extracted local vessel radius from the medialness filter. The resulting coarse estimates of the vessels are used as initialization for a graph-cut segmentation. Once the vessels are segmented, the diameters of the pulmonary artery (PA) and the ascending aorta (AA) and the PA : AA ratio are automatically calculated both in a single axial slice and in a 10 mm volume around the automatically extracted PA bifurcation level. The method is evaluated on noncontrast CT scans from the Danish Lung Cancer Screening Trial (DLCST). Segmentation accuracy is determined by comparing with manual annotations on 25 CT scans. Intraclass correlation (ICC) between manual and automatic diameters, both measured in axial slices at the PA bifurcation level, is computed on an additional 200 CT scans.Repeatability of the automated 3D volumetric diameter and PA : AA ratio calculations (perpendicular to the vessel axis) are evaluated on 118 scan-rescan pairs with an average in-between time of 3 months. Results: We obtained a Dice segmentation overlap of 0.94 ± 0.02 for pulmonary arteries and 0.96 ± 0.01 for the aorta, with a mean surface distance of 0.62 ± 0.33 mm and 0.43 ± 0.07 mm, respectively. ICC between manual and automatic in-slice diameter measures was 0.92 for PA, 0.97 for AA, and 0.90 for the PA : AA ratio, and for automatic diameters in 3D volumes around the PA bifurcation level between scan and rescan was 0.89, 0.95, and 0.86, respectively.

In this study, it was investigated to what extent linear auto regressive models with external input (ARX) and auto regressive moving average models with external input (ARMAX) could be used to describe the inside air temperature of an unheated, naturally ventilated greenhouse under Western European conditions. Outside air temperature and relative humidity, global solar radiation, and cloudiness of the sky were used as the input variables. Firstly, different models were built for the first and middle week of each season. The models were suitable to describe the greenhouse temperature evolution satisfactorily, except for the ventilation periods, apparently due to the non-linear effect of ventilation strategies. It was also observed that ARX models performed better than ARMAX models. None of the input variables could be omitted from models for a complete year. It was found that the application of a single model structure for a complete year required frequent retuning. Retuning when the goodness of fit falls below a pre-set threshold, proved to be more efficient than retuning at fixed time intervals in maintaining high accuracy.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

The work aimed at developing a MRI-guided protocol for the visualization of the release of material entrapped in liposomes stimulated by the local application of pulsed low-intensity non-focused ultrasound (pLINFU). The task was achieved by formulating liposomes filled up with the clinically approved paramagnetic agent gadoteridol, because the release of the agent from the nanovesicles is accompanied by a significant MRI signal enhancement. The protocol was validated in vivo on mice-bearing subcutaneous syngeneic B16 melanoma and i.v. injected with the paramagnetic liposomes. Upon exposing tumor to pLINFU (3 MHz, insonation time 2 min, duty cycle 50%) few minutes after liposomes injection, a signal enhancement of ca. 35% was detected. The effective release of the agent was confirmed by the strong enhancement measured in kidneys calyx and bladder due to the rapid renal excretion of the agent released in the tumor.

Crucial to all cancer therapy modalities, is a strong correlation between treatment and effect. Predictability of therapy success/failure allows for the optimization of treatment protocol and aids in the decision of whether additional treatment is necessary to prevent tumour progression. This work evaluated the relationship between cancer treatment and effect for intratumoural infusions of liposome-encapsulated 186 Re to head and neck squamous cell carcinoma xenografts of nude rats. Absorbed dose calculations using a dose point kernel convolution technique showed significant intratumoural dose heterogeneity due to the short range of the beta-particle emissions. The use of three separate tumour infusion locations improved dose homogeneity compared to a single infusion location as a result of a more uniform radioactivity distribution. An improved doseresponse correlation was obtained when using EUD calculations based on a generic set of radiobiological parameters (R 2 = 0.84) than when using average tumour absorbed dose (R 2 = 0.22). Varying radiobiological parameter values over ranges commonly used for all types of tumours showed little effect on EUD calculations which suggests that individualized parameter use is of little significance as long as the intratumoural dose heterogeneity is taken into consideration in the dose-response relationship. The improved predictability achieved when using EUD calculations for this cancer therapy modality may be useful for treatment planning and evaluation.

Event‐related functional magnetic resonance imaging (fMRI) was applied to investigate blood oxygen level dependent (BOLD) responses in the human auditory system. Auditory fMRI is hindered by the disturbing acoustical noise of echo planar imaging (EPI). A sparse acquisition technique was used in which the delayed hemodynamic response was imaged at discrete sampling time‐points after a brief auditory stimulus. Long repetition times (10 heartbeats (HBs)) were used to avoid interactions between the activation due to the sound stimulation and scanner noise. In addition, only a single slice was acquired, to ensure that the scanner noise was minimal in duration and intensity. The image acquisition was triggered by the HB to prevent artifacts from cardiac‐related brainstem motion. An image was acquired every 10th HB. Significant hemodynamic BOLD time‐course responses were measured from the primary and secondary auditory cortices, as well as the inferior colliculi in the brainstem. No system...

Patient-led surveillance is a promising new model of follow-up care following excision of localized melanoma. OBJECTIVE To determine whether patient-led surveillance in patients with prior localized primary cutaneous melanoma is as safe, feasible, and acceptable as clinician-led surveillance. DESIGN, SETTING, AND PARTICIPANTS This was a pilot for a randomized clinical trial at 2 specialist-led clinics in metropolitan Sydney, Australia, and a primary care skin cancer clinic managed by general practitioners in metropolitan Newcastle, Australia. The participants were 100 patients who had been treated for localized melanoma, owned a smartphone, had a partner to assist with skin self-examination (SSE), and had been routinely attending scheduled follow-up visits.

Aim: The aim of this study was to assess the potential of using video screening to interpret the results of paediatric eye examinations. Design: Prospective multi-centred, blinded study. Methods: Children aged 5 months to 11 years referred to a paediatric ophthalmology centre were enrolled in the study. Outcome measures included the degree of agreement between examiners for assessment of various aspects of paediatric eye examination. In Phase 1, children were individually assessed in the clinic by three different examiners to determine the level of agreement. In Phase 2 a video recording was made of the first ophthalmologist examining the children. The other two examiners viewed the video recordings to make their diagnoses. Areas of assessment included lid function, pupillary function, ocular motility, strabismus, nystagmus, torticollis and facial asymmetry. Agreement between examiners was measured using Gwet's agreement coefficient (AC1). Results: A total of 27 patients in Phase 1 (mean age 4.0 years) and 160 children in Phase 2 (mean age 4.8 years) underwent clinical and video-recorded screening. In Phase 1, all but one area of ocular examination (heterotropia) achieved !84% agreement between three examiners. In Phase 2, there was greater variation between direct clinical examination and interpretation of video findings, ranging from 55-100% agreement. Conclusion: Using experienced clinicians and changing only one variable in Phase 2 (the method of assessment -direct examination versus video interpretation), the results show the possible usefulness of video-recorded screening as a means of assessing children. Further research is indicated to assess the accuracy of ophthalmologists interpreting video recordings of eye examinations performed by trained non-eye-care professionals.

Aim The aim of this study was to assess the potential of using video screening to interpret the results of paediatric eye examinations. Design Prospective multi-centred, blinded study. Methods Children aged 5 months to 11 years referred to a paediatric ophthalmology centre were enrolled in the study. Outcome measures included the degree of agreement between examiners for assessment of various aspects of paediatric eye examination. In Phase 1, children were individually assessed in the clinic by three different examiners to determine the level of agreement. In Phase 2 a video recording was made of the first ophthalmologist examining the children. The other two examiners viewed the video recordings to make their diagnoses. Areas of assessment included lid function, pupillary function, ocular motility, strabismus, nystagmus, torticollis and facial asymmetry. Agreement between examiners was measured using Gwet’s agreement coefficient (AC1). Results A total of 27 patients in Phase 1 (mea...

Purpose: Many interventional procedures require the precise placement of needles or therapy applicators (tools) to correctly achieve planned targets for optimal diagnosis or treatment of cancer, typically leveraging the temporal resolution of ultrasound (US) to provide real-time feedback. Identifying tools in two-dimensional (2D) images can often be time-consuming with the precise position difficult to distinguish. We have developed and implemented a deep learning method to segment tools in 2D US images in near real-time for multiple anatomical sites, despite the widely varying appearances across interventional applications. Methods: A U-Net architecture with a Dice similarity coefficient (DSC) loss function was used to perform segmentation on input images resized to 256⨯256 pixels. The U-Net was modified by adding 50 % dropouts and the use of transpose convolutions in the decoder section of the network. The proposed approach was trained with 917 images and manual segmentations from prostate/gynecologic brachytherapy, liver ablation, and kidney biopsy/ablation procedures, as well as phantom experiments. Real-time data augmentation was applied to improve generalizability and doubled the dataset for each epoch. Post-processing to identify the tool tip and trajectory was performed using two different approaches, comparing the largest island with a linear fit to random sample consensus (RANSAC) fitting. Comparing predictions from 315 unseen test images to manual segmentations, the overall median [first quartile, third quartile] tip error, angular error, and DSC were 3.5 [1.3, 13.5] mm, 0.8 [0.3, 1.7]°, and 73.3 [56.2, 82.3] %, respectively, following RANSAC post-processing. The predictions with the lowest median tip and angular errors were observed in the gynecologic images (median tip error: 0.3 mm; median angular error: 0.4°) with the highest errors in the kidney images (median tip error: 10.1 mm; median angular error: 2.9°). The performance on the kidney images was likely due to a reduction in acoustic signal associated with oblique insertions relative to the US probe and the increased number of anatomical interfaces with similar echogenicity. Unprocessed segmentations were performed with a mean time of approximately 50 ms per image. We have demonstrated that our proposed approach can accurately segment tools in 2D US images from multiple anatomical locations and a variety of clinical interventional procedures in This article is protected by copyright. All rights reserved near real-time, providing the potential to improve image guidance during a broad range of diagnostic and therapeutic cancer interventions.

Purpose: Limited treatment options exist for patients with malignant biliary obstruction caused by pancreaticobiliary cancer. The aim of this study was to validate the feasibility of using intrabiliary radiofrequency hyperthermia (RFH) to enhance local chemotherapy administration to cholangiocarcinoma. Materials and Methods: GFP/lentivirus-transduced human cholangiocarcinoma cells (Mz-ChA-1) were treated with various concentrations of gemcitabine and the half maximal inhibitory concentration (IC50) was determined. For in vitro evaluation, Mz-ChA-1 cells were cultured in four-chamber slides and treated by using (a) 20-min RFH at approximately 42 degrees celsius plus 500-mM gemcitabine; (b) 20-min RFH-only; (c) 500-mM gemcitabine-only; and (d) no treatment to serve as a control. Cell viabilities were assayed using trypan blue exclusion. Each experiment was repeated six times. For in vivo evaluation, cells were subcutaneously implanted into the flanks of 24 nu/nu nude mice. When the tumor size reached approximately 5mm in diameter, 25mg/kg of gemcitabine was injected into the tumor followed by RFH at approximately 421C for 20 min. Whole body fluorescent optical imaging and 14T MRI, including T2WI and diffusion-weighted imaging were used to follow up therapeutic effects at 1, 7, and 14 days after treatment. HE staining and confocal microscopy were performed to establish image/histology correlation. Results: The IC50 of gemcitabine for Mz-ChA-1 cells at 96hrs is 500 mM. The in vitro experiments demonstrate that RFH-enhanced chemotherapy can significantly inhibit tumor cells growth, compared with chemotherapy only and the RFH only group (0.58Ϯ0.10 vs 0.72Ϯ0.8 and 0.58Ϯ0.10 vs 0.65Ϯ0.11, po0.05). The in vivo experiments show inhibition of tumor growth and decreased GFP-signal on optical imaging, post treatment with RF hyperthermia and gemcitabine. Histology confirmed the therapeutic effect of RFH-enhanced chemotherapy on the tumors. Conclusion: RFH can enhance the killing effect of chemotherapy on cholangiocarcinomas, which may open new avenues to effectively manage pancreatobiliary malignancies.

We consider systems that are well modelled as networks that evolve in time, which we call Moving Neighborhood Networks. These models are relevant in studying cooperative behavior of swarms and other phenomena where emergent interactions arise from ad hoc networks. In a natural way, the time-averaged degree distribution gives rise to a scale-free network. Simulations show that although the network may have many noncommunicating components, the recent weighted time-averaged communication is sufficient to yield robust synchronization of chaotic oscillators. In particular, we contend that such time-varying networks are important to model in the situation where each agent carries a pathogen (such as a disease) in which the pathogen's lifecycle has a natural time-scale which competes with the time-scale of movement of the agents, and thus with the networks communication channels.

Two scaffolds of chitosan/sodium alginate/hydroxyapatite (Ch/NaAlg/Hap) 1:1:0.2 and 1:1:0.6 were evaluated in the prevention of bisphosphonate-induced jaw osteonecrosis. Two groups of rats (n 5 24, according to the euthanasia time: 15 or 30 days after the last Zoledronic acid (ZA) administration) were subdivided in four subgroups (n 5 6): I -Control (saline 1 teeth extraction); II -ZA 0.6 mg/kg 1 teeth extraction; III -ZA 1 teeth extraction 1 scaffold 1:1:0.2; IV -ZA 1 teeth extraction 1 scaffold 1:1:0.6. Jaws were evaluated histologically and blood was evaluated for hematological and biochemical parameters. Histopathology showed significant osteonecrosis in AZ group. The scaffold's implantation, despite the inflammatory process, were able to prevent the osteonecrosis. In the 15-day euthanasia group, an increase in red blood cells and platelets was observed in the subgroup II. Hemoglobin and hematocrit decreased in subgroup IV compared to II. Hepatic transaminases and creatinine concentration increased significantly in subgroup II. Calcium concentration increased in subgroup IV compared to II. In the 30-day euthanasia group, no differences among the groups were observed for any parameter. Scaffolds proved to be efficient and safe to liver and kidney function. Some hematological parameters were altered by the scaffold, but returned to normal concentrations over time. V

Background With the explosion of techniques for recording electrical brain activity, our recognition of neurodiversity has expanded significantly. Yet, uncertainty exists regarding sex differences in electrical activity during sleep and whether these differences, if any, are associated with social parameters. We synthesised existing evidence applying the PROGRESS-Plus framework, which captures social parameters that may influence brain activity and function. Methods We searched five databases from inception to December 2024, and included English language peer-reviewed research examining sex differences in electrical activity during sleep in healthy participants. We performed risk of bias assessment following recommended criteria for observational studies. We reported results on sex differences by wave frequency (delta, theta, alpha, sigma, beta, and gamma) and waveforms (spindle and sawtooth), positioning results across age-related developmental stages. We created visualizations of ...

Study Design. Time series monitoring changes in titanium and stainless steel rod curvature kept at a constant temperature of 37 C as a function of time. Objectives. To assess the possibility of loss of curvature in titanium rods after scoliosis surgery. Summary of Background Data. Titanium rods have gained use in scoliosis surgery due to their excellent biocompatibility, while allowing medical personnel to obtain undistorted magnetic resonance imaging scans following surgery. However, the impression of several clinicians has been that when screw pullout and/or loss of sagittal balance occurs, it may be due to the rods losing some of their curvature. Methods. Five 6-mm rods of differing compositions and lengths (titanium 300 and 100 mm, stainless steel 300 and 100 mm, prebent titanium 85 mm) were bent at room temperature with a 3-point rod bender, then placed in an incubator at 37 C. Digital photographs were taken every 2 weeks and analyzed to extract the radius of curvature of each rod. Results. The Ti rods had a significantly decreasing curvature with time. The prebent Ti and stainless steel rods did not exhibit significant change in curvature. Conclusions. Titanium rods bent at room temperature and then exposed to body temperature over time tend to exhibit "metal memory"; they gradually revert to their original shape. This may result in loss of sagittal balance and/or proximal screw pullout.

The electromyogram of the L1-L7 multifidus muscles of the in vivo cat were recorded while applying a prolonged steady displacement to the lumbar spine through the L4 -L5 supraspinous ligament, simulating a moderate anterior flexion. Objective. To demonstrate that tension-relaxation and laxity of the viscoelastic structures (ligaments, discs, and capsules) induced by prolonged static flexion of the spine results in loss of reflexive muscular stabilizing activity and in muscular disorders that may lead to or are associated with low back pain. Summary of Background. Epidemiologic data show that prolonged loading of the spine, such as in some occupational activities, can cause low back pain and muscle spasms. Direct experimental evidence linking prolonged loading to a decrease in spinal stability, low back pain, and muscle spasms was not found. It was hypothesized, however, that mechanoreceptors in the viscoelastic structures, when strained, reflexively activate the multifidus muscles to maintain intervertebral stability; that the reflexive muscular activity decreases with stress-relaxation and laxity in the viscoelastic structures; and that when severe strain and possible damage of the viscoelastic structures occurs with time, nociceptive receptors elicit spasms in the musculature and possible pain. Methods. The lumbar spine of seven in vivo cat preparations was displaced through the L4 -L5 supraspinous ligament into moderate flexion that was steadily maintained for 50 minutes while intramuscular electromyograms were recorded from each of the multifidus muscles of L1-L2 through L6 -L7. Load and electromyogram were continuously monitored and recorded. Five additional preparations were used as controls, in which dissection and recordings were identical, but the lumbar flexion was excluded. Results. Prolonged flexion of the lumbar spine resulted in initial reflexive electromyogram from the multifidus muscles that decreased to approximately 5% of its initial value as tension-relaxation began in the viscoelastic structures within the first 3 minutes, after which, random and unpredictable electromyogram discharges (i.e., spasms) of high amplitude were recorded from different levels. In some preparations the spasms were present in L1-L4, and in others in all the levels. In other preparations the spasms were recorded only at L5 and L6. The onset of the spasms was also unpredictable, because they were initiated in some cases within 2-3 minutes after the spine was loaded. In other cases, the spasms were observed anytime during the test period and up to 20 minutes after the load was removed. Spasms were also observed in the spinalis and longissimus muscles. Conclusions. Prolonged flexion of the lumbar spine results in tension-relaxation and laxity of its viscoelastic structures, loss of reflexive muscular activity within 3 minutes and electromyogram spasms in the multifidus and other posterior muscles.

The effect of tendons viscoelastic stiffness on the dynamic response of the cat's tibialis anterior muscle under isometric conditions was determined. It was shown that the dynamic response model of the muscle derived under sinusoidal contraction-relaxation in the range of 20-80 % of its maximal isometric tension was not statistically different before and after the disection of the whole distal tendon. It was suggested that under isometric conditions in the force range of 2c-80 % of the maximal, the tendon acts as a very stiff force transmission linkage without significantly modifying the muscle's performance.

Muscle surface displacement is a mechanical event taking place simultaneously with the tension generation at the tendon. The two phenomena can be studied by the surface mechanomyogram signal (MMG) (produced by a laser distance sensor) and the force signal (from a load cell). The aim of this paper was to provide data on the reliability of the laser detected MMG in muscle mechanics research. To this purpose it was veri"ed if the laser detected MMG was suitable to estimate a frequency response in the cat medial gastrocnemius and its frequency response was compared with the one retrieved by the force signal at the tendon level. The force and MMG from the exposed medial gastrocnemius of four cats were analysed. The frequency response was investigated by sinusoidally changing the number of orderly recruited motor units, in di!erent trials, in the 0.4}6 Hz range. It resulted that it was possible to model the force and MMG frequency response by a critically damped second-order system with two real double poles and a pure time delay. On the average, the poles were at 1.83 Hz (with 22.6 ms delay) and at 2.75 Hz (with 38 ms delay) for force and MMG, respectively. It can be concluded that MMG appears to be a reliable tool to investigate the muscle frequency response during stimulated isometric contraction. Even though not statistically signi"cant, the di!erences in the second-order system parameters suggest that di!erent components of the muscle mechanical model may speci"cally a!ect the force or MMG.