Table of contents

In this paper, the authors review the field of parallax error (PE) minimization in positron emission tomography (PET) imaging systems by using depth of interaction (DOI) capable concepts. The review includes apparatus as well as an overview of various methods described in the literature. It also discusses potential advantages gained via these approaches, as discussed with reference to various metrics and tasks, particularly in the improvement of spatial resolution (SR) performance. Furthermore, the authors emphasize limitations encountered in the context of DOI decoding, which can be a considerable pitfall depending on the task of interest.

Objective: We aim to propose a definition for a new class of in-body medical devices located in the superficial skin layers, called insertables; to provide an overview of their technological capabilities and challenges, and to summarize current applications and potential future use cases. Methods: A scoping, unsystematic review was conducted to gain an understanding of insertables and identify their clinical applications. Several information sources were used including: (i) peer-reviewed scientific literature; (ii) market research reports and (iii) the Derwent Innovation intellectual property database. An analysis of commercially available insertables and those under development was performed. Results: Desirable characteristics of insertables are: (i) noninvasiveness; (ii) ease of application, positioning and removal; (iii) multi-functionality; (iv) flexible in-body life-span and (v) patient-friendliness. Nineteen insertables were identified, spanning application areas from cardiac monitoring and continuous glucose monitoring to drug delivery. In the near future, a dozen insertables are expected to be brought to market in application areas ranging from analyte detection to electroencephalogram monitoring and measurement of intraocular pressure. Conclusion: Insertables combine useful features of implantables and wearable medical devices in a single offering. Insertables have the potential to deliver clinically useful, reliable physiological data and therapy with negligible patient discomfort and risk.

Adequate reproduction of low contrast image detail is essential for accurate diagnosis in diagnostic radiology. Artinis CDRAD and Leeds Test Object TO20 are commercially available test objects that can be used to test this aspect of imaging performance in digital radiography. Automated analysis software is available for both test objects (CDRAD Analyser and AutoPIA (TO20)). This study evaluated and compared both test objects and software, including their sensitivity to changes in exposure parameters and image processing. Images of the test objects were acquired in scatter and scatter-free environments and analysed using a range of metrics derived from automated analysis, visual assessment and manual contrast-to-noise ratio measurements. The CNR (TO20) and correctly identified holes (%) (CDRAD) were found to be the most sensitive to changes in exposure conditions. The total number of detected discs (TO20) was the least sensitive. None of the image quality metrics was sensitive to a change in image processing. Other methods, such as anthropomorphic phantoms, would therefore be required to evaluate changes in clinical image processing. The results of this investigation help to inform best use of these test objects in routine quality control and image quality benchmarking for optimisation.

Several research teams have developed computational phantoms in polygonal-mesh (PM) and/or Non-Uniform Rational B-Spline format, but it has not been systematically evaluated if the existing voxel phantoms are still dosimetrically valid. We created three voxel phantoms with the resolutions of 1,000, 125, and 1 mm³ and simulated the irradiation in antero-posterior geometry with photons of 0.1, 1, and 10 MeV using voxel Monte Carlo codes, and compared the energy deposition to their organs/tissues with the values from the original PM phantom using mesh Monte Carlo codes. The coefficient of variation in energy deposition overall showed about five-fold decrease as the voxel resolution increased but differences were mostly less than 5% for any voxel resolution. We conclude that PM phantoms and mesh Monte Carlo techniques may not be necessary for external photon exposure (0.1–10 MeV) and the existing voxel phantoms can provide enough dosimetric accuracy in those exposure conditions.

In bone-drilling research, thermal osteonecrosis regions have only begun to be investigated. This study evaluates the thermal osteonecrosis regions and bone temperature elevations induced by drilling parameters in drilling of human cortical bone. The finite element method (FEM) was used to simulate the drilling simulation. The simulation results were then validated with the experimental bone-drilling test. A new method called dimensionless weightage was proposed to evaluate the parameters that generate minimum thermal injury in bone-drilling. The FEM results displayed the thermal injury in the bone as a function of osteonecrosis diameter (OD), osteonecrosis depth (OH) and maximum bone temperature elevation (Tmax). These results allow precise evaluation of bone-drilling parameters' influences on thermal damage. Results revealed that with the recommended parameter ranges, Tmax, OD, and OH could be reduced up to 110.0 °C, 9.96 mm and 4.56 mm, respectively. This work represents a step toward the optimization of bone-drilling parameters, which can provide an accurate approximation of thermal damage in bone-drilling compared with previous research. Moreover, this work contributes valuable insights for engineers and clinicians to identify the favorable ranges of bone-drilling parameters in bone surgeries.

Near-Infrared Spectroscopy (NIRS) is a non-invasive brain imaging technique involving the quantification of oxy and deoxy-hemoglobin concentrations resolved from the measurement of Near-Infrared (NIR) light attenuation within the tissue. Previous studies have shown that NIR light is more influenced by the optical properties of the superficial layers than those of the deeper target layers such as cortex. NIR light produced by the Laser source penetrates deeper regions of the tissue rather than the LED source although Laser needs more expensive instrumentation. In this study, we investigate the effect of Uniform and Gaussian beam profiles on the enhancement of LED light penetration depth. The latter beam profiles were generated and compared using Flat and Aspherical lenses applied to the LED sources. In order to increase the signal to noise ratio, the lenses were also applied to the light detector. For performance analysis, two experiments were carried out by scanning the intra space of a liquid phantom by static and dynamic (pulsating) absorbers. Monte Carlo simulations were also carried out to be compared with the experiment. The results showed that Gaussian beam profile and in particular, Bi-Convex lenses applied to both source and detector leads to a greater light penetration depth in the liquid phantom close to that of a Laser source.

Quantitative dual-energy computed tomography may improve the accuracy of treatment planning in radiation therapy. Of special interest are algorithms that can estimate material composition of the imaged object. One example of such an algorithm is the 2D model-based iterative reconstruction algorithm DIRA. The aim of this work is to extend this algorithm to 3D so that it can be used with cone-beams and helical scanning. In the new algorithm, the parallel FBP method was replaced with the approximate 3D FBP-based PI-method. Its performance was tested using a mathematical phantom consisting of six ellipsoids. The algorithm substantially reduced the beam-hardening artefact and the artefacts caused by approximate reconstruction after six iterations. Compared to Alvarez-Macovski's base material decomposition, DIRA-3D does not require geometrically consistent projections and hence can be used in dual-source CT scanners. Also, it can use several tissue-specific material bases at the same time to represent the imaged object.

Voltage-sensitive dye imaging (VSDi) is an accurate imaging method that use small intensity changes of fluorescent dyes emission to capture the brain activity. In this technique, little artifacts can produce large signals interfering with the main signals and reducing the validity of the experiment. In this study, we studied the effect of two image registration methods to rectify VSDi noises due to the movements of anesthetized rat brain in vivo. The first method is image registration on the basis of image intensity and the second method is applied in steerable pyramid domain and reduces movements by zeroing out phase shifts. The resulting images bring more distinct brain signals in response to a whisker stimulation.

Background Methods for faller classification and gait patterns using portable and reliable equipment are still a challenge when considered an active and healthy aging population, in particular for large-scale applications. In this study, we investigated the patterns that could identify elderly faller by means of the acceleration gait data. Method Gait frequency pattern study of active older than 60 years participants divided into three groups according to the fall history in the last year: 10 non-fallers, 10 sporadic fallers and 10 recurrent fallers. The subjects performed 6MWT, with a triaxial accelerometer allocated at the waist, with 200 Hz sampling rate. Magnitude information was extracted to analyze the acceleration curves. The comparison between the groups was performed through the chi-squared test, ANOVA and Kruskal-Wallis test. Results Average age of the participants was 75.13 ± 6.37 years (76.6% women). While it was not possible to differentiate fallers through the 6MWT, statistical differences were found in variables extracted from segmented acceleration curves. The first and third largest frequency amplitudes measured when participants are turning during the test showed discriminative capability between sporadic fallers and the other groups (p = 0.018; 0.014, respectively). Statistical difference was found also from the difference between the maximum magnitude in frequency of the complete signal in relation to the turning movement between recurrent fallers and the remaining groups (p = 0.035), while the third main frequency magnitude difference between walking and turning showed significant difference between sporadic fallers and the others (p = 0.030). The best result considering ROC analysis achieved AUC of 0.807, sensitivity of 0.80 and specificity of 0.75. Conclusion and Relevance Frequency features extracted from the combination of the accelerometer and the test can contribute to clinical practice and to scientific area, providing a low-cost diagnosis with a wearable sensor, allowing large-scale applications. Considering specific gait events are important for this task since our results indicate there is more discriminative capability when comparing the turning movement with other gait patterns.

We evaluated small radiological regions of the parenchymal tissue in mammograms -micro-parenchymal (MP) patterns—for breast cancer risk assessment. We adapted path-based analysis, a computer vision technique, in order to build a model of the distribution of MP patterns in mammograms from a training population sample. Subsequently, the model was utilized to infer the level of risk of individual women based on the distribution of MP patterns in test mammograms. We validated our method using a pilot case/control study with 114 women diagnosed with cancer and 114 healthy controls matched by age, screening year and mammographic system. Experiments with 5-fold cross validation showed a statistically significant positive association between the MP-based risk scores and breast cancer risk with an OPERA (odds per standard deviation of the risk score) value of 1.66 (p-value < 0.001) and an area under the receiver operating characteristic curve (AUC) of 0.653. Results retain their statistical significance after adjusting for visual and quantitative breast densities, widely known imaging biomarkers for breast cancer risk. This work provides experimental evidence that there are specific MP patterns identifiable as cues of breast cancer and prompt the validation of these results in larger datasets.

Silver nanoparticle (AgNP) has potent anti-microbial activity & chitosan has wound healing activity. L-Glutamic acid is a wound healing promoting agent. So AgNP & L-glutamic acid loaded chitosan hydrogel would be a promising formulation for topical applications like wound healing. But instability of AgNP is the main problem to develop such a topical gel. We synthesized AgNP conjugated chitosan microparticle (SNCCM) as a stable source of AgNP. In aqueous medium, the release of AgNP was triggered at pH ≤ 4.5. The optimum pH was 4.5. The released AgNP was of ∼27 nm size. The SNCCM particles had 9.86 × 10¹² AgNP conjugated per mg of dried product. The geometric mean diameter of dried SNCCM particles was 590 ± 1.0 μm, whereas the average weight was 0.51 ± 0.05 mg. So, exact number of SNCCM particles can be dissolved in aqueous medium of pH 4.5 to get the desired dose of AgNP in-situ. The optimum gel had pH of 4.5 & particle content of 1.47 × 10¹³ AgNP ml⁻¹. The viscosity and spreadibility of hydrogel were 22 780 ± 1.24 cp and 20 ± 4.7 gm-cm/s respectively. The hydrogel was equally effective against both Gram +ve and Gram −ve bacteria. The diameters of its zone of inhibition were 37.62 ± 3.04 mm against S. aureus & 37.65 ± 2.97 mm against E. coli.

Objective: The speed of pressure pulses traveling through the blood, the pulse wave velocity (PWV), is a metric that provides substantial information about the passive and active elasticity of the blood vessels. Therefore, PWV is a valuable parameter in the diagnosis of cardiovascular and vessel-related neurological diseases. The purpose of this study was to investigate whether a novel, simple, easy-to-use, photoplethysmography-based Multi Photodiode Array (MPA) provides PWV measurements that agree with measurements done with more complicated and harder-to-use systems currently used in clinical practice. Methods: An often-used vascular perturbation that changes the conduit artery vasomotor tone during reactive hyperemia was imposed on thirty healthy volunteers. The MPA was used alongside and its results compared to those of a commonly used measurement device, the Biopac-system, during flow-mediated dilation (FMD). This way it was investigated if measurements with these systems, measuring over two different, but partly overlapping vessel trajectories agree. Results: The baseline absolute PWV values were significantly lower for the MPA as compared to the Biopac-system. Additionally, Bland-Altman plots and Pearson's correlation tests suggested good agreement between the two PWV measurement techniques during the FMD. Conclusion: Measuring PWV with the MPA in clinical practice is feasible and provides reliable data. Significance: The MPA may substantially simplify PWV measurements and may enable long-term PWV monitoring as long as one is aware of the relation between PWV and the vascular trajectory over which it is measured.

Compressed sensing (CS) based four dimensional (4D) cone-beam (CB) computed tomography (CT) reconstruction intrinsically is a multi-objective optimization problem. In practice, however, often a heuristically chosen single objective cost function is minimized. In this paper Pareto-frontier analysis was utilized to explore the image quality of the multi-objective solution space. The 4D-CBCT CS reconstruction was solved as an unconstrained optimization problem with the objective function consisting of data fidelity, spatial sparsity term (with regularization parameter λ) and temporal sparsity term (with regularization parameter β). Data fidelity was defined by an l₂-norm term and the sparsity was extracted by the total-variation (TV) norm. The Pareto front was explored for a large range of λ and β parameter combinations optimized using Neterov's descent method. Image quality was evaluated using correlation ratio (CR), mutual information (MI), structural similarity index (SSI), and contrast-to-noise ratio (CNR) on both phantom and clinical data. Higher image quality metrics were obtained with the CS optimized 4D-CBCT compared to Feldkamp (FDK) reconstructed 4D-CBCT. The optimal parameter values, however, were distinctly different for the different image quality metrics, scans and regions-of-interest. For the phantom data, the optimized CBCT have similar numerical results by CR and MI, but the results differ for SSI. For clinical data, it was found that $\lambda \in [0.53,0.78]\cup \beta \in [0.32,0.73]$ kept the CS CBCT with 15% difference to the CBCT of optimal CNR. The optimal regularization parameter values in CS optimized 4D-CBCT were found to be patient and image quality metric dependent. The regularization should therefore be tailored to specific clinical applications.

Pneumonia, tuberculosis, asthma, cystic fibrosis, etc are known as acute pulmonary disorders which are leading to the inefficiency of the respiratory system. Owing to the infection and inflammation caused by diseases, the patient's respiratory system is impaired and in the absence of proper treatment, it loses normal function. In the present study, to the modeling of oxygen transfer phenomena from the alveoli to the pulmonary capillary, the respiratory unit is considered as a simplified 3D model based on microfluidic device geometry. Then, by applying the physiological respiratory conditions on the presented model, the fluid flow and mass transfer equations for blood and airflow through the membrane in microchannels have been coupled and solved using Comsol Multiphysics software. The most remarkable result to emerge from the initial data is that the oxygen saturation has been in the physiological range and it confirms the proposed microfluidic model to the aim of this study. After attaining to the optimized geometrical model, by applying various conditions of the disease, including obstruction caused by infection and changes in concentration and thickness of the mucous layer formed on the respiratory membrane, the blood oxygenation during the diseases have been investigated. The results of the work show the changes in oxygen transferred from the alveoli to the lung capillaries during the inspiration process at different stages of obstruction under the influence of infection. It was pointed out that the effect of increasing of mucous layer thickness is greater than the mucous concentration in reducing blood oxygenation. According to the results, the discrepancy of the patient's blood oxygen content relative to the physiological range is almost compensable by varying the oxygen concentration of the intake air. The oxygen concentration required to supply the blood oxygen deficit is proposed for several modes.

Purpose: Previously we developed a PCTV method to enhance the edge sharpness for low-dose CBCT reconstruction. However, the iterative deformable registration method used for deforming edges from planning-CT to on-board CBCT is time-consuming and user-dependent. This study aims to automate and accelerate PCTV reconstruction by developing an unsupervised CNN model to bypass the conventional deformable registration. Methods: The new method uses unsupervised CNN model for deformation prediction and PCTV reconstruction. An unsupervised CNN model with a u-net structure was used to predict deformation vector fields (DVF) to generate on-board contours for PCTV reconstruction. Paired 3D image volumes of prior CT and on-board CBCT are inputs and DVF are predicted without the need of ground truths. The model was initially trained on brain MRI images, and then fine-tuned using our lung SBRT data. This method was evaluated using lung SBRT patient data. In the intra-patient study, the first n−1 day's CBCTs are used for CNN training to predict nth day edge information (n = 2, 3, 4, 5). 45 half-fan projections covering 360˚ from nth day CBCT is used for reconstruction. In the inter-patient study, the 10 patient images including CT and first day's CBCT are used for training. Results from Edge-preserving (EPTV), PCTV and PCTV-CNN are compared. Results: The cross-correlations of the predicted edge map and the ground truth were on average 0.88 for both intra-patient and inter-patient studies. PCTV-CNN achieved comparable image quality as PCTV while automating the registration process and reducing the registration time from 1–2 min to 1.4 s. Conclusion: It is feasible to use an unsupervised CNN to predict daily deformation of on-board edge information for PCTV based low-dose CBCT reconstruction. PCTV-CNN has a great potential for enhancing the edge sharpness with high efficiency for low-dose CBCT to improve the precision of on-board target localization and adaptive radiotherapy.

Purpose: Computed tomography (CT) represents the standard of treatment planning in radiotherapy. Calculation of dose distribution requires proper energy-dependent curves to convert Hounsfield Units into relative to water electron densities (rED). To possibly reduce the patient dose while maintaining optimal image quality, it could be useful to modulate x-ray tube potential (kVp) based on patient size, but this practice requires the use of several conversion curves in the treatment planning system (TPS). The DirectDensity^TM (DD) algorithm, recently developed by Siemens Healthcare, uses projection data to reconstruct images directly proportional to rEDs, regardless of the used kVp. The purpose of this study was to evaluate this algorithm for clinical use in radiotherapy. Methods: Image quality was evaluated on Catphan images reconstructed with standard and DD algorithms. The CIRS Electron Density Phantom, with its several tissue-equivalent inserts, was then used to assess the accuracy of reconstructed rEDs against those certified at different tube voltages. Finally, the treatment plans calculated on clinical images reconstructed with standard and DD algorithms were compared. Results: DD showed an image quality comparable to standard algorithms except for the contrast: DD causes a loss in contrast (up to 69%) for materials densities greater than 1.1 g cm⁻³. CIRS images analysis proved the rEDs reconstruction accuracy except for the metal inserts: titanium rED was underestimated up to 40% when kVp was reduced. Nevertheless, minimal dosimetric differences were found between treatment plans calculated in different body regions. Conclusions: The DD algorithm allows to plan radiotherapy treatments on CT images acquired at tube potentials optimized both for the anatomical region and patient size, without complicating the clinical workflow with tube potential specific calibration procedures. However, the presence of contrast medium and metal implants can limit the applications of this algorithm in clinical practice.

We introduce a methodology for acquisition and analysis of infrared (IR) images, picturing the metabolic heat emission from the human skin. Then we analyze the radiometric asymmetries in the patients with DM2 in comparison to the natural asymmetries, represented by the control group. In this regard, we introduce three indices (TAI, SAI, TtAI) with conditions for disclosing asymmetries displayed on images acquired in passive mode (the natural thermal emission, NTE). Then, the indices are adapted for analysis of IR-images acquired in what we brand as active mode (the NTE is altered by means of a controlled external stimulus). Out of the passive mode, the TAI and TtAI indices show the best diagnostic performance, with values of sensitivity and specificity of 89% and 72%, and 83% and 78%, respectively. Instead, from the active mode analysis we get 86% of sensitivity and 83% of specificity for the TRI index. We report data obtained form IR-images of 36 patients with Diabetes Mellitus Type II (DM2) and 18 non-diabetic controls. For both groups the image acquisition is made in passive and active mode, picturing the anterior and posterior views of the lower limbs. With this analysis, we manage to unveil the contra-lateral radiometric asymmetries of the legs, along with the differences between patients and controls. Finally, we report the consistency of these indices with glucose and glycated hemoglobin (HbA1c), known to be the golden clinical variables used to diagnose DM2.

Pancreatic cancer is the fourth most common cause of cancer-related fatalities as there are a limited number of tools to diagnose this disease in its early stages. Pancreatitis is characterized as an inflammation of the pancreatic tissue due to an excess amount of pancreatic enzymes remaining in the organ. Both of these diseases result in a stiffening of the tissue which makes them suitable for the use of elastography techniques as a diagnostic method. However, these methods typically assume that the tissue is purely elastic when biological tissue is inherently viscoelastic. The attenuation measuring ultrasound shear elastography (AMUSE) method, which measures both attenuation and shear wave velocity was used to characterize the viscoelasticity of pancreatic tissue. This method was tested in ex vivo normal porcine samples that were also stiffened in formalin and in vivo by conducting studies in healthy human subjects. Ex vivo testing showed ranges of phase velocity, group velocity, and phase attenuation values of 1.05–1.33 m s⁻¹, 0.83–1.12 m s⁻¹, and 183–210 Np m⁻¹. After immersing the ex vivo tissue in formalin there was a distinguishable difference between normal and stiffened tissue. This study produced percent difference ranges of phase velocity, group velocity, and phase attenuation from 0 to 100 min in formalin of 30.0%–56.5%, 38.2%–58.6%, and 55.8%–64.8%, respectively. The ranges of phase velocity, group velocity, and phase attenuation results in human subjects were 1.53–1.60 m s⁻¹, 1.76–1.91 m s⁻¹, and 196–204 Np m⁻¹, respectively. These results were within a similar range reported by other elastography techniques. Further work with the AMUSE method in subjects with pancreatitis and cancer is needed to determine its effectiveness in showing a difference between healthy and diseased tissue in humans.

Utah electrode arrays (UEAs) enable the recording of neuronal activity that informs the understanding of cortical connectivity and function, and can be used to control brain-machine/computer interfaces. However, UEAs have shown a reduced ability to resolve single unit activity (SUA) over time, prompting efforts such as the use of alternative insulation materials and reliance of local field potentials (LFPs) to improve device robustness and stability of neuroprosthetic control signals, respectively. The effect of different electrode insulation materials on LFP stability, particularly with UEAs, has not been extensively investigated, especially in rats, which provide a well-studied model for behavior and motor cortex injury. Here, we report the chronic stability of LFPs from both Parylene-C- and amorphous silicon carbide-encapsulated UEAs implanted in the rat motor cortex. We observed a decrease in bandpower in anesthetized rats for both array types that converged to the same magnitude at 30 weeks. In awake, freely-behaving rats however, there was relatively stable bandpower in both array types across individual frequency bands. In total, our results are consistent with studies performed in non-human primates, suggesting that chronic LFP stability trends are similar across both animal models.

In 2004, Gortz et al performed the first and only electrical measurements of human embryonal carcinoma NTera2/cl.D1 (NT2/hNT) neurons in vitro. His conclusions shaped our perspective about the electrical characteristics of this cell type and, since burst-like behaviour of the neurons was not observed as occurs in primary cultures, he cautioned how one should be careful in using such cells for human therapeutic approaches. Since then, several authors have demonstrated chemically that hNT neurons express ubiquitous neuronal markers with their chemical expression being directly compared to that of human primaries and how they are a valid alternative to them, leading to their successful use for cell transplantation in stroke therapy. However, whilst the scientific community had identified the similarity of chemical expression of hNTs to primaries there still remained an 'odd piece in the puzzle' as the cells' electrical characteristics appeared incongruent, not matching the burst-like behaviour typically observed in primary neuron cultures. In this article, we re-examine the electrical characteristics of hNT neurons with a customised, low-noise recording system. With this recording system, we observe for the first time that hNT neurons do indeed exhibit burst-like behaviour, providing an exhaustive quantification of the bursts which we relate to strong network formation and hence update and revise the original work. The significance of this work is that it rebalances the scientific community's perspective on the electrical characteristics of hNT neurons. This work provides the final electrical piece to the hNT neuron's profile aligning its narrative to be complementary to the hNT neuron's chemical expression and similar to primary neurons. For the first time, we can now completely consider, both electrically and chemically, the hNT neuron as a valid alternative to primary neurons.

Breast cancer has one of the highest mortality rates usually due to metastatic development. Mammograms are the current standard of diagnosis; however due to the low sensitivity and high rate of misdiagnosis, patients either experience false positives or negatives leading to overdiagnosis and overtreatment. One of key disadvantages of mammograms is their failed ability to differentiate between a dense breast and a tumor, usually leading to more mammograms and more expensive diagnostic tools. In order to provide a widely available imaging tool, targeted gold nanoparticles have been developed. Gold nanoparticles have been designed with annexin V surface modification to specifically bind phosphatidylserine expressing tumor cells and tumor vasculature. In vitro and in vivo studies showed a significant increase in contrast with targeted nanoparticles. Tumors as small as 4 mm were detectable 4 h post-injection, providing evidence of a promising, sensitive tool for early breast cancer diagnosis.

Electrical impedance mammography (EIM), as one of the EIT medical applications, is applied for diagnostics and imaging of the breast. Quality of reconstructed images in this method depends on precision of the EIM hardware and efficiency of the image reconstruction algorithm. One of the linearized methods in EIT image reconstruction is Weighted Back-Projection (WBP). The purpose of this paper is to present a novel method, which is a modified version of the current 3D WBP algorithm (MWBP), to improve the quality of reconstructed images in electrical impedance mammography. In order to calibrate the 3D WBP algorithm with regards to real equipotential surfaces and output results, some attempts have been made to model the real EIM conditions in terms of body shape and electrode positions by means of a saline-filled phantom. We have proposed a few modifications which improve the quality of images greatly, in terms of sensitivity, resolution, contrast, and accuracy in size and position of objects under imaging. The mentioned modifications contain: changing the problem assumptions, adding a new weighting function to the current 3D WBP equation, and defining an exciting radius for the pixel being reconstructed. The final results (containing phantom and in vivo images) prove the efficiency of the proposed modifications.

Current in-vitro biodegradation test methods for characterizing bioabsorbable polymer implants including ASTM F1635-11, focus on testing mechanical and chemical properties of samples under static conditions. These tests oversimplify the implant service environment and yield limited data due to the lack of fluid flow, stresses, and pressures. The effects of the helical or spiral blood flow observed in arterial vessels are of particular interest for biodegradable polymer cardiovascular stents due to its promising biomedical uses and relatively recent discovery. In this study, a novel 3D printed prototype flow device was designed and developed to simulate in-vivo conditions including flow rates, flow characteristics, pressures, temperatures, and chemical environment. The in-vitro biodegradation behavior of poly(ε-caprolactone) (PCL), in phosphate buffer solution (PBS) was used to study the influence of flow conditions compared to a standard static ASTM method over 5 weeks. Characterization of the polymer degradation was performed by evaluating changes in weight loss, molecular weight and the degree of crystallinity as a function of time. The number average molecular weight of the polymer showed the largest decline, decreasing linearly with time by 22% and 5% for the samples tested using the flow device and ASTM method, respectively. Similarly, the degree of crystallinity was found to increase linearly by 16% and 6% for the flow device and ASTM method, respectively. Helical/spiral flow at the flow rates as low as 1 cm³ s⁻¹ were found to enhance the bulk degradation of PCL by up to 80% when compared to the static ASTM method. A combination of bulk and surface erosion mechanisms were proposed for the degradation behavior of the PCL in the flow prototype. This indicates that by more accurately mimicking physiological conditions, including blood dynamics, this 3D printed prototype can serve as an improved method for testing bioabsorbable and biodegradable polymers for implanted devices.

Purpose: The intent of this work was to evaluate the ability of our 200 kV kilovoltage arc therapy (KVAT) system to treat realistic lung tumors without exceeding dose constraints to organs-at-risk (OAR). Methods and Materials: Monte Carlo (MC) methods and the McO optimization framework generated and inversely optimized KVAT treatment plans for 3 SABR lung cancer patients. The KVAT system was designed to treat deep-seated lesions with kilovoltage photons. KVAT delivers dose to roughly spherical PTVs and therefore non-spherical PTVs were divided into spherical sub-volumes. A prescription dose of 12 Gy/fx × 4 fractions was planned to 90% of the PTV volume. KVAT plans were compared to VMC++ calculated, 6 MV stereotactic ablative radiotherapy (SABR) treatment plans. Dose distributions, dose volume histograms, gradient index (GI), planned mean doses and plan treatment times were calculated. Dose constraints for organs-at-risk (OAR) were taken from RTOG 101. Results: All plans, with the exception of the rib dose calculated in one of the KVAT plans for a peripheral lesion, were within dose-constraints. In general, KVAT plans had higher planned doses to OARs. KVAT GI values were 5.7, 7.2 and 8.9 and SABR values were 4.6, 4.1, and 4.7 for patient 1, 2 and 3, respectively. KVAT plan treatment times were 49, 65 and 17 min for patients 1, 2 and 3, respectively. Conclusions: Inverse optimization and MC methods demonstrated the ability of KVAT to produce treatment plans without exceeding TG 101 dose constraints to OARs for 2 out of 3 investigated lung cancer patients.

Bone marrow plays an important role on the mechanical properties of trabecular bone. Its effect on the mechanical properties of porcine trabecular bone is studied in this paper. Uniaxial compression at a low strain rate (0.01 s⁻¹ to 20% strain) and stress relaxation tests (600 s at 85, 70 and 55% of the max. load) were done on 90 different femur samples. Half the samples were treated to extract the bone marrow. The average pore size of the trabecular network was 0.280 ± 0.056 mm. Higher values of elastic modulus (37%), 0.2% yield stress (48%), maximum stress (39%), strain at maximum stress (54%), and toughness (300%), were found for the samples which had the bone marrow extracted and were saturated with a saline solution. A linear relation between the applied load and the relaxation stress of ${\sigma }_{rel}=0.76{\sigma }_{o}$ was found, which means that the trabecular bone behaves as a linear viscoelastic material. A mathematical approximation of the relaxation response was done using a Kohlrausch-Williams-Watts model for viscoelastic materials. Results show that it is essential to consider the viscoelastic behavior that the marrow has on the mechanical properties of the trabecular bone. The effect that the bone marrow has on the stress relaxation was found to be negligible at low strain rates and in the elastic stage of deformation.

In this investigation, the anti-proliferative activity of a novel molybdenum complex was distinguished on LNCaP (as an androgen-dependent), PC3 (as an androgen-independent) cancer cells, and normal PBD2-fib cells (as a control) using MTT assay, flow cytometry, RT-qPCR, and western blotting. The MoS₂ was prepared by the hydrothermal method, and the synthetic MoS₂ characterized using XRD, EDX, FESEM, HRTEM, and Raman spectroscopies to confirm the success of the synthesis and the unique crystal structure. The cells were treated with different concentrations of MoS₂ (0, 5, 10, 20, 35 and 50 μg ml⁻¹) for 24, 48 and 72 h. The obtained results showed that the IC50 values for LNCaP (21.02 ± 0.09 μg ml⁻¹) and PC3 (23.03 ± 0.07 μg ml⁻¹) were significantly lower than that recorded for normal fibroblast cells (41.56 ± 0.012 μg ml⁻¹). Flow cytometry findings demonstrated that the complex is effective in reducing cancer cell viability via apoptosis. RT-qPCR data showed a decrease in BCL2 expression and increases in BAX and P53 gene expression, which were also correlated with the synthetic complex response. The expression of P53 protein increased in LNCaP and PC3 cells after treating with MoS₂. Also, these data show the anti-tumor properties of synthetic molybdenum complexes in prostate cancer cells. To conclude, the results indicated that the novel design of nanoparticles can be created a new generation of nano-therapeutics strategies in different types of cancer.

Quantum dot (QD) aggregate formation is essential, especially, in nanoparticle-based drug delivery systems. Imaging of these targeted QD aggregates exposes information about the the treatment of many diseases including cancer. Scanning Acoustic Microscopy (SAM) is a non-invasive and rapid imaging modality, which can obtain qualitative and quantitative features simultaneously. In our study, acoustic impedance microscopy of QD aggregates was performed by SAM for evaluating the potential of SAM in the detection of lead-sulphide (PbS), graphene and cadmium-telluride/cadmium sulphide (CdTe/CdS) quantum dot aggregates for the first time. Absorption spectra of QDs, obtained with an ultraviolet-visible spectrometer, and fluorescence spectra of QD aggregates, obtained with an inverted fluorescence microscope, are also demonstrated. The success of imaging quantum dot aggregates by SAM indicated the potential of SAM in monitoring the micro-environment of the disease and also the therapeutic effect of the drug-loaded QD aggregates.

Objective. This work aims to present a deeper investigation of the classification performance achieved by a motor imagery (MI) EEG-based brain-computer interface (BCI) using functional connectivity (FC) measures as features. The analysis is performed for two different datasets and analytical setups, including an information-theoretic based FC estimator (correntropy). Approach. In the first setup, using data acquired by our group, correntropy was compared to Pearson and Spearman correlations for FC estimation followed by graph-based feature extraction and two different classification strategies—linear discriminant analysis (LDA) and extreme learning machines (ELMs) - coupled with a wrapper for feature selection in the mu (7-13 Hz) and beta (13-30 Hz) frequency bands. In the second setup, the BCI competition IV dataset 2a was considered for a broader comparison. Main results. For our own database the correntropy / degree centrality / ELM approach resulted in the most solid framework, with overall classification error as low as 5%. When using the BCI competition dataset, our best result provided a performance comparable to those of the top three competitors. Significance. Correntropy was shown to be the best FC estimator in all analyzed situations in the first experimental setup, capturing the signal temporal behavior and being less sensitive to outliers. The second experimental setup showed that the inclusion of different frequency bands can bring more information and improve the classification performance. Finally, our results pointed towards the importance of the joint use of different graph measures for the classification.

Hypergranulation, bacterial infection, and device dislodgment are common complications associated with percutaneous gastronomy (PG) tube placement for enteral feeding largely attributable to delayed stoma tract maturation around the device. Stoma tract maturation is a wound-healing process that requires collective and complete migration of an advancing epithelial layer. While it is widely accepted that micropatterned surfaces enhance cell migration when cells are cultured directly on the substrate, few studies have investigated the influence of apical contact guidance from micropatterned surfaces on cell migration, as occurs during stoma tract formation. Here, we developed 2D and 3D in vitro epithelial cell migration assays to test the effect of various Sharklet micropatterns on apically-guided cell migration. The 2D modified scratch wound assay identified a Sharklet micropattern (+10SK50×50) that enhanced apical cell migration by 4-fold (p = 0.0105) compared to smooth controls over the course of seven days. The best-performing micropattern was then applied to cylindrical prototypes with the same outer diameter as a pediatric PG tube. These prototypes were evaluated in the novel 3D migration assay where magnetic levitation aggregated cells around prototypes to create an artificial stoma. Results indicated a 50% increase (p < 0.0001) in cell migration after seven days along Sharklet-micropatterned prototypes compared to smooth controls. The Sharklet micropattern enhanced apically-guided epithelial cell migration in both 2D and 3D in vitro assays. These data suggest that the incorporation of a Sharklet micropattern onto the surface of a PG tube may accelerate cell migration via apical contact, improve stoma tract maturation, and reduce skin-associated complications.

A new absorption spectroscopy method which enables rapid measurement of the diffusion coefficient of Fe³⁺ in gelatin gel used in dosimetry was investigated. The physical approach, the preparation and the experimental application of this new method were tested on the EasyDosit dosimetry gel and the results were validated by MRI measurement. The diffusion coefficients measured on this gel were then compared with those of the other gels presented in the literature. This gel, which is considered stable, has a small post-irradiation ion diffusion, despite the absence of a complexing or crosslinking agent. The diffusion coefficients of a range of dosimetry gels containing different proportions of gelatin were also measured and the results show diffusion coefficients D from 3.21.10⁻¹⁰ m².s⁻¹ to 2.41.10⁻¹⁰ m².s⁻¹.

The purpose of the current study was to formulate ethosomal transdermal polymeric patch containing losartan potassium for the treatment of hypertension. Ethosomes are the soft, malleable vesicles which in one of the most widely known novel and non-invasive drug delivery system. At the very onset, ethosomes were prepared by varying the concentration of lipids then the prepared ethosomes were incorporated in the prepared Eudragit RS100 and Eudragit RL100 patch. Preformulation studies, FTIR and DSC analysis showed that the drug and excipients do not have any interaction. After that the prepared ethosomal formulation was characterized for the particle size, zeta potential, PDI, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM), % encapsulation efficiency and in-vitro drug release study. The patch was evaluated for the weight variation, thickness, folding endurance, tensile strength, %moisture content, in-vitro release study, in-vivo study, and stability study. The optimized ethosomal formulation EF5 shows a particle size of 112.2 ± 1.3 and zeta potentials of −59 ± 0.8 mV along with the 89.21 ± 2.82 % encapsulation of losartan potassium and 86.45 ± 0.02 release of drug in 72 h from the ethosomes. In-vivo study shows that an optimized patch significantly treats hypertension as compared to the losartan potassium. The transdermal patch shows maximum stability at 4 °C/60 ± 5RH. These results suggest that the transdermal delivery of losartan potassium in the form of ethosomal transdermal polymeric patch can provide a sustained effect in the treatment of hypertension.

Mesh products are critical for successful long term surgical repair of many anatomic defects, including hernias and pelvic prolapse. Biocompatibility of polymeric mesh depends on the foreign body response- how the tissues react to physicochemical properties, including porosity and mesh 'weight'. We postulate that effective surface area, the total filament area in contact with the tissues, is an important variable for long-term repair strength. We present a technique utilizing synchrotron x-radiation microComputed Tomography (microCT) to calculate the effective surface area of polymeric meshes. Six representative polypropylene-based hernia meshes, including composite meshes, were studied: Ethicon PROLENE^TM, Ethicon PROLENE^TMSoft Mesh, Ethicon PHYSIOMESH^TM, Ethicon ULTRAPRO^TM, Atrium PROLITE^TM Mesh, and Bard^® Soft Mesh. Ethicon PROLENE^TM , a heavy weight mesh, had the highest effective surface area at 6.44 cm² cm⁻² and Ethicon ULTRAPRO^TM, a composite light-weight mesh, had the lowest effective surface area at 0.62 cm² cm⁻². We conclude that this technique can reliably be used to further classify mesh, as manufacturers and surgeons continue to optimize the safety profile of these implants.

Purpose: The range precision in carbon ion therapy is extremely sensitive to tissue density variations. A high energy carbon beam, after crossing a high-gradient edge parallel to the beam direction, suffers from range mixing leading to the detection of multiple Bragg peaks (BPs) varying intensity and water equivalent thickness (WET). The purpose of this work was to introduce a model that determines the position of a high-gradient edge based on information acquired from carbon transmission imaging. Methods: A model was derived to determine the lateral distance between the irradiation beam propagation axis and the edge position. To validate it, carbon beams were simulated and propagated through two parametric phantoms: (1) a bone cube in a water tank and (2) a semi-cylindrical bone insert in a water tank. The method was tested in a lung tumor case where range mixing led to more than two BPs being detected, requiring an iterative BP decomposition to determine the fraction of carbon ions crossing the materials surrounding the edge of interest. Results: The theoretical model predicted the edge position relative to the beam position with an error ≤1 mm for all studied cases with a maximum dose delivered of 24 μGy. Conclusions: The method presented here is a proof of principle. It does not take into account clinical uncertainties. However, this approach provided promising results suggesting that future extension to assess the impact of clinical uncertainties should be performed.

Surgery, chemotherapy and radiotherapy remain as the major treatment strategies for cancers. Some agents such as anti-cancer drugs have capacity to enhance the radiation sensitivity of cancer cells at G2/M phase, leading to an improved radiotherapeutic efficacy. BI6727 is an ATP-competitive polo-like kinase 1 (Plk 1) inhibitor and an anti-cancer drug. Using the radio-resistant 9L rat gliosarcoma cells as model, we examined the effect of BI6727 on cell growth and assessed the chemo-radiotherapeutic efficiency between 150 kVp conventional irradiation (dose rate of 0.76 Gy min⁻¹) and 66 keV synchrotron x-ray broad beam irradiation (dose rate of 46 Gy s⁻¹). Our studies showed that BI6727 significantly caused cell growth arrest at G2/M phase and inhibited 9L cell proliferation with EC₅₀ of 58.1 nM. In combinatory treatment, irradiation of BI6727-treated 9L cells with synchrotron x-rays at a dose rate of 46 Gy s⁻¹ resulted in significant reduction of the cell survival compared to the conventional x-rays at a dose rate of 0.76 Gy min⁻¹. These results indicated that Plk1 inhibitor BI6727 enhanced radio-sensitization of 9L cells in a dose rate dependent manner. For clinical application, irradiation with high dose rate is a promising strategy to improve chemo-radiotherapeutic efficacy for gliosarcoma cancer.

Bioprinting offers an alternative approach for tissue engineering and exhibits the great potential to play a key role in personalized medicine. One of the major advantages of bioprinting is its capability of achieving the homogeneous distribution of cells within large tissue scaffolds. Microspheres have been used for controlled release of bioactive molecules in tissue engineering. Recently studies show that microspheres, especially positively charged, could promote the vascularized tissue formation. This study aims to develop a bioprinted scaffold containing microspheres. The double emulsion system, water in oil in water (W/O/W), was used to produce the microspheres considering its advantage for controlled release of small molecules. Design Expert^® Software was used to optimize the microsphere production process and chitosan coating was performed to provide the positively charged surface of the microspheres. Fourier-transform infrared spectroscopy (FTIR) and confocal microscopic analysis confirmed the successful formation of the microspheres as well as the loading of bioactive molecules, e.g., estradiol (E2), into the microspheres. Bioprintability of the microsphere incorporated bioink was tested. The results indicated that microspheres did not adversely affect the bioprinting process. This novel tissue scaffold shows great promise for tissue engineering applications.

This note aims to introduce and share with a broader community a collection of sixteen anatomically and numerically accurate high-resolution, 2-manifold CAD compatible head models intended for electromagnetic simulation (neuromodulation and neuroimaging) tasks. Our experience has shown that these models may be quite useful when testing software performance and convergence in realistic anatomical scenarios or performing side-by-side software comparisons. The collection is based on MRI data from the Human Connectome Project (HCP) segmented using the SimNIBS processing pipeline. The average number of triangular surface facets in a model is 866,000, the average triangle quality is 0.25, the average edge length is 1.48 mm, and the average surface mesh density or resolution is 0.57 points per mm². This mesh resolution corresponds approximately to the resolution of the high-quality 3 T images. Each model contains skin, skull, CSF (cerebrospinal fluid), GM (gray matter), cerebellum, WM (white matter), and ventricles 2-manifold compartments. The companion mesh processing tools within the MATLAB platform include evaluating cross-section model topology, shell deformations, and model refinement (oversampling). The models are fully compatible with ANSYS Electronics Desktop, SimNIBS, CST Studio Suite, Sim4Life/SEMCAD, and other electromagnetic software packages.

Introduction: To correlate dose from ionizing radiation with cell kill probability, viability and clonogenic assays are often performed following in vitro irradiation of cells in 96-well culture plates. The objective of this work was to examine how dose to adherent cells in 96-well culture plates depended on the conditions in which the irradiations were performed. The aim was to provide support for standardized irradiation setup conditions so that in vitro cell assays can be more precisely compared. Materials and Methods: 96-well culture plates were exposed to a 6 MV photon beam from a linear accelerator. Dose measurements were performed by securing a piece of EBT3 Gafchromic film to the underside of each plate. Each well contained either 200 μl of tap water or canine osteosarcoma cells (OSCA 40) in 200 μl of media. Exposures were performed to assess the dependence of dose to the depth of measurement, the thickness of the backscatter material, the field size, and the position of a plate within the treatment field. Results: Culture plate doses demonstrated a strong dependence on backscatter material thickness and field size. Providing less than 0.5 cm of water equivalent backscatter material resulted in a mean measured underdose of more than 3% for a 30 × 30 cm² field. Decreasing the field size to 13 × 9 cm² yielded a mean measured dose within 0.5% of the prescribed dose. At the central-axis depth where maximum dose occurs (d_max = 1.5 cm), irradiation of four plates simultaneously resulted in a mean measured dose 3.5% higher than measurements of single plates placed in the center of the field. Conclusions: Inadequate consideration of in vitro irradiation setup conditions is likely to result in discrepancies between prescribed and delivered doses. Such discrepancies can be minimized by providing 5 cm of backscatter material and 10 cm of buildup material; and by exposing one centrally located plate at a time.