Table of contents

Monte Carlo methods apply various physical models, either condensed history (CH) or track structure (TS), to simulate the passage of radiation through matter. Both CH and TS models continue to be applied to radiation dosimetry investigations on a micro and nano scale. However, as there has been no systematic comparison of the use of these models for such applications there can be no quantification of the uncertainty that is being introduced by the choice of physics model. A comparison of CH and TS models available in Geant4, along with a quantification of the differences in calculated quantities on a micro and nano scale, has been undertaken in this study. A sphere of liquid water was simulated, with an incident beam of monoenergetic electrons with kinetic energy between 50 eV and 10 keV. The energy deposition (typical of microdosimetry) and number of ionisations (typical of nanodosimetry), per incident particle, were recorded in a water sphere with diameter varying between 1 nm and 1 m. The simulations were repeated using the following physics packages: Livermore (CH), Penelope (CH) and Geant4-DNA (TS). Results indicated that substantial differences were present between calculated physical quantities, depending on the physics model, target diameter and ratio of the target diameter and mean track length of the incident electron. In the case of the smallest targets, the calculated energy deposition was higher when using the CH models, while the number of ionisations was typically underestimated. In larger targets the energy deposition was in good agreement for all physics models, however the number of ionisations was significantly underestimated by the CH approach, in some cases by almost two orders of magnitude. Regarding CH models, the parameter that had the greatest impact on the results was found to be the threshold of production of secondary particles; when this was minimised the CH and TS results showed the best agreement.

Currently, TLDs and Gafchromic EBT3 film are commonly used for skin dose measurement during Total Skin Electron Therapy. However, measurements using these dosimeters are time consuming due to post-irradiation processing requirements. The MOSkin has advantages of being a small physical size with a 0.55 μm thick gate oxide and a water equivalent depth of 0.07 mm while providing real-time dosimetry. Measurements of the MOSkin's dosimetric characteristics were performed using a 6 MeV electron beam with an Elekta Infinity linear accelerator. For the TSET measurements, doses measured with the MOSkin were directly compared to TLDs and Gafchromic EBT3 film using a 6 MeV high dose rate electron beam. A 6 mm Perspex spoiler was placed and aligned perpendicularly to the beam in order to lower the effective beam energy and improve dose homogeneity. The MOSkin showed good dose linearity (R² = 0.9986) and dose rate independence for a 6 MeV electron beam and behaved very similarly to the other types of dosimeters that are commonly used in vivo dosimetry. For the TSET measurements, all three detector types showed a very similar trend of dose readings over the range of measurement points. Therefore, the MOSkin is an effective skin dosimeter for TSET dosimetry.

Despite impressive progress in molecular biology and genetics over the last decades, the key question is still unanswered—why the genetic code is triplet and what information it keeps and transfers over translation. Unexpectedly, the answer comes not from biology but from spin physics and computational quantum chemistry. The study aims to shed light on how mRNA sees the right tRNA and what sort of communication ensures the codon–anticodon recognition. The data rests on the quantum mechanical/molecular mechanical quantum chemistry computations of the mRNA-tRNA fragments differing in 61 codon–anticodon nucleotide triplets coding 20 canonical amino acids.

Background and aims. The lower esophageal sphincter (LES) regulates transport of ingested substances from the esophagus to the stomach. However, little is known about the muscle fiber spatial arrangement. Diffusion tensor magnetic resonance imaging (DT-MRI) can reveal microscopic details about tissue architecture. The aim of this study was to quantitatively describe the muscle fiber arrangement in the 3D model of the LES region. Methods. A 50 kg pig was used. After tissue fixation, a 7 × 7 × 7 cm³ tissue sample of the distal esophagus, the proximal stomach, and the diaphragmatic crura was prepared for DT-MRI scanning. The fiber angles were computed in the LES region. Results. The fibers were distributed heterogeneously across the muscle layer of the LES region. In the proximal LES region, the fibers showed a helical crossing pattern with fiber angles ±77.3 to about ±15.0° from longitudinal muscle layer (LM) to circumferential muscle layer (CM). The gastroesophageal flap valve (GEV) was found in the distal LES region and the fibers throughout the GEV were circumferentially distributed. In the distal LES region excluding the GEV, the muscle fibers transferred from axial direction with fiber angle distribution peaks at ±72.5 in LM to the oblique direction with fiber angles peaks at −47.3° in CM. Conclusions. This is the first study that quantitatively demonstrated the smooth muscle fiber distributions in the lower esophagus and the fiber transition through the wall. The results on the myoarchitecture structure from this study will be useful for future LES computational modeling analysis.

Tissue deformation simulations for pre-operative planning or intra-operative guidance of medical procedures require accurate patient-specific models and are commonly performed using the Finite Element Method (FEM). Since only a small part of the entire body is typically observed with medical imaging, the deformation models are often limited to a relatively small region-of-interest (ROI). Surrounding this ROI, one then needs to define suitable boundary conditions for an accurate simulation. Conventionally, boundary conditions are set arbitrarily or heuristically at chosen model locations; typically as either zero-displacement or -force constraint, which obviously are suboptimal where ROI borders are neither fixed (e.g. on bone) or free (e.g. skin facing the air). In this work, we present a novel boundary-condition formulation, called compliance boundary conditions (CBC), which approximate the effect of anatomy outside this ROI and augment this onto the ROI border nodes. CBC can be parametrized from observed tissue displacements, e.g. tracked in ultrasound (US) or magnetic-resonance imaging. It is inherently embedded in the FEM deformation model to be used for computing any interaction response. CBC is a generalization of conventional boundary constraints, where the typical zero-displacement and -force constraints are obtained at the two extremes of the given CBC parameter. We demonstrate CBC for linear- and quadratic-strain FEM models in 2D and 3D numerical phantoms, for which different element/integration formulations and the effect of noise are studied. CBC is shown to reduce displacement errors for both 2D and 3D numerical phantoms by more than 50% compared to conventional boundary conditions. We also present CBC on tissue-mimicking gelatin phantom experiments from displacements observed in US images. In an application scenario of simulating needle insertion for prostate brachytherapy, CBC is shown to reduce seed placement errors by more than 70% compared to conventional boundary conditions.

The increase in the incidence of ocular discomfort has primarily been attributed to: contact lens wear, refractive surgery, meibomian gland dysfunction, and the aging population. Efforts to diagnose, treat and understand the underlying causes have been impeded by a lack of suitable methods to quantify ocular surface sensitivity. Traditional instruments are either inaccurate, difficult to use or not generally available. A new method is presented that utilizes a liquid jet to generate a precisely controlled stimulus to the ocular surface. The stimuli are adjustable in strength to determine sensitivity thresholds for either mechanical, thermal or chemical stimulation. Technical details are described and calibration methods and results are presented for three modes of operation. At the heart of the instrument is a microprocessor controlled microvalve which can operate at a frequency of up to 4 kHz to precisely control flow of the ejected liquid. The stimulus strength can be varied either by the ejected volume or the velocity. Repeatability for the ejected volume was established over a range of different control parameter settings: temperature, pressure, working distance, operating mode and volume. For 10 repeats, the maximum standard deviation was less than 3% of the mean of ejected volume for any particular setting. The maximum error for the lateral targeting of the liquid jet for the 30 mm distance between nozzle and target surface was less than ±0.5 mm. A simplified mathematical model is presented to physically quantify the stimulus strength. Based on the liquid jet concept, a new instrument was developed and technically validated that can apply a precisely controlled stimulus to an ocular surface to determine mechanical, and potentially thermal and chemical sensitivity threshold levels. The strength and the positioning of the applied stimulus can be precisely controlled. Temporal and spatial aspects of corneal sensation can also be investigated with this new instrument.

Feasibility studies were performed to evaluate the potential for dose reduction when investigating cervical spine trauma using multidetector CT (MDCT), without reducing fracture detectability. The studies utilised both in vitro phantom work and low-dose (LD) clinical images from archive. Test phantoms were constructed using dry human cervical vertebrae suspended inside tissue equivalent material. Vertebrae were modified with fine osteotomies to simulate fracture lines. A LightSpeed VCT 64-slice scanner (GE Healthcare Medical Systems, Milwaukee, WI) was employed to scan the phantom using a series of tube current (mA) settings and constant tube voltage (kVp). The phantom was also scanned using the manufacturer's programme for automatic tube current modulation (TCM). The recommended TCM tube current table ranges were found to be set to high values (120–600 mA); therefore further modified TCM exposures were made with lower minimum value of 50 mA. Images were assessed under standard clinical review conditions. Low-dose CT series from clinical PET/CT examinations on clinical archive were also evaluated to explore their suitability to visualise cortices and other bony characteristics. Preliminary indications are that image assessments of critical bony features can be achieved with a high degree of confidence when the radiation dose is reduced by a factor of two. Dose Length Product (DLP), was used for relative comparisons between examinations. Using the standard TCM's DLP as the reference value, bony features were visualised suitably using 60–80 mA and a tube current of 60 mA would lead to a halving of the total DLP to 130 mGy cm. Just reducing the lower limit of the TCM selection range to 50 mA led to a more than 58% reduction in DLP. Our study demonstrates that there is potential for radiation dose reduction during routine clinical imaging for cervical spine trauma and provides supporting evidence for a clinical study.

Background. Hemodynamic changes and consequent low-density lipoprotein (LDL) filtration play an important role in the atherosclerotic plaque development of coronary arteries. In this pilot controlled case study, we aimed to investigate the correlation between parameters derived from computational fluid dynamics (CFD) simulation and risks (both current and long-term) of coronary atherosclerosis. Methods. We reconstructed geometric models from the baseline computed tomography (CT) angiography of two subjects, one patient and one healthy control, and performed CFD simulations. We estimated the current risk of ischemia by fractional flow reserve (FFR). We estimated the potential risk of plaque development by wall shear stress (WSS) and LDL filtration rate with follow-up clinical imaging validation. We investigated the effects of simulation methods (transient/static) and rheological models (Newtonian/Carreau–Yasuda) by comparing the corresponding results (FFR, WSS and LDL filtration rate) in the patient's left anterior descending coronary artery. Results. In baseline CFD simulation, FFR indicated mild current ischemic risk of the patient, in accordance with existing angina pectoris. Baseline WSS and LDL filtration rate results were related with in vivo plaque development. The plaque-growth locations in follow-up CT angiogram coincided with areas of low WSS and high LDL filtration rate in the baseline simulation. The LDL filtration rate delineated more specific risky areas than WSS. Between transient and static results, the difference of FFR was less than 5% in the whole model. As to WSS and LDL filtration rate the transient/static difference was within 20% in most areas, but rose up to 50% for WSS and even higher for LDL filtration rate, in areas with low WSS and high LDL filtration rate. As to rheological effects, Newtonian/Carreau–Yasuda difference was negligible for FFR throughout the model, within 30% for WSS and LDL filtration rate in major areas, and 50% or higher in certain segments where low WSS and high LDL filtration rate existed. Conclusion. CFD results appeared to be related with in vivo development of coronary atherosclerosis. Simulated FFR and its threshold value 0.8 demonstrated the ischemic risk. Both WSS and LDL filtration rate could indicate areas of plaque growth.

Objective. A major goal of brain–computer-interface (BCI) technology is to assist disabled people with everyday activities. Although lots of information is available on typical movement procedures, integration of this knowledge is rarely found in motor BCI decoding solutions. Approach. Here, we apply a hidden Markov model (HMM) based approach for continuous decoding of finger movements from electrocorticographic recordings from three human subjects. Information about relative frequencies of consecutive finger movements is included in the decoding routine using so-called bi-gram models. Main results. The presented method achieves accuracies up to 73% for continuous decoding of finger movements. Prior knowledge (PK) incorporation further increases decoding accuracies by up to 12.5% (absolute) in a generic BCI setting and by up to 22% in a more specific, task-related setup. Significance. The results provide evidence for the importance of PK incorporation for motor BCI decoding. We show that this can be done conveniently using HMM decoders. Our results strongly suggest the extension of the use of HMMs from conventional speech-related topics (like spelling devices) towards motor BCI solutions.

The purpose of this work is to introduce the design of a transmission x-ray target suitable to be used in kilovoltage x-ray tubes such as those employed in orthovoltage x-ray therapy. The target consists of a 20 μm thick tungsten slab deposited on top of a 1 mm copper plate. Monte Carlo simulation is used to determine both the energy absorbed in the tungsten and copper slabs, and also to calculate the characteristics of the resultant x-ray production. The absorbed energy distribution in the target is then fed into a finite element software to determine the heat distribution and its evolution in time as a function of both the electron current incident on the target and the focal spot size. A cooling system is proposed and modeled based on these results to prevent the target assembly from melting. Absorbed dose rates in water are also calculated for both the proposed transmission and a standard reflection target as a function of the incident electron current. We show that, compared to the reflection target, our design increases by more than 100% the emission of x-rays, and that the proposed cooling system is capable of operating at a sustained power rating above 4 kW.

The use of iterative reconstruction (IR) in computed tomography (CT) has become a useful tool for improved image quality or for reduced dose in CT examinations. In this study, the image quality of the two different Siemens IR algorithms, sinogram affirmed iterative reconstruction (SAFIRE) and advanced modelled iterative reconstruction (ADMIRE), were evaluated and compared. Differences between the Stellar detector and the conventional detector and similarities between scanners with the same detector and IR algorithm were also examined. The objective image quality parameters modulation transfer function (MTF) and noise power spectrum (NPS) were measured on a Catphan 600 phantom (The Phantom Laboratory Incorporated, NY) for five different Siemens CT scanners. MTF was calculated from the circular edge of the sensitometry targets in Catphan to facilitate measurements at different contrasts and dose levels. The results showed that the image quality was improved by using ADMIRE compared to SAFIRE on the same CT scanner equipped with the Stellar detector for certain specific tasks. The MTF was higher for the three low contrast objects when the sharp reconstruction kernel was applied. The CT scanners equipped with the Stellar detector showed an improved image quality compared to the CT scanners equipped with the conventional detector. Larger differences in MTF and NPS were observed between the detectors than between SAFIRE and ADMIRE.

Purpose. Pre-clinical determination of reasonable simplified examination protocols before clinical application to assess the performance of a direct digital radiography (DDR) system. Material and methods. The experimental setup consists of a DDR system with fixed flat-panel detector (CsI). A phantom with low-contrast structures (LCS) was examined in two settings in order to simulate standard radiographs: (1) small peripheral joints like the wrist (no patient phantom, no anti-scatter grid) and (2) big proximal joints like the hip (20 cm water tank patient simulation and with an anti-scatter grid). Setup (1) was manually exposed at 55 kV/2 mAs, 60 k V/1.6 mAs and 65 k V/1.25 mAs. Setup (2) was automatically exposed at 1.6, 2.5, 4 and 6 μGy per kV-setting (80 ± 5 kV). Contrast-detail curves (CDC) were generated by analyzer software. Results. Exposures of setup (1) showed similar CDC (p = 0.99) with a decreasing curve with larger diameter of LCS. In all exposures of setup (2) CDC were similar for all kV-settings (p > 0.93) with a decreasing curve with larger LCS diameter. CDC insignificantly decrease with increasing exposure dose (p > 0.38). Conclusion. Low-contrast detectability was independent of kV and marginally dependent on the dose, both within a certain range. This could be used to further reduce radiation dose and simplify examination protocols to be tested in a further clinical study.

A single human oesophageal adenocarcinoma cell (OE33) has been imaged using aperture infrared scanning near-field optical microscopy (IR-SNOM) in transmission and reflection and also by Fourier-transform infrared (FTIR) microspectroscopy in transmission only. This work presents the first images obtained in both transmission and reflection of the same specimen using the aperture IR-SNOM technique. The results have been used to compare the two SNOM modes and also the two techniques, which have complementary capabilities. The SNOM technique necessitates a very stable source and a careful choice of wavelengths, since it is too slow to yield images at the thousands of wavelengths obtained with FTIR. However the SNOM technique is not diffraction limited and with careful fabrication of tips can yield images with high spatial resolution. There is no significant correlation between the SNOM images obtained in transmission and reflection and the correlations between images obtained at different wavelengths vary with the different imaging modes. These results are attributed to the strong dependence of the evanescent wave on both the wavelength and the distance between the tip and the source of the signal within the sample. While both transmission and reflection SNOM images show some correlation with topography this is not a dominant effect. These results indicate that with suitable calibration a combination of reflection and transmission aperture IR-SNOM measurements has the potential to reveal information on the depth distribution of the chemical structure of a specimen.

Electroporation is the creation of pores in a cell by applying an external electrical field and creating a voltage in the range of 200 mV–1 V across the cell's membrane. This process is used intentionally in order to introduce chemicals, drugs or DNA into a cell. A model was created to determine whether electroporation would occur during the use of the signals typically used during functional electrical stimulation of skin and if it occurs what effect it has on the overall impedance of skin. Results from the simulation show that there is a threefold reduction in the electrical impedance of the cells.

Regenerative ligament and tendon repair scaffolds have been highly researched, yet few match the mechanical properties of native tissue, while fewer drugs have been explored for enhancing cell infiltration into the damaged tissue. Here a nanofiber scaffold of silk fibroin (SF)–collagen blend is explored as a biologically enhanced matrix, along with a therapeutic agent (bone morphogenetic protein-13, [BMP-13]) for connective tissue regeneration. SF and collagen were blended and electrospun to form fibrous scaffolds with 1.15 ± 0.08 μm diameter fibers. These scaffolds were crosslinked with either methanol or ethanol. Crosslinking with methanol resulted in significantly higher mechanical strength compared to ethanol treated scaffolds (2.92 ± 0.21 MPa versus 1.13 ± 0.08 MPa, respectively). Adipose-derived stem cells showed robust cell attachment and proliferation on SF–collagen scaffolds, with confocal imaging suggesting cellular alignment and spreading. BMP-13 growth factor is further shown to promote cell migration into SF–collagen scaffolds. In all, electrospun SF with telocollagen produces a regenerative matrix with enhanced tensile strength. BMP-13 improves cellular infiltration into electrospun SF–collagen scaffolds and may prove a potent chemotactic agent for enhancing ligament and tendon repair.

Current actigraphic sleep/wake detection algorithms have predominantly been validated against polysomnography, although the accuracy of such validations is dependent on the degree to which the timestamps of these two methods of data collection are synchronised. We created and validated an algorithm to temporally align actigraphy and polysomnography data using a sample of 100 healthy young adults, recruited from a pool of participants in the Western Australian Pregnancy Cohort (Raine) Study. Each participant underwent one night of polysomnography with simultaneous wrist actigraphy (Actigraph GT3X+). Our alignment algorithm incorporates the raw acceleration data and considers the best alignment when the sum of the products of acceleration and polysomnography values are maximised. Segments of the night of various lengths and locations were considered as input values in addition to several values for the maximum allowable discrepancy. The optimal input values were determined by comparing accuracies, sensitivities and specificities calculated from two commonly used sleep/wake classification methods, and then validated using a simulation study. Validation suggested that our alignment algorithm can successfully align polysomnography and actigraphy timestamps. This allows for more accurate and detailed actigraphic sleep/wake detection algorithms to be created, thus strengthening the use of actigraphy as an appropriate method for sleep detection.

Efficient cancer cell capture has been previously demonstrated on functionalized surfaces with defined nanotopography such as nanoscale texture. However, conventional additive and subtractive methods to achieve nanotexture require access to specialized nanofabrication equipment within a dedicated cleanroom environment. Here, we present a technique to create flexible polydimethylsiloxane (PDMS) surfaces with high roughness (R_q ∼ 680 nm) using a molding approach that can be performed in a standard laboratory environment. We also demonstrate a one-step integration of nanotextured PDMS into a reversibly sealed easy access modular microfluidic platform to simplify cell capture workflows (e.g. cell introduction, capture, and isolation). In our proof of concept, we characterize nanotextured PDMS surfaces and investigate the effect of increased surface area on cancer cell adhesion strength and capture compared to non-textured (plain) PDMS. We found that cells attached more strongly to antibody-functionalized nanotextured surfaces (26% ± 5% increase in threshold fluid shear stress, τ_50%) and captured 71% ± 19% more cancer cells than functionalized plain surfaces. Our reversibly sealed microfluidic platform enabled a user-friendly method to access cells for post-capture analysis, and we report an efficient nucleic acid isolation process. We anticipate the easy fabrication, one-step microfluidic integration, and streamlined experimental workflow will simplify the incorporation of nanotextured substrates in applications that investigate cell–surface interactions.

In this study we present the development of a prototype device, designed for micro-magnetic stimulation of excitable cells in vitro. Each platform consists of a 6 × 6 two-dimensional array of micro-coils, in an attempt to achieve highly localised magnetic flux patterns. The coils are fabricated with standard micro-fabrication techniques, including steps of photolithography, dry etching and electroplating. The further interfacing of the micro-magnetic chip into a biocompatible platform is also described. The samples are characterised electrically, while a finite element method simulation study is performed and reveals a 141 mV-strong electric potential induced in the vicinity of a micro-coil. Since applications in neuronal cells is our primary focus, modelling with NEURON software is used for demonstrating the capability of the platform to activate adjacent cells. Finally, an experimental validation of the proof of concept is performed with the measurement of induced current into a custom-made phantom gel that shows similar electric properties with brain tissue.

Increasingly complex radiotherapy techniques require additional machine-specific quality control (QC). The extra time required for such tests is in addition to existing, well-established QC required for standard linac deliveries. Additional time for QC can be in direct conflict with current cost saving driven practice and patient scheduling. One approach to create additional time for machine specific QC is to review current processes and the frequencies of well-established QC tests. In this work, the potential to transfer radiation field size, asymmetric jaw alignment, multi-leaf collimator (MLC) transmission and MLC rotation tests from film analysis to analysis of digital EPID images was investigated. In-house software was developed in MATLAB^® and commissioned for each test by comparison to film. Following commissioning, EPID analysis was introduced into routine use and the results and trends for these tests from 10 Varian linacs were analysed over 5 yr. Radiation field size measurements were found to be smaller than film due to the steeper penumbra in EPID profiles. This effect was field size dependent. By correcting for this, EPID and film measurements agreed within 0.0 ± 0.5 mm (mean ± 1SD), with drifts of ≤0.3 mm yr⁻¹ in field size measurements. The EPID profile response also results in overestimation of asymmetric jaw alignment measurements, which when accounted for permitted the junction gap to be maintained within ±2 mm. Junction gap was found to drift at <0.15 mm yr⁻¹. EPID assessment of MLC transmission and MLC rotation were also achievable and maintained within tolerance with trend analysis verifying current recommendations for annual assessment. Overall, a shift from film to EPID analysis for radiation field size, asymmetric jaw alignment, MLC transmission and MLC rotation tests saved 9.5 h machine time and 6.7 h subsequent analysis time annually per linac. This will be further increased as trend analysis over 5 yr has indicated the potential to reduce the frequency of some tests.

Early diagnosis is key for successfully treating many life-threatening diseases, such as cancer. Traditional diagnostic techniques, such as enzyme-linked immunosorbent assay, often fail or are not capable of detecting molarities in the early stages of disease progression. To address this unmet need, we integrated dielectrophoresis and fluorescence in a single device and utilized them to detect biomarker molecules. Prior to detection, target biomolecules were immobilized on polystyrene bead surfaces and fluorescently labeled. We then used the dielectrophoretic force to concentrate beads on specific areas within the device and measured the fluorescence intensity of the sample. To demonstrate the detection of biomolecules, we have used the technique to quantify avidin molecules in human serum samples. We have found that the measured fluorescence is proportional to the molarity of avidin molecules. Our results also indicate that this technique can detect pM molarities within about 15 min. Therefore, our technique has great potential for use in the detection of early stage of disease progression.

Current drug development using functional polymers is one of the major tasks for enhancing effectiveness and reducing the side effects in cancer therapeutics. To achieve this immense goal, human hair keratin and model drugs rutin-quercetin (Ru-Qr) were chosen to formulate nanoparticles (NPs). Drug delivery is a core path to produce significant biological activity, and in this connection, the current study was designed to produce highly stable Ru-Qr NPs and their characterization such as the encapsulation of Ru-Qr, the nature, molecular shape, particle size, stability and polydispersity index by Fourier transform infrared spectroscopy, x-ray diffraction, scanning electron microscopy, transmission electron microscopy and Zetasizer analyzer. Based on a literature report, the drug targets 521P and 5P21 were chosen to perform in silico study. The observed in silico study reports showed the strong interaction of NPs and binding pockets of H-Ras P21 proto-oncogene. In this respect, the importance of NPs prompted us to study the biodistribution and in vitro anticancer activity by using cancer cell lines. The investigation of biodistribution showed that it penetrated after 3 d of injection, up to 14% in the liver, 18% in the kidneys, 8% in the spleen, 3% in the heart and 0% in the brain. At 50 μg ml⁻¹ concentration, the NPs displayed 78.02% viability in the normal liver cell line and 95.60% cytotoxicity in the HeLa cell line. The obtained results showed the active NPs enhancing controlled, site-specific drug delivery and they can serve as a novel nanodrug in the management of cancer.

The near-infrared photothermal ability of pristine surfactant-exfoliated graphene was studied and demonstrated through the thermal ablation of mammalian NG108-15 cells. The graphene microsheets were prepared with polyethylene glycol triblock surfactants to improve biocompatibility while achieving high yields using a scalable and low-cost production method without the need for costly and time-consuming purification steps. The cytotoxicity of the surfactant-coated graphene was studied and it showed moderate toxicity. The ability of the exfoliated graphene to withstand extreme temperature cycling was demonstrated, highlighting the suitability of this material for multiple thermal ablation exposures. The pristine nature of the graphene sheets results in greater absorption in the near-infrared compared with graphene oxide or reduced graphene oxide. The photothermal transduction efficiency was also enhanced and determined to be ≈80% at 808 nm leading to the high efficacy of pristine graphene as an ablation agent.

We propose a novel comprehensive model of the dynamic multileaf collimator (MLC) sequencing problem under the sliding window technique. While the majority of research regarding MLC sequencing has lain dormant for years, leaf sequencing is currently done via 'black-box' implementations in clinical cancer treatment planning software. As such, it is unclear which leaf motion and fluence transmission parameters are included in these models, given their widely varying analytic and heuristic treatment in the existing literature. We hypothesize that an explicit, comprehensive model may fill an essential role in further research into intensity modulated radiation therapy and volumetric modulated arc therapy. To this end, we consolidate considerations of leaf motion (maximum velocity, finite acceleration), transmission (through-leaf, inter-leaf via tongue and groove) and novel formulations for penumbra across both dimensions of the field. In addition, we formulate our model to utilize these varying transmission effects to optimally sequence leaves with the goal of creating a fluence with pixel size smaller than the narrowest leaf width. To evaluate the proposed model, we have optimized MLC leaf sequencing on 25 prostate, 25 head and neck, 25 pelvis and 35 breast cancer fluence fields. The output sequenced fluences with and without constraints were compared with the corresponding reference fluences, respectively, by the performance of root mean square error and gamma index analysis. The acceptance criteria of 0.5%/0.5 mm and 1%/1 mm were used with a 0%, 5% and 10% low intensity threshold, respectively. Under the consideration of aforementioned constraints, the model can sequence the reference fluence successfully with the percentage of gamma passing rate ranging from 82.23 ± 3.89 to 99.78 ± 0.16 at 0.5%/0.5 mm and from 88.24 ± 1.89 to 99.98 ± 0.03 at 1%/1 mm across all low intensity thresholds and four treatment sites.

¹⁹²Ir high-dose-rate superficial brachytherapy (HDR-SBT) has been delivered as a postoperative radiotherapy to prevent recurrence of keloids in Nippon Medical School Hospital. However, extra radiation exposure for organs at risk is a concern because high-energy gamma rays penetrate more deeply than electrons at the energies typically used for therapy. Therefore, a system which can evaluate absorbed dose in the affected area and radiation exposure to tissue and organs based on the actual geometry in HDR-SBT was developed using the PHITS Monte Carlo code and a MIRD-5 phantom in our previous work. In this study, the absorbed dose was measured in a simple geometry using a water-equivalent phantom and radio-photoluminescence glass dosimeters to verify the evaluation accuracy of absorbed dose calculated by the developed system. We find that, accounting for the transit dose component and the energy dependence analytically, the calculations by PHITS underestimate the absorbed dose by 10.2% to 19.0% (average 15.5% ± 1.9%) compared to the measurements. The sensitivity-correction procedure was considered to be the main reason for the difference between the measured and calculated absorbed dose of the dosimeters.

Conduits currently used to reconstruct the right ventricular outflow tract (RVOT) have no growth potential and require reoperations, resulting in an increased level of morbidity and mortality. This work investigates the effect of electrospinning parameters on the mechanical properties and biocompatibility of bioresorbable tubular scaffolds, as part of a programme to develop a tissue-engineered valved tube for RVOT replacement. Electrospinning was used to develop tubular scaffolds of polydioxanone, with the experimental parameters systematically varied. Three electrospinning parameters (volume of liquid, flow rate, and speed of mandrel rotation) were investigated, and their effects on the mechanical properties and cellular response of the scaffolds were analysed using uniaxial tensile tests, cell viability and cytotoxicity assays. Mechanical properties were compared to those of the native RVOT reported in the literature. Increasing the mandrel rotation speed tended to increase fibre alignment slightly, and an increase from 50 to 500 rpm led to more profound rises in the stress at failure and Young's modulus. An increase in flow rate also increased the rigidity of the tubes. Cell viability and cytotoxicity assays showed all the tubes produced to have excellent biocompatibility. Through variation of the processing parameters, it is possible to tune mechanical properties of medical-grade polymer tubes over a wide range. Electrospinning therefore offers great promise in the development of scaffolds to match the properties of the native RVOT, paving the way to a future bioresorbable device to replace the RVOT in children.

Objective. Previous human steady state visual evoked potential (SSVEP) experiments have yielded different results regarding the range of stimulus frequencies in which period doubling (PD) behavior is observed. This study aims at obtaining experimental and statistical data regarding the frequency range of PD generation and also investigates other characteristics of PD. Approach. In two sets of experiments, seven subjects were presented a sinusoidal flickering light stimulus with frequencies varying from 15 to 42 Hz. To observe the short term variations in PD generation, another set of 5 successive experiments were performed on five subjects with 10 min breaks in between. To obtain the SSVEP responses, filtering, signal averaging and power spectral density (PSD) estimation were applied to the recorded electroencephalogram. From the PSD estimates, subharmonic occurrence rates were calculated for each experiment and were used along with ANOVA for interpreting the outcomes of the short term repeatability experiments. Main results. Although fundamental (excitation frequency) and second harmonic components appear in almost all SSVEP spectra, there is considerable inter-subject and intra-subject variability regarding PD occurrence. PD occurs for all stimulus frequencies from 15 to 42 Hz when all subjects are considered together. Furthermore, the statistical analyses of short term repeatability experiments suggest that in the short term, PD generation is consistent when all frequencies are considered together but for a single frequency significant short term differences occur. There also is considerable variation in the ratio of subharmonic amplitude to fundamental amplitude across different frequencies for a given subject. Significance. Important results and statistical data are obtained regarding PD generation. Our results indicate that modeling studies should attempt to generate PD for a broader range of stimulus frequencies. It is argued that SSVEP based brain–computer interface applications would likely benefit from the utilization of subharmonics in classification.

We discuss efficient algorithms for the accurate forward and reverse evaluation of the discrete Fourier–Bessel transform as numerical tools to assist in the 2D polar convolution of two radially symmetric functions, relevant, e.g., to applications in computational biophotonics. In our survey of the numerical procedure we account for the circumstance that the objective function might result from a more complex measurement process and is, in the worst case, known on a finite sequence of coordinate values, only. We contrast the performance of the resulting algorithms with a procedure based on a straight forward numerical quadrature of the underlying integral transform and asses its efficienty for two benchmark Fourier–Bessel pairs. Application to the problems of finite-size beam-shape convolution in polar coordinates and prediction of photoacoustic transients observed in experiments are used to illustrate the versatility and computational efficiency of the numerical procedure. Further, we address the important issue of testing research code written in the python scripting language by using its off-the-shelf unit testing library unittest.

Optical microscopy has been one of the most important tools for visualizing biological samples since the seventeenth century. Recently, with the advances in femtosecond laser technology, all the nonlinear optical processes have now been included as optical microscopy methods, and second harmonic generation (SHG) microscopy has emerged as a powerful new optical imaging tool with applications in medicine and biology. Here we use SHG microscopy to obtain images of 76 prostate biopsies on histological slides. Multiple samples from the excised prostates of patients who underwent a radical prostatectomy were evaluated. The samples were collected from prostate positions as in needle biopsy procedures. The results show the collagen fiber architecture among malignant acini, and analysis of the fiber orientation in the images reveals that the collagen fibers become more aligned at higher malignancy grades. Furthermore, we find that the degree of fiber alignment correlates directly with the Gleason patterns.

Transit-based in vivo EPID dose reconstruction algorithms need to correct for the couch attenuation at the exit side of the patient. In this study, two couch attenuation models are presented. The simple 0D model applies a single pixel-independent correction which is gantry angle and energy dependent. The more complex 2D model incorporates the dimensions and the treatment position of the couch to apply a pixel-specific correction by calculating the couch radiological thickness during delivery. The models were first described and then validated with measurements made on a phantom against measured couch attenuation maps and TPS data. There was a critical range of gantry angle values in which 2D models were required to accurately reconstruct the delivered dose. This was corroborated with the in vivo 2D dose verification results of 200 IMRT anterior fields. Without a couch attenuation model, the in vivo reconstructed isocentre dose value was on average 2.6% ± 1.0% (1SD) lower. In the in vivo 3D dose verification of 80 VMAT arcs and 75 IMRT treatments, both models showed comparable results. Without a couch attenuation model, the in vivo reconstructed PTV_D50 value was on average 1.2% ± 0.5% (1SD) lower. The 0D and 2D couch attenuation models are generic and directly suitable for implementation in an in vivo EPID dosimetry solution.

Objective: Event related potentials (ERPs) are phenomena that produce alterations on the spectral power of different bands synced with stimuli presentation. Such a perspective overlooks that the spectral power time series present spontaneous oscillations, the dynamics of which have been associated with the state of health and could be also linked to superior processes such as attention, memory, or cognition. In this work, amplitude of the ERP has been associated with dynamics of the power spectral density (PSD) time series. Approach: Data from a public P3 speller database were analyzed. Statistics about latency, amplitude and scalp distribution of the ERP confirm correct task realization. The spectral power over alpha, beta and gamma bands were correlated with ERP amplitude, considering such estimations time-locked with stimuli presentation. Additionally, PSD time series over the same bands were constructed using a sliding window not synced with stimulation. From these time series, a scaling exponent was computed using a detrended fluctuation analysis approach, and such indices were correlated with ERP amplitude of all registered electrodes. Main results: The correlation between ERP amplitude and scaling exponents of PSD series achieve statistical significance in almost all channels and for all analyzed bands (excepting alpha at C4). In particular, beta and gamma PSD series achieve R² values above 0.6 for Cz. Meanwhile, the correlation analysis with time-locked PSD achieves a statistically significant relationship with ERP amplitude ($p\lt 0.05$) but with a coefficient of determination (R²) below 0.2, only for gamma and alpha over the C4 and Pz channels. Significance: The ERP amplitude and scaling exponent of the PSD time series show an anticorrelated behavior, suggesting that larger ERP amplitudes are elicited when the PSD series are less autocorrelated, similar to white noise, further suggesting that the processes involved in the generation of such dynamics could be related to the mechanisms of cognitive responses.

Few children with cancer in low- and middle-income countries (LMICs) have access to proton therapy. Evidence exists to support replacing photon therapy with proton therapy to reduce the incidence of secondary malignant neoplasms (SMNs) in childhood cancer survivors. The purpose of this study was to estimate the potential reduction in SMN incidence and in SMN mortality for pediatric medulloblastoma (MB) patients in LMICs if proton therapy were made available to them. For nine children of ages 2–14 years, we calculated the equivalent dose in organs or tissues at risk for radiogenic SMNs from therapeutic and stray radiation for photon craniospinal irradiation (CSI) in a LMIC and proton CSI in a high-income country. We projected the lifetime risks of SMN incidence and SMN mortality for every SMN site with a widely-used model from the literature. We found that the average total lifetime attributable risks of incidence and mortality were very high for both photon CSI (168% and 41%, respectively) and proton CSI (88% and 26%, respectively). SMNs having the highest risk of mortality were lung cancer (16%), non-site-specific solid tumors (16%), colon cancer (5.9%), leukemia (5.4%), and for girls breast cancer (5.0%) after photon CSI and non-site-specific solid tumors (12%), lung cancer (11%), and leukemia (4.8%) after proton CSI. The risks were higher for younger children than for older children and higher for girls than for boys. The ratios of proton CSI to photon CSI of total risks of SMN incidence and mortality were 0.56 (95% CI, 0.37–0.75) and 0.64 (95% CI, 0.45–0.82), respectively, averaged over this sample group. In conclusion, proton therapy has the potential to lessen markedly subsequent SMNs and SMN fatalities in survivors of childhood MB in LMICs, for example, through regional centralized care. Additional methods should be explored urgently to reduce therapeutic-field doses in organs and tissues at risk for SMN, especially in the lungs, colon, and breast tissues.

Chitin membranes containing nanosilver were evaluated for use as antimicrobial wound dressings. Chitin at a concentration of 0.25% dissolved in 5% lithium chloride-dimethylacetamide and nanosilver synthesized by gamma irradiation were used for fabrication of chitin-nanosilver membranes. UV–vis spectroscopy and energy dispersive x-ray (EDX) analysis with scanning electron microscopy (SEM) were used to confirm the presence of silver nanoparticles. Fluid absorption capacity, moisture vapour transmission rate, antimicrobial activity, effect on cell viability, in vitro wound healing property and the silver elution profile were determined, to assess the wound dressing properties of the chitin-nanosilver membranes. The antimicrobial efficacy of chitin membranes containing silver nanoparticles was observed against a broad range of microbes such as Acinetobacter baumanii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris and Candida albicans. The chitin-nanosilver membranes prepared with 100 ppm silver resulted in 6-log to 8-log reduction in viable counts after 24 h and had a positive impact on fibroblast proliferation. The fluid handling capacity, cell viability test and silver elution profile indicate that the chitin-nanosilver dressing can contribute to effective management of infected wounds. In vitro studies have demonstrated the antimicrobial activity and wound-healing properties of chitin membranes containing nanosilver.

This work presents a method to improve the separation of edge crystals in PET block detectors. As an alternative to square-shaped crystal arrays, we used an array of triangular-shaped crystals. This increases the distance between the crystal centres at the detector edges potentially improving the separation of edge crystals. To test this design, we have compared the flood histograms of two 4 × 4 scintillator arrays in both square and triangular configurations. The quality of the flood histogram was quantified using the fraction of events positioned in the correct crystal based on a 2D Gaussian fit of the segmented flood histograms. In the first study, the two crystal arrays were coupled with the SiPM directly using optical grease, and the flood histogram quality for the edge and corner crystals in the triangular-shaped array were much better than that for those crystals in the square-shaped array. The average light collection efficiency for the triangular-shaped array was 5.9% higher than that for the square-shaped array. The average energy resolution for the triangular and square shape array were 11.6% and 13.2% respectively. In the second study, two light guides with thickness 1 mm and 2 mm were used between the crystal arrays and the SiPM. The thicker lightguide degraded the light collection efficiency and energy resolution due to the light loss introduced by the light guide. However, in the 2 mm thick lightguide case, the flood histogram quality for the edge and corner crystals in the square-shaped array were improved due to better separation of those crystals in the flood histogram. Comparing the performance of the two crystal arrays with three different light guides, the triangular-shaped crystal array with no lightguide gave the best performance.

Wideband current sources that can work stable over a wide frequency range with large load variations are critical for the performance of electrical impedance spectrum (EIS) measurements. In this paper, we design a wideband mirrored current source (MCS) using two simple differential difference amplifiers (DDA) AD830. PSpice simulation and measurement were performed on load resistances from 100 Ω to 1500 Ω over the frequencies up to 1 MHz. The maximum variation of the output current is less than 0.5% over the whole bandwidth and the output impedance is 4.2 MΩ at 100 Hz and greater than 185 kΩ at 1 MHz. Moreover, less than 1% linearity error (the V_IN versus the I_OUT) of the output current I_OUT from 1 mA to 20 mA was achieved by sweeping the input voltage signal V_IN from 0.1 V to 2 V at 100 Hz, 1 kHz and 10 kHz respectively. The DDA-based wideband MCS has high accuracy, linearity and simple structure, which may improve the performance of EIS measurements and other relevant applications.

The sharpness of cutting edges and apexes is crucial in the performance of various medical devices. A method of medical needle finishing, consisting of large area ion beam sputtering, is introduced and studied. Significant deburring, edge sharpening and surface modification of the needles is demonstrated by an experiment. The influences of working gas composition and total ion fluence on the resulting needle properties are emphasized. It was shown that the utilization of an Ar/dry air mixture (37/6) resulted in a significant improvement in surface morphology, compared to pure Ar sputtering. The effect of gas composition is discussed in terms of concurrent material sputtering and chemisorption of reactive species. Needle sharpening aspects studied using microscopy techniques were confirmed by measuring the force required to push a needle through a plastic film. The puncture force of an as-grinded needle was reduced by ∼50% by means of the reported method.

Body electrical loss analysis (BELA) is a measurement of the electrical losses caused by the human abdomen when placed into an alternating magnetic field. This study aimed at finding a prediction formula for visceral fat area (VFA) from BELA. Thirty-eight test subjects covering the body mass index of 19.6–39.4 kg m⁻² and the waist circumference of 78–128 cm underwent BELA, single-frequency electrical abdominal impedance measurement (SAI), conventional bioelectrical impedance analysis and cross-sectional magnetic resonance imaging (MRI). The BELA was compared with the amount of visceral and subcutaneous fat calculated from MR images. The strongest correlation between BELA and VFA (r = 0.61, SEE = 59.30) was found at the height of umbilicus +5 cm, and it tended to decrease when the measurement height was lowered. The correlation to subcutaneus fat area (SFA) at the height of umbilicus +5 cm was r = 0.43 (lower is better), and it tended to increase when the measurement height was lowered. The correlation of BELA to VFA in the evaluation cohort is not strong enough to tolerate obtaining the prediction formula for VFA by regression among BELA and MRI. Also the large SEE value suggests a poor agreement with MRI. Thus the results suggest that in its current form BELA cannot be applied as a diagnostic device to measure visceral fat. Although SAI can help in identifying the abdominal SF layer thickness, it did not help when applied to BELA analysis.

Regenerated Silk fibroin (SF) from Bombyxmori has emerged in recent years as candidates for wound dressing due to its excellent biocompatibility and low inflammatory response. Cirsium Japonicum DC (CJDC) is a kind of Chinese herb medicine with evident hemostatic and anti-inflammatory analgesic effect. In this study, we aimed to manufacture a novel green electrospun SF nanofibrous matrice loading ingredients extracted from CJDC which should be useful in hemostasis as well as wound healing. FTIR spectra showed that the CJDC extracts were successfully loaded into the SF nanofibrous matrices, which appeared morphology of porous mesh structure. The as-prepared matrices inherited the good skin affinity and hemocompatibility of SF, as indicated by the skin cell viability assay and hemolysis test in vitro. Furthermore, according to the results of plasma recalcification profiles test, the incorporation of CJDC extracts significantly improved the hemostatic performance of SF nanofibrous matrices. Interestingly, the SF nanofibrous matrices loading CJDC components extracted by petroleum ether (peE-CJDC@SF) showed the best antihemorrhagic activity among the tested samples (with astringent time of 9.5 min), even better than some clinically used products such as absorbable gelatin sponge (AGS) and aseptic hemostyptic gauze (AHG). Our findings suggested the peE-CJDC@SF nanofibrous matrices could be a promising candidate using as hemostatic material and wound dressing.

In this paper, a new set of tumour phantoms for the experimental evaluation of Microwave Breast Imaging (MBI) as a method to diagnose breast cancer is presented. The phantoms were based on previously developed numerical models that had been clinically validated, supporting the appropriateness of the phantoms for the development of experimental systems. The proposed tumour phantom set was developed using polyurethane rubber with graphite and carbon-black powders and is the first to incorporate a large number of different shapes and levels of spiculation to emulate different levels of tumour malignancy. A series of spherical, non-spiculated targets was fabricated to model benign tumours, and a series of targets with irregular shapes and increasing spiculation was fabricated to model malignant tumours. The tumour phantoms can be combined with a variety of breast phantoms fabricated with the same method, which are unique in their diversity of glandular tissue content. The modular design of the phantom set allows for tumour and breast phantoms to be dynamically combined, creating an experimental test platform for MBI with a total of 154 cases. Moreover, the dielectric properties of the phantoms display good agreement with the literature, and the phantoms are constructed using materials that have demonstrated stable properties over time. Results also demonstrate how the shape and level of spiculation of a tumour can influence microwave reflections, and therefore impact the performance of imaging and diagnostic systems.

Electrical impedance measurements of biological tissues, also referred to as bioimpedance, quantify the passive electrical properties of these materials. The motivation behind collecting these measurements is to provide details regarding the electrochemical structures and processes within these tissues. Bioimpedance measures have recently been investigated as a method to monitor morphological and physiological changes that occur in skeletal muscle during contraction as well as result from fatigue. Objective: To investigate the effect of exercise intensity during a fatiguing protocol of the biceps brachii on the electrical impedance changes of biceps tissue due to an isotonic protocol. Approach: Resistance (R) and reactance (X) measurements were collected from the right and left biceps of 18 participants pre and post execution of a fatiguing protocol using an isotonic exercise to task failure at two intensities, either 60% (N = 10) or 75% (N = 8) of their assessed one-repetition maximum strength. Main Results: There were significant differences (p < 0.05) between the pre and post fatigue R and X within groups due to the exercise protocol. But no significant differences (p > 0.05) of the R and X between groups at different intensities and no significant differences (p > 0.05) of changes between the left and right biceps in both groups. Significance: These results show that the level of exercise intensity did not significantly impact the changes in electrical impedance of the biceps tissue between the two intensity groups in this study when the same fatigue criteria are used, which is an important consideration when using EIM to monitor changes as a result of fatigue and exercise related injury.

The early detection of metastatic cells can lead to better prognosis and higher survival rate. These cells have the capacity to travel through the circulatory system and invade other tissues. Often the symptoms for metastasis are not evident until cancer incapacitates a secondary organ. Hence, early detection is crucial. An imaging-based approach with a contour detection technique is presented here to distinguish metastatic breast cancer cells from benign cells when captured on anti-EGFR aptamer modified glass substrates. Metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells were studied. The temporal tracking of cells showed that metastatic cells depicted prominent morphological changes, whereas the benign cells did not show such behavior. The metastatic cells showed rapid changes in their shapes by protruding/retracting cell membranes. The images of each type of cells captured on functionalized substrates were analyzed, and morphology changes were quantified with similarity and distance analysis. Low similarity coefficients and high distance values meant larger morphology changes. The metastatic cells showed lower similarity coefficients and higher distance metric values (average Hausdorff distance = 2.8 a.u.; average Mahalanobis distance = 0.7 a.u.) than non-metastatic cells (average Hausdorff distance = 1.5 a.u.; average Mahalanobis distance = 0.31 a.u.). These parameters were successfully used to detect 52% of metastatic cells from a cell mixture that imitated breast tissue. This approach can be used for detecting metastatic potential of a given sample towards precise therapy for a patient.

Biodegradable materials suitable for medical application with improved corrosion resistance and good biocompatibility along with enhanced mechanical properties are the need of the hour. Such properties in Mg-Zn-Ca glass forming alloy used as a metal matrix can be obtained through proper reinforcement. Hydroxyapatite (HA) which is a mineral constituent of natural bone has a wide range of medical applications because of its excellent biocompatibility and bioactivity. They promote bone cell adhesion and osteoblastic proliferation. In the present study, the influence of HA particle (HA_p) addition on the glass forming ability, corrosion resistance, mechanical behavior and cytocompatibility of Mg₆₆Zn₃₀Ca₄ alloy has been investigated. The addition of HA_p decreases the glass forming ability of Mg₆₆Zn₃₀Ca₄ alloy. Significant improvement in corrosion resistance along with marginal improvement in mechanical properties is observed upon addition of HA_p. Moreover, HA_p incorporation into Mg₆₆Zn₃₀Ca₄ metallic glass has enhanced the cell viability and cell adhesion of human osteoblast-like cell (MG63) cells, complementing the excellent biocompatibility, bioactivity, osteoconductivity and osteoinductivity of hydroxyapatite mineral due to its biomimetic nature. HA reinforcement is not only a promising approach to improve the corrosion resistance, but also offers a biomimitic interface to enhance osseointegration and overall competence of orthopedic implants.

The effect of electromagnetic radiation on neurons has been studied extensively both experimentally and computationally. As for dendrites, these studies are mostly limited to the morphological aspects such as branching and not basically conductance. The effect of low frequency electric field radiation on the electrophysiological characteristics of dendrites is studied theoretically. The study is based on incorporating the effect of electric field components inside the modified cable equation and considering the geometry variation of the structure. The effect of different ionic components has been included with the aid of the Connor–Stevens model and the governing equation is then solved computationally. The results of the simulation indicate that the dendrites are physiologicaly sensitive to the radiation field. Variation in the electrophysiological aspects, including the firing rate, the conduction velocity, the pulse broadening and the latency are more pronounced in response to the external stimuli in the dendrites and are enhanced in the frequency range of 100 Hz to 10 kHz. To the best of our knowledge, the interaction of an electric field with non-uniform radius dendrites has not been studied nor modeled. The results of this study could be useful not only as a barrier to neurotoxicity of low frequency radiation, but also as a potential application in the treatment of neurophysiological disorders.

Objective. A growing demand exists for eco-friendly, low-power charge storage devices for both biomedical and neuro-electrical applications, with a push towards the use of biocompatible and bio-tolerable electrodes and eco-friendly electrolytes that could be easily integrated with wearable electronics. Approach. One of the promising bio-tolerable, biomedical materials is nano cerium oxide, which finds wide applications in biology and medicine, namely spinal cord injury, radiotherapy, cardio-protection, etc. Here, nano cerium oxide was used as an electrode material to test whether such a bio-tolerable material could be used in bioelectrical and neuro-electrical applications. Main results. We developed a symmetric charge storage device using nano-ceria electrodes coated with fructose (a fruit sugar that is neutral to diabetes patients). This device attains a potential window of +0.8 V to −0.8 V in the presence of an aqueous electrolyte, Na₂SO₄, which is an eco-friendly electrolyte. The device retains 85% of the specific capacitance (∼350 F g⁻¹) and peak current density of 12 mA cm⁻² after completion of 10 000 cycles, thus highlighting the stability of the newly developed device. Further, the device could be used to operate DC fans and other solid state electronic devices. The CeO₂ electrode was tested in biologically relevant fluids, namely phosphate buffered saline and Leibovitz (L-15) medium, and found to be functioning and stable. Significance. Bio-tolerable nano cerium oxide electrodes could find new and innovative applications in bio-electronics, electro-therapy, neuro-electronics, charge storage and wearable electronics.

Microwave ablation is a promising treatment for kidney cancer. Accurate knowledge of the dielectric properties of biological tissues is vital for quantifying the safety, reliability and accuracy of ablation, among other microwave medical treatments and diagnostic technologies. In dielectric studies to date, the heterogeneity within the kidney has not been considered, and the kidney has been treated as a fully homogeneous organ. Therefore, the available dielectric data of the kidney is not as thorough and accurate as it could be. For this reason, in this study, dielectric measurements are performed over a broad frequency range to quantitatively investigate the difference between the dielectric properties of various regions of the kidney and to develop an anatomically accurate dielectric profile of the kidney. All measurements are conducted on freshly excised porcine kidney samples, and confounders impacting dielectric data are controlled and related metadata recorded. The results demonstrate a considerable difference of up to 49% between the dielectric properties of different regions of the kidney. The findings in this paper suggest that the heterogeneity within the kidney should be taken into consideration in order to obtain an accurate representation of the actual dielectric properties. Additionally, a two-pole Cole-Cole model is fitted to the measured data of the different regions of the kidney and the model parameters presented for reference. The anatomically accurate dielectric profile of kidney provided in this paper will support the development of more effective and reliable microwave medical treatments.

An electroporation device was developed to introduce transient membrane pores and, consequently, enhance membrane permeability in living cells in a controllable manner. The validity of this platform was assessed on six non-small cell lung cancer (NSCLC) cell lines using different fluorescent dyes. Interestingly, it was found that the electroporation efficiency of these cells, i.e. the percentage of cells with membrane pores created, decreases significantly (from ∼60% to 30%) as their resistivity against Erlotinib increases, demonstrating the potential of such approach as a screening tool for assessing drug resistance in tumours in the future. Furthermore, we showed that the inverse relationship between the electroporation efficiency and Erlotinib resistance is likely due to the fact that NSCLC cell lines with higher drug resistivity appear to have lower cortical tensions and hence make it harder for membrane pores to be created, consistent with existing electroporation theories.

Lidocaine hydrochloride is used as an anesthetic in many clinical applications. This short communication investigates the effect of complete substitution of lidocaine hydrochloride for deionized (DI) water on the physico-chemical properties of two novel glass polyalkenoate cements. Substituting DI water with lidocaine hydrochloride resulted in cements with shorter working times but comparable setting times and mechanical properties. Fourier transform infrared spectroscopy confirmed that the setting reaction in cements containing DI water and lidocaine hydrochloride was completed within 24 h, post cement preparation and maturation. Further, it was explained that lidocaine hydrochloride binds to poly(acrylic) acid (PAA) due to electrostatic forces between the positively charged amino group of lidocaine hydrochloride and the carboxylic group of the PAA, resulting in a compact poly-complex precipitate.

The fabrication of titanium-based biocompatible alloys with good wear resistance and a low elastic modulus remains a challenge for researchers. In the present study, titanium niobium alloys with compositions of Ti-35Nb-4Sn, Ti-29Nb-13Ta-7Zr and Ti-24Nb-4Zr-8Sn were fabricated using vacuum arc re-melting. The alloys were solution-annealed, then their microstructure was characterized using field emission scanning electron microscopy, their hardness determined by microhardness measurements, their phase determined using x-ray diffraction analysis and their elastic modulus determined by nano-hardness measurements. Subsequently, the wear resistance of the samples was determined by in vitro testing with a pin-on-disc wear-testing machine using 500 g, 1000 g and 1500 g loads in Ringer's solution. The results reveal an increase in the wear resistance of the alloys by one order of magnitude as compared to conventional Ti-based alloys. The improvement in wear resistance is due to (a) the synergistic effect of the volume fraction ratio of the β versus α phases, (b) the variation in the composition and hardness of the individual α and β phases and (c) the variation in the size, morphology and distribution of the α and β phases for each of the alloys. The elastic modulus of the fabricated alloys was much lower than conventionally used alloys and matched well with the modulus of human bone.

A small circular field used in stereotactic radiosurgery is obtained using a cone accessory attached to a LINAC. Such beam modification requires that the LINAC jaws be set to a specific size, an adjustment which, in many cases, must be explicitly made by the LINAC operator. Given that treatment planning systems are commissioned with correct jaw settings, it is difficult to quantify the leakage dose to the patient when the jaw setting is larger than recommended. However, there are documented cases indicating that the resulting overexposure can lead to long-term disability and death. This study quantifies the dose differences between correct and incorrect jaw settings by simulating a realistic treatment plan using a Varian LINAC with a BrainLab circular cone accessory. Using Monte Carlo methods, the details of the LINAC head and cone accessory were simulated, with calculated doses benchmarked against measurements. Calculations were based on a realistic treatment plan for right side trigeminal neuralgia delivering 90 Gy using a 6 MV (4 mm cone) beam with 7 arcs. The calculated doses to target and normal tissue with jaws set correctly (5 × 5 cm²) and incorrectly (settings ranging from 10 × 10 cm² to 20 × 20 cm²) were then compared. Incorrect jaw settings resulted in an increase in the target dose of less than 6%. This implies that pre-treatment QA based only on point dose measurements at the isocenter will not detect jaw setting errors. However, extremely high doses (>25 Gy) occurred 5 cm away from the isocenter. For example, dose to 50% of the volume, D₅₀, in the eyes increased from 15 cGy with the correct jaw setting to 5318 cGy with an incorrect jaw setting of 20 × 20 cm². D₅₀ in the brain increased from 27 cGy with the correct jaw setting to 4335 cGy for a setting of 20 × 20 cm². The leakage radiation is shown to originate beyond the outer edge of the beam limiting cone (outer radius = 5 cm). Leakage dose can reach 15%, 40%, and 60% of target dose when incorrect jaw settings of 10 × 10 cm², 15 × 15 cm² and 20 × 20 cm² are used in the beam delivery.

In medical imaging, clinicians, researchers and technicians have begun to use 3D printing to create specialized phantoms to replace commercial ones due to their customizable and iterative nature. Presented here is the design of a 3D printed open source, reusable magnetic resonance imaging (MRI) phantom, capable of flood-filling, with removable samples for measurements of contrast agent solutions and reference standards, and for use in evaluating acquisition techniques and image reconstruction performance. The phantom was designed using SolidWorks, a computer-aided design software package. The phantom consists of custom and off-the-shelf parts and incorporates an air hole and Luer Lock system to aid in flood filling, a marker for orientation of samples in the filled mode, and bolt and tube holes for assembly. The cost of construction for all materials is under $90. All design files are open-source and available for download. To demonstrate utility, B₀ field mapping was performed using a series of gadolinium concentrations in both the unfilled and flood-filled mode. An excellent linear agreement (R² > 0.998) was observed between measured relaxation rates (R₁, R₂) and gadolinium concentration. The phantom provides a reliable setup to test data acquisition and reconstruction methods and verify physical alignment in alternative nuclei MRI techniques (e.g. carbon-13 and fluorine-19 MRI). A cost-effective, open-source MRI phantom design for repeated quantitative measurement of contrast agents and reference standards in preclinical research is presented. Specifically, the work is an example of how the emerging technology of 3D printing improves flexibility and access for custom phantom design.

Three dimensional (3D) porous scaffold based bone tissue engineering can possibly serve as an alternative approach to repairing severe bone injuries. The present study was carried out to evaluate the impact of 3D porous silk fibroin (SF)–polyvinyl alcohol (PVA) based scaffolds on human osteoblast-like (MG63) cell attachment and proliferation in vitro. SF and PVA blended porous scaffolds (3:1 ratio) with tunable porosity and mechanical properties were prepared by a freeze drying method in a solvent-free system. Citric acid plays a dual role of cross-linking and a gas foaming reaction with sodium bicarbonate (NaHCO₃). Porosity was induced by gas foaming using different weight fractions (0.5%, 1.0%, 1.5% and 2.0% w/v) of NaHCO₃. The developed scaffolds were characterized for porosity, swelling ratio, compressive and biodegradation properties. The scaffolds were proved to be non-toxic to the osteoblast-like cells in MTT assay. The DNA content of the cells attached to the scaffolds was also estimated. The cell attachment and proliferation onto the scaffolds were studied using SEM. The study highlights the potential of such 3D scaffolds with controlled porosity as an effective biomaterial for bone regeneration.

The gamma evaluation method is widely used for accurate quantitative comparison of measured dose distribution and treatment plan verification in intensity-modulated radiotherapy. In the case of field-in-field (FIF) plans, the standard gamma criterion fails to distinguish clinically significant differences in planned and actual dose distributions. The proposed modified gamma evaluation algorithm takes into account only high-dose-gradient regions in calculating the value of the gamma criterion. The aim of this study is to test the new algorithm in FIF plans, evaluating the test's sensitivity to dose, segment size and shape, and compare it with a commercially available gamma algorithm. For this study, several clinical cases were modeled using MATLAB® software. For segment shape and size tests a 20 × 20 cm base field was modeled. Randomly shaped rectangular segment fields with sizes from 5% to 50% of the base field area with 5% increments were added to the base field. Dose distribution was calculated using MATLAB® for use as a starting point to make distorted plans with segments displaced to simulate patient movement or positioning errors during irradiation. For sensitivity tests a 20 × 20 cm base field and rectangular segment with an area of 5% of the base field was added at the center. For the reference, 120 dose units were prescribed, 100 for the base field and 20 for the segment. Dose modulation was done by altering the segment dose in steps of two dose units per measurement. Segment dose-modulated fields were compared with the reference using the modified gamma criterion. Pixel acceptance criteria were based on dose difference ∆DM = 3% and distance-to-agreement (DTA) ∆dM = 3 mm. Only pixels in those regions where the dose gradient exceeded 5% were used; and 95% of all pixels in the region should be within this criterion for the treatment plan to be accepted. Comparison with commercially available gamma evaluation software demonstrated that the standard criterion is not able to detect clinically significant shifts of 5 mm in the FIF plans, but the new algorithm detected all shifts before they exceeded 3 mm. In turn, the commercial gamma criterion showed a higher dose sensitivity: dose alterations larger than two dose units show a steep drop of 'passed' pixel number below the 95% threshold level.

The multi-leaf collimator (MLC) dosimetric leaf gap (DLG) offset and transmission are measured parameters which influence the dosimetric accuracy of radiation therapy treatment plans. An international consortium developed an efficient method of automatically measuring the two-dimensional MLC DLG and transmission using the electronic portal imaging device (EPID) on multiple Varian TrueBeam linacs incorporating Millennium and high definition (HD) MLCs. Quality control was implemented as part of each test. Results were compiled including comparisons to baseline measurements and between machines. Validations were accomplished using ion chambers (IC) and a 2D IC array. Sensitivity was investigated by introducing deliberate leaf position offsets, repeatability was assessed, and performance was analyzed using statistical process control methods. The EPID measured DLG (EDLG) and transmission were consistently smaller than the IC measured DLG and transmission for all machines tested. EDLG variations across two dimensions averaged more than 0.24 mm for both Millennium and HD MLCs, demonstrating that leaf-to-leaf DLG variations should be assessed for both MLC types. The two-dimensional correlation coefficient between the IC array and EPID measurements was at least 0.937. A nearly linear relationship between changes in the EPID measured leaf gap and actual leaf positions was measured, with R² > 0.999. EDLG results were analyzed as a difference relative to a baseline EDLG measurement for each machine, a metric we labeled the leaf offset constancy (LOC). The maximum change in LOC out of the 20 repeatability tests was −0.094 mm. The LOC QC process was found to be capable (C_pk > 1) for 4 machines using a ± 0.15 mm specification limit. LOC results showed that leaves may deviate from their reference positions at a level that approaches dosimetric significance for small stereotactic and highly modulated treatment fields, with average excursions measuring up to 0.21 mm for a Millennium MLC and 0.16 mm for a HD MLC. The effects of initialization, gantry angle, and common repairs are also reported.

3D fabrication techniques are rapidly expanding in the field of scaffold development for cell culture and tissue engineering. Herein we report the realization of free-standing PEGDA hydrogel architectures by using two-photon lithography. The morphological and immunofluorescence characterization of neuro2A cells revealed a tridimensional colonization featuring multiple neuritic extensions per cell as well as the expression of β-tubulin neuronal marker and actin microfilaments. The results open new perspectives in the continuous quest for structured biomaterials able to provide a favorable environment to cells and at the same time not interfering with imaging protocols necessary for a clear scenario of the cell seeding.

Purpose. Synthetic meshes are now widely used for a repair of various tissue defects. Polypropylene meshes (PPMs), the type most frequently used for repair of abdominal wall defects, have some disadvantages, therefore the development of new mesh materials for reconstructive surgery is an important topic. A TiNi-based alloy superelastic mesh implant has been compared with a PPM in the Wistar rat model. Experimental. A midline resection abdominal wall defect (2 cm × 3 cm) was treated with a mesh implant (2.5 cm × 3.5 cm). Three groups of 20 animals were assessed: (1) a TiNi-based alloy mesh (TNM) group with the defect managed by a TiNi-based wire woven implant; (2) a PPM group with the defect repaired by Optomesh®; and (3) a no-mesh (NM) group treated without the use of any prosthetic material for systemic reaction to implant control. Evaluation of both mesh implantations was carried out on days 14, 28, 56 and 90 after surgery. The following data were compared: general condition of the animals, macroscopic evaluation of the implant area and microscopic evaluation of the tissue surrounding the mesh with the use of scanning electron and light optical microscopy. Results. All the animals from NM group developed hernias. The PPM group showed satisfactory results, although some complications like implant dislocation (6/20) and hernia recurrence (5/20) were noted. In the TNM group neither shrinkage nor implant dislocation were observed. Compared with the PPM group, the TNM group was characterized by no inflammation reaction and better integration with tissues. Conclusions. Suppression of inflammation response together with a more physiological wall remodeling process than with PPM makes TNM an attractive concept for abdominal wall defect reconstruction. Since there was neither shrinkage nor dislocation of the TNM itself it may be suitable for intraperitoneal management. The essence of enhanced biocompatibility is due to stress–strain mechanical behavior of TNM and its surface oxycarbonitride layer, which facilitate its incorporation. Summarizing, TNM was found to be a very promising material for the repair of abdominal wall defects in clinical practice. Ideally TNM would be applied in circumstances when there are indications for the management of large hernias by PPM.