Table of contents

A discrimination between the two different types of acute stroke (ischemic and hemorrhagic) is accomplished by the implementation of both the Inverse problem of electroencephalography (EEG) technique and the method of principal components analysis (PCA). The study was based on electroencephalograms (EEGs) recorded from patients that had suffered from stokes. The brain activity was simulated with a realistic head model excited by electric dipoles, which in the present work were allowed only to rotate about a fixed origin. Combining the calculated surface potentials of the head model and the EEG recordings, the inverse problem algorithm converged to a solution giving an equivalent dipole that included all the information needed to distinguish each type of stroke. Alternatively, PCA technique was implemented directly on the EEG recordings in order to reveal potentially hidden patterns underlying the recordings. For this purpose, the corresponding techniques developed within our previous work, are exploited herein for the processing of patients' EEGs. It is observed that indeed both equivalent dipole and PCA or its alternative proper orthogonal decomposition approaches were able to discriminate the two types of stroke.

The aim of mechanical ventilation (MV) is to provide sufficient breathing support for critically ill patients with respiratory failure in the intensive care unit (ICU). However, the application of inappropriate MV settings can result in ventilator induced lung injury (VILI) and exacerbate respiratory dysfunction. To prevent VILI, respiratory mechanics properties such as elastance and resistance can be estimated at the bedside to guide MV settings. Different models or methods provide different information and have unique advantages and disadvantages. In this study, the respiratory mechanics of 25 respiratory failure patients were determined using the first order model (FOM) and a viscoelastic model (VEM). The patients underwent different respiratory manoeuvres and their identified respiratory mechanics using these models are studied and compared with a standard clinical method in estimating respiratory mechanics. The results show that both models were able to capture patient-specific mechanics and responses. The FOM was able to provide higher correlation to the standard clinical method while the VEM provides a physiologically more plausible representation.

The aim of this study was to develop a new safe and effective hemostatic gauze material by promoting in situ thrombin induction on the surface of gauze, and the optimal preparation conditions were determined by varying the CaCl₂ concentration, reaction time, and temperature. Under each condition, the thrombin amount (optical density) and plasma clotting time were measured, and the results showed that the best condition for preparation of this new gauze/plasma composite (GP) is a CaCl₂ concentration of 0.08 mol l⁻¹ at 35 °C for 2.5 h. Temporal and water stability tests showed that the gauze is washable and can be stored without loss of quality. Furthermore, the water and blood absorption and whole blood clotting time were compared between the GP and oxidized cellulose (OC), demonstrating that the hemostatic effect of the new material was similar to that of OC; however, the thermophysical stability of GP was superior to that of OC. The good hemostatic effect of the new hemostatic gauze was verified in a rabbit artery bleeding model, which is considered to be due to the presence of thrombin on its surface. These results are expected to provide important guidance in the continued search for new types of hemostatic gauze.

Metallic implants are widely used in orthopaedic and orthodontic applications. However, generally surface treatment of the metallic surfaces is necessary to render them more biologically active. Herein, we describe a direct write printing method to modify metallic implant surfaces with biocompatible polymers with microscale precision. Application of polymeric micropatterns on metallic implant surfaces can (i) improve their interaction with the host tissue, (ii) enable the delivery of growth factors, antibiotics, anti-inflammatory cytokines etc from the implant surface and (iii) can control the immune responses to the implant via controlling the attachment of immune cells, such as macrophages. Surface patterns with a resolution of less than 50 μm can be created using an electro hydrodynamic (EHD) printing, a template-free and single-step process. We present a revised EHD printing method for the deposition of parallel strips of photocrosslinkable, cell adhesive polymeric composites with spacing of around 20 μm onto medical grade titanium substrates. Optimization of voltage, feeding rate and collection speed resulted in regular structures via very rapid movement of the grounded rotating collector driven to equivalent of the linear surface speed of above 100 cm s⁻¹. In the experimental part a mixture of chemically modified PEG /gelatin was deposited onto a conductive titanium substrate with different surface pretreatments with an area of 400 mm². Acid etched or UV treated titanium surfaces improved the stability of the printed structures. Polymeric lines induced temporary orientation of human monocytes (THP-1) and induced a thicker cell multilayer formation by 3T3 fibroblasts (p < 0.05). Staining of the monocytes for M1(CD80) and M2 (CD206) macrophage markers on the patterned surface showed mixed populations with higher anti-inflammatory cytokine secretion compared to tissue culture plastic control. The results demonstrate the suitability of this method for the preparation of biomaterials with structured surfaces on large areas and with desired chemical composition.

The uncertainties in water equivalent thickness (WET) and accuracy of dose estimation using a virtual CT (vCT), generated from deforming the planning CT (pCT) onto the daily cone-beam CT (CBCT), were comprehensively evaluated in the context of lung malignancies and passive scattering proton therapy. The validation methodology utilized multiple CBCT datasets to generate the vCTs of twenty lung cancer patients. A correction step was applied to the vCTs to account for anatomical modifications that could not be modeled by deformation alone. The CBCT datasets included a regular CBCT (rCBCT) and synthetic CBCTs created from the rCBCT and rescan CT (rCT), which minimized the variation in setup between the vCT and the gold-standard image (i.e., rCT). The uncertainty in WET was defined as the voxelwise difference in WET between vCT and rCT, and calculated in 3D (planning target volume, PTV) and 2D (distal and proximal surfaces). The uncertainty in WET based dose warping was defined as the difference between the warped dose and a forward dose recalculation on the rCT. The overall root mean square (RMS) uncertainty in WET was 3.6 ± 1.8, 2.2 ± 1.4 and 3.3 ± 1.8 mm for the distal surface, proximal surface and PTV, respectively. For the warped dose, the RMS uncertainty of the voxelwise dose difference was 6% ± 2% of the maximum dose (%mD), using a 20% cut-off. The rCBCT resulted in higher uncertainties due to setup variability with the rCT; the uncertainties reported with the two synthetic CBCTs were similar. The vCT followed by a correction step was found to be an accurate alternative to rCT.

Electrical impedance tomography (EIT) has been investigated as a potential non-invasive method for breast cancer imaging for more than two decades. However, since EIT requires direct contact with the boundary, electrode positioning and boundary movement have always been considered as two of the sources of errors and artifacts. A breast can be deformed due to its natural structure. Therefore, if the breast is deformed on purpose, each deformation can provide one new set of independent EIT measurements data. More independent data provides more information from the same region of interest. In this hypothesis, information gathered with different deformations is combined, in all cases we assumed that shape and electrode positions measured by other means. Simulations have been carried out to verify the hypothesis, and results show improvements in the detectability of the early stage tumor in depth.

Real-time, quantitative characterization of cells at single-cell resolution, particularly while maintaining their intrinsic properties and without affecting cellular processes, is of primary importance in modern biological assays. Dielectrophoresis is a label-free, real-time, and quantitative technique, and is amenable to integration with other techniques, thus providing new and powerful tools for biology and medicine. In this study we present dielectrophoresis as a characterization tool for Mycobacterium smegmatis single cells. Understanding how phenotypically variant M. smegmatis cells respond dielectrophoretically when subject to the same electric field, could reveal underlying membrane altering mechanisms related to cell death, drug-tolerance, and drug-resistance. In this study, we dielectrophoretically characterized live, heat-treated and antibiotic-treated bacteria. Our results present quantifications of cellular behaviors associated with membrane-specific cell damages and demonstrate adequacy of dielectrophoretic devices in point-of-care diagnostic and monitoring for bacterial infections.

The scope of the present work was to evaluate the role of the complex refractive index in optical diffusion studies for imaging purposes. In particular, phosphor materials and their corresponding optical transmission characteristics play significant role in x-ray detectors, cathode ray tubes, microscopy techniques, white LED applications and have an impact on other scientific fields including chemical, energy, optoelectronic and space industries. The complex refractive index is associated with the optical attenuation capabilities of phosphor materials, either scattering or absorption, which in turn influences their imaging characteristics. In order to examine the complex refractive index effects, a simulation model was developed by taking into account the following: (i) phosphors of different layer thickness, 100 μm (thin layer) and 200 μm (thick layer), (ii) packing density 50%, (iii) three values of light wavelengths 400, 550, and 700 nm, and (iv) particle diameter in the range 10–10 mm. The complex refractive index was considered to vary: (a) from 1.5 up to 2.0 the real part and (b) from 10⁻⁶ up to 10⁻⁴ the imaginary part. The role of the complex refractive index on the optical parameters was examined within the framework of Mie scattering theory. Optical diffusion was assessed through Monte Carlo simulation techniques and the most important conclusion of the results was the achievement of improved phosphor spatial resolution by increasing the real part of the refractive index and not the imaginary one.

The use of traditional electrical impedance tomography (EIT) in cardiac thermal imaging is limited due to the high level of impedance complexity in body structure and noise. In this paper, two commercial available multi-electrode arrays (MEA), St Jude Medical (SJM) Ensite MEA and Biosense-Webster constellation, were studied to investigate the possibility to use in cardiac EIT. It has been found that the constellation has suitable electrode contact impedance, phase angle and shunt capacitance for common EIT devices while the MEA has better design features to improve sensitivity. Simulation showed that internal array configuration improves the distinguishability of an anomaly in saline tank through z-score and Graz consensus reconstruction algorithm for EIT parameters. Overall the MEA showed better z-score and amplitude response than the constellation and has the potential to be used in internal cardiac EIT for further studies.

In this paper we present a portable magnetocardiography device. The focus of this development was delivering a rapid assessment of chest pain in an emergency department. The aim was therefore to produce an inexpensive device that could be rapidly deployed in a noisy unshielded ward environment. We found that induction coil magnetometers with a coil design optimised for magnetic field mapping possess sufficient sensitivity ($104\,{\rm{fT}}{{\rm{Hz}}}^{-1/2}$ noise floor at 10 Hz) and response ($813\,{\rm{fT}}\,{\mu {\rm{V}}}^{-1}$ at 10 Hz) for cycle averaged magnetocardiography and are able to measure depolarisation signals in an unshielded environment. We were unable to observe repolarisation signals to a reasonable fidelity. We present the design of the induction coil sensor array and signal processing routine along with data demonstrating performance in a hospital environment.

Deep brain stimulation (DBS) provides a valuable platform for recording local field potentials (LFP) during surgery for studying the mechanisms of brain diseases and DBS therapy. Long-term neural activity monitoring remains a necessity for research on some neurodegenerative disorders and closed-loop DBS systems. A neurostimulator with recording ability has been developed as a research tool and a medical device. This study investigates the feasibility of chronic electrophysiological studies using neurostimulator (model G102RS) for recording LFP. Recent studies have suggested that oscillatory beta band activity can be used as a biomarker of Parkinson's disease (PD). Here, subthalamic LFP recordings were obtained from (i) a group of PD patients undergoing DBS therapy, (ii) the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned monkey model of PD, and (iii) a PD patient with an implanted neurostimulator. A total of 55/60 LFP datasets measured from the PD patients at rest during the operation contained spectral peaks in beta band as pathophysiological oscillations. These oscillations were strongly suppressed during DBS. The long-term animal experiment and the clinical implant demonstrated that the G102RS can adequately record the long-term frequency band-specific amplitude fluctuations such as the beta band activity. The device could identify the suppression of the beta band activity during DBS. Together, these data demonstrate the use of this medical device for chronic electrophysiological studies.

The aim of the present study is to synthesize hydroxyapatite from seashell and to explore its biocompatibility in vitro. Nano-crystalline hydroxyapatite (HAp) ceramics were successfully fabricated by a mechanochemical method using clam seashells and phosphoric acid. The CaO and H₃PO₄ acid at different w.t% ratios i.e. 1:0.75, 1:1.25, 1:1.5 and 1:1.75, were ball milled and then heat treated at 1000 °C for 3 h to complete reactions. The synthesized powders were characterized using x-ray diffraction (XRD), FTIR spectroscopy, scanning electron microscope and high resolution transmission electron microscopy. XRD results showed that the average crystallite size of the powder varies from 53 to 67 nm and crystallinity of powder found to be in the range of 88% and 96%. In vitro biocompatibility studies were carried out using osteoblast (MG63) and fibroblast cells (NIH3T3), demonstrated non-toxic nature of the seashell derived HAp powder.

Water-dispersible iron oxide nanoparticles (NPs) consistently demonstrated a significant interest in the field of biomedical applications. Through this report, we present the synthesis of monodispersed magnetite NPs with an excellent water-dispersibility by employing a modified thermal decomposition method. Synthesized NPs were characterized by x-ray diffraction, transmission electron microscopy, x-ray photoelectron spectroscopy, vibrating sample magnetometry and cytotoxicity assay. From the results, it is evident that the NPs are highly crystalline, of spherical morphology with diameters of 20 ± 1 nm, superparamagnetic, and cytocompatible. Finally, we probed NPs as a T₂-weighted contrast agent in magnetic resonance Imaging which resulted in relatively high r₂ values. Therefore, the NPs could be effectively used as a potential candidate for various biological applications.

In this paper, a new method for the automatic classification of seizures based on time-frequency image (TFI) of electroencephalogram (EEG) signals is proposed. Automatic classification of seizures is a crucial part of the diagnosis and treatment of epileptic seizures. TFI has been obtained by the smoothed pseudo Wigner-Ville distribution (SPWVD) based time-frequency representation (TFR) of EEG signal. The contrast stretching based pre-processing is used to increase the dynamic range of image pixels of TFI. The TFI has been segmented into rhythms of EEG signals based on frequency-bands. The features extracted from segmented images have been used as input, set to least squares support vector machines (LS-SVM) classifier together with the linear kernel, radial basis function (RBF), Mexican hat wavelet, and Morlet wavelet kernel functions for automatic classification of seizure from EEG signals. The proposed method for classification of EEG signals has provided better classification accuracy than other existing methods. The experimental results are presented to show the effectiveness of the proposed method for the classification of seizure from EEG signals.

In diffuse optical tomography (DOT) the main objective is to estimate the absorption coefficent and the reduced scattering coefficient of a certain media given a set of boundary measurements. Biological tissues contains many objects such as arteries, skin and fat whose optical properties are rather different than those of the media. When these values are near to those of the background, linear techniques are usually used to estimate them. However, certain objects, such as tumors, may have properties which cannot be well estimated with linear models. In this article we present a non-linear approach for the frequency-domain problem based on an improvement of the extended Kalman filter (EKF) which is used in estimation-observation problems, and modified to the DOT parameter estimation problem. The EKF allows to incorporate prior information of the measurement noise as well as certain characteristics of the objective media. We show that the proposed methodology is equivalent to existing methods but can be applied to other schemes such as model reduction as suggested in previous works. Some computer simulations as well as experimental results are shown to validate our proposal.

Background and Purpose. The goal of this project was the dosimetric characterization of a mini-beam collimator across three clinically beam matched medical linear accelerators (linacs). Methods and Materials. The beam quality (%DD(10)), peak-to-valley dose ratio (PVDR), collimator factor $({\rm{C}}{{\rm{F}}}_{{f}_{{\rm{m}}{\rm{i}}{\rm{n}}{\rm{i}}}}^{w}),$ and relative output $({\rm{O}}{{\rm{F}}}_{{f}_{{\rm{m}}{\rm{i}}{\rm{n}}{\rm{i}}}}^{w})$ were obtained for 6 MV mini-beam collimated fields of various sizes on three clinically beam matched Varian iX medical linear accelerators. Monte Carlo simulations of the mini-beam collimated fields were used to correlate the experimental results to the accelerators' electron beam full width-half maximum (FWHM) incident on the Bremsstrahlung target. Results. The beam quality of the mini-beam collimated field on all three linear accelerators agreed with that of the open field beam to within ±1%. PVDR on the different linacs varied by up to ±8.1% from the mean. Similarly, the collimator factors varied from the mean by up to ±3.6%. However, changes in the mini-beam collimated field due to changes in collimator inclination with respect to the beam central axis or field size were consistent across the three linacs. The collimator factors of the linacs were found to decrease by up to 7.1% in response to changes in inclination of less than 0.1°, and have an inverse relationship to field size. Monte Carlo simulations indicated that the disagreement in collimator factor can be linked to variation in the spatial width of the electron beam incident on the Bremsstrahlung target. Conclusion. A mini-beam collimator has been dosimetrically characterized on three clinically beam matched medical linear accelerators. Discrepancies in the mini-beam collimated field characteristics were observed across accelerators. Monte Carlo simulation revealed that these differences were related to the linac electron beam FWHM.

A noninvasive investigation to ascertain the severity of dengue was conducted on 44 hospitalized dengue hemorrhagic fever (DHF) subjects, male and female aged between 3 and 14 years using bioelectrical impedance analysis. Among the 44 subjects, 30 subjects were confirmed with NS1 positive at the time of admission, whose blood investigations such as haematocrit (HCT), platelet (PLT) count, aspartate aminotransferase (AST) level and alanine aminotransferase (ALT) level was taken for classification of risk under low risk and high risk DHF. For comparison, BIA of 53 healthy controls was also taken. To provide a better and accurate estimate, a dual frequency method is proposed to calculate body fluid volumes such as total body water (TBW), extracellular fluid (ECF) and intracellular fluid (ICF). The impedance at 100 kHz is used to estimate TBW while impedance at 5 kHz to estimate ECF. Statistical analysis identifies that the ratio of ECF/ICF estimated using the proposed dual frequency method, shows significant difference between control and DHF risk groups and also shows good correlation with the blood investigation results. In addition, statistical analysis of proposed ECF/ICF method on other fever subjects indicate significant difference with DHF.

Introduction. Several medical physicists have moved to a statistical process control-oriented approach to learn more about the intrinsic performance of radiotherapy equipment. Our aim is to report how gauge repeatability and reproducibility (R&R) and sensitivity and specificity studies can provide optimal specifications for radiotherapy-beam calibration checks. Methods. A team of three medical physicists performed gauge R&R studies on 6 megavolt (MV) photon, and 4, 9, and 15-megaelectron volt electron-beams. The operator order was randomized to reduce time-related biases. Checks were performed accurately using ionization chambers with a water phantom. These gauge R&R studies allowed us to determine the proportion of variation due to the repeatability, operator, and beam-to-beam components associated with repeated beam-calibration checking. We then calculated the conditional probabilities of misclassifying the check results as a false accept (β = 1–sensitivity) and a false reject (δ = 1–specificity) by changing the beam calibration specifications. Using this information we plotted the receiver operating characteristic curves in order to identify the sensitivity and specificity settings that maximize detection. Results. The main component of variation was due to the operator; the repeatability component was less than 30%. The intrinsic variation component for 6 MV photon-beams was approximately 20%, whereas it was over 34% for electron-beams. The optimal specification bands expressed as a percentage of the mean were ±0.7% for 6 MV photons and ±0.9% for electron-beams. Optimal sensitivity was over 50%, whereas specificity was not less than 0.995. The very low δ indicates that the system is unlikely to reject a correct beam calibration. However, the high β shows that should we require high levels of precision and therefore adopt such optimized specifications, the probability of accepting a drifted beam calibration would be fairly high. Therefore, the combination of 'medical physicist, water phantom, and ionization chamber' is an excellent tool for correctly adjusting beam calibrations to their specifications; moreover, this procedure could also be further improved in order to detect drifts in beam calibrations if the specifications required were to tighten in the future. Conclusion. Calculating the optimal specifications is feasible and leads to a very high detection specificity, but with low sensitivity. The operator-associated variation component contributed the most to the overall variation in check results. The beam calibration procedure might need to be adapted if the demand for precision in radiotherapy increases.

The photoacoustic (PA) field calculation using a Green's function approach for nonspherical axisymmetric fluid particles is discussed. The PA fields have been computed for spheroidal droplets, Chebyshev particles and normal and pathological red blood cells (RBCs) over a large frequency band (10–1000 MHz). Theoretically constructed RBC contours have been fitted using the Legendre polynomial expansion for parametrization of cell shapes. It is shown that first minimum of the PA spectrum appears at a lower frequency as the width of the particle along the direction of measurement increases. The spectra for higher order (n = 6, 8) Chebyshev particles resembled that of an equivalent sphere up to first minimum. The first minimum for a stomatocyte appeared (420 MHz) much earlier compared to that (640 MHz) of normal RBC when measured along the direction of the symmetry axis; whereas the locations were 310 and 240 MHz, respectively from a perpendicular direction. The evaluation of cellular morphology might be feasible by analyzing the single particle PA spectrum.

This work presents an in-depth analysis into the dependencies of radiosensitisation on x-ray beam energy, particle morphology and particle concentration for ${{\rm{Ta}}}_{2}{{\rm{O}}}_{5}$ nanostructured particles (NSPs). A maximum sensitisation enhancement ratio of 1.46 was attained with irradiation of a 10 MV x-ray photon beam on 9L cells exposed to the less aggregated form of NSPs at 500 μg ml⁻¹. A significant increase in sensitisation of 30% was noted at 150 kVp for irradiation of the less aggregated form of tantalum pentoxide NSPs compared to its more agglomerated counterpart. Interestingly, no differences in sensitisation were observed between 50 and 500 μg ml⁻¹ for all beam energies and NSPs tested. This is explained by a physical 'shell effect', where by the NSPs form layers around the cells (observed using confocal microscopy), with the inner layers contributing to enhancement, while the outer layers shield the cell from damage.

The aim of this study was to develop a new barrier membrane from ureasil–polyether hybrid materials for guided bone regeneration. The membrane was prepared via the sol–gel route by using polyethylene oxide and polypropylene oxide polymer blends; dexamethasone was used as a drug model for in vitro release testing. Membrane swelling was monitored by small-angle x-ray scattering (SAXS) measurement and bone formation was investigated by microtomography. In vitro drug release testing revealed sustained profiles that could be controlled by varying the proportions of the polymers. SAXS analysis showed that the polymer blend can control the high swelling observed when using ureasil–polyethylene oxide material. Histological results revealed that the ureasil–polyether blend promoted local inflammation similar to the response caused by commercial collagen membrane. The results of microtomography showed that the osteo-regeneration of bone defects by using ureasil–polyether membranes was similar to the effect promoted by commercial collagen membrane. These results indicate that ureasil–polyether membranes are promising candidates for barrier membrane, considering their low cost, luminescence, control of drug release, ease of handling, and biocompatibility.

The dielectric properties of biological tissues have been studied widely over the past half-century. These properties are used in a vast array of applications, from determining the safety of wireless telecommunication devices to the design and optimisation of medical devices. The frequency-dependent dielectric properties are represented in closed-form parametric models, such as the Cole–Cole model, for use in numerical simulations which examine the interaction of electromagnetic (EM) fields with the human body. In general, the accuracy of EM simulations depends upon the accuracy of the tissue dielectric models. Typically, dielectric properties are measured using a linear frequency scale; however, use of the logarithmic scale has been suggested historically to be more biologically descriptive. Thus, the aim of this paper is to quantitatively compare the Cole–Cole fitting of broadband tissue dielectric measurements collected with both linear and logarithmic frequency scales. In this way, we can determine if appropriate choice of scale can minimise the fit error and thus reduce the overall error in simulations. Using a well-established fundamental statistical framework, the results of the fitting for both scales are quantified. It is found that commonly used performance metrics, such as the average fractional error, are unable to examine the effect of frequency scale on the fitting results due to the averaging effect that obscures large localised errors. This work demonstrates that the broadband fit for these tissues is quantitatively improved when the given data is measured with a logarithmic frequency scale rather than a linear scale, underscoring the importance of frequency scale selection in accurate wideband dielectric modelling of human tissues.

Electrical capacitance tomography (ECT) has been widely used for industrial applications, but it is rarely used in the medical field. Considering its advantages of being non-radioactive and its fast speed, ECT has the potential for medical applications by generating real-time images. This paper introduces a new method of using ECT for visualising the tooth surface as a potential online imaging technique for endodontic therapy. A two-planar ECT sensor is designed for this purpose. With two electrode arrays, both cross-sectional and longitudinal images are obtained, providing 2.5 D information. Simulation was performed using COMSOL 3.5, and 3D models were generated. A single premolar was tested using an impedance analyser based ECT system to collect capacitance data from the fabricated two-planar sensors, and images were reconstructed using linear back-projection (LBP) and Landweber iteration algorithms. The initial results show that the ECT system with a two-planar ECT sensor can be used to visualise a single tooth surface, confirming the feasibility of the method.

The velocity of the propagating arterial pulse wave (pulse wave velocity, PWV) has been proposed as an unobtrusive and possibly continuous surrogate measure of systolic blood pressure (SBP). PWV is derived from the arrival time of the blood pulse at a peripheral arterial location, most often the finger. Reported performances were not yet accurate enough for clinical application but good enough as an unobtrusive surrogate in other settings. However, the finger PPG is not an ideal location in the home setting as it obstructs hand movement and can suffer from peripheral vasomotion and orthostatic pressure changes. In this paper we examine the viability of other pulse arrival locations for the measurement of PWV. PWV was derived to the finger (most common location), wrist (less obtrusive location), ear (more proximal) and ankle (more distal). Correlation analysis for PWV from each location with SBP was performed and the calibration procedure was studied. Wrist PWV accuracy is found to be comparable to finger PWV in terms of correlation and estimation error with SBP. The ear PWV, being a theoretically favorable location, is shown to have a larger inter-subject variance in the calibration procedure compared to other locations. Ankle PWV shows stable calibration parameters across subjects but Bland-Altmann analysis reveals unusual error trends. In conclusion, while results indicate that all sensor locations are usable to some extent, there are still some distinct properties associated with each sensor location that should be taken into account when designing an SBP algorithm based on PWV.

Monitoring of blood oxygen saturation (SpO₂) of the neonate is essential to the quality of health care provided on a neonatal intensive care unit (NICU). Current sensors are usually placed at the hand or foot, which are dependent of a peripheral blood supply. When the peripheral blood circulation of neonates is compromised conventional peripheral pulse oximeters, in many cases, fail to operate accurately or at all. A new reflectance anterior fontanelle (ANTF) SpO₂ sensor and instrumentation has been developed to investigate SpO₂s from the neonatal fontanelle. The hypothesis is that perfusion at a central site should be preserved at times of compromised peripheral circulation. Fifteen neonates on an NICU (9 male, 6 female) with a median age of 7 d (IQR = 41.5 d) were selected for monitoring. ANTF photoplethysmographic (PPG) signals were monitored for a maximum period of 2 h. The developed system and custom made sensors were successful at acquiring good quality signals at both wavelengths necessary for pulse oximetry calculations. ANTF SpO₂s, estimated from the acquired PPGs, were in broad agreement with SpO₂s obtained from the commercial foot pulse oximeter. A Bland and Altman analysis of the differences between SpO₂s from the fontanelle PPG sensor and the commercial device show a relatively small mean difference ($d=\pm 2.2 \%$), but with a wide variation ($2s=\pm 17.4 \%$) this observation may be due to the varied levels of ill health patients and is backed up by comparing the commercial device SpO₂ readings at the same moment a blood gas sample was taken ($d=4.8 \% ,2s=\pm 15.8 \%$).

Diffusion and transport of complex fluids in porous media have attracted significant interests not only due to their unique mechanics but also their close relevance to various biological systems. In this paper, we exhibit direct real-time visualization of the planar diffusion patterns of a nanofluid that is microfluidically injected and confined in the dermal layer of living mouse skin. An in vivo fluorescence bioimaging method enables the physiological monitoring of spatiotemporally-resolved diffusion behavior of fluorescent magnetic nanoparticle suspensions which are transcutaneously and continuously infused into the dermis using a microneedle-micropump device. We discuss the possible mechanism of this quasi-2D diffusion process based on a convection–diffusion model and future applications in the context of bioengineering, including magnetic hyperthermia and controlled drug delivery.

The volume magnetic susceptibility (χ_v) and Vickers hardness (HV) of Au–Ta and Au–Nb alloys were investigated for use as magnetic resonance imaging (MRI)-compatible alloys for biomedical applications. χ_v of the Au–Ta alloys did not depend on the phase constitution but did depend on the alloy composition. Therefore, heat treatment hardly affected χ_v of the Au–Ta alloys, and only alloys with Ta contents near 15 were possibly MRI-compatible. In contrast, χ_v of the Au–Nb alloys depended on the phase constitution. Therefore, both the alloy composition and heat treatment can be used to widely control χ_v of Au–Nb alloys, and Au–xNb alloys (x ≥ 6.8) can be made MRI-compatible by optimizing χ_v using heat treatment. HV of the Au–15Ta alloy was smaller than that of pure Ti even after heat treatment, whereas HV of the MRI-compatible Au–Nb alloys was possibly higher than that of pure Ti after heat treatment. The saturated χ_v values of the Au–Nb alloys after heat treatment at 800 °C are compatible with the hypothesis that χ_v of an alloy is the average χ_v of each phase of the alloy based on the rule of mixtures. This hypothesis supports the tailoring of χ_v by controlling the alloy composition and heat treatment.

Purpose. To investigate the patient radiation dose saving of grid-less x-ray mammography acquisitions compared with conventional full-field digital mammography (FFDMG). Methods and materials. The Siemens Inspiration MAMMOMAT PRIME system with software based scatter correction was used to investigate the dose saving in grid-less acquisition compared with conventional full-field digital mammography (FFDMG) acquisitions. A Piranha 657 solid-state detector was used to measure the entrance exposure. The entrance exposure was directly measured on different PMMA thicknesses of 20–70 mm in steps of 10 mm. The PMMA block thicknesses were then converted to an equivalent compressed breast tissue thicknesses. The average glandular dose (AGD) is calculated. Results. Dose reduction in both the directly measured entrance exposure and the calculated AGD is between 13% and 32% in the grid-less mammography acquisition. The contrast to noise ratio calculated in the grid-less and the FFDMG acquisition also was the same. Conclusion. It was possible to save patient dose (13%–32%) in grid-less mammography acquisition without affecting the image quality.

A blood oxygenation-level dependent (BOLD) functional magnetic resonance imaging (fMRI) study produces a four-dimensional (4D) complex-valued data set. Conventional magnitude-based brain functional mapping is an indirect measure of brain activity due to a dataflow in a cascade of MRI transformations (e.g., a dipole convolution). The MRI transformations also impose a MRI parameter dependence to BOLD fMRI data (e.g. the dependence on B₀ and T_E). By solving an inverse MRI problem, we may reconstruct a brain magnetic susceptibility source distribution (denoted by χ) from a brain MR image, thereby achieving a more direct representation of the vascular origin than the MRI data representation. For a complex-valued BOLD fMRI dataset, we can extract net BOLD phase responses (δP) through a complex division, and then reconstruct BOLD susceptibility responses (δχ) therefrom. In this paper, we compare the functional maps depicted in different dataspaces (magnitude image, δP image, δχ source) based on numeric characterizations of activation blobs by pattern analysis. Through an experimental demonstration with high-field (7 T) and high-resolution (0.5 mm in-plane) finger-tapping experiment, we show that the δχ-depicted functional map reveals task-evoked bidirectional BOLD δχ responses at the motor cortex region. The positive and negative activations are spatially separated and balanced, indicating conservation of concurrent excitations and inhibitions. We also observe that the source-depicted activation spots are more compact than the image-depicted spots, which is attributed to the dipole effect removal by inverse MRI.

Respiratory-induced motions are prone to degrade the positron emission tomography (PET) signal with the consequent loss of image information and unreliable segmentations. This phantom study aims to assess the discrepancies relative to stationary PET segmentations, of widely used semi-automatic PET segmentation methods on heterogeneous target lesions influenced by motion during image acquisition. Three target lesions included dual F-18 Fluoro-deoxy-glucose (FDG) tracer concentrations as high- and low tracer activities relative to the background. Four different tracer concentration arrangements were segmented using three SUV threshold methods (Max40%, SUV40% and 2.5SUV) and a gradient based method (GradientSeg). Segmentations in static 3D-PET scans (PET_sta) specified the reference conditions for the individual segmentation methods, target lesions and tracer concentrations. The motion included PET images followed a 4D-PET (PET_4D) and a 3D-PET (PET_mot) scan protocol. Moreover, motion-corrected PET images (PET_deb) were derived from the PET_mot images. Segmentations in PET_4D, PET_mot and PET_deb were compared to the PET_sta segmentations according to volume changes (ΔVol) and an error estimate (lowUptake_error) for the lesion part covering the low tracer concentration. In PET_4D images, all segmentation methods provided lowUptake_error estimates equivalent to PET_sta segmentations and, except for the Max40% segmentations, a slight volume expansion. In the PET_mot images, the GradientSeg method results in an average 0.43 increased volume and an overestimation of 0.33 for the lowUptake_error. The most accurate segmentations in PET_mot, relative to PET_sta, were accomplished by the 2.5SUV and SUV40% methods. In the PET_deb images, the GradientSeg method solitary provided segmentations equivalent to segmentation in PET_sta images. The use of FDG with various tracer concentrations revealed, according to PET_sta images, that the most constant segmentations for motion-corrected PET images (PET_4D or PET_deb) were achieved using the GradientSeg method. In the absence of PET_4D or PET_deb images, the 2.5SUV and SUV40% methods are most consistent to PET_sta segmentations.

A promising approach to treating liver cancer with radiotherapy, is using a combination of a conformal technique, such as carbon ion-beam therapy, and beam gating. This study aims to assess the dosimetric implications, in a dose planning and verification study, of the use of gated internal target volume (ITV_gate) when beam gating is used. Patients were immobilised with abdominal compression and a subset of these patients were treated using beam gating. The delivered dose was reconstructed. Significant dose degradation in the clinical target volume (CTV) due to the patient's motion was identified. In addition, new plan optimisations were performed for the PTV_gate, obtained from the geometric union of the phase-CTVs in the gating window. Finally, the concept of CTV expansion, including water equivalent path length variations (PTV_gWEPL), was evaluated. When breathing was regular in amplitude, dose planning to the PTV_gate resulted in a reduction in the dose delivered to healthy liver tissue without compromising the target coverage. In contrast, the use of PTV_gWEPL concept resulted in a delivered plan with minor deviations from the planned treatment. The planned dose for the two concepts was verified in a 3D-motion water phantom. The mean relative deviations between measurements and the reconstructed dose were below 5% and were therefore within the clinically acceptable range for treatment.

Purpose. The inherent difficulty of identifying liver and pancreas tumors without intravenous contrast creates the need for implanted metal fiducials to visualize tumor position and motion in stereotactic body radiation therapy (SBRT). Unfortunately, the invasive procedure of implanting fiducials carries a risk of toxicity, introduces a treatment delay, and creates streak artifacts on treatment planning images, which can hinder tumor identification. A fiducial-less motion management strategy would improve the safety, tolerability, and availability of abdominal SBRT. We hypothesized that upper abdominal tumor motion would correlate with the motion of nearby organs and could thereby serve as a fiducial-less proxy for tumor motion. Methods. We retrospectively identified fifteen patients with pancreatic cancer or liver cancer treated with SBRT. The liver, superior mesenteric artery, and celiac artery were delineated on 4DCT images and used to predict tumor position. The correlation with tumor motion was quantified with Pearson correlation coefficients (r), and accuracy of the tumor position prediction was expressed as the mean absolute error. Results. The majority of motion with respiration occurred in the superior–inferior (SI) direction with an average of 6.4 mm (range 2.4–11.3 mm) for pancreatic and 13.0 mm (range 6.4–21.2 mm) for liver tumors. In the SI direction we found a tight correlation between liver and tumor motion in pancreas cancer patients (r = 0.92 ± 0.10), and liver tumor patients (r = 0.97 ± 0.02). Using the liver as surrogate, predicted tumor location was on average 0.5 mm from the actual position and not greater than 3.0 mm. Conclusions. This study demonstrates a potential correlation of normal organ and tumor motion which could serve as a fiducial-less surrogate for SBRT in the upper abdomen as on-site 4D volumetric imaging becomes available during treatment. Moving this motion management strategy into the clinic requires additional research to optimize 4D image quality and understand inter-fraction reproducibility.

Flattening filter free (FFF) linear accelerators (linacs) are increasingly being used to deliver external beam radiotherapy. Advantages of FFF include lower out-of-field dose to the patient due to reduced head scatter, and shorter treatment times due to increased dose rate. The ion recombination factor (k_ion) is known to increase linearly with dose per pulse in pulsed photon beams. This variation is neglected when performing relative dosimetry in flattened beams, however could be significant in the higher dose rates encountered with FFF. k_ion has been derived from theory and measured using Jaffe plots and two voltage analysis for three ionisation chambers at a range of depths and points off-axis in 6 and 10 MV FFF beams produced by an Elekta Versa HD linac. The chambers under investigation were the PTW 30013 'Farmer' (0.60 cc), the Exradin A1SL (0.053 cc) and the IBA CC04 (0.04 cc). The effect of neglecting ion recombination corrections in commissioning data was quantified using a 1D gamma analysis (1%/2 mm) on depth dose curves and beam profiles. The largest variation in k_ion was for a Farmer chamber in a 10 MV FFF beam, where k_ion varied by up to 1.2% ± 0.15% (95% CL) between different points in a water tank. The Farmer variation with depth was comparable to that measured by Kry et al (2012 J. Appl. Clin. Med. Phys.13 318–325). Other chambers exhibited negligible changes in k_ion. It was concluded that neglecting ion recombination in relative measurements at 6 MV FFF would have a negligible effect on dosimetric accuracy. Furthermore k_ion could be safely neglected when acquiring relative data with small volume chambers for commissioning 10 MV FFF, although may need to be accounted for if relative data are acquired with a Farmer chamber and when routine energy checks are performed.

The main aim of this work is to facilitate generation of the extended cardiac and torso (XCAT) phantom with focus on automated and simplified generation of four-dimensional computed tomography (4DCT) simulated images. A comprehensive graphical user interface (GUI) was developed to expedite phantom generation, processing and 4DCT image generation. The use of irregularly shaped patient-specific tumors with the XCAT phantom, a capability that is not implemented in the current version of the application, was also addressed. XCAT phantoms were generated to demonstrate the GUIs functionality. The following GUI functions were demonstrated; (a) generation of 4DCT images using respiratory motion signal; (b) generation of maximum intensity image from 4DCT images; (c) insertion of irregularly shaped tumors from DICOM files; (d) exporting XCAT data to DICOM format and importing to an Eclipse treatment planning system. An open source, publicly available graphical interface for the XCAT phantom was developed. The graphical interface is capable of generating a wide variety of phantoms to simulate 4DCT acquisition images. The graphical interface is also able to incorporate irregularly shaped tumors within the XCAT framework. The graphical interface is freely distributed for imaging research.

Heart rate variability (HRV) analysis has been used as a quantitative marker of the autonomous nervous system activity to measure mental stress. Wearable sensors have been emerging as a solution to collect HRV data for stress assessment in a real context, however such studies raise additional requirements. The wearable system must be minimally obtrusive to allow the subjects to perform their tasks without interference, and inconspicuous to avoid the anxiety associated with wearing medical devices in public. The purpose of this study was to quantify the accuracy trade-off in the use of a chest band heart rate sensor that is less intrusive and less costly than a wearable electrocardiogram (ECG). The HRV metrics extracted from a chest band heart rate monitor, Zephyr HxM^TM (Zph^TM), were compared with those extracted from an ECG certified medical device, Vital Jacket^TM (VJ^TM). The two systems were worn simultaneously under laboratory conditions by a population of 14 young and healthy subjects, aged 20 to 26 years, under the stress induced by the Trier Social Stress Test (TSST) procedure. The results showed a mean difference between RR intervals of 9 ms; a root-mean square error (RMSE) of less than 8% and a Pearson's correlation higher than 0.946, considering all TSST phases. In the HRV analysis, the average of all normal intervals (AVNN) showed errors less than 2% between the two systems with a correlation higher than 0.99 for all TSST phases. We thus conclude that the used chest band sensor represents an alternative to the current wearable medical devices to monitor RR intervals, and could be used for mental stress monitoring similar to the TSST protocol.

Objectives. To assess the feasibility of a new wearable, wireless ultrasonic device, the URIKA bladder monitor (UBM), in the detection of a full bladder in children with dysfunctional voiding (DV). Methods. This observational study included 14 children with DV who were subjected to an UBM monitoring session of 1.5–2 h. Transabdominal ultrasound (TUS) images were made as reference. The UBM measured the anterior–posterior bladder dimension by an ultrasound transducer, mounted in an elastic belt around the lower abdomen. Level of agreement between both methods was estimated by Bland–Altman analysis. Receiver operating characteristics (ROC) analysis was performed to determine a full bladder threshold for the studied population. Results. In 13 out of 14 patients, the UBM measured properly. Maximum bladder dimensions detected by the UBM and TUS were 6.69 ± 1.53 cm and 4.79 ± 0.99 cm respectively. Bland–Altman analysis showed a negative bias of −0.90 cm (limits of agreement: −4.1/+2.3 cm). ROC analysis resulted in a sensitivity and specificity of 78.3% and 100%, for a bladder dimension threshold of 5.03 cm. When this threshold was implemented a priori, the full bladder detection rate would have been 71%. In children younger than 10 years, this would be 100% (n = 5). Conclusion. The UBM is able to detect a full bladder with a detection rate of 71%, if a 5.03 cm threshold would be implemented. In patients younger than 10 years, the detection rate would be 100%. Future research will focus on increasing the UBM's accuracy and investigating the effect of UBM alarm treatment in children with urinary incontinence.

Osteoporosis has been characterized as a skeletal disorder of reduced bone strength that leads to an increased risk of fracture. As the age of the person grows, early diagnosis of the disease is necessary to maintain good bone strength and to avoid unbearable fractures. While the disease cannot be reversed, it can be effectively managed by detecting bone density variations. Recently introduced non-stationary thermal wave imaging techniques have gained wide acceptance in the thermal non-destructive testing research community due to their merits over the conventional methods. This paper attempts to test the capabilities of one of the widely used non-stationary thermal imaging techniques to characterize the severity of osteoporosis in the modeled human bone. A 3D finite element analysis has been carried out to model a multilayered bone having different density variations, with tissue, skin and muscle over layers. Obtained results from frequency domain analysis scheme has been studied in order to detect the density variations with improved test sensitivity.