Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.

Calcium ions promote osteogenic differentiation and mineralization of human dental pulp cells : implication for pulp capping materials

Calcium (Ca) is the main element of most pulp capping materials and plays an essential role in mineralization. Different pulp capping materials can release various concentrations of Ca ions leading to different clinical outcomes. The purpose of this study was to investigate the effects of various concentrations of Ca ions on the growth and osteogenic differentiation of human dental pulp cells (hDPCs). Different concentrations of Ca ions were added to growth culture medium and osteogenic inductive culture medium. A Cell Counting Kit-8 (CCK-8) was used to determine the proliferation of hDPCs in growth culture medium. Osteogenic differentiation and mineralization were measured by alkaline phosphatase (ALP) assay, Alizarin red S/von kossa staining, calcium content quantitative assay. The selected osteogenic differentiation markers were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Within the range of 1.8–16.2 mM, increased concentrations of Ca ions had no effect on cell proliferation, but led to changes in osteogenic differentiation. It was noted that enhanced mineralized matrix nodule formation was found in higher Ca ions concentrations; however, ALP activity and gene expression were reduced. qRT-PCR results showed a trend towards down-regulated mRNA expression of type I collagen (COL1A2) and Runx2 at elevated concentrations of Ca ions, whereas osteopontin (OPN) and osteocalcin (OCN) mRNA expression was significantly up-regulated. Ca ions content in the culture media can significantly influence the osteogenic properties of hDPCs, indicating the importance of optimizing Ca ions release from dental pulp capping materials in order to achieve desirable clinical outcomes.

Why publish?

Anybody who has attempted to publish some aspect of their work in an academic journal will know that it isn’t as easy as it may seem. The amount of preparation required of a manuscript can be quite daunting. Besides actually writing the manuscript, the authors are faced with a number of technical requirements. Each journal has their own formatting requirements, relating not only to section headings and text layout, but also to very small details such as placement of commas in reference lists. Then, if presenting data in the form of figures, this must be formatted so that it can be understood by the readership, and most journals still require that the data be in a format which can be read when printed in black-and-white. Most daunting (and important) of all, for the article to be scientifically valid it must be absolutely true in the representation of the work reported (i.e. all data must be shown unless a strong justification exists for removing data points), and this might cause angst in the mind of the authors when the results aren’t clear or possibly contradict the expected or desired result.

Monte Carlo verification of gel dosimetry measurements for stereotactic radiotherapy

The quality assurance of stereotactic radiotherapy and radiosurgery treatments requires the use of small-field dose measurements that can be experimentally challenging. This study used Monte Carlo simulations to establish that PAGAT dosimetry gel can be used to provide accurate, high resolution, three-dimensional dose measurements of stereotactic radiotherapy fields. A small cylindrical container (4 cm height, 4.2 cm diameter) was filled with PAGAT gel, placed in the parietal region inside a CIRS head phantom, and irradiated with a 12 field stereotactic radiotherapy plan. The resulting three-dimensional dose measurement was read out using an optical CT scanner and compared with the treatment planning prediction of the dose delivered to the gel during the treatment. A BEAMnrc DOSXYZnrc simulation of this treatment was completed, to provide a standard against which the accuracy of the gel measurement could be gauged. The three dimensional dose distributions obtained from Monte Carlo and from the gel measurement were found to be in better agreement with each other than with the dose distribution provided by the treatment planning system's pencil beam calculation. Both sets of data showed close agreement with the treatment planning system's dose distribution through the centre of the irradiated volume and substantial disagreement with the treatment planning system at the penumbrae. The Monte Carlo calculations and gel measurements both indicated that the treated volume was up to 3 mm narrower, with steeper penumbrae and more variable out-of-field dose, than predicted by the treatment planning system. The Monte Carlo simulations allowed the accuracy of the PAGAT gel dosimeter to be verified in this case, allowing PAGAT gel to be utilised in the measurement of dose from stereotactic and other radiotherapy treatments, with greater confidence in the future.

Application of a new discreet form of Gauss’ theorem for measuring volume

Volume measurements are useful in many branches of science and medicine. They are usually accomplished by acquiring a sequence of cross sectional images through the object using an appropriate scanning modality, for example x-ray computed tomography (CT), magnetic resonance (MR) or ultrasound (US). In the cases of CT and MR, a dividing cubes algorithm can be used to describe the surface as a triangle mesh. However, such algorithms are not suitable for US data, especially when the image sequence is multiplanar (as it usually is). This problem may be overcome by manually tracing regions of interest (ROIs) on the registered multiplanar images and connecting the points into a triangular mesh. In this paper we describe and evaluate a new discreet form of Gauss’ theorem which enables the calculation of the volume of any enclosed surface described by a triangular mesh. The volume is calculated by summing the vector product of the centroid, area and normal of each surface triangle. The algorithm was tested on computer-generated objects, US-scanned balloons, livers and kidneys and CT-scanned clay rocks. The results, expressed as the mean percentage difference ± one standard deviation were 1.2 ± 2.3, 5.5 ± 4.7, 3.0 ± 3.2 and −1.2 ± 3.2% for balloons, livers, kidneys and rocks respectively. The results compare favourably with other volume estimation methods such as planimetry and tetrahedral decomposition.

Volume estimation from multiplanar 2D ultrasound images using a remote electromagnetic position and orientation sensor

A system is described for calculating volume from a sequence of multiplanar 2D ultrasound images. Ultrasound images are captured using a video digitising card (Hauppauge Win/TV card) installed in a personal computer, and regions of interest transformed into 3D space using position and orientation data obtained from an electromagnetic device (Polbemus, Fastrak). The accuracy of the system was assessed by scanning 10 water filled balloons (13-141 ml), 10 kidneys (147  200 ml) and 16 fetal livers (8  37 ml) in water using an Acuson 128XP/10 (5 MHz curvilinear probe). Volume was calculated using the ellipsoid, planimetry, tetrahedral and ray tracing methods and compared with the actual volume measured by weighing (balloons) and water displacement (kidneys and livers). The mean percentage error for the ray tracing method was 0.9 ± 2.4%, 2.7 ± 2.3%, 6.6 ± 5.4% for balloons, kidneys and livers, respectively. So far the system has been used clinically to scan fetal livers and lungs, neonate brain ventricles and adult prostate glands.

Frank-starling control of a left ventricular assist device

A physiological control system was developed for a rotary left ventricular assist device (LVAD) in which the target pump flow rate (LVADQ) was set as a function of left atrial pressure (LAP), mimicking the Frank-Starling mechanism. The control strategy was implemented using linear PID control and was evaluated in a pulsatile mock circulation loop using a prototyped centrifugal pump by varying pulmonary vascular resistance to alter venous return. The control strategy automatically varied pump speed (2460 to 1740 to 2700 RPM) in response to a decrease and subsequent increase in venous return. In contrast, a fixed-speed pump caused a simulated ventricular suction event during low venous return and higher ventricular volumes during high venous return. The preload sensitivity was increased from 0.011 L/min/mmHg in fixed speed mode to 0.47L/min/mmHg, a value similar to that of the native healthy heart. The sensitivity varied automatically to maintain the LAP and LVADQ within a predefined zone. This control strategy requires the implantation of a pressure sensor in the left atrium and a flow sensor around the outflow cannula of the LVAD. However, appropriate pressure sensor technology is not yet commercially available and so an alternative measure of preload such as pulsatility of pump signals should be investigated.

A CAD interface for GEANT4

Often CAD models already exist for parts of a geometry being simulated using GEANT4. Direct import of these CAD models into GEANT4 however,may not be possible and complex components may be diffcult to define via other means. Solutions that allow for users to work around the limited support in the GEANT4 toolkit for loading predefined CAD geometries have been presented by others, however these solutions require intermediate file format conversion using commercial software. Here within we describe a technique that allows for CAD models to be directly loaded as geometry without the need for commercial software and intermediate file format conversion. Robustness of the interface was tested using a set of CAD models of various complexity; for the models used in testing, no import errors were reported and all geometry was found to be navigable by GEANT4. Funding source: Cancer Australia (Department of Health and Ageing) Research Grant 614217

The effect of very small air gaps on small field dosimetry

The purpose of this study was to investigate the effect of very small air gaps (less than 1 mm) on the dosimetry of small photon fields used for stereotactic treatments. Measurements were performed with optically stimulated luminescent dosimeters (OSLDs) for 6 MV photons on a Varian 21iX linear accelerator with a Brainlab μMLC attachment for square field sizes down to 6 mm × 6 mm. Monte Carlo simulations were performed using EGSnrc C++ user code cavity. It was found that the Monte Carlo model used in this study accurately simulated the OSLD measurements on the linear accelerator. For the 6 mm field size, the 0.5 mm air gap upstream to the active area of the OSLD caused a 5.3 % dose reduction relative to a Monte Carlo simulation with no air gap. A hypothetical 0.2 mm air gap caused a dose reduction > 2 %, emphasizing the fact that even the tiniest air gaps can cause a large reduction in measured dose. The negligible effect on an 18 mm field size illustrated that the electronic disequilibrium caused by such small air gaps only affects the dosimetry of the very small fields. When performing small field dosimetry, care must be taken to avoid any air gaps, as can be often present when inserting detectors into solid phantoms. It is recommended that very small field dosimetry is performed in liquid water. When using small photon fields, sub-millimetre air gaps can also affect patient dosimetry if they cannot be spatially resolved on a CT scan. However the effect on the patient is debatable as the dose reduction caused by a 1 mm air gap, starting out at 19% in the first 0.1 mm behind the air gap, decreases to < 5 % after just 2 mm, and electronic equilibrium is fully re-established after just 5 mm.

Radiotherapy Monte Carlo simulation using cloud computing technology

Cloud computing allows for vast computational resources to be leveraged quickly and easily in bursts as and when required. Here we describe a technique that allows for Monte Carlo radiotherapy dose calculations to be performed using GEANT4 and executed in the cloud, with relative simulation cost and completion time evaluated as a function of machine count. As expected, simulation completion time decreases as 1=n for n parallel machines, and relative simulation cost is found to be optimal where n is a factor of the total simulation time in hours. Using the technique, we demonstrate the potential usefulness of cloud computing as a solution for rapid Monte Carlo simulation for radiotherapy dose calculation without the need for dedicated local computer hardware as a proof of principal. Funding source Cancer Australia (Department of Health and Ageing) Research Grant 614217

Orthopaedics and Trauma Queensland Annual Report 2011

Orthopaedics and Trauma Queensland, a Centre for Research and Education in Musculoskeletal Disorders, is an internationally recognised research group that is developing into an international leader in research and education. It provides a stimulus for research, education and clinical application within the international orthopaedic and trauma communities. Orthopaedics and Trauma Queensland develops and promotes the innovative use of engineering and technology, in collaboration with surgeons, to provide new techniques, materials, procedures and medical devices. Its integration with clinical practice and strong links with hospitals ensure that the research will be translated into practical outcomes for patients. The group undertakes clinical practice in orthopaedics and trauma and applies core engineering skills to challenges in medicine. The research is built on a strong foundation of knowledge in biomedical engineering, and incorporates expertise in cell biology, mathematical modelling, human anatomy and physiology and clinical medicine in orthopaedics and trauma. New knowledge is being developed and applied to the full range of orthopaedic diseases and injuries, such as knee and hip replacements, fractures and spinal deformities.

Drugs, labels and (p)ill-fitting boxes : ADHD and children who are hard to teach

In offering a critical review of the problem we call “ADHD” this paper progresses in three stages. The first two parts juxtapose the dominant voices emanating from the literature in medicine and psychology, highlighting some interdependency between these otherwise competing interest groups. In part three, the nature of the relationship between these groups and the institution of the school is considered, as is the role that the school may play in the psycho-pathologisation of fidgety, distractible, active children who prove hard to teach. In so doing, the author provides an insight as to why the problem we call “ADHD” has achieved celebrity status in Australia and what the effects of that may be for children who come to be described in these ways.

A pre-treatment verification tool for IMRT based on EPID measurements and a GEANT4 back projection application

The aim of this work is to develop software that is capable of back projecting primary fluence images obtained from EPID measurements through phantom and patient geometries in order to calculate 3D dose distributions. In the first instance, we aim to develop a tool for pretreatment verification in IMRT. In our approach, a Geant4 application is used to back project primary fluence values from each EPID pixel towards the source. Each beam is considered to be polyenergetic, with a spectrum obtained from Monte Carlo calculations for the LINAC in question. At each step of the ray tracing process, the energy differential fluence is corrected for attenuation and beam divergence. Subsequently, the TERMA is calculated and accumulated to an energy differential 3D TERMA distribution. This distribution is then convolved with monoenergetic point spread kernels, thus generating energy differential 3D dose distributions. The resulting dose distributions are accumulated to yield the total dose distribution, which can then be used for pre-treatment verification of IMRT plans. Preliminary results were obtained for a test EPID image comprised of 100 9 100 pixels of unity fluence. Back projection of this field into a 30 cm9 30 cm 9 30 cm water phantom was performed, with TERMA distributions obtained in approximately 10 min (running on a single core of a 3 GHz processor). Point spread kernels for monoenergetic photons in water were calculated using a separate Geant4 application. Following convolution and summation, the resulting 3D dose distribution produced familiar build-up and penumbral features. In order to validate the dose model we will use EPID images recorded without any attenuating material in the beam for a number of MLC defined square fields. The dose distributions in water will be calculated and compared to TPS predictions.