A simulation study of BrachyShade, a shadow-based internal source tracking system for HDR prostate brachytherapy

© 2018 Commonwealth of Australia. Department of Education and Training, and Department of Industry, Innovation and Science.. This paper presents a simulation study of BrachyShade, a proposed internal source-tracking system for real time quality assurance in high dose rate prostate brachytherapy. BrachyShade consists of a set of spherical tungsten occluders located above a pixellated silicon photodetector. The source location is estimated by minimising the mean squared error between a parametric model of the shadow image and acquired images of the shadows projected on the detector plane. A novel algorithm is finally employed to correct the systemic error resulting from Compton scattering in the medium. The worst-case error obtained with BrachyShade for a 13.5 ms image acquisition is less than 1.3 mm in the most distant part of the treatment volume, while for 75% of source locations an error of less than 0.42 mm was achieved

A new virtual ring-based system matrix generator for iterative image reconstruction in high resolution small volume PET systems

© 2015 Institute of Physics and Engineering in Medicine. A common approach to improving the spatial resolution of small animal PET scanners is to reduce the size of scintillation crystals and/or employ high resolution pixellated semiconductor detectors. The large number of detector elements results in the system matrix - an essential part of statistical iterative reconstruction algorithms - becoming impractically large. In this paper, we propose a methodology for system matrix modelling which utilises a virtual single-layer detector ring to greatly reduce the size of the system matrix without sacrificing precision. Two methods for populating the system matrix are compared; the first utilises a geometrically-derived system matrix based on Siddon's ray tracer method with the addition of an accurate detector response function, while the second uses Monte Carlo simulation to populate the system matrix. The effectiveness of both variations of the proposed technique is demonstrated via simulations of PETiPIX, an ultra high spatial resolution small animal PET scanner featuring high-resolution DoI capabilities, which has previously been simulated and characterised using classical image reconstruction methods. Compression factors of and are achieved using this methodology for the system matrices produced using the geometric and Monte Carlo-based approaches, respectively, requiring a total of 0.5-1.2 GB of memory-resident storage. Images reconstructed from Monte Carlo simulations of various point source and phantom models, produced using system matrices generated via both geometric and simulation methods, are used to evaluate the quality of the resulting system matrix in terms of achievable spatial resolution and the CRC, CoV and CW-SSIM index image quality metrics. The Monte Carlo-based system matrix is shown to provide the best image quality at the cost of substantial one-off computational effort and a lower (but still practical) compression factor. Finally, a straightforward extension of the virtual ring method to a three dimensional virtual cylinder is demonstrated using a 3D DoI PET scanner

Analytical Modelling and Simulation of Single and Double Cone Pinholes for Real-Time In-Body Tracking of an HDR Brachytherapy Source

© 2016 IEEE. The choice of pinhole geometry is a critical factor in the performance of pinhole-collimator-based source tracking systems for brachytherapy QA. In this work, an analytical model describing the penetrative sensitivity of a single-cone pinhole collimator to photons emitted from a point source is derived. Using existing models for single-cone resolution and double-cone sensitivity and resolution, the theoretical sensitivity and resolution of the single-cone collimator are quantitatively compared with those of a double-cone collimator with an equivalent field of view. Monte Carlo simulations of the single and double-cone pinhole collimators using an accurate 3D model of a commercial high dose rate brachytherapy source are performed to evaluate the relative performance of each geometry for a novel real-time HDR brachytherapy QA system, HDR BrachyView. The theoretical penetrative sensitivity of the single-cone pinhole is shown to be higher than the double-cone pinhole, which is in agreement with the results from the Monte Carlo simulations. The wider pinhole response function of the single-cone collimator results in a larger total error between the projected center of the source and the estimated center of mass of the source projection for the single-cone collimator, with the greatest error (at the maximum FoV angle) being 0.54 mm for the double-cone pinhole and 1.37 mm for the single-cone at θ = 60°. The double-cone pinhole geometry is determined to be the most appropriate choice for the pinhole collimator in the HDR BrachyView probe

BrachyView, a novel in-body imaging system for HDR prostate brachytherapy: Experimental evaluation

© 2015 American Association of Physicists in Medicine. Purpose: This paper presents initial experimental results from a prototype of high dose rate (HDR) BrachyView, a novel in-body source tracking system for HDR brachytherapy based on a multipinhole tungsten collimator and a high resolution pixellated silicon detector array. The probe and its associated position estimation algorithms are validated and a comprehensive evaluation of the accuracy of its position estimation capabilities is presented. Methods: The HDR brachytherapy source is moved through a sequence of positions in a prostate phantom, for various displacements in x, y, and z. For each position, multiple image acquisitions are performed, and source positions are reconstructed. Error estimates in each dimension are calculated at each source position and combined to calculate overall positioning errors. Gafchromic film is used to validate the accuracy of source placement within the phantom. Results: More than 90% of evaluated source positions were estimated with an error of less than one millimeter, with the worst-case error being 1.3 mm. Experimental results were in close agreement with previously published Monte Carlo simulation results. Conclusions: The prototype of HDR BrachyView demonstrates a satisfactory level of accuracy in its source position estimation, and additional improvements are achievable with further refinement of HDR BrachyView's image processing algorithms

Radiation dose enhancement at tissue-tungsten interfaces in HDR brachytherapy

© 2014 Institute of Physics and Engineering in Medicine. HDR BrachyView is a novel in-body dosimetric imaging system for real-time monitoring and verification of the source position in high dose rate (HDR) prostate brachytherapy treatment. It is based on a high-resolution pixelated detector array with a semi-cylindrical multi-pinhole tungsten collimator and is designed to fit inside a compact rectal probe, and is able to resolve the 3D position of the source with a maximum error of 1.5 mm. This paper presents an evaluation of the additional dose that will be delivered to the patient as a result of backscatter radiation from the collimator. Monte Carlo simulations of planar and cylindrical collimators embedded in a tissue-equivalent phantom were performed using Geant4, with an 192Ir source placed at two different source-collimator distances. The planar configuration was replicated experimentally to validate the simulations, with a MOSkin dosimetry probe used to measure dose at three distances from the collimator. For the cylindrical collimator simulation, backscatter dose enhancement was calculated as a function of axial and azimuthal displacement, and dose distribution maps were generated at three distances from the collimator surface. Although significant backscatter dose enhancement was observed for both geometries immediately adjacent to the collimator, simulations and experiments indicate that backscatter dose is negligible at distances beyond 1 mm from the collimator. Since HDR BrachyView is enclosed within a 1 mm thick tissue-equivalent plastic shell, all backscatter radiation resulting from its use will therefore be absorbed before reaching the rectal wall or other tissues. dosimetry, brachytherapy, HD

Proteomics: in pursuit of effective traumatic brain injury therapeutics

Effective traumatic brain injury (TBI) therapeutics remain stubbornly elusive. Efforts in the field have been challenged by the heterogeneity of clinical TBI, with greater complexity among underlying molecular phenotypes than initially conceived. Future research must confront the multitude of factors comprising this heterogeneity, representing a big data challenge befitting the coming informatics age. Proteomics is poised to serve a central role in prescriptive therapeutic development, as it offers an efficient endpoint within which to assess post-TBI biochemistry. We examine rationale for multifactor TBI proteomic studies and the particular importance of temporal profiling in defining biochemical sequences and guiding therapeutic development. Lastly, we offer perspective on repurposing biofluid proteomics to develop theragnostic assays with which to prescribe, monitor and assess pharmaceutics for improved translation and outcome for TBI patients

Prevalence of Disorders Recorded in Dogs Attending Primary-Care Veterinary Practices in England

Purebred dog health is thought to be compromised by an increasing occurence of inherited diseases but inadequate prevalence data on common disorders have hampered efforts to prioritise health reforms. Analysis of primary veterinary practice clinical data has been proposed for reliable estimation of disorder prevalence in dogs. Electronic patient record (EPR) data were collected on 148,741 dogs attending 93 clinics across central and south-eastern England. Analysis in detail of a random sample of EPRs relating to 3,884 dogs from 89 clinics identified the most frequently recorded disorders as otitis externa (prevalence 10.2%, 95% CI: 9.1-11.3), periodontal disease (9.3%, 95% CI: 8.3-10.3) and anal sac impaction (7.1%, 95% CI: 6.1-8.1). Using syndromic classification, the most prevalent body location affected was the head-and-neck (32.8%, 95% CI: 30.7-34.9), the most prevalent organ system affected was the integument (36.3%, 95% CI: 33.9-38.6) and the most prevalent pathophysiologic process diagnosed was inflammation (32.1%, 95% CI: 29.8-34.3). Among the twenty most-frequently recorded disorders, purebred dogs had a significantly higher prevalence compared with crossbreds for three: otitis externa (P = 0.001), obesity (P = 0.006) and skin mass lesion (P = 0.033), and popular breeds differed significantly from each other in their prevalence for five: periodontal disease (P = 0.002), overgrown nails (P = 0.004), degenerative joint disease (P = 0.005), obesity (P = 0.001) and lipoma (P = 0.003). These results fill a crucial data gap in disorder prevalence information and assist with disorder prioritisation. The results suggest that, for maximal impact, breeding reforms should target commonly-diagnosed complex disorders that are amenable to genetic improvement and should place special focus on at-risk breeds. Future studies evaluating disorder severity and duration will augment the usefulness of the disorder prevalence information reported herein

CCR3 and Choroidal Neovascularization

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in industrialized countries. The “wet” AMD, characterized by the development of choroidal neovacularization (CNV), could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A) in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin) targeting for CNV

Prime movers : mechanochemistry of mitotic kinesins

Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation