A probability model for anatomical robust optimisation in head and neck cancer proton therapy

Objective: Develop an anatomical model based on the statistics of the population data and evaluate the model for anatomical robust optimisation in head and neck (H\&N) cancer proton therapy. Approach: Deformable Image Registration (DIR) was used to build the probability model (PM) that captured the major deformation from patient population data and quantified the probability of each deformation. A cohort of 20 nasopharynx patients was included in this retrospective study. Each patient had a planning CT and 6 weekly CTs during radiotherapy. We applied the model to 5 test patients. Each test patient used the remaining 19 training patients to build the PM and estimate the likelihood of a certain anatomical deformation to happen. For each test patient, a spot-scanning proton plan was created. The PM was evaluated using proton spot location deviation and dose distribution. Main results: Using the proton spot range, the PM can simulate small non-rigid variations in the first treatment week within 0.21 ±0.13 mm. For overall anatomical uncertainty prediction, the PM can reduce anatomical uncertainty from 4.47±1.23 mm (no model) to 1.49±1.08 mm at week 6. The 95% confidence interval (CI) of dose metric variations caused by actual anatomical deformations in the first week is -0.59 ± -0.31 % for low-risk CT D95, and 0.84±3.04 Gy for parotid Dmean. On the other hand, the 95% CI of dose metric variations simulated by the PM at the first week is -0.52 ± -0.34\% for low-risk CTV D95, and 0.58 ±2.22 Gy for parotid Dmean. Significance: The PM improves the estimation accuracy of anatomical uncertainty compared to the previous models and does not depend on the acquisition of the weekly CTs during the treatment. We provided a solution to quantify the probability of an anatomical deformation. The potential of the model for anatomical robust optimisation is discussed

Determination of beam quality correction factors for the Roos plane-parallel ionisation chamber exposed to very high energy electron (VHEE) beams using Geant4

Detailed characterisation of the Roos secondary standard plane-parallel ionisation chamber has been conducted in a novel 200 MeV Very High Energy Electron (VHEE) beam with reference to the standard 12 MeV electron calibration beam used in our experimental work. Stopping-power-ratios and perturbation factors have been determined for both beams and used to calculated the beam quality correction factor using the Geant4 general purpose MC code. These factors have been calculated for a variety of charged particle transport parameters available in Geant4 which were found to pass the Fano cavity test. Stopping-power-ratios for the 12 MeV electron calibration beam quality were found to agree within uncertainties to that quoted by current dosimetry protocols. Perturbation factors were found to vary by up-to 4% for the calibration beam depending on the parameter configuration, compared with only 0.8% for the VHEE beam. Beam quality correction factors were found to describe an approximately 10% lower dose than would be originally calculated if a beam quality correction were not accounted for. Moreover, results presented here largely resolve unphysical chamber measurements, such as collection efficiencies greater than 100%, and assist in the accurate determination of absorbed dose and ion recombination in secondary standard ionisation chambers

Integrated-mode proton radiography with 2D lateral projections

Integrated-mode proton radiography leading to water equivalent thickness (WET) maps is an avenue of interest for motion management, patient positioning, and in vivo range verification. Radiographs can be obtained using a pencil beam scanning setup with a large 3D monolithic scintillator coupled with optical cameras. Established reconstruction methods either (1) involve a camera at the distal end of the scintillator, or (2) use a lateral view camera as a range telescope. Both approaches lead to limited image quality. The purpose of this work is to propose a third, novel reconstruction framework that exploits the 2D information provided by two lateral view cameras, to improve image quality achievable using lateral views. The three methods are first compared in a simulated Geant4 Monte Carlo framework using an extended cardiac torso (XCAT) phantom and a slanted edge. The proposed method with 2D lateral views is also compared with the range telescope approach using experimental data acquired with a plastic volumetric scintillator. Scanned phantoms include a Las Vegas (contrast), 9 tissue-substitute inserts (WET accuracy), and a paediatric head phantom. Resolution increases from 0.24 lp/mm (distal) to 0.33 lp/mm (proposed method) on the simulated slanted edge phantom, and the mean absolute error on WET maps of the XCAT phantom is reduced from 3.4 to 2.7 mm with the same methods. Experimental data from the proposed 2D lateral views indicate a 36\% increase in contrast relative to the range telescope method. High WET accuracy is obtained, with a mean absolute error of 0.4 mm over 9 inserts. Results are presented for various pencil beam spacing ranging from 2 to 6 mm. This work illustrates that high quality proton radiographs can be obtained with clinical beam settings and the proposed reconstruction framework with 2D lateral views, with potential applications in adaptive proton therapy

Evaluation of Monte Carlo to support commissioning of the treatment planning system of new pencil beam scanning proton therapy facilities

To demonstrate the potential of Monte Carlo (MC) to support the resource-intensive measurements that comprise the commissioning of the treatment planning system (TPS) of new proton therapy facilities.

Approach: Beam models of a pencil beam scanning system (Varian ProBeam) were developed in GATE (v8.2), Eclipse proton convolution superposition algorithm (v16.1, Varian Medical Systems) and RayStation MC (v12.0.100.0, RaySearch Laboratories), using the beam commissioning data. All models were first benchmarked against the same commissioning data and validated on seven spread-out Bragg peak (SOBP) plans. Then, we explored the use of MC to optimise dose calculation parameters, fully explore the performance and limitations of TPS in homogeneous fields and support the development of patient-specific quality assurance (PSQA) processes. We compared the dose calculations of the TPSs against measurements (DDTPSvs.Meas.) or GATE (DDTPSvs.GATE) for an extensive set of plans of varying complexity. This included homogeneous plans with varying field-size, range, width, and range-shifters (RSs) (n=46) and PSQA plans for different anatomical sites (n=11).

Results: The three beam models showed good agreement against the commissioning data, and dose differences of 3.5% and 5% were found for SOBP plans without and with RSs, respectively. DDTPSvs.Meas.and DDTPSvs.GATEwere correlated in most scenarios - for example, in homogeneous fields the Pearson's correlation coefficient was 0.92 and 0.68 for Eclipse and RayStation, respectively. The standard deviation of the differences between GATE and measurements (±0.5% for homogeneous and ±0.8% for PSQA plans) was applied as tolerance when comparing TPSs with GATE. 72% and 60% of the plans were within the GATE predicted dose difference for both TPSs, for homogeneous and PSQA cases, respectively.

Significance: Developing and validating a MC beam model early on into the commissioning of new proton therapy facilities can support the validation of the TPS and facilitate comprehensive investigation of its capabilities and limitations

Development of optimised tissue-equivalent materials for proton therapy

OBJECTIVE: In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy. APPROACH: A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence. MAIN RESULTS: Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8 % for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1-2 % for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1-2 % of the experimental RSP, confirming their suitability as clinical phantom materials. SIGNIFICANCE: We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry

SSTR2 in Nasopharyngeal Carcinoma:Relationship with Latent EBV Infection and Potential as a Therapeutic Target

SIMPLE SUMMARY: Nasopharyngeal cancer (NPC) is a malignant epithelial tumor endemic to parts of Asia and associated with infection by the Epstein–Barr virus (EBV) in these regions. The cancer is often detected at a late stage which is associated with poor outcomes (63% 5-year survival). Advances for the management of this disease have remained largely stagnant and treatment relies primarily on radiotherapy and chemotherapy, as well as surgery when indicated. Nevertheless, our understanding of its underlying biology has grown rapidly in the past two decades, laying the foundation for the development of improved therapeutics which have the potential to improve outcomes. This review offers a comprehensive, up-to-date summary of this disease, with a focus on the role of somatostatin receptor 2 (SSTR2) in NPC and how this increased knowledge may lead to improved diagnosis and management of this disease. ABSTRACT: Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor, most commonly located in the pharyngeal recess and endemic to parts of Asia. It is often detected at a late stage which is associated with poor prognosis (5-year survival rate of 63%). Treatment for this malignancy relies predominantly on radiotherapy and/or systemic chemotherapy, which can be associated with significant morbidity and impaired quality of life. In endemic regions NPC is associated with infection by Epstein–Barr virus (EBV) which was shown to upregulate the somatostatin receptor 2 (SSTR2) cell surface receptor. With recent advances in molecular techniques allowing for an improved understanding of the molecular aetiology of this disease and its relation to SSTR2 expression, we provide a comprehensive and up-to-date overview of this disease and highlight the emergence of SSTR2 as a key tumor biomarker and promising target for imaging and therapy

Trait Conscientiousness and the Personality Meta-Trait Stability are Associated with Regional White Matter Microstructure

Establishing the neural bases of individual differences in personality has been an enduring topic of interest. However, while a growing literature has sought to characterize grey matter correlates of personality traits, little attention to date has been focused on regional white matter correlates of personality, especially for the personality traits agreeableness, conscientiousness and openness. To rectify this gap in knowledge we used a large sample (n > 550) of older adults who provided data on both personality (International Personality Item Pool) and white matter tract-specific fractional anisotropy (FA) from diffusion tensor MRI. Results indicated that conscientiousness was associated with greater FA in the left uncinate fasciculus (β = 0.17, P < 0.001). We also examined links between FA and the personality meta-trait ‘stability’, which is defined as the common variance underlying agreeableness, conscientiousness, and neuroticism/emotional stability. We observed an association between left uncinate fasciculus FA and stability (β = 0.27, P < 0.001), which fully accounted for the link between left uncinate fasciculus FA and conscientiousness. In sum, these results provide novel evidence for links between regional white matter microstructure and key traits of human personality, specifically conscientiousness and the meta-trait, stability. Future research is recommended to replicate and address the causal directions of these associations

Study protocol for the translating research in elder care (TREC): building context – an organizational monitoring program in long-term care project (project one)

<p>Abstract</p> <p>Background</p> <p>While there is a growing awareness of the importance of organizational context (or the work environment/setting) to successful knowledge translation, and successful knowledge translation to better patient, provider (staff), and system outcomes, little empirical evidence supports these assumptions. Further, little is known about the factors that enhance knowledge translation and better outcomes in residential long-term care facilities, where care has been shown to be suboptimal. The project described in this protocol is one of the two main projects of the larger five-year Translating Research in Elder Care (TREC) program.</p> <p>Aims</p> <p>The purpose of this project is to establish the magnitude of the effect of organizational context on knowledge translation, and subsequently on resident, staff (unregulated, regulated, and managerial) and system outcomes in long-term care facilities in the three Canadian Prairie Provinces (Alberta, Saskatchewan, Manitoba).</p> <p>Methods/Design</p> <p>This study protocol describes the details of a multi-level – including provinces, regions, facilities, units within facilities, and individuals who receive care (residents) or work (staff) in facilities – and longitudinal (five-year) research project. A stratified random sample of 36 residential long-term care facilities (30 urban and 6 rural) from the Canadian Prairie Provinces will comprise the sample. Caregivers and care managers within these facilities will be asked to complete the TREC survey – a suite of survey instruments designed to assess organizational context and related factors hypothesized to be important to successful knowledge translation and to achieving better resident, staff, and system outcomes. Facility and unit level data will be collected using standardized data collection forms, and resident outcomes using the Resident Assessment Instrument-Minimum Data Set version 2.0 instrument. A variety of analytic techniques will be employed including descriptive analyses, psychometric analyses, multi-level modeling, and mixed-method analyses.</p> <p>Discussion</p> <p>Three key challenging areas associated with conducting this project are discussed: sampling, participant recruitment, and sample retention; survey administration (with unregulated caregivers); and the provision of a stable set of study definitions to guide the project.</p

A Multi-Element Detector System for Intelligent Imaging: I-ImaS

I-ImaS is a European project aiming to produce new, intelligent x-ray imaging systems using novel APS sensors to create optimal diagnostic images. Initial systems concentrate on mammography and encephalography. Later development will yield systems for other types of radiography such as industrial QA and homeland security. The I-ImaS system intelligence, due to APS technology and FPGAs, allows real-time analysis of data during image acquisition, giving the capability to build a truly adaptive imaging system with the potential to create images with maximum diagnostic information within given dose constraints. A companion paper deals with the DAQ system and preliminary characterization. This paper considers the laboratory x-ray characterization of the detector elements of the I-ImaS system. The characterization of the sensors when tiled to form a strip detector will be discussed, along with the appropriate correction techniques formulated to take into account the misalignments between individual sensors within the array. Preliminary results show that the detectors have sufficient performance to be used successfully in the initial mammographic and encephalographic I-ImaS systems under construction and this paper will further discuss the testing of these systems and the iterative processes used for intelligence upgrade in order to obtain the optimal algorithms and setting

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders