High-order geometric integrators for the variational Gaussian approximation

Among the single-trajectory Gaussian-based methods for solving the time-dependent Schr\"{o}dinger equation, the variational Gaussian approximation is the most accurate one. In contrast to Heller's original thawed Gaussian approximation, it is symplectic, conserves energy exactly, and may partially account for tunneling. However, the variational method is also much more expensive. To improve its efficiency, we symmetrically compose the second-order symplectic integrator of Faou and Lubich and obtain geometric integrators that can achieve an arbitrary even order of convergence in the time step. We demonstrate that the high-order integrators can speed up convergence drastically compared to the second-order algorithm and, in contrast to the popular fourth-order Runge-Kutta method, are time-reversible and conserve the norm and the symplectic structure exactly, regardless of the time step. To show that the method is not restricted to low-dimensional systems, we perform most of the analysis on a non-separable twenty-dimensional model of coupled Morse oscillators. We also show that the variational method may capture tunneling and, in general, improves accuracy over the non-variational thawed Gaussian approximation.Comment: 17 pages, 11 figure

In silico modelling of tumour margin diffusion and infiltration: Review of current status

Extent: 16p.As a result of advanced treatment techniques, requiring precise target definitions, a need for more accurate delineation of the Clinical Target Volume (CTV) has arisen. Mathematical modelling is found to be a powerful tool to provide fairly accurate predictions for the Microscopic Extension (ME) of a tumour to be incorporated in a CTV. In general terms, biomathematical models based on a sequence of observations or development of a hypothesis assume some links between biological mechanisms involved in cancer development and progression to provide quantitative or qualitative measures of tumour behaviour as well as tumour response to treatment. Generally, two approaches are taken: deterministic and stochastic modelling. In this paper, recent mathematical models, including deterministic and stochastic methods, are reviewed and critically compared. It is concluded that stochastic models are more promising to provide a realistic description of cancer tumour behaviour due to being intrinsically probabilistic as well as discrete, which enables incorporation of patient-specific biomedical data such as tumour heterogeneity and anatomical boundaries.Fatemeh Leyla Moghaddasi, Eva Bezak, and Loredana Marc

Evaluation of current clinical target volume definitions for glioblastoma using cell-based dosimetry stochastic methods

Determination of an optimal clinical target volume (CTV) is complex and remains uncertain. The aim of this study was to develop a glioblastoma multiforme (GBM) model to be used for evaluation of current CTV practices for external radiotherapy.The GBM model was structured as follows: (1) a Geant4 cellular model was developed to calculate the absorbed dose in individual cells represented by cubic voxels of 20 μm sides. The system was irradiated with opposing 6 MV X-ray beams. The beams encompassed planning target volumes corresponding to 2.0- and 2.5-cm CTV margins; (2) microscopic extension probability (MEP) models were developed using MATLAB(®) 2012a (MathWorks(®), Natick, MA), based on clinical studies reporting on GBM clonogenic spread; (3) the cellular dose distribution was convolved with the MEP models to evaluate cellular survival fractions (SFs) for both CTV margins.A CTV margin of 2.5 cm, compared to a 2.0-cm CTV margin, resulted in a reduced total SF from 12.9% ± 0.9% to 3.6% ± 0.2%, 5.5% ± 0.4% to 1.2% ± 0.1% and 11.1% ± 0.7% to 3.0% ± 0.2% for circular, elliptical and irregular MEP distributions, respectively.A Monte Carlo model was developed to quantitatively evaluate the impact of GBM CTV margins on total and penumbral SF. The results suggest that the reduction in total SF ranges from 3.5 to 5, when the CTV is extended by 0.5 cm.The model provides a quantitative tool for evaluation of different CTV margins in terms of cell kill efficacy. Cellular platform of the tool allows future incorporation of cellular properties of GBM.L. Moghaddasi, E. Bezak and W. Harriss-Phillip

Diagnostic value of D-dimer�s serum level in Iranian patients with cerebral venous thrombosis

Cerebral venous thrombosis (CVT) is a longterm debilitating vascular brain disease with high morbidity and mortality. It may be associated with rise in D-dimer level. The aim of this study was to examine this potential association and identify the critical D-dimer cut-off level corresponding to increase the risk of CVT. This case-control study was conducted on two groups of patients with and without CVT attending the Rasool Akram Hospital (Iran) during 2014 and 2015. D-dimer levels were measured by the rapid sensitive D-dimer assay. Data were analyzed by Spearman�s correlation coefficient test, independent-samples t-test, backward-selection multiple linear regression and multiple binary logistic regression analyses. Sensitivity-specificity tests were used to detect D-dimer cut-off for CVT. Differences between the D-dimer levels of the case and control groups were significant (P<0.001). It showed that each level of increase in the number of symptoms could increase the risk of thrombosis occurrence for about 3.5 times. All symptom types except for headache were associated with D-dimer level, while headache has negative association with D-dimer level. D-dimer cut-off point for CVT diagnosis was estimated at 350 ng/mg. We concluded that D-dimer serum level significantly rises in CVT patients. A rounded cut-off point of 350 ng/mg can be used as a diagnostic criterion for CVT prediction. © L. Hashami et al., 2016

ExploreASL: an image processing pipeline for multi-center ASL perfusion MRI studies

Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners. The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice. ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow. ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice

Geant4 beam model for boron neutron capture therapy: investigation of neutron dose components

Boron neutron capture therapy (BNCT) is a biochemically-targeted type of radiotherapy, selectively delivering localized dose to tumour cells diffused in normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal neutron capture by stable [Formula: see text]B nuclei resulting in emission of short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose of the current work was to develop and validate a Monte Carlo BNCT beam model and to investigate contribution of individual dose components resulting of neutron interactions. A neutron beam model was developed in Geant4 and validated against published data. The neutron beam spectrum, obtained from literature for a cyclotron-produced beam, was irradiated to a water phantom with boron concentrations of 100 μg/g. The calculated percentage depth dose curves (PDDs) in the phantom were compared with published data to validate the beam model in terms of total and boron depth dose deposition. Subsequently, two sensitivity studies were conducted to quantify the impact of: (1) neutron beam spectrum, and (2) various boron concentrations on the boron dose component. Good agreement was achieved between the calculated and measured neutron beam PDDs (within 1%). The resulting boron depth dose deposition was also in agreement with measured data. The sensitivity study of several boron concentrations showed that the calculated boron dose gradually converged beyond 100 μg/g boron concentration. This results suggest that 100μg/g tumour boron concentration may be optimal and above this value limited increase in boron dose is expected for a given neutron flux.Leyla Moghaddasi, Eva Beza

Imaging of tumor characteristics and molecular pathways with PET: developments over the last decade toward personalized cancer therapy

Purpose: Improvements in personalized therapy are made possible by the advances in molecular biology that led to developments in molecular imaging, allowing highly specific in vivo imaging of biological processes. Positron emission tomography (PET) is the most specific and sensitive imaging technique for in vivo molecular targets and pathways, offering quantification and evaluation of functional properties of the targeted anatomy. Materials and Methods: This work is an integrative research review that summarizes and evaluates the accumulated current status of knowledge of recent advances in PET imaging for cancer diagnosis and treatment, concentrating on novel radiotracers and evaluating their advantages and disadvantages in cancer characterization. Medline search was conducted, limited to English publications from 2007 onward. Identified manuscripts were evaluated for most recent developments in PET imaging of cancer hypoxia, angiogenesis, proliferation, and clonogenic cancer stem cells (CSC). Results: There is an expansion observed from purely metabolic-based PET imaging toward antibody-based PET to achieve more information on cancer characteristics to identify hypoxia, proangiogenic factors, CSC, and others. 64Cu-ATSM, for example, can be used both as a hypoxia and a CSC marker. Conclusions: Progress in the field of functional imaging will possibly lead to more specific tumor targeting and personalized treatment, increasing tumor control and improving quality of life.Loredana Gabriela Marcu, Leyla Moghaddasi and Eva Beza

Evaluation of Durum Wheat Lines for Tolerance to Early Season Cold via Early Planting

Cold stress is one of the environmental factors that affect planting date of durum wheat in mountainous North West areas of Iran. To study tolerance of 36 Durum wheat lines for cold, an experiment was conducted in mid winter (mid of February) at the Agricultural Research Station of Islamic Azad University, Tabriz Branch, in 2007. Experimental design used was simple lattice. The results of analysis of variance showed that the lines under study responded differently to cold as to traits like percentage of survival, yield and its components. This indicates existence of genetic diversity among durum wheat lines. Percentage of survival of the lines 30, 5, 16, 27, 31 and 35 were for higher than those at other lines. Thus, they can be considered to be tolerant to early season cold. Comparison of means showed that lines 35, 31, 16 and 5 possessed higher percentage of survival and other percent survival also correlated positive with plant height, number of fertile spike seed yield and 1000 grain weight. As a whole line 35 was found to be more tolerant to early season cold than the others were. Cluster analysis was divided 36 lines into three groups. Lines in the third group possessed higher percentage of survival, plant height, number of fertile spike, biomass and high yield than their over all means