Pre-operative apparent diffusion coefficient values and tumour region volumes as prognostic biomarkers in glioblastoma: correlation and progression-free survival analyses
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01.12.2019 |
Durand-Muñoz C.
Flores-Alvarez E.
Moreno-Jimenez S.
Roldan-Valadez E.
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Insights into Imaging |
10.1186/s13244-019-0724-8 |
0 |
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© 2019, The Author(s). Objectives: Glioblastoma (GB) contains diverse histologic regions. Apparent diffusion coefficient (ADC) values are surrogates for the degree of number of cells within the tumour regions. Because an assessment of ADC values and volumes within tumour sub-compartments of GB is missing in the literature, we aimed to evaluate these associations. Methods: A retrospective cohort of 48 patients with GB underwent segmentation to calculate tumour region volumes (in cubic centimetre) and ADC values in tumour regions: normal tissue, enhancing tumour, proximal oedema, distal oedema, and necrosis. Correlation, Kaplan-Meier, and Cox hazard regression analyses were performed. Results: We found a statistically significant difference among ADC values for tumour regions: F (4, 220) = 166.71 and p ≤.001 and tumour region volumes (necrosis, enhancing tumour, peritumoural oedema): F (2, 141) = 136.3 and p ≤.001. Post hoc comparisons indicated that the only significantly different mean score was the peritumoural volume in oedema region (p <.001). We observed a positive significant correlation between ADC of distal oedema and peritumoural volume, r =.418, df = 34, and p =.011. Cox proportional hazards regression analysis considering only tumour region volumes provided an almost significant model: − 2 log-likelihood = 146.066, χ 2 (4) = 9.303, and p =.054 with a trend towards significance of the hazard function: p =.067 and HR = 1.077 for the non-enhancing tumour volume. Conclusions: ADC values together with volumes of oedema region might have a role as predictors of progression-free survival (PFS) in patients with GB; we recommend a routine MRI assessment with the calculation of these biomarkers in GB.
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A higher order approximate static condensation method for multi-material diffusion problems
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15.10.2019 |
Zhiliakov A.
Svyatskiy D.
Olshanskii M.
Kikinzon E.
Shashkov M.
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Journal of Computational Physics |
10.1016/j.jcp.2019.06.044 |
1 |
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© 2019 Elsevier Inc. The paper studies an approximate static condensation method for the diffusion problem with discontinuous diffusion coefficients. The method allows for a general polygonal mesh which is unfitted to the material interfaces. Moreover, the interfaces can be discontinuous across the mesh edges as typical for numerical reconstructions using the volume or moment-of-fluid methods. We apply a mimetic finite difference method to solve local diffusion problems and use P1 (mortar) edge elements to couple local problems into the global system. The condensation process and the properties of the resulting algebraic system are discussed. It is demonstrated that the method is second order accurate on smooth solutions and performs well for problems with high contrast in diffusion coefficients. Experiments also show the robustness with respect to position of the material interfaces against the underlying mesh.
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Finite volume method for coupled subsurface flow problems, I: Darcy problem
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15.10.2019 |
Terekhov K.
Vassilevski Y.
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Journal of Computational Physics |
10.1016/j.jcp.2019.06.009 |
0 |
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© 2019 Elsevier Inc. The article introduces a finite-volume method for the Darcy problem in heterogeneous anisotropic media. The method is based on the mixed formulation for the pressure and its gradient. The method is stable despite collocation of both pressure and its gradient at cell centers and demonstrates the first order convergence on numerous benchmarks as well as good monotonicity property. The method produces quasi-definite matrix, which is numerically shown to have good asymptotics of the condition number. Our flux discretization method is a realization of our more general concept of stable flux discretization for saddle-point systems with vector of several unknowns. In this paper this vector is composed of pressure and its gradient and the saddle-point system is the mixed formulation of the Darcy problem.
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Physiologically based mathematical modelling of solute transport within the epidermis and dermis
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05.10.2019 |
Calcutt J.
Anissimov Y.
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International Journal of Pharmaceutics |
10.1016/j.ijpharm.2019.118547 |
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© 2019 Elsevier B.V. The stratum corneum is the main barrier to transdermal drug delivery which has previously resulted in mathematical modelling of solute transport in the skin being primarily directed at this skin layer. However, for topical treatment and skin toxicity studies, the concentration in the epidermis and dermis is important and needs to be modelled mathematically. Hitherto, mathematical models for viable skin layers typically simplified the clearance of solute by blood, either assuming sink condition at the top of the skin capillary loops or assuming a distributed clearance in the dermis. This paper is an attempt to develop a physiologically based mathematical model of drug transport in the viable skin. It incorporates explicit modelling of the capillary loops within the dermis and employs COMSOL Multiphysics® software to model the transport in three dimensions. Previously derived simplified models were compared to the results from this new numerical model. The results of this comparison showed that the simplified model reasonably described the average concentration in the viable skin layers when parameters of the models were chosen appropriately. When the recruitment of the capillary loops in the dermis was full and the top of capillary loops was at a depth of 100μm, the effective depth to place a sink condition in the simpler models was found to be at 150μm. However, when there was only partial recruitment of the capillaries, the effective depth increased to 180μm. The presented modelling is also essential for determining a transdermal flux when the stratum corneum barrier is compromised by such methods as microporation, application of chemical enhancers or microneedles.
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Added value of diffusion-weighted MRI for nodal radiotherapy planning in pelvic malignancies
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01.10.2019 |
Sushentsev N.
Martin H.
Rimmer Y.
Barrett T.
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Clinical and Translational Oncology |
10.1007/s12094-019-02068-0 |
1 |
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© 2019, Federación de Sociedades Españolas de Oncología (FESEO). Purpose: To evaluate the added value of diffusion-weighted imaging (DWI) to T2-weighted imaging (T2WI) for improved identification of pelvic lymph nodes (LN) by radiation oncologists. Methods/patients: This retrospective study included 20 patients with histopathologically proven node-negative prostate cancer. All patients underwent 3T-MRI of the prostate; matched axial T2WI and DWI sequences were assessed by an experienced uro-radiologist as the reference standard. Consultant and specialist registrar radiation oncologists were asked to identify all LN first on T2WI alone (read 1) and then on T2WI and DWI combined (read 2); LN were measured in size and divided into true positives (TP), false positives (FP) and false negatives (FN). Sensitivity, positive predictive value (PPV) and false negative rate (FNR) were then calculated and compared using Pearson’s Chi square test. Results: A total of 177 LN comprised the reference standard. 16 TP, 16 FP and 161 FN LN (sensitivity 9.0%, PPV 50.0%, FNR 91.0%) and 124, 15 and 53 LN (70.1%, 89.2%, 30%) were identified by reader 1 on reads 1 and 2, respectively; χ2 (2, N = 385) = 137.8, p < 0.0001. 27, 21 and 150 LN (15.3%, 56.3%, 84.8%) and 120, 13 and 57 LN (67.8%, 90.2%, 32.2%) were identified by reader 2 on the two reads; χ2 (2, N = 388) = 102.4, p < 0.0001. Conclusions: Adding DWI to T2WI significantly improved identification of pelvic LN by radiation oncologists and can therefore be regarded as a useful LN contouring technique for RT planning in pelvic malignancies.
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Investigation of the Size Distribution for Diffusion-Controlled Drug Release From Drug Delivery Systems of Various Geometries
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01.08.2019 |
Spiridonova T.
Tverdokhlebov S.
Anissimov Y.
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Journal of Pharmaceutical Sciences |
10.1016/j.xphs.2019.03.036 |
2 |
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© 2019 American Pharmacists Association® Various drug delivery systems (DDSs) are often used in modern medicine to achieve controlled and targeted drug release. Diffusional release of drugs from DDSs is often the main mechanism, especially at early times. Generally, average dimensions of DDS are used to model the drug release, but our recent work on drug release from fibers demonstrated that taking into account diameter distribution is essential. This work systematically investigated the effect of size distribution on diffusional drug release from DDSs of various geometric forms such as membranes, fibers, and spherical particles. The investigation clearly demonstrated that the size distribution has the largest effect on the drug release profiles from spherical particles compared to other geometric forms. Published experimental data for drug release from polymer microparticles and nanoparticles were fitted, and the diffusion coefficients were determined assuming reported radius distributions. Assuming the average radius when fitting the data leads to up to 5 times underestimation of the diffusion coefficient of drug in the polymer.
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Compartmental modeling of skin transport
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01.09.2018 |
Amarah A.
Petlin D.
Grice J.
Hadgraft J.
Roberts M.
Anissimov Y.
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European Journal of Pharmaceutics and Biopharmaceutics |
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1 |
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© 2018 Elsevier B.V. The primary objective of this study is to introduce a simple and flexible mathematical approach which models transport processes in skin using compartments. The main feature of the presented approach is that the rate constants for exchange between compartments are derived from physiologically relevant diffusional transport parameters. This allows for better physical interpretation of the rate constants, and limits the number of parameters for the compartmental model. The resulting compartmental solution is in good agreement with previously published solutions for the diffusion model of skin when ten or more compartments are used. It was found that the new compartmental model with three compartments provided a better fit of the previously publish water penetration data than the diffusion model. Two special cases for which it is difficult to implement the diffusion model were considered using our compartmental approach. In both cases the compartmental model predictions agreed well with the diffusion model.
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Recent updates on whole-body MRI in oncology
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01.01.2018 |
Subbotin Y.
Bakhtiozin R.
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Russian Electronic Journal of Radiology |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: In recent years, whole-body MRI have been increasingly used in the field of oncological radiology owing to its advantages such as: yield of high-quality diagnostic information in relatively short scan time, lack of radioisotope or intravenous contrast use, and comparingly low examination cost in contrast to traditional nuclear medicine techniques. Aim of this article is to bring the overview of whole-body MRI as a technique and current applications of its use in oncological radiology.
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Diffusion tensor magnetic resonance imaging in the diagnosis of white matter lesion in middle-aged patients with uncomplicated essential hypertension
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01.01.2018 |
Parfenov V.
Ostroumova T.
Ostroumova O.
Perepelov V.
Perepelova E.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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5 |
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© 2018 Ima-Press Publishing House. All rights reservbed. Diffusion tensor magnetic resonance imaging (DT-MRI) is the only noninvasive technique that makes it possible to study white matter microstructure in vivo and to quantify the images obtained. Objective: to study white matter in middle-aged treatment-naïve patients with uncomplicated grade 1-2 essential hypertension (EH), by using DT-MRI. Patients and methods. The investigation enrolled 82 people aged 40-59 years (41 patients with EH and 41 healthy individuals (a control group)). Twenty-four blood pressure monitoring and brain MRI were performed in different modes (T1 MPRAGE, T2 TSE, T2 FLAIR, and DTI). Results. White matter hyperintensities (WMHs) were found in 7.3% of the healthy individuals and in 53.7% of the hypertensive patients (p=0.0002). The latter had significantly lower fractional anisotropy (FA) values in the white matter of the left inferior frontal gyrus than the healthy individuals (0.39±0.06 and 0.45±0.09, respectively; p< 0.001). FA was lower in the hypertensive patients than in the healthy individuals not only in the presence of WMHs (the left inferior frontal gyrus white matter was 0.397±0.071 and 0.45±0.09, respectively; p=0.009; the genu of the corpus callosum was 0.79±0.04 and 0.81±0.05, respectively; p=0.045), but also in the absence of WMHs (the left inferior frontal gyrus white matter was 0.378±0.073 and 0.45±0.09, respectively; p=0.0007). Discussion. The treatment-naïve patients with uncomplicated grade 1-2 EH with short-term (2,3 year) duration were found to have significantly lower FA values in the left inferior frontal gyrus white matter than the healthy normotensive subjects of the same age. Thus, the microstructural integrity of white matter is impaired in middle-aged hypertensive patients even at the earliest disease stages. Conclusion. Middle-aged treatment-naive patients with uncomplicated grade 1-2 EH have lower FA in the left inferior frontal gyrus white matter even in the absence of WMHs.
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Competing mechanisms of stress-assisted diffusivity and stretch-activated currents in cardiac electromechanics
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01.01.2018 |
Loppini A.
Gizzi A.
Ruiz-Baier R.
Cherubini C.
Fenton F.
Filippi S.
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Frontiers in Physiology |
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3 |
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Copyright © 2018 Loppini, Gizzi, Ruiz-Baier, Cherubini, Fenton and Filippi. We numerically investigate the role of mechanical stress in modifying the conductivity properties of cardiac tissue, and also assess the impact of these effects in the solutions generated by computational models for cardiac electromechanics. We follow the recent theoretical framework from Cherubini et al. (2017), proposed in the context of general reaction-diffusion-mechanics systems emerging from multiphysics continuum mechanics and finite elasticity. In the present study, the adapted models are compared against preliminary experimental data of pig right ventricle fluorescence optical mapping. These data contribute to the characterization of the observed inhomogeneity and anisotropy properties that result from mechanical deformation. Our novel approach simultaneously incorporates two mechanisms for mechano-electric feedback (MEF): stretch-activated currents (SAC) and stress-assisted diffusion (SAD); and we also identify their influence into the nonlinear spatiotemporal dynamics. It is found that (i) only specific combinations of the two MEF effects allow proper conduction velocity measurement; (ii) expected heterogeneities and anisotropies are obtained via the novel stress-assisted diffusion mechanisms; (iii) spiral wave meandering and drifting is highly mediated by the applied mechanical loading. We provide an analysis of the intrinsic structure of the nonlinear coupling mechanisms using computational tests conducted with finite element methods. In particular, we compare static and dynamic deformation regimes in the onset of cardiac arrhythmias and address other potential biomedical applications.
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