MRI-based parameter inference for cerebral perfusion modelling in health and ischaemic stroke.

Cerebral perfusion modelling is a promising tool to predict the impact of acute ischaemic stroke treatments on the spatial distribution of cerebral blood flow (CBF) in the human brain. To estimate treatment efficacy based on CBF, perfusion simulations need to become suitable for group-level investigations and thus account for physiological variability between individuals. However, computational perfusion modelling to date has been restricted to a few patient-specific cases. This study set out to establish automated parameter inference for perfusion modelling based on neuroimaging data and thus enable CBF simulations of groups. Magnetic resonance imaging (MRI) data from 75 healthy senior adults were utilised. Brain geometries were computed from healthy reference subjects' T1-weighted MRI. Haemodynamic model parameters were determined from spatial CBF maps measured by arterial spin labelling (ASL) perfusion MRI. Thereafter, perfusion simulations were conducted in 75 healthy cases followed by 150 acute ischaemic stroke cases representing an occlusion and CBF cessation in the left and right middle cerebral arteries. The anatomical fitness of the brain geometries was evaluated by comparing the simulated grey (GM) and white matter (WM) volumes to measurements in healthy reference subjects. Strong positive correlations were found in both tissue types (GM: Pearson's r 0.74, P<0.001; WM: Pearson's r 0.84, P<0.001). Haemodynamic parameter tuning was verified by comparing the total volumetric blood flow rate to the brain in healthy reference subjects and simulations (Pearson's r 0.89, P<0.001). In acute ischaemic stroke cases, the simulated infarct volume using a perfusion-based estimate was 197±25 ml. Computational predictions were in agreement with anatomical and haemodynamic values from the literature concerning T1-weighted, T2-weighted, and phase-contrast MRI measurements in healthy scenarios and acute ischaemic stroke cases. The acute stroke simulations did not capture small infarcts (left tail of the distribution), which could be explained by neglected compensatory mechanisms, e.g. collaterals. The proposed parameter inference method provides a foundation for group-level CBF simulations and for in silico clinical stroke trials which could assist in medical device and drug development.

On the Sensitivity Analysis of Porous Finite Element Models for Cerebral Perfusion Estimation.

Computational physiological models are promising tools to enhance the design of clinical trials and to assist in decision making. Organ-scale haemodynamic models are gaining popularity to evaluate perfusion in a virtual environment both in healthy and diseased patients. Recently, the principles of verification, validation, and uncertainty quantification of such physiological models have been laid down to ensure safe applications of engineering software in the medical device industry. The present study sets out to establish guidelines for the usage of a three-dimensional steady state porous cerebral perfusion model of the human brain following principles detailed in the verification and validation (V&V 40) standard of the American Society of Mechanical Engineers. The model relies on the finite element method and has been developed specifically to estimate how brain perfusion is altered in ischaemic stroke patients before, during, and after treatments. Simulations are compared with exact analytical solutions and a thorough sensitivity analysis is presented covering every numerical and physiological model parameter. The results suggest that such porous models can approximate blood pressure and perfusion distributions reliably even on a coarse grid with first order elements. On the other hand, higher order elements are essential to mitigate errors in volumetric blood flow rate estimation through cortical surface regions. Matching the volumetric flow rate corresponding to major cerebral arteries is identified as a validation milestone. It is found that inlet velocity boundary conditions are hard to obtain and that constant pressure inlet boundary conditions are feasible alternatives. A one-dimensional model is presented which can serve as a computationally inexpensive replacement of the three-dimensional brain model to ease parameter optimisation, sensitivity analyses and uncertainty quantification. The findings of the present study can be generalised to organ-scale porous perfusion models. The results increase the applicability of computational tools regarding treatment development for stroke and other cerebrovascular conditions.

A porous circulation model of the human brain for in silico clinical trials in ischaemic stroke.

The advancement of ischaemic stroke treatment relies on resource-intensive experiments and clinical trials. In order to improve ischaemic stroke treatments, such as thrombolysis and thrombectomy, we target the development of computational tools for in silico trials which can partially replace these animal and human experiments with fast simulations. This study proposes a model that will serve as part of a predictive unit within an in silico clinical trial estimating patient outcome as a function of treatment. In particular, the present work aims at the development and evaluation of an organ-scale microcirculation model of the human brain for perfusion prediction. The model relies on a three-compartment porous continuum approach. Firstly, a fast and robust method is established to compute the anisotropic permeability tensors representing arterioles and venules. Secondly, vessel encoded arterial spin labelling magnetic resonance imaging and clustering are employed to create an anatomically accurate mapping between the microcirculation and large arteries by identifying superficial perfusion territories. Thirdly, the parameter space of the problem is reduced by analysing the governing equations and experimental data. Fourthly, a parameter optimization is conducted. Finally, simulations are performed with the tuned model to obtain perfusion maps corresponding to an open and an occluded (ischaemic stroke) scenario. The perfusion map in the occluded vessel scenario shows promising qualitative agreement with computed tomography images of a patient with ischaemic stroke caused by large vessel occlusion. The results highlight that in the case of vessel occlusion (i) identifying perfusion territories is essential to capture the location and extent of underperfused regions and (ii) anisotropic permeability tensors are required to give quantitatively realistic estimation of perfusion change. In the future, the model will be thoroughly validated against experiments.

A possibility of element specific detection in HPLC by means of MIP-AES coupled with hydraulic high pressure nebulization.

An interface for coupling hydraulic high pressure nebulization (HHPN) with microwave induced plasma (MIP) atomic emission spectrometry (AES) is described. An appropriate spray chamber and aerosol desolvation system has been constructed for matching the HHPN generated aerosol flow with the loading capacity of toroidal argon and cylindrical helium MIP sources. The system has been optimized for aqueous solutions. Nanogram amounts of metals and nonmetals could be detected by the HHPN-MIP-AES technique developed. The HHPN devices are directly compatible with HPLC solvent flow, therefore they can be directly coupled with HPLC separations in aqueous media.

[Invasive amebiasis]. / Invazív amoebiasis.

There has only a small number of invasive amoebiasis cases occurred in Hungary up to now. Introducing two of our cases we would like to call attention on these cases coming mainly from tropical countries or having been just transiently there invasive amoebiasis should also be considered. Modern diagnostic imaging technics are of importance in differential diagnosis in showing antibodies against amoebas (!) because amoebas frequently cannot be directly shown from the patients in the invasive stage. Both ulcerous amoebic colitis and amoebic liver abscesses can be treated with drugs affecting amoebas in deep tissues (metronidazole, emetine, and its derivates, etc.).