Piotr Orlowski

Modelling of pH dynamics in brain cells after stroke

The identification of salvageable brain tissue is a major challenge at stroke presentation. Standard techniques used in this context, such as the perfusion–diffusion mismatch, remain controversial. There is thus a need for new methods to help guide treatment. The potential role of pH imaging in this context is currently being investigated. Intracellular pH varies as a function of local perfusion, intracellular energy stores and time. Low pH triggers the production of free radicals and affects the calcium balance of the cells, which may lead to apoptosis and cell death. Thus, the characterization of pH dynamics may have predictive value for cell death after stroke, particularly when combined with novel imaging techniques. Therefore, we have extended an existing model of brain cellular metabolism to simulate the pH response of cells to ischaemia. Simulation results for conditions of reduced cerebral blood flow show good agreement for the evolution of intracellular pH with previously reported measurements and encourage the development of quantitative pH imaging to validate the predictive value of pH.

Computational modelling for the embolization of brain arteriovenous malformations

Treatment of arteriovenous malformations (AVMs) of the brain often requires the injection of a liquid embolic material to reduce blood flow through the malformation. The type of the liquid and the location of injection have to be carefully planned in a pre-operative manner. We introduce a new model of the interaction of liquid embolic materials with blood for the simulation of their propagation and solidification in the AVM. Solidification is mimicked by an increase of the materials viscosity. Propagation is modelled by using the concept of two-fluids modelling and that of scalar transport. The method is tested on digital phantoms and on one anatomically derived patient AVM case. Simulations showed that intuitive behaviour of the two-fluid system can be confirmed and that two types of glue propagation through the malformation can be reproduced. Distinction between the two types of propagation could be used to identify fistulous and plexiform compartments composing the AVM and to characterize the solidification of the embolic material in them.

Modelling of the physiological response of the brain to ischaemic stroke

Identification of salvageable brain tissue is a major challenge when planning the treatment of ischaemic stroke. As the standard technique used in this context, the perfusion–diffusion mismatch, has not shown total accuracy, there is an ongoing search for new imaging protocols that could better identify the region of the brain at risk and for new physiological models that could, on the one hand, incorporate the imaged parameters and predict the evolution of the condition for the individual, and, on the other hand, identify future biomarkers and thus suggest new directions for the design of imaging protocols. Recently, models of cellular metabolism after stroke and blood–brain barrier transport at tissue level have been introduced. We now extend these results by developing a model of the propagation of key metabolites in the brains extracellular space owing to stroke-related oedema and chemical concentration gradients between the ischaemic and normal brain. We also couple the resulting chemical changes in the extracellular space with cellular metabolism. Our work enables the first patient-specific simulations of stroke progression with finite volume models to be made.

Towards Treatment Planning for the Embolization of Arteriovenous Malformations of the Brain: Intranidal Hemodynamics Modeling

This paper presents a patient-derived model for the simulation of the hemodynamics of arteriovenous malformations of the brain (BAVM). This new approach is a step toward the simulation of the outcome of the embolization of the BAVM during treatment planning. More specifically, two aspects of the planning are pursued: simulation of the change of blood flow in the brain vasculature after the blocking of the malformation and simulation of the transport of the embolic liquid. The method we propose is tested on 3 BAVM cases of varying complexity. Twenty two out of 24 main BAVM flow paths have been identified well by simulation.

Image-based simulation of brain arteriovenous malformation hemodynamics

A novel image-based patient-specific simulation method has been developed incorporating computational fluid dynamics (CFD) and porous media principles which presents, for the first time, patient-specific blood flow through an arteriovenous malformation of the brain (BAVM). The new approach constructs an image-based geometric model of a malformation where the BAVM nidus is modelled as a porous medium. The method has been applied to a brain BAVM case with two feeding and four draining vessels. A qualitative comparison of the simulation results with blood flow imaging data shows the promise of the approach and suggests that the method may find application in planning for BAVM treatment.

A model for the optimization of anti-inflammatory treatment with chemerin.

Routine treatment of mild to moderate pain with a combination of non-steroidal anti-inflammatory drugs such as paracetamol in combination with corticoid opioids can lead to severe complications including death from gastrointestinal injury or to drug dependence. There is a need for the development of new safer drugs. Chemerin is a mediator promoting resolution of inflammation and it is then a promising candidate for a new treatment. A pilot experimental work using the zymosan-induced peritonitis model has found that injecting extra chemerin resulted in an approximately 1% reduction in the total number of inflammatory cells recruited. This paper combines and adapts existing mathematical models of inflammation to reproduce these results and to explore the therapeutic potential of chemerin through simulations. Analysis of the model predicts that the injection of chemerin at a concentration of 2000 ng ml−1 within the first 5 min of inflammation onset leads to maximal inflammation inhibition. The degree of inhibition is shown to be sensitive to data used for the fit with a mean inhibition of 22 ± 3.7% for a series of remove-one bootstrap tests, whereas optimal chemerin injection parameters were not. Overall sensitivity analysis identifies parameters of the model that need to be measured more accurately or with increased sampling rate to improve model robustness and confirm chemerins therapeutic potential.

An approach to the symbolic representation of brain arteriovenous malformations for management and treatment planning

IntroductionThere is currently no standardised approach to arteriovenous malformation (AVM) reporting. Existing AVM classification systems focuses on angioarchitectural features and omit haemodynamic, anatomical and topological parameters intuitively used by therapists.MethodsWe introduce a symbolic vocabulary to represent the state of an AVM of the brain at different stages of treatment. The vocabulary encompasses the main anatomic and haemodynamic features of interest in treatment planning and provides shorthand symbols to represent the interventions themselves in a schematic representation.ResultsThe method was presented to 50 neuroradiologists from14 countries during a workshop and graded 7.34 ± 1.92 out of ten for its usefulness as means of standardising and facilitating communication between clinicians and allowing comparisons between AVM cases. Feedback from the survey was used to revise the method and improve its completeness. For an AVM test case, participants were asked to produce a conventional written report and subsequently a diagrammatic report. The two required, on average, 6.19 ± 2.05 and 5.09 ± 3.01 min, respectively. Eighteen participants said that producing the diagram changed the way they thought about the AVM test case.ConclusionIntroduced into routine practice, the diagrams would represent a step towards a standardised approach to AVM reporting with consequent benefits for comparative analysis and communication as well as for identifying best treatment strategies.

Erratum to: An approach to the symbolic representation of brain arteriovenous malformations for management and treatment planning[Neuroradiology, 10.1007/s00234-013-1307-x]

Introduction There is currently no standardised approach to arteriovenous malformation (AVM) reporting. Existing AVM classification systems focuses on angioarchitectural features and omit haemodynamic, anatomical and topological parameters intuitively used by therapists.

A Mathematical Model of Cellular Metabolism During Ischemic Stroke and Hypothermia

Stroke is a major cause of death and disability worldwide. Therapeutic hypothermia is a potentially useful neuroprotective treatment. A mathematical model of brain metabolism during stroke is extended here to simulate the effect of hypothermia on cell survival. Temperature decreases were set to reduce chemical reaction rates and slow diffusion through ion channels according to the Q10 rule. Heat delivery to tissues was set to depend on metabolic heat generation rate and perfusion. Two cooling methods, scalp and vascular, were simulated to approximate temperature variation in the brain during treatment. Cell death was assumed to occur at continued cell membrane depolarization. Simulations showed that hypothermia to 34.5 °C induced within 1-1.5 h of stroke onset could extend cell survival time by at least 5 h in tissue with perfusion reduced by 80% of normal. There was good agreement between simulated metabolite dynamics and those reported in rat model studies.