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Modeling and Simulation of Microdialysis in the Deep Brain Structures
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
2012 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Microdialysis is a method for monitoring of the local biochemical environment in a region of interest. The method uses a catheter, mimicking the function of a blood capillary, to sample substances from the surrounding medium through diffusion. A recent application for microdialysis is the sampling of neuroactive substances in the deep brain, or basal ganglia, during deep brain stimulation (DBS) for patients with Parkinson’s disease. The basal ganglia consist of nuclei interconnected by chemical synapses, and it is hypothesized that the levels of neurotransmitter substances around the synapses are affected by DBS treatment. In order to relate the microdialysis data to their anatomical origin and to the effects of DBS, it is suitable to estimate the tissue volume which is sampled during a microdialysis experiment. In this thesis, the maximum tissue volume of influence (TVImax) for a microdialysis catheter was simulated and evaluated using the finite element method (FEM), to allow interpretation of biochemical data in relation to anatomical structures.

A FEM model for simulation of the TVImax for a microdialysis catheter placed in grey brain matter was set up, using Fick’s law of diffusion. The model was used to investigate the impact of the analyte diffusion coefficient (D), the tissue tortuosity (λ) and the loss rate constant (k) on the size of the TVImax by regression analysis. Using relevant parameter intervals, the radius of the TVImax of a neurotransmitter was estimated to 0.85 ± 0.25 mm. A microdialysis experiment on calf brain tissue showed agreement with the regression model. A heterogeneous anisotropic FEM model based on diffusion tensor imaging (DTI) showed that the radius of the TVImax may vary by up to 0.5 mm as a consequence of local tissue properties, which was reasonable in relation to the 95% confidence interval from the regression estimation. The TVImax was simulated and patient-specifically visualized in relation to MRI images for four patients undergoing microdialysis in parallel to DBS. The size of the TVImax showed to be relevant in relation to the basal ganglia nuclei, and the obtained microdialysis data indicated that the biochemical response to DBS depends on the catheter position. The simulations of the TVImax were combined with patient-specific DBS electric field simulations, for further interpretation of the results in relation to the effects of DBS.

In conclusion, simulations and visualizations of the TVImax allowed relating microdialysis data to its anatomical origin. Detailed knowledge about the parameters affecting the microdialysis sampling volume is valuable for the current application as well as other applications related to the migration of analytes in tissue.

Abstract [sv]

Mikrodialys är en metod som används för studera lokala nivåer av biokemiska substanser i ett specifict organ eller struktur. Metoden använder sig av en kateter med ett semipermeabelt membran, över vilket utbyte av substanser sker genom diffusion. Mikrodialys har nyligen använts för att studera nivåer av neurotransmittorer i de djupa hjärnstrukturerna, ävan kallade basala ganglierna, under djup hjärnstimulering (DBS) för patienter med Parkinsons sjukdom. De basala ganglierna består av ett antal millimeterstora hjärnstrukturer, sammankopplade via biokemiska synapser, och nivåerna av signalsubstanser runt dessa synapser tros påverkas av DBS. För att relatera mikrodialysmätningarna till dess anatomiska ursprung, och till effekterna av DBS, är det önskvärt att få en uppskattning av den vävnadsvolym som påverkar mätningen från en mikrodialyskateter. Målet med denna licentiatavhandling har varit att simulera och utvärdera den maximala påverkansvolymen (TVImax) för en mikrodialyskateter med hjälp av finita element-metoden (FEM), för att underlätta tolkningen av de biokemiska data som samlats in.

En FEM-modell sattes upp för att simulera TVImax för en kateter placerad i grå hjärnvävnad, baserat på Ficks diffusionslag och lämpliga rand- och initialvillkor. Modellen användes för att göra en regressionsanalys av hur TVImax påverkades av analytens diffusionskoefficient (D), hjärnvävnadens tortuositet (λ) och analytens nedbrytningshastighet (k), och radien för TVImax för en neurotransmitter uppskattades till 0.85 ± 0.25 mm då fysiologiskt relevanta parameterintervall användes. En experimentell studie av mikrodialys på hjärnvävnad från kalv gav god överensstämmelse med simuleringsresultaten. En heterogen och anisotrop FEM-modell sattes upp med hjälp av diffusionstensordata (DTI), vilket visade att lokala vävnadsegenskaper påverkar diffusionen av analyter i de basala ganglierna med upp till 0.5 mm i enighet med den regressionsmodell som tagits fram. TVImax simulerades och visualiserades sedan i relation till MRI-bilder för fyra patienter som genomgått mikrodialys parallellt med DBS. Målområdena för mikrodialysmätningarna visade sig skilja mellan patienterna, och den insamlade mikrodialysdatan indikerade att den biokemiska responsen på DBS berodde på kateterns position. För att ytterligare underlätta tolkningen av resultatet i relation till effekterna av DBS, kombinerades TVImax-simuleringarna med simuleringar av det elektriska fältet runt DBS-elektroderna.

Sammanfattningsvis kan simuleringar av TVImax vara en hjälp vid den fysiologiska tolkningen av insamlad mikrodialysdata, vilket underlättar jämförelser mellan patienter. Detaljerad kunskap om de parametrar som påverkar samplingsvolymen för en mikrodialyskateter är värdefulla både för den aktuella applikationen, och övriga applikationer relaterade till diffusion av substanser i vävnad.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. , 52 p.
Series
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1549
National Category
Engineering and Technology Natural Sciences Medical Engineering
Identifiers
URN: urn:nbn:se:liu:diva-84277ISBN: 978-91-7519-805-7 (print)OAI: oai:DiVA.org:liu-84277DiVA: diva2:558437
Presentation
2012-10-19, IMT1, plan 13, Campus US, Linköpings universitet, Linköping, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2016-05-04Bibliographically approved
List of papers
1. A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis
Open this publication in new window or tab >>A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis
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2011 (English)In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 49, no 12, 1459-1469 p.Article in journal (Refereed) Published
Abstract [en]

Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 × 10(-6) cm(2)/s was estimated to 0.85 ± 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results.

Place, publisher, year, edition, pages
Springer Publishing Company, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72911 (URN)10.1007/s11517-011-0841-0 (DOI)000297550600012 ()22081236 (PubMedID)
Available from: 2011-12-09 Created: 2011-12-09 Last updated: 2017-06-19Bibliographically approved
2. Simulations and visualizations for interpretation of brain microdialysis data during deep brain stimulation
Open this publication in new window or tab >>Simulations and visualizations for interpretation of brain microdialysis data during deep brain stimulation
Show others...
2012 (English)In: IEEE Engineering in Medicine and Biology Society (EMBC), 2012, IEEE , 2012, 6438-6441 p.Conference paper, Published paper (Refereed)
Abstract [en]

Microdialysis of the basal ganglia was used in parallel to deep brain stimulation (DBS) for patients with Parkinson’s disease. The aim of this study was to patientspecifically simulate and visualize the maximum tissue volume of influence (TVImax) for each microdialysis catheter and the electric field generated around each DBS electrode. The finite element method (FEM) was used for the simulations. The method allowed mapping of the anatomical origin of the microdialysis data and the electric stimulation for each patient. It  was seen that the sampling and stimulation targets differed among the patients, and the results will therefore be used in the future interpretation of the biochemical data.

Place, publisher, year, edition, pages
IEEE, 2012
Series
IEEE Engineering in Medicine and Biology Society Conference Proceedings, ISSN 1557-170X
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84275 (URN)10.1109/EMBC.2012.6347468 (DOI)000313296506155 ()23367403 (PubMedID)9781424441198 (ISBN)9781424441204 (ISBN)9781457717871 (ISBN)
Conference
34th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2012), 28 August - 1 September 2012, San Diego, CA, USA
Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2017-06-19Bibliographically approved
3. The effect of tissue heterogeneity and anisotropy on microdialysis of the deep brain
Open this publication in new window or tab >>The effect of tissue heterogeneity and anisotropy on microdialysis of the deep brain
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Microdialysis of the basal ganglia was recently used to study changes of neurotransmitter levels in relation to deep brain stimulation (DBS). In order to estimate the anatomical origin of the microdialysis data, the maximum tissue volume of influence (TVImax) for a microdialysis catheter was simulated and visualized using the finite element method (FEM). In the current study the impact of brain heterogeneity and anisotropy on the TVImax was investigated, using diffusion tensor imaging (DTI) to create a second-order tensor model of the basal ganglia. The results were presented using descriptive statistics, indicating that the mean radius of the TVImax varied by up to 0.5 mm (n = 98444) for FEM simulations based on DTI compared to a homogeneous and isotropic reference model. The internal capsule and subthalamic area showed significantly higher anisotropy (p < 0.0001, n = 600) than the putamen and the globus pallidus, in accordance with theory. It was concluded that the size of the TVImax remained small enough to be relevant in relation to the anatomical structures of interest, and that local tissue properties should be accounted for when relating the microdialysis data to their anatomical targets.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-84276 (URN)
Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2016-05-04Bibliographically approved

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