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Biophysical modelling in diffusion MRI: The role of tissue microstructure and water exchange

Nilsson, Markus LU (2011)
Abstract (Swedish)
Popular Abstract in Swedish

En magnetkamera kan med hjälp av diffusionsviktad bildtagning användas för att avbilda hjärnans nervsystem. Denna teknik kan utnyttjas för studier av hur hjärnans delar är sammankopplade, men även för att indirekt mäta egenskaper hos hjärnans mikrostruktur. Detta avhandlingsarbete vidareutvecklar de biofysikaliska modeller och mätmetoder som används för denna indirekta avbildning.



Genom specialiserade mätningar, framförallt i vitsubstans hos friska försökspersoner och i hjärnvävnad påverkad av ischemisk stroke, demonstrerades att utbyteshastigheten för vatten som diffunderar i olika mikroskopiska omgivningar i hjärnan påverkar den diffusionsviktade bildsignalen. Simuleringar av... (More)
Popular Abstract in Swedish

En magnetkamera kan med hjälp av diffusionsviktad bildtagning användas för att avbilda hjärnans nervsystem. Denna teknik kan utnyttjas för studier av hur hjärnans delar är sammankopplade, men även för att indirekt mäta egenskaper hos hjärnans mikrostruktur. Detta avhandlingsarbete vidareutvecklar de biofysikaliska modeller och mätmetoder som används för denna indirekta avbildning.



Genom specialiserade mätningar, framförallt i vitsubstans hos friska försökspersoner och i hjärnvävnad påverkad av ischemisk stroke, demonstrerades att utbyteshastigheten för vatten som diffunderar i olika mikroskopiska omgivningar i hjärnan påverkar den diffusionsviktade bildsignalen. Simuleringar av detta fenomen visade att utbyteshastigheten går att beräkna från bildsignalen. Även axonens diameter kan beräknas, om experimentets så kallade upplösningsförmåga är tillräckligt hög, men denna förmåga bestäms av hårdvaran i magnetkameran. Kunskap om utbyteshastigheten och axondiametern kan vara av vikt vid studier av hjärnans utveckling och ge ökad kunskap om hjärnans funktion.



Vissa nerver, framför allt utanför kraniet, består av axoner vars banor är vågformade, de undulerar. När sådan nervvävnad sträcks ut eller komprimeras förändras undulationernas egenskaper. Simuleringar visar att detta fenomen borde ge upphov till förändringar i parametrar som är mätbara med magnetkameran, något som potentiellt kan användas för att studera perifera nerver.



Denna avhandling beskriver även utveckling av en ny metod för att bestämma vattnets utbyteshastighet. Metoden validerades genom experiment på vanlig bakjäst upplöst i vatten där både NMR spektrometrar, som liknar magnetkameror för provrör, och en klinisk magnetkamera användes. Studier visade att denna teknik kan användas för att bestämma vattnets utbyteshastighet i vitvävnad och i hjärntumörer. Därigenom möjliggörs undersökningar som ökar vår kunskap om vattenutbyte i hjärnans mikrostruktur och om hur denna påverkas vid sjukdom. (Less)
Abstract
Diffusion MRI is widely used to study brain structure in vivo. While this technique is often applied to investigations of brain connectivity, it can also be used to infer specific information about the tissue microstructure; for example, to estimate the axon diameter. In the present work, the role of tissue microstructure and water exchange in biophysical models employed in diffusion MRI was investigated. Specialised diffusion measurements were performed in white matter of healthy volunteers and in subacute stroke lesions. The results showed that exchange between microenvironments with different diffusivities contributes to the outcome of the diffusion MRI experiment.



Concerns regarding the accuracy and precision of... (More)
Diffusion MRI is widely used to study brain structure in vivo. While this technique is often applied to investigations of brain connectivity, it can also be used to infer specific information about the tissue microstructure; for example, to estimate the axon diameter. In the present work, the role of tissue microstructure and water exchange in biophysical models employed in diffusion MRI was investigated. Specialised diffusion measurements were performed in white matter of healthy volunteers and in subacute stroke lesions. The results showed that exchange between microenvironments with different diffusivities contributes to the outcome of the diffusion MRI experiment.



Concerns regarding the accuracy and precision of model-parameter estimates were addressed by using Monte Carlo simulations of the diffusion MRI experiment. The results showed that axon diameters can be accurately estimated above the resolution limit of the experiment. The fraction of water restricted to the axons, however, became underestimated at high exchange rates, although a remedy for this problem was suggested. Additional simulations showed the importance of modelling the three-dimensional structural properties of nerves containing undulating axons. Neglecting the presence of such undulations could result in overestimation of axon diameters. Stretching or compression of tissue comprising undulating axons may result in alterations of the diffusivity possible to detect by diffusion MRI.



The filtered exchange imaging (FEXI) method was developed in order to improve the sensitivity of diffusion MRI to diffusional water exchange. Measurements on yeast cell suspensions using NMR spectrometers and a clinical MRI scanner were used to validate the method. FEXI was successfully applied to determine the water exchange rate in the healthy human brain and in a brain tumour, showing that systematic investigation of the water exchange rate in vivo is possible.



In conclusion, this work improved the feasibility of using clinical MRI scanners to investigate tissue microstructure and the rate of water exchange. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Alexander, Daniel, Department of Computer Science, Centre for Medical Image Computing and Computer Science, University College London, United Kingdom
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Diffusion, MRI, tissue microstructure, water exchange, Monte Carlo simulations, white matter
publisher
Division of Radiation Physics, Lund University
defense location
Föreläsningssal 3, Centralblocket, Lund, Skånes universitetssjukhus
defense date
2011-10-21 09:15
language
English
LU publication?
yes
id
fe33349f-2754-4fbc-b64d-08aa35912429 (old id 2166371)
date added to LUP
2011-09-23 10:23:44
date last changed
2016-09-19 08:45:14
@phdthesis{fe33349f-2754-4fbc-b64d-08aa35912429,
  abstract     = {Diffusion MRI is widely used to study brain structure in vivo. While this technique is often applied to investigations of brain connectivity, it can also be used to infer specific information about the tissue microstructure; for example, to estimate the axon diameter. In the present work, the role of tissue microstructure and water exchange in biophysical models employed in diffusion MRI was investigated. Specialised diffusion measurements were performed in white matter of healthy volunteers and in subacute stroke lesions. The results showed that exchange between microenvironments with different diffusivities contributes to the outcome of the diffusion MRI experiment. <br/><br>
<br/><br>
Concerns regarding the accuracy and precision of model-parameter estimates were addressed by using Monte Carlo simulations of the diffusion MRI experiment. The results showed that axon diameters can be accurately estimated above the resolution limit of the experiment. The fraction of water restricted to the axons, however, became underestimated at high exchange rates, although a remedy for this problem was suggested. Additional simulations showed the importance of modelling the three-dimensional structural properties of nerves containing undulating axons. Neglecting the presence of such undulations could result in overestimation of axon diameters. Stretching or compression of tissue comprising undulating axons may result in alterations of the diffusivity possible to detect by diffusion MRI.<br/><br>
<br/><br>
The filtered exchange imaging (FEXI) method was developed in order to improve the sensitivity of diffusion MRI to diffusional water exchange. Measurements on yeast cell suspensions using NMR spectrometers and a clinical MRI scanner were used to validate the method. FEXI was successfully applied to determine the water exchange rate in the healthy human brain and in a brain tumour, showing that systematic investigation of the water exchange rate in vivo is possible.<br/><br>
<br/><br>
In conclusion, this work improved the feasibility of using clinical MRI scanners to investigate tissue microstructure and the rate of water exchange.},
  author       = {Nilsson, Markus},
  keyword      = {Diffusion,MRI,tissue microstructure,water exchange,Monte Carlo simulations,white matter},
  language     = {eng},
  publisher    = {Division of Radiation Physics, Lund University},
  school       = {Lund University},
  title        = {Biophysical modelling in diffusion MRI: The role of tissue microstructure and water exchange},
  year         = {2011},
}