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  • DANMARKS TEKNISKE UNIVERSITET

    BACHELOR PROJEKT

    Investigating acute changes in brain structure in response to experimentally induced changes in serotonergic function

    Julie Hjorth SAABYEMarissa Kavony ULAGARAJAH

    Kongens Lyngby 2009

    IMM-B.Sc-2009-3

  • Technical University of DenmarkInformatics and Mathematical ModellingBuilding 321, DK-2800 Kongens Lyngby, DenmarkPhone: +45 45253351, Fax: +45 45882673reception@imm.dtu.dkwww.imm.dtu.dk

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    mailto:reception@imm.dtu.dk

  • Abstract

    This bachelor project consists of the investigation of acute changes in the brain structure due to the neurotransmitter serotonin. The project aims to find and hence investigate whether there are changes of the grey matter in the brain.In order to perform the above mentionened analysis, data has been recorded by using a magnetic resonance scanner. The software program Statistical Parametric Mapping 5 (SPM5) has been used to analyse the data. During the data analysis a wide range of operations have been used, e.g. spatial normalization, modulation, smoothing and others. The program is constructed in a particular manner that enables analysis of the structural changes in each individual voxel. This procedure is called Voxel-Based Morphometry (VBM). The background for this project consists of an experiment based on a number of volunteers, who have been given different kinds of medication that each regulate the concentration of serotonin in the brain. For the analysis of the results, statistics have been used in the form of paired t-test through matrix computations.

    Furthermore the goal of this project is to simplify the complexity of the technical terms in a way so that it is easy for the reader to get a top down approch. This has been achieved through a range of smaller but more detailed sections. Thereby the reader can relate to both the technicality and the physiology of this analysis.

    Through the comprehension and interpretation of the data and the results, the conclusion of the project is that the changes that occur have little significance. The reason for this is firstly because areas of interest vanished after the FDR correction was applied. Secondly, the p-value had to be adjusted in a way that increased the level of significance. And finally the amount of subjects which have been used was too small a sample. These three reasons play a very important role of accepting the structural changes that have been detected. One must admit that although interesting areas have been found, a more thorough investigation, in which the above mentioned uncertainties have been improved, is needed.

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  • Forord

    Dette projekt er fremstillet ved Institut for Informatik og Matematisk Modulering (IMM) ved Danmarks Tekniske Universitet (DTU) som hovedforml til opnelse af Bsc. graden i Medicin og Teknologi. Projektet har primrt foreget i samarbejde med Danish Research Centre for Magnetic Resonance (DRCMR) p Hvidovre Hospital og IMM ved DTU.

    I projektet arbejdes med voxel-baseret morformetri ved hjlp af data taget med en MR-scanner. Et program, som bearbejder billederne med hensyn til statistik, parametre og kortlgning, er anvendt.

    Dette projekt er blevet vejledt af Professor Lars Kai Hansen ved IMM, DTU. Herudover har Professor Hartwig Siebner (Prof., MD, PhD), Julian Macoveanu (PhD, Msc.), William Baar (Msc. Psych., PhD) samt Arnold Skimminge (Msc., PhD stud.) fra CIMBI, Hvidovre Hospital, DRCMR vret med til vejledning.

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  • Tak til

    Vi takker vores vejleder Lars Kai Hansen ved IMM, DTU for hans vejledning til skriveprocessen.

    Herudover takker vi Arnold Skimminge for hans hjlp til databehandlingen i SPM5.

    Slutteligt takker vi William Baar, Hartwig Siebner og Julian Macoveanu for fortolkningen af resultaterne.

    _________________________________________Julie Hjorth Saabye s062286 D. 2/6-2009

    og

    ________________________________________________Marissa Kavony Ulagarajah s051907 D. 2/6-2009

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  • Indholdsfortegnelse

    Abstract.................................................................................................................................................3Forord...................................................................................................................................................4Tak til....................................................................................................................................................5Liste over forkortelser..........................................................................................................................8Notation og symbolforklaring..............................................................................................................9Introduktion........................................................................................................................................10Teori....................................................................................................................................................11

    1. Hjernens struktur........................................................................................................................111.1 Storhjernen og dens komponenter.......................................................................................121.2 Hjernens andre dele.............................................................................................................121.3 Gr og hvid substans...........................................................................................................14

    2. Serotonin....................................................................................................................................142.1 Serotoninsystemet...............................................................................................................152.2 5-HT receptorer samt serotoninproduktion........................................................................162.3 Tryptophan..........................................................................................................................19

    2.3.1 Akut Tryptophan Depletion (ATD)..............................................................................192.4 SSRI Citalopram..............................................................................................................192.5 Ketanserin...........................................................................................................................20

    3. MRI - Magnetic Resonance Imaging.........................................................................................203.1 MPRAGE............................................................................................................................23

    Forsgsbeskrivelse.............................................................................................................................244. Forsgspersoner.........................................................................................................................245. Forsget.....................................................................................................................................24

    Databehandling...................................................................................................................................256. Dataoptagelse og filformat.........................................................................................................257. Databehandling i SPM5.............................................................................................................25

    7.1 Unified Segmentering og spatial normalisering..................................................................267.1.1 Segmentering p basis af voxel-intenstitet..................................................................267.1.2 Biaskorrektion............................................................................................................287.1.3 Segmentering p basis af tissue probability maps.......................................................297.1.4 Deformerbare TMP'er..................................................................................................307.1.5 Spatial normalization...................................................................................................31

    7.2 Modulering..........................................................................................................................317.3 Smoothing...........................................................................................................................32

    General Liner Model........................................................................................................................358. Matrixformulering.....................................................................................................................359. Parret t-test.................................................................................................................................37

    9.1 Hypoteseformulering af en parret t-test..............................................................................379.2 False Discovery Rate (FDR)...............................................................................................399.3 Familywise Error (FWE) og Bonferroni korrektion ..........................................................40

    Resultater............................................................................................................................................4110. Kontrolscanning versus Ketanserin.........................................................................................41

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  • 10.1 Kontrolscanning > Ketanse