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Automated morphometry of transgenic mouse brains in MR images Scheenstra, A.E.H.

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Automated morphometry of transgenic mouse brains in MR images

Scheenstra, A.E.H.

Citation

Scheenstra, A. E. H. (2011, March 24). Automated morphometry of transgenic mouse brains in MR images. Retrieved from https://hdl.handle.net/1887/16649

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/16649

Note: To cite this publication please use the final published version (if applicable).

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Colophone

About the cover

The displayed mouse is a C57BL/6J mouse, which is the most widely used inbred strain and the first to have its genome sequenced. The mirrored image of the mouse represents its genetically modified relative, which has the same genome except for one gene that codes for a certain disease.

Automated morphometry of transgenic mouse brains in MR images Scheenstra, Alize Elske Hiltje

Printed by Ipskamp Drukkers, Enschede, The Netherlands

ISBN-13: 978-90-9026004-4

©2011 A.E.H. Scheenstra, Leiden, The Netherlands

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, record- ing, or any information storage and retrieval system, without permission in writing from the copyright owner.

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Automated morphometry of transgenic mouse brains

in MR images

Automatische morfometrie van transgene muizenhersenen in MR beelden

Proefschrift ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van de Rector Magnificus Prof. mr. P.F. van der Heijden , volgens besluit van het College voor Promoties

te verdedigen op donderdag 24 maart 2011 klokke 16:15 uur

door

Alize Elske Hiltje Scheenstra geboren te Gouda

in 1981

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Promotiecommissie

Promotor: Prof. dr. ir. J.H.C. Reiber Co-promotor: Dr.ir. J. Dijkstra

Overige leden: Prof. dr. M. van Buchem

Prof. dr. D. Rueckert (Imperial College London ) dr. L. van der weerd

This work was carried out in the ASCI graduate school.

ASCI dissertation series number 229.

I want an empty line here

This work was supported by funds from CYTTRON within the BSIK program (Besluit subsidies investeringen kennisinfrastructuur).

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Voor Riena van Rijn - Haasnoot I want an empty line here Ter nagedachtenis aan Hiltje Scheenstra - Betlehem

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Contents

1 Introduction 1

1.1 Transgenic mouse models . . . 1

1.2 Mouse brain anatomy . . . 3

1.3 High resolution magnetic resonance imaging . . . 3

1.4 Aim of the thesis . . . 5

1.5 Thesis outline . . . 6

2 Morphometry on rodent brains 7 2.1 Introduction . . . 9

2.2 Volumetry . . . 9

2.3 Automated morphometry . . . 9

2.4 Method comparison . . . 11

2.5 Limitations to automated morphometry . . . 12

2.A Multiple-test correction . . . 13

3 Early detection of Alzheimer’s disease in MR images 15 3.1 Introduction . . . 17

3.2 Alzheimer mouse models . . . 17

3.3 Relaxometry . . . 19

3.4 Analysis and models of plaque burden . . . 23

3.5 Cerebral amyloid angiopathy . . . 24

3.6 Volumetric methods . . . 26

3.7 Texture analysis . . . 27

3.8 Discussion and conclusion . . . 28

3.A The most commonly used AD mouse models . . . 32

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Contents

4 Automated segmentation of mouse brains 35

4.1 Introduction . . . 37

4.2 Materials and methods . . . 38

4.3 Results . . . 42

4.4 Discussion . . . 47

4.5 Conclusion . . . 49

5 The generalized Moore-Rayleigh test 51 5.1 Introduction . . . 53

5.2 The Moore-Rayleigh test . . . 54

5.3 The two-sample test . . . 62

5.4 Results . . . 67

5.5 Discussion . . . 71

5.A The Fisher distribution . . . 73

6 The 3D Moore-Rayleigh test as tool for brain morphometry 77 6.1 Introduction . . . 79

6.2 Method . . . 81

6.3 Results . . . 84

6.4 Discussion . . . 92

7 Quantitative morphometry on migraine mouse models 95 7.1 Introduction . . . 97

7.2 Materials and methods . . . 98

7.3 Results . . . 100

7.4 Discussion . . . 104

8 Summary and conclusions 107 8.1 Summary and conclusions . . . 107

8.2 Future work . . . 109

9 Samenvatting en aanbevelingen 111 9.1 Samenvatting en conclusies . . . 111

9.2 Aanbevelingen . . . 113

Bibliography 115

Publications 137

Acknowledgements 139

Curriculum vitae 141

List of Figures 143

List of Tables 149

List of Abbrevations 151

viii

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