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Tractographic Methods Employed in the Visual Pathway

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Tractographic Methods Employed in the Visual Pathway CHARACTERISATION OF THE OPTIC RADIATIONS IN CHILDREN IN HEALTH AND DISEASE Say Ayala Soriano A thesis submitted for the degree of Doctor of Philosophy University College London January 2016 1 DECLARATION I, Say Ayala Soriano, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 ABSTRACT The normal and abnormal development of the optic radiations through childhood was examined in terms of their anatomical development, using MRI tractography, and their functional development, using visual evoked potentials (VEPs). Neurosurgical applications of these imaging techniques were assessed. Control cohorts of 74 children and 13 adults were recruited from Great Ormond Street Hospital. The anatomical development of the optic radiations in children from birth was described using tractography. A novel method to improve tractography analysis using VEP data was developed. VEP-enhanced tractography showed a more defined optic radiation in the gathering of the visual cortex, which caused a significant reduction in the mean FA in the adult cohort. Paediatric patients diagnosed with optic nerve hypoplasia (ONH) were recruited and 23 were compared with a matched control cohort using tractography. ONH patients presented reduced mean FA in the left optic radiation. TBSS analysis of the DTI scans showed that white matter FA was also lower in other areas of the brain outside of the visual system. Two paediatric seizure patient cohorts were recruited: 21 patients with a single episode of prolonged febrile convulsions and 20 regular users of anti-epileptic medicines. Both cohorts were compared with matched control cohorts using DTI tractography. The anti-epileptic user cohort presented lower mean FA at the front of both optic radiations, but the prolonged febrile convulsions cohort had no statistically-significant differences in mean FA, compared to controls. Two brain tumour case studies demonstrated that tractography is a valuable surgical tool in complicated paediatric neurosurgical cases where detailed description of white matter tracts can improve the surgical outcome and assist with counselling patients. Two hydrocephalus case studies demonstrated that VEP-enhanced tractography offers a novel method to identify white matter tracts in cases where conventional imaging techniques provide very limited information due to highly-distorted anatomies. 3 DEDICATION I dedicate this thesis to my parents, Antonia Soriano Baeza and Pablo Ayala Hernandez, for their unwavering support and encouragement throughout my lifelong long journey of learning. I also dedicate this work to my partner, Paul Dodds, who has given me constant encouragement and support during my PhD research. 5 ACKNOWLEDGEMENTS I was supported by two supervisors, Alki Liasis of Great Ormond Street Hospital and Chris Clark of University College London. Alki supported and encouraged me during the most difficult periods; without him, this thesis would not have been possible. Chris helped to plan the project and his contribution to editing this thesis was invaluable. I am also very grateful to Dr Dorothy Thompson, a consultant neurophysiologist at Great Ormond Street Hospital, who helped me with patient recruitment and VEP recordings, as did Ruth Lyons and Tessa Mellow. In the Ophthalmology Department of Great Ormond Street Hospital, Eva Gajdosova and Olga Alvarez Bulnes helped me greatly with patient recruitment for the study, for which I will always be grateful. Staff from the Radiology Department of Great Ormond Street Hospital, in particular Tina Banks, helped with patient MRI scanning. Finally, I would like to thank colleagues from the Developmental Imaging and Biophysics Section of the Institute of Child Heath at UCL, who helped with MRI analyses and with whom I shared some patient recruitment. These include Michael Yoong, Jonathan Clayden, Ai Wern Chung and in particular Kiran Seunarine. 7 CONTENTS 1 Introduction ..................................................................................... 27 1.1 Development of the human visual system ................................................. 28 1.1.1 Functional development through childhood .................................. 28 1.1.2 Anatomical development through childhood................................. 29 1.2 Abnormal development of the visual system ............................................. 30 1.3 Understanding visual system development ................................................ 31 1.3.1 Functional testing........................................................................... 31 1.3.2 Imaging techniques ........................................................................ 32 1.4 Overview of this study ............................................................................... 32 1.4.1 Objectives ...................................................................................... 33 1.4.2 Academic contribution................................................................... 34 1.4.3 Overview of this thesis .................................................................. 34 2 Understanding and observing the visual system.......................... 37 2.1 Anatomical description of the visual system ............................................. 38 2.1.1 Retina ............................................................................................. 39 2.1.2 Optic nerve..................................................................................... 40 2.1.3 Optic chiasm .................................................................................. 41 2.1.4 The optic tracts .............................................................................. 42 2.1.5 Lateral geniculate nucleus ............................................................. 43 2.1.6 Optic radiations .............................................................................. 43 2.1.7 Primary visual cortex ..................................................................... 45 2.2 Anatomical dissection of the visual system ............................................... 47 2.3 Development of and variations in the visual system ................................. 50 9 2.3.1 Development of the visual system in the newborn ........................ 50 2.3.2 Development of the visual system through childhood .................. 52 2.3.3 Inter-subject anatomical variations in the visual system ............... 52 2.4 Principles of MRI and DTI ........................................................................ 53 2.4.1 Physical principles of MRI ............................................................ 53 2.4.2 Diffusion imaging .......................................................................... 55 2.4.3 Diffusion tensor imaging ............................................................... 56 2.4.4 Limitations of DTI for describing the architecture of the human brain ............................................................................................... 58 2.5 Principles of tractography .......................................................................... 59 2.5.1 Deterministic tractography ............................................................ 60 2.5.2 Probabilistic tractography .............................................................. 60 2.5.3 Limitations of DTI tractography for describing the visual system 61 2.6 Principles of VEPs ..................................................................................... 62 2.6.1 Physical principles of VEPs .......................................................... 62 2.6.2 Flash stimuli .................................................................................. 65 2.6.3 Pattern reversal stimuli .................................................................. 66 2.7 Studying the optic radiations using tractography and VEPs ...................... 67 3 MRI, DTI and tractography methodologies ................................ 69 3.1 Patient recruitment ..................................................................................... 69 3.1.1 Developing the scanning protocol using adult controls ................. 70 3.1.2 Scanning procedures for children .................................................. 70 3.2 MRI scans .................................................................................................. 71 3.2.1 DTI scans ....................................................................................... 73 3.2.2 T1 sequence ................................................................................... 75 3.3 MRI image processing ............................................................................... 75 10 3.4 Tractography analysis ................................................................................ 76 3.4.1 Placement of the ROI-LGN seed points ........................................ 77 3.4.2 Placement of the mid-optic radiation waypoint ............................. 77 3.4.3 Exclusion ROI ............................................................................... 79 3.4.4 Tract probability map .................................................................... 79 3.4.5 Tract FA and MD calculation ........................................................ 80 3.4.6 Optic radiation length measurements ............................................ 83 3.5 Comparison of 1×60 and 3×20 scans ......................................................... 84 3.6 Reliability of the tractography
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