Radiological studies on hippocampal development. Morphological variants and their relationship to epilepsy. Dragan Bajic ! " #$ %&'( )0$0 1!02!( 343 56( ( 72!( 8$ 9@( A696 6BC9D E 2 3 E " E F22 GH"! E I"PQ 72 #$ ' "!" R'2Q S1"( Q A696Q T3" R! U"$ $Q I23" V 2 T2 WQ X! E& 03( 3 "2 00 $$!3( W2 E& 3Q D6 Q Q XRS8 B5@9B99D6Y9A9DY9`Q !3 E $( 2 2"$ !"! E E$3 2 2"$ !"! '2"2 2 $ 2 2 Q !3 2 "( 2 2"$ !"! ' " 2 2"$! 0 ! E$Q )E "$ ( 2 2"$! 2 E$ "! 3 #Q XE 2 " 2 "$ 2 2"$! $ 2 ! E$Q 72 " " "$ 2"$ GXUXPQ 72 $ E 2 ! ' ! 2 Ea!" E XUX 9" " "2 ! # 2 $ E 2 2"$ 3 !3 $! E!Q I3" " GITP $3 E A69 9D6 9" ! 1" ' ! '2! 0'3 "" Q XUX ' E! 9B b c! E " GA6 E9 @ PQ `6b E 2 A69 2 XUX Gd6 E9( d 329( 9Y PQ 72 EE" ' " 3E" Ge6Q6APQ ADb E 2 $ 2 XUXQ 72 Ea!" ' 3E" 232 2 "Q 72 "! ' $ XUXQ ddb E 2 T" D5b E 2 "3" 3c 2 XUXQ XUX " 3 E ! " $ 2 E 2 Q f !! #$ E 9Y6 $! "2 ' cQ 72 3 #$ ' A`9Ad %g Ad "2( AD9A@ %g 5A "2( AB9`Y %g Yd "2Q XUX ' E! D6b( ADb 9db( "Q 72 Ea!" EE" ' 2 "2 e AD %g h AD %g ' " 3E" Ge 6Q669PQ H$ AD %g '( 2 Ea!" E XUX $ 2 2 ! !Q ITX E Y` E! '2! " 23 ' ' ' 3Q 72 ITX ' E$ 3 '0 G%gP 9599@ Y6 %g 9B9`D 72 2"$ !"! ' ( 9 !( `D E! %g 959`AQ 72 E 2$ ' %g `AQ 72 !"! ' " %g A9 2 ( !( ' E$ %g `` ' Q X AYiY` E! Gd9bP( 2 2"$ $ ' $$" A` E!( 2 32 2 EQ ITX( S $( U"$!( W ! ! !" ## $ %&'()*+)#% p 3 S1" A696 XRS8 B5@9B99D6Y9A9DY9` !C CC!!C99`9BBY G2Cii!Q0 Qiq!r!C CC!!C99`9BBYP TO MY FAMILY Ne mogu vratiti vrijeme koje nisam proveo sa vama ali ste zauvijek u mojim mislima i mom srcu. LIST OF PAPERS This thesis is based on the following studies, which will be referred to in the text by their Roman numerals. I. Bajic D, Wang C, Kumlien E, Mattsson P, Lundberg S, Eeg-Olofsson O, Raininko R.: Incomplete inversion of the hippocampus - a common developmental anomaly. Eur Radiol. 2008 Jan;18(1):138-42. II. Bajic D, Kumlien E, Mattsson P, Lundberg S, Wang C, Raininko R.: Incomplete hippocampal inversion - is there a relation to epilepsy? Eur Radiol. 2009 Oct;19(10):2544-50. III. Bajic D, Ewald U, Raininko R.: Hippocampal development at gestation weeks 23 to 36. An ultrasound study on preterm neonates. Neuroradiology. 2010 Jun;52(6):489-94. IV. Bajic D, Canto Moreira N, Wikström J, Raininko R.: Asymmetric hippocampal development is common. A fetal magnetic resonance study. Variation and asymmetry of the fetal hippocampus. Manuscript submitted. TABLE OF CONTENTS LIST OF PAPERS ..................................................................................................................................... 5 TABLE OF CONTENTS .......................................................................................................................... 7 ABBREVIATIONS ................................................................................................................................... 9 INTRODUCTION ....................................................................................................................................11 Milestones in brain research ............................................................................................................................. 11 History of imaging with CT and MRI ........................................................................................................... 11 History of limbic system research ................................................................................................................12 History of the hippocampus research...........................................................................................................12 Limbic lobe/ system, short overview of the anatomy ....................................................................................... 13 Hippocampal embryology ................................................................................................................................. 14 Hippocampal anatomy and functions ............................................................................................................... 16 Hippocampal pathology .................................................................................................................................... 18 Imaging in hippocampus assessment ................................................................................................................ 19 US ................................................................................................................................................................. 19 CT ................................................................................................................................................................. 19 MRI ............................................................................................................................................................... 19 PET ............................................................................................................................................................... 19 SPECT ...........................................................................................................................................................20 MRS ..............................................................................................................................................................20 Diffusion M RI ...............................................................................................................................................20 Introduction to present studies ..........................................................................................................................20 AIMS OF THE STUDY ......................................................................................................................... 21 MATERIALS AND METHODS ........................................................................................................... 23 Subjects .............................................................................................................................................................23 Children and adults (paper I and II) ............................................................................................................23 Premature neonates (paper III) ...................................................................................................................23 Fetuses (paper IV) ........................................................................................................................................23 MR methodology in children and adults (paper I and II) .................................................................................24 Prestudy –validation of the MR technique ...................................................................................................24 Studies of the children and adults (paper I and II) ......................................................................................24 Ultrasound methodology on premature neonates (Paper III) ...........................................................................26 MR methodology in fetuses (paper IV) ............................................................................................................27 Statistical analysis for all studies ......................................................................................................................28 RESULTS ............................................................................................................................................... 29 [ ..................................................29 Occurrence of the IHI in the non-epileptic and epileptic populations (Paper II) .............................................30 Control g roup ...............................................................................................................................................30 Epilepsy patient groups ................................................................................................................................30 Laterality and distribution of the total and partial forms of the IHI .................................................................30 Control g roup ...............................................................................................................................................30 Epilepsy patient groups ................................................................................................................................30 [ ..................................................................... 32 Ultrasound study on preterm neonates (Paper III) ........................................................................................... 32 MRI study on fetuses (Paper IV) ...................................................................................................................... 32 DISCUSSION .......................................................................................................................................... 35 Studies on the hippocampal development ......................................................................................................... 35 Studies focusing on the morphological variants of the hippocampus and their relation to some epilepsy syndromes ........................................................................................................ 39 CONCLUSIONS ....................................................................................................................................