Dentate imaging: methods and applications

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1 Dentate imaging: methods and applications Dagmar Timmann Department of Neurology University of Duisburg-Essen, Germany

2 Cerebellar output via deep nuclei Folie 2 Brodal 2010

3 Cerebellar nuclei Fastigial Dentate Emboliform [anterior interposed] Globose [posterior interposed] Folie 3 Duvernoy s Atlas 2009

4 Extensions of cerebellar nuclei x (mm) y (mm) z (mm) Dentate 13.8 (2.0) 18.2 (2.3) 13.9 (2.0) Emboliform 4.7 (0.8) 7.7 (1.6) 3.6 (1.1) Globose 1.6 (0.7) 3.2 (1.0) 2.6 (0.8) Fastigial 4.3 (0.5) 4.8 (0.8) 2.6 (0.8) Folie 4 Kozlowa Neurosci Behav Physiol 1984

5 Cerebellar nuclei dorsal microgyric ventral macrogyric Folie 5 Schmahmann s Atlas 2000

6 Functional subdivisions of the dentate Rostral Caudal by courtesy of Fahad Sultan Monkey dentate flatmap Folie 6 Strick et al. Ann Rev Neurosci 2009

7 Iron content in the cerebellar nuclei after Perl s iron staining before Perl s iron staining by courtesy of Arnulf Koeppen Folie 7

8 MRI imaging of the cerebellar nuclei Susceptibility-weighted imaging (SWI; T2*) Diedrichsen et al. Neuroimage 2011 Duvernoy s Atlas Springer 2009 Quantitative T1 and Proton density maps Deoni and Catani Neuroimage 2007 Magnetization transfer maps (MT) Helms et al. Neuroimage 2009 Diffusion tensor imaging (DTI) Du et al. J Neurol 2010 Folie 8

9 SWI images Susceptibility effects increase with increasing field strength allowing for better spatial resolution. 1.5 T 3 T 7 T 1.6 mm 1 mm mm 3 46 year old healthy male Folie 9

10 7T SWI images [0.5 mm 3 ] dorsal Folie 10

11 7T SWI images [0.5 mm 3 ] Folie 11

12 Structural dentate imaging Applications 1. Volumetric measurements 2. Visualization of lesions in individual patients 3. Generation of MRI atlases Folie 12

13 Volumetric measurements Perl s iron staining of the dentate nucleus Control Friedreich s ataxia (FRDA) by courtesy of Arnulf Koeppen Folie 13

14 Cerebellum [% TICV] Friedreich s ataxia (FRDA) MRI-based volume of the cerebellum and dentate nuclei FRDA Controls 7T MRI 0.5 x 0.5 x 0.5 mm 3 Folie 14 Rabe et al. in preparation Dentate [% TICV]

15 Volume of one dentate nucleus mm 3 MRI; spatial resolution Diedrichsen et al T; 0.5 mm 3 Du et al T; 2.2 mm 3 Deoni and Catani T; 0.9x0.9x1.0 mm 3 Dimitrova et al T; 1.15x0.86x1.5 mm 3 Höpker Histology Folie Dentate 15 thickness mm» partial volume effects

16 Individual dentate lesions SCA (superior cerebellar artery) stroke 1.5T MPRAGE sagittal coronal axial Folie 16

17 Individual dentate lesions SCA (superior cerebellar artery) stroke 7T SWI 0.5 mm 3 Folie 17

18 Individual dentate lesions Dorsal view Folie 18

19 MRI atlas (1) of the nuclei Dimitrova et al. Neuroimage 2002 Axial Coronal Sagittal 1.5T, T2*- weighted FLASH sequence n = 1, 5 averages, 1x1x1.2 mm 3 SPM Folie 19 normalization

20 MRI atlas (2) of the nuclei Dimitrova et al. Neuroimage 2006: probabilistic atlas No distinction between dentate and interposed nuclei Fastigial nuclei not included SPM normalization n = 63 Folie 20

21 MRI atlas (3) of the nuclei Diedrichsen et al. Neuroimage 2011: probabilistic atlas Max overlap 77% 93.3% 94% 1. Improved spatial resolution (0.5 mm 3 ) using 7T SWI 2. SUIT normalization Folie 21

22 MRI atlas (3) of the nuclei Diedrichsen et al. Neuroimage 2009, 2011: probabilistic atlases Maximum probability maps cerebellar cortex and nuclei Interposed n = 23 Folie 22 SPM, FLIRT-FSL, SUIT normalized data sets

23 Lesion symptom mapping Lesion overlap (N = 17) Folie 23

24 ROI-driven SUIT normalization Functional MRI of the dentate EPI coronal Dentate ROI 7T fmri Diedrichsen Folie 24 et al. Neuroimage 2011

25 ROI-driven SUIT normalization Functional MRI of the dentate SUIT template Dentate (hull) template Folie Diedrichsen 25 et al. Neuroimage 2011

26 ROI-driven normalization of the dentate 77% 93.3% 94% 100% Max overlap Folie 26 Diedrichsen et al. Neuroimage 2011

27 Somatotopy of the cerebellar cortex 7T fmri Manni and Petrosini Nat Rev Neurosci 2004 Folie 27 Küper et al. Hum Brain Mapp 2011

28 Somatotopy of the dentate nucleus 7T fmri Folie 28 Küper et al. Hum Brain Mapp 2011

29 Somatotopy of the dentate nucleus Rostral Caudal Strick et al. Ann Rev Neurosci 2009 Folie 29

30 ROI-driven SUIT normalization Structural MRI of the dentate SWI (1.5T) Dentate ROI MPRAGE (1.5T) Lesion ROI Folie 30

31 ROI-driven SUIT normalization Normalized lesion on dentate SUIT template Superimposed group data Folie 31

32 Conclusions High-resolution structural MRI allows to directly visualize dentate nuclei in individual patients Extent of dentate lesions can be mapped including volumetric measures ROI-driven SUIT normalization allows for meaningful dentate fmri ROI-driven SUIT normalization is also an option for dentate lesion symptom mapping Folie 32

33 Essen Michael Küper Roxana Stefanescu Markus Thürling Dagmar Timmann Erwin L. Hahn Institute Stefan Maderwald Mark E. Ladd London Jörn Diedrichsen German Research Foundation DFG TI 239/9-1;10-1 Marie Curie Initial Training Grant (EU)

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