Dr. A.M. van Cappellen van Walsum (Anne-Marie), MD, PhD.

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1 Dr. A.M. van Cappellen van Walsum (Anne-Marie), MD, PhD. Assistant Professor Anatomy Anatomist, specialised in Neuroanatomy in relation to Imaging. Principal Investigator MIRA-Neuro Imaging (NIM)-Neuroanatomy, University of Twente. Visiting Adress: Radboud University Medical Centre Nijmegen, Donders Institute for Brain, Cognition and Behaviour, The Netherlands. Department of Anatomy P +31 (0) P +31 (0) (secr) F +31 (0) Researchline: Anatomy of Human Brain Networks Mission statement The purpose of this research line is to investigate the plasticity of structural networks and related vascularisation in the human brain. The translational research reaches from validation of imaging techniques towards the use of these techniques in the clinic practice. Research areas Improving and validation DWI tractography We investigate the structural brainnetworks in normal and affected human brain. The imaging technique which can be used to measure structural connectivity such as DWI tractography is an important measurement tool. This tool still is in development and improvement of the technique and validation is still needed. In vivo and ex vivo measurements are performed on 1.5T, 3T and on high resolution 7T and 11.7T MRI systems.

2 - SWI-informed diffusion tensor tractography. (Kleinnijenhuis et al. Neuroimage, 2011). Anatomical white matter tracts better separated in Meyer s loop (needed in neurosurgery). - Validation of DWI-tractography with post-mortem human brain tissue. The focus is on the white matter and gray matter interface because this area is difficult to visualize in DWI tractography and very important in constructing brainnetworks. DWI (11.7T) sample human visual cortex in white matter and cortex showing orientation. Work of Kleinnijenhuis et al. Luxol Fast Blue staining showing white matter fibre orientation. Work of BMT student Sikma. In vivo human brainnetworks - Brain parcellation In this project mathemathical techniques and DWI data are used to parcellate the cortex of the brain. The ultimate challenge is to create both an in vivo atlas of the human brain and an individual reliable parcellation.

3 Visual cortex V1 with fmri Visual cortex V1 with random walks method. Work of Nijhuis et al. - Structural hubs In this project hubs, or brain areas which are highly connected with other regions in the brain, are identified and visualized. The hubs correspond with known anatomical areas called heteromodal association areas. Damage of such areas has clinical impact. Structural hubs as measured with DWI tractography and graph theoretical methods. Work of Nijhuis et al. - Connectivity of visual networks In this project the connectivity of the visual human cortex is measured with anatomical and functional (rs fmri).

4 Structural brainnetwork of the visual cortex (DWI tractography). - Vascularization of brainnetworks (collaboration in VIP Brainnetworks, Prof Norris) In this study the vascularisation of the networks in the precuneus of the parietal lobe is investigated with arterial spin labelling (ASL MRI). The hypothesis is that this brain area is more preserved from ischemic damage compared to other brainareas because there is a collateral blood supply to this brainarea. Clinical studies of lesions and brainnetworks The developed MRI techniques can be used in clinical research. Which this approach, the (structural) networks and subsequent plasticity in many diseases can be investigated. The results may lead to better diagnosis, recovery-prediction and revalidation monitoring. - Subcortical ischemic stroke the effect on the cortex is investigated in patients with subcortical ischemic stroke. The effects on the cortex are measured both in vivo (MRI) as ex vivo (pathology post mortem). This project is in collaboration with the Donders Institute and the departments of Neurology and Neuroradiology in Essen, Germany. - Lesion study of patients with visual stroke and plasticity after training In this study the plasticity of the brainnetworks is studied before and after training in patients with a stable visual stroke. - Neurosurgery of the cerebellum and mutism This project is in collaboration with the department of Neurosurgery (UMCN). Patients with lesions in the cerebellum (infarct, tumour, post surgery) suffer often from mutism. With anatomical, MRI and clinical studies we investigate the mechanism leading to these symptoms after lesions of the cerebellum. Also the use of DWI tractography before surgery will be investigated.

5 In vivo 3T DWI with tractography showing connections of the dentate-thalamic tract including the crossing. Work of Oscar Geessink, student Technical Medicine, M2 stage. Dissection of the human brain showing part of the dentate-thalamic tract. - Postanoxic encephalopathy (collaboration in VIP Brainnetworks, Prof van Putten) Decision making is still extremely difficult in the medical policy in patients on the intensive care. Purpose is to investigate the correlation between EEG patterns as measured on the Intensive Care in patients with postanoxic encephalopathy and changes in the synapses of the cortex as measured with histology in post mortem human brain samples. Research projects granted VIP Brain Networks ( ), Pieken in de Delta (MIRA, UMCN, Donders Centre, Siemens, ANT-Neuro and TMS-i). PhD students E. Nijhuis (NIM) M. Kleinnijenhuis (Anatomy, VIP-Brain Networks project) Students Tom Konert (M2 TG) Kirsten Becker (bachelor BMT) Alumni Oscar Geessink (M2 TG) Kees Jan Sikma (master BMT) Projects for (master) students at the department of Anatomy

6 1. Validation of MRI (DTI/SWI) with histological techniques and white matter dissection (Klingler) in post mortem human brain. Collaboration with the department of Neurosurgery UMCN. 2. Plasticity after training in patients with stroke in visual cortex and visual neglect. Plasticity in connectivity. Data analysis of resting state fmri, DTI and ASL data. 3. Vascularisation of the human brain in relation to ASL. Literature and data analysis. 4. Brain dissection for education and plastination purposes Publications - Kleinnijenhuis M, Barth M, Alexander DC, van Cappellen van Walsum AM, Norris, DG. SWI-informed diffusion tensor tractography. Neuroimage. Structure Tensor Informed Fiber Tractography (STIFT) by combining gradient echo MRI and diffusion weighted imaging. Neuroimage 2011: Oct 28 - Stam CJ, de Haan W, Daffertshofer A, Jones BF, Manshanden I, van Cappellen van Walsum AM, Montez T, Verbunt JP, de Munck JC, van Dijk BW, Berendse HW, Scheltens P. Graph theoretical analysis of magnetoencephalographic functional connectivity in Alzheimer's disease. Brain :132 : Stam CJ, Jones BF, Zuiderwijk I, van Cappellen van Walsum A.M., Montez T, Verbunt JPA, de Munck JC, van Dijk BW, Berendse HW, Scheltens P. Magnetoencephalographic evaluation of resting-state connectivity in Alzheimer s disease. Neuroimage 2006: 29: - Pijnenburg YAL, van de Made Y, van Cappellen van Walsum A-M, Knol DJ, Scheltens Ph, Stam CJ. EEG synchronization likelihood in mild cognitive impairment and Alzheimer's disease during a working memory task. Clin Neurophysiol 2004:115(6): van Cappellen van Walsum A-M, Pijnenburg YAL, van Dijk BW, Berendse HW, Scheltens Ph, Stam CJ. A neural complexity measure applied to MEG data in Alzheimer s disease. Clin Neurophysiol 2003: 114: van Cappellen van Walsum AM, Rijpkema M, Heerschap A, Oeseburg B, Nijhuis JG, Jongsma HW. Cerebral energy metabolism and intracellular ph, as measured with in vivo 31 P- MR spectroscopy, in relation to systemic acid-base balance in fetal sheep during hypoxia. Pediatr Res 2003; 54: Stam CJ, Breakspear M, van Cappellen van Walsum A-M, van Dijk BW. Nonlinear synchronization in EEG and whole head MEG recordings of healthy subjects. Hum Brain Mapping 2003; 19: Baayen JC, de Jongh A, Stam CJ, de Munck JC, Jonkman JJ, Trenite DG, Berendse HW, van Cappellen van Walsum A-M, Heimans JJ, Puligheddu M, Castelijns JA, Vandertop WP. Localisation of slow wave activity in patients with tumor-associated epilepsy. Brain Topogr 2003: 16(2): van Cappellen van Walsum AM, Jongsma HW, Wevers RA, Nijhuis JG, Crevels J, Engelke UF, De Abreu RA, Moolenaar SH, Oeseburg B, Nijland R. 1H-NMR spectroscopy of cerebrospinal fluid of fetal sheep during hypoxia-induced acidemia and recovery. Pediatr Res 2002; 52(1): Stam CJ, van Cappellen van Walsum A-M, Pijnenburg YAL, Berendse HW, de Munck HJ, Scheltens Ph, van Dijk BW. Generalized synchronization of MEG recordings in Alzheimer s disease: evidence for involvement of the gamma band. J Clin Neurophysiol 2002; 19: Stam CJ, van Cappellen van Walsum A-M, Micheloyannis, S. Variability of EEG synchronization during a working memory task in healthy subjects. Int J Psychophysiology 2002; 46:

7 - van Cappellen van Walsum AM, Jongsma HW, Wevers R, Nijhuis JG, Crevels J, Engelke UF, Moolenaar SH, Oeseburg B, Nijland R. Hypoxia in fetal lambs: a study with 1 H-NMR spectroscopy of cerebrospinal fluid. Pediatr Res 2001; 49: van Cappellen van Walsum AM, Heerschap A, Nijhuis JG, Oeseburg B, Jongsma HW. Hypoxia, the subsequent systemic metabolic acidosis, ands its relation with cerebral metabolites. An in vivo study in fetal lambs with proton magnetic resonance spectroscopy. Am J Obstet Gynecol 1999; 181: van Cappellen van Walsum AM, Heerschap A, Nijhuis JG, Oeseburg B, Jongsma HW. Proton magnetic resonance spectroscopy of fetal lamb brain during hypoxia. Am J Obstet Gynecol 1998; 179: Abstracts, conferences (2011>) - Kleinnijenhuis M, Barth M, Zerbi V, Sikma KJ, Küsters B, Slump CH, Norris DG, Ruiter D, van Cappellen van Walsum A-M. In vitro layer-specific Diffusion Weighted Imaging in human primary visual cortex. International School Of Clinical Neuroanatomy, Sicily, Italy,May Kleinnijenhuis M, Sikma KJ, Barth M, Dederen J, Zerbi V, Küsters B, Ruiter D, Slump CH, van Cappellen van Walsum A-M. - Validation of Diffusion Weighted Imaging of cortical anisotropy by means of a histological stain for myelin. In vitro cortical DWI shows layer-specific diffusion. HBM 2011, Quebec, Canada. - Nijhuis E, van Cappellen van Walsum A, Norris DG. Mapping hubs in the neocortical structural network of the human brain. HBM 2011, Quebec, Canada. - Kleinnijenhuis M, Barth M, Zerbi V, Sikma KJ, Küsters B, Slump CH, Norris DG, Ruiter D, van Cappellen van Walsum A-M. In vitro layer-specific Diffusion Weighted Imaging in human primary visual cortex. Doorwerth Conference Brain circuitry 2011, Oral presentation. - Kleinnijenhuis M, Sikma KJ, Barth M, Dederen J, Zerbi V, Küsters B, Ruiter D, Slump CH, van Cappellen van Walsum A-M. - Validation of Diffusion Weighted Imaging of cortical anisotropy by means of a histological stain for myelin. Benelux-ISMRM Kleinnijenhuis M, Sikma KJ, Barth M, Dederen J, Zerbi V, Küsters B, Ruiter D, Slump CH, van Cappellen van Walsum A-M. Validation of diffusion weighted imaging of cortical anisotropy by means of a histological stain for myelin. ISMRM 2011, Montreal, Canada. - Nijhuis E, van Cappellen van Walsum A, Norris DG. Mapping hubs in the neocortical structural network of the human brain. ISMRM 2011, Montreal, Canada. Oral presentation. - Sikma KJ, Kleinnijenhuis M, Barth M, Dederen PJ, Küsters B, Slump CH, van Cappellen van Walsum A-M. Validating tractography from DWI/SWI data with 3D reconstructed histological data of post mortem human brain tissue. Nederlandse Anatomen Vereniging, congress Steenbeecke C and van Cappellen van Walsum A-M. Digitale instaptoets ter voorbereiding van het hersendissectiepracticum. NVMO 2011, The Netherlands.

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