Available online at www.sciencedirect.com Computerized Medical Imaging and Graphics 32 (2008) 150–158 Fractal dimension analysis of MR images reveals grey matter structure irregularities in schizophrenia Anca-Larisa Sandu a,* , Inge-Andre Rasmussen Jr. b , Arvid Lundervold c , Frank Kreuder d , Gesche Neckelmann e , Kenneth Hugdahl a,f,1 , Karsten Specht a,g a Department of Biological and Medical Psychology, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway b Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway c Department of Biomedicine, University of Bergen, Bergen, Norway d Center for Neuropsychological Research, University of Trier, Trier, Germany e Department of Radiology, Haukeland University Hospital Bergen, Norway f Division of Psychiatry, Haukeland University Hospital, Bergen, Norway g Department of Medical Engineering, Haukeland University Hospital, Bergen, Norway Received 2 March 2007; received in revised form 1 October 2007; accepted 29 October 2007 Abstract The fractal dimension (FD) was used to reveal brain structure irregularities in patients with schizophrenia. FD provides a unique way of quantifying the shape complexity of cortical folding of the human brain. MR images were obtained from seven patients with schizophrenia that were compared with six healthy control subjects. The MR images were first segmented, and the FD was calculated for the grey/white matter boundary for the whole brain and the hemispheres separately, using the box-counting and Minkowski–Bouligand methods. The results showed that the patients had larger FD values than the controls, for the whole brain volume and right hemisphere. © 2007 Elsevier Ltd. All rights reserved. Keywords: Fractal dimension; Brain imaging; Schizophrenia 1. Introduction In addition to recent demonstrations of neurocognitive impairments in schizophrenia, involving both behavioural [1] and brain mapping data [2], studies of brain morphology have consistently shown grey matter (GM) abnormalities in schizophrenia [3–11], in individuals at high risk for developing schizophrenia [12,13] and in first-episode patients [14]. Other studies have shown that this is not a side-effect of medication [15]. Further evidence is given by the meta-analysis by Shap- leske et al. [16] and recent overviews by Shenton [17], Chitnis and Ellison-Wright [18], and Niznikiewicz et al. [19]. Although different MRI techniques have been used, with dif- ferent subgroups of patients, the majority of the studies have * Correspondingauthor. Tel.: +4755586221; fax: +4755589872. E-mail address: anca.sandu@psybp.uib.no (A.-L. Sandu). 1 The present research was financially supported by a grant to Kenneth Hug- dahl from the Alfried Krupp von Bohlen und Halbach Stiftung, Germany. revealed substantial GM loss in the superior (STG) and mid- dle temporal gyri (MTG) (including the hippocampus), middle frontal gyrus (MFG), and anterior cingulate (AC). Studies of cognitive impairment in schizophrenia have implicated the same brain areas, e.g. the link of executive and attentional working memory to the prefrontal cortex [20]; verbal memory to the hip- pocampus [3,21] and loss of initiative and apathy to the anterior cingulate cortex [18]. MR morphological studies provide a measure of voxel-based differences in GM volume or density, or of differences in corti- cal thickness, between patients with schizophrenia and healthy control subjects. There is, however, reason to believe that also other aspects of brain morphology factors may be abnormal in schizophrenia, e.g. the gross cortical surface structure. It has been reported in other brain-related disorders, e.g. reading- and learning-disability, that an increased rate of microdysgenesis of the cortex is present, with abundance of ectopias, i.e. neurons that are out of place and microgyrification [22,23]. Such struc- tural abnormalities were found mostly in the perisylvian and anterior vascular border regions. Interestingly, asymmetry in 0895-6111/$ – see front matter © 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.compmedimag.2007.10.005