Volumetrics of the caudate nucleus: Reliability and validity of a new manual tracing protocol Jeffrey Chee Leong Looi a,b, ⁎ , Olof Lindberg b , Benny Liberg b , Vanessa Tatham a , Rajeev Kumar a,c , Jerome Maller d , Ellen Millard a , Perminder Sachdev e,f , Göran Högberg g , Marco Pagani h,i , Lisa Botes j , Eva-Lena Engman j , Yi Zhang j , Leif Svensson j , Lars-Olof Wahlund b a Research Centre for the Neurosciences of Ageing, Academic Unit of Psychological Medicine, Australian National University Medical School, The Canberra Hospital, Australian Capital Territory, Australia b Karolinska Institute, Department of Neurobiology, Caring Sciences & Society, Division of Clinical Geriatrics, Stockholm, Sweden c Consultation-Liaison Psychiatry, Department of Psychological Medicine, National University of Singapore, Singapore d Alfred Psychiatry Research Centre, Monash University & Centre for Mental Health Research, Australian National University, Canberrra, Australia e School of Psychiatry, Faculty of Medicine, University of New South Wales, Prince of Wales Hospital, Sydney, Australia f Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia g Department of Clinical Neuroscience, Section for Psychiatry, Huddinge, Karolinska Institute, Stockholm, Sweden h Institute of Cognitive Sciences and Technologies, CNR, Rome, Italy i Department of Nuclear Medicine, Karolinska Hospital, Stockholm, Sweden j Karolinska University Hospital, Hospital Physics and Radiology, Stockholm, Sweden Received 20 November 2006; received in revised form 25 June 2007; accepted 16 July 2007 Abstract Our aim was to develop a reliable and valid manual segmentation protocol for tracing the caudate nucleus in MRI for volumetric and, potentially, shape analysis of the caudate. Using the protocol, two inter- and intra-rater reliability studies were conducted using five different raters on two different image analysis platforms (ANALYZE, Mayo Biomedical Imaging Resource, Rochester MN, USA, and HERMES, Nuclear Diagnostics AB, Stockholm, Sweden). Reference images for the detailed protocol are described. Two studies were performed. In study 1, the intra-rater class correlation ICC(1,1) for an experienced rater (JCLL) using this protocol for caudate nucleus volumes was evaluated by repeating right and left caudate measurements on 10 scans (20 comparisons) and was 0.972. The inter-rater class correlation ICC(1,k) with OL was 0.922 on 5 scans (10 comparisons) and with BL was 0.960 on 5 scans (10 comparisons). In study 2, VT obtained an intra-rater class correlation of 0.9 on 5 scans (involving 10 comparisons, e.g. right and left caudate). The inter-rater class correlation ICC(1,k) was 0.988 on 5 scans (again involving 10 comparisons) with EM. We therefore developed a novel, reliable and reference image-based, method of outlining the caudate nucleus on axial MRI scans, usable in two different image analysis laboratories, across two different sets number of tracers reliably, and across software Available online at www.sciencedirect.com Psychiatry Research: Neuroimaging 163 (2008) 279 – 288 www.elsevier.com/locate/psychresns ⁎ Corresponding author. Research Centre for the Neurosciences of Ageing, Academic Unit of Psychological Medicine, Australian National University Medical School, Building 4, Level 2, The Canberra Hospital, PO Box 11, Woden ACT 2605, Australia. Tel.: +61 2 6205 1977; fax: +61 2 6244 4964. E-mail address: Jeffrey.looi@act.gov.au (J.C.L. Looi). 0925-4927/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2007.07.005