Parkinson’s disease and local atrophy in subcortical nuclei: insight from shape analysis Federico Nemmi a, b, * , 1 , Umberto Sabatini c , Olivier Rascol a, b, d, e, f , Patrice Péran a, b a INSERM, Imagerie cérébrale et handicaps neurologiques, UMR 825, CHU PURPAN, Toulouse, France b Université de Toulouse, UPS, Imagerie cérébrale et handicaps neurologiques, UMR 825, CHU PURPAN, Toulouse, France c Radiology Department, Santa Lucia Foundation, Rome, Italy d Centre Hospitalier Universitaire de Toulouse, Service de Neurologie, CHU PURPAN, Toulouse, France e Service de Pharmacologie Clinique, Faculté de Médecine, Toulouse, France f Inserm, Centre d’Investigation Clinique 9302, CHU Purpan, Toulouse, France article info Article history: Received 25 March 2014 Received in revised form 17 June 2014 Accepted 8 July 2014 Keywords: Discrimination Shape analysis Parkinson’s disease T1 imaging abstract Parkinson’s disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, inducing dopaminergic depletion in the striatum. Recently, subcortical nuclei shape analysis based on T1 imaging has been used in PD pathology. The present study aimed to test the hypothesis that changes in local volume detectable with T1-weighted imaging are concomitant with PD and may be used as biomarkers. We compared 21 PD patients and 20 control subjects using gray matter density and subcortical nuclei volume and shape. We also tested correlations between these parameters and clinical scales. A linear discriminant analyses was carried out using global volume and local atrophy. The dif- ferences revealed between the 2 groups were volume differences in the putamen and shape differences in the putamen and the caudate nucleus. A correlation was found between shape and motor symptoms. The discriminant analysis performed using local atrophy values led to the best classification. Our results show that shape analysis contributes valuable information to investigations concerning PD patients and helps to discriminate these patients from control subjects. Ó 2014 Elsevier Inc. All rights reserved. 1. Introduction Parkinson’s disease (PD) is a neurodegenerative disorder char- acterized behaviorally by tremor at rest, bradykinesia and rigidity (Litvan et al., 2003), and physiopathologically by loss of dopami- nergic neurons in the substantia nigra pars compacta (Bergman and Deuschl, 2002), inducing dopaminergic depletion in the striatum, especially in its caudal portion and the head of the caudate nucleus (Lang and Obeso, 2004; Rodriguez-Oroz et al., 2009). Although studies exploring cerebral modification related to PD often focus on the striatum (Pitcher et al., 2012), it is common knowledge that pathophysiological modifications go far beyond the sole putamen and caudate nucleus, reaching many other subcortical nuclei and cortical areas, including, for example, the thalamus (Del Tredici et al., 2002), further perturbing the basal ganglia-thalamocortical loops (Alexander et al., 1986). An in vivo quantification of early PD pathophysiological changes using neuroimaging could be helpful for the diagnosis of the dis- ease and also serve as a biomarker for disease progression and treatment monitoring. Recent magnetic resonance imaging (MRI) studies have reported promising results when investigating PD using advanced MRI methods such as iron quantification (Martin et al., 2008) or multimodal approaches (Menke et al., 2009; Peran et al., 2010). One of the most widely used sequences in MRI studies is the T1- weighted volumetric technique (T1-3D). T1-3D can be acquired in all scanners whatever their magnetic field. It is a fast acquisition sequence commonly used in conventional clinical MRI protocols. That is why T1-3D is widely used in MRI protocols devoted to the study of degenerative diseases, especially in Alzheimer’s disease. The technique is used to quantify atrophy by using various kinds of image analysis (e.g., volumetric analysis, gray matter density anal- ysis and so forth). In Alzheimer’s disease, T1-3D has been demon- strated to be useful in the volumetric assessment of the hippocampal formation to evaluate disease progression (Barnes et al., 2009). Similarly, in Huntington’s disease, the T1-3D * Corresponding author at: INSERM, Imagerie cérébrale et handicaps neuro- logiques, UMR 825, 31024 Toulouse, France. Tel.: þ33 393339813253; fax: þ33 0562746163. E-mail address: federico.nemmi@gmail.com (F. Nemmi). 1 Present address: Department of Neuroscience, Klingberg Laboratory, Karolinska Institute, Stockholm, Sweden. Contents lists available at ScienceDirect Neurobiology of Aging journal homepage: www.elsevier.com/locate/neuaging 0197-4580/$ e see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.010 Neurobiology of Aging xxx (2014) 1e10