Assessment of Global and Regional Diffusion Changes along White Matter Tracts in Parkinsonian Disorders by MR Tractography

et al. (2013) Assessment of Global and Regional Diffusion Changes along White Matter Tracts in Parkinsonian Disorders by MR Tractography. PLoS ONE 8(6): e66022. doi:10.1371/journal.pone.0066022 Assessment of Global and Regional Diffusion Changes along White Matter Tracts in Parkinsonian Disorders by MR Tractography Yulia Surova 0 Filip Szczepankiewicz 0 Jimmy La tt 0 Markus Nilsson 0 Bengt Eriksson 0 Alexander Leemans 0 Oskar Hansson 0 Danielle van Westen 0 Christer Nilsson 0 Wang Zhan, University of Maryland, College Park, United States of America 0 1 Department of Clinical Sciences, Neurology, Lund University, Lund, Sweden, 2 Department of Neurology Lund, Ska ne University Hospital, Lund, Sweden, 3 Department of Medical Radiation Physics, Lund University, Lund, Sweden, 4 Center for Medical Imaging and Physiology, Ska ne University Hospital, Lund, Sweden, 5 Lund University Bioimaging Center, Lund University, Lund, Sweden, 6 Clinical Memory Research Unit, Department of Clinical Sciences Malmo , Lund University, Sweden, 7 Image Sciences Institute, University Medical Center Utrecht , Utrecht , The Netherlands , 8 Department of Clinical Sciences, Diagnostic Radiology, Lund University , Lund , Sweden Purpose: The aim of the study was to determine the usefulness of diffusion tensor tractography (DTT) in parkinsonian disorders using a recently developed method for normalization of diffusion data and tract size along white matter tracts. Furthermore, the use of DTT in selected white matter tracts for differential diagnosis was assessed. Methods: We quantified global and regional diffusion parameters in major white matter tracts in patients with multiple system atrophy (MSA), progressive nuclear palsy (PSP), idiopathic Parkinson's disease (IPD) and healthy controls). Diffusion tensor imaging data sets with whole brain coverage were acquired at 3 T using 48 diffusion encoding directions and a voxel size of 26262 mm3. DTT of the corpus callosum (CC), cingulum (CG), corticospinal tract (CST) and middle cerebellar peduncles (MCP) was performed using multiple regions of interest. Regional evaluation comprised projection of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and the apparent area coefficient (AAC) onto a calculated mean tract and extraction of their values along each structure. Results: There were significant changes of global DTT parameters in the CST (MSA and PSP), CC (PSP) and CG (PSP). Consistent tract-specific variations in DTT parameters could be seen along each tract in the different patient groups and controls. Regional analysis demonstrated significant changes in the anterior CC (MD, RD and FA), CST (MD) and CG (AAC) of patients with PSP compared to controls. Increased MD in CC and CST, as well as decreased AAC in CG, was correlated with a diagnosis of PSP compared to IPD. Conclusions: DTT can be used for demonstrating disease-specific regional white matter changes in parkinsonian disorders. The anterior portion of the CC was identified as a promising region for detection of neurodegenerative changes in patients with PSP, as well as for differential diagnosis between PSP and IPD. - Funding: This research was supported by the Swedish Parkinson foundation, the Swedish Science Council grants through the Linnaeus project BAGADILICO, the Swedish Parkinson Academy and research funds from province of Skane University Hospital and state grants (inclusively ALF) and in part by the Swedish Cancer Society (GrantNo CAN 2009/1076 and CAN 2012/597). The funders had no role in study design, data collection and analysis, decision to publish and preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. . These authors contributed equally to this work. Idiopathic Parkinsons disease (IPD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), are the most common neurodegenerative disease entities in what is often called parkinsonian disorders. Outside specialized centers and in the early stages of the diseases, clinical differential diagnosis can often be difficult because of similarity of symptoms and lack of diagnostic markers. Several imaging methods have been shown to be of benefit in the differential diagnosis of different parkinsonian disorders [1]. Diffusion tensor imaging (DTI) [23] with calculation of the fractional anisotropy (FA) and mean diffusivity (MD) have been used in the diagnostic evaluation of IPD, PSP and MSA [410]. Measurement of MD in basal ganglia structures can differentiate between IPD and MSA/PSP, while FA and MD values within specific white matter tracts can be helpful in differentiating PSP and the parkinsonian variant of MSA (MSA-P) from both each other and from IPD [1119]. Few studies have been performed using diffusion tensor tractography (DTT) [20] in parkinsonian disorders. In a pilot study, we have previously shown that disease-specific degenerative changes can be demonstrated by DTT in MSA and PSP [4] and some of these findings have recently been confirmed [2122]. However, global measurements of diffusion parameters in whole white matter tracts might overlook regional changes along a tract [2324]. The aim of the present study was to investigate diffusion properties in major white matter tracts of patients with different parkinsonian disorders, employing DTT with an alternative processing scheme to be able to investigate both global and regional changes in larger nerve tracts [2532]. We focused on three conventional parameters: FA, MD and radial diffusivity (RD) as well as a new measure of tract cross-sectional surface area - the apparent area coefficient (AAC) [30]. We demonstrate both tract-specific and disease-specific variations in DTT parameters along white matter tracts, which might form a basis for future studies of differential diagnosis and disease monitoring in parkinsonian disorders. Materials and Methods Ethics Statement The Ethics Committee of Lund University approved this study. All study participants gave written consent for participation in the study, which was performed in accordance with the provisions of the Helsinki Declaration. Subjects The study included 54 subjects: thirty-eight patients presenting parkinsonian syndromes and sixteen healthy controls. Patients were recruited from the Neurology and Memory Clinics at Skane University Hospital and Landskrona Hospital, Sweden. Patients with a clinical diagnosis of probable IPD (n = 10), PSP (n = 16) and MSA-P (n = 12) according to established criteria [3335] were included in the study. Clinical diagnoses were made by two neurologists experienced in parkinsonian disorders (C.N. and B.E). Out of the 16 patients with a diagnosis of probable PSP, all presented gradually progressive disorders with an age of onset 40 years or older, symmetry of symptoms (rigidity, bradykinesia); all patients presented both gaze palsy and prominent postural instability with falls within t (...truncated)