Stefano Zanigni1,2, Stefania Evangelisti1,2, Claudia Testa1,2, David Neil Manners1,2, Giovanna Calandra-Buonaura1,3, Maria Guarino4, Anna Gabellini3,5, Luisa Sambati1,3, Pietro Cortelli1,3, Raffaele Lodi1,2, and Caterina Tonon1,2

1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, 2Policlinico S.Orsola-Malpighi, Functional MR Unit, Bologna, Italy, 3IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, 4Policlinico S.Orsola-Malpighi, Neurology Unit, Bologna, Italy, 5Ospedale Maggiore, Neurology Unit, Bologna, Italy


We applied a probabilistic tractography FSL-based method to evaluate alterations in the cortico-spinal tract (CST), middle and superior cerebellar peduncles (MCP and SCP, respectively) in 90 patients with neurodegenerative parkinsonisms (Progressive Supranuclear Palsy, Multiple System Atrophy, and Parkinson’s disease). Patients and healthy controls were evaluated on a 1.5T GE scanner. DTI metrics were evaluated in the whole CST, MCP and SCP tracts, and in addition, an along tract analysis for CST has been performed. We found that specific patterns of neurodegeneration within these specific tracts are evident and that they reflect the neuropathological and clinical profile of each syndrome.


To evaluate alterations in the cortico-spinal tract (CST), middle and superior cerebellar peduncles (MCP and SCP, respectively) by using a probabilistic tractography method in a large sample of patients with neurodegenerative parkinsonisms: Progressive Supranuclear Palsy – Richardson’s Syndrome (PSP-RS), Multiple System Atrophy, Cerebellar and Parkinsonian variants (MSA-C and –P, respectively) patients compared to Parkinson’s disease (PD) patients and healthy controls (HC).


We enrolled in the study 90 patients with a clinical diagnosis of neurodegenerative parkinsonism according to current criteria1-3 and 27 HC, comparable for age and sex. All subjects underwent a standardized brain MR protocol including 25-direction diffusion imaging sequences on a 1.5 T scanner (GE Signa HDx 15). We applied the FSL probabilistic tractography algorithm4-5 in order to reconstruct the CSTs, the MCPs and SCPs (Figure 1). The connectivity maps were normalized by dividing values of connectivity by the waytotal, a number returned by the tractography algorithm that corresponds to the total number of generated tracts that have not been rejected by target masks criteria. Fractional Anisotropy (FA), Mean Diffusivity (MD), Axial Diffusivity (AD) and Radial Diffusivity (RD) were evaluated. For the CST we also performed an along-tract analysis consisting in the subdivision of the tract into 100 percentiles along the z direction in each subject-specific space, allowing a comparison of the corresponding segments among different subjects. We performed an ANCOVA test followed by post hoc tests to compare FA, MD, AD, RD and tract volume within all the whole tracts. When DTI parameters were compared, sex, age and tract volume normalized by TIV were added as covariates of no interest, while, when comparing the volume of the tract, sex, age and TIV were added as covariates of no interest. For the along-tract analysis, we performed comparisons at each percentile and adding as covariates of no interest sex, age and percentile-specific volume of the tract normalized by TIV when comparing DTI parameters and TIV when comparing the along-tract volume. Comparisons were performed with a permutation-based nonparametric method, correcting for multiple comparisons by controlling the family-wise error rate. Moreover, results were then corrected for multiple comparisons with Bonferroni method (p<0.0038, 13 comparisons).


Main demographic and clinical features of the study sample are reported in Figure 2. Whole-tract ANCOVA analysis of CST showed significant differences (p<0.05) among groups in all DTI metrics bilaterally (Table 3, Table 2 supplementary). The results of the post-hoc analysis are reported in Figure 3. The along tract analysis of CST showed a bilateral increase in MD in PSP-RS compared to PD and HC in the part of the tract passing through the corona radiata (Figure 4). We found no volumetric differences in CST segments among groups.The whole-tract ANCOVA analysis of MCPs yielded significant differences (p<0.05) among groups in all DTI metrics bilaterally and in left MCP volume (Figure 3). The results of post-hoc analysis are shown in Figure 3. The whole tract ANCOVA analysis of SCPs showed significant (p<0.05) differences among groups in all DTI metrics and tract volume bilaterally (Figure 3). The results of post-hoc analysis are shown in Figure 3.


Our study demonstrated a specific pattern of neurodegeneration, involving CST, MCPs and SCPs. In particular, we demonstrated bilateral neurodegenerative changes in both CSTs and SCPs in our PSP-RS sample, according with previous neuropathological and neuroimaging evidences6-9. Notably, CST neurodegenerative alterations were limited to the portion of the tract within the corona radiata; this portion of the tract includes neurons belonging to the corticostriatal tract, whose alterations have been related to motor control deficits and behavioural/cognitive dysfunction10. MSA-C displayed predominant neurodegenerative changes in MCPs, and with a smaller extent to SCPs. This pattern of neurodegeneration is typical of this disorder in which cerebellar dysfunction is usually prominent6,11-12. The MSA-P group showed significant alterations in MCPs compared to PD and HC: these changes are in line with the clinical and neuropathological description of this MSA variant in which cerebellar alterations are present, compared to PD and HC, and they are usually milder when compared to MSA-C6,9,12.


Atypical parkinsonisms are characterized by disease-specific patterns of white matter alterations, reflecting the neuropathology and the clinical features of the disorder, and these changes can be detected in vivo by using probabilistic tractography. These results contribute to the understanding of the physiopathology of neurodegenerative parkinsonisms, supporting the role of advanced brain MR analysis of targeted regions of interest in the in vivo differential diagnosis among parkinsonisms.


No acknowledgement found.


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Figure 1. Masks used for tractography reconstruction. A: masks for CST on PLIC (green) and pons (in red) masks and the segmentation of the precentral gyrus by FreeSurfer shown on 3D cortical reconstruction from a PSP-RS patient. B: masks for MCP (in red) and SCP (in green).

Figure 2. Demographic and clinical data of the study sample. AAE: age at evaluation; DD: disease duration; H-Y: Hoehn–Yahr modified scale; *Significant (p < 0.05) differences among groups: AAE: HC<PD and PSP-RS>MSA-C, HC and PD; H-Y: PD<MSA-P and PSP-RS. ** no significant differences among groups.

Figure 3. Whole-tract analysis of CST, MCP and SCP: results of comparisons between subgroups. *: bilateral difference, L: left, R: right

Figure 4. Along-tract results for MD in left and right CST: plot of the median values along percentiles for each group.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)