Diffusion Tensor Imaging reveals microstructural brain changes in patients with Progressive supranuclear palsy

Introduction: Progressive supranuclear palsy (PSP) is an atypical Parkinson syndrome associated with progressive, postural axial rigidity, which often leads to fall and vertical supranuclear gaze palsy. Neuropathologically PSP is defined by the accumulation of neurofibrillary tau tangles in neurons and glial cells in basal ganglia, diencephalon, brainstem. Additionally atrophy is described in the subthalamic nucleus and brainstem, especially the midbrain tectum and the superior cerebellar peduncle. However, routine clinical MRI does not correspond to those findings. We used whole-head Diffusion Tensor Imaging (DTI) to investigate, if DTI can identify microstructural brain changes in patients with PSP.

Material and Methods: Whole-head DTI scans were obtained from 13 PSP patients and 10 age-matched healthy controls. The raw data was motion and eddy corrected and fractional anisotropy (FA), axial and radial diffusivity maps were calculated for each subject. The maps were registered by the TBSS processing stream and a white matter Skeleton was extracted for each subject. These skeletonised maps underwent a voxel-wise statistical test. In earlier studies a correlation between a decrease in axial diffusivity and axonal degeneration as well as a correlation between an increase in radial diffusivity and dysmyelination was shown. The FA gives general information about microstructural changes.

Results: We found significant decrease of the axial diffusivity (p<0.0001) in the cerebral white matter, the pons and the right substantia nigra. A significant increase (p<0.0001) of the radial diffusivity was found in the superior cerebellar peduncle, the fornix, the corpus callosum, and the frontal cortex. These changes were not overlapping. Also a significant decrease (p<0.0001) of the FA was found in all the those areas, except the substantia nigra, where the FA was slightly increased, and the pons.

Discussion: This is the first report of disease-specific microstructural brain changes in the MRI of PSP patients using DTI. Our results suggest potential neuronal damage in the cerebellum, the pons and the right substantia nigra and potential myelin degeneration in the superior cerebellar peduncle, the fornix, the corpus callosum and the frontal cortex. Those areas with altered brain structure are consistent with described patterns of neurodegneration in PSP patients. DTI therefore bears the potential of a new tool for the early and differenzial diagnosis of PSP.