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. 2016 Feb;139(Pt 2):495-508.
doi: 10.1093/brain/awv361. Epub 2015 Dec 24.

Free-water imaging in Parkinson's disease and atypical parkinsonism

Affiliations

Free-water imaging in Parkinson's disease and atypical parkinsonism

Peggy J Planetta et al. Brain. 2016 Feb.

Abstract

Conventional single tensor diffusion analysis models have provided mixed findings in the substantia nigra of Parkinson's disease, but recent work using a bi-tensor analysis model has shown more promising results. Using a bi-tensor model, free-water values were found to be increased in the posterior substantia nigra of Parkinson's disease compared with controls at a single site and in a multi-site cohort. Further, free-water increased longitudinally over 1 year in the posterior substantia nigra of Parkinson's disease. Here, we test the hypothesis that other parkinsonian disorders such as multiple system atrophy and progressive supranuclear palsy have elevated free-water in the substantia nigra. Equally important, however, is whether the bi-tensor diffusion model is able to detect alterations in other brain regions beyond the substantia nigra in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy and to accurately distinguish between these diseases. Free-water and free-water-corrected fractional anisotropy maps were compared across 72 individuals in the basal ganglia, midbrain, thalamus, dentate nucleus, cerebellar peduncles, cerebellar vermis and lobules V and VI, and corpus callosum. Compared with controls, free-water was increased in the anterior and posterior substantia nigra of Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy. Despite no other changes in Parkinson's disease, we observed elevated free-water in all regions except the dentate nucleus, subthalamic nucleus, and corpus callosum of multiple system atrophy, and in all regions examined for progressive supranuclear palsy. Compared with controls, free-water-corrected fractional anisotropy values were increased for multiple system atrophy in the putamen and caudate, and increased for progressive supranuclear palsy in the putamen, caudate, thalamus, and vermis, and decreased in the superior cerebellar peduncle and corpus callosum. For all disease group comparisons, the support vector machine 10-fold cross-validation area under the curve was between 0.93-1.00 and there was high sensitivity and specificity. The regions and diffusion measures selected by the model varied across comparisons and are consistent with pathological studies. In conclusion, the current study used a novel bi-tensor diffusion analysis model to indicate that all forms of parkinsonism had elevated free-water in the substantia nigra. Beyond the substantia nigra, both multiple system atrophy and progressive supranuclear palsy, but not Parkinson's disease, showed a broad network of elevated free-water and altered free-water corrected fractional anisotropy that included the basal ganglia, thalamus, and cerebellum. These findings may be helpful in the differential diagnosis of parkinsonian disorders, and thereby facilitate the development and assessment of targeted therapies.

Keywords: Parkinson’s disease; diffusion MRI; extracellular space; multiple system atrophy; progressive supranuclear palsy.

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Figures

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Non-invasive biomarkers are needed to support differential diagnosis in Parkinsonian disorders. Using a bi-tensor diffusion model, Planetta et al. examine structural differences between Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. A cross-validated machine learning procedure using regions of interest consistent with pathology studies separates groups with excellent accuracy.
Figure 1
Figure 1
Regions of interest and control regions of interest. ASN = anterior substantia nigra; CC1 = corpus callosum region 1; CC2 = corpus callosum region 2; CN = caudate nucleus; DN = dentate nucleus; GP = globus pallidus; IPL = inferior parietal lobule; LB V = cerebellar lobule V; LB VI = cerebellar lobule VI; MCP = middle cerebellar peduncle; MOG = middle occipital gyrus; PPN = pedunculopontine nucleus; PSN = posterior substantia nigra; PUT = putamen; RN = red nucleus; SCP = superior cerebellar peduncle; STN = subthalamic nucleus; THA = thalamus; VER = vermis.
Figure 2
Figure 2
Mean difference in free-water values in each region of interest for Parkinson’s disease-control (top), MSA-control (middle), and PSP-control (bottom). ASN = anterior substantia nigra; CC1 = corpus callosum region 1; CC2 = corpus callosum region 2; CN = caudate nucleus; DN = dentate nucleus; GP = globus pallidus; LB V = cerebellar lobule V; LB VI = cerebellar lobule VI; MCP = middle cerebellar peduncle; MSA = multiple system atrophy; PD = Parkinson’s disease; PPN = pedunculopontine nucleus; PSN = posterior substantia nigra; PSP = progressive supranuclear palsy; PUT = putamen; RN = red nucleus; SCP = superior cerebellar peduncle; STN = subthalamic nucleus; THA = thalamus; VER = vermis. Asterisks denote a significant difference after correction for multiple comparisons.
Figure 3
Figure 3
Mean difference in free-water-corrected fractional anisotropy values in each region of interest for Parkinson’s disease-control (top), MSA-control (middle), and PSP-control (bottom). ASN = anterior substantia nigra; CC2 = corpus callosum region 2; CN = caudate nucleus; LB VI = cerebellar lobule VI; MCP = middle cerebellar peduncle; MSA = multiple system atrophy; PD = Parkinson’s disease; PSN = posterior substantia nigra; PSP = progressive supranuclear palsy; PUT = putamen; SCP = superior cerebellar peduncle; STN = subthalamic nucleus; THA = thalamus; VER = vermis. Asterisks denote a significant difference after correction for multiple comparisons.

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