TY - JOUR
T1 - Multimodal neuroimaging relationships in progressive supranuclear palsy
AU - Sintini, Irene
AU - Schwarz, Christopher G.
AU - Senjem, Matthew L.
AU - Reid, Robert I.
AU - Botha, Hugo
AU - Ali, Farwa
AU - Ahlskog, J. Eric
AU - Jack, Clifford R.
AU - Lowe, Val J.
AU - Josephs, Keith A.
AU - Whitwell, Jennifer L.
N1 - Funding Information:
Dr.’s Whitwell, Josephs, Ali, Botha and Schwarz receive funding from the NIH. Matthew Senjem owns stock in Align Technology, Inc, Gilead Sciences, Inc., Globus Medical Inc., Inovio Biomedical Corp., Johnson & Johnson, LHC Group, Inc., Medtronic, Inc., Mesa Laboratories, Natus Medical Incorporated, Oncothyreon, Inc., Parexel International Corporation, Varex Imaging Corporation. Dr. Lowe serves is a consultant for Bayer Schering Pharma, Philips Molecular Imaging, Piramal Imaging and GE Healthcare and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, the NIH (NIA, NCI), and the MN Partnership for Biotechnology and Medical Genomics. Dr. Jack serves on a scientific advisory board for Eli Lilly & Company and on an independent data safety monitoring board for Roche but he receives no personal compensation from any commercial entity. He receives research support from the NIH, and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
Funding Information:
The study was funded by the National Institutes of Health , grants R01-NS89757 , R01-DC12519 and R21-NS94684 . We would like to greatly thank Avid Radiopharmaceuticals, for their support in supplying the AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation needed for this work.
PY - 2019/9
Y1 - 2019/9
N2 - Progressive supranuclear palsy is characterized primarily by 4R tau inclusions, atrophy in the brainstem and basal ganglia, and neurodegeneration along the dentatorubrothalamic tract, which are measurable in vivo using flortaucipir PET, T1-weighted MRI, and MRI with diffusion tensor imaging (DTI). However, little is known about how these processes relate to each other. The aim of this study was to investigate multimodal associations between flortaucipir PET uptake, tissue volume loss on structural MRI and white matter tract disruption on DTI. Thirty-four patients with progressive supranuclear palsy and 29 normal controls underwent flortaucipir PET, MRI and DTI. Voxel-wise comparison was performed between patients and controls. Sparse canonical correlations analysis was applied on regional measurements of flortaucipir uptake, tissue volume, fractional anisotropy and mean diffusivity of the PSP population. Pearson's correlation coefficients were assessed across modalities on the regions identified by the sparse canonical correlation analyses. Sparse canonical correlation analyses identified associations between elevated flortaucipir uptake in the cerebellar dentate, red nucleus and subthalamic nucleus and decreased volume in the same regions, and decreased fractional anisotropy and increased mean diffusivity in tracts including the superior cerebellar peduncle, sagittal striatum and posterior corona radiata. Furthermore, decreased fractional anisotropy and increased mean diffusivity in the body of the corpus callosum and anterior and superior corona radiata were related to volume loss in the frontal lobe. Tau uptake measured by flortaucipir PET appears to be related to the neurodegenerative process of progressive supranuclear palsy, including reduced tissue volume and white matter tract degeneration.
AB - Progressive supranuclear palsy is characterized primarily by 4R tau inclusions, atrophy in the brainstem and basal ganglia, and neurodegeneration along the dentatorubrothalamic tract, which are measurable in vivo using flortaucipir PET, T1-weighted MRI, and MRI with diffusion tensor imaging (DTI). However, little is known about how these processes relate to each other. The aim of this study was to investigate multimodal associations between flortaucipir PET uptake, tissue volume loss on structural MRI and white matter tract disruption on DTI. Thirty-four patients with progressive supranuclear palsy and 29 normal controls underwent flortaucipir PET, MRI and DTI. Voxel-wise comparison was performed between patients and controls. Sparse canonical correlations analysis was applied on regional measurements of flortaucipir uptake, tissue volume, fractional anisotropy and mean diffusivity of the PSP population. Pearson's correlation coefficients were assessed across modalities on the regions identified by the sparse canonical correlation analyses. Sparse canonical correlation analyses identified associations between elevated flortaucipir uptake in the cerebellar dentate, red nucleus and subthalamic nucleus and decreased volume in the same regions, and decreased fractional anisotropy and increased mean diffusivity in tracts including the superior cerebellar peduncle, sagittal striatum and posterior corona radiata. Furthermore, decreased fractional anisotropy and increased mean diffusivity in the body of the corpus callosum and anterior and superior corona radiata were related to volume loss in the frontal lobe. Tau uptake measured by flortaucipir PET appears to be related to the neurodegenerative process of progressive supranuclear palsy, including reduced tissue volume and white matter tract degeneration.
KW - DTI
KW - MRI
KW - Multimodal imaging
KW - PSP
KW - Tau-PET
UR - http://www.scopus.com/inward/record.url?scp=85068231220&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068231220&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2019.07.001
DO - 10.1016/j.parkreldis.2019.07.001
M3 - Article
C2 - 31279635
AN - SCOPUS:85068231220
VL - 66
SP - 56
EP - 61
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
SN - 1353-8020
ER -