Tau deposition and white matter fiber integrity in traumatic brain injury: an [¹⁸F]T807 PET and diffusion tensor imaging study

Objectives [¹⁸F]T807 was developed for PET imaging of tau protein aggregates which are of interest in a range of neuropathologies including traumatic brain injury (TBI). Diffusion tensor imaging (DTI) tractography allows assessment of white matter fiber integrity. Our goal was to determine if tau deposition correlated with neuronal bundle damage in TBI.

Methods Ten subjects (5 controls and 5 TBI: 4 with multiple mild concussions from profession in contact sports [1 with concurrent ALS], 1 with severe injury from automotive accident) underwent dynamic [¹⁸F]T807 PET and DTI. [¹⁸F]T807 distribution volume ratio (DVR) was estimated by Logan analysis with cerebellar input. MRI data were acquired on a 3T Siemens Trio. Tractograms were generated by Diffusion Toolkit and visualized with the companion software TrackVis.

Results Cortical areas with high [¹⁸F]T807 uptake generally had comparatively low DTI track density. In corpus callosum (CC), the subject with severe injury had high [¹⁸F]T807 binding (DVR=1.9 vs 0.9 in controls) and low density of fibers (813 tracks passing through the CC vs 2419 in matched control). A former pro football player had high [¹⁸F]T807 uptake (DVR=1.6) in left lateral occipital/temporal cortex with low density of fibers (23 tracks) relative to the contralateral side (DVR=1.1, 169 tracks). Similar findings were observed in two more of the former pro athletes; the last had discernible abnormalities on neither [¹⁸F]T807 nor DTI images. Notably, T1-weighted anatomical MR images showed no macrostructural changes where [¹⁸F]T807 and DTI abnormalities were seen.

Conclusions TBI subjects with focal [¹⁸F]T807 uptake showed accompanying reductions in DTI track density. Measurements of tau deposition and fiber damage may together improve our understanding of microstructural and molecular pathologies associated with brain injury and aid in testing novel therapies.