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IC‐P‐197: Regional TAU‐PET Uptake Patterns and Their Association with Braak Staging, Cognition, and Onset of ad‐Dementia
Author(s) -
Lowe Val J.,
Wiste Heather J.,
Fang Ping,
Senjem Matthew L.,
Boeve Bradley F.,
Josephs Keith A.,
Murray Melissa E.,
Kantarci Kejal,
Jones David T.,
Schwarz Christopher G.,
Knopman David S.,
Petersen Ronald C.,
Jack Clifford R.,
Vemuri Prashanthi
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.228
Subject(s) - precuneus , posterior cingulate , psychology , cognitive impairment , dementia , medicine , nuclear medicine , audiology , neuroscience , cortex (anatomy) , cognition , disease
imaging tauopathies such as Alzheimer’s disease (AD). Increased uptake of [F]AV-1451 in AD patients compared with healthy controls (HC) has been shown, with a strong correlation between tracer uptake and cognitive decline. These studies quantified tau load using the standardized uptake value ratio (SUVr) derived from a static [F]AV-1451 scan (80-100 min post injection). SUVr may, however, be flow dependent and, especially for longitudinal studies, should be validated against a fully quantitative approach. The objective of this study was to identify the optimal tracer kinetic model for measuring tau load using [F]AV-1451. Methods: Following intravenous injection of 22868 MBq [F]AV-1451, 130 min dynamic PET scans were performed in 3 biomarker confirmed AD patients and 3 HC. Combined continuous and manual arterial blood sampling was used to obtain a metabolite corrected plasma input function. PVELABwith the Hammers template was used to delineate regions of interest (ROIs) on a co-registered T1 weighted MRI scan. Next, regional time-activity curves were generated by projecting these ROIs onto the dynamic PET frames. These curves were analyzed using reversible and non-reversible single and two tissue compartment models, both with and without a blood volume parameter. Results: The reversible single tissue compartment model (1T2k_VB) was the preferred model for all HC. For AD patients, however, model preference shifted towards a reversible two tissue compartment model (2T4k_VB), as shown in Figure 1, especially for ROIs with high distribution volume (VT > 9 mL cm). In HC, a good correlation (R 1⁄4 1.00, slope 1⁄4 1.01) was observed between VT derived from 1T2k_VB and 2T4k_VB, indicating that 2T4k_VB is the best model for group comparisons. Figure 2 shows 2T4k_VB derived VTfor several (AD specific) ROIs. Figure 2 also suggests that cerebellum may be used as a reference region in AD. Conclusions:The relationship between model preference and VT suggests that (higher) tau load may be reflected by a second tissue compartment. Although further studies are needed, it seems that consistent VT values across subjects can be obtained using a reversible two tissue compartment model.