Title | Quantitative evaluation of tau PET tracers F-THK5351 and F-AV-1451 in Alzheimer's disease with standardized uptake value peak-alignment (SUVP) normalization. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Chen J, Li Y, Pirraglia E, Okamura N, Rusinek H, de Leon MJ |
Corporate Authors | Alzheimer’s Disease Neuroimaging Initiative |
Journal | Eur J Nucl Med Mol Imaging |
Volume | 45 |
Issue | 9 |
Pagination | 1596-1604 |
Date Published | 2018 07 |
ISSN | 1619-7089 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Aminopyridines, Brain, Carbolines, Female, Humans, Male, Middle Aged, Positron-Emission Tomography, Quinolines |
Abstract | PURPOSE: Off-target binding in the reference region is a challenge for recent tau tracers F-AV-1451 and F-THK5351. The conventional standardized uptake value ratio (SUVR) method relies on the average uptake from an unaffected tissue sample, and therefore is susceptible to biases from off-target binding as well as variability among individuals in the reference region. We propose a new method, standardized uptake value peak-alignment (SUVP), to reduce the bias of the SUVR, and improve the quantitative assessment of tau deposition. METHODS: The SUVP normalizes uptake values by their mode and standard deviation. Instead of using a reference region, the SUVP derives the contrast from unaffected voxels over the whole brain. Using SUVP and SUVR methods, we evaluated the global and regional tau binding of F-THK5351 and F-AV-1451 on two independent cohorts (N = 18 and 32, respectively), each with cognitively normal (NL) subjects and Alzheimer's disease (AD) subjects. RESULTS: Both tracers showed significantly increased binding for AD in the targeted cortical areas. In the temporal cortex, SUVP had a higher classification success rate (CSR) than SUVR (0.96 vs 0.89 for F-THK5351; 0.86 vs 0.75 for F-AV-1451), as well as higher specificity under fixed sensitivity around 0.80 (0.70 vs 0.45 specificity for F-THK5351; 1.00 vs 0.78 for F-AV-1451). In the cerebellar cortex, an AD-NL group difference with effect size (Cohen's d) of 0.62 was observed for AV-1451, confirming the limitation of the SUVR approach using this region as a reference. A smaller cerebellar effect size (0.09) was observed for THK5351. CONCLUSION: The SUVP method reduces the bias of the reference region and improves the NL-AD classification compared to the SUVR approach. |
DOI | 10.1007/s00259-018-4040-1 |
Alternate Journal | Eur J Nucl Med Mol Imaging |
PubMed ID | 29704038 |
PubMed Central ID | PMC6174003 |
Grant List | R01 AG022374 / AG / NIA NIH HHS / United States R01 HL111724 / HL / NHLBI NIH HHS / United States R01 AG035137 / AG / NIA NIH HHS / United States R21 AG032554 / AG / NIA NIH HHS / United States R01 AG013616 / AG / NIA NIH HHS / United States U01 AG024904 / AG / NIA NIH HHS / United States R01 HL118624 / HL / NHLBI NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States R01 AG012101 / AG / NIA NIH HHS / United States T32 AG052909 / AG / NIA NIH HHS / United States |
Related Institute:
Brain Health Imaging Institute (BHII)