Premium
Compensating for choroid plexus based off‐target signal in the hippocampus using [ 18 F]flortaucipir PET
Author(s) -
Pawlik Daria,
Leuzy Antoine,
Strandberg Olof,
Smith Ruben
Publication year - 2020
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 - 10.1002/alz.041800
Subject(s) - choroid plexus , hippocampal formation , voxel , hippocampus , nuclear medicine , medicine , cerebrospinal fluid , neuroscience , pathology , radiology , central nervous system , psychology
Background The hippocampus is an important region to study in Alzheimer’s disease (AD) since it is an early site of tau accumulation. Accurate quantification of hippocampal tau signal using the most common tau‐PET tracer 18 F‐flortaucipir is complicated, however, by off‐target binding in the adjacent choroid plexus. We here present a novel method for compensating for this off‐target choroid plexus signal. Method It has been shown that off‐target binding in the choroid plexus is higher using 18 F‐flortaucipir compared to the recently developed tau tracer 18 F‐RO948. Using data from 30 patients that underwent both 18 F‐flortaucipir and 18 F‐RO948 PET, we created a binary hippocampal mask where 18 F‐flortaucipir signal was higher than 18 F‐RO948 signal (Figure 1). This mask, representing voxels affected by off‐target binding from the choroid plexus, was then applied to 18 F‐flortaucipir PET‐scans from 145 patients across the AD‐spectrum. In this way the off‐target component was excluded. Results were analysed with and without partial volume error correction (PVEc/non‐PVEc). Results We found that unmasked hippocampal standardized uptake value ratios (SUVR) were significantly correlated to choroid plexus SUVRs using both non‐PVEc (r = 0.28, p < 0.001) and PVEc data (r = 0.18, p < 0.05) (Figure 2a‐b). After applying the mask these correlations disappeared (Figure 2c‐d). We next tested the diagnostic accuracy in separating cognitively impaired (CI) from cognitively unimpaired (CU) subjects using receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) from ROC analysis increased after masking from 0.79 (95% C.I., 0.72–0.87) to 0.84 (95% C.I., 0.77–0.91) for non‐PVEc data, and from 0.80 (95% C.I., 0.72–0.87) to 0.83 (95% C.I., 0.77–0.90) for PVEc data (Figure 3). Correlations between 18 F‐flortaucipir hippocampal SUVR and MMSE improved significantly for masked vs unmasked data, both with (r = ‐0.50 vs. r = ‐0.45) and without (r = ‐0.50 vs. r = ‐0.44) PVEc. Similar results were found using the ADAS‐Cog Delayed Word Recall test. Conclusion Correcting 18 F‐flortaucipir hippocampal SUVR for spill‐in from the choroid plexus using an off‐target mask is feasible, increases the diagnostic accuracy of hippocampal SUVRs and improves correlation with cognitive measures. Importantly, the proposed mask provided better results than applying PVE correction alone.