Compensating for choroid plexus based off-target signal in the hippocampus using 18F-flortaucipir PET
Pawlik, Daria LU
; Leuzy, Antoine
LU
; Strandberg, Olof
LU
and Smith, Ruben
LU
(2020)
In NeuroImage
221.
- Abstract
Purpose: The hippocampus is affected by tau pathology early in Alzheimer's disease (AD) development. Accurate quantification of hippocampal tau signal using the tau-PET tracer 18F-flortaucipir is complicated, however, by off-target binding in the adjacent choroid plexus. We here present a new method for compensating for this off-target choroid plexus signal. Methods: As off-target binding in the choroid plexus is known to be higher using 18F-flortaucipir compared to 18F-RO948, we created a binary hippocampal mask in template space where 18F-flortaucipir signal was higher than 18F-RO948, using data from 30 patients that underwent both 18F-flortaucipir and... (More)
Purpose: The hippocampus is affected by tau pathology early in Alzheimer's disease (AD) development. Accurate quantification of hippocampal tau signal using the tau-PET tracer 18F-flortaucipir is complicated, however, by off-target binding in the adjacent choroid plexus. We here present a new method for compensating for this off-target choroid plexus signal. Methods: As off-target binding in the choroid plexus is known to be higher using 18F-flortaucipir compared to 18F-RO948, we created a binary hippocampal mask in template space where 18F-flortaucipir signal was higher than 18F-RO948, using data from 30 patients that underwent both 18F-flortaucipir and 18F-RO948 PET. This mask, presumably representing hippocampal voxels affected by off-target binding from the choroid plexus, was then converted to native space and applied as an exclusion mask to 145 patients across the AD-spectrum scanned with 18F-flortaucipir. As an alternative approach exclusion masks were generated by expanding the choroid plexus ROI in native space. Results were analysed both without and with partial volume error correction (non-PVEc/PVEc). Results: Unmasked hippocampal standardized uptake value ratios (SUVR) were significantly correlated to choroid plexus SUVRs using both non-PVEc (p < 0.001, r = 0.28) and PVEc data (p < 0.05, r = 0.18). After applying the mask, however, these correlations disappeared. The diagnostic accuracy in separating cognitively impaired (CI) from cognitively unimpaired (CU) subjects improved after masking, from an AUC of 0.792 (95% C.I.,0.715–0.869) to 0.837 (95% C.I.,0.768–0.906) for non-PVEc data (p < 0.001), and from 0.798 (95% C.I.,0.722–0.873) to 0.834 (95% C.I.,0.766–0.903) for PVEc data (p < 0.001). The correlations to memory improved significantly for MMSE for unmasked vs. masked data both without (r = −0.440 vs. r = −0.499, p < 0.001) and with (r = −0.454 vs. r = −0.503, p < 0.001) PVEc. Similar results were found using the ADAS-Cog Delayed Word Recall test. Conclusion: Choroid plexus off-target binding interferes with the estimation of true hippocampal retention using 18F-flortaucipir PET. Using a mask to correct for this off-target signal, we improved the diagnostic accuracy of 18F-flortaucipir in the hippocampus and the correlation between 18F-flortaucipir hippocampal SUVR and cognitive measures.
(Less)
- author
- Pawlik, Daria
LU
; Leuzy, Antoine
LU
; Strandberg, Olof
LU
and Smith, Ruben
LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, Flortaucipir, Hippocampus, PET, Tau
- in
- NeuroImage
- volume
- 221
- article number
- 117193
- publisher
- Elsevier
- external identifiers
-
- pmid:32711062
- scopus:85088992562
- ISSN
- 1053-8119
- DOI
- 10.1016/j.neuroimage.2020.117193
- language
- English
- LU publication?
- yes
- id
- 49fc43bf-7bf2-49d9-b8f0-90600ec454a7
- date added to LUP
- 2020-08-11 11:33:32
- date last changed
- 2024-04-03 10:45:47
@article{49fc43bf-7bf2-49d9-b8f0-90600ec454a7,
abstract = {{<p>Purpose: The hippocampus is affected by tau pathology early in Alzheimer's disease (AD) development. Accurate quantification of hippocampal tau signal using the tau-PET tracer <sup>18</sup>F-flortaucipir is complicated, however, by off-target binding in the adjacent choroid plexus. We here present a new method for compensating for this off-target choroid plexus signal. Methods: As off-target binding in the choroid plexus is known to be higher using <sup>18</sup>F-flortaucipir compared to <sup>18</sup>F-RO948, we created a binary hippocampal mask in template space where <sup>18</sup>F-flortaucipir signal was higher than <sup>18</sup>F-RO948, using data from 30 patients that underwent both <sup>18</sup>F-flortaucipir and <sup>18</sup>F-RO948 PET. This mask, presumably representing hippocampal voxels affected by off-target binding from the choroid plexus, was then converted to native space and applied as an exclusion mask to 145 patients across the AD-spectrum scanned with <sup>18</sup>F-flortaucipir. As an alternative approach exclusion masks were generated by expanding the choroid plexus ROI in native space. Results were analysed both without and with partial volume error correction (non-PVEc/PVEc). Results: Unmasked hippocampal standardized uptake value ratios (SUVR) were significantly correlated to choroid plexus SUVRs using both non-PVEc (p < 0.001, r = 0.28) and PVEc data (p < 0.05, r = 0.18). After applying the mask, however, these correlations disappeared. The diagnostic accuracy in separating cognitively impaired (CI) from cognitively unimpaired (CU) subjects improved after masking, from an AUC of 0.792 (95% C.I.,0.715–0.869) to 0.837 (95% C.I.,0.768–0.906) for non-PVEc data (p < 0.001), and from 0.798 (95% C.I.,0.722–0.873) to 0.834 (95% C.I.,0.766–0.903) for PVEc data (p < 0.001). The correlations to memory improved significantly for MMSE for unmasked vs. masked data both without (r = −0.440 vs. r = −0.499, p < 0.001) and with (r = −0.454 vs. r = −0.503, p < 0.001) PVEc. Similar results were found using the ADAS-Cog Delayed Word Recall test. Conclusion: Choroid plexus off-target binding interferes with the estimation of true hippocampal retention using <sup>18</sup>F-flortaucipir PET. Using a mask to correct for this off-target signal, we improved the diagnostic accuracy of <sup>18</sup>F-flortaucipir in the hippocampus and the correlation between <sup>18</sup>F-flortaucipir hippocampal SUVR and cognitive measures.</p>}},
author = {{Pawlik, Daria and Leuzy, Antoine and Strandberg, Olof and Smith, Ruben}},
issn = {{1053-8119}},
keywords = {{Alzheimer's disease; Flortaucipir; Hippocampus; PET; Tau}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{NeuroImage}},
title = {{Compensating for choroid plexus based off-target signal in the hippocampus using <sup>18</sup>F-flortaucipir PET}},
url = {{http://dx.doi.org/10.1016/j.neuroimage.2020.117193}},
doi = {{10.1016/j.neuroimage.2020.117193}},
volume = {{221}},
year = {{2020}},
}