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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.

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organization
publishing date
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
  • scopus:85088992562
  • pmid:32711062
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
2020-08-19 08:50:36
@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 &lt; 0.001, r = 0.28) and PVEc data (p &lt; 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 &lt; 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 &lt; 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 &lt; 0.001) and with (r = −0.454 vs. r = −0.503, p &lt; 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},
  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},
}