Published May 12, 2022 | Version v1
Journal article Open

Impact of cerebral blood flow and amyloid load on SUVR bias

  • 1. Amsterdam UMC, Vrije Universiteit Amsterdam, Radiology and Nuclear Medicine, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
  • 2. IXICO Plc, London, UK
  • 3. NIMTLab, Faculty of Medicine, Geneva University, Geneva, Switzerland Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals, Geneva, Switzerland
  • 4. Edinburgh Imaging, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
  • 5. Amsterdam UMC, Vrije Universiteit Amsterdam, Radiology and Nuclear Medicine, Amsterdam Neuroscience, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands UCL, Institutes of Neurology and Healthcare Engineering, London, UK
  • 6. Barcelonaβeta Brain Research Centre, Pasqual Maragall Foundation, Barcelona, Spain Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain

Description

Abstract:

Background: Despite its widespread use, the semi-quantitative standardized uptake value ratio (SUVR) may be biased compared with the distribution volume ratio (DVR). This bias may be partially explained by changes in cerebral blood flow (CBF) and is likely to be also dependent on the extent of the underlying amyloid-β (Aβ) burden. This study aimed to compare SUVR with DVR and to evaluate the effects of underlying Aβ burden and CBF on bias in SUVR in mainly cognitively unimpaired participants. Participants were scanned according to a dual-time window protocol, with either [18F]flutemetamol (N = 90) or [18F]florbetaben (N = 31). The validated basisfunction-based implementation of the two-step simplified reference tissue model was used to derive DVR and R1 parametric images, and SUVR was calculated from 90 to 110 min post-injection, all with the cerebellar grey matter as reference tissue. First, linear regression and Bland–Altman analyses were used to compare (regional) SUVR with DVR. Then, generalized linear models were applied to evaluate whether (bias in) SUVR relative to DVR could be explained by R1 for the global cortical average (GCA), precuneus, posterior cingulate, and orbitofrontal region.

Results: Despite high correlations (GCA: R2 ≥ 0.85), large overestimation and proportional bias of SUVR relative to DVR was observed. Negative associations were observed between both SUVR or SUVRbias and R1, albeit non-significant.

Conclusion: The present findings demonstrate that bias in SUVR relative to DVR is strongly related to underlying Aβ burden. Furthermore, in a cohort consisting mainly of cognitively unimpaired individuals, the effect of relative CBF on bias in SUVR appears limited.

Notes

This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115952. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA. This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained herein.

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Funding

AMYPAD – Amyloid imaging to Prevent Alzheimer’s Disease – Sofia ref.: 115952 115952
European Commission
EMIF – European Medical Information Framework 115372
European Commission