Improving Choroid Plexus Segmentation in the Healthy and Diseased Brain: Relevance for Tau-PET Imaging in Dementia

Article type: Research Article

Authors: Tadayon, Ehsan^{a; *} | Moret, Beatrice^{a; b; c} | Sprugnoli, Giulia^{a; d} | Monti, Lucia^e | Pascual-Leone, Alvaro^{a; f; g; h} | Santarnecchi, Emiliano^{a; i; *} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Berenson-Allen Center for Noninvasive Brain Stimulation and Division for Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA | [b] Department of General Psychology, University of Padova, Padova, Italy | [c] Human Inspired Technology Research Centre, University of Padova, Padova, Italy | [d] Radiology Unit, Department of Medicine and Surgery, University of Parma, Parma, Italy | [e] Unit of Neuroimaging and Neurointervention, Santa Maria Alle Scotte Medical Center, Siena, Italy | [f] Hinda and Arthur Marcus Institute for Aging Research and Center for Memory Health, Hebrew SeniorLife, Boston, MA, USA | [g] Guttmann Brain Health Institute, Guttmann Institut, Universitat Autonoma, Barcelona, Spain | [h] Department of Neurology, Harvard Medical School, MA, USA | [i] Brain Investigation and Neuromodulation Laboratory, Department of Medicine, Surgery and Neuroscience, Unit of Neurology and Clinical Neurophysiology, Siena Medical School, Siena, Italy

Correspondence: [*] Correspondence to: Ehsan Tadayon, MD, and Emiliano Santarnecchi, PhD, Berenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. E-mails: [email protected]; [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wpcontent/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Recent studies have revealed the possible role of choroid plexus (ChP) in Alzheimer’s disease (AD). T1-weighted MRI is the modality of choice for the segmentation of ChP in humans. Manual segmentation is considered the gold-standard technique, but given its time-consuming nature, large-scale neuroimaging studies of ChP would be impossible. In this study, we introduce a lightweight segmentation algorithm based on the Gaussian Mixture Model (GMM). We compared its performance against manual segmentation as well as automated segmentation by Freesurfer in three separate datasets: 1) patients with structural MRIs enhanced with contrast (n = 19), 2) young healthy subjects (n = 20), and 3) patients with AD (n = 20). GMM outperformed Freesurfer and showed high similarity with manual segmentation. To further assess the algorithm’s performance in large scale studies, we performed GMM segmentations in young healthy subjects from the Human Connectome Project (n = 1,067), as well as healthy controls, mild cognitive impairment (MCI), and AD patients from the Alzheimer’s Disease Neuroimaging Initiative (n = 509). In both datasets, GMM segmented ChP more accurately than Freesurfer. To show the clinical importance of accurate ChP segmentation, total AV1451 (tau) PET binding to ChP was measured in 108 MCI and 32 AD patients. GMM was able to reveal the higher AV1451 binding to ChP in AD compared with MCI. Our results provide evidence for the utility of the GMM in accurately segmenting ChP and show its clinical relevance in AD. Future structural and functional studies of ChP will benefit from GMM’s accurate segmentation.

Keywords: Alzheimer’s disease, choroid plexus, magnetic resonance imaging, tau PET

DOI: 10.3233/JAD-190706

Journal: Journal of Alzheimer's Disease, vol. 74, no. 4, pp. 1057-1068, 2020