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Dynamic ¹¹C-PiB PET shows cerebrospinal fluid flow alterations in Alzheimer’s disease and multiple sclerosis

Lookup NU author(s): Professor David BrooksORCiD

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by Society of Nuclear Medicine, 2019.

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Abstract

Cerebrospinal fluid plays an important role in the clearance of solutes and maintenance of brain homeostasis. Early detection of diminished brain waste clearance could serve a vital role in the prevention, effective treatment, and early diagnosis of some neurological disorders, although a proper biomarker is missing. ¹¹C-PiB PET was recently proposed as a tool for detection of CSF clearance alterations in Alzheimer’s disease. The current study seeks to investigate the magnitude of ¹¹C-PiB PET signal in the lateral ventricles of an independent group of Alzheimer’s and mild cognitive impairment subjects. We have also evaluated multiple sclerosis as a model of disease with CSF clearance alterations without amyloid-beta tissue accumulation. A set of Alzheimer’s and mild cognitive impairment subjects and a set of multiple sclerosis subjects with matched healthy controls underwent MRI and dynamic ¹¹C-PiB PET. Manual lateral ventricle regions of interest were generated from MRI data. PET data was analysed using a simplified reference tissue model with cerebellum or a supervised reference region, for the Alzheimer’s and multiple sclerosis datasets, respectively. Magnitude of ¹¹C-PiB signal in the lateral ventricles was calculated as area under curve from 35 to 80 minutes and standard uptake value ratio (SUVR) from 50 to 70 minutes. Compartmental modelling analysis was performed on a separate dataset containing Alzheimer’s and matched healthy control data with an arterial input function to further understand the kinetics of the lateral ventricular ¹¹C-PiB signal and better interpret our results. Analysis of variance revealed significant group differences in lateral ventricular SUVR across the Alzheimer’s, mild cognitive impairment, and healthy control groups (p=0.004). Additional pairwise comparisons revealed significantly lower lateral ventricular SUVR in Alzheimer’s disease compared to healthy controls (p<0.001) and compared to mild cognitive impairment (p=0.029). Lateral ventricular SUVR was also significantly lower in multiple sclerosis patients compared to healthy controls (p=0.008). Compartmental modelling analysis revealed significantly lower uptake rates of ¹¹C-PiB signal from the blood (p=0.005) and from the brain tissue (p=0.004) to the lateral ventricles in Alzheimer’s patients compared to healthy controls. This analysis also revealed significantly lower clearance of ¹¹C-PiB signal out of the lateral ventricles in Alzheimer’s patients compared to healthy controls (p=0.002). Overall, these results indicate that dynamic ¹¹C-PiB PET can be used to observe pathological changes in cerebrospinal fluid dynamics and that cerebrospinal fluid-mediated clearance is reduced in Alzheimer’s disease and multiple sclerosis compared to healthy controls.

Publication metadata

Author(s): Schubert JJ, Veronese M, Marchitelli L, Bodini B, Tonietto M, Stankoff B, Brooks DJ, Bertoldo A, Edison P, Turkheimer FE

Publication type: Article

Publication status: Published

Journal: Journal of Nuclear Medicine

Year: 2019

Volume: 60

Issue: 10

Pages: 1452-1460

Print publication date: 01/10/2019

Online publication date: 08/03/2019

Acceptance date: 20/02/2019

Date deposited: 27/02/2019

ISSN (print): 0161-5505

ISSN (electronic): 1535-5667

Publisher: Society of Nuclear Medicine

URL: https://doi.org/10.2967/jnumed.118.223834

DOI: 10.2967/jnumed.118.223834

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