Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

Simon J Schreiner; Xinyang Liu; Anton F Gietl; Michael Wyss; Stefanie C Steininger; Esmeralda Gruber; Valerie Treyer; Irene B Meier; Andrea M Kälin; Sandra E Leh; Alfred Buck; Roger M Nitsch; Klaas P Pruessmann; Christoph Hock; Paul G Unschuld

doi:10.3389/fnagi.2014.00240

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

Front Aging Neurosci. 2014 Sep 9:6:240. doi: 10.3389/fnagi.2014.00240. eCollection 2014.

Authors

Affiliations

¹ Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich Zürich, Switzerland.
² Department of Radiology, Harvard Medical School, Brigham and Women's Hospital Boston, MA, USA.
³ Department of Information Technology and Electrical Engineering, Institute for Biomedical Engineering, University of Zürich and ETH Zürich Zürich, Switzerland.
⁴ Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich Zürich, Switzerland ; Division of Nuclear Medicine, University of Zürich Zürich, Switzerland.
⁵ Division of Psychiatry Research and Psychogeriatric Medicine, University of Zürich Zürich, Switzerland ; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University Medical Center New York, NY, USA.
⁶ Division of Nuclear Medicine, University of Zürich Zürich, Switzerland.

Abstract

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity.

Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm-Bonferroni correction for multiple testing.

Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82).

Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD.

Keywords: 7 Tesla; FLAIR; MRI; PiB-PET; aging; amyloid beta.