Quantitative Susceptibility Mapping of Amyloid-β Aggregates in Alzheimer’s Disease with 7T MR

Article type: Research Article

Authors: Tiepolt, Solveig^{a; 1; *} | Schäfer, Andreas^{b; f; 1} | Rullmann, Michael^{a; b} | Roggenhofer, Elisabeth^{b; g} | Netherlands Brain Bank^c | Gertz, Hermann-Josef^d | Schroeter, Matthias L.^{b; e} | Patt, Marianne^a | Bazin, Pierre-Louis^b | Jochimsen, Thies H.^a | Turner, Robert^b | Sabri, Osama^{a; 1} | Barthel, Henryk^{a; 1}

Affiliations: [a] Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany | [b] Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany | [c] Netherlands Institute for Neuroscience, Amsterdam, Netherlands | [d] Department of Psychiatry, University of Leipzig, Leipzig, Germany | [e] Clinic for Cognitive Neurology, University Leipzig, Germany | [f] Siemens Healthcare GmbH, Diagnostic Imaging, Magnetic Resonance, Research & Development, Erlangen, Germany | [g] LREN, Department for Clinical Neurosciences, CHUV, University of Lausanne, Lausanne, Switzerland

Correspondence: [*] Correspondence to: Solveig Tiepolt, MD, Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany. Tel.: +49 341 9718264; Fax: +49 341 9718009; E-mail: solveig.tiepolt@medizin.uni-leipzig.de.

Note: [1 ] These authors contributed equally to this work.

Abstract: Background:PET imaging is an established technique to detect cerebral amyloid-β (Aβ) plaques in vivo. Some preclinical and postmortem data report an accumulation of redox-active iron near Aβ plaques. Quantitative susceptibility mapping (QSM) at high-field MRI enables iron deposits to be depicted with high spatial resolution. Objective:Aim of this study was to examine whether iron and Aβ plaque accumulation is related and thus, whether 7T MRI might be an additive diagnostic tool to Aβ PET imaging. Methods:Postmortem human Alzheimer’s disease (AD) and healthy control (HC) frontal gray matter (GM) was imaged with 7T MRI which resulted in T1 maps and QSM. Aβ plaque load was determined by histopathology. In vivo, 10 Aβ PET-positive AD patients (74.1±6.0a) and 10 Aβ PET-negative HCs (67.1±4.4a) underwent 7T MR examination and QSM maps were analyzed. Severity of cognitive deficits was determined by MMSE. Results:Postmortem, the susceptibility of Aβ plaque-containing GM were higher than those of Aβ plaque-free GM (0.011±0.002 versus – 0.008±0.003 ppm, p < 0.001). In vivo, only the bilateral globus pallidus showed significantly higher susceptibility in AD patients compared to HCs (right: 0.277±0.018 versus – 0.009±0.009 ppm; left: 0.293±0.014 versus – 0.007±0.012 ppm, p < 0.0001). The pallidal QSM values were negatively correlated with those of the MMSE (r = – 0.69, p = 0.001). Conclusion:The postmortem study revealed significant susceptibility differences between the Aβ plaque-containing and Aβ plaque-free GM, whereas in vivo only the QSM values of the globus pallidus differed significantly between AD and HC group. The pallidal QSM values correlated with the severity of cognitive deficits. These findings encourage efforts to optimize the 7T-QSM methodology.

Keywords: Alzheimer’s disease, amyloid, iron accumulation, quantitative susceptibility mapping, 7T MRI

DOI: 10.3233/JAD-180118

Journal: Journal of Alzheimer's Disease, vol. 64, no. 2, pp. 393-404, 2018