Ultra-High Field MRI in Alzheimer’s Disease: Effective Transverse Relaxation Rate and Quantitative Susceptibility Mapping of Human Brain In Vivo and Ex Vivo compared to Histology

Article type: Research Article

Authors: Tuzzi, Elisa^{a; b; *} | Balla, David Z.^c | Loureiro, Joana R.A.^{a; b; d} | Neumann, Manuela^{e; f} | Laske, Christoph^{f; g} | Pohmann, Rolf^a | Preische, Oliver^{f; g} | Scheffler, Klaus^{a; b} | Hagberg, Gisela E.^{a; b}

Affiliations: [a] Department for High Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tübingen, Germany | [b] Department for Biomedical Magnetic Resonance, Eberhard Karl’s University, Tübingen and University Hospital, Tübingen, Germany | [c] Department for Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Tübingen, Germany | [d] Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, CA, USA | [e] Department of Neuropathology, University Hospital, Tübingen, Germany | [f] German Center for Neurodegenerative Diseases (DZNE) Tübingen, Germany | [g] Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany

Correspondence: [*] Correspondence to: Elisa Tuzzi, MSc, Biomedizinische Magnetresonanz, Otfried Müller Str. 51, 72076, Tübingen, Germany. Tel.: 07071/29 87385; E-mail: [email protected].

Abstract: Alzheimer’s disease (AD) is the most common cause of dementia worldwide. So far, diagnosis of AD is only unequivocally defined through postmortem histology. Amyloid plaques are a classical hallmark of AD and amyloid load is currently quantified by Positron Emission tomography (PET) in vivo. Ultra-high field magnetic resonance imaging (UHF-MRI) can potentially provide a non-invasive biomarker for AD by allowing imaging of pathological processes at a very-high spatial resolution. The first aim of this work was to reproduce the characteristic cortical pattern previously observed in vivo in AD patients using weighted-imaging at 7T. We extended these findings using quantitative susceptibility mapping (QSM) and quantification of the effective transverse relaxation rate (R2*) at 9.4T. The second aim was to investigate the origin of the contrast patterns observed in vivo in the cortex of AD patients at 9.4T by comparing quantitative UHF-MRI (9.4T and 14.1T) of postmortem samples with histology. We observed a distinctive cortical pattern in vivo in patients compared to healthy controls (HC), and these findings were confirmed ex vivo. Specifically, we found a close link between the signal changes detected by QSM in the AD sample at 14.1T and the distribution pattern of amyloid plaques in the histological sections of the same specimen. Our findings showed that QSM and R2* maps can distinguish AD from HC at UHF by detecting cortical alterations directly related to amyloid plaques in AD patients. Furthermore, we provided a method to quantify amyloid plaque load in AD patients at UHF non-invasively.

Keywords: Alzheimer’s disease, amyloid-β, amyloid plaque load, biomarkers, effective transverse relaxation rate, histology, quantitative susceptibility mapping, ultra-high field

DOI: 10.3233/JAD-190424

Journal: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1481-1499, 2020