Imaging beta amyloid aggregation and iron accumulation in Alzheimer's disease using quantitative susceptibility mapping MRI

• Published in: NeuroImage (Orlando, Fla.) Vol. 191; pp. 176 - 185
• Main Authors: Gong, Nan-Jie, Dibb, Russell, Bulk, Marjolein, van der Weerd, Louise, Liu, Chunlei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2019; Elsevier Limited
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - analysis; Amyloid precursor protein; Animals; Beta amyloid; Biomarkers; Brain Mapping - methods; Humans; Image Processing, Computer-Assisted - methods; Iron; Iron - analysis; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Magnetic susceptibility; Mapping; Mice; Mice, Transgenic; Morphology; Neurodegenerative diseases; Neurofibrillary tangles; Neuroimaging; Neuroimaging - methods; Pathology; Peptide mapping; Peptides; Plaque, Amyloid - diagnostic imaging; Plaque, Amyloid - pathology; Proteins; Senile plaques; Transgenic mice; β-Amyloid; Beta amyloid; Iron; Magnetic resonance imaging; Alzheimer's disease; Magnetic susceptibility
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2019.02.019

Beta amyloid is a protein fragment snipped from the amyloid precursor protein (APP). Aggregation of these peptides into amyloid plaques is one of the hallmarks of Alzheimer's disease. MR imaging of beta amyloid plaques has been attempted using various techniques, notably with T2* contrast. The non-invasive detectability of beta amyloid plaques in MR images has so far been largely attributed to focal iron deposition accompanying the plaques. It is believed that the T2* shortening effects of paramagnetic iron are the primary source of contrast between plaques and surrounding tissue. Amyloid plaque itself has been reported to induce no magnetic susceptibility effect. We hypothesized that aggregations of beta amyloid would increase electron density and induce notable changes in local susceptibility value, large enough to generate contrast relative to surrounding normal tissues that can be visualized by quantitative susceptibility mapping (QSM) MR imaging. To test this hypothesis, we first demonstrated in a phantom that beta amyloid is diamagnetic and can generate strong contrast on susceptibility maps. We then conducted experiments on a transgenic mouse model of Alzheimer's disease that is known to mimic the formation of human beta amyloid but without neurofibrillary tangles or neuronal death. Over a period of 18 months, we showed that QSM can be used to longitudinally monitor beta amyloid accumulation and accompanied iron deposition in vivo. Individual beta amyloid plaque can also be visualized ex vivo in high resolution susceptibility maps. Moreover, the measured negative susceptibility map and positive susceptibility map could provide histology-like image contrast for identifying deposition of beta amyloid plaques and iron. Finally, we demonstrated that the diamagnetic susceptibility of beta amyloid can also be observed in brain specimens of AD patients. The ability to assess beta amyloid aggregation non-invasively with QSM MR imaging may aid the diagnosis of Alzheimer's disease. •We demonstrated in a phantom experiment that beta amyloid has diamagnetic susceptibility contrary to previous hypothesis.•This diamagnetic susceptibility can be measured and used to monitor longitudinal accumulation of beta amyloid in a mouse model and even visualize individual plaques.•The diamagnetic susceptibility map provided image contrast for identifying dominating magnetic sources of beta amyloid plaques, which were validated by histology.•The ability to image and quantify beta amyloid aggregation non-invasively with MRI may aid the diagnosis of Alzheimer’s disease.