Exploration of cortical ß-Amyloid load in Alzheimer’s disease using quantitative susceptibility mapping at 9.4T

Early detection of β-Amyloid (Aβ) deposits in Alzheimer’s disease (AD) patients may enable treatment in the early stages of the disease. To date, there are no validated, specific, and non-invasive routines for early Aβ detection which are suitable for clinical practice. Ultra-high resolution quantitative susceptibility mapping (QSM) at 14.1T has previously shown different contrasts in cortical areas of an AD sample that resembled distinct Aβ spatial patterns in histological sections of the same specimen. These contrasts appeared different in the QSM from a healthy control (HC) sample where, instead, no plaques were detected. In a few cases, this distinction in the cortical magnetic effects (para- and diamagnetic) between AD and HC was also observed in vivo using ultra- high resolution single-echo Acquisition Weighted (AW) gradient echo MRI at 9.4T. Based on this evidence, a method to quantify the paramagnetic and diamagnetic effects of Aβ to possibly distinguish between AD and HC was developed. In this study, we extended those results and explored the ability to use QSM to estimate β-Amyloid plaque load in the cortex of 7 elderly patients with early AD and 7 healthy age-matched HC. Besides ultra-high resolution AW images, we acquired lower resolution multi-echo (MTE) data and compared the previously used RESHARP- based method for background removal (“AW-filter”, with a high Tikhonov term and a small kernel size) with a method widely used in the literature (“mild-filter”, with a low-regularization term and a large kernel size) for the MTE processing. Paramagnetic and diamagnetic QSM changes were assessed in 16 cortical areas. All methods enabled the detection of regions with high QSM values (up to 45 ppb in AD and up to 25 ppb in HC) and known as early Aβ accumulation areas in AD progression. A distinct cortical pattern was observed at both spatial resolutions using the AW-filter. This was not the case with the mild-filter at the lower resolution. AW-QSM outperformed MTE maps with the AW-filter for the detection of areas with prominent cortical paramagnetic effects, including regions where Aβ accumulation happens in the earliest AD stages, such as the precuneus and posterior cingulate cortex. Diamagnetic changes were more prominent than the paramagnetic effects regardless of the spatial resolution used and this difference was further enhanced with the mild-filter. This explorative study points toward the development of more accessible clinical methods to non-invasively detect effects of Aβ accumulation in AD patients by exploring cortical features that can be detected by ultra-high field QSM at different spatial resolutions. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the EU-LAC Foundation [Grant #16/T01-0118] and the German Research Foundation Max Planck Society ERC. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics Review Board of the Eberhard Karl′s University of Tübingen I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.