Non-invasive visualization of amyloid-beta deposits in Alzheimer amyloidosis mice using magnetic resonance imaging and fluorescence molecular tomography

Abstract

Abnormal cerebral accumulation of amyloid-beta peptide (Aβ) is a major hallmark of Alzheimer’s disease. Non-invasive monitoring of Aβ deposits enables assessing the disease burden in patients and animal models mimicking aspects of the human disease as well as evaluating the efficacy of Aβ-modulating therapies. Previous in vivo assessments of plaque load have been predominantly based on macroscopic fluorescence reflectance imaging (FRI) and confocal or two-photon microscopy using Aβ-specific imaging agents. However, the former method lacks depth resolution, whereas the latter is restricted by the limited field of view preventing a full coverage of the large brain region. Here, we utilized a fluorescence molecular tomography (FMT)-magnetic resonance imaging (MRI) pipeline with the curcumin derivative fluorescent probe CRANAD-2 to achieve full 3D brain coverage for detecting Aβ accumulation in the arcAβ mouse model of cerebral amyloidosis. A homebuilt FMT system was used for data acquisition, whereas a customized software platform enabled the integration of MRI-derived anatomical information as prior information for FMT image reconstruction. The results obtained from the FMT-MRI study were compared to those from conventional planar FRI recorded under similar physiological conditions, yielding comparable time courses of the fluorescence intensity following intravenous injection of CRANAD-2 in a region-of-interest comprising the brain. In conclusion, we have demonstrated the feasibility of visualizing Aβ deposition in 3D using a multimodal FMT-MRI strategy. This hybrid imaging method provides complementary anatomical, physiological and molecular information, thereby enabling the detailed characterization of the disease status in arcAβ mouse models, which can also facilitate monitoring the efficacy of putative treatments targeting Aβ.