Computed tomography of amyloid plaques in a mouse model of Alzheimer's disease using diffraction enhanced imaging

Abstract

Our understanding of early development in Alzheimer's disease (AD) is clouded by the scale at which the disease progresses; amyloid beta (Aβ) plaques, a hallmark feature of AD, are small (∼50 μm) and low contrast in diagnostic clinical imaging techniques. Diffraction enhanced imaging (DEI), a phase contrast x-ray imaging technique, has greater soft tissue contrast than conventional radiography and generates higher resolution images than magnetic resonance microimaging. Thus, in this proof of principle study, DEI in micro-CT mode was performed on the brains of AD-model mice to determine if DEI can visualize Aβ plaques. Results revealed small nodules in the cortex and hippocampus of the brain. Histology confirmed that the features seen in the DEI images of the brain were Aβ plaques. Several anatomical structures, including hippocampal subregions and white matter tracks, were also observed. Thus, DEI has strong promise in early diagnosis of AD, as well as general studies of the mouse brain.

Variability in contrast agent uptake by different but similar stem cell types

“…15,[17][18][19][20] However, the sensitivity of MRI is limited when compared with other imaging modalities such as X-ray computed tomography (CT), positron emission tomography (PET) and optical imaging. [21][22][23] In order to detect cells by MRI, it is necessary to pre-label them with MR-visible contrast agents. The majority of studies have used iron oxide-based nanoparticles (NPs) due to their relatively high sensitivity and their acceptable biocompatibility.…”

Amyloid-β imaging with PET in Alzheimer’s disease: is it feasible with current radiotracers and technologies?

“…In this calculation, we take the average radius of the sphere to be 25 µm [36]. Now assume that a voxel with no amyloid activity (i.e., background only) has unit concentration.…”

“…This effect is especially severe for structures that are less than 2.5 times the spatial resolution of the PET system, as measured by the full-width at half-maximum [35]. Since amyloid plaques are, on average, approximately 50 µm in diameter and the spatial resolution of PET is normally in the range of 2 to 3 mm for high-resolution systems and 5 to 7 mm for standard scans, the partial-volume effect should theoretically be factored heavily into amyloid imaging and should not be overlooked [36,37]. And yet Wong et al explicitly state that in a phase I clinical study of florbetapir partial-volume correction was not undertaken in the analysis of data [6].…”

A Dedicated Micro-Tomography Beamline For The Australian Synchrotron

“…It will be well suited for imaging small tissue samples and samples from small animal models of human disease. Excellent data have already been obtained at similar facilities overseas for many applications such as imaging Alzheimer's plaques [1] and microstructure of bone [2] (see also Figure 1). The high throughput capability will enable scans of large numbers of samples in order to generate the statistical validation required in biomedical studies …”