Improvement of Microscopic MR Imaging of Amyloid Plaques with Targeting and Non-Targeting Contrast Agents

Overaccumulation of β-amyloid in the brain is believed to be a primary event in the development of Alzheimer's disease (AD). This amyloid is the target of drugs currently under development for the treatment of AD, which makes imaging amyloid plaques essential. Magnetic resonance imaging (MRI) has the resolution required to resolve these microscopic lesions (∼ 50 μm). In the absence of any contrast agent, the source of MR contrast in the amyloid plaques comes from the accumulation of iron, which shows as hypointense spots in T2, T2* or susceptibility-weighted images. Iron deposition in the brain is an age-related phenomenon and its accumulation occurs mainly in iron-rich regions. For plaques weakly loaded with iron, whose detection is much more challenging, the use of exogenous contrast agents (CA) becomes necessary. This article describes (1) targeted CAs made of a paramagnetic element like Gadolinium linked to a pharmacophore that targets amyloid, and (2) non-targeted CAs, an alternative to enhance amyloid plaque visualization. A background on CAs is also presented, and current issues related to contrast-enhanced MR imaging, including difficulties in delivering these agents across the blood-brain barrier, are also discussed.