Improved Imaging of an MR Molecular Agent Using Driven Feedback Contrast Enhancement

Millikelvin Technologies, Llc, Marblehead MA

Investigators

Abstract

Project Summary Amyloid-targeting radioactive PET agents have revolutionized screening of Alzheimer?s Disease (AD) patients. Amyloid PET agents (e.g. florbetapir) have enabled definitive rule-out of the disease, and patient selection for the testing of anti-amyloid therapies. However, PET requires administration of a radioactive tracer. An MRI based agent would enable lower cost, more accessible and safer imaging for screening and longitudinal therapeutic monitoring. Recently a low toxicity nanoparticle molecular imaging agent named ADx, designed for MR imaging of amyloid plaque, has been developed. The ADx nanoparticle is a liposome containing targeting ligands and a high density of gadolinium (Gd). The ligands bind to A? fibrils associated with amyloid plaque in the brain, while the role of the Gd is to enhance MR image contrast between protons located in tissue near the ADx and those located farther away in the body. ADx is a promising molecular MR imaging agent that can be used to image amyloid plaques in the brain, without subjecting the patient to a radioactive burden. Work to date on ADx imaging of amyloid plaques has all been conducted at 1 Tesla. This is because the nanoparticle, like many Gd liposomal structures, is most effective at producing image contrast at relatively low field. This has hampered research on the nanoparticle because most clinical machines operate at higher fields of 1.5 Tesla to 3 Tesla; unless addressed, it will also impact potential translation to humans. The present proposal exploits accelerated radiation damping (ARD) using driven feedback to improve imaging of a Gd liposomal agent such as ADx. Under such conditions, the magnetization vector of the protons is rotated back towards (or away from) equilibrium at a rate that is under operator control. The degree of change in the proton magnetization vector depends on the linewidth of the protons. The ADx nanoparticle produces strong local changes in proton linewidth. Hence protons near the nanoparticle?ie, near the amyloid plaque to which the nanoparticle is bound-- will have much less of their magnetization vector changed as a result of establishing ARD conditions. This will produce strong contrast between them and protons in the body located farther away. This will be the first application of feedback driven ARD to improve image contrast on a molecular targeting agent. Significantly, in the MKT approach, feedback driven contrast is complementary, not competitive, to any T1 weighting also used to provide contrast. Thus it will serve to amplify existing T1 contrast produced by the ADx nanoparticle.