Imaging research extended to map Alzheimer's disease

Prof. Ling-Jian Meng and his group are extending functional X-ray imaging techniques they developed for mapping trace metals in living animals to allow for 3-D imaging of iron, copper, and zinc in brain tissues of mice carrying Alzheimer’s disease.

The National Institutes of Health awarded Meng and his collaborators a $2M grant in 2018 to develop X-ray Fluorescence Emission Tomography (XFET) imaging techniques to map metal-based compounds used to enhance radiation therapy in brain cancer treatment. The system was designed to achieve dramatically improved sensitivity to a broad range of metal elements such as gold, palladium and hafnium that emit fluorescence X-rays. Nanoparticles containing those metals are thought to aid cancer therapy by enhancing cancer-specific X-ray absorption and by generating radio-dynamic effects to target cancer cells.

Now, with additional NIH support of about $700K, the scientists are modifying the XFET system to allow imaging of lighter metals – iron, copper and zinc – known to be important in the pathobiology of Alzheimer’s disease.

Many common neurodegenerative diseases, including Alzheimer’s, involve the misfolding and aggregation of a naturally occurring protein that eventually leads to progressive neuron deterioration. Unusual concentrations and distributions in the brain of naturally occurring iron, copper, and zinc are associated with Alzheimer’s, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), prion diseases, and Huntington’s disease.

However, the precise roles of metals in the disease progression are largely unknown. Metals such as iron and copper are capable of forming reactive oxygen species that can damage proteins, DNA, and lipids through oxidative modification. While specific proteins usually chaperone these naturally occurring metals through the cell to minimize undesirable outcomes, disruptions to the process can be toxic. The precise mechanism that causes disruptions remains an active area of research, especially in the context of diagnosing and treating neurodegenerative diseases.

Meng and his group will develop a novel X-ray fluorescence emission tomography (PXFET) technique in which polarized X-rays are generated to excite target metals in the object. A geometrically optimized emission tomography system will be designed to collect the fluorescence X-ray signals. This technique potentially can offer a much lowered detection limit for trace metals when compared to the current benchtop XFET techniques.

Additionally, the researchers are developing a unique single photon emission computed tomography (SPECT) magnetic resonance (MR) imaging platform for in-vivo 3-D autoradiography of genetic mouse models for Alzheimer’s. The system, based on a novel artificial compound eye (ACE) design, would enable new imaging procedures not feasible with the current generation of SPECT instrumentations. The Meng group is currently working to make the MR/SPECT technology more robust and user-friendly for wider dissemination of this technology to regular biology labs carrying out molecular imaging research.