Spatial Frequency Domain Imaging: Applications in Preclinical Models of Alzheimer's Disease.

摘要

A clinical challenge in Alzheimer's disease (AD) is diagnosing and treating patients earlier, before symptoms of cognitive dysfunction occur. A good screening test would be sensitive to the AD brain pathology, safe, and cost-effective. Diffuse optical imaging, which measures how non-ionizing light is absorbed and scattered in tissue, may fulfill these three parameters. We imaged the brains of transgenic AD mouse models in vivo with a quantitative, camera-based, diffuse optical imaging technology called spatial frequency domain imaging (SFDI) to characterize near-infrared (650-970nm) optical biomarkers of AD. Compared to age-matched control mice, we found a decrease in light absorption — due to lower oxygenated and total hemoglobin concentrations in the brain — correlating to decreased blood vessel volume and density in histology. Light scattering also increased in AD mice, correlating to brain structural changes caused by neuron loss and activation of inflammatory cells. Furthermore, inhaled gas challenges revealed brain vascular function was diminished. To investigate how AD affects the small changes in blood perfusion caused by increased brain activity, we built a new SFDI system from a commercial light-emitting diode microprojector and off-the-shelf optical components and cameras to measure optical properties in the visible range (460-632nm). Our measurements showed a reduced amplitude and duration of blood vessel dilation to increased brain activity in the AD mice. Altogether, this work increased our understanding of AD pathogenesis, explored optical biomarkers of AD, and improved technology access to other research labs. These results and technologies can further be used to facilitate longitudinal drug therapy trials in mice and provide a roadmap to diffuse optical spectroscopy studies in humans.