CIF: Small: Super-Resolution Imaging in a Heavily Scattering Environment Enabled by Spatiotemporal Data

点击翻译按钮获取中文摘要

In this project, a mathematical and computational framework will be developed to allow the precise location of signal emissions in a heavy scattering domain using sensor data measured at various locations as a function of time. While the application space can span all wave types, the primary focus of this project is to directly image neuron activity throughout the mammalian brain for the first time using fluorescence. It is currently impossible to image at a depth of much more than about one tenth of a millimeter in tissue using light, and other ways of measuring brain activity, including magnetic resonance imaging (MRI) of blood oxygen and of manganese, are unable to provide details of activity at the same time-scale as that of individual neuron activation. Therefore, despite multifaceted research efforts to date, much remains unknown about the brain. The project presents a path towards whole-brain imaging using spatio-temporal optical reporters designed to monitor changes in calcium ion concentrations associated with neuron activation. This approach has a substantial potential to impact neuroscience and the treatment of brain disorders. For instance, the effort could provide a means to obtain new information that is relevant for developing an understanding and hence a treatment of Alzheimer's disease and Parkinson's disease, as well as epilepsy. More generally, the project could lead to a means to image protein conformation inside tissue, thereby providing a window to many central nervous system diseases involving protein mis-folding and aggregation. The underlying principle to be investigated is the use of temporal data obtained at a set of spatial positions to obtain the precise locations of a large set of emitters in a complex, multiple scattering environment. Measured fluorescence from calcium reporters as a function of time and position around the brain provides the necessary spatio-temporal data that would allow the in-vivo imaging of neuron activity throughout a mammalian brain for the first time. A point fluorescent emitter constraint enables the description of the calcium ion reporters within a localization framework. Prior work suggests that a spatial resolution of tens of microns through centimeters of tissue may be achievable, allowing neuron-scale resolution in the brain. There are two primary aims. First, a high-resolution neuron activation reporter localization method for whole-brain imaging will be developed. Simulated and measured spatio-temporal data from realistic printed phantoms will be incorporated into a nonlinear optimization framework with a diffusion equation forward model and solved using a multi-resolution analysis, both in the photon-counting regime and where there is ample signal at the detectors. Second, data will be obtained from microscope measurements of neurons with calcium channel labeling. This will yield local signaling and prior model information that could be incorporated into an in-vivo approach. Neuron signaling data will also be obtained under controlled amounts of scatter to investigate localization efficacy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.