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

CIF：小：时空数据支持的高散射环境中的超分辨率成像

• 批准号: 1909660
• 负责人: Kevin Webb
• 金额: $ 49.68万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1909660&HistoricalAwards=false
• 关键词: CIF; Small; Super; Resolution; Imaging

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.

在该项目中，将开发一个数学和计算框架，以使用在时间的函数上在各个位置测量的传感器数据在重散射域中的精确位置。虽然应用空间可以跨越所有波动类型，但该项目的主要重点是首次使用荧光直接对整个哺乳动物大脑的神经元活动进行成像。目前，不可能使用光在组织中的十分之一毫米和其他测量大脑活动的方法（包括血液氧和锰的磁共振成像（MRI）和锰的其他方法）无法提供与单个神经元激活相同的时间尺度上的活动详细信息。因此，尽管迄今为止进行了多方面的研究工作，但大脑仍然未知。该项目使用时空光学记者为全脑成像提供了一条途径，旨在监测与神经元激活相关的钙离子浓度的变化。这种方法具有影响神经科学和脑部疾病治疗的巨大潜力。例如，这种努力可以提供一种获得与发展理解，因此对阿尔茨海默氏病和帕金森氏病的治疗以及癫痫病有关的新信息的方法。更普遍地，该项目可能导致组织内部蛋白质构象的一种手段，从而为许多中枢神经系统疾病提供了一个窗口，涉及蛋白质误折叠和聚集。 要研究的基本原理是使用在一组空间位置获得的时间数据，以在复杂的多个散射环境中获得一组发射器的精确位置。从钙报告中测得的荧光作为大脑周围时间和位置的函数，提供了必要的时空数据，该数据将首次允许整个哺乳动物大脑的神经元活性进行体内成像。点荧光发射极约束可以在本地化框架内描述钙离子记者。先前的工作表明，可以通过厘米的组织空间分辨率可以实现，从而可以实现大脑的神经元尺度分辨率。有两个主要目标。首先，将开发用于全脑成像的高分辨率神经元激活报告方法。来自现实的印刷幻影的模拟和测量时空数据将与扩散方程式前进模型合并到非线性优化框架中，并使用多分辨率分析求解，包括在光子计数方案中，以及在检测器处有足够的信号。其次，将从具有钙通道标记的神经元的显微镜测量值获得数据。这将产生可以将可以纳入体内方法中的本地信号传导和先前的模型信息。神经元信号传导数据还将在受控数量的分散量下获得，以调查定位疗效。该奖项反映了NSF的法定任务，并认为使用基金会的知识分子优点和更广泛的影响审查标准，认为值得通过评估来获得支持。

项目成果

Localization of Fluorescent Targets in Deep Tissue With Expanded Beam Illumination for Studies of Cancer and the Brain

• DOI: 10.1109/tmi.2020.2972200
• 发表时间: 2020-07-01
• 期刊: IEEE TRANSACTIONS ON MEDICAL IMAGING
• 影响因子: 10.6
• 作者: Bentz, Brian Z.;Mahalingam, Sakkarapalayam M.;Webb, Kevin J.
• 通讯作者: Webb, Kevin J.

Eigenchannel analysis of super-resolution far-field sensing with a randomly scattering analyzer

使用随机散射分析仪进行超分辨率远场传感的特征通道分析

• DOI: 10.1103/physreva.107.023518
• 发表时间: 2023
• 期刊: Physical Review A
• 影响因子: 2.9
• 作者: Patel, Justin A.;Luo, Qiaoen;Webb, Kevin J.
• 通讯作者: Webb, Kevin J.

Multiresolution Localization With Temporal Scanning for Super-Resolution Diffuse Optical Imaging of Fluorescence

• DOI: 10.1109/tip.2019.2931080
• 发表时间: 2020-01-01
• 期刊: IEEE TRANSACTIONS ON IMAGE PROCESSING
• 影响因子: 10.6
• 作者: Bentz，Brian Z.;Lin，Dergan;Webb，Kevin J.
• 通讯作者: Webb，Kevin J.