Multimodal probes for multiscale calcium imaging

用于多尺度钙成像的多模态探针

基本信息

批准号：
10154098
负责人：
Alan Jasanoff
金额：
$ 23.18万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10154098
关键词：
Acids Analytical Chemistry BRAIN initiative Behavior Behavioral Brain Calcium Calcium Binding Calcium Signaling Cell Fractionation Cells Charge Chelating Agents Chemicals Complex Contrast Media Development Esters Ethane Fluorescence Functional Magnetic Resonance Imaging Gadolinium Goals Histology Image In Vitro Individual Ionophores Ions Lanthanoid Series Elements Magnetic Resonance Imaging Magnetism Measurement Measures Mediating Metals Methodology Methods Modality Molecular Morphologic artifacts Neurons Optics Performance Permeability Porphyrins Property Rattus Reporter Research Personnel Resolution Role Signal Transduction Source Techniques Technology Testing Texaphyrin Titrations Transition Elements Validation Variant Yttrium base design experimental study fluorescence imaging fluorophore hydrophilicity imaging agent imaging capabilities imaging modality in vivo innovation multimodality neurodevelopment neuroimaging non-invasive imaging novel novel strategies optical imaging optoacoustic tomography photoacoustic imaging relating to nervous system response sensor spatiotemporal tool validation studies

项目摘要

A major goal of the BRAIN Initiative is to promote the development of neural activity measurement tools that bridge between spatial scales, so that the processing roles of individual neurons and microcircuits can be related to broader regional or brain-wide dynamics. Here we propose to create novel chemical probes of neuronal cal- cium signaling that will enable cross-modal comparison of readouts obtained at multiple scales, using both inva- sive and noninvasive imaging methods. Using these multifunctional probes, investigators will be able to record wide-field neural activity dynamics at varying depths and spatiotemporal resolutions from well-defined molecular sources that permit precise interpretation, without the potential for artifacts associated with parallel application of disparate probe modalities. This will be particularly valuable for validation and use of the probes in noninvasive imaging modalities, for which probe technologies are still relatively rudimentary and untested, and relating wide- field signals to micron-resolution optical results could be especially informative. The new probes we will create are derived from a cell-permeable aromatic chelator called texaphryin (Tex). Complexes of Tex variants with different metal ions function as potent fluorophores, photoacoustic reporters, and T1-weighted contrast agents for magnetic resonance imaging (MRI). We recently discovered that combining paramagnetic Tex complexes with calcium-responsive moieties such as 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) results in strong calcium-dependent contrast changes, thus providing a promising basis for synthesis of sensors suitable for simultaneous or parallel measurement by MRI, optical, and photoacoustic readouts. In this project, we will synthesize and optimize the multimodal sensors, evaluate their optical and magnetic imaging capabilities, and begin in vivo validation studies that directly exploit the unique advantages these novel probes offer. These experiments will establish a first-of-its-kind molecular platform with potentially powerful capability for multimodal analysis of neural activity dynamics across spatial and temporal scales in a variety of species and behavioral contexts.

大脑计划的主要目标是促进神经活动测量工具的开发空间尺度之间的桥梁，以便可以相关的单个神经元和微电路的处理作用到更广泛的区域或脑部动力学。在这里，我们提议创建神经元的新化学问题 CIUM信号传导将使用两种inva- Sive和无创成像方法。使用这些多功能问题，调查人员将能够记录在不同深度和时空分辨率的不同深度和时空分辨率下的宽视野神经活动动力学允许精确解释的来源，而无需与并行应用相关的伪影不同的探针方式。这对于验证和使用无创探针特别有价值成像方式，探针技术仍然相对较基本且未经测试，并且与广泛的相关微分分辨率光学结果的现场信号可能特别有用。我们将创建的新问题源自称为Texaphryin（Tex）的可渗透芳香螯合剂。 Tex变体的复合体不同的金属离子充当有效的荧光团，光声记者和T1加权对比剂用于磁共振成像（MRI）。我们最近发现，将顺磁性Tex复合物结合在一起钙反应部分，例如1,2-双（O-氨基苯基）乙烷-N，N，N'，N'-二乙酸（BAPTA）导致强烈依赖钙的对比变化，从而为合成传感器提供了希望的基础适用于MRI，光学和光声读数的同时或平行测量。在这个项目中，我们将合成和优化多模式传感器，评估其光学和磁成像功能，并开始进行体内验证研究，这些研究直接利用这些新型探针提供的独特优势。这些实验将建立一个具有潜在强大功能的多模式功能的第一分子平台分析各种物种和行为的空间和时间尺度跨时空尺度的神经活动动力学的分析上下文。