Development of a 3D-VR Structural Analysis Software Ecosystem for SCI/D Research

我们提出的小型项目的目标是：1)开发更高效、更易于访问和更准确的3D 使用虚拟现实(VR)和神经数据无边界(NWB)数据标准的结构分析工作流， 2)将此软件/硬件生态系统实施到我们当前的神经病理学SCI/D研究计划中 疼痛和痉挛。通过开发3D-VR结构分析软件生态系统(3D-VR SASE)，我们将 大力拓展本中心未来翻译研究的实验范围和能力。我们会 为实现本项目的目标，在两个具体目标上进行实验。 在具体目标1中，我们将建立一个基于VR的三维结构分析软件环境(3D-VR SASE) 这将扩大我们研究树突棘可塑性异常的动态变化的能力 SCI/D。我们的退伍军人管理局中心已经运行了成像系统，使我们能够执行大量 中枢神经系统损伤的解剖学研究。然而，我们的项目轨迹现在已经严重超出了容量 这些系统中，没有满足我们需求的商业工具，也没有正在开发中的商业工具。因此，要扩展 能力，我们将开发更快、更准确的重建/可视化 硬件/软件生态系统与我们中心建立的NWB数据标准解决方案。 在具体目标2中，我们将对3D-VR SASE平台进行验证。我们使用公开的可用来演示它的效用 并使用转基因报告小鼠的脊髓组织对树突棘进行研究。 我们将利用该分析平台进行两个实验研究。首先，我们将重建神经元图像 来自王冠挑战的堆栈，这是一项公共神经科学比赛，旨在鼓励 改进神经元形态追踪的算法方法的发展。王冠挑战 提供高质量的光学显微镜图像和既定的规格，使我们能够对我们的VR评分 对照“黄金标准”跟踪使用准确度度量的跟踪。第二，我们将进行回溯性研究 死后脊髓组织中树突棘的大动态范围(WDR)背角神经元的研究 来自我们之前的研究。WDR神经元之所以引起人们的兴趣，是因为它们在提升中投射纤维 脊髓丘脑束，是通往丘脑VPL伤害性处理区的主要痛觉通路。另外， WDR神经元中树突棘发育不良与神经病理性疼痛有关。 总而言之，该项目将开发3D-VR SASE工作流程，以提高分析速度，3D 可视化和神经解剖重建，并执行NWB数据标准。灵活性和 3D-VR SASE平台的广泛应用将促进我们目前的SCI/D研究计划以及研究 在美国退伍军人中也很普遍的其他慢性疾病的神经解剖病理学，例如， 阿尔茨海默病、创伤后应激障碍、多发性硬化症、脑损伤。总体而言，我们预计这项工作将有力地扩大我们中心的 未来翻译研究的实验范围和能力。

The goal of our proposed Small Project is: 1) to develop a more efficient, accessible, and accurate 3D structural analysis workflow using virtual reality (VR) and the Neurodata Without Borders (NWB) data standard, and 2) to implement this software/hardware ecosystem into our current SCI/D research program in neuropathic pain and spasticity. By developing this 3D-VR Structural Analysis Software Ecosystem (3D-VR SASE), we will powerfully expand our Center's experimental reach and capacity for translational studies in the future. We will carry out experiments in two Specific Aims to address the goal of this Project. In Specific Aim 1, we will establish a VR-based 3D structural analysis software environment (3D-VR SASE) that will expand our ability to investigate the dynamic changes in abnormal dendritic spine plasticity associated SCI/D. Our VA Center already operates imaging systems that have allowed us to perform a multitude of anatomical studies of the injured CNS. However, our project trajectory has now severely outpaced the capacity of these systems, and no commercial tools for our needs are available or in-development. Thus, to expand the capabilities of our current hardware, we will develop a faster, more accurate reconstruction/visualization hardware/software ecosystem with the established NWB data standard solution in our Center. In Specific Aim 2, we will validate the 3D-VR SASE platform. We demonstrate its utility using publicly available neuronal datasets and perform a study of dendritic spines using spinal cord tissue of transgenic reporter mice. We will perform two experimental studies with the analysis platform. First, we will reconstruct neuronal image stacks from the DIADEM challenge, which is a public neuroscience competition designed to encourage the development of algorithmic methods for improved neuron morphological tracing. The DIADEM challenge provides high-quality light-microscopy images with established specifications that allow us to score our VR traces using metrics of accuracy against a “gold standard” trace. Second, we will perform a retrospective study of dendritic spines in wide-dynamic range (WDR) dorsal horn neurons in post-mortem spinal tissue collected from our previous study. WDR neurons have been of interest because they project fibers in the ascending spinothalamic tract, a major pain pathway to the thalamic VPL nociceptive processing region. Additionally, dendritic spine dysgenesis in WDR neurons has been associated with neuropathic pain. In summary, this project will develop the 3D-VR SASE workflow that increases analytical speed, 3D visualization and neuroanatomical reconstruction, and implements the NWB data standard. The flexibility and broad utility of the 3D-VR SASE platform will facilitate our current SCI/D research program as well as the study of neuroanatomical pathologies in other chronic diseases that are also prevalent among US Veterans, e.g., Alzheimer's disease, PTSD, MS, TBI. Overall, we expect this work will powerfully expand our Center's experimental reach and capacity for translational studies in the future.