AI-driven biomarker analysis of intact whole brains imaged at micron and sub-micron resolution

抽象的。全器官3D免疫组织化学正在给神经科学领域带来革命性的变化，使 对神经细胞和神经学标志物在健康人群大脑中的分布的前所未有的洞察 和疾病。LifeCanvas Technologies处于空间蛋白质组学新领域的前沿，提供了 整个器官保存、组织清除、免疫组织化学标记和成像的完整工作流程。 然而，这类研究的一个持续挑战是需要快速、可重复和严格地量化 来自整个器官成像工作的TB大小的数据集。虽然在应用人工智能方面取得了进展 智能(AI)工具，支持检测神经组织中的细胞和亚细胞标记，一刀切 由于生物分子的变化，算法不足以分析复杂的、信息丰富的大脑数据集 细胞中的表达模式(如核、胞浆、膜结合)和特定区域的异质性 密度和神经细胞类型。然而，以标记模式的子集为目标的人工智能驱动的算法可以 在提供足够的培训数据的情况下是有效的。LifeCanvas Technologies LCT处于最佳位置 开发高精度的算法，通过其对大容量的访问来服务于广泛的检测任务 包含多种标记表达模式的全器官图像数据的合同研究 组织和用户基础。LCT提议开发一个数据分析程序SmartAnalytics，该程序将 在用户友好的软件包中嵌入一套人工智能算法，以识别标记的细胞位置和 在细胞和亚细胞分辨率下描述整个大脑的形态特征。具体来说， LCT将使用完整的3D免疫标记小鼠大脑来设计人工智能算法，以检测成像的标记细胞 细胞分辨率，并生成用于分割亚微米图像的标记特征的进一步算法 决议。来自LCT合同研究组织和学术合作的数据将继续提供 返回以改进和扩展SmartAnalytics中可用的检测算法库，以及这些 开发将推动客户进一步采用和增强该软件的未来版本。 SmartAnalytics将指导用户完成模型应用、质量控制测试和生成输出 产品数据和汇总统计等。总而言之，SmartAnalytics将是一个不断发展的用户- 友好的工作流程执行程序，使神经科学家能够充分利用他们的3D图像数据， 推动在大脑功能、发育和疾病方面的新发现。

Abstract. Whole-organ 3D immunohistochemistry is revolutionizing the field of neuroscience, enabling unprecedented insight into the distribution of neural cells and neurological markers throughout the brain in health and disease. LifeCanvas Technologies is at the forefront of the new field of spatial proteomics, providing a complete workflow for whole-organ preservation, tissue clearing, immunohistochemical labeling, and imaging. Nevertheless, an ongoing challenge for such studies is the need to rapidly, reproducibly and rigorously quantify terabyte-sized datasets from whole-organ imaging efforts. While progress has been made in applying Artificial Intelligence (AI) tools to enable detection of cellular and sub-cellular markers in neural tissue, one-size-fits-all algorithms are inadequate for analyzing complex, information-rich brain datasets due to varying biomolecular expression patterns (e.g. nuclear, cytoplasmic, membrane-bound) and region-specific heterogeneities in cell density and neural cell types. However, AI-driven algorithms targeting a subset of labeling patterns can be effective provided the availability of adequate training data. LifeCanvas Technologies LCT is optimally positioned to develop highly accurate algorithms serving a wide range of detection tasks through its access to high volumes of whole-organ image data containing a variety of label expression patterns via its Contract Research Organization and user base. LCT proposes to develop a data analysis program, SmartAnalytics, which will embed a suite of AI algorithms within a user-friendly software package to identify labeled cell locations and characterize morphological features across the whole brain at cellular and sub-cellular resolution. Specifically, LCT will use intact, 3D immunolabeled mouse brains to design AI algorithms to detect labeled cells imaged at cellular resolution and generate further algorithms for the segmentation of labeled features imaged at sub-micron resolution. Data from LCT’s Contract Research Organization and academic collaborations will be continually fed back to improve and expand the library of detection algorithms available within SmartAnalytics, and these developments will drive further customer adoption and enhancement of future versions of the software. SmartAnalytics will guide users through model application, quality-control testing, and the generation of output products such as figures and summary statistics. In summary, SmartAnalytics will be an evolving and user- friendly workflow execution program that enables neuroscientists to take full advantage of their 3D image data, driving new discoveries in brain function, development and disease.