Development of a high-throughput Scattering Polarimeter for studying the connectivity of the nucleus basalis of Meynert in the human brain

该项目的目标是实现一种散射偏振仪，它独特地结合了最先进的脑组织光散射和偏振测量，并首次能够揭示大量脑体积中复杂的、交叉的神经纤维路径，例如Meynert基底核及其与大脑皮质区域的连接。解开大脑中高度复杂和密集生长的神经纤维网络是了解其结构和功能以及辅助脑部手术的关键。显微技术3D偏振光成像(3D-PLI)以微米级的分辨率确定整个组织学脑切片中神经纤维路径的空间轨迹。然而，它不提供有关组织成分的信息，并在包含交叉纤维的像素中留下不确定性。随着衰减成像(DI)的发展，一种有潜力的新成像技术已经被开发出来，它有可能区分不同的组织成分(例如，具有不同纤维直径的区域)。最近开发的散射光成像(SLI)技术终于可以通过从多个不同角度照射大脑部分并研究产生的散射光模式来恢复交叉神经纤维的个别方向。将所有这三种技术结合在一个系统(散射偏振仪)中，将以微米级的分辨率揭示单个3D纤维的取向，无论是在神经纤维密集的区域还是在神经纤维交叉的区域。然而，在目前的测量程序中，SLI测量需要几个小时(需要数千个照明角度)，因此无法测量较大的解剖结构或神经纤维网络。因此，该项目的一个中心目标是利用压缩传感减少所需的测量时间--这是一种在数据采集过程中已经采用了数据压缩方法的方法。通过这种方式，将实现高通量散射偏振仪，从而能够对许多连续的大脑切片进行组合测量，并对更大的大脑体积进行多模式图像分析。新系统将被用来创建Meynert基底核(NBM)的组织模型，NBM在记忆、注意力、视觉功能和运动控制方面发挥着重要作用。研究表明，对NBM进行低频率、深部脑刺激有利于治疗阿尔茨海默氏症或帕金森氏症等神经退行性痴呆。为了成功治疗，需要在大脑中精确定位电极。因此，详细了解NBM纤维通路及其与大脑皮质区域的连接是至关重要的。新的高通量散射旋光仪将用于测量大的大脑体积(包含NBM和皮质区)，以揭示微观细节的复杂神经纤维路径和交叉，为更好地治疗神经退行性痴呆提供关键知识。

The aim of this project is to realize a Scattering Polarimeter that uniquely combines state-of-the-art light scattering and polarization measurements of brain tissue and enables for the first time to reveal the intricate, crossing nerve fiber pathways in large brain volumes, such as the nucleus basalis of Meynert and its connections to cortical brain areas. Unraveling the highly complex and densely grown network of nerve fibers in the brain is key to understanding its structure and function and to assist brain surgery. The microscopy technique 3D Polarized Light Imaging (3D-PLI) determines the spatial course of nerve fiber pathways in whole histological brain sections with micrometer resolution. However, it does not provide information about the tissue composition and leaves uncertainties in pixels containing crossing fibers. With Diattenuation Imaging (DI), a promising new imaging technique has been developed that has the potential to distinguish different tissue compositions (e.g. regions with different fiber diameters). The recently developed technique Scattered Light Imaging (SLI) finally allows to retrieve the individual orientations of crossing nerve fibers, by illuminating brain sections from many different angles and studying the resulting patterns of scattered light. Combining all three techniques in one system (Scattering Polarimeter) will reveal the individual 3D fiber orientations with micrometer resolution, both in regions with densely packed and crossing nerve fibers. However, with the current measurement procedure, SLI measurements take several hours (requiring thousands of illumination angles) so that measurements of larger anatomical structures or nerve fiber networks are not feasible. One central aim of this project is therefore to reduce the required measurement time, using compressed sensing – a method that employs data compression approaches already during data acquisition. In this way, a high-throughput Scattering Polarimeter will be realized that enables combined measurements of many consecutive brain sections and multi-modal image analysis of larger brain volumes. The new system will be used to create a tissue model of the nucleus basalis of Meynert (NBM), which plays an important role in memory, attention, visual function, and motor control. Studies have shown that low-frequency, deep brain stimulation of the NBM are beneficial for the treatment of neurodegenerative dementias such as Alzheimer’s or Parkinsons’ disease. For successful treatment, precise positioning of electrodes in the brain is required. Hence, a detailed knowledge about the NBM fiber pathways and their connections to cortical brain areas is crucial. The new high-throughput Scattering Polarimeter will be used to measure a large brain volume (containing the NBM and cortical areas) to reveal the intricate nerve fiber pathways and crossings at microscopic detail, providing crucial knowledge for better treatment of neurodegenerative dementias.