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

该项目的目的是实现一种散射偏振仪，它独特地结合了最先进的光散射和脑组织的偏振测量，并首次能够揭示大脑体积中复杂的交叉神经纤维通路，例如Meynert基底核及其与大脑皮层区域的连接。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并协助脑外科手术的关键。显微镜技术3D偏振光成像（3D-PLI）以微米分辨率确定整个组织学脑切片中神经纤维通路的空间过程。然而，它不提供关于组织组成的信息，并且在包含交叉纤维的像素中留下不确定性。通过Diattenuation Imaging（DI），开发了一种有前途的新成像技术，该技术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）。最近开发的技术散射光成像（SLI）最终允许检索交叉神经纤维的个体方向，通过从许多不同的角度照射大脑切片并研究散射光的结果模式。将所有三种技术结合在一个系统（散射偏振仪）中，将以微米分辨率揭示单个3D纤维方向，无论是在密集排列的区域还是交叉的神经纤维区域。然而，使用当前的测量程序，SLI测量需要几个小时（需要数千个照明角度），使得较大解剖结构或神经纤维网络的测量不可行。因此，该项目的一个中心目标是使用压缩传感来减少所需的测量时间，压缩传感是一种在数据采集期间已经采用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，其能够对许多连续脑切片进行组合测量，并对较大脑体积进行多模态图像分析。新系统将用于创建Meynert基底核（NBM）的组织模型，该模型在记忆，注意力，视觉功能和运动控制中起着重要作用。研究表明，NBM的低频深部脑刺激有利于治疗神经退行性痴呆，如阿尔茨海默氏症或帕金森氏病。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纤维通路及其与皮质脑区的连接至关重要。新的高通量散射偏振仪将用于测量大的大脑体积（包含NBM和皮质区域），以揭示微观细节的复杂神经纤维通路和交叉点，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.