Department of Surgery, Division of Neurosurgery, College of Medicine , University of Saskatchewan , 107 Wiggins Road , Saskatoon , Saskatchewan S7N 5E5 , Canada.
Geological Sciences, College of Arts & Science , University of Saskatchewan , 114 Science Place , Saskatoon , Saskatchewan S7N 5E2 , Canada.
ACS Chem Neurosci. 2018 May 16;9(5):886-893. doi: 10.1021/acschemneuro.7b00382. Epub 2018 Jan 30.
Stroke exacts a heavy financial and economic burden, is a leading cause of death, and is the leading cause of long-term disability in those who survive. The penumbra surrounds the ischemic core of the stroke lesion and is composed of cells that are stressed and vulnerable to death, which is due to an altered metabolic, oxidative, and ionic environment within the penumbra. Without therapeutic intervention, many cells within the penumbra will die and become part of the growing infarct, however, there is hope that appropriate therapies may allow potential recovery of cells within this tissue region, or at least slow the rate of cell death, therefore, slowing the spread of the ischemic infarct and minimizing the extent of tissue damage. As such, preserving the penumbra to promote functional brain recovery is a central goal in stroke research. While identification of the ischemic infarct, and the infarct/penumbra boundary is relatively trivial using classical histology and microscopy techniques, accurately assessing the penetration of the penumbra zone into undamaged brain tissue, and evaluating the magnitude of chemical alterations in the penumbra, has long been a major challenge to the stroke research field. In this study, we have used synchrotron-based X-ray fluorescence imaging to visualize the elemental changes in undamaged, penumbra, and infarct brain tissue, following ischemic stroke. We have employed a Gaussian mixture model to cluster tissue areas based on their elemental characteristics. The method separates the core of the infarct from healthy tissue, and also demarcates discrete regions encircling the infarct. These regions of interest can be combined with elemental and metabolic data, as well as with conventional histology. The cell populations defined by clustering provide a reproducible means of visualizing the size and extent of the penumbra at the level of the single cell and provide a critically needed tool to track changes in elemental status and penumbra size.
中风会带来沉重的经济和财务负担，是死亡的主要原因，也是幸存者长期残疾的主要原因。半影围绕着中风病变的缺血核心，由处于应激状态且易死亡的细胞组成，这是由于半影区内代谢、氧化和离子环境的改变所致。如果没有治疗干预，半影区内的许多细胞将死亡并成为不断增大的梗死的一部分，但是，有希望的是，适当的治疗可能允许该组织区域内的潜在细胞恢复，或者至少减缓细胞死亡的速度，从而减缓缺血性梗死的扩散并最大程度地减少组织损伤。因此，保护半影区以促进大脑功能的恢复是中风研究的核心目标。虽然使用经典组织学和显微镜技术可以相对轻松地识别缺血性梗死和梗死/半影边界，但准确评估半影区向未受损脑组织的渗透程度，并评估半影区的化学变化程度，一直是中风研究领域的主要挑战。在这项研究中，我们使用基于同步加速器的 X 射线荧光成像技术来可视化中风后未受损、半影和梗死脑组织中的元素变化。我们采用了高斯混合模型根据其元素特征对组织区域进行聚类。该方法将梗死核心与健康组织分开，并划定了围绕梗死的离散区域。这些感兴趣区域可以与元素和代谢数据以及常规组织学相结合。聚类定义的细胞群体提供了一种可重现的方法来可视化单个细胞水平的半影大小和范围，并提供了跟踪元素状态和半影大小变化所需的关键工具。
