Sir Peter Mansfield Imaging Centre, School of Medicine, The University of Nottingham, Nottingham, United Kingdom.
School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.
PLoS One. 2019 Feb 21;14(2):e0212002. doi: 10.1371/journal.pone.0212002. eCollection 2019.
Neuroinflammation plays an important role in the pathogenesis of a range of brain disorders. Non-invasive imaging of neuroinflammation is critical to help improve our understanding of the underlying disease mechanisms, monitor therapies and guide drug development. Generally, MRI lacks specificity to molecular imaging biomarkers, but molecular MR imaging based on chemical exchange saturation transfer (CEST) can potentially detect changes of myoinositol, a putative glial marker that may index neuroinflammation. In this pilot study we aimed to investigate, through validation with immunohistochemistry and in vivo magnetic resonance spectroscopy (MRS), whether CEST imaging can reflect the microglial response to a mild inflammatory challenge with lipopolysaccharide (LPS), in the APPSwe/ PS1 mouse model of Alzheimer's disease and wild type controls. The response to the immune challenge was variable and did not align with genotype. Animals with a strong response to LPS (Iba1+, n = 6) showed an increase in CEST contrast compared with those who did not (Iba1-, n = 6). Changes of myoinositol levels after LPS were not significant. We discuss the difficulties of this mild inflammatory model, the role of myoinositol as a glial biomarker, and the technical challenges of CEST imaging at 0.6ppm.
神经炎症在一系列脑部疾病的发病机制中起着重要作用。神经炎症的无创成像对于帮助我们深入了解潜在的疾病机制、监测治疗方法和指导药物开发至关重要。一般来说，MRI 缺乏对分子成像生物标志物的特异性，但基于化学交换饱和传递（CEST）的分子 MRI 有可能检测到肌醇的变化，肌醇是一种潜在的神经胶质标志物，可能可以作为神经炎症的指标。在这项初步研究中，我们旨在通过免疫组织化学和体内磁共振波谱（MRS）验证，研究 CEST 成像是否可以反映小胶质细胞对脂多糖（LPS）轻度炎症挑战的反应，这在阿尔茨海默病的 APPswe/PS1 小鼠模型和野生型对照中。免疫挑战的反应是可变的，与基因型不一致。对 LPS 反应强烈的动物（Iba1+，n = 6）与反应不强烈的动物（Iba1-，n = 6）相比，CEST 对比有所增加。LPS 后肌醇水平的变化不显著。我们讨论了这种轻度炎症模型的困难、肌醇作为神经胶质生物标志物的作用，以及在 0.6ppm 时 CEST 成像的技术挑战。
