弥散加权磁共振波谱（DW-MRS）对 LPS 诱导的人神经胶质形态变化敏感：一项初步研究。
Diffusion-weighted MR spectroscopy (DW-MRS) is sensitive to LPS-induced changes in human glial morphometry: A preliminary study.
机构信息
Department of Neuroscience, Brighton and Sussex Medical School, Brighton, UK.
C. J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands.
出版信息
Brain Behav Immun. 2022 Jan;99:256-265. doi: 10.1016/j.bbi.2021.10.005. Epub 2021 Oct 18.
BACKGROUND
Low-dose lipopolysaccharide (LPS) is a well-established experimental method for inducing systemic inflammation and shown by microscopy to activate microglia in rodents. Currently, techniques for in-vivo imaging of glia in humans are limited to TSPO (Translocator protein) PET, which is expensive, methodologically challenging, and has poor cellular specificity. Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) sensitizes MR spectra to diffusion of intracellular metabolites, potentially providing cell-specific information about cellular morphology. In this preliminary study, we applied DW-MRS to measure changes in the apparent diffusion coefficients (ADC) of glial and neuronal metabolites to healthy participants who underwent an LPS administration protocol. We hypothesized that the ADC of glial metabolites will be selectively modulated by LPS-induced glial activation.
METHODS
Seven healthy male volunteers, (mean 25.3 ± 5.9 years) were each tested in two separate sessions once after LPS (1 ng/Kg intravenously) and once after placebo (saline). Physiological responses were monitored during each session and serial blood samples and Profile of Mood States (POMS) completed to quantify white blood cell (WBC), cytokine and mood responses. DW-MRS data were acquired 5-5½ hours after injection from two brain regions: grey matter in the left thalamus, and frontal white matter.
RESULTS
Body temperature, heart rate, WBC and inflammatory cytokines were significantly higher in the LPS compared to the placebo condition (p < 0.001). The ADC of the glial metabolite choline (tCho) was also significantly increased after LPS administration compared to placebo (p = 0.008) in the thalamus which scaled with LPS-induced changes in POMS total and negative mood (Adj R = 0.83; p = 0.004).
CONCLUSIONS
DW-MRS may be a powerful new tool sensitive to glial cytomorphological changes in grey matter induced by systemic inflammation.
背景
低剂量脂多糖（LPS）是一种成熟的诱导全身炎症的实验方法，通过显微镜观察到其在啮齿动物中激活小胶质细胞。目前，用于人类体内神经胶质成像的技术仅限于 TSPO（转位蛋白）PET，该技术昂贵、方法学上具有挑战性且细胞特异性差。弥散加权磁共振波谱（DW-MRS）使 MR 谱对细胞内代谢物的扩散敏感，有可能提供关于细胞形态的细胞特异性信息。在这项初步研究中，我们应用 DW-MRS 来测量接受 LPS 给药方案的健康参与者的神经胶质和神经元代谢物的表观扩散系数（ADC）的变化。我们假设 LPS 诱导的神经胶质激活将选择性调节神经胶质代谢物的 ADC。
方法
7 名健康男性志愿者（平均年龄 25.3±5.9 岁），每人分别在 LPS（1ng/Kg 静脉内）和安慰剂（盐水）后各进行两次单独的测试。在每次测试过程中监测生理反应，并完成情绪状态简表（POMS）以量化白细胞（WBC）、细胞因子和情绪反应。在注射后 5-5½ 小时，从两个脑区采集 DW-MRS 数据：左侧丘脑的灰质和额叶白质。
结果
与安慰剂相比，LPS 组的体温、心率、WBC 和炎症细胞因子显著升高（p<0.001）。与安慰剂相比，LPS 给药后丘脑的神经胶质代谢物胆碱（tCho）的 ADC 也显著增加（p=0.008），与 LPS 诱导的 POMS 总分和负性情绪变化呈正相关（调整后的 R=0.83；p=0.004）。
结论
DW-MRS 可能是一种新的强大工具，可敏感地检测全身炎症引起的灰质神经胶质细胞形态变化。
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