研究动态
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磁共振成像用于评估携带着胶质母细胞瘤的老鼠模型在禁食时大脑反应,作为癌症厌食的模型。

Magnetic resonance imaging to assess the brain response to fasting in glioblastoma-bearing rats as a model of cancer anorexia.

发表日期:2023 Apr 10
作者: Irene Guadilla, Sara González, Sebastián Cerdán, Blanca Lizarbe, Pilar López-Larrubia
来源: CANCER IMAGING

摘要:

全球能量平衡是一个重要的过程,由大脑紧密调节,而在癌症发展过程中经常出现失调。胶质母细胞瘤 (GBM) 是最受关注的恶性肿瘤之一,但其食欲相关障碍,如厌食/消瘦症状,仍然不太清楚。我们在成年雄性 GBM 承载 (n = 13) 或对照 Wistar 大鼠 (n = 12) 中执行锰强化磁共振成像 (MEMRI),并随后进行扩散张量成像 (DTI)。采用广义线性模型方法评估禁食对涉及全球能量代谢调节的不同脑区的影响: 皮层,海马,下丘脑和丘脑。在肿瘤承载的动物的对侧选择这些区域,在对照鼠的左半球选择。额外进行了两个 GBM (n = 5) 或健康队列 (n = 6) 的 DTI-only 实验,以评估锰输注对扩散测量的影响。MEMRI 结果显示,自由进食的 GBM 动物皮层 (p-value <0.001) 和丘脑 (p-value <0.05) 的 T1 值较对照组低,与 Mn2+ 积累增加一致。无论在对照组还是在 GBM 组中,无论喂食还是禁食,都没有报告 MEMRI-detectable 差异。在 MnCl2-infused 队列中,DTI 研究显示,任何动物队列中从进食到禁食状态都没有平均扩散率 (MD) 差异。然而,在仅进行 DTI 的一组采集后,健康对照鼠中的 MD 值显著降低 (p-value <0.001),而 GBM 组与对照组在进食状态下所有区域 (但丘脑除外) 中的 MD 值也显著降低 (p-value <0.01)。因肿瘤的浸润性质,在肿瘤承载的大鼠中,由于分数各向异性 (FA) 降低,这在两组扩散集中都被检测到,其中 (p-value <0.01) 和没有 Mn2+ 给药的 (p-value <0.001)。我们的结果显示,在 GBM 动物的饥饿相关区域发生了一种改变的生理大脑反应,可通过 DTI 检测,但无法通过 MEMRI 获得。此外,目前的结果显示,Mn2+ 引起神经毒性炎症,通过 MD 变化干扰扩散 MRI 来检测胃口诱导的响应。©2023年。作者。
Global energy balance is a vital process tightly regulated by the brain that frequently becomes dysregulated during the development of cancer. Glioblastoma (GBM) is one of the most investigated malignancies, but its appetite-related disorders, like anorexia/cachexia symptoms, remain poorly understood.We performed manganese enhanced magnetic resonance imaging (MEMRI) and subsequent diffusion tensor imaging (DTI), in adult male GBM-bearing (n = 13) or control Wistar rats (n = 12). A generalized linear model approach was used to assess the effects of fasting in different brain regions involved in the regulation of the global energy metabolism: cortex, hippocampus, hypothalamus and thalamus. The regions were selected on the contralateral side in tumor-bearing animals, and on the left hemisphere in control rats. An additional DTI-only experiment was completed in two additional GBM (n = 5) or healthy cohorts (n = 6) to assess the effects of manganese infusion on diffusion measurements.MEMRI results showed lower T1 values in the cortex (p-value < 0.001) and thalamus (p-value < 0.05) of the fed ad libitum GBM animals, as compared to the control cohort, consistent with increased Mn2+ accumulation. No MEMRI-detectable differences were reported between fed or fasting rats, either in control or in the GBM group. In the MnCl2-infused cohorts, DTI studies showed no mean diffusivity (MD) variations from the fed to the fasted state in any animal cohort. However, the DTI-only set of acquisitions yielded remarkably decreased MD values after fasting only in the healthy control rats (p-value < 0.001), and in all regions, but thalamus, of GBM compared to control animals in the fed state (p-value < 0.01). Fractional anisotropy (FA) decreased in tumor-bearing rats due to the infiltrate nature of the tumor, which was detected in both diffusion sets, with (p-value < 0.01) and without Mn2+ administration (p-value < 0.001).Our results revealed that an altered physiological brain response to fasting occurred in hunger related regions in GBM animals, detectable with DTI, but not with MEMRI acquisitions. Furthermore, the present results showed that Mn2+ induces neurotoxic inflammation, which interferes with diffusion MRI to detect appetite-induced responses through MD changes.© 2023. The Author(s).