Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA.
J Cereb Blood Flow Metab. 2020 Jan;40(1):100-115. doi: 10.1177/0271678X18803948. Epub 2018 Oct 18.
Glioma growth can cause pervasive changes in the functional connectivity (FC) of brain networks, which has been associated with re-organization of brain functions and development of functional deficits in patients. Mechanisms underlying functional re-organization in brain networks are not understood and efforts to utilize functional imaging for surgical planning, or as a biomarker of functional outcomes are confounded by the heterogeneity in available human data. Here we apply multiple imaging modalities in a well-controlled murine model of glioma with extensive validation using human data to explore mechanisms of FC disruption due to glioma growth. We find gliomas cause both local and distal changes in FC. FC changes in networks proximal to the tumor occur secondary to hemodynamic alterations but surprisingly, remote FC changes are independent of hemodynamic mechanisms. Our data strongly implicate hemodynamic alterations as the main driver of local changes in measurements of FC in patients with glioma.
脑肿瘤的生长会导致大脑网络功能连接（FC）的普遍改变，这与患者大脑功能的重新组织和功能缺陷的发展有关。大脑网络功能重组的机制尚不清楚，而利用功能成像进行手术规划或作为功能结果的生物标志物的努力，因现有人类数据的异质性而受到阻碍。在这里，我们在广泛使用人类数据进行验证的脑肿瘤的良好控制的小鼠模型中应用了多种成像方式，以探索脑肿瘤生长导致 FC 破坏的机制。我们发现脑肿瘤既导致局部也导致 FC 的远端改变。肿瘤附近网络的 FC 变化是继发于血液动力学改变，但令人惊讶的是，远程 FC 变化与血液动力学机制无关。我们的数据强烈表明，血液动力学改变是导致脑肿瘤患者 FC 测量局部变化的主要驱动因素。
