Toh Cheng Hong, Siow Tiing Yee, Castillo Mauricio
Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou, Tao-Yuan, Taiwan.
Chang Gung University College of Medicine, Tao-Yuan, Taiwan.
Front Oncol. 2021 Oct 13;11:725354. doi: 10.3389/fonc.2021.725354. eCollection 2021.
The proliferation of microvessels with increased permeability is thought to be the cause of peritumoral brain edema (PTBE) in metastases. The contribution of the glymphatic system to the formation of PTBE in brain metastases remains unexplored. We aimed to investigate if the PTBE volume of brain metastases is related to glymphatic dysfunction.
A total of 56 patients with brain metastases who had preoperative dynamic susceptibility contrast-enhanced perfusion-weighted imaging for calculation of tumor cerebral blood volume (CBV) and diffusion tensor imaging for calculations of tumor apparent diffusion coefficient (ADC), tumor fractional anisotropy (FA), and analysis along perivascular space (ALPS) index were analyzed. The volumes of PTBE, whole tumor, enhancing tumor, and necrotic and hemorrhagic portions were manually measured. Additional information collected for each patient included age, sex, primary cancer, metastasis location and number, and the presence of concurrent infratentorial tumors. Linear regression analyses were performed to identify factors associated with PTBE volume.
Among 56 patients, 45 had solitary metastasis, 24 had right cerebral metastasis, 21 had left cerebral metastasis, 11 had bilateral cerebral metastases, and 11 had concurrent infratentorial metastases. On univariable linear regression analysis, PTBE volume correlated with whole tumor volume ( = -0.348, = 0.009), hemorrhagic portion volume ( = -0.327, = 0.014), tumor ADC ( = 0.530, <.001), and ALPS index ( = -0.750, <.001). The associations of PTBE volume with age, sex, tumor location, number of tumors, concurrent infratentorial tumor, enhancing tumor volume, necrotic portion volume, tumor FA, and tumor CBV were not significant. On multivariable linear regression analysis, tumor ADC ( = 0.303; = 0.004) and ALPS index ( = -0.624; < 0.001) were the two independent factors associated with PTBE volume.
Metastases with higher tumor ADC and lower ALPS index were associated with larger peritumoral brain edema volumes. The higher tumor ADC may be related to increased periarterial water influx into the tumor interstitium, while the lower ALPS index may indicate insufficient fluid clearance. The changes in both tumor ADC and ALPS index may imply glymphatic dysfunction, which is, at least, partially responsible for peritumoral brain edema formation.
微血管增生且通透性增加被认为是转移性肿瘤周围脑水肿（PTBE）的病因。脑淋巴系统对脑转移瘤中PTBE形成的作用尚不清楚。我们旨在研究脑转移瘤的PTBE体积是否与脑淋巴功能障碍有关。
共分析了56例脑转移瘤患者，这些患者术前行动态磁敏感对比增强灌注加权成像以计算肿瘤脑血容量（CBV），并行扩散张量成像以计算肿瘤表观扩散系数（ADC）、肿瘤分数各向异性（FA）以及沿血管周围间隙分析（ALPS）指数。手动测量PTBE、整个肿瘤、强化肿瘤以及坏死和出血部分的体积。为每位患者收集的其他信息包括年龄、性别、原发癌、转移部位和数量以及是否存在幕下并发肿瘤。进行线性回归分析以确定与PTBE体积相关的因素。
56例患者中，45例为单发转移，24例为右侧脑转移，21例为左侧脑转移，11例为双侧脑转移，11例有幕下并发转移。单变量线性回归分析显示，PTBE体积与整个肿瘤体积（r = -0.348，P = 0.009）、出血部分体积（r = -0.327，P = 0.014）、肿瘤ADC（r = 0.530，P <.001）以及ALPS指数（r = -0.750，P <.001）相关。PTBE体积与年龄、性别、肿瘤位置、肿瘤数量、幕下并发肿瘤、强化肿瘤体积、坏死部分体积、肿瘤FA以及肿瘤CBV之间的关联不显著。多变量线性回归分析显示，肿瘤ADC（r = 0.303；P = 0.004）和ALPS指数（r = -0.624；P < 0.001）是与PTBE体积相关的两个独立因素。
肿瘤ADC较高且ALPS指数较低的转移瘤与较大的肿瘤周围脑水肿体积相关。较高的肿瘤ADC可能与动脉周围水流入肿瘤间质增加有关，而较低的ALPS指数可能表明液体清除不足。肿瘤ADC和ALPS指数的变化可能意味着脑淋巴功能障碍，这至少部分导致了肿瘤周围脑水肿的形成。
