Abstract：
OBJECTIVE: The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS).
METHODS: In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions.
RESULTS: Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (β = -0.004, p = 0.026), tumor grade (β = -0.114, p = 0.011), and IDH genotype (β = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (β = -0.005, p < 0.001), tumor grade (β = -0.144, p < 0.001), IDH genotype (β = 0.154, p < 0.001), tumor volume (β = -0.002, p = 0.001), and peritumoral edema volume (β = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (β = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (β = -0.003, p = 0.022), IDH status (β = 0.132, p = 0.001), and tumor volume (β = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001).
CONCLUSIONS: GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.
METHODS: In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions.
RESULTS: Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (β = -0.004, p = 0.026), tumor grade (β = -0.114, p = 0.011), and IDH genotype (β = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (β = -0.005, p < 0.001), tumor grade (β = -0.144, p < 0.001), IDH genotype (β = 0.154, p < 0.001), tumor volume (β = -0.002, p = 0.001), and peritumoral edema volume (β = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (β = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (β = -0.003, p = 0.022), IDH status (β = 0.132, p = 0.001), and tumor volume (β = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001).
CONCLUSIONS: GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.
摘要：
目的：本研究的目的是通过使用沿血管周围间隙（ALPS）的扩散张量图像分析，非侵入性地探讨神经胶质瘤中的淋巴系统（GS）及其与神经胶质瘤特征和预后的关系。
方法：在2015年4月至2021年11月期间，所有经病理证实未接受手术的单半球神经胶质瘤患者，化疗,放射治疗,或立体定向活检;谁没有严重的脑变形;谁接受了术前常规和先进的全脑弥散加权成像;和谁的数据是可用的和不妥协纳入本研究.年龄和性别匹配的健康对照（HCs）进行了扩散加权成像也包括在内。ALPS指数是根据扩散图计算的，允许对GS进行非侵入性分析。在所有胶质瘤患者中测量对侧ALPS指数，并在无同侧半球严重变形的胶质瘤患者中测量了同侧ALPS指数。根据肿瘤分级，比较胶质瘤患者和HCs之间的ALPS指数。IDH基因型,肿瘤和水肿体积，和肿瘤的位置。进一步分析胶质瘤双侧ALPS指数与肿瘤特征的相关性。使用Kaplan-Meier生存曲线和对数秩检验以及单变量和多变量Cox回归进行生存分析。
结果：91例单半球胶质瘤患者（33例女性，本研究包括平均年龄46±13岁）和59个年龄和性别匹配的HC。胶质瘤组与HC组相比，同侧ALPS指数下降，不管肿瘤分级，IDH基因型,肿瘤和水肿体积，或肿瘤位置（p≤0.048），而对侧ALPS指数在高级别胶质瘤中下降，IDH野生型,水肿体积较大，不同的肿瘤体积和位置（p≤0.009）。无论肿瘤级别如何，同侧与对侧ALPS指数均较低，IDH基因型,肿瘤和水肿体积，或肿瘤位置（p≤0.044）。一元线性回归显示年龄(β=-0.004,p=0.026),肿瘤分级（β=-0.114，p=0.011），IDH基因型(β=0.120,p=0.008)与胶质瘤同侧ALPS指数相关。年龄（β=-0.005，p<0.001），肿瘤分级（β=-0.144，p<0.001），IDH基因型（β=0.154，p<0.001），肿瘤体积（β=-0.002，p=0.001），胶质瘤瘤周水肿体积(β=-0.002,p<0.001)与对侧ALPS指数相关。多元线性回归分析显示肿瘤分级(β=-0.125,p=0.005)与同侧ALPS指数独立相关。年龄（β=-0.003，p=0.022），IDH状态（β=0.132，p=0.001），和肿瘤体积（β=-0.002，p<0.001）与对侧ALPS指数独立相关。Kaplan-Meier分析显示，低和高对侧ALPS组之间的生存时间不同（log-rank=10.574，p=0.001）。单变量Cox回归分析表明，对侧ALPS指数较低与较短的生存时间有关（HR0.095，p=0.005）。多变量Cox回归分析显示IDH状态是生存的唯一独立因素（HR0.138，p<0.001）。
结论：脑胶质瘤中GS功能受损，且与肿瘤特征相关，对侧GS功能较差与生存时间较短有关。
方法：在2015年4月至2021年11月期间，所有经病理证实未接受手术的单半球神经胶质瘤患者，化疗,放射治疗,或立体定向活检;谁没有严重的脑变形;谁接受了术前常规和先进的全脑弥散加权成像;和谁的数据是可用的和不妥协纳入本研究.年龄和性别匹配的健康对照（HCs）进行了扩散加权成像也包括在内。ALPS指数是根据扩散图计算的，允许对GS进行非侵入性分析。在所有胶质瘤患者中测量对侧ALPS指数，并在无同侧半球严重变形的胶质瘤患者中测量了同侧ALPS指数。根据肿瘤分级，比较胶质瘤患者和HCs之间的ALPS指数。IDH基因型,肿瘤和水肿体积，和肿瘤的位置。进一步分析胶质瘤双侧ALPS指数与肿瘤特征的相关性。使用Kaplan-Meier生存曲线和对数秩检验以及单变量和多变量Cox回归进行生存分析。
结果：91例单半球胶质瘤患者（33例女性，本研究包括平均年龄46±13岁）和59个年龄和性别匹配的HC。胶质瘤组与HC组相比，同侧ALPS指数下降，不管肿瘤分级，IDH基因型,肿瘤和水肿体积，或肿瘤位置（p≤0.048），而对侧ALPS指数在高级别胶质瘤中下降，IDH野生型,水肿体积较大，不同的肿瘤体积和位置（p≤0.009）。无论肿瘤级别如何，同侧与对侧ALPS指数均较低，IDH基因型,肿瘤和水肿体积，或肿瘤位置（p≤0.044）。一元线性回归显示年龄(β=-0.004,p=0.026),肿瘤分级（β=-0.114，p=0.011），IDH基因型(β=0.120,p=0.008)与胶质瘤同侧ALPS指数相关。年龄（β=-0.005，p<0.001），肿瘤分级（β=-0.144，p<0.001），IDH基因型（β=0.154，p<0.001），肿瘤体积（β=-0.002，p=0.001），胶质瘤瘤周水肿体积(β=-0.002,p<0.001)与对侧ALPS指数相关。多元线性回归分析显示肿瘤分级(β=-0.125,p=0.005)与同侧ALPS指数独立相关。年龄（β=-0.003，p=0.022），IDH状态（β=0.132，p=0.001），和肿瘤体积（β=-0.002，p<0.001）与对侧ALPS指数独立相关。Kaplan-Meier分析显示，低和高对侧ALPS组之间的生存时间不同（log-rank=10.574，p=0.001）。单变量Cox回归分析表明，对侧ALPS指数较低与较短的生存时间有关（HR0.095，p=0.005）。多变量Cox回归分析显示IDH状态是生存的唯一独立因素（HR0.138，p<0.001）。
结论：脑胶质瘤中GS功能受损，且与肿瘤特征相关，对侧GS功能较差与生存时间较短有关。
