Background: The invasion of glioblastoma cells beyond the visible tumor margin depicted by conventional neuroimaging is believed to mediate recurrence and predict poor survival. Radiomic biomarkers that are associated with the direction and extent of tumor infiltration are, however, non-existent. Methods: Patients from a single center with newly diagnosed glioblastoma (n= 7) underwent preoperative Q-space magnetic resonance imaging (QSI; 3T, 64 gradient directions, b = 1000 s/mm2) between 2018 and 2019. Tumors were manually segmented, and patterns of inter-voxel coherence spatially intersecting each segmentation were generated to represent tumor-associated tractography. One patient additionally underwent regional biopsy of diffusion tract- versus non-tract-associated tissue during tumor resection for RNA sequencing. Imaging data from this cohort were compared with a historical cohort ofn= 66 glioblastoma patients who underwent similar QSI scans. Associations of tractography-derived metrics with survival were assessed usingt-tests, linear regression, and Kaplan–Meier statistics. Patient-derived glioblastoma xenograft (PDX) mice generated with the sub-hippocampal injection of human-derived glioblastoma stem cells (GSCs) were scanned under high-field conditions (QSI, 7T, 512 gradient directions), and tumor-associated tractography was compared with the 3D microscopic reconstruction of immunostained GSCs. Results: In the principal enrollment cohort of patients with glioblastoma, all cases displayed tractography patterns with tumor-intersecting tract bundles extending into brain parenchyma, a phenotype which was reproduced in PDX mice as well as in a larger comparison cohort of glioblastoma patients (n= 66), when applying similar methods. Reconstructed spatial patterns of GSCs in PDX mice closely mirrored tumor-associated tractography. On a Kaplan–Meier survival analysis ofn= 66 patients, the calculated intra-tumoral mean diffusivity predicted the overall survival (p= 0.037), as did tractography-associated features including mean tract length (p= 0.039) and mean projecting tract length (p= 0.022). The RNA sequencing of human tissue samples (n= 13 tumor samples from a single patient) revealed the overexpression of transcripts which regulate cell motility in tract-associated samples. Conclusions: QSI discriminates tumor-specific patterns of inter-voxel coherence believed to represent white matter pathways which may be susceptible to glioblastoma invasion. These findings may lay the groundwork for future work on therapeutic targeting, patient stratification, and prognosis in glioblastoma.
背景：胶质母细胞瘤细胞在常规神经影像学可见肿瘤边界之外的侵袭被认为是导致复发并预示不良生存期的关键因素。然而，目前尚缺乏能够反映肿瘤浸润方向与程度的影像组学生物标志物。方法：2018年至2019年间，单中心新诊断胶质母细胞瘤患者（n=7）术前接受Q空间磁共振成像（QSI；3T，64梯度方向，b=1000 s/mm²）。通过人工分割肿瘤区域，生成空间上交叉贯穿各分割区域的体素间相干性模式，以表征肿瘤相关纤维束成像。其中1例患者在肿瘤切除过程中额外接受了扩散纤维束相关区域与非纤维束相关区域的定向活检，用于RNA测序分析。该队列影像数据与历史队列中66例接受相似QSI扫描的胶质母细胞瘤患者进行比较。采用t检验、线性回归及Kaplan-Meier统计方法评估纤维束成像衍生指标与生存期的关联性。通过海马下区注射人源胶质母细胞瘤干细胞构建患者来源异种移植小鼠模型，在高场强条件下进行扫描（QSI，7T，512梯度方向），并将肿瘤相关纤维束成像与免疫染色胶质母细胞瘤干细胞的三维显微重建结果进行对比。结果：在主要入组的胶质母细胞瘤患者队列中，所有病例均显示肿瘤交叉纤维束延伸至脑实质的纤维束成像模式。应用相同方法在PDX小鼠及扩大对照队列（n=66）中均重现该表型。PDX小鼠中重建的胶质母细胞瘤干细胞空间分布模式与肿瘤相关纤维束成像高度吻合。对66例患者的Kaplan-Meier生存分析显示，肿瘤内平均扩散率可预测总生存期（p=0.037），纤维束成像相关特征包括平均纤维束长度（p=0.039）和平均投射纤维束长度（p=0.022）同样具有预测价值。人类组织样本RNA测序（来自单例患者的13个肿瘤样本）显示，纤维束相关样本中调控细胞运动性的转录本表达上调。结论：QSI技术能够识别肿瘤特异性体素间相干性模式，这些模式可能代表易受胶质母细胞瘤侵袭的白质通路。该发现可为未来胶质母细胞瘤的靶向治疗、患者分层及预后评估研究奠定基础。
肿瘤(癌症)患者之家