Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA.
J Neurooncol. 2011 Oct;105(1):91-101. doi: 10.1007/s11060-011-0567-8. Epub 2011 Mar 26.
Microscopic invasion of tumor cells and undetected tumor proliferation is the primary reason for a dismal prognosis in glioblastoma patients. Identification and quantification of spatially localized brain regions undergoing high rates of cell migration and proliferation is critical for improving patient survival; however, there are currently no non-invasive imaging biomarkers for estimating proliferation and migration rates of human gliomas in vivo. To accomplish this, we developed CIMPLE (cell invasion, motility, and proliferation level estimates) image maps using serial diffusion MRI scans and a solution to a glioma growth model equation. CIMPLE represent a novel method of quantifying the level of aggressive malignant behavior. In the current pilot study, we demonstrate the utility of CIMPLE maps to predict progression free survival (PFS) and overall survival (OS) in 26 recurrent glioblastoma patients treated with bevacizumab from our Neuro-Oncology database. Voxel-wise estimates of cell proliferation rate predicted spatial regions of contrast enhancement in 35% of patients. A linear correlation was found between the mean proliferation rate and progression-free survival (PFS; P < 0.0001) as well as overall survival (OS; P = 0.0093). Similarly, the mean proliferation rate was able to stratify patients with early and late PFS as well as OS.
肿瘤细胞的微观浸润和未检测到的肿瘤增殖是胶质母细胞瘤患者预后不良的主要原因。识别和量化经历高细胞迁移和增殖速率的空间局部脑区对于提高患者生存率至关重要；然而，目前尚无用于估计体内人类脑胶质瘤增殖和迁移速率的非侵入性成像生物标志物。为了实现这一目标，我们使用一系列扩散 MRI 扫描和一个胶质瘤生长模型方程的解开发了 CIMPLE（细胞侵袭、运动和增殖水平估计）图像图。CIMPLE 代表了一种定量评估侵袭性恶性行为水平的新方法。在当前的试点研究中，我们展示了 CIMPLE 图谱在我们的神经肿瘤学数据库中接受贝伐单抗治疗的 26 例复发性胶质母细胞瘤患者中预测无进展生存期 (PFS) 和总生存期 (OS) 的效用。细胞增殖率的体素估计预测了 35%的患者的对比增强的空间区域。在无进展生存期 (PFS；P < 0.0001) 和总生存期 (OS；P = 0.0093) 方面均发现了平均增殖率与之间的线性相关性。同样，平均增殖率能够对 PFS 以及 OS 的早期和晚期患者进行分层。
