Cambridge Brain Tumour Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, UK; Department of Neurosurgery, Shanghai General Hospital (originally named "Shanghai First People's Hospital"), Shanghai Jiao Tong University School of Medicine, China; EPSRC Centre for Mathematical Imaging in Healthcare, University of Cambridge, UK.
Cambridge Brain Tumour Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, UK; Department of Neurosurgery, Chang Gung Memorial Hospital, Keelung, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.
Radiother Oncol. 2019 May;134:17-24. doi: 10.1016/j.radonc.2019.01.008. Epub 2019 Jan 31.
Glioblastoma exhibits profound intratumoral heterogeneity in perfusion. Particularly, low perfusion may induce treatment resistance. Thus, imaging approaches that define low perfusion compartments are crucial for clinical management.
A total of 112 newly diagnosed glioblastoma patients were prospectively recruited for maximal safe resection. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from diffusion and perfusion imaging, respectively. Based on the overlapping regions of lowest rCBV quartile (rCBV) with the lowest ADC quartile (ADC) and highest ADC quartile (ADC) in each tumor, two low perfusion compartments (ADC-rCBV and ADC-rCBV) were identified for volumetric analysis. Lactate and macromolecule/lipid levels were determined from multivoxel MR spectroscopic imaging. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier's and multivariate Cox regression analyses, to evaluate the effects of compartment volume and lactate level on survival.
Two compartments displayed higher lactate and macromolecule/lipid levels compared to contralateral normal-appearing white matter (each P < 0.001). The proportion of the ADC-rCBV compartment in the contrast-enhancing tumor was associated with a larger infiltration on FLAIR (P < 0.001, rho = 0.42). The minimally invasive phenotype displayed a lower proportion of the ADC-rCBV compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADC-rCBV compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005).
Our results suggest that the ADC-rCBV compartment may potentially indicate a clinically measurable resistant compartment.
脑胶质瘤在灌注方面表现出明显的瘤内异质性。特别是，低灌注可能导致治疗耐药。因此，定义低灌注区域的成像方法对于临床管理至关重要。
共前瞻性招募了 112 例新诊断的脑胶质瘤患者进行最大安全切除。分别从扩散和灌注成像中计算表观扩散系数（ADC）和相对脑血容量（rCBV）。基于每个肿瘤中 rCBV 最低四分位数（rCBV）与 ADC 最低四分位数（ADC）和 ADC 最高四分位数（ADC）重叠区域，为体积分析确定了两个低灌注区（ADC-rCBV 和 ADC-rCBV）。从多体素磁共振波谱成像中测定乳酸和大分子/脂质水平。采用 Kaplan-Meier 和多变量 Cox 回归分析评估容积和乳酸水平对生存的影响，分析无进展生存期（PFS）和总生存期（OS）。
与对侧正常外观的白质相比，两个区室显示出更高的乳酸和大分子/脂质水平（均 P < 0.001）。增强肿瘤中 ADC-rCBV 区室的比例与 FLAIR 上更大的浸润相关（P < 0.001，rho = 0.42）。微创表型的 ADC-rCBV 区室比例低于局灶性（P = 0.031）和弥漫性表型（无统计学意义）。多变量 Cox 回归显示，ADC-rCBV 区室中的乳酸水平较高与生存恶化相关（PFS：HR 2.995，P = 0.047；OS：HR 4.974，P = 0.005）。
我们的研究结果表明，ADC-rCBV 区室可能潜在地提示临床上可测量的耐药区室。
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