Del Mar Álvarez-Torres María, Juan-Albarracín Javier, Fuster-Garcia Elies, Bellvís-Bataller Fuensanta, Lorente David, Reynés Gaspar, Font de Mora Jaime, Aparici-Robles Fernando, Botella Carlos, Muñoz-Langa Jose, Faubel Raquel, Asensio-Cuesta Sabina, García-Ferrando Germán A, Chelebian Eduard, Auger Cristina, Pineda Jose, Rovira Alex, Oleaga Laura, Mollà-Olmos Enrique, Revert Antonio J, Tshibanda Luaba, Crisi Girolamo, Emblem Kyrre E, Martin Didier, Due-Tønnessen Paulina, Meling Torstein R, Filice Silvano, Sáez Carlos, García-Gómez Juan M
Universitat Politècnica de València, BDSLab, Instituto Universitarios de Tecnologías de la Información y Comunicaciones (ITACA), Valencia, Spain.
Oslo University Hospital, Department of Diagnostic Physics, Oslo, Norway.
J Magn Reson Imaging. 2020 May;51(5):1478-1486. doi: 10.1002/jmri.26958. Epub 2019 Oct 26.
Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE).
To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols.
Multicenter retrospective study.
In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study.
FIELD STRENGTH/SEQUENCE: 1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium-based contrast agent-enhanced T -weighted MRI, T - and FLAIR T -weighted, and dynamic susceptibility contrast (DSC) T * perfusion.
We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBV ) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed.
Uniparametric Cox regression; Kaplan-Meier test; Mann-Whitney test.
The rCBV derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate-" and "high-vascular" groups (P < 0.05). The Mann-Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02-0.685; LAT: P = 0.010-0.769; IPE: P = 0.093-0.939; VPE: P = 0.016-1.000).
The rCBV calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability.
3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1478-1486.
胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，其特征为血管的异质性和异常性。肿瘤内部及水肿区域的血管生境可分为以下几种亚型：高血管生成性肿瘤（HAT）、低血管生成性肿瘤（LAT）、浸润性外周水肿（IPE）和血管源性外周水肿（VPE）。
考虑到采集方案的中心间变异性，验证胶质母细胞瘤患者血管生境的血流动力学标志物与总生存期（OS）之间的关联。
多中心回顾性研究。
来自参与NCT03439332临床研究的7个欧洲中心的184例胶质母细胞瘤患者。
场强/序列：1.5T（54例患者）或3.0T（130例患者）。钆喷酸葡胺对比剂增强前及增强后的T加权MRI、T加权和液体衰减反转恢复序列（FLAIR）T加权以及动态磁敏感对比（DSC）T*灌注成像。
我们分析术前MRI，以确定每个生境处的最大相对脑血容量（rCBV）与总生存期之间的关联。此外，还测试了这些标志物将患者分为“血管性”组的分层能力。同时评估了各中心之间标志物的变异性。
单参数Cox回归；Kaplan-Meier检验；Mann-Whitney检验。
源自HAT、LAT和IPE生境的rCBV与患者总生存期显著相关（P<0.05；风险比[HR]分别为1.05、1.11、1.28）。此外，这些标志物可将患者分为“中度血管性”和“高度血管性”组（P<0.05）。Mann-Whitney检验未发现大多数中心在标志物方面存在显著差异（HAT：P=0.02-0.685；LAT：P=0.010-0.769；IPE：P=0.093-0.939；VPE：P=0.016-1.000）。
在HAT、LAT和IPE生境处计算得到的rCBV已被验证为胶质母细胞瘤患者治疗前阶段具有临床相关性的预后生物标志物。本研究证明了血流动力学组织特征（HTS）生境在评估GBM血管异质性及其与患者预后的关联方面的稳健性，且不受中心间变异性的影响。
3 技术效能阶段：2 J.Magn.Reson.Imaging 2020;51:1478-1486。
