TY - JOUR
T1 - Low perfusion compartments in glioblastoma quantified by advanced magnetic resonance imaging and correlated with patient survival
AU - Li, Chao
AU - Yan, Jiun Lin
AU - Torheim, Turid
AU - McLean, Mary A.
AU - Boonzaier, Natalie R.
AU - Zou, Jingjing
AU - Huang, Yuan
AU - Yuan, Jianmin
AU - van Dijken, Bart R.J.
AU - Matys, Tomasz
AU - Markowetz, Florian
AU - Price, Stephen J.
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/5
Y1 - 2019/5
N2 - Background and purpose: 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. Materials and methods: 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 L ) with the lowest ADC quartile (ADC L ) and highest ADC quartile (ADC H ) in each tumor, two low perfusion compartments (ADC H -rCBV L and ADC L -rCBV L ) 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. Results: 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 L -rCBV L 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 L -rCBV L compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADC L -rCBV L compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005). Conclusions: Our results suggest that the ADC L -rCBV L compartment may potentially indicate a clinically measurable resistant compartment.
AB - Background and purpose: 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. Materials and methods: 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 L ) with the lowest ADC quartile (ADC L ) and highest ADC quartile (ADC H ) in each tumor, two low perfusion compartments (ADC H -rCBV L and ADC L -rCBV L ) 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. Results: 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 L -rCBV L 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 L -rCBV L compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADC L -rCBV L compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005). Conclusions: Our results suggest that the ADC L -rCBV L compartment may potentially indicate a clinically measurable resistant compartment.
KW - Diffusion imaging
KW - Glioblastoma
KW - Heterogeneity
KW - Perfusion imaging
KW - Radioresistance
KW - Tumor habitat imaging
UR - http://www.scopus.com/inward/record.url?scp=85060758871&partnerID=8YFLogxK
U2 - 10.1016/j.radonc.2019.01.008
DO - 10.1016/j.radonc.2019.01.008
M3 - Article
C2 - 31005212
AN - SCOPUS:85060758871
SN - 0167-8140
VL - 134
SP - 17
EP - 24
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
ER -