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Low Perfusion Compartments in Glioblastoma Quantified by Advanced Magnetic Resonance Imaging and Correlated with Patient Survival

View ORCID ProfileChao Li, Jiun-Lin Yan, Turid Torheim, Mary A. McLean, Natalie R. Boonzaier, Yuan Huang, Jianmin Yuan, Bart RJ Van Dijken, Tomasz Matys, Florian Markowetz, Stephen J. Price
doi: https://doi.org/10.1101/180521
Chao Li
1Cambridge Brain Tumour Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK;
2Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China (CL);
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  • ORCID record for Chao Li
  • For correspondence: cl109@outlook.com
Jiun-Lin Yan
1Cambridge Brain Tumour Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK;
3Department of Neurosurgery, Chang Gung Memorial Hospital, Keelung, Taiwan;
4Chang Gung University College of Medicine, Taoyuan, Taiwan;
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Turid Torheim
5Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK;
6CRUK & EPSRC Cancer Imaging Centre in Cambridge and Manchester, Cambridge, UK;
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Mary A. McLean
5Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK;
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Natalie R. Boonzaier
1Cambridge Brain Tumour Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK;
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Yuan Huang
7Department of Radiology, University of Cambridge, Cambridge, UK;
9EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging, University of Cambridge, Cambridge, UK;
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Jianmin Yuan
7Department of Radiology, University of Cambridge, Cambridge, UK;
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Bart RJ Van Dijken
10Department of Radiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
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Tomasz Matys
7Department of Radiology, University of Cambridge, Cambridge, UK;
8Cancer Trials Unit Department of Oncology, Addenbrooke’s Hospital, Cambridge, UK;
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Florian Markowetz
5Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK;
6CRUK & EPSRC Cancer Imaging Centre in Cambridge and Manchester, Cambridge, UK;
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Stephen J. Price
1Cambridge Brain Tumour Imaging Laboratory, Division of Neurosurgery, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK;
11Wolfson Brain Imaging Centre, Department of Clinical Neuroscience, University of Cambridge, Cambridge, UK;
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Abstract

Background Glioblastoma exhibits profound intratumoral heterogeneity in blood perfusion, which may cause inconsistent therapy response. Particularly, low perfusion may create hypoxic microenvironment and induce resistant clones. Thus, developing validated imaging approaches that define low perfusion compartments is crucial for clinical management.

Methods A total of 112 newly-diagnosed supratentorial glioblastoma patients were prospectively recruited for maximal safe resection. Preoperative MRI included anatomical, dynamic susceptibility contrast (DSC), diffusion tensor imaging (DTI) and chemical shift imaging (CSI). The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from DTI and DSC respectively. Using thresholding methods, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified. Volumetric analysis was performed. Lactate and macromolecule/lipid levels were determined from multivoxel spectroscopy. Progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan-Meier and multivariate Cox regression analyses.

Results Two compartments displayed higher lactate and macromolecule/lipid levels than normal controls (each P < 0.001), suggesting hypoxic and pro-inflammatory microenvironment. The proportional volume of ADCL-rCBVL compartment was associated with a larger infiltration area (P < 0.001, rho = 0.42). Lower lactate in this compartment was associated with a less invasive phenotype visualized on DTI. Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with a worse survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005).

Conclusions The ADCL-rCBVL compartment represent a treatment resistant sub-region associated with glioblastoma invasiveness. This approach was based on clinically available imaging modalities and could thus provide crucial pretreatment information for clinical decision making.

Footnotes

  • Funding This study was funded by a National Institute for Health Research (NIHR) Clinician Scientist Fellowship (SJP, project reference NIHR/CS/009/011); CRUK core grant C14303/A17197 and A19274 (FM lab); Cambridge Trust and China Scholarship Council (CL & SW); the Chang Gung Medical Foundation and Chang Gung Memorial Hospital, Keelung, Taiwan (JLY); CRUK & EPSRC Cancer Imaging Centre in Cambridge & Manchester (FM & TT, grant C197/A16465); NIHR Cambridge Biomedical Research Centre (TM & SJP).

  • Conflict of Interest: none

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 25, 2018.
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Low Perfusion Compartments in Glioblastoma Quantified by Advanced Magnetic Resonance Imaging and Correlated with Patient Survival
Chao Li, Jiun-Lin Yan, Turid Torheim, Mary A. McLean, Natalie R. Boonzaier, Yuan Huang, Jianmin Yuan, Bart RJ Van Dijken, Tomasz Matys, Florian Markowetz, Stephen J. Price
bioRxiv 180521; doi: https://doi.org/10.1101/180521
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Low Perfusion Compartments in Glioblastoma Quantified by Advanced Magnetic Resonance Imaging and Correlated with Patient Survival
Chao Li, Jiun-Lin Yan, Turid Torheim, Mary A. McLean, Natalie R. Boonzaier, Yuan Huang, Jianmin Yuan, Bart RJ Van Dijken, Tomasz Matys, Florian Markowetz, Stephen J. Price
bioRxiv 180521; doi: https://doi.org/10.1101/180521

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