MRI-Based Assessment of Brain Tumor Hypoxia: Correlation with Histology

Author:

Arzanforoosh Fatemeh12ORCID,Van der Velden Maaike1,Berman Avery J. L.34ORCID,Van der Voort Sebastian R.12,Bos Eelke M.25ORCID,Schouten Joost W.25,Vincent Arnaud J. P. E.25,Kros Johan M.6ORCID,Smits Marion127ORCID,Warnert Esther A. H.12ORCID

Affiliation:

1. Department of Radiology & Nuclear Medicine, Erasmus MC, 3015 GD Rotterdam, The Netherlands

2. Brain Tumour Center, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands

3. Department of Physics, Carleton University, Ottawa, ON K1S 5B6, Canada

4. Institute of Mental Health Research, Royal Ottawa Mental Health Centre, University of Ottawa, Ottawa, ON K1N 6N5, Canada

5. Department of Neurosurgery, Erasmus MC Cancer Institute, 3015 GD Rotterdam, The Netherlands

6. Department of Pathology, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands

7. Medical Delta, 2629 JH Delft, The Netherlands

Abstract

Cerebral hypoxia significantly impacts the progression of brain tumors and their resistance to radiotherapy. This study employed streamlined quantitative blood-oxygen-level-dependent (sqBOLD) MRI to assess the oxygen extraction fraction (OEF)—a measure of how much oxygen is being extracted from vessels, with higher OEF values indicating hypoxia. Simultaneously, we utilized vessel size imaging (VSI) to evaluate microvascular dimensions and blood volume. A cohort of ten patients, divided between those with glioma and those with brain metastases, underwent a 3 Tesla MRI scan. We generated OEF, cerebral blood volume (CBV), and vessel size maps, which guided 3–4 targeted biopsies per patient. Subsequent histological analyses of these biopsies used hypoxia-inducible factor 1-alpha (HIF-1α) for hypoxia and CD31 for microvasculature assessment, followed by a correlation analysis between MRI and histological data. The results showed that while the sqBOLD model was generally applicable to brain tumors, it demonstrated discrepancies in some metastatic tumors, highlighting the need for model adjustments in these cases. The OEF, CBV, and vessel size maps provided insights into the tumor’s hypoxic condition, showing intertumoral and intratumoral heterogeneity. A significant relationship between MRI-derived measurements and histological data was only evident in the vessel size measurements (r = 0.68, p < 0.001).

Funder

Dutch Cancer Society

Dutch Research Council entitled “Food for thought: Oxygen delivery to the brain”

Dutch Research Council open technology program

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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