Hypoxia and perfusion in breast cancer: simultaneous assessment using PET/MR imaging

• Published in: European radiology 2021-01, Vol.31 (1), p.333-344
• Main Authors: Carmona-Bozo, Julia C., Manavaki, Roido, Woitek, Ramona, Torheim, Turid, Baxter, Gabrielle C., Caracò, Corradina, Provenzano, Elena, Graves, Martin J., Fryer, Tim D., Patterson, Andrew J., Gilbert, Fiona J.
• Format: Article
• Language: English
• Subjects: Breast; Breast cancer; Breast Neoplasms - diagnostic imaging; Correlation analysis; Diagnostic Radiology; Female; Fluorine isotopes; Heterogeneity; Histology; Humans; Hypotheses; Hypoxia; Hypoxia - diagnostic imaging; Imaging; Internal Medicine; Interventional Radiology; Lesions; Magnetic Resonance Imaging; Medical imaging; Medicine; Medicine & Public Health; Neuroradiology; Parameters; Perfusion; Positron emission; Positron emission tomography; Radiology; Temporal variations; Tomography; Treatment resistance; Tumors; Ultrasound
• ISSN: 0938-7994; 1432-1084
• DOI: 10.1007/s00330-020-07067-2

Objectives Hypoxia is associated with poor prognosis and treatment resistance in breast cancer. However, the temporally variant nature of hypoxia can complicate interpretation of imaging findings. We explored the relationship between hypoxia and vascular function in breast tumours through combined 18 F-fluoromisonidazole ( 18 F-FMISO) PET/MRI, with simultaneous assessment circumventing the effect of temporal variation in hypoxia and perfusion. Methods Women with histologically confirmed, primary breast cancer underwent a simultaneous 18 F-FMISO-PET/MR examination. Tumour hypoxia was assessed using influx rate constant K i and hypoxic fractions (%HF), while parameters of vascular function ( K trans , k ep , v e , v p ) and cellularity (ADC) were derived from dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI, respectively. Additional correlates included histological subtype, grade and size. Relationships between imaging variables were assessed using Pearson correlation ( r ). Results Twenty-nine women with 32 lesions were assessed. Hypoxic fractions > 1% were observed in 6/32 (19%) cancers, while 18/32 (56%) tumours showed a %HF of zero. The presence of hypoxia in lesions was independent of histological subtype or grade. Mean tumour K trans correlated negatively with K i ( r  = − 0.38, p  = 0.04) and %HF ( r  = − 0.33, p  = 0.04), though parametric maps exhibited intratumoural heterogeneity with hypoxic regions colocalising with both hypo- and hyperperfused areas. No correlation was observed between ADC and DCE-MRI or PET parameters. %HF correlated positively with lesion size ( r  = 0.63, p  = 0.001). Conclusion Hypoxia measured by 18 F-FMISO-PET correlated negatively with K trans from DCE-MRI, supporting the hypothesis of perfusion-driven hypoxia in breast cancer. Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that combined assessment may be needed for disease characterisation, which could be achieved using simultaneous multimodality imaging. Key Points • At the tumour level, hypoxia measured by 18 F-FMISO-PET was negatively correlated with perfusion measured by DCE-MRI, which supports the hypothesis of perfusion-driven hypoxia in breast cancer. • No associations were observed between 18F-FMISO-PET parameters and tumour histology or grade, but tumour hypoxic fractions increased with lesion size. • Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that the combined hypoxia-perfusion statu