Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion

Wouter van Elmpt, Catharina M L Zegers, Bart Reymen, Aniek J G Even, Anne-Marie C Dingemans, Michel Oellers, Joachim E Wildberger, Felix M Mottaghy, Marco Das, Esther G C Troost, Philippe Lambin, Wouter van Elmpt, Catharina M L Zegers, Bart Reymen, Aniek J G Even, Anne-Marie C Dingemans, Michel Oellers, Joachim E Wildberger, Felix M Mottaghy, Marco Das, Esther G C Troost, Philippe Lambin

Abstract

Purpose: Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level.

Methods: A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes.

Results: At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p = 0.014), hypoxic fraction (-0.60, p = 0.025) and TBR (-0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia.

Conclusion: The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia.

Keywords: DCE CT; FDG PET; HX4; Hypoxia PET; Image analysis; Multiparametric.

Figures

Fig. 1
Fig. 1
Example of multiparametric imaging in a patient with NSCLC in the right lower lobe. Left to right: CT image with the primary tumour delineated (in red), metabolic activity imaged with FDG PET/CT, hypoxia imaged with HX4 PET/CT, and perfusion parameters (blood flow and blood volume) depicted with DCE CT
Fig. 2
Fig. 2
Relationships between hypoxic volumes (left two plots) and average hypoxic TBR (right two plots) and averaged perfusion parameters blood flow and blood volume in the primary tumour in each patient. Hypoxic volume is defined as the volume within the primary tumour with a TBR >1.2. Tumours with larger hypoxic volumes or increased TBR levels have impaired blood flow
Fig. 3
Fig. 3
Venn diagrams showing schematically the overlap between the high metabolic regions (FDG, red), hypoxic regions with a TBR of >1.2 (HX4, green) and increased perfusion blood flow regions (DCE CT, blue) in each patient. The patients are ordered according to the amount of overlap between hypoxia and blood flow. The diagram on the right shows the average overlap volumes for all patients. Venn diagrams for hypoxic regions defined using a TBR of >1.4 are shown in Supplementary Fig. 1

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