Session Item

Hypoxia promotes tumour development, progression and treatment resistance. Oxygen-enhanced (OE)-MRI has shown promise as a non-invasive method of mapping and quantifying hypoxia; the oxygen-induced change in longitudinal relaxation rate (ΔR₁) can identify normoxic tumour and distinguish this from hypoxic tumour, which has no demonstrable oxygen-induced change in ΔR₁. This technique has previously detected hypoxia modification in patients with non-small cell lung cancer (Salem 2019 CCR). We hypothesised that ΔR₁ could be developed in head and neck (H&N) squamous cell carcinoma. 

Participants were recruited after written informed consent to an ethics approved study. Imaging was performed on a 1.5 T Philips Ingenia MR-RT system.

Sequences were optimised in 4 healthy volunteers and included anatomical imaging, quantitative T₁ measurement (3D inversion recovery turbo field echo, inversion times (TI) = 100, 500, 800, 1100, 4300 ms) and a dynamic OE acquisition using the same sequence as for T₁ measurement with TI = 1100 ms, temporal resolution = 12 s. Gas delivery during dynamic series: scans 1-25 (medical air; 21% O₂), 26-70 (100% O₂) and 71-91 (medical air; 21% O₂). A gas blender ensured a flow rate of 15 l/min via a high concentration mask.

A finalised protocol was run in a further 6 healthy volunteers, each imaged twice (8 ± 3 days apart), and in 4 patients with H&N carcinoma, imaged 1 or 2 times at baseline and then once during chemoradiotherapy (CTRT). 

Analysis used MATLAB (Mathworks). Quantitative T₁ maps enabled conversion of signal change to ΔR₁ (where ΔR₁ = R_1,O2 – R_1,air). In volunteers, regions of interest were positioned in three tissue regions; the nasal concha (NC), tongue and brain. Mean ΔR₁ values and within-subject coefficient of variation (wCV) were obtained for each tissue. Patient tumour volumes were delineated on T₁ weighted post gadolinium contrast images. ΔR₁ was measured for each tumour and tissue volume at each visit. 

Volunteer ΔR₁ curves for the two visits for the NC, tongue and brain regions are shown in Figure 1. Mean ΔR_1,NC = 0.059 ± 0.027 s^-1 (p < 0.001, ΔR₁ change); ΔR_1,Tongue = 0.001 ± 0.012 s^-1 (p = 0.86); ΔR_1,Brain = 0.005 ± 0.005 s^-1 (p = 0.04) (Figure 1a-c), indicating that NC provided consistent, significant change. wCV for NC was 21.0% (Figure 1d). Patient ΔR_1,NC = 0.056 ± 0.026 s^-1 (p < 0.001), indicating successful gas delivery. ΔR₁ increased in the primary tumour in all four patients two to four weeks after commencing CTRT (p=0.04), and has good baseline repeatability (n=2) (Figure 2). 

We have translated OE-MRI for use in patients with H&N cancer. Healthy volunteer data identified the NC as a consistent and repeatable reference region to demonstrate technique quality control on a per subject basis. Patient data demonstrated successful clinical translation. All 4 patients had increase in ΔR₁ in the primary tumour during CTRT, consistent with reduction in hypoxia during therapy. Trial recruitment is ongoing.