Optimising oxygen-enhanced MRI for patients with head and neck carcinoma

Abstract

Purpose or Objective 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. Materials and Methods 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 = R1,O2 – R1,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. Results Volunteer ΔR1 curves for the two visits for the NC, tongue and brain regions are shown in Figure 1. Mean ΔR1,NC = 0.059 ± 0.027 s-1 (p < 0.001, ΔR1 change); ΔR1,Tongue = 0.001 ± 0.012 s-1 (p = 0.86); ΔR1,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 ΔR1,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). Conclusion 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.