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DEMONSTRATION OF THE RELATIONSHIP BETWEEN OXYGEN DELIVERY AND CONTRAST AGENT DELIVERY IN HUMAN GLIOMA USING COMBINED OEMRI AND DCE-MRI

Introduction Tumour hypoxia has been linked to progression and metastasis and is also known to affect sensitivity to treatment. Oxygen-enhanced MRI (OEMRI) is a proposed non-invasive method to investigate oxygen delivery and consumption in tumour tissue that is based on observing changes in T1. Under normoxic conditions, an oxygen gas challenge results in an increase of paramagnetic molecular oxygen dissolved in the blood plasma, leading to a signal change on T1-weighted images in arteries and certain tissues, including tumours. Initial clinical results have shown regional correlations between signal changes during OEMRI and those during DCE-MRI in abdominal and pelvic tumours [1]. More recently, pre-clinical results in a glioma model have shown significant R1 changes in both a positive and negative direction during a normobaric oxygen gas challenge [2]. The aim of this work was to analyse a human glioma dataset that included both OEMRI and DCE-MRI to establish if similar phenomena are apparent in humans and to investigate the oxygen-enhanced R1 changes and the regional correlations between these and DCE-MRI parameters. Methods Patients Ethical approval was granted. 4 patients with glioma were recruited and informed consent was obtained. Imaging OEMRI: Subjects were scanned on a 3.0 T Achieva scanner (Philips Healthcare, Best, the Netherlands) with an 8 channel SENSE head coil. Subjects sequentially breathed medical air and 100% O2 (15 l/min) through a non-rebreathing face-mask. 3D T1 maps were acquired using spoiled gradient echo sequences with the variable flip angle technique [3] (TE=1.1 ms, TR=3.5 ms; flip angles =2°, 5°, 10°, 16°; matrix 128 x 128 x 25, 1.8 mm x 1.8 mm x 4.2 mm, 4 signal averages): 11 maps during the breathing of air, and then 12 during the breathing of O2. DCE-MRI: Breathing gas was changed back to air, and a baseline 3D T1 map was acquired, followed by 100 T1-weighted spoiled gradient echo volumes (TE=1.1 ms, TR=3.5 ms; flip angle=15°, matrix 128x128x25, 1.8 mm x 1.8 mm x 4.2 mm). Contrast agent was injected after 10 time points. Analysis OEMRI Images were registered using the 3D rigid body algorithm in FLIRT [4] to correct for possible patient motion. T1 values were converted to R1, and baseline drift was corrected using a linear regression fit [5]. Maps of mean R1 and standard deviation were calculated for air and oxygen inhalation, and then ΔR1 was calculated on a voxel-wise basis. Area under the O2 ΔR1 curve (IAUCOE) was calculated. A t-test (p≤0.05) was carried out to determine voxels with a significant positive or negative ΔR1 on oxygen. Tumour VOIs were delineated on the initial acquisition and applied to the time series for all subjects. VOIs were then created for regions within the tumour with significant positive or negative ΔR1. DCE-MRI: T1-weighted signal intensity was converted to contrast agent concentration. Initial area under the concentration curve up to 120 seconds postinjection (IAUCGd) was calculated. Results Figure 1 shows the R1 change for regions with significant positive (red) and negative (blue) ΔR1 during oxygen inhalation averaged over all tumours (n = 4). 12 % of voxels in all tumours showed a significant positive ΔR1 and 34% showed a significant negative ΔR1. DCE contrast agent uptake curves for the same regions are shown in figure 2. Figure 3 shows glioma IAUCOE (left) and IAUCGd (right) maps for a single slice in two subjects.