Background

Despite an aggressive treatment, about 50% of patients diagnosed with glioma decease within 5 years. Therefore, improving both diagnostic imaging and treatments are essential for these patients. It is not only a prolonged survival that is desirable, but also a good quality of life. In many cases, patients undergo surgery, subsequently followed by a combination of chemotherapy and radiation therapy. The ionising radiation is focused on the pre-surgical location of the tumour, including margins into unaffected areas. The treatment is delivered five times a week during six weeks, each day a dose of 2 Gy is given up to a total of 60 Gy. A disadvantage of the interventions is that the therapy affects not only the tumour, but also to some extent the surrounding tissue. Which can result in cognitive dysfunction thus effecting quality of life. Standard clinical routine prescribes conventional MRI in the pre- and post-operative setting and also during follow-up after treatment. In this study relaxometry was used to analyse normal appearing white matter (NAWM) after radiation therapy in gliomas.

Aim

Detecting changes, such as demyelination, in normal appearing white matter (NAWM) caused by radiation therapy using quantitative MRI (qMRI).

Material & methods

The qMRI sequence SyMRI MaGiC (GE Healthcare) was added to the conventional clinical MR-protocol when scanning 10 high grade glioma patients. The axial scans had a FOV of 220 x 180 mm² and voxel size of 0.43 x 0.43 x 5 mm³. A total of 24 slices were collected with a total scan time of 5:55 min. Images reconstructed/calculated were T1- and T2- maps, proton density map and myelin concentration map, as well as synthetic T2-weighted images. Images were reconstructed using SyMRI (SyntheticMR AB). Relaxation rates R₁ and R₂ were calculated from the reconstructed T1 and T2-maps. Changes in NAWM were detected by comparing differences of mean values in ROIs from different time-points, compared with the pre-operative MRI. ROIs were placed in up to 14 anatomical regions. ROIs were not placed if tumour or oedema was/had been present at that location. An example of the T2-weighted images with ROI-placement and absorbed dose as an overlay is shown in Fig. 1. The quantitative maps of R₁, R₂, proton density and myelin concentration are also shown for one patient with four follow-up examinations. Association between changes were then analysed as a function of absorbed dose from radiation therapy and time after treatment.

Results

A significant decrease in myelin concentration (-2.2%) between pre-operative and 1^st follow-up images was observed, and also a corresponding increase in PD (1.5%). No significant changes in R₁ were observed although there was a significant change (0.3 s^-1) in R₂. Associations between dose and time are shown in Fig 2. With time and low dose, the PD-value and myelin concentration returned to baseline, while for high doses (>30 Gy) there was an increase with time. R₂ returned to baseline with time, but independent of dose level. A more pronounced change was seen for higher doses.

Discussion and conclusion

qMRI can be used succesfully in a clinical setting during longitudinal follow-up after therapy of glioma patients for detecting changes in tissue parameters such as R₂, PD and myelin concentration. It is important to note that the observed changes was a consequence of chemoradiotherapy; they were not observed in the post-operative images after surgery. After therapy a demyelination was observed and for low doses, but not for high doses, myelin concentration returned to baseline with time. The severity of the demyelination and remyelination depended on the accumulated amount of ionising radiation. Our analysis showed that the effects were not due to oedema, as R₂ did not decrease.

References

Warntjes, J.B., O. Dahlqvist, and P. Lundberg, Novel method for rapid, simultaneous T1, T2*, and proton density quantification. Magn Reson Med, 2007. 57(3): p. 528-37.

Warntjes, J.B., et al., Rapid magnetic resonance quantification on the brain: Optimization for clinical usage, in MAGNETIC RESONANCE IN MEDICINE. 2008, John Wiley & Sons, Ltd: United States. p. 320-329.