Monitoring temozolomide treatment of low-grade glioma with proton magnetic resonance spectroscopy

Abstract

Assessment of low-grade glioma treatment response remains as much of a challenge as the treatment itself. Proton magnetic resonance spectroscopy ((1)H-MRS) and imaging were incorporated into a study of patients receiving temozolomide therapy for low-grade glioma in order to evaluate and monitor tumour metabolite and volume changes during treatment. Patients (n=12) received oral temozolomide (200 mg m(-2) day(-1)) over 5 days on a 28-day cycle for 12 cycles. Response assessment included baseline and three-monthly magnetic resonance imaging studies (pretreatment, 3, 6, 9 and 12 months) assessing the tumour size. Short (TE (echo time)=20 ms) and long (TE=135 ms) echo time single voxel spectroscopy was performed in parallel to determine metabolite profiles. The mean tumour volume change at the end of treatment was -33% (s.d.=20). The dominant metabolite in long echo time spectra was choline. At 12 months, a significant reduction in the mean choline signal was observed compared with the pretreatment (P=0.035) and 3-month scan (P=0.021). The reduction in the tumour choline/water signal paralleled tumour volume change and may reflect the therapeutic effect of temozolomide.

Figure 1

A series of images from patient #5 demonstrating the reduction in tumour volume apparent on FLAIR (top) and T2W-FSE (bottom) images. Images displayed are from (A) pretreatment and post-treatment at (B) 3 months, (C) 6 months, (D) 9 months and (E) 12 months. Note the visible reduction in abnormal signal intensity on the FLAIR image during the course of the patient's treatment with temozolomide. A postsurgical cavity (seen as low signal in the axial images) is situated immediately posterior to the abnormal high signal intensity. (The cross hairs in each image indicate the magnetic isocentre. Where the voxel is not represented as a single square was due to the obliquity of the underlying reference images).

Figure 2

Long echo time (TE=135 ms, left of figure) and short echo time (TE=20 ms, right of figure) STEAM spectra obtained from patient #5 during temozolomide treatment: (A) pretreatment, (B) at 3 months, (C) at 6 months and (D) 9 months. Within both series a progressive decrease in the choline/creatine ratio is observed, suggesting a reduced membrane metabolism and diminishing cellular density. Also note the increasing conspicuity of the NAA peak. N-acetyl aspartate is a specific neuronal marker and may reflect the regression of tumoral tissue and repopulation of normal brain matter.

Figure 3

Mean choline and mean volume expressed as a percentage for all 12 patients completing the 12 months of treatment. The % choline is calculated by normalising the TE=135 ms signal to water. For each patient all post-treatment values were normalised to the pretreatment volume and choline data. The error bars represent the s.e. associated with the mean. Note the almost parallel trend in the reduction of tumour choline and volume.