Integration method of 3D MR spectroscopy into treatment planning system for glioblastoma IMRT dose painting with integrated simultaneous boost

Abstract

Background: To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT).

Methods: For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE).

Results: Fusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and ≤1.15° for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (p < 0.05).

Conclusions: Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies.

Figure 1

3D-MRSI acquisition before radiation therapy treatment of a 53 year-old unresected patient with confirmed glioblastoma located in the right capsulo-thalamic region (first row, the volume of acquisition is framed in red). On the T1-Gd anatomic MR images showing contrast-enhancing disease, the MRSI volume of interest is defined on a voxel by voxel basis,when alteration of metabolites spectra is observed, the voxel is rejected (green frame on second row). The anatomic-metabolic maps are computed from the above defined volume of interest (third row), the maximum Cho/NAA ratio values are encoded in red color and are respectively from left to right 2.27, 2.30, 1.52 and 1.15. The first two metabolite maps which present ratios of Cho/NAA ≥ 2.00 suggest metabolic tumor activity. Regions of interest corresponding to ratio of Cho/NAA ≥ 2.00 are obtained after normalization and threshold based segmentation from the anatomic-metabolic images, these ROIs are highlighted in red (last row). Note on the first image (last row) that the location of the abnormal spectroscopic region is different and below the contrast-enhancing area.

Figure 2

Flow chart of the image processing steps to integrate MRSI-defined regions with abnormal Cho/NAA ratio values into RT TPS.

Figure 3

Comparison of dose plans between 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT. 60-Gy 3D-CRT and 60-Gy IMRT plans (respectively Figures3a and 3b) have one PTV1 color-washed in blue. The integration of Cho/NAA abnormal volumes defines new target relative to MRSI, i.e. PTV2 color-washed in red (Figure 3c), PTV1 is the same. The isodoses of 68.4 Gy (thick red isodose) and 57 Gy (thick dark blue isodose) represent 95% of the prescribed dose respectively 72 Gy and 60 Gy on the PVT2 and PTV1. The isodose volumes of 54 Gy (pink), 50 Gy (green), 36 Gy (purple) and 18 Gy (light blue) for organs at risk sparing are also plotted.

Figure 4

Comparison of the doses received by OAR between 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT for all patients (P1 to P16). Doses relative to 60-Gy 3D-CRT are drawn in white, grey for 60-Gy IMRT and black for 72-Gy SIB-IMRT. No significant difference is found when considering the maximum dose received by 1% of the optic chiasm (41.63 vs 45.47 and 42.08 Gy, p > 0.088) (Figure 4a). For the brainstem, the maximum dose received by 1% of the organ is significantly lower (57.01 vs 44.30 and 44.00 Gy, p < 0.001) in 60-Gy IMRT and 72-Gy SIB-IMRT (Figure 4b). Histograms of dose-volumes relative to normal brain comparing 60-Gy 3D-CRT (white), 60-Gy IMRT (grey) and 72-Gy SIB-IMRT (balck) are shown on Figure 4c. No significant difference is found when considering the V18 (p > 0.326). 60-Gy IMRT and 72-Gy SIB-IMRT were significantly smaller for V36 and V50 (19 and 20 vs. 23%, p = 0.049,7 and 7 vs. 12%, p < 0.001). No significant differences for V36 and V50 were found between 72-Gy SIB-IMRT and 60-Gy IMRT (p = 0.605).