Advanced Imaging Techniques for Radiotherapy Planning of Gliomas

Abstract

The accuracy of target delineation in radiation treatment (RT) planning of cerebral gliomas is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Conventional magnetic resonance imaging (MRI), including contrast-enhanced T1-weighted and fluid-attenuated inversion recovery (FLAIR) sequences, represents the current standard imaging modality for target volume delineation of gliomas. However, conventional sequences have limited capability to discriminate treatment-related changes from viable tumors, owing to the low specificity of increased blood-brain barrier permeability and peritumoral edema. Advanced physiology-based MRI techniques, such as MR spectroscopy, diffusion MRI and perfusion MRI, have been developed for the biological characterization of gliomas and may circumvent these limitations, providing additional metabolic, structural, and hemodynamic information for treatment planning and monitoring. Radionuclide imaging techniques, such as positron emission tomography (PET) with amino acid radiopharmaceuticals, are also increasingly used in the workup of primary brain tumors, and their integration in RT planning is being evaluated in specialized centers. This review focuses on the basic principles and clinical results of advanced MRI and PET imaging techniques that have promise as a complement to RT planning of gliomas.

Keywords: FET; PET; advanced MRI; amino acid radiopharmaceuticals; diffusion-weighted imaging; glioma; hypoxia; magnetic resonance spectroscopy; perfusion-weighted imaging; radiation treatment planning.

Figure 1

Integration of multiple white matter tracts as depicted by MR Tractography in the tomotherapy RT planning. (A,C) Post-surgical MR tractography analysis of a glioblastoma (GBM) patient: The upper image (A) shows the reconstructed tracts in the contralateral (healthy) hemisphere, while the lower image (C) shows the tracts surrounding the surgical cavity in the ipsilateral (affected) hemisphere. CST = corticospinal tract; IFOF = Inferior fronto-occipital fasciculus; UNC = uncinate fasciculus; SLF = superior longitudinal fasciculus. (B) Comparison of dose distributions for the original plan (on the left) and the tract-optimized plan (on the right), showing the different dose conformation outside the target and the preservation of relevant tracts. (D). The dose-volume histograms (DVH) data for the two planning modalities in B is shown. DVH for each tract in the original plan is represented with solid lines, while DVH for each tract in the new plan incorporating the fibers is represented with dotted lines. ‘I’ indicates ipsilateral tracts, while ‘C’ indicates contralateral tracts. A significant reduction of the dose delivered to tracts was observed when fibers were included in the optimization process, which was more relevant for contralateral tracts. No significant differences were found in PTV coverage between the original plans and the optimized plans incorporating fiber tracts (solid and dotted red lines). Adapted with permission from [87].

Figure 2

Integration of advanced MRI sequences in a Gamma Knife radiosurgical planning of a 44-year-old male patient with recurrent WHO grade III astrocytoma after multimodal first-line therapy and recent redo surgery with maximum safe resection. Axial (upper row) and coronal (bottom row) views of contrast-enhanced T1-weighted (A) and fluid-attenuated inversion recovery (FLAIR) (B) MRI images, co-registered with relative cerebral blood volume (rCBV) map (C) and apparent diffusion coefficient (ADC) map (D), demonstrating how different sequences identify different volumes of disease. The final target was determined as the nodule showing hyper-intensity in post-contrast T1-weighted sequences, hypo-intensity in ADC maps, and elevated perfusion values on the rCBV map.

Figure 3

The mismatch between contrast-enhanced T1-weighted MRI and 3,4-dihydroxy-6-[¹⁸F]fluoro-L-phenylalanine (F-DOPA) PET/CT in a 45-year-old female patient with recurrent GBM after multimodal first-line therapy. Two axial contrast-enhanced T1-weighted images (A,C) along with corresponding F-DOPA PET/CT slices (B,D) identifying different volumes of disease.

Figure 4

Example of a volumetric modulated arc therapy (VMAT) sequential boost of radiation to hypoxia-positive recurrent GBM. T2-weighted and contrast-enhanced T1-weighted MRI sequences were acquired along with ⁶⁴Cu-diacetyl-bis(N⁴-methylthiosemicarbazone) (ATSM) PET on a hybrid 3T PET/MR scanner, three hours after radiopharmaceutical injection (A,B). 37.5 Gy were delivered in 15 daily fractions to the surgical cavity followed by a boost of radiation (5 Gy) to the ⁶⁴Cu-ATSM-positive tumor region, indicating chronic hypoxia (C,D).

Figure 5

Integration of F-DOPA PET/CT in a LINAC-based radiosurgical planning of a 55-year-old female patient with recurrent GBM. (A) shows GTV based on contrast-enhanced T1-weighted MRI images; (B) shows remarkable F-DOPA uptake extending beyond contrast-enhancement. The final target volume was delineated by taking into account the F-DOPA-positive signal (C). Three-month follow-up (D) shows tumor progression at the site of pre-RT increased F-DOPA uptake, despite salvage irradiation.