Multimodal neuroimaging of gliomatosis cerebri: a case series of four patients

Abstract

In the latest World Health Organization classification of brain tumors, gliomatosis cerebri has been redefined to varying subsets of diffuse gliomas; however, the term is still used to describe gliomas with infiltrative growth into three or more cerebral lobes. These tumors are frequently misdiagnosed and difficult to treat due to their atypical presentation using structural imaging modalities including computed tomography and T1/T2-weighted magnetic resonance imaging (MRI). In this retrospective case series, we compared clinical MRI to amino acid positron emission tomography (PET) to assess the potential value of PET in the assessment of the extent of tumor involvement and in monitoring disease progression. We report the clinical course and serial multimodal imaging findings of four patients. Each patient presented at varying points in disease progression with widespread glioma brain involvement and was evaluated at least once by amino acid PET using alpha-[¹¹C]methyl-L-tryptophan ([¹¹C]-AMT). Increased uptake of [¹¹C]-AMT was detected in a subset of non-enhancing brain lesions and detected tumor invasion before MRI signs of tumor in some regions. Increased uptake of [¹¹C]-AMT was also detected in tumorous regions not detected by perfusion MRI or MR spectroscopy. Metabolic response to treatment was also observed in two patients. Overall, these data are consistent with and expand upon previous reports using other amino acid PET tracers in gliomatosis and show the potential added value of this imaging modality to clinical MRI in the detection and monitoring of these diffusely infiltrative tumors.

Keywords: Positron emission tomography; [11C]-AMT; amino acid; glioma; gliomatosis; magnetic resonance imaging; neuroimaging.

Fig. 1.

Representative axial image planes from the 2011 scans of patient 1: co-registered [¹¹C]-AMT-PET/MRI post-gadolinium (T1-gad) images in the upper panel and corresponding FLAIR images in the lower panel. The images demonstrate multiple [¹¹C]-AMT-accumulating lesions in the right parietal, left medial frontal, left insular, and left inferior temporal regions (arrows), which also showed an increased signal on FLAIR images but no contrast enhancement. FLAIR showed additional brain regions with high signal but low uptake of [¹¹C]-AMT, consistent with edema. Note that high uptake of [¹¹C]-AMT in the basal ganglia, occipital cortex, and cerebellum is physiologic.

Fig. 2.

Representative axial brain images for patient 2. (a) T1 MRI with gadolinium fused with [¹¹C]-AMT-PET image, the red arrow highlights the left contrast-enhancing thalamic lesion with SUV ratio of 3.96, the yellow arrow highlights the right non-enhancing thalamus lesion with an SUV ratio of 1.4. (b) [¹¹C]-AMT-PET image (c) T1 gadolinium image, (d) T2 image.

Fig. 3.

Representative axial images for patient 3 from July 2017. (a) T1 MRI with gadolinium fused with [¹¹C]-AMT-PET image, with the red arrow highlighting the left medial temporal lesion with SUV ratio of 1.74. (b) [¹¹C]-AMT-PET image, (c) T2/FLAIR image, (d) T1 post-gadolinium image.

Fig. 4.

Representative axial images for patient 4 from February 2017, before receiving TTFields therapy (a–d) and from April 2017, two months after starting TTFields treatment combined with bevacizumab and irinotecan (e–h). (a) T1 post-gadolinium MRI fused with [¹¹C]-AMT-PET image, the yellow arrow highlights the left temporal lesion with SUV ratio of 2.5 and the red arrow highlighting the right frontal DVM lesion (SUV ratio of 1.6). (b) [¹¹C]-AMT-PET image, (c) T1 gadolinium image, (d) T2 image. Repeated AMT-PET in April 2017 showed a new area with high uptake of [¹¹C]-AMT in the right inferior medial region (SUV ratio = 1.6). (e) T1 MRI with gadolinium fused with [¹¹C]-AMT-PET image, red arrow highlighting the new frontal lesion. The left temporal lesion showed a decreased SUV ratio (1.4) compared to the first study. (f) [¹¹C]-AMT-PET image, (g) T1 gadolinium image, (h) T2 image. TTFields, Tumor Treatment Fields.

Fig. 5.

Representative images for patient 4 from July 2017 demonstrating additional, non-enhancing lesions with increased uptake of [¹¹C]-AMT including left frontal (red arrow, SUV ratio = 1.98), right periventricular (yellow arrow, SUV ratio = 1.86), and right frontal (green arrow, SUV ratio = 2.49) lesions that emerged during continuing TTFields therapy: (a) T1 MRI with gadolinium fused with [¹¹C]-AMT-PET image with three new frontal lesions highlighted. (b) [¹¹C]-AMT-PET image, (c) T1 gadolinium image. (d) T1 MRI with gadolinium fused with [¹¹C]-AMT-PET image of a new high right frontal lesion highlighted by red arrow (SUV ratio = 2.2); (e) [¹¹C]-AMT-PET image, (f) T1 MRI with gadolinium image.