Imaging Spectrum of the Developing Glioblastoma: A Cross-Sectional Observation Study

Abstract

Glioblastoma (GBM) has the typical radiological appearance (TRA) of a centrally necrotic, peripherally enhancing tumor with surrounding edema. The objective of this study was to determine whether the developing GBM displays a spectrum of imaging changes detectable on routine clinical imaging prior to TRA GBM. Patients with pre-operative imaging diagnosed with GBM (1 January 2014-31 March 2022) were identified from a neuroscience center. The imaging was reviewed by an experienced neuroradiologist. Imaging patterns preceding TRA GBM were analyzed. A total of 76 out of 555 (14%) patients had imaging preceding TRA GBM, 57 had solitary lesions, and 19 had multiple lesions (total = 84 lesions). Here, 83% of the lesions had cortical or cortical/subcortical locations. The earliest imaging features for 84 lesions were T2 hyperintensity/CT low density (n = 18), CT hyperdensity (n = 51), and T2 iso-intensity (n = 15). Lesions initially showing T2 hyperintensity/CT low density later showed T2 iso-intensity. When CT and MRI were available, all CT hyperdense lesions showed T2 iso-intensity, reduced diffusivity, and the following enhancement patterns: nodular 35%, solid 29%, none 26%, and patchy peripheral 10%. The mean time to develop TRA GBM from T2 hyperintensity was 140 days and from CT hyperdensity was 69 days. This research suggests that the developing GBM shows a spectrum of imaging features, progressing through T2 hyperintensity to CT hyperdensity, T2 iso-intensity, reduced diffusivity, and variable enhancement to TRA GBM. Red flags for non-TRA GBM lesions are cortical/subcortical CT hyperdense/T2 iso-intense/low ADC. Future research correlating this imaging spectrum with pathophysiology may provide insight into GBM growth patterns.

Keywords: brain; computed tomography; glioblastoma; magnetic resonance imaging.

Figure 1

Derivation of lesions that did not show TRA GBM. Total number of lesions = 84; 57 solitary lesions and 27 with >1 locus. 20 of the 57 solitary lesions had tissue sampling when imaging never showed TRA GBM, so-called non-typical GBM.

Figure 2

Examples of the imaging of non-typical GBM at the time of tissue sampling. Case 1: 72-year-old female presented with sudden-onset dysphasia. Unenhanced (non-intravenous contrast administration) CT (NC CT) showed a hyperdense lesion in the posterior aspect of the left superior temporal gyrus (arrow). MRI obtained on the same day showed that the lesion had corresponding T2 iso, solid enhancement, and reduced diffusivity (high B1000, low apparent diffusion coefficient (ADC)). Case 2: 74-year-old female was referred for memory impairment. Unenhanced CT showed a hyperdense lesion in the right superior parietal lobule (two contiguous CT slices shown). No MRI was obtained due to the patient having an incompatible permanent pacemaker. Unenhanced CT at day 11 showed post-biopsy appearances with small volume pneumocephalus within the hyperdense lesion. Case 3: 62-year-old male presented with left-sided weakness. Unenhanced CT showed a hyperdense lesion in the right thalamus (left image). Post-biopsy unenhanced CT (right image) with frontal subdural pneumocephalus and small focus of pneumocephalus at the biopsy site. MRI was contraindicated. Case 4: 50-year-old male presented with a seizure. Unenhanced CT revealed a hyperdense lesion in the right inferior parietal lobule. MRI at day 30 showed corresponding T2 iso, reduced diffusivity, and solid enhancement. Case 5: 56-year-old female presented with a seizure. Unenhanced CT at day 0 showed a hyperdense lesion in the right temporal lobe. MRI on day 17 showed that the lesion was T2 iso, had internal reduced diffusivity with corresponding solid enhancement. Case 6: 52-year-old female presented with a seizure. Hyperdense lesion in the anterior aspect of the right superior frontal gyrus on unenhanced CT at day 0. This had corresponding T2 iso and reduced diffusivity on MRI obtained on day 2. T1-weighted post-gadolinium (T1Gd) imaging obtained on day 3 and day 13 showed solid tumoral enhancement increasing in size over the 10-day interval. Case 7: 56-year-old male presented with a seizure. Unenhanced CT demonstrated a hyperdense lesion in the left paracentral lobule with surrounding low attenuation in left frontal and parietal lobes. MRI on day 1 revealed a T2 iso infiltrative lesion with a focus of reduced diffusivity and tiny dot of solid enhancement in the area of hyperdensity shown on the initial CT. MRI at day 33 showed a solid tumor (no necrosis) with a greater volume of solid enhancement at the site of prior CT hyperdensity. The Box in the top right of the image shows two enlarged examples of GBM where the tumor signal on T2-weighted imaging is isointense (T2 iso) to grey matter (taken from Cases 4 and 6). NC CT—non-contrast CT, T2W—T2-weighted, B1000—DWI, ADC—apparent diffusion coefficient map of DWI, T1Gd—T1-weighted post-gadolinium.

Figure 3

Examples of solitary lesions with TRA GBM at tissue diagnosis that had preceding imaging. Case 1: 56-year-old male presented with seizures. Unenhanced CT on day 0 showed a hyperdense lesion in the left frontal lobe. This had corresponding T2 iso signal with reduced diffusivity and central nodular enhancement on MRI day 6. TRA GBM followed on MRI day 98. Case 2: 53-year-old female presented with several days of intermittent left-sided anesthesia. Initial unenhanced CT day 0 showed a focus of hyperdensity within the posterior aspect of the right insula (arrow) with adjacent cortical low density. MRI day 5 revealed an infiltrative glioma within the right inferior parietal lobule and right insular with the focus of prior CT hyperdensity corresponding to T2 iso signal, reduced diffusivity and containing a tiny dot of enhancement (arrows). MRI day 102 showed TRA GBM at the site of the prior CT hyperdense focus but relative stability of the rest of the non-enhancing tumor. Case 3: 63-year-old male presented with seizures. Unenhanced CT day 0 revealed two abnormal areas: a hyperdense focus anteriorly in the right superior frontal gyrus (vertical arrow) and subcortical hypodensity in the right middle frontal gyrus (horizontal arrows). These foci were linked by hypodensity (not shown) correlating with one diffuse tumor. MRI day 29 demonstrated interval growth of the previously hyperdense lesion, showing TRA GBM with enhancing periphery and central necrosis. Note how the peripheral tumoral tissue shows T2 iso solid signal with reduced diffusivity and enhancement. MRI day 29 also showed progression of the previously low-density lesion but not to TRA GBM. This lesion was shown to infiltrate into the deep white matter of the right centrum semiovale, contain areas of reduced diffusivity but no enhancement. TRA GBM—typical radiological appearance of glioblastoma, NC CT—non-contrast CT, T2W—T2-weighted, B1000—DWI, ADC—apparent diffusion coefficient map of DWI, T1Gd—T1-weighted post-gadolinium.

Figure 4

Examples of early GBM progressing through T2 hyperintensity to T2 iso and CT hyperdensity prior to showing TRA GBM. Case 1: 68-year-old male presented with dysphasia at day 96 leading to unenhanced CT investigation, which showed a solitary hyperdense lesion in the anterolateral aspect of the left parietal lobe, bordering the left supramarginal gyrus. MRI at day 172 showed TRA GBM with central necrosis and peripheral enhancement. MRI at day 0 obtained for an 8-week history of left-sided hearing loss revealed subtle cortical expansion at the site of future GBM (arrows) with no reduced diffusivity. On MRI day 37 the cortical expansion was more apparent showing relative growth to day 0. Case 2: 59-year-old male with progressively worsening headaches. MRI day 0 showed small foci of T2 signal hyperintensity in the cortex of the right precuneus (small arrow) and within the posterior aspect of the right parahippocampal gyrus (long vertical arrow). Neither the focus of T2 signal hyperintensity showed reduced diffusivity nor enhancement. Note the smooth dural thickening and enhancement on the T1Gd images. MRI day 87 showed interval growth of the lesion in the right precuneus with some central necrosis and peripheral enhancement. The lesion in the right parahippocampal gyrus had also grown relative to day 0 and continued to show facilitated diffusion and nonenhancement. The working diagnosis at the time of day 0 and day 87 was granulomatosis with polyangiitis, as the patient was ANCA positive and had no other known cause for dural enhancement. MRI day 193 showed growth at both lesion sites with TRA GBM. Note the new small ovoid focus of cortical T2 iso in the left inferior frontal gyrus (arrows), showing concomitant reduced diffusivity but no enhancement. An unenhanced CT obtained 3 days later, on day 196, showed corresponding CT hyperdensity in the lesion in the left inferior frontal gyrus and this subsequently developed into TRA GBM on MRI day 216. Note also the cortical T2 iso-lesion laterally in the posterior aspect of the left frontal lobe on MRI day 216 (3 vertical arrows), not clearly represented on CT day 196 (3 vertical arrows). This subsequently progressed to TRA GBM on MRI day 390 after showing growth and T2 iso signal on MRI day 300 with concomitant high B1000 signal but without enhancement (MRI day 300 was obtained 2 week after the patient’s third cycle of adjuvant TMZ—no RT was given as the patient declined whole brain RT, which was deemed the only valid RT option). Additionally, note TRA GBM within the splenium of the corpus callosum on MRI day 390 representing local progression of the original lesion (3 weeks following the patients sixth cycle of adjuvant TMZ). TRA GBM—typical radiological appearance of glioblastoma, NC CT—non-contrast CT, C+ CT—intravenous contrast-enhanced CT, T2W—T2-weighted, B1000—DWI, ADC—apparent diffusion coefficient map of DWI, T1Gd—T1-weighted post-gadolinium, RT—radiotherapy, TMZ—temozolomide, ANCA—antineutrophilic cytoplasmic antibody.