Association of ADC of hyperintense lesions on FLAIR images with TERT promoter mutation status in glioblastoma IDH wild type

Abstract

Background: Although mutations in telomerase reverse transcriptase (TERT) promoter (TERTp) are the most common alterations in glioblastoma (GBM), predicting TERTp mutation status by preoperative imaging is difficult. We determined whether tumour-surrounding hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) were superior to those of contrast-enhanced lesions (CELs) in assessing TERTp mutation status using magnetic resonance imaging (MRI).

Methods: This retrospective study included 114 consecutive patients with primary isocitrate dehydrogenase (IDH)-wild-type GBM. The apparent diffusion coefficient (ADC) and volume of CELs and FLAIR hyperintense lesions (FHLs) were determined, and the correlation between MRI features and TERTp mutation status was analyzed. In a subset of cases, FHLs were histopathologically analyzed to determine the correlation between tumor cell density and ADC.

Results: TERTp mutations were present in 77 (67.5%) patients. The minimum ADC of FHLs was significantly lower in the TERTp-mutant group than in the TERTp-wild-type group (mean, 958.9 × 10^-3 and 1092.1 × 10^-3 mm²/s, respectively, P < 0.01). However, other MRI features, such as CEL and FHL volumes, minimum ADC of CELs, and FHL/CEL ratio, were not significantly different between the two groups. Histopathologic analysis indicated high tumor cell density in FHLs with low ADC.

Conclusion: The ADC of FHLs was significantly lower in IDH-wild-type GBM with TERTp mutations, suggesting that determining the ADC of FHLs on preoperative MRI might be helpful in predicting TERTp mutation status and surgical planning.

Keywords: Apparent diffusion coefficients (ADC); Fluid-attenuated inversion recovery hyperintense lesion; Glioblastoma; Telomerase reverse transcriptase (TERT).

Figure 1:

Image analysis of preoperative magnetic resonance imaging scans. Several regions of interest (ROIs) of hyperintense lesions on fluid-attenuated inversion recovery (FLAIR) high lesion (FHLs) at least 3 mm away from (a) the contrast-enhanced lesion (CEL) on (b) FLAIR. (c) Next, apparent diffusion coefficients (ADCs) of corresponding ROIs in FHLs were calculated on the ADC map. CEL and FHL volumes were measured after image fusion of contrast-enhanced T1-weighted and FLAIR images. (d) Segmentations of CEL and FHL were based on differences in signal intensity using the semiautomatic “smartbrush” tool. (e) Finally, 3D volumetric evaluations of CELs and FHLs were performed. FHL: FLAIR high lesion.

Figure 2:

Bar graphs show the comparison of minimum apparent diffusion coefficients values of (a) contrast-enhanced lesions and (b) FLAIR hyperintense lesions between the groups without or with telomerase reverse transcriptase promoter mutations. Relationships between the two groups were evaluated using the Mann–Whitney U-test (*P < 0.05).

Figure 3:

Histological features of FLAIR hyperintense lesions. (a) Note sparse tumor cells in a tissue sample collected from a lesion with high apparent diffusion coefficient (ADC) (1534.9 × 10⁻³ mm²/s). (b) Note high tumor cell density in a tissue sample collected from a lesion with low ADC (1272.5 × 10⁻³ mm²/s). (c) There was a trend toward a negative correlation between ADC and tumor cell density, although a statistically significant correlation could not be observed due to the small number of tumor samples.