Non-invasive assessment of glioma microstructure using VERDICT MRI: correlation with histology

Abstract

Purpose: This prospective study evaluated the use of vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT) MRI to investigate the tissue microstructure in glioma. VERDICT-derived parameters were correlated with both histological features and tumour subtype and were also used to explore the peritumoural region.

Methods: Fourteen consecutive treatment-naïve patients (43.5 years ± 15.1 years, six males, eight females) with suspected glioma underwent diffusion-weighted imaging including VERDICT modelling. Tumour cell radius and intracellular and combined extracellular/vascular volumes were estimated using a framework based on linearisation and convex optimisation. An experienced neuroradiologist outlined the peritumoural oedema, enhancing tumour and necrosis on T2-weighted imaging and contrast-enhanced T1-weighted imaging. The same regions of interest were applied to the co-registered VERDICT maps to calculate the microstructure parameters. Pathology sections were analysed with semi-automated software to measure cellularity and cell size.

Results: VERDICT parameters were successfully calculated in all patients. The imaging-derived results showed a larger intracellular volume fraction in high-grade glioma compared to low-grade glioma (0.13 ± 0.07 vs. 0.08 ± 0.02, respectively; p = 0.05) and a trend towards a smaller extracellular/vascular volume fraction (0.88 ± 0.07 vs. 0.92 ± 0.04, respectively; p = 0.10). The conventional apparent diffusion coefficient was higher in low-grade gliomas compared to high-grade gliomas, but this difference was not statistically significant (1.22 ± 0.13 × 10^-3 mm²/s vs. 0.98 ± 0.38 × 10^-3 mm²/s, respectively; p = 0.18).

Conclusion: This feasibility study demonstrated that VERDICT MRI can be used to explore the tissue microstructure of glioma using an abbreviated protocol. The VERDICT parameters of tissue structure correlated with those derived on histology. The method shows promise as a potential test for diagnostic stratification and treatment response monitoring in the future.

Key points: • VERDICT MRI is an advanced diffusion technique which has been correlated with histopathological findings obtained at surgery from patients with glioma in this study. • The intracellular volume fraction measured with VERDICT was larger in high-grade tumours compared to that in low-grade tumours. • The results were complementary to measurements from conventional diffusion-weighted imaging, and the technique could be performed in a clinically feasible timescale.

Keywords: Brain neoplasms; Cancer; Diagnostic imaging; Diffusion magnetic resonance imaging; Glioma.

Fig. 1

a Box and whisker plot illustrating the cell radius as measured by VERDICT MRI and pathology for low-grade glioma (LGG) and high-grade glioma (HGG). b H&E staining from a low-grade glioma shown in Fig. 2. c H&E staining from a high-grade glioma also shown in Fig. 2

Fig. 2

a–f Representative images from a low-grade glioma. a Axial post-gadolinium 3D T1-weighted imaging (T1WI). b Intracellular volume fraction. c Cell radius maps. d Axial T2WI. e Extracellular volume fraction. f ADC map, with a scale of × 10⁻⁶ mm²/s. Colour maps for b, c, e have been superimposed on the greyscale image from a with the colour scale shown for each image. g–l Representative images from a high-grade glioma. g Axial post-gadolinium 3D T1WI. h Intracellular volume fraction. i Cell radius maps. j Axial T2WI. k Extracellular volume fraction. l ADC map, with a scale of × 10⁻⁶ mm²/s. Colour maps for h, i, k have been superimposed on the greyscale image from a with the colour scale shown for each image

Fig. 3

Box and whisker plot showing intracellular (IC) volume fraction and extracellular (EC) volume fraction for both low-grade glioma (LGG) and high-grade glioma (HGG) derived from the VERDICT MRI model

Fig. 4

Apparent diffusion coefficient (ADC) values for low-grade glioma (LGG) and high-grade glioma (HGG) as derived from conventional DWI