Quantitative MRI demonstrates abnormalities of the third ventricle subventricular zone in neurofibromatosis type-1 and sporadic paediatric optic pathway glioma

Abstract

Background: The subventricular zone of the third ventricle (TVZ) is a germinal stem cell niche, identified as the possible location of optic pathway glioma (OPG) cell origin. Paediatric OPGs are predominantly diagnosed as low-grade astrocytomas, which are either sporadic or are associated with neurofibromatosis type-1 (NF1). These tumours often cause a significant impairment to visual acuity (VA). Infiltrative/invasive tumour activity is associated with increased apparent diffusion coefficient (ADC) and cerebral blood flow (CBF). This study aimed to determine whether TVZ imaging features differed between sporadic-OPG, NF1-OPG and controls, and whether the ADC and CBF profile at the germinal stem cell niche (the TVZ) correlated with the primary outcome of VA.

Methods: ADC and CBF MRI data were acquired from 30 paediatric OPG patients (median age 6 years; range 8 months-17 years), along with VA measurements, during clinical surveillance of their tumour. Values for mean ADC and maximum CBF were measured at the TVZ, and normalized to normal-appearing grey matter. These values were compared between the two OPG groups and the healthy control subjects, and multivariate linear regression was used to test the linear association between these values and patient's VA.

Results: In the TVZ, normalized mean ADC was higher in NF1-associated OPG patients (N = 15), compared to both sporadic OPG patients (N = 15; p = 0.010) and healthy controls (N = 14; p < 0.001). In the same region, normalized maximum CBF was higher in sporadic OPG patients compared to both NF1-OPG patients (p = 0.016) and healthy controls (p < 0.001). In sporadic OPG patients only, normalized mean ADC in the TVZ was significantly correlated with visual acuity (R² = 0.41, p = 0.019). No significant correlations were found between TVZ CBF and ADC values and visual acuity in the NF1-associated OPG patients.

Conclusion: Quantitative MRI detects TVZ abnormalities in both sporadic and NF1-OPG patients, and identifies TVZ features that differentiate the two. TVZ features may be useful MRI markers of interest in future predictive studies involving sporadic OPG.

Keywords: Neurofibromatosis type-1; Optic pathway glioma; Paediatric; Quantitative magnetic resonance imaging; Third ventricle subventricular zone.

Graphical abstract

Fig. 1

(A) The subventricular zone of the third ventricle (TVZ) and its cytoarchitecture. The TVZ lines the ventricle and is composed of an ependymal later, an age-dependent hypocellular gap and an astrocytic ribbon which faces the transition zone into the parenchyma. The ependymal layer makes up the ventricle wall and is interiorly exposed to cerebral spinal fluid (blue) and exteriorly exposed to the hypocellular layer. In children, the sub-ependymal zone, which is composed of the hypocellular layer and astrocytic ribbon is a cellular collection ~3 mm in size. At the sub-ependymal zone, stem cells migrate outwards and/or downwards into the transition zone. In a normal setting, young optic pathway cells migrate via chain migration to the optic nerves, where their progenitors mature. In the cancer setting, cancer stem cells react to and interact with the parenchyma microenvironment and are classically known to invade rather than migrate. (B) Anatomical positioning of the TVZ relative to the third ventricle, thalamus, hypothalamus and optic pathway. The thalamus (magenta) surrounds the third ventricle and is located superior to the hypothalamus (yellow), which forms the inferior aspect and floor of the third ventricle, and also lies superior to the optic chiasm and optic tracts (blue). The TVZ (cyan) lines the inferior-lateral surface of the third ventricle and inferiorly runs through the lower aspect of the thalamus to the hypothalamus. In this figure, the TVZ is superimposed by the inferior component of hypothalamus. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Identifying voxels of the TVZ and eliminating partial volume effects in an NF1 patient. A 2 mm exclusion gap (white) was placed directly adjacent to the anterior-inferior aspect of the third ventricle wall, visualized on a T2-weighted image (A), and was confined by the anterior and posterior borders of the ventricle. The TVZ transition zone voxels (cyan) were placed directly adjacent to the exclusion gap. Measures of the ADC (B) and nCBF (C) in the TVZ voxels were collected. Focal abnormal signal intensities (red) and tumour were excluded from TVZ ROIs. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Boxplots comparing TVZ nADC_mean and TVZ nCBF_max values in sporadic OPG patients, NF1-associated OPG patients, and control participants. Significant differences are indicted in the figure: * p < 0.05, *** p < 0.001.

Fig. 4

Scatter plots summarizing TVZ nCBF_max and nADC_mean correlations with mean logMAR score, in NF1-associated and sporadic OPG patients. The best-fit and confidence interval lines from the linear models are illustrated, along with the R² and p values for model.