Increased Apparent Diffusion Coefficient And Thickness In The Optic Nerve Is Associated With Visual Acuity Loss In Optic Pathway Glioma
Patrick W. Hales1, Kshitij Mankad2, Patricia O'Hare2, Victoria Smith2, Darren Hargrave2, and Christopher Clark1

1Developmental Imaging & Biophysics Section, University College London Institute of Child Health, London, United Kingdom, 2Great Ormond Street Children's Hospital, London, United Kingdom


Conventional MRI sequences have so far failed to provide imaging biomarkers that reliably differentiate asymptomatic optic pathway glioma (OPG) tumours from those which cause visual impairment. ADC maps are now acquired as standard in most institutions, and despite their typically limited resolution, may provide quantitative assessment of tumour invasion of the optic nerve. We measured ADC and optic nerve thickness using standard clinical imaging sequences in OPG patients, in conjunction with visual assessment. We found that the product of ADC and nerve thickness showed a significant correlation with visual acuity, and was significantly increased in patients who had gone blind.


Optic pathway glioma (OPG) is a childhood tumour of the visual pathways, sometimes associated with neurofibromatosis type 1. Despite being characterized as low-grade, OPGs can be difficult to manage, as they tend to follow a highly unpredictable clinical course, with poor correlation between conventional imaging features and visual loss 1. As such, similarly appearing tumours can range from stable, asymptomatic lesions, to aggressive lesions with relentless progression resulting in loss of vision. As diffusion-weighted imaging (DWI) is now performed routinely in many hospitals, we investigated if DWI can help to predict visual acuity in OPG patients.

Materials and Methods

Data Acquisition

We collated longitudinal DWI and visual assessment data from OPG patients treated at our institution between 2009-2014. The exclusion criteria were patients with less than 3 concurrent imaging and visual assessment measurements, and patients in which visual acuity (VA) was not measured using the standardised logMAR chart 2. The remaining cohort consisted of 11 patients (4 male), each with imaging and visual assessments acquired at 7 time points on average (range 3-15). The mean age (±SD) at first MRI was 4.0 ± 2.5 years, and the mean period of assessment was 2.4 ± 1.5 years. MRI was performed on a 1.5 T Siemens Avanto (Erlangen, Germany), and the DWI protocol consisted of a 2D EPI readout with b-values of 0 and 1000 s/mm2 and resolution of 1.8 mm in-plane (interpolated to 0.90 mm), with 5.0 mm thick slices.

Post Processing

The clinical T2w images acquired during each imaging session were used to draw a region of interest (ROI) over the entire tumour volume. These images were also used to measure the thickness of the optic nerves (tON), which was defined as the maximum measureable width of the optic nerve anterior to the optic chiasm. The ADC maps acquired in the same imaging session were registered to the T2w images to calculate the median ADC in the entire tumour ROI (ADCtumour). Median ADC was also measured in each optic nerve (ADCON), by placing ROIs over the optic nerves in each ADC map (Figure 1).

Data Analysis

MRI and visual assessment data for all time points, in all patients, were pooled for analysis. A linear regression model was used to determine the relationship between VA in the eye with the highest logMAR score and ADCtumour (higher logMAR scores indicate poorer vision). In addition, as VA was assessed independently in each eye, linear regression was used to model VA vs. both ADCON and tON for the corresponding eye. Patients for which no quantitative logMAR score could be measured, due to the patient either being too young or having lost vision completely (i.e. no perception of light), were excluded from this part of the analysis. Additionally, for eyes with no perception of light, ADCON and tON measurements were compared (group-wise) to eyes with measureable logMAR values, using an un-paired t test.


No correlation was found between VA (logMAR score) and ADCtumour (N=42 measurements, p=0.85). However, a significant positive correlation was found between VA and both ADCON (p=0.00043) and tON (p=0.014) in the corresponding eye (N=80 measurements). The product of the two regressors (ADCON ·Ÿ tON) also produced a significant positive correlation with VA (p=0.0017, Figure 2a). For the group-wise comparison between eyes with no perception of light vs. eyes with measureable logMAR values, the ADCON ·Ÿ tON parameter produced the most significant difference between the two groups (p=4.2x10-10, Figure 2b).


Our results indicate that both increased ADC and thickness in the optic nerve predict poorer vision in the corresponding eye, and the product of these measurements provides a metric that correlates with logMAR assessment of vision, and is significantly higher in patients who have lost their vision. A previous study found higher ADC in the entire tumour volume may predict visual decline in OPG patients 3, however in this study we found increased ADC in the optic nerve is a better predictor of VA. Increased ADC and nerve thickness in this region is likely to be due to tumour invasion causing disruption of the nerve fibres, and previous studies have shown reduced fractional anisotropy (using DTI) in the optic radiations in OPG patients 4. However, ADC maps are more widely available than DTI data in many institutions, and our results indicate that the combined ADCON ·Ÿ tON parameter may provide a useful metric for identifying tumours which are likely to cause visual impairment.


The authors would like to thank Great Ormond Street Children's Charity for funding this work.


1. Ahn Y, Cho B-K, Kim S-K, Chung Y-N, Lee CS, Kim IH et al. Optic pathway glioma: outcome and prognostic factors in a surgical series. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg 2006; 22: 1136–1142.

2. Sloan LL. New test charts for the measurement of visual acuity at far and near distances. Am J Ophthalmol 1959; 48: 807–813.

3. Yeom KW, Lober RM, Andre JB, Fisher PG, Barnes PD, Edwards MSB et al. Prognostic role for diffusion-weighted imaging of pediatric optic pathway glioma. J Neurooncol 2013; 113: 479–483.

4. de Blank PMK, Berman JI, Liu GT, Roberts TPL, Fisher MJ. Fractional anisotropy of the optic radiations is associated with visual acuity loss in optic pathway gliomas of neurofibromatosis type 1. Neuro-Oncol 2013; 15: 1088–1095.


Figure 1 (A) ADC map acquired in an OPG patient. (B) ROIs overlaid on the ADC map, indicating the right (red) and left (blue) optic nerves. (C) Optic nerve thickness measurements made on a T2w image in the same patient. (D) T2w image indicating tumour involvement beyond the optic nerves in the same patient, with the ROI indicating the tumour volume shown in yellow in (E).

Figure 2 (A) Plot of ADCON Ÿ· tON vs. visual acuity measured in the corresponding eye. The solid line and shaded area represent the linear fit and 95% confidence interval respectively (p=0.0017). (B) Box and whisker plot (with data points overlaid) of ADCON ·Ÿ tON in eyes which were classified as having no perception of light, and eyes with measureable vision.

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)