MRI identifies disrupted cerebral development in medulloblastoma patients

Abstract

Cognitive decline in survivors of medulloblastoma is commonly attributed to radiation- and chemotherapy-induced brain microstructural alterations. Factors preceding this adjuvant therapy, such as disrupted brain development or resection surgery, may affect brain microstructure but have not been thoroughly explored in medulloblastoma. The aim of this study was to assess cortical thickness and microstructural integrity of the cerebrum prior to adjuvant therapy in medulloblastoma patients. Cross-sectional image data were acquired of medulloblastoma patients (n = 30) after surgery but before adjuvant therapy and compared with data from healthy controls (n = 35) matched for age range (12-22 years). Biomarkers of microstructural integrity include fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity. Thickness, surface area and volume were estimated for parcels of neocortex to evaluate potential morphology differences. Participants with medulloblastoma showed increased diffusivity parameters (mean, axial and radial diffusivity) and decreased fractional anisotropy, within nearly all white and grey matter parcels of the cerebrum, compared with healthy controls. Medulloblastoma participants additionally showed decreased cortical thickness in sub-regions of frontal, parietal, temporal and paracentral cortex. Broad cerebral microstructural alterations in medulloblastoma patients following surgery but before initiation of radiation or chemotherapy suggest that cerebellar insult, by tumour development or tumour resection, likely contributes to compromised integrity of cerebral grey and white matter. Locations of cortical thinning suggest that cerebellar insult may impair normal growth in cerebral regions responsible for executive function, language and attention-cognitive domains typically affected in medulloblastoma survivors.

Keywords: DTI; MRI; brain development; medulloblastoma.

graphical abstract

Figure 1

Participant enrolment flowchart. Flowchart shows participant enrolment in the study.

Figure 2

Group comparison of control subjects and MB patients. Group comparison of healthy control subjects and MB patients after controlling for age and ventricular volume for the 12 parameters assessed across brain regions. The colour bar demonstrates the mapping of the t-statistic from white (Negative 6) to black (Positive 6) through varying shades of orange. Each sector of the circle represents a different region. Each ring of the figure shows t-statistic for a different metric, as demonstrated at the 12 O’clock position of the figure. Specific GM and WM regions are outlined in black if the difference between control and MB groups is statistically significant (P < 0.05).

Figure 3

Cortical MD t-statistic displayed on cortical surfaces.  t-statistic values of the cortical MD are displayed on cortical surfaces. The colour bar demonstrates the mapping of the t-statistic from green (Negative 6) to magenta (Positive 6) through varying shades. Darker shades of magenta in the middle frontal gyrus, precuneus, posterior aspect of the medial prefrontal cortex and cingulate gyri indicate maximum increase in MD compared with the healthy control subjects. The changes seen in frontal poles and temporal poles, entorhinal and parahippocampal gyri were not statistically significant.

Figure 4

Cortical thickness t-statistic displayed on cortical surfaces.  t-statistic values of the cortical thickness are displayed on cortical surfaces that demonstrate bilateral asymmetry. The colour bar demonstrates the mapping of the t-statistic from green (Negative 6) to magenta (Positive 6) through varying shades. Darker shades of green indicate statistically significant decrease in cortical thickness compared with the healthy control subjects in the left superior and inferior frontal, left paracentral lobule, left inferior parietal, left supra-marginal and middle temporal gyrus, right inferior frontal gyri, right paracentral lobule, right inferior parietal, right inferior temporal and right supra-marginal gyri. There was also a statistically significant increase in cortical thickness compared with the healthy control subjects in the right peri-calcarine cortex.