Relationship Between Microstructural Alterations and Cognitive Decline After Whole-Brain Radiation Therapy for Brain Metastases: An Exploratory Whole-Brain MR Analysis Based on Neurite Orientation Dispersion and Density Imaging

Abstract

Background: Cognitive impairment frequently occurs in patients with brain metastases (BM) after whole-brain radiotherapy (WBRT). It is crucial to explore the underlying mechanisms of cognitive impairment in BM patients receiving WBRT.

Purpose: To detect brain microstructural alterations in patients after WBRT by neurite orientation dispersion and density imaging (NODDI), and evaluate the performance of microstructural alterations in predicting cognitive impairment.

Study type: Prospective.

Population: Twenty-six patients (seven female; mean age, 60.9 years).

Field strength/sequence: 3-T, multi-shell diffusion-weighted single-shot echo-planar sequence. Three-dimensional magnetization-prepared rapid acquisition with gradient echo sequence.

Assessment: Mini-mental state examination (MMSE) evaluations were conducted prior to, following, 1 and 3 months after WBRT. The diffusion data were collected twice, 1 week before and 1 week after WBRT. NODDI analysis was conducted to assess microstructural alterations in whole brain (orientation dispersion index, neurite density index, volume fraction of isotropic water molecules). Reliable change indices (RCI) of MMSE were used to measure cognitive decline. The performance of support vector machine models based on NODDI parameters and clinical features (prednisone usage, tumor volume, etc.) in predicting MMSE-RCI was evaluated.

Statistical tests: Paired t-test to assess alterations of NODDI measures and MMSE during follow-up. Statistical significance level of P-value <0.05.

Results: Significantly decreased MMSE score was found at 3 months after WBRT. After WBRT, corpus callosum, medial prefrontal cortex, limbic lobe, occipital lobe, parietal lobe, putamen, globus pallidus lentiform, and thalamus demonstrated damage in NODDI parameters. The predicted MMSE-RCI based on NODDI features was significantly associated with the measured MMSE-RCI at 1 month (R = 0.573; P = 0.003) and 3 months (R = 0.687; P < 0.0001) after WBRT.

Data conclusion: Microstructural alterations in several brain regions including the middle prefrontal and limbic cortexes were observed in patients with BM following WBRT, which may contribute to subsequent cognitive decline.

Evidence level: 2 TECHNICAL EFFICACY: Stage 2.

Keywords: brain metastases; cognitive function; neurite orientation dispersion and density imaging; radiotherapy.