Early Stage Markers of Late Delayed Neurocognitive Decline Using Diffusion Kurtosis Imaging of Temporal Lobe in Nasopharyngeal Carcinoma Patients

Abstract

Purpose: To determine whether the early assessment of temporal lobe microstructural changes using diffusion kurtosis imaging (DKI) can predict late delayed neurocognitive decline after radiotherapy in nasopharyngeal carcinoma (NPC) patients. Methods and Materials: Fifty-four NPC patients undergoing intensity-modulated radiotherapy (IMRT) participated in a prospective DKI magnetic resonance (MR) imaging study. MR imaging was acquired prior to IMRT (-0), 1 month (-1), and 3 (-3) months after IMRT. Kurtosis (Kmean, Kax, Krad) and Diffusivity (Dmean, Dax, Drad) variables in the temporal lobe gray and white matter were computed. Neurocognitive function tests (MoCA) were administered pre-radiotherapy and at 2 years post-IMRT follow-up. All the patients were divided into neurocognitive function decline (NFD group) and neurocognitive function non-decline groups (NFND group) according to whether the MoCA score declined ≥3 2 years after IMRT. All the DKI metrics were compared between the two groups, and the best imaging marker was chosen for predicting a late delayed neurocognitive decline. Results: Kurtosis (Kmean-1, Kmean-3, Kax-1, Kax-3, Krad-1, and Krad-3) and Diffusivity (Dmean-1 and Dmean-3) of white matter were significantly different between the two groups (p<0.05). Axial Kurtosis (Kax-1, Kax-3) of gray matter was significantly different between the two groups (p<0.05). By receiver operating characteristic (ROC) curves, Kmean-1 of white matter performed best in predicting of MoCA scores delayed decline (p<0.05). The radiation dose was also significantly different between NFD and NFND group (p=0.031). Conclusions: Temporal lobe white matter is more vulnerable to microstructural changes and injury following IMRT in NPC. Metrics derived from DKI should be considered as imaging markers for predicting a late delayed neurocognitive decline. Both temporal lobe white and gray matter show microstructural changes detectable by DKI. The Kmean early after radiotherapy has the best prediction performance.

Cognitive Decline following Radiotherapy of Head and Neck Cancer: Systematic Review and Meta-Analysis of MRI Correlates

“…Patient age ranged between 20 and 71 (median 49). Three studies were categorised as case-control longitudinal studies [ 39 , 40 , 41 , 43 ] with investigation done as early as one day after radiotherapy completion to 6 months later and four as prospective cross-sectional studies [ 29 , 36 , 37 , 42 ]. Several types of imaging investigation were done, such as functional magnetic resonance imaging (fMRI), diffusion kurtosis imaging (DKI) and three-dimensional brain volume imaging (3D-BRAVO) in monitoring patients brain structure with imaging done at 1.5 and 3.0 Tesla.…”

“…From the findings, most studies reported a MoCA score <26 to define cognitive impairment. Only one study [ 37 ] adjusted for patient’s education and age. All studies also reported changes in the post-MRI findings corresponding to lower MoCA scores post-RT ( Table 2 ).…”

“…Significant volume losses in the bilateral hippocampus, bilateral GCL, left subiculum (SUB), and the right molecular layer was correlated with rapid cognitive function decline [ 41 ]. According to Wu et al [ 37 ], Kurtosis mean-1 of white matter could predict late delayed neurocognitive impairment through changes in MoCA scores post-RT with the sensitivity of 84.2% and specificity of 87.5% in the receiver operating (ROC) curve. However, the study done by Sharma et al [ 44 ] displayed voluminous, diffuse, radiation-induced white matter hyperintensities; changes were not associated with any neurocognitive assessments.…”

“…Abnormal connection of sensorimotor and cingulo-opercular networks with cerebellum shown might also imply the radiation-induced motor deficits and cognitive function abnormalities, especially attention changes [ 36 ]. Significant reduction in bilateral temporal lobe volume after RT [ 40 ] and differences in its white and grey matters among the neurocognitive function decline (NFD) group [ 37 ] suggests the dependency of changes in brain microstructure on radiation dose. Negative correlations were also displayed between the volume of the bilateral hippocampus, bilateral granule cell layer (GCL), and right middle lobe (ML) to mean dose of the ipsilateral hippocampus [ 41 ] and maximum irradiation dose of the right temporal lobe to the right insular FC within the salience network [ 29 ] ( Table 4 ).…”

“…However, studies on the early stages of impairment are scarce, with much focus on the late delayed effects of radiation treatment [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. It is essential to understand that cognitive impairment occurs almost immediately following radiotherapy treatment and proper monitoring is necessary [ 36 , 37 ]. In this review, we summarise, through a systematic review, the role of neurocognitive and MRI assessments in monitoring the cognitive decline in head and neck patients.…”