adiotherapy-induced cognitive dysfunction is a severe complication following radiotherapy for nasopharyngeal carcinoma (NPC). Our previous studies have demonstrated that abnormalities in brain function and structural connectivity after radiotherapy play a significant role in the occurrence of radiation-induced cognitive dysfunction. However, the key risk factors and underlying neural mechanisms remain unclear. Research has shown that increased blood-brain barrier (BBB) permeability after radiotherapy is an important mechanism leading to cognitive dysfunction, and different APOE gene subtypes can regulate BBB permeability. Therefore, APOE gene polymorphisms are likely to influence post-radiotherapy vascular barrier permeability in NPC patients, thereby affecting their brain function and structural connectivity changes, and ultimately impacting their cognitive function. This project aims to establish a longitudinal brain imaging database for NPC patients with different APOE genotypes before and after radiotherapy, based on previous research findings. The project will integrate dynamic contrast-enhanced MRI (DCE-MR), resting-state functional MRI (fMRI), and diffusion spectrum imaging (DSI) techniques. By comparing DCE-derived metrics across different genotype groups, the study seeks to identify brain regions with BBB damage differences between APOE genotype groups before and after radiotherapy. Furthermore, it will investigate how BBB damage in these brain regions mediates functional and structural connectivity abnormalities, and their relationship with radiation-induced cognitive dysfunction. The goal is to clarify the neural regulation mechanism of APOE gene polymorphisms in radiation-induced cognitive dysfunction and to identify risk factors for radiation-induced cognitive dysfunction. This research will provide a theoretical basis and valuable reference for the individualized prevention and treatment of radiation-induced cognitive dysfunction.
Study Type
OBSERVATIONAL
Enrollment
300
1. Resting-state fMRI: Use the Gradient Echo Echo Planar Imaging (GRE-EPI) sequence with the following parameters: repetition time (TR) = 2000 ms, echo time (TE) = 30 ms, flip angle (FA) = 90°, slice thickness = 3.0 mm, slice spacing = 0.8 mm, field of view (FOV) = 240 mm × 240 mm, matrix = 128 × 128, in-plane resolution = 64 × 64, 39 axial slices scanned, 240 dynamic scans. 2. DSI: Use diffusion-sensitive imaging (DSI) with 64 diffusion directions, b-values of 0 and 1000 s/mm², TR = 3000 ms, TE = 64 ms, number of excitations (NEX) = 1, matrix = 112 × 112, FOV = 224 mm × 224 mm, slice thickness = 2 mm, no spacing between slices, full brain coverage, and 75 slices scanned. 3. Three-dimensional brain structural MRI: Sagittal data acquisition is performed with the following parameters: TR = 8.16 ms, TE = 3.18 ms, inversion time (TI) = 800 ms, flip angle (FA) = 8°, matrix = 256 × 256, FOV = 256 mm × 256 mm, voxel size = 1 mm × 1 mm × 1 mm, and 176 slices scanned.
Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy
Guangzhou, Guangdong, China
Change in Blood-Brain Barrier Permeability as Measured by Ktrans Values from DCE-MRI
The change in blood-brain barrier permeability will be quantified using the volume transfer constant (Ktrans) derived from Dynamic Contrast-Enhanced MRI (DCE-MRI). Ktrans values will be measured at baseline (pre-radiotherapy) and at 18 months post-radiotherapy. The difference in Ktrans values between these time points will be calculated to assess the change in permeability.
Time frame: From enrollment to 18 months after the completion of radiotherapy
Change in Functional Connectivity as Measured by Resting-State fMRI
Functional connectivity will be assessed using resting-state functional MRI (fMRI). The strength of functional connections between specific brain regions, particularly those identified as having significant blood-brain barrier damage, will be measured at baseline and at 18 months post-radiotherapy. The change in functional connectivity strength will be calculated and reported.
Time frame: From enrollment to 18 months after the completion of radiotherapy
Change in Structural Connectivity as Measured by Diffusion Spectrum Imaging (DSI)
Structural connectivity will be evaluated using Diffusion Spectrum Imaging (DSI). The integrity of white matter tracts, particularly those connecting regions with significant blood-brain barrier damage, will be measured at baseline and at 18 months post-radiotherapy. The change in structural connectivity, as indicated by metrics such as fractional anisotropy (FA) and mean diffusivity (MD), will be calculated and reported.
Time frame: From enrollment to 18 months after the completion of radiotherapy
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