Nasopharyngeal Carcinoma
Conditions
Brief summary
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.
Interventions
OTHERUsing DCE-MRI, fMRI, and DSI, establish a longitudinal brain functional and structural imaging database for three groups of nasopharyngeal carcinoma patients before and 18 months after radiotherapy.
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.
Sponsors
Sun Yat-sen University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Patients newly diagnosed with nasopharyngeal carcinoma, pathologically confirmed, and who have not received anti - tumor treatments such as surgery, induction chemotherapy, or radiotherapy. All patients are of Han ethnicity and right - handed. Patients are aged between 20 and 60 years old, with an educational level of junior high school or above. The clinical stage of the included patients is AJCC 8th edition stage I - IVa, without distant metastasis, and patients are scheduled to receive intensity - modulated radiotherapy (IMRT) according to the clinical plan. Patients have no other serious systemic diseases except nasopharyngeal carcinoma. There is no intracranial invasion of nasopharyngeal carcinoma. Routine MRI examinations (including T1WI, T2WI, and FLAIR) are negative. The baseline basic cognitive assessment scales (MoCA and MMSE) before radiotherapy are normal. Patients have no family history of mental illness. Patients have no history of neurological diseases or head trauma. After fully understanding the experimental content, the subjects agree to participate in this project and sign the informed consent form
Exclusion criteria
Patients diagnosed with Alzheimer's disease (AD) before being included. AD is diagnosed by psychiatrists according to the 9th Revision of the International Classification of Diseases, Clinical Modification (ICD - 9 - CM). Patients with intracranial lesions detected by routine MRI examinations. Patients with contraindications to magnetic resonance examinations. Patients with concurrent other diseases. Patients with tumor recurrence who need re - radiotherapy, or those who cannot adhere to and complete IMRT treatment. Left - handed or ambidextrous patients. Patients with a history of head trauma or mental/neurological diseases. Patients aged less than 20 or more than 60 years old. Patients with serious systemic diseases such as heart, lung, or kidney diseases. Patients with diabetes or hypertension. Patients who cannot cooperate to complete the neurocognitive scale tests.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood-Brain Barrier Permeability as Measured by Ktrans Values from DCE-MRI | From enrollment to 18 months after the completion of radiotherapy | 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. |
| Change in Functional Connectivity as Measured by Resting-State fMRI | From enrollment to 18 months after the completion of radiotherapy | 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. |
| Change in Structural Connectivity as Measured by Diffusion Spectrum Imaging (DSI) | From enrollment to 18 months after the completion of radiotherapy | 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. |
Countries
China
Outcome results
None listed