Surface-Based Falff: A Potential Novel Biomarker for Prediction of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma

Abstract

Radiation encephalopathy (RE) is an important potential complication in patients with nasopharyngeal carcinoma (NPC) who undergo radiotherapy (RT) that can affect the quality of life. However, a functional imaging biomarker of pre-symptomatic RE has not yet been established. This study aimed to assess radiation-induced gray matter functional alterations and explore fractional amplitude of low-frequency fluctuation (fALFF) as an imaging biomarker for predicting or diagnosing RE in patients with NPC. A total of 60 patients with NPC were examined, 21 in the pre-RT cohort and 39 in the post-RT cohort. Patients in the post-RT cohort were further divided into two subgroups according to the occurrence of RE in follow-up: post-RT non−RE (n = 21) and post-RT REprovedinfollow−up (n = 18). Surface-based and volume-based fALFF were used to detect radiation-induced functional alterations. Functional derived features were then adopted to construct a predictive model for the diagnosis of RE. We observed that surface-based fALFF could sensitively detect radiation-induced functional alterations in the intratemporal brain regions (such as the hippocampus and superior temporal gyrus), as well as the extratemporal regions (such as the insula and prefrontal lobe); however, no significant intergroup differences were observed using volume-based fALFF. No significant correlation between fALFF and radiation dose to the ipsilateral temporal lobe was observed. Support vector machine (SVM) analysis revealed that surface-based fALFF in the bilateral superior temporal gyri and left insula exhibited impressive performance (accuracy = 80.49%) in identifying patients likely to develop RE. We conclude that surface-based fALFF may serve as a sensitive imaging biomarker in the prediction of RE.

Extracranial 125I Seed Implantation Allows Non-invasive Stereotactic Radioablation of Hippocampal Adult Neurogenesis in Guinea Pigs

“…Another application of the extracranial 125 I radiation method is to explore the extent, time course, and cellular feature of the recovery of HAN in mammalian brain, which may be also clinically relevant to radiation encephalopathy ( Kickingereder et al, 2014 ; Weusthof et al, 2021 ; Zhang et al, 2021 ). The SGZ contains a pool of neural stem cells that are quiescent or undergoing proliferation, with the latter event leading to both neuronal and glial genesis ( Del Bigio, 1999 ; Fares et al, 2019 ; Gage, 2019 ).…”

Structure–Function Decoupling: A Novel Perspective for Understanding the Radiation-Induced Brain Injury in Patients With Nasopharyngeal Carcinoma

“…Imaging data were acquired on a Magnetom Tim Trio 3T scanner (Siemens, Munich, Germany) using blood oxygen level-dependent (BOLD) and three-dimensional T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) sequences. Scanning parameters for BOLD and three-dimensional (3D) T1 MPRAGE sequences are documented in our previous studies (Zhang et al, 2018(Zhang et al, , 2020a(Zhang et al, , 2021. Briefly, for the BOLD sequence, the parameters were as follows: repetition time (TR) = 2,400 ms, echo time (TE) = 30 ms, field of view (FOV) = 230 mm × 230 mm, matrix size = 64 × 64, time points = 240, flip angle = 90 • , and 40 axial slices.…”

“…Recently, several studies have used non-invasive functional magnetic resonance imaging (fMRI) techniques to examine radiation-induced structural and functional alterations in gray matter (GM; Lin et al, 2017 ; Ding et al, 2018 ; Zhang et al, 2018 , 2021 ). Several studies of voxel-based morphometry (VBM) and surface-based morphometry have reported radiation-induced cortical volume, cortical thickness, and surface area abnormalities in multiple brain regions, such as the bilateral temporal lobes, the precentral gyrus, and the inferior parietal lobule (IPL; Lv et al, 2014 ; Lin et al, 2017 ; Zhang et al, 2021 ). Similarly, more recent fMRI studies have also documented altered regional neuronal activity and functional connectivity (FC) in the intratemporal and extratemporal lobes ( Ma et al, 2017 ; Qiu et al, 2018 ; Zhang et al , 2020a , 2021 ; Zhao et al, 2021 ).…”

“…Several studies of voxel-based morphometry (VBM) and surface-based morphometry have reported radiation-induced cortical volume, cortical thickness, and surface area abnormalities in multiple brain regions, such as the bilateral temporal lobes, the precentral gyrus, and the inferior parietal lobule (IPL; Lv et al, 2014 ; Lin et al, 2017 ; Zhang et al, 2021 ). Similarly, more recent fMRI studies have also documented altered regional neuronal activity and functional connectivity (FC) in the intratemporal and extratemporal lobes ( Ma et al, 2017 ; Qiu et al, 2018 ; Zhang et al , 2020a , 2021 ; Zhao et al, 2021 ). However, on close inspection of the distribution of the affected brain regions in previous structural and functional studies, we observed an interesting phenomenon; the affected brain regions with radiation-induced structural abnormalities were not well matched with those revealed by studies in the functional domain.…”

“…Subsequently, we applied a machine learning strategy to evaluate the prediction ability of the ReHo/VBM metric for RE. Given our previously reported divergent patterns of radiation-induced structural and functional alterations in the GM of patients with NPC ( Zhang et al, 2018 , 2020c , 2021 ), we hypothesized that the ReHo/VBM metric will be an effective imaging metric that reflects the radiation-induced altered structure–function relationship in patients with NPC. Our objectives for performing this study were as follows: (1) to investigate the ReHo/VBM alterations in the normal-appearing GM in patients with NPC, followed by RT; and (2) to build a predictive model for identifying the patients with NPC who are likely to develop RE.…”