Radiation-induced glymphatic dysfunction in patients with nasopharyngeal carcinoma: a study using diffusion tensor image analysis along the perivascular space.

Radiation encephalopathy (RE) refers to radiation-induced brain necrosis and is a life-threatening complication in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT), and radiation-induced pre-symptomatic glymphatic alterations have not yet been investigated. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index to examine the pre-symptomatic glymphatic alterations in NPC patients following RT. A total of 109 patients with NPC consisted of Pre-RT (n = 35) and Post-RT (n = 74) cohorts were included. The post-RT NPC patients, with normal-appearing brain structure at the time of MRI, were further divided into Post-RT-RE- (n = 58) and Post-RT-RE+ (n = 16) subgroups based on the detection of RE in follow-up. We observed lower DTI-ALPS left index, DTI-ALPS right index and DTI-ALPS whole brain index in post-RT patients than that in pre-RT patients (p < 0.05). We further found that post-RT-RE+ patients demonstrated significantly lower DTI-ALPS right (p = 0.013), DTI-ALPS whole brain (p = 0.011) and marginally lower DTI-ALPS left (p = 0.07) than Post-RT non-RE patients. Significant negative correlations were observed between the maximum dosage of radiation-treatment (MDRT) and DTI-ALPS left index (p = 0.003) as well as DTI-ALPS whole brain index (p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that DTI-ALPS whole brain index exhibited good performance (AUC = 0.706) in identifying patients more likely developing RE. We concluded that glympathic function was impaired in NPC patients following RT and DTI-ALPS index may serve as a novel imaging biomarker for diagnosis of RE.

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

Radiation-induced functional and structural brain alterations are well documented in patients with nasopharyngeal carcinoma (NPC), followed by radiotherapy (RT); however, alterations in structure-function coupling remain largely unknown. Herein, we aimed to assess radiation-induced structure-function decoupling and its importance in predicting radiation encephalopathy (RE). We included 62 patients with NPC (22 patients in the pre-RT cohort, 18 patients in the post-RT-RE+ve cohort, and 22 patients in the post-RT-RE-ve cohort). A metric of regional homogeneity (ReHo)/voxel-based morphometry (VBM) was used to detect radiation-induced structure-function decoupling, which was then used as a feature to construct a predictive model for RE. Compared with the pre-RT group, patients in the post-RT group (which included post-RT-RE+ve and post-RT-RE-ve) showed higher ReHo/VBM coupling values in the substantia nigra (SN), the putamen, and the bilateral thalamus and lower values in the brain stem, the cerebellum, the bilateral medial temporal lobes (MTLs), the bilateral insula, the right precentral and postcentral gyri, the medial prefrontal cortex (MPFC), and the left inferior parietal lobule (IPL). In the post-RT group, negative correlations were observed between maximum dosage of RT (MDRT) to the ipsilateral temporal lobe and ReHo/VBM values in the ipsilateral middle temporal gyrus (MTG). Moreover, structure-function decoupling in the bilateral superior temporal gyrus (STG), the bilateral precentral and postcentral gyri, the paracentral lobules, the right precuneus and IPL, and the right MPFC exhibited excellent predictive performance (accuracy = 88.0%) in identifying patients likely to develop RE. These findings show that ReHo/VBM may be a novel effective imaging metric that reflects the neural mechanism underlying RE in patients with NPC.

Radiation optic neuropathy diagnosis in nasopharyngeal carcinoma patients with radiation encephalopathy.

AIM: To develop a suitable radiation optic neuropathy (RON) diagnostic model based on optical coherence tomography angiography (OCTA) and to reveal the correlation between endocrine and OCTA indexes in nasopharyngeal carcinoma (NPC) patients with radiation encephalopathy (RE). METHODS: This retrospective cross-sectional study included seventy-seven male NPC patients with RE following radiotherapy (41 non-RON and 36 RON). Endocrine and OCTA indexes were collected. The macular and peripapillary vessel density (VD) were automatically analyzed using AngioVue 2.0 of the RTVue XR Avanti device. The OCTA indexes were included in the multivariable binary logistic regression model between non-RON and RON. For all RE patients, a multiple linear regression was performed between each of the OCTA indexes and the endocrine indexes. RESULTS: Compared to non-RON, enlarged foveal avascular zone (FAZ) area, reduced superficial vascular plexus (SVP) VD and radial peripapillary capillary plexus density, reduced full retinal thickness, ganglion cell complex thickness and peripapillary retinal nerve fiber layer thickness were observed in RON. Foveal VD in the SVP was included in the RON diagnostic model. Free triiodothyronine (FT3) showed a significantly negative correlation with the FAZ area but showed a significantly positive correlation with foveal VD in the SVP and deep vascular plexus, peripapillary VD and thickness and parafoveal and perifoveal thickness. CONCLUSIONS: OCTA may be useful for diagnosing RON in male NPC patients with RE following radiotherapy. Reduced FT3 and foveal VD in SVP may be sensitive in screening RON in these patients.

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

Adult hippocampal neurogenesis (AHN) is important for multiple cognitive functions. We sort to establish a minimal or non-invasive radiation approach to ablate AHN using guinea pigs as an animal model. 125I seeds with different radiation dosages (1.0, 0.8, 0.6, 0.3 mCi) were implanted unilaterally between the scalp and skull above the temporal lobe for 30 and 60 days, with the radiation effect on proliferating cells, immature neurons, and mature neurons in the hippocampal formation determined by assessment of immunolabeled (+) cells for Ki67, doublecortin (DCX), and neuron-specific nuclear antigen (NeuN), as well as Nissl stain cells. Spatially, the ablation effect of radiation occurred across the entire rostrocaudal and largely the dorsoventral dimensions of the hippocampus, evidenced by a loss of DCX+ cells in the subgranular zone (SGZ) of dentate gyrus (DG) in the ipsilateral relative to contralateral hemispheres in reference to the 125I seed implant. Quantitatively, Ki67+ and DCX+ cells at the SGZ in the dorsal hippocampus were reduced in all dosage groups at the two surviving time points, more significant in the ipsilateral than contralateral sides, relative to sham controls. NeuN+ neurons and Nissl-stained cells were reduced in the granule cell layer of DG and the stratum pyramidale of CA1 in the groups with 0.6-mCi radiation for 60 days and 1.0 mCi for 30 and 60 days. Minimal cranial trauma was observed in the groups with 0.3- 1.0-mCi radiation at 60 days. These results suggest that extracranial radiation with 125I seed implantation can be used to deplete HAN in a radioactivity-, duration-, and space-controllable manner, with a "non-invasive" stereotactic ablation achievable by using 125I seeds with relatively low radioactivity dosages.

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

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 REproved infollow-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.

Long-term recurrence and brain metastasis of nasopharyngeal carcinoma mimicking cystic radiation encephalopathy relapse: a case report.

BACKGROUND: During medical imaging, cystic radiation encephalopathy and brain metastasis are difficult to differentiate, and hence they are easily misdiagnosed. To our knowledge, a nasopharyngeal carcinoma recurrence after more than seven years with cerebral metastasis that mimicked cystic radiation encephalopathy has not been reported. CASE PRESENTATION: A 52-year-old man was admitted to the hospital owing to weakness of the right limb for one month, which increased in intensity for three days. He had been diagnosed with nasopharyngeal carcinoma in 2011, which was treated by radiotherapy. The patient successively developed cystic radiation encephalopathy and brain metastasis from the nasopharyngeal carcinoma, which mimicked cystic radiation encephalopathy relapse. Left frontotemporal craniotomy, surgical resection of brain metastasis, and repair of the skull base and dura were performed. Postoperative computed tomography showed that midline deviation recovered, and brain edema was reduced. CONCLUSIONS: This report is significant because brain metastasis from nasopharyngeal carcinoma can masquerade as a benign entity and cause fatal consequences. In patients presenting with cystic radiation encephalopathy, brain metastasis should be considered as a differential diagnosis.

Radiation-Induced Optical Coherence Tomography Angiography Retinal Alterations in Patients With Nasopharyngeal Carcinoma.

Aim: The aim of the study was to investigate the early neurovascular alterations of the retina in radiation encephalopathy (RE) patients with normal-ranged visual acuity after radiotherapy for nasopharyngeal carcinoma. Methods: Fifty-five RE patients and 54 healthy age-matched subjects were enrolled in this retrospective cross-sectional case-control study. The best corrected visual acuity (LogMAR) of the included eye should not be more than 0. The vessel density and thickness of different locations in the retina were acquired automatically using optical coherence tomography angiography (OCTA). The data were then compared between the RE patients and the controls. The location included the whole retina, the superficial vascular plexus (SVP)/the ganglion cell complex (GCC), the deep vascular plexus (DVP), and the choroid in the macular area, as well as the inside disc and peripapillary area in the optic nerve head (ONH). The risk factors in OCTA retinal impairments were analyzed using a backward multiple linear regression. The relationships between mean deviation (MD) and pattern standard deviation (PSD) in the visual field (VF) and the OCTA parameters were also analyzed in RE patients. Results: The vessel density of the GCC was significantly reduced in RE patients compared with controls (p = 0.018), and the reductions were mainly shown in the parafoveal (p = 0.049) and perifoveal fields (p = 0.006). The thickness of the GCC was correspondingly reduced (whole image GCC mean thickness: p = 0.044; parafoveal thickness: p = 0.038; perifoveal thickness: p = 0.038). In addition, the sub-foveal choroidal thickness (p = 0.039) was also reduced in RE patients. The vessel density of the GCC (R 2 = 0.643) and DVP (R 2 = 0.777) had a significant positive correlation with high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (ApoA1) and had a significant negative correlation with age (GCC: HDL-C, ß = 29.89, p = 0.005; ApoA1, ß = 78.92, p = 0.002; age, ß = -0.886, p = 0.001; DVP: HDL-C, ß = 40.09, p = 0.003; ApoA1, ß = 62.65, p = 0.013; age, ß = -1.31, p = 0.001). The vessel density of the GCC also had a significant negative correlation with apolipoprotein B (ApoB) (ß = -32.18, p = 0.006). In the VF, MD had a significant positive correlation with the vessel density inside disc (R 2 = 0.241, ß = 0.304, p = 0.045), whereas PSD showed a significant negative correlation with the vessel density inside disc and the average GCC thickness, respectively (R 2 = 0.437; vessel density inside disc, ß = -0.358, p = 0.004; average GCC thickness, ß = -0.510, p < 0.001). Conclusion: With the aid of OCTA, we found that neurovascular alterations of the retina may exist in RE patients with normal-ranged visual acuity. Herein, we suggest the implementation of OCTA to assist ophthalmologists in the early detection and consistent monitoring of radiation-related eye diseases to avoid delayed diagnosis.

Pre-symptomatic local brain activity and functional connectivity alterations in nasopharyngeal carcinoma patients who developed radiation encephalopathy following radiotherapy.

Radiation encephalopathy (RE) is a common complication in patients with nasopharyngeal carcinoma (NPC) who have received radiotherapy (RT), and recent neuroimaging studies have shown brain alterations in Post-RT patients prior to RE. However, whether there are functional alterations between those Post-RT patients who are proved to have RE in follow-up and those who do not develop it remains largely unknown. Here, we used resting state functional MRI to explore regional homogeneity (ReHo) and functional connectivity (FC) alterations in Post-RT patients with (Post-RT RE proved; n = 18) or without (Post-RT non-RE; n = 22) RE at follow-up, also making comparisons with a Pre-RT group (n = 23). Compared with the Pre-RT group, patients in Post-RT non-RE and Post-RT RE proved groups showed concurrent increased and decreased ReHo values in different brain regions inside and/or outside the radiation field, with the alterations in ReHo tending to increase if RE occurred. Seed-based FC analysis showed that compared with the Post-RT non-RE group, patients in the Post-RT RE proved group had different changing patterns of FC between a region of interest (ROI) in the right temporal lobe and distant brain regions (mainly in the sensorimotor system and default mode network). Receiver operating characteristic (ROC) curve analysis showed that the altered ReHo value in the ROI had excellent diagnostic performance for differentiating NPC patients who developed RE in follow-up from those who did not, with an area under the curve (AUC) value of 0.94. These ReHo and FC findings may provide new insights into the early diagnosis of RE.

Cortical Surface Area Rather Than Cortical Thickness Potentially Differentiates Radiation Encephalopathy at Early Stage in Patients With Nasopharyngeal Carcinoma.

Radiation encephalopathy (RE) is one of the most severe complications in nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT). However, the morphological alteration of early RE is insufficiently investigated. We aimed to investigate the cortical thickness and surface area alterations in NPC patients with or without RE in the follow-up. A total of 168 NPC patients each underwent a single scan and analysis at various times either Pre-RT (n = 56) or Post-RT (n = 112). We further divided the Post-RT NPC patients into three groups based on the time of the analysis following RT (Post-RTwithin 6 months and Post-RT7-12 months) or whether RE signs were detected in the analysis (Post-RTRE proved in follow-up). We confined the vertex-wise analyses of the cortical thickness and surface area to the bilateral temporal lobes. Interestingly, we revealed a gradual increase in the cortical surface area of the temporal lobe with increasing time after RT within the Post-RTRE proved in follow-up group, consistent with the between-group findings, which showed a significant increase in cortical surface area in the Post-RTRE proved in follow-up group relative to the Pre-RT group and the Post-RTwithin 6 months group. By contrast, such a trend was not observed in the cortical thickness findings. We concluded that the cortical surface area, rather than cortical thickness, may serve as a potential biomarker for early diagnosis of RE.

Dynamic MRI follow-up of radiation encephalopathy in the temporal lobe following nasopharyngeal carcinoma radiotherapy.

The natural course of radiation encephalopathy following nasopharyngeal carcinoma (NPC) radiotherapy remains poorly understood. The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and evolution of radiation encephalopathy. A series of 162 follow-up MRI examinations from 68 NPC patients with radiation encephalopathy in the temporal lobes were analyzed retrospectively. Each component of radiation encephalopathy was defined as follows: i) contrast enhanced lesions were enhanced lesions on contrast enhanced T1-weighted images (T1WI); ii) white matter lesions were lesions of homogeneous hyperintensity on T2-weighted images (T2WI) and hypointensity on T1WI; iii) cysts were round or oval well-defined lesions of hyperintensity on T2WI; iv) hemosiderin deposition were nodular or annular hypointense lesions with lower hypointense than normal white matter on both T1WI and T2WI; v) gray matter lesions were defined as disruption or erosion of hyperintensity in the cortex on T2WI. Contrast enhanced lesions, white matter lesions, gray matter lesions, cysts and hemosiderin deposition were detected in 105 (100.0%), 98 (93.3%), 94 (89.5%), 2 (1.7%) and 2 (1.7%) cases of the 105 initial diagnosed temporal lobe lesions. Contrast enhanced lesions were the most commonly observed, followed by white matter lesions, gray matter lesions, temporal lobe atrophy, cysts and hemosiderin deposition. In addition, 12 new lesions were identified during the follow-up, 4 of which presented as solid enhanced nodular lesions. Importantly, in 11 of the 117 (9.4%) affected temporal lobes, solid enhanced nodular lesions were observed to be the only initial abnormalities to occur. For those enhanced nodular lesions measuring <0.8 cm, no necrosis could be detected. On the contrary, all the contrast enhanced lesions measuring >2.0 cm exhibited a necrotic core. To the best of our knowledge, the present study revealed for the first time solid enhanced nodular lesions as the earliest MRI abnormalities of radiation encephalopathy following NPC radiotherapy.

Effect of psychological intervention on the mental conditions and the quality of life of patients with radiation encephalopathy / 现代临床护理

Objective To explore the effect of psychological intervention on the mental conditions and the quality of life of patients with radiation encephalopathy(REP).Methods thirty-five patients with REP from radiotherapy for nasopharyngeal carcinoma were divided into the control group(n=17)and the experiment group(n=18)according to their registration sequence. The control group was managed with conventional nursing,and the experiment group with individualized psychological intervention in addition to routine nursing for 12 weeks.The two groups were compared in terms of depression and quality of life by Hamilton Depression rating Scale(HAMD)and The short-form health survey questionnaire(SF-36).Results The two groups before treatment showed no statistical difference in scores by HAMD and SF-36(P>0.05).The experiment group was superior to the control group after intervention in depression and quality of life(P<0.01).Conclusion Psychological intervention may alleviate REP in the patients at poor psychological status and improve their quality of life.

Clinical characteristics with radiation encephalopathy after intensity-modulated radiotherapy in nasopharyngeal carcinoma patients: analysis of 42 cases / 中华放射医学与防护杂志

Objective To explore the incidence, clinical characteristics, and prognosis of radiation encephalopathy (REP) in nasopharyngeal carcinoma (NPC) patients after intensity-modulated radiotherapy (IMRT). Methods 870 NPC patients confirmed pathologically and without distant metastasis received radical IMRT,570 of which received chemotherapy simultaneously,and followed up for 6 -104 months (with a median of 40 months),undergoing magnetic resonance imaging (MRI) once every 3 months within the first 3 years after treatment and then once every year.The clinical manifestations were observed.In 29 of these 42 patients diagnosed as with REP,the dose distributions of REP lesions were evaluated.Results 4.83％ of the NPC patients (42/870) were diagnosed as with REP.There were 39 cases with pure temporal lesion (bilateral in 6 cases),with a median latency period of 30 months (6 -56 months),2 cases with pure cerebral stem lesion both with a latency period of 14 months,and one case with lesions in temporal lobe and cerebral stem with the latency period of 18 months.REP was not observed in the stage T1-2 patients.The incidence rate of REP was 3.09％ for the stage T3 patients and 14.35％ for the stage T4 patients.Twenty-two patients underwent following-up MRI after initial diagnosis of REP.After medication or surgical treatment the conditions became better or stable in the most cases. Dosimetric analysis of 32 injured temporal lobes in 29 patients found that the maximal dose was in the contrastenhanced lesions in 27 injured temporal lobes and in edema regions in 5 injured temporal lobes.For each patient,the maximal dose in the normal temporal lobe was lower than that in the injured temporal lobe.In the same patient,the maximal dose,minimal dose,and mean dose of contrast-enhanced lesions were all higher than those in the edema region.Conclusions The incidence of REP after IMRT is high,especially in local advanced NPC patients. Active treatment stabilizes or improves the REP condition. REP is positively correlated with dose of irradiation to brain tissue.

Een zeldzame oorzaak van dementie: de bestralingsencephalopathie.

We describe the clinical history of a 49-year old woman, who demonstrated progressive personality changes more than twenty years after radiation of a pituitary adenoma (prolactinoma), with apathy, loss of initiative, memory deficits, postural instability, dysarthria and faecal incontinence. Neuropsychological assessment showed impulsivity, loss of overview, desinhibition, fluctuating deficits of attention, and memory disturbances. MRI-scanning of the brain revealed a cystic lesion along the right ventricle. The clinical picture and the findings of the other investigations are typical for dementia due to radiation encephalopathy. Such a long period between radiation and cognitive deterioration is rare, although it has been described before.