Modulation Effects of the CEP128 Gene on Radiotherapy-Related Brain Injury: A Longitudinal Structural Study Using Multi-Parametric Brain MR Images.

BACKGROUND: The promoter variant rs17111237 in the CEP128 closely relates to radiotherapy (RT)-related brain necrosis in nasopharyngeal carcinoma (NPC) patients. PURPOSE: To explore RT-related dynamic alterations in brain morphology and their potential genetic mechanism, and to explore the modulatory effects of CEP128 genetic variants on RT-related brain morphological alterations in NPC patients. STUDY TYPE: Prospective, longitudinal. POPULATION: One hundred one patients with histopathologic ally-proven NPC (age 41.64 ± 9.63, 46 male), analyzed at baseline (pre-RT), 3-months post-RT and 6 months post-RT, and 19 sex-, age- and education-matched healthy controls. FIELD STRENGTH/SEQUENCE: 3D gradient echo brain volume (3D-BRAVO) and diffusion-weighted single-shot spin-echo echo-planar sequences at 3.0 T. ASSESSMENT: rs17111237 in CEP128 was detected by Sanger sequencing. Structural and diffusion images were processed with FreeSurfer and FSL. Morphometric similarity network (MSN) was constructed with nine cortical indices derived from structural and diffusion images. STATISTICAL TESTS: One-way ANOVA, chi-square test. Pearson's correlation analysis was conducted to measure the relationship between CEP128 gene-expression level in human brain and MSN alterations. Repeated analysis of variance performed to assess group differences in MSN and the modulatory effects of the CEP128 gene within patients. Significance level: P < 0.05, false-discovery rate correction. RESULTS: RT-related significant widespread MSN alterations were observed in the cortices of NPC patients. Notably, regional MSN alterations had a weak but significant negative correlation with the cortical pattern of CEP128 gene expression (r = -0.152). Furthermore, rs17111237 in the CEP128 had significant modulatory effects on the observed MSN alterations in NPC patients, with the modulatory effects being most obvious at 3 months post-RT. CONCLUSIONS: MSN has potential to serve as a sensitive biomarker to detect RT-related brain injury. Inter-brain regional and inter-patient variability of RT-related brain injuries may be attributed to the cortical expression of the CEP128 gene and the modulatory effects of the promoter variant rs17111237 in CEP128. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Pretreatment MRI-Based Radiomics for Prediction of Rectal Cancer Outcome: A Discovery and Validation Study.

RATIONALE AND OBJECTIVES: Accurate prediction of local recurrence or distant metastasis is critical for developing individualized therapies for locally advanced rectal cancer (LARC) patients after standard therapy. This study aims to develop and validate a multiparameter MRI-based radiomics signature (RS) for prognostic prediction in LARC patients receiving neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME) and to explore the ability of RS for personalized survival risk stratification. MATERIALS AND METHODS: In this multi-center study, 454 patients who received nCRT and TME and completed 3 years of follow-up participated. RS was constructed for prognostic prediction based on features extracted from pretreatment multiparameter MRI in a training cohort (TC; n = 298), which was tested in an internal validation cohort (IVC; n = 75) and further validated in an independent external validation cohort (EVC; n = 81). Furthermore, the ability of RS for personalized survival risk stratification was explored using the Kaplan-Meier survival curves. RESULTS: The RS model showed satisfactory accuracy for prognostic prediction with AUCs of 0.83, 0.81 and 0.82 in the TC, IVC and EVC, respectively. In addition, RS helped to refine risk stratification for LARC patients on the basis of significantly different 3-year disease-free survival rates, independent of their pathological stage, pre-surgery CEA, and even treatment modality. CONCLUSIONS: The proposed RS can be used not only to predict local recurrence or distant metastasis but also to serve as an effective postoperative survival risk stratification tool for clinicians to facilitate decision-making for LARC patients receiving standard treatment.

Multiphase and multiparameter MRI-based radiomics for prediction of tumor response to neoadjuvant therapy in locally advanced rectal cancer.

BACKGROUND: To develop and validate radiomics models for prediction of tumor response to neoadjuvant therapy (NAT) in patients with locally advanced rectal cancer (LARC) using both pre-NAT and post-NAT multiparameter magnetic resonance imaging (mpMRI). METHODS: In this multicenter study, a total of 563 patients were included from two independent centers. 453 patients from center 1 were split into training and testing cohorts, the remaining 110 from center 2 served as an external validation cohort. Pre-NAT and post-NAT mpMRI was collected for feature extraction. The radiomics models were constructed using machine learning from a training cohort. The accuracy of the models was verified in a testing cohort and an independent external validation cohort. Model performance was evaluated using area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The model constructed with pre-NAT mpMRI had favorable accuracy for prediction of non-response to NAT in the training cohort (AUC = 0.84), testing cohort (AUC = 0.81), and external validation cohort (AUC = 0.79). The model constructed with both pre-NAT and post-NAT mpMRI had powerful diagnostic value for pathologic complete response in the training cohort (AUC = 0.86), testing cohort (AUC = 0.87), and external validation cohort (AUC = 0.87). CONCLUSIONS: Models constructed with multiphase and multiparameter MRI were able to predict tumor response to NAT with high accuracy and robustness, which may assist in individualized management of LARC.

Transcriptional expression of radiation-induced early cortical morphological alterations and its association with radiation necrosis in patients with nasopharyngeal carcinoma.

PURPOSE: To explore the effects of standard radiotherapy on cortical morphology and its potential transcriptional expression, and to determine the predictive power of cortical morphological measurement at the early stage for radiation necrosis (RN) occurrence within 3 years post-radiotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: 185 NPC patients participated. Pre-treatment and post-radiotherapy (1-3 months) structural MRI were collected longitudinally and prospectively. Multiple cortical morphological indices were compared between pre-treatment and post-radiotherapy. Brain-wide gene expression was used to assess the transcriptional profiles associated with radiation-induced cortical morphological changes. Machine learning was used to construct predictive models for RN with cortical morphological alterations at the early stage. RESULTS: Relative to pre-treatment, NPC patients exhibited a widespread reduction in cortical volume (CV) and cortical thickness (CT) post-radiotherapy (p < 0.001). Partial least squares regression analysis revealed that radiotherapy-related cortical atrophy was closely related to transcriptional profiles (p < 0.001), with the most correlated genes enriched in ATPase Na+/K+ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Furthermore, models constructed with cortical morphological features at 1-3 months post-radiotherapy had favorable predictive power for RN occurrence in NPC patients within 3-year follow-up, the area under the curve was 0.854 and 0.843 for CV and CT, respectively. CONCLUSIONS: NPC patients exhibited widespread cortical atrophy at 1-3 months post-radiotherapy, which was closely correlated with dysfunction of the ATPase Na+/K+ transporting alpha-1 and alpha-3 polypeptide and respiratory electron transport chain. Cortical morphology at 1-3 months post-radiotherapy may serve as an early biomarker for identifying RN.

The efficacy and safety of conventional transcatheter arterial chemoembolization combined with PD-1 inhibitor and anti-angiogenesis tyrosine kinase inhibitor treatment for patients with unresectable hepatocellular carcinoma: a real-world comparative study.

Aim: We sought to evaluate the efficacy and safety of conventional transcatheter arterial chemoembolization (cTACE) sequentially combined with systemic treatment by programmed cell death protein 1 (PD-1) inhibitor and anti-angiogenesis tyrosine kinase inhibitor (Anti-angiogenesis TKI) in patients with unresectable hepatocellular carcinoma (HCC). Materials and methods: One hundred and forty-seven advanced HCC patients who received PD-1 inhibitors and TKIs as first-line systemic treatment between August 2019 and April 2021 were collected retrospectively. Fifty-four patients were finally included and divided into cTACE and no-cTACE groups, according to whether cTACE treatment was performed within 8 weeks before systemic treatment. The tumor objective response ratio (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared between the groups. Significant factors affecting PFS and OS were determined by Cox regression. Results: Thirty-one patients received cTACE followed by systemic treatment and 23 patients received systemic treatment only. The ORRs of the cTACE group were 48.4% (after two cycles of systemic treatment) and 51.6% (after four cycles of systemic treatment), while those of the no-cTACE group were only 17.4% and 21.7%. cTACE patients also had a longer median PFS (11.70 vs. 4.00 months, P = 0.031) and median OS (19.80 vs. 11.6 months, P = 0.006) than no-cTACE patients. Regression analyses indicated that cTACE therapy and Eastern Cooperative Oncology Group performance status were independent risk factors for PFS and OS. AEs by type were similar between the cTACE and no-cTACE groups, except for liver function injury, which was more common among cTACE patients. Fourteen patients suffered with grade 1-2 of rash in 21 patients with objective response, while only 10 patients suffered with rash in 33 patients without objective response, the adjusted hazard ratio (HR) was 4.382 (1.297-14.803). Conclusions: The combination of cTACE and PD-1 inhibitors and anti-angiogenesis TKIs as therapy significantly improved markers of treatment efficacy, including ORR, PFS, and OS, in unresectable HCC patients, while no more serious AEs recorded in this population compared to those receiving systemic treatment alone. Skin rash might be a predict factor to the efficacy of PD-1 inhibitors and TKI treatment.

Divergent white matter changes in patients with nasopharyngeal carcinoma post-radiotherapy with different outcomes: a potential biomarker for prediction of radiation necrosis.

OBJECTIVES: To investigate the effects of standard radiotherapy on temporal white matter (WM) and its relationship with radiation necrosis (RN) in patients with nasopharyngeal carcinoma (NPC), and to determine the predictive value of WM volume alterations at the early stage for RN occurrence at the late-delay stage. METHODS: Seventy-four treatment-naive NPC patients treated with standard radiotherapy were longitudinally followed up for 36 months. Structural MRIs were collected at multiple time points during the first year post-radiotherapy. Longitudinal structural images were processed using FreeSurfer. Linear mixed models were used to delineate divergent trajectories of temporal WM changes between patients who developed RN and who did not. Four machine learning methods were used to construct predictive models for RN with temporal WM volume alterations at early-stage. RESULTS: The superior temporal gyrus (STG) had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. Patients with RN showed more rapid atrophy than those with NRN. A predictive model constructed with temporal WM volume alterations at early-stage post-radiotherapy had good performance for RN; the areas under the curve (AUC) were 0.879 and 0.806 at 1-3 months and 6 months post-radiotherapy, respectively. Moreover, the predictive model constructed with absolute temporal volume at 1-3 months post-radiotherapy also presented good performance; the AUC was 0.842, which was verified by another independent dataset (AUC = 0.773). CONCLUSIONS: NPC patients with RN had more sharp atrophy in the STG than those with NRN. Temporal WM volume at early-stage post-radiotherapy may serve as an in vivo biomarker to identify and predict RN occurrence. KEY POINTS: • The STG had divergent atrophy trajectories in NPC patients with different outcomes (RN vs. NRN) post-radiotherapy. • Although both groups exhibited time-dependent atrophy in the STG, the patients with RN showed a more rapid volume decrease than those with NRN. • Temporal WM volume alteration (or absolute volume) at the early stage could predict RN occurrence at the late-delay stage after radiotherapy.

Longitudinal study of irradiation-induced brain functional network alterations in patients with nasopharyngeal carcinoma.

BACKGROUND: To investigate radiotherapy (RT)-related brain network changes in patients with nasopharyngeal carcinoma (NPC) over time and develop least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) models to predict RT-related brain network changes. METHODS: 36 NPC patients were followed up at four timepoints: baseline, within 3 months (acute), 6 months (subacute), and 12 months (delayed) post-RT. 15 comparable healthy controls (HCs) were finally included and followed up in parallel. Functional neuroimaging data, dose-volume parameters of bilateral temporal lobes and Montreal Cognitive Assessment (MoCA) were acquired. Graph theoretical analysis and mixed-design analysis of variance were performed to investigate how the brain global and nodal changes were affected by RT. Multivariate logistic regression NTCP models were developed. LASSO with nested cross-validation strategy was used to select features. The relationships between network changes and MoCA changes were also examined. RESULTS: Significant changes were detected in nodal efficiency (NE) in NPC patients but not in HCs over time. Altered NE was distributed in the bilateral frontal, temporal lobes and the right insula, which showed a "decrease-increase/recovery" pattern over time. Among all models, the model for predicting NE changes of STG.R showed a relatively good performance (area under the receiver operating curve: 0.68), and D20cc and V20 to right temporal lobe outperformed in this model. CONCLUSION: Our findings indicate that RT-induced brain injury begin at the acute period and follow a recovery over time. Furthermore, our study presents prediction models for brain dysfunction based on the dosimetric and clinical parameters.

Prediction of Hepatocellular Carcinoma Response to Transcatheter Arterial Chemoembolization: A Real-World Study Based on Non-Contrast Computed Tomography Radiomics and General Image Features.

OBJECTIVE: To construct a predictive model of short-term response and overall survival for transcatheter arterial chemoembolization (TACE) treatment in hepatocellular carcinoma (HCC) patients based on non-contrast computed tomography (NC-CT) radiomics and clinical features. METHODS: Ninety-four HCC patients who underwent CT scanning 1 week before the first TACE treatment were retrospectively recruited and divided randomly into a training group (n = 47) and a validation group (n = 47). NC-CT radiomics data were extracted using MaZda software, and the compound model was calculated from radiomics and clinical features by logistic regression. The performance of the different models was compared by examining the area under the receiver operating characteristic curve (AUC). The prediction of prognosis was evaluated using survival analysis. RESULTS: Thirty NC-CT radiomic features were extracted and analyzed. The compound model was formed using four NC-CT run-length matrix (RLM) features and general image features, which included the maximum diameter (cm) of the tumor and the number of tumors (n). The AUCs of the model for TACE response were 0.840 and 0.815, whereas the AUCs of the six-and-twelve grade were 0.754 and 0.750 in the training and validation groups, respectively. HCC patients were divided into two groups using the cutoff value of the model: a group in which the TACE-response led to good survival and a group in which TACE-nonresponse caused poor prognosis. CONCLUSION: Radiomic features from NC-CT predicted TACE-response. The compound model generated by NC-CT radiomics and clinical features is effective and directly predicts TACE-response and overall survival. The model may be used repeatedly and is easy to operate.

Divergent effects of irradiation on brain cortical morphology in patients with nasopharyngeal carcinoma: one-year follow-up study using structural magnetic resonance imaging.

BACKGROUND: Increasing evidence indicates that radiotherapy (RT)-induced brain cortical deficits may play a critical role in developing radiation encephalopathy in patients with nasopharyngeal carcinoma (NPC). However, the evolutional processes of RT-induced cortical injury have not been sufficiently investigated. This study investigates RT-induced effects on cortical morphology using longitudinal structural magnetic resonance imaging (MRI) in NPC patients. METHODS: Using MRI-based morphometry with surface-based measures, we evaluated the longitudinal alterations of cortical volume (CV), cortical thickness (CT), and cortical surface area (CSA) in 104 NPC patients at pre-RT (n=104), within 3 months post-RT (n=92), 6 months post-RT (n=71), and 9-12 months post-RT (n=52). Twenty healthy controls were also evaluated in parallel. Linear mixed models were used to investigate the trajectories of RT-related changes in cortical brain morphology and its association with irradiation dose, with healthy controls data being used to construct a normal age-related benchmark. The level of statistical significance was set at P<0.05, corrected for multiple comparisons. RESULTS: The results showed that RT-related longitudinal alterations in cortical morphology underwent two diverse patterns during the first year of follow up in NPC patients. The temporal cortices (including the bilateral superior temporal gyrus, middle temporal gyrus, temporal pole, parahippocampal and fusiform gyrus, and the right inferior temporal and right transverse temporal gyrus), the basal occipital cortices (the right lingual gyrus and lateral occipital gyrus), and the basal frontal cortices (the right lateral orbitofrontal gyrus) showed time-dependent attenuation in cortical morphology indices. Furthermore, these effects on multiple cortices were dose-dependent, suggesting they were RT-associated. In contrast, in the left rostral middle frontal gyrus, there was a time-dependent increase in CT. CONCLUSIONS: Our preliminary findings revealed divergent effects of irradiation on cortical brain morphology. These results contribute to a more comprehensive understanding of the underlying neural mechanisms of irradiation-related neurotoxic effects on cortical brain morphology and will help guide the investigation of critically neuroprotective strategies.

Standard radiotherapy for patients with nasopharyngeal carcinoma results in progressive tract-specific brain white matter alterations: A one-year follow-up via diffusion tensor imaging.

BACKGROUND AND PURPOSE: Radiation therapy (RT)-induced neurocognitive disability may be mediated by brain tissue damage. The aim of the present study was to investigate the effects of standard RT on normal brain tissue via in vivo neuroimaging in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: A total of 146 newly diagnosed NPC patients who were treated with standard RT were longitudinally followed up at multiple time points during the first year post-RT, with 19 comparable healthy controls followed up in parallel serving as normal age-related benchmarks. Magnetic resonance diffusion tensor imaging was used to evaluate longitudinal brain white matter tract changes in NPC patients. The relationships between RT-related white matter changes, hippocampal atrophy, and cognitive impairment were also assessed. RESULTS: Bilateral cingulate angular bundle (CAB) fibers had progressive diffusion reduction [radial diffusivity (RD) and mean diffusivity] over time (P < 0.05, corrected for multiple comparisons) in NPC patients during the first year after RT. RT-associated progressive RD reduction in the left CAB correlated with longitudinal atrophy of the ipsilateral hippocampus (P = 0.033). Additionally, RT-associated progressive RD reduction in the left CAB correlated with progressive cognitive impairment in NPC patients post-RT (P = 0.048). CONCLUSION: We present evidence of progressive RT-associated changes in the bilateral CAB in NPC patients, which may underlie RT-related cognitive impairment. These findings illustrate that the use of white matter tract alterations as potential biomarkers to detect RT-related brain injury in NPC patients may be useful for better understanding the pathogenesis of RT-induced cognitive decline.

Irradiation-related longitudinal white matter atrophy underlies cognitive impairment in patients with nasopharyngeal carcinoma.

To longitudinally investigate alterations in cerebral white matter volume as a function of irradiation dose and time after standard radiotherapy in nasopharyngeal carcinoma patients and to determine how these alterations are related to radiotherapy-associated neurocognitive dysfunction.A total of 120 nasopharyngeal carcinoma patients were included in the present study. Longitudinal structural magnetic resonance imaging was performed at pre-radiotherapy and 1-3, 6, and 9-12 months post-radiotherapy. Twenty healthy controls were recruited and followed up with in parallel. Structural images were processed via FreeSurfer. The Montreal Cognitive Assessment was performed to evaluate cognitive function of the participants. Linear mixed models and general linear models were used to evaluate different trajectories and the relationship between white matter volume and cognition in patients and controls within approximately 12 months of follow-up.Selective and time-dependent white matter atrophy was observed in the right parahippocampal gyrus, right inferior temporal gyrus, right middle temporal gyrus, right fusiform gyrus, and left insular cortex in post-radiotherapy patients compared to the controls. Moreover, radiotherapy-associated white matter atrophy in the right parahippocampal gyrus exhibited a dose-dependent pattern, whereas radiotherapy-associated white matter atrophy in the right inferior temporal gyrus was correlated with progressive cognitive impairment in patients.Taken together, our findings illustrate that white matter volume alterations can be used as a potential biomarker to detect radiotherapy-related subtle brain injury in nasopharyngeal carcinoma patients, which may help further elucidate the pathogenesis of radiation-induced cognitive decline and facilitate studies on cognition-sparing radiotherapy.

The Utility of Texture Analysis Based on Breast Magnetic Resonance Imaging in Differentiating Phyllodes Tumors From Fibroadenomas.

Background: The preoperative diagnosis of phyllodes tumors (PTs) of the breast is critical to appropriate surgical treatment. However, reliable differentiation between PT and fibroadenoma (FA) remains difficult in daily clinical practice. The purpose of this study was to investigate the utility of breast MRI texture analysis for differentiating PTs from FAs. Materials and Methods: Forty-two PTs and 42 FAs were enrolled in this retrospective study. Clinical and conventional MRI features (CCMF) and MRI texture analysis were used to distinguish between PT and FA. Texture features were extracted from the axial short TI inversion recovery T2-weighted (T2W-STIR), T1-weighted pre-contrast, and two contrast-enhanced series (first contrast and third contrast). The Mann-Whitney U test was used to select statistically significant features of texture analysis and CCMF. Using a linear discriminant analysis, the most discriminative features were determined from statistically significant features. The K-nearest neighbor classifier and ROC curve were applied to evaluate the diagnostic performance. Results: With a higher classification accuracy (89.3%) and an AUC of 0.89, the texture features on T2W-STIR outperformed the texture features on other MRI sequences and CCMF. The AUC of the combination of CCMF with texture features on T2W-STIR was significantly higher than that of CCMF or texture features on T2W-STIR alone (p < 0.05). Based on the result of the classification accuracy (95.2%) and AUC (0.95), the diagnostic performance of the combination strategy performed better than texture features on T2W-STIR or CCMF separately. Conclusions: Texture features on T2W-STIR showed better diagnostic performance compared to CCMF for the distinction between PTs and FAs. After further validation of multi-institutional large datasets, MRI-based texture features may become a potential biomarker and be a useful medical decision tool in clinical trials having patients with breast fibroepithelial neoplasms.

Aberrant Brain Activity at Early Delay Stage Post-radiotherapy as a Biomarker for Predicting Neurocognitive Dysfunction Late-Delayed in Patients With Nasopharyngeal Carcinoma.

Background: Increasing evidence indicates that early radiation-induced subtle cerebral changes may be the precursors to permanent brain dysfunction at the late-delayed (LDS) post-radiotherapy (RT) stage. In this study, we aim to track the RT-related longitudinal brain activity in nasopharyngeal carcinoma (NPC) patients and to determine whether early abnormal brain activity can predict late neurocognitive dysfunction after RT. Methods: Thirty-three NPC patients were finally included and longitudinally followed up at the following time points: prior to treatment initiation, early-delayed stage (EDS, 1-3 months), and LDS (six months) after RT. Fifteen comparable healthy controls (HCs) were finally included and followed up in parallel. Montreal Cognitive Assessment (MoCA) was used to assess the general cognitive function. Brain activity was recorded via resting-state fMRI and regional homogeneity (ReHo). A whole-brain voxel-wise-based one-way repeated-measure analysis of variance (ANOVA) was conducted to evaluate the longitudinal ReHo changes among the three time points for NPC patients and HCs, respectively. Results were reported at the significant level of a threshold of two-tailed voxel-wise P < 0.01 and cluster level P < 0.05 with Gaussian Random Field (GRF) correction. Finally, the efficacies of the aberrant ReHo at EDS for predicting the cognitive impairment at LDS in NPC patients were evaluated. Results: Significant differences were detected in ReHo among the three time points in NPC patients but not in HCs. Aberrant ReHo was distributed in the bilateral cerebellum, the right temporal lobe, and the left insular areas, which showed different dynamic changes patterns over time. Logistic regression model combining the mean ReHo, age, and irradiation dose on the bilateral temporal lobe had the highest diagnostic efficiency according to the area under the curve (AUC) score (AUC = 0.752, P = 0.023). Conclusions: The post-RT brain activity revealed by ReHo in NPC patients was dynamic, complex, and multifactorial. Furthermore, the combination of the aberrant ReHo at EDS, age, and irradiation dose may serve as a potential biomarker of the RT-induced cognitive impairments at LDS.

Changes in functional brain networks and neurocognitive function in Chinese gynecological cancer patients after chemotherapy: a prospective longitudinal study.

BACKGROUND: Previous neurocognitive assessments in non-central nervous system cancers highlight the high incidence of neurocognitive dysfunction in this study population. However, there have been few studies exploring neurocognitive dysfunction induced by chemotherapy in gynecological cancer patients. This prospective longitudinal study was conducted to assess neurocognitive functioning and functional brain networks in Chinese gynecological cancer patients pre- and post-chemotherapy, while additionally including age-matched healthy subjects as the control group. METHODS: All research participants were evaluated using a resting-state functional magnetic resonance imaging and neurocognition assessment. Behavioral data were conducted using SPSS for descriptive statistics, correlation and comparison analyses. Preprocessing of MRI (Magnetic Resonance Imaging) data and network analyses were performed using GRETNA (Graph Theoretical Network Analysis). RESULTS: A total of 40 subjects joined this study, with 20 subjects in each group. With the exception of the mean of psychomotor speed, there was no significant difference pre-chemotherapy between patients and healthy controls in neurocognitive test mean scores (Ps > 0.05). During the post-chemotherapy assessment, there were significant differences in the mean scores of neurocognitive tests (including Digit Span tests, verbal memory, immediate recall, delayed recall, and information processing speed tests) (all Ps < 0 .05). Longitudinal graph analysis revealed statistically significant differences in the patient group, with significant decreases in both local efficiency (P < 0.01) and global efficiency (P = 0.04). Lower raw TMT-A scores were significantly associated with lower local efficiency (r = 0.37, P = 0.03). Lower verbal memory scores were statistically significant and associated with lower global efficiency (r = 0.54, P = 0.02) in the patient group, but not in the healthy control group. CONCLUSIONS: This study found that the risk of brain function and neurocognitive changes following chemotherapy could potentially guide patients in making appropriate treatment decisions, and this study may identify a cohort that could be suited for study of an intervention.

Radiation-induced hippocampal atrophy in patients with nasopharyngeal carcinoma early after radiotherapy: a longitudinal MR-based hippocampal subfield analysis.

Increasing evidence indicates that radiation-induced injury to the hippocampus may play a critical role in neurocognitive dysfunction in patients with nasopharyngeal carcinoma (NPC). However, few studies have assessed RT-induced hippocampal structural alterations in these patients early after radiotherapy (RT). In this study, 58 NPC patients were longitudinally followed up prior to treatment initiation as well as 3 and 6 months after RT, respectively. Twenty comparable normal controls were recruited and followed up in parallel. A novel magnetic resonance imaging (MRI)-based automated method was used to label hippocampal subfields. The linear mixed model was employed to evaluate longitudinal changes in the volumes of the whole hippocampus and seven hippocampal subfields. Time-dependent volume reduction was observed in the bilateral hippocampus, as well as in the bilateral granule cell layer (GCL), bilateral cornu ammonis 1 (CA1), bilateral molecular layer (ML), and bilateral subiculum (SUB) in NPC patients, but not in controls. Moreover, volume deficits in the bilateral hippocampus, bilateral GCL, and right ML showed dose-dependent patterns, and high volume losses in the bilateral hippocampus, bilateral GCL, left SUB, and right ML were associated with a rapid decline in cognitive function. Our findings demonstrated that the hippocampal subfields were selectively injured by irradiation-related early neurotoxic effects, which might account for cognitive impairment in NPC patients at an early stage after RT. Further, structural MRI could serve as a potential noninvasive imaging biomarker for the early detection of radiation effects on the hippocampus in NPC patients after RT.

Longitudinal brain structural alterations in patients with nasopharyngeal carcinoma early after radiotherapy.

Background and purpose: To investigate effects of radiotherapy on normal brain tissue using in vivo neuroimaging in patients with nasopharyngeal carcinoma (NPC). Methods and materials: We used longitudinal MRI to monitor structural brain changes during standard radiotherapy in patients newly diagnosed with NPC. We assessed volumetric measures in 63 patients at 2-3 time points before and after radiotherapy, with 20 NPC-free participants as normal controls. Images were processed using validated software (FreeSurfer). Automated results were inspected visually for accuracy. We examined changes in volume of the whole brain, gray matter, white matter, and ventricles, as well as in cerebral volumes partitioned into temporal, frontal, parietal, and occipital lobes. A linear mixed model was used to evaluate longitudinal changes in these measurements. Statistical significance was evaluated at p < 0.05, which was corrected for multiple comparisons. Results: Volumes of the gray matter, and bilateral temporal lobes decreased in a time-dependent manner, whereas ventricle volume showed a time-dependent increase after radiotherapy. No volume changes were detected in NPC patients before radiotherapy when compared normal controls. No volume changes were detected in the subcohort of patients after completion of induction chemotherapy but prior to initiation of radiotherapy. Changes of bilateral temporal lobe volume correlated with irradiation dose in this region. Expansion of the ventricles correlated with a reduction in cognition assessment. Conclusions: We detected significant and progressive radiotherapy-associated structural changes in the brains of patients with NPC who were treated with standard radiotherapy, especially in the bilateral temporal lobe in which the effect was dose-dependent. Expansion of the ventricles can serve as an imaging marker for treatment-related reduction in cognitive function. Future studies with longer follow-ups are needed to evaluate morphometric changes long-term after radiotherapy.

Network-level dysconnectivity in patients with nasopharyngeal carcinoma (NPC) early post-radiotherapy: longitudinal resting state fMRI study.

In this study, we seek to longitudinally investigate the network-level functional connectivity (FC) alternations and its association with irradiation dose and cognition changes in the early stage post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients. We performed independent component analysis (ICA) of resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) from 39 newly diagnosed NPC patients before receiving treatment (baseline), and 3 months post-RT. the default mode network (DMN), salience network (SN), and executive control network (ECN) were extracted with well-validated software (GIFT). Inter-network connectivity was assessed using the functional network connectivity (FNC) toolbox. The inter- and intra-network FC was compared between time points, and the z value of FC alternation was correlated with the RT dose value and cognitive changes. Compared with baseline, the FC of the left anterior cingulate cortex (ACC) within the DMN, and the right insular within the SN, significantly reduced 3 months post-RT, with greater effects at higher doses in the right insular. Bilateral ECN FC was also significantly lower 3 months post-RT compared to the baseline. Chemotherapy was not associated with inter- and intra- network FC change. We found intra- and inter-network FC disruption in NPC patients 3 months post-RT, with the right insular showing a dose-dependent effect. Thus, this network-level FC may serve as a potential biomarker of the RT-induced brain functional impairments, and provide valuable targets for further functional recovery treatment.

Aberrant interhemispheric functional and structural connectivity in heroin-dependent individuals.

Models of heroin addiction emphasize the role of disrupted frontostriatal circuitry supporting cognitive control processes. However, heroin addiction-related alterations in functional and structural interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. The corpus callosum (CC), which connects homologous regions of the cortex, is the major conduit for information transfer between the cerebral hemispheres and represents a structural connectivity index between hemispheres. We compared interhemispheric voxel-mirrored homotopic connectivity (VMHC) and CC volume between 45 heroin dependent-individuals (HDIs) and 35 non-addict individuals. We observed significant reduction of VMHC in a number of regions, particularly the striatum/limbic system regions, and significant decrease in splenium and genu sub-regions of CC in HDI. Importantly, within HDI, VMHC in the dorsal lateral prefrontal cortex (DLPFC) correlated with genu CC volume, VMHC in the putamen, VMHC in the DLPFC and genu CC volume and splenium CC volume were negatively correlated with heroin duration and impulsivity traits. Further analyses demonstrated that impairment of VMHC of bilateral DLPFC partially mediated the association between genu CC volumes decreased and increased impulsivity in HDI. Our results reveal a substantial impairment of interhemispheric coordination in the HDI. Further, interhemispheric connectivity correlated with the duration of heroin abuse and higher impulsivity behavior in HDI. Our findings provide insight into a heroin addicts' related pathophysiology and reinforce an integrative view of the interhemispheric cerebral functional and structural organization.

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

OBJECTIVES: To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. METHODS: We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. RESULTS: We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. CONCLUSIONS: These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. KEY POINTS: • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.