Postoperative myopic shift and visual acuity rehabilitation in patients with bilateral congenital cataracts.

Background: This study aimed to explore the postoperative myopic shift and its relationship to visual acuity rehabilitation in patients with bilateral congenital cataracts (CCs). Methods: Bilateral CC patients who underwent cataract extraction and primary intraocular lens implantations before 6 years old were included and divided into five groups according to surgical ages (<2, 2-3, 3-4, 4-5, and 5-6 years). The postoperative myopic shift rates, spherical equivalents (SEs), and the best corrected visual acuity (BCVA) were measured and analyzed. Results: A total of 1,137 refractive measurements from 234 patients were included, with a mean follow-up period of 34 months. The postoperative mean SEs at each follow-up in the five groups were linearly fitted with a mean R2 = 0.93 ± 0.03, which showed a downtrend of SE with age (linear regression). Among patients with a follow-up of 4 years, the mean postoperative myopic shift rate was 0.84, 0.81, 0.68, 0.24, and 0.28 diopters per year (D/y) in the five age groups (from young to old), respectively. The BCVA of those with a surgical age of <2 years at the 4-year visit was 0.26 (LogMAR), and the mean postoperative myopic shift rate was 0.84 D/y. For patients with a surgical age of 2-6 years, a poorer BCVA at the 4-year visit was found in those with higher postoperative myopic shift rates (r = 0.974, p = 0.026, Pearson's correlation test). Conclusion: Performing cataract surgery for patients before 2 years old and decreasing the postoperative myopic shift rates for those with a surgical age of 2-6 years may benefit visual acuity rehabilitation.

Surgical approach to and morphology of visually significant persistent pupillary membranes.

PURPOSE: To characterize the morphology of persistent pupillary membranes (PPMs) in pediatric patients and explore the corresponding surgical approaches. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Prospective observational study. METHODS: Consecutive pediatric patients with PPMs who underwent surgery from April 2020 to July 2022 were included. PPM morphology was assessed and categorized according to its anatomic relationship with crystalline lens and distribution of iris strands. The surgical approaches for different morphologies of PPMs were described in detail. The visual outcome and operation-related complications were recorded. RESULTS: 31 eyes from 19 patients were included with the mean age of 7.2 years. 3 morphological variants of PPMs were observed: type I (51.6%, 16/31), a spider-like appearance and no adhesion to the anterior lens capsule (ALC); type II (38.7%, 12/31), a loose central adherence to the ALC and partially thick iris strands attached to the iris collarette; type III (9.7%, 3/31), a tight central adherence to the ALC and only silk-like iris strands. Surgeries were performed with a natural pupil size in type I, while dilated pupil in the other types. The adhesions between PPM and the ALC were separated by viscoelastic injection in type II and by discission needles in type III. The corrected distance visual acuity was significantly improved from 0.34 ± 0.18 logMAR preoperatively to 0.17 ± 0.09 logMAR postoperatively ( P < .001). No operation-related complications were observed during 9.5-month follow-up. CONCLUSIONS: PPMs were categorized into 3 types according to their different morphologies, which helped to determine the best surgical strategy.

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.

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.

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.

Novel compound heterozygous variants of the SEC23A gene in a Chinese family with cranio-lenticulo-sutural dysplasia based on data from a large cohort of congenital cataract patients.

BACKGROUND: Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). METHODS: We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. RESULTS: Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. CONCLUSION: This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.

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.

Whole-Exome Sequencing and Copy Number Analysis in a Patient with Warburg Micro Syndrome.

Warburg Micro syndrome (WARBM) is an autosomal recessive neuro-ophthalmologic syndrome characterized by microcephaly, microphthalmia, congenital cataracts, cortical dysplasia, corpus callosum hypoplasia, spasticity, and hypogonadism. WARBM is divided into four subtypes according to the causative genes, of which RAB3GAP1 (OMIM# 602536) accounts for the highest proportion. We collected detailed medical records and performed whole-exome sequencing (WES) for a congenital cataract patient. A novel heterozygous frameshift RAB3GAP1 variant was detected in a boy with a rare ocular phenotype of bilateral membranous cataracts accompanied by a persistent papillary membrane. Further copy number variation (CNV) analysis identified a novel deletion on chromosome 2q21.3 that removed 4 of the 24 exons of RAB3GAP1. The patient was diagnosed with WARBM following genetic testing. The present study expands the genotypic and phenotypic spectrum of WARBM. It suggests applying whole exome sequencing (WES) and CNV analysis for the early diagnosis of syndromic diseases in children with congenital cataracts.

Two Polysaccharides from Liupao Tea Exert Beneficial Effects in Simulated Digestion and Fermentation Model In Vitro.

Liupao tea is an important dark tea, but few studies on purified Liupao tea polysaccharide (TPS) are reported in the literature. In this study, two TPSs, named TPS2 and TPS5, with molecular weights of 70.5 and 133.9 kDa, respectively, were purified from Liupao tea. TPS2 contained total sugar content (53.73% ± 1.55%) and uronic acid content (35.18% ± 0.96%), while TPS5 was made up of total sugar (51.71% ± 1.1%), uronic acid (40.95% ± 3.12%), polyphenols (0.43% ± 0.03%), and proteins (0.11% ± 0.07%). TPS2 and TPS5 were composed of Man, Rha, GlcA, Glc, Gal, and Ara in the molar ratios of 0.12:0.69:0.20:0.088:1.60:0.37 and 0.090:0.36:0.42:0.07:1.10:0.16, respectively. The effects of TPS2 and TPS5 on digestion and regulation of gut microbiota in hyperlipidemic rats were compared. In simulated digestion, TPS5 was degraded and had good antioxidant effect, whereas TPS2 was not affected. The bile acids binding capacities of TPS2 and TPS5 were 42.79% ± 1.56% and 33.78% ± 0.45%, respectively. During in vitro fermentation, TPS2 could more effectively reduce pH, promote the production of acetic acid and propionic acid, and reduce the ratio of Firmicutes to Bacteroidetes. TPS5 could more effectively promote the production of butyric acid and increase the abundance of genus Bacteroides. Results indicate that polysaccharides without polyphenols and proteins have better antidigestibility and bile acid binding. Meanwhile, polysaccharides with polyphenols and proteins have a better antioxidant property. Both have different effects on the gut microbiota.

Broadening the genotypic and phenotypic spectrum of MAF in three Chinese Han congenital cataracts families.

Pathogenic variants in the v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue (MAF) encoding a transcription factor (from a unique subclass of basic leucine zipper transcription factors) are associated with isolated congenital cataracts (CCs) and Aymé-Gripp syndrome (AYGRPS). We collected detailed disease histories from, and performed comprehensive ophthalmic and systemic examinations in 269 patients with CCs; we then performed whole-exome sequencing. Pathogenicity assessments were evaluated using multiple predictive tools. The clinical validities of the reported gene-disease relationships for MAF genes (MAF-CCs and MAF-AYGRPS) were assessed using the ClinGen gene curation framework. We identified two novel (c.173C>A, p.Thr58Asn and c.947T>C, p. Leu316Pro) variants and one known (c.173C>T, p.Thr58Ile) MAF missense variant in three patients. We described novel phenotypes including cleft palate, macular hypoplasia, and retinal neovascularization in the peripheral avascular area and analyzed the genotype-phenotype correlations. We demonstrated associations of variants in the MAF C-terminal DNA-binding domain with CCs and associations of variants in the N-terminal transactivation domain of MAF with AYGRPS. We thus expand the genotypic and phenotypic spectrum of the MAF gene. The ClinGen gene curation framework results suggested that variants in different domains of MAF are associated with different diseases.

Unusual Presentation in WAGR Syndrome: Expanding the Phenotypic and Genotypic Spectrum of the Diseases.

The deletion of chromosome 11p13 involving the WT1 and PAX6 genes has been shown to cause WAGR syndrome (OMIM #194072), a rare genetic disorder that features Wilms' tumor, aniridia, genitourinary anomalies, as well as mental retardation. In this study, we expand the genotypic and phenotypic spectrum of WAGR syndrome by reporting on six patients from six unrelated families with different de novo deletions located on chromosome 11p13. Very rare phenotypes of lens automated absorption and lens thinning were detected in four of the six patients. We assessed the involvement of the ARL14EP gene in patients with and without severe lens abnormalities and found that its deletion may worsen the lens abnormalities in these patients.

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.

Visual Function in Children With Posterior Lens Opacities Before and After Surgery.

PURPOSE: To evaluate the visual function before and after cataract surgery in children with congenital posterior lens opacities as well as the factors associated with a good visual outcome. DESIGN: Perspective case-series study. METHODS: Pediatric patients with posterior lens opacities who underwent cataract surgery were recruited in this study. The cataract type, location, area of opacities, and strabismus were examined perioperatively. Moreover, visual acuity, modulation transfer function (MTF), ocular aberrations, and stereopsis were measured before and after cataract surgery. RESULTS: Sixty-nine eyes of 63 patients were studied. The mean age of patients at surgery was 6.5 ± 2.9 years. Visual function including corrected distance visual acuity (CDVA), MTF cutoff frequency, and ocular aberrations were significantly affected in eyes with posterior lens opacities. Postoperatively, CDVA was significantly improved from 0.81 ± 0.53 logMAR to 0.40 ± 0.40 logarithm of the minimum angle of resolution (logMAR) (P < .001). Thirty-nine patients (56.5%) achieved a final VA of 20/40 or better. Moreover, MTF cutoff values were significantly improved, and total ocular aberrations were decreased after cataract removal (both P < .001). The stereopsis was also improved postoperatively (P < .001). The multivariate analysis of the risk factors for postoperative CDVA showed that worse preoperative CDVA, larger size of lens opacities, and mean keratometry were the risk factors (all P < .05). CONCLUSIONS: Visual function can be significantly decreased in children with posterior lens opacities, and surgery was effective in improving visual function. Patients with a CDVA of 0.52 logMAR or better, a size of lens opacity <6.5 mm2 and smaller mean keratometry had a greater CDVA postoperatively.

Mesoporous silica nanoparticle-embedded lanthanide organic polyhedra for enhanced stability, luminescence and cell imaging.

We report here a simple but efficient "ship-in-a-bottle" synthetic strategy for increasing the stability and luminescence performance of LOPs by embedding them into mesoporous silica nanoparticles (MSNs). Three types of hybrid materials, i.e. Eu8L12@MSNs, Eu8L12@MSNs-NH2 and Eu8L12@MSNs-biotin, have been prepared and characterized by FT-IR, TGA, SEM and TEM. Photo-optical measurements confirmed that the photoluminescence quantum yields in water have been greatly improved from 5.50% for pristine Eu8L12 to 44.04% for Eu8L12@MSNs-biotin, along with fast disassembly for the former and the optical performance has been maintained for the latter under acidic conditions (pH = 4). Moreover, compared to Eu8L12, Eu8L12@MSNs and Eu8L12@MSNs-NH2, the biotin-modified hybrid material Eu8L12@MSNs-biotin has exhibited much enhanced fluorescence-imaging ability toward the MDA-MB-231 human breast cancer cells, with significantly reduced dosage of the complex. Our work provides a useful strategy for the functionalization of multinuclear lanthanide organic assemblies toward their biosocial applications.

Effectiveness of surgical management of malignant glaucoma in phakic eyes.

AIM: To assess the effectiveness of core vitrectomy-phacoemulsification-intraocular lens (IOL) implantation-capsulo-hyaloidotomy in treating phakic eye at least 1mo after the onset of malignant glaucoma. METHODS: A retrospective analysis were performed on malignant glaucoma patients treated in Zhongshan Ophthalmic Center between 2016 and 2018. Demographic and clinical data were described. The preoperative and postoperative visual acuity (VA), intraocular pressure (IOP), number of IOP-lowering medications used, and anterior chamber depth (ACD) of the case series were compared by Wilcoxon signed-rank test. RESULTS: Thirteen phakic eyes with long time intervals between onset and surgery were identified in this case series. Core vitrectomy-phacoemulsification-IOL implantation-capsulo-hyaloidotomy reduced the IOP (P=0.046) and the number of IOP-lowering medications used (P=0.004), deepened the ACD (P=0.005). Complete success was achieved in 38.5% of the eyes, and anatomical success was achieved in 100% of the eyes without any recurrence. The only postoperative complication observed is corneal endothelial decompensation. It occurred in two cases. CONCLUSION: Core vitrectomy-phacoemulsification-IOL implantation-capsulo-hyaloidotomy is safe and effective for treatment of long onset phakic malignant glaucoma.

Intraoperative OCT for the assessment of posterior capsular integrity in pediatric cataract surgery.

PURPOSE: To study the morphology of the posterior lens cortex and posterior capsules (PCs) in pediatric patients with posterior lens opacities using intraoperative optical coherence tomography (iOCT). SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Prospective observational study. METHODS: Pediatric patients with posterior lens opacities were imaged using iOCT during cataract surgery. The morphology of the posterior lens cortex and PC, along with the common patterns to indicate PC integrity, was assessed. Moreover, PC rent during surgery was observed. RESULTS: A total of 62 eyes from 53 patients were included. The mean age of patients was 3.8 years. 4 morphological variants of posterior lens opacity were observed: type I (34/62 [54.8%]) with an intact PC; type II (20/62 [32.3%]) with an intact PC, which protruded into the anterior vitreous; type III (3/62 [4.8%]) with a deficient PC and an inability to delineate the PC; and type IV (5/62 [8.1%]) with dense opacity and an inability to characterize the posterior cortex and PC. Phacoemulsification could be performed in types I and II. In types III and IV, manual nucleus removal was performed instead of phacoemulsification. 3 cases (100%) of type III PC dehiscence developed during surgery, whereas no cases developed PC dehiscence of other types. CONCLUSIONS: The morphology of the PC and posterior lens cortex in pediatric posterior lens opacities could be categorized, and PC integrity could be assessed using iOCT, which was useful to guide surgical strategies and increase safety in pre-existing PC dehiscence in pediatric cataract surgery.

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.