Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Metal deposits associated with brain atrophy in the deep gray matter nucleus in Wilson's disease.

Regional atrophy and metal deposition are typical manifestations in Wilson's disease, but their relationship has not been systematically investigated. We aim to investigate the association of regional brain atrophy and metal deposition in the deep gray matter nucleus at MRI in Wilson's disease. We acquired the structural and susceptibility mapping and performed a cross-sectional comparison of volume and susceptibility in deep gray matter nucleus. The most extensive and severe atrophy was detected in brain regions in neuro-Wilson's disease, as well as the most widespread and heaviest metal deposits. Metal deposits were significantly negatively correlated with volume in the bilateral thalamus, caudate, and putamen. None of correlation was found between the clinical score with volume or susceptibility in the focused regions. In the 1-year follow-up analysis, the volume of right thalamus, globus pallidus, and brainstem and the susceptibility of the left caudate have decreased significantly as the symptom improvement. In Wilson's disease, phenotypes have varied scope and extend of volumetric atrophy and metal deposits. This study is expected to take the lead in revealing that in neuro-Wilson's disease, greater regional atrophy associated with heavier metal deposits in Wilson's disease. Moreover, after 1-year treatment, the imaging data have changed as the patient's condition improvement.

Tumor Multiregional Mean Apparent Propagator (MAP) Features in Evaluating Gliomas-A Comparative Study With Diffusion Kurtosis Imaging (DKI).

BACKGROUND: Glioma classification affects treatment and prognosis. Reliable imaging methods for preoperatively evaluating gliomas are essential. PURPOSE: To evaluate tumor multiregional mean apparent propagator (MAP) features in glioma diagnosis and to compare those with diffusion-kurtosis imaging (DKI). STUDY TYPE: Retrospective study. SUBJECTS: 70 untreated glioma patients (31 LGGs (low-grade gliomas), 34 women; mean age, 47 ± 12 years, training (60%, n = 42) and testing cohorts (40%, n = 28)). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-MRI using q-space Cartesian grid sampling with 11 different b-values. ASSESSMENT: Tumor multiregional MAP (mean squared displacement (MSD); q-space inverse variance (QIV); non-Gaussianity (NG); axial/radial non-Gaussianity (NGAx, NGRad); return-to-origin/axis/plane probability (RTOP, RTAP, and RTPP)); and DKI metrics (axial/mean/radial kurtosis (AK, MK, and RK)) on tumor parenchyma (TP) and peritumoral areas (PT) in histopathologically gliomas grading and genotyping were assessed. STATISTICAL TESTS: Mann-Whitney U; Kruskal-Wallis; Benjamini-Hochberg; Bonferroni-correction; receiver operating curve (ROC) and area under curve (AUC); DeLong's test; Random Forest (RF). P value<0.05 was considered statistically significant after multiple comparisons correction. RESULTS: Compared with LGGs, MSD, and QIV were significantly lower in TP, whereas NG, NGAx, NGRad, RTOP, RTAP, RTPP, and DKI metrics were significantly higher in HGGs (high-grade gliomas) (P ≤ 0.007), as well as in isocitrate-dehydrogenase (IDH)-mutated than IDH-wildtype gliomas (P ≤ 0.039). These trends were reversed for PT (tumor grades, P ≤ 0.011; IDH-mutation status, P ≤ 0.012). ROC analysis showed that, in TP, DKI metrics performed best in TP (AUC 0.83), whereas in PT, RTPP performed best (AUC 0.77) in glioma grading. AK performed best in TP (AUC 0.77), whereas MSD and RTPP performed best in PT (AUC 0.73) in IDH genotyping. Further RF analysis with DKI and MAP demonstrated good performance in grading (AUC 0.91, Accuracy 82%) and IDH genotyping (AUC 0.87, Accuracy 79%). DATA CONCLUSION: Tumor multiregional MAP features could effectively evaluate gliomas. The performance of MAP may be similar to DKI in TP, while in PT, MAP may outperform DKI. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Quantitative susceptibility mapping evaluation of glioma.

OBJECTIVES: To comprehensively evaluate the glioma using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Forty-two patients (18 women; mean age, 45 years) with pathologically confirmed gliomas were retrospectively included. All the patients underwent conventional and advanced MRI examinations (QSM, DWI, MRS, etc.). Five patients underwent paired QSM (pre- and post-enhancement). Four Visually Accessible Rembrandt Image (VASARI) features and intratumoural susceptibility signal (ITSS) were observed. Three ROIs each were manually drawn separately in the tumour parenchyma with relatively high and low magnetic susceptibility. The association between the tumour's magnetic susceptibility and other MRI parameters was also analysed. RESULTS: Morphologically, gliomas with heterogeneous ITSS were more similar to high-grade gliomas (p = 0.006, AUC: 0.72, sensitivity: 70%, and specificity: 73%). Heterogeneous ITSS was significantly associated with tumour haemorrhage, necrosis, diffusion restriction, and avid enhancement but did not change between pre- and post-enhanced QSM. Quantitatively, tumour parenchyma magnetic susceptibility had limited value in grading gliomas and identifying IDH mutation status, whereas the relatively low magnetic susceptibility of the tumour parenchyma helped identify oligodendrogliomas in IDH mutated gliomas (AUC = 0.78) with high specificity (100%). The relatively high tumour magnetic susceptibility significantly increased after enhancement (p = 0.039). Additionally, we found that the magnetic susceptibility of the tumour parenchyma was significantly correlated with ADC (r = 0.61) and Cho/NAA (r = 0.40). CONCLUSIONS: QSM is a promising candidate for the comprehensive evaluation of gliomas, except for IDH mutation status. The magnetic susceptibility of tumour parenchyma may be affected by tumour cell proliferation. KEY POINTS: • Morphologically, gliomas with a heterogeneous intratumoural susceptibility signal (ITSS) are more similar to high-grade gliomas (p = 0.006; AUC, 0.72; sensitivity, 70%; and specificity, 73%). Heterogeneous ITSS was significantly associated with tumour haemorrhage, necrosis, diffusion restriction, and avid enhancement but did not change between pre- and post-enhanced QSM. • Tumour parenchyma's relatively low magnetic susceptibility helped identify oligodendroglioma with high specificity. • Tumour parenchyma magnetic susceptibility was significantly correlated with ADC (r = 0.61) and Cho/NAA (r = 0.40).

Structural alterations of spinocerebellar ataxias type 3: from pre-symptomatic to symptomatic stage.

OBJECTIVES: To investigate and characterize the structural alterations of the brain in SCA3, and their correlations with the scale for the assessment and rating of ataxia (SARA) and normal brain ATXN3 expression. METHODS: We performed multimodal analyses in 52 SCA3 (15 pre-symptomatic) and healthy controls (HCs) (n = 35) to assess the abnormalities of gray and white matter (WM) of the cerebrum, brainstem, and cerebellum via FreeSurfer, SUIT, and TBSS, and their associations with disease severity. Twenty SCA3 patients (5 pre- and 15 symptomatic) were followed for at least a year. Besides, we uncovered the normal pattern of brain ATXN3 spatial distribution. RESULTS: Pre-symptomatic patients showed only WM damage, mainly in the cerebellar peduncles, compared to HCs. In the advanced stage, the WM damage followed a caudal-rostral pattern. Meanwhile, continuous nonlinear structure damage was characterized by brainstem volumetric reduction and relatively symmetric cerebellar and basal ganglia atrophy but spared the cerebral cortex, partially explained by the ATXN3 overexpression. The bilateral pallidum, brainstem, and cerebellar peduncles demonstrated a very large effect size. Besides, all these alterations were significantly correlated with SARA; the pons (r = -0.65) and superior cerebellar peduncle (r = -0.68) volume demonstrated a higher correlation than the cerebellum with SARA. The longitudinal study further uncovered progressive atrophy of pons in symptomatic SCA3. CONCLUSIONS: Significant WM damage starts before the ataxia onset. The bilateral pallidum, brainstem, and cerebellar peduncles are the most vulnerable targets. The volume of pons appears to be the most promising imaging biomarker for a longitudinal study. TRIAL REGISTRATION: ClinicalTrial ID: ChiCTR2100045857 ( http://www.chictr.org.cn/edit.aspx?pid=55652&htm=4 ) KEY POINTS: • Pre- SCA3 showed WM damage mainly in cerebellar peduncles. Continuous brain damage was characterized by brainstem, widespread, and relatively symmetric cerebellar and basal ganglia atrophy. • Volumetric abnormalities were most evident in the bilateral pallidum, brainstem, and cerebellar peduncles in SCA3. • The volume of pons might identify the disease progression longitudinally.

Pediatric meningioma with a Novel MAML2-YAP1 fusion variant: a case report and literature review.

BACKGROUND: Pediatric meningioma with YAP1 fusion is a rare subset of meningiomas. Currently, there are lack of integrated clinical, radiological, and pathological features on this subset. Here, we reported a case of pediatric meningioma with a novel MAML2-YAP1 fusion variant and reviewed the relevant literature. CASE PRESENTATION: We presented a case of 12-year-old boy with meningioma adjacent to the superior sagittal sinus and falx. Simpson grade II gross total resection was performed after diagnosis. Pathologically, he was diagnosed as WHO grade I meningothelial meningioma with rhabdoid features. A next-generation sequencing-based gene panel was performed to determine the molecular features for potential treatment, and a novel MAML2-YAP1 fusion break point was identified. CONCLUSION: Pediatric meningioma with the fusion of YAP1 and MAML2 genes is more likely to have pathological features of rhabdiod cells, which needs to be validated in large-scale studies for exploring better treatment under the integrated diagnosis.

Diffusion kurtosis imaging in evaluating gliomas: different region of interest selection methods on time efficiency, measurement repeatability, and diagnostic ability.

OBJECTIVES: Comparing the diagnostic efficacy of diffusion kurtosis imaging (DKI) derived from different region of interest (ROI) methods in tumor parenchyma for grading and predicting IDH-1 mutation and 1p19q co-deletion status of glioma patients and correlating with their survival data. METHODS: Sixty-six patients (29 females; median age, 45 years) with pathologically proved gliomas (low-grade gliomas, 36; high-grade gliomas, 30) were prospectively included, and their clinical data were collected. All patients underwent DKI examination. DKI maps of each metric were derived. Three groups of ROIs (ten spots, ROI-10s; three biggest tumor slices, ROI-3s; and whole-tumor parenchyma, ROI-whole) were manually drawn by two independent radiologists. The interobserver consistency, time spent, diagnostic efficacy, and survival analysis of DKI metrics based on these three ROI methods were analyzed. RESULTS: The intraexaminer reliability for all parameters among these three ROI methods was good, and the time spent on ROI-10s was significantly less than that of the other two methods (p < 0.001). DKI based on ROI-10s demonstrated a slightly better diagnostic value than the other two ROI methods for grading and predicting the IDH-1 mutation status of glioma, whereas DKI metrics derived from ROI-10s performed much better than those of the ROI-3s and ROI-whole in identifying 1p19q co-deletion. In survival analysis, the model based on ROI-10s that included patient age and mean diffusivity showed the highest prediction value (C-index, 0.81). CONCLUSIONS: Among the three ROI methods, the ROI-10s method had the least time spent and the best diagnostic value for a comprehensive evaluation of glioma. It is an effective way to process DKI data and has important application value in the clinical evaluation of glioma. KEY POINTS: • The intraexaminer reliability for all DKI parameters among different ROI methods was good, and the time spent on ROI-10 spots was significantly less than the other two ROI methods. • DKI metrics derived from ROI-10 spots performed the best in ROI selection methods (ROI-10s, ten-spot ROIs; ROI-3s, three biggest tumor slices ROI; and ROI-whole, whole-tumor parenchyma ROI) for a comprehensive evaluation of glioma. • The ROI-10 spots method is an effective way to process DKI data and has important application value in the clinical evaluation of glioma.

Diagnostic accuracy and potential covariates for machine learning to identify IDH mutations in glioma patients: evidence from a meta-analysis.

OBJECTIVES: To assess the diagnostic accuracy of machine learning (ML) in predicting isocitrate dehydrogenase (IDH) mutations in patients with glioma and to identify potential covariates that could influence the diagnostic performance of ML. METHODS: A systematic search of PubMed, Web of Science, and the Cochrane library up to 1 August 2019 was conducted to collect all the articles investigating the diagnostic performance of ML for prediction of IDH mutation in glioma. The search strategy combined synonyms for 'machine learning', 'glioma', and 'IDH'. Pooled sensitivity, specificity, and their 95% confidence intervals (CIs) were calculated, and the area under the receiver operating characteristic curve (AUC) was obtained. RESULTS: Nine original articles assessing a total of 996 patients with glioma were included. Among these studies, five divided the participants into training and validation sets, while the remaining four studies only had a training set. The AUC of ML for predicting IDH mutation in the training and validation sets was 93% (95% CI 91-95%) and 89% (95% CI 86-92%), respectively. The pooled sensitivity and specificity were, respectively, 87% (95% CI 82-91%) and 88% (95% CI 83-92%) in the training set and 87% (95% CI 76-93%) and 90% (95% CI 72-97%) in the validation set. In subgroup analyses in the training set, the combined use of clinical and imaging features with ML yielded higher sensitivity (90% vs. 83%) and specificity (90% vs. 82%) than the use of imaging features alone. In addition, ML performed better for high-grade gliomas than for low-grade gliomas, and ML that used conventional MRI sequences demonstrated higher specificity for predicting IDH mutation than ML using conventional and advanced MRI sequences. CONCLUSIONS: ML demonstrated an excellent diagnostic performance in predicting IDH mutation of glioma. Clinical information, MRI sequences, and glioma grade were the main factors influencing diagnostic specificity. KEY POINTS: • Machine learning demonstrated an excellent diagnostic performance for prediction of IDH mutation in glioma (the pooled sensitivity and specificity were 88% and 87%, respectively). • Machine learning that used conventional MRI sequences demonstrated higher specificity in predicting IDH mutation than that based on conventional and advanced MRI sequences (89% vs. 85%). • Integration of clinical and imaging features in machine learning yielded a higher sensitivity (90% vs. 83%) and specificity (90% vs. 82%) than that achieved by using imaging features alone.

Regional morphometric abnormalities and clinical relevance in Wilson's disease.

BACKGROUND: Morphology builds Wilson's disease's clincal basis. OBJECTIVES: To detect and quantify regional morphometric abnormalities, in terms of both volume and shape, in patients with Wilson's disease. METHODS: Twenty-seven Wilson's disease patients and 24 healthy controls were enrolled. Specific brain structures, including the bilateral caudate, putamen, globus pallidus, thalamus, amygdala, hippocampus, red nucleus, and substantia nigra (SN), were automatically extracted from each participant's T1 -weighted image. Volume abnormalities and correlations with the modified Young scale were investigated. Furthermore, vertex-based shape analysis was performed to explore region-specific morphometric abnormalities. RESULTS: Significant global volume atrophy and local shape abnormalities were detected and quantified in the bilateral caudate, putamen, globus pallidus, thalamus, amygdala, red nucleus, and SN. Morphometric abnormalities of the caudate, putamen, and thalamus were strong, whereas those of the globus pallidus, amygdala, red nucleus, and SN were weaker. No hippocampal abnormalities were observed. The modified Young scale was found to correlate significantly with the volumes of the bilateral putamen and the right globus pallidus. Shape analysis revealed subregion-specific atrophy of the bilateral caudate and putamen. They were concentrated in the subregions that project to the limbic and executive cortices. Significant region-specific atrophy was also detected in the bilateral thalamic subregions that project to the primary motor, sensory, and premotor cortices. CONCLUSIONS: We found significant morphometric abnormalities of specific structures of interest in patients with Wilson's disease, both globally and locally. These morphometric abnormalities may serve as useful imaging biomarkers for Wilson's disease. © 2019 International Parkinson and Movement Disorder Society.

Comparative analysis of the diffusion kurtosis imaging and diffusion tensor imaging in grading gliomas, predicting tumour cell proliferation and IDH-1 gene mutation status.

INTRODUCTION: Few studies have applied diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) for the comprehensive assessment of gliomas [tumour grade, isocitrate dehydrogenase-1 (IDH-1) mutation status and tumour proliferation rate (Ki-67)]. This study describes the efficacy of DKI and DTI to comprehensively evaluate gliomas, compares their results. METHODS: Fifty-two patients (18 females; median age, 47.5 years) with pathologically proved gliomas were prospectively included. All cases underwent DKI examination. DKI (mean kurtosis: MK, axial kurtosis: Ka, radial kurtosis: Kr) and DTI (mean diffusivity: MD, fractional anisotropy: FA) maps of each metric was derived. Three ROIs were manually drawn. RESULTS: MK, Ka, Kr and FA were significantly higher in HGGs than in LGGs, whereas MD was significantly lower in HGGs than in LGGs (P < 0.01). ROC analysis demonstrated that MK (specificity: 100% sensitivity: 79%) and Ka (specificity: 96% sensitivity: 82%) had the same and highest (AUC: 0.93) diagnostic value. Moreover, MK, Ka, and Kr were significantly higher in grade III than II gliomas (P ≦ 0.01). Further, DKI and DTI can significantly identify IDH-1 mutation status (P ≦ 0.03). Ka (sensitivity: 74%, specificity: 75%, AUC: 0.72) showed the highest diagnostic value. In addition, DKI metrics and MD showed significant correlations with Ki-67 (P ≦ 0.01) and Ka had the highest correlation coefficient (rs = 0.72). CONCLUSIONS: Compared with DTI, DKI has great advantages for the comprehensive assessment of gliomas. Ka might serve as a promising imaging index in predicting glioma grading, tumour cell proliferation rate and IDH-1 gene mutation status.

A study of neurite orientation dispersion and density imaging in wilson's disease.

BACKGROUND: Previous studies have indicated that neurite orientation dispersion and density imaging (NODDI) could be used as a biomarker for detecting microstructural changes of brain. PURPOSE: To quantitatively evaluate the changes in basal ganglia (BG) and thalamus in Wilson's disease (WD) by NODDI and assess the correlation between parameters and disease severity. STUDY TYPE: Prospective case-control study. POPULATION: In total, 24 WD patients and 25 age- and sex-matched normal controls were involved in this study. FIELD STRENGTH/SEQUENCE: EPI diffusion-weighted MR images (b-values = 0, 1000, and 2000 with 30 diffusion gradient directions) were acquired on a 3T scanner. ASSESSMENT: Diffusion data were analyzed using voxel-based analysis. NODDI indices including intracellular volume fraction (Vic), orientation dispersion index (ODI), and isotropic volume fraction (Viso) were estimated from the BG and thalamus. The disease severity was assessed by two experienced neurologists based on the Global Assessment Scale (GAS). The relative importance of NODDI indices in diagnosing WD and predictive accuracy were also analyzed. STATISTICAL TESTING: The Shapiro-Wilk test, Student's t-test, χ2 test, Mann-Whitney-Wilcoxon test, Spearman rank correlation coefficient analysis and random-forest analysis were used for statistical analyses. RESULTS: The Vic and ODI in the BG and thalamus were significantly lower in WD patients than normal controls, while the Viso in the BG and thalamus were significantly higher (P < 0.01). The Vic in the putamen and ODI in the globus pallidus were negatively correlated with clinical severity (rvic = -0.727, P < 0.001; rodi = -0.705, P < 0.001). The Vic in the putamen was the most valuable predictor for diagnosing WD and the prediction accuracy of NODDI was 95.92%. DATA CONCLUSION: NODDI can effectively evaluate the changes of microstructure and metabolism during copper deposition in WD, and thus, it is likely to be useful in detecting the changes in the brain of this disease and assessing its progression. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2018;48:423-430.

Noninvasive evaluation of the glymphatic system in diffuse gliomas using diffusion tensor image analysis along the perivascular space.

OBJECTIVE: The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS). METHODS: In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions. RESULTS: Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (ß = -0.004, p = 0.026), tumor grade (ß = -0.114, p = 0.011), and IDH genotype (ß = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (ß = -0.005, p < 0.001), tumor grade (ß = -0.144, p < 0.001), IDH genotype (ß = 0.154, p < 0.001), tumor volume (ß = -0.002, p = 0.001), and peritumoral edema volume (ß = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (ß = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (ß = -0.003, p = 0.022), IDH status (ß = 0.132, p = 0.001), and tumor volume (ß = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001). CONCLUSIONS: GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

Looking through the imaging perspective: the importance of imaging necrosis in glioma diagnosis and prognostic prediction - single centre experience.

BACKGROUND: The aim of the study was to investigate the diagnostic value of imaging necrosis (Imnecrosis) in grading, predict the genotype and prognosis of gliomas, and further assess tumor necrosis by dynamic contrast-enhanced MR perfusion imaging (DCE-MRI). PATIENTS AND METHODS: We retrospectively included 150 patients (104 males, mean age: 46 years old) pathologically proved as adult diffuse gliomas and all diagnosis was based on the 2021 WHO central nervous system (CNS) classification. The pathological necrosis (Panecrosis) and gene mutation information were collected. All patients underwent conventional and DCE-MRI examinations and had been followed until May 31, 2021. The Imnecrosis was determined by two experienced neuroradiologists. DCE-MRI derived metric maps have been post-processed, and the mean value of each metric in the tumor parenchyma, peritumoral and contralateral area were recorded. RESULTS: There was a strong degree of inter-observer agreement in defining Imnecrosis (Kappa = 0.668, p < 0.001) and a strong degree of agreement between Imnecrosis and Panecrosis (Kappa = 0.767, p < 0.001). Compared to low-grade gliomas, high-grade gliomas had more Imnecrosis (85.37%, p < 0.001), and Imnecrosis significantly increased with the grade of gliomas increasing. And Imnecrosis was significantly more identified in IDH-wildtype, 1p19q-non-codeletion, and CDKN2A/B-homozygous-deletion gliomas. Using multivariate Cox regression analysis, Imnecrosis was an independent and unfavorable prognosis factor (Hazard Ratio = 2.113, p = 0.046) in gliomas. Additionally, extravascular extracellular volume fraction (ve) in tumor parenchyma derived from DCE-MRI demonstrated the highest diagnostic efficiency in identifying Panecrosis and Imnecrosis with high specificity (83.3% and 91.9%, respectively). CONCLUSIONS: Imnecrosis can provide supplementary evidence beyond Panecrosis in grading, predicting the genotype and prognosis of gliomas, and ve in tumor parenchyma can help to predict tumor necrosis with high specificity.

HLA Alleles Associate with Insulin Autoimmune Syndrome.

In recent years, there have been hundreds of reports on insulin autoimmune syndrome (IAS) globally; however, fewer than a hundred patients have undergone genetic testing. Our objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 *0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 *0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 *0301/DQB1 *0302.

Sixty-four-slice computed tomography angiography of perigastric veins with image fusion.

OBJECTIVE: The objective of this study was to assess the efficacy and clinical value of 64-slice computed tomography angiography (CTA) with image fusion for demonstrating the perigastric venous anatomy. METHODS: Twenty-six patients with gastric cancer underwent abdominal CTA examinations. Computed tomography angiography of stomach and perigastric veins and arteries were reconstructed and fused using volume-rendering technique. The inflow and courses of perigastric veins as well as the spatial relationship among the perigastric veins, arteries, and stomach were compared with surgery. RESULTS: Compared with surgical findings, the visualization rate of the 7 perigastric veins on CTA was 90.9% to 100%. There was a statistically significant decrease in number of short gastric veins identified on CTA compared with surgery (P = 0.004). There was no statistically significant difference between the 2 modalities in detecting other perigastric veins including the left gastric vein, right gastric vein, right gastroepiploic vein, left gastroepiploic vein, posterior gastric vein, and gastrocolic trunk (P = 0.317, P = 0.157, P = 1, P = 1, P = 0.317, P = 1, respectively). CONCLUSIONS: Sixty-four-slice CTA with image fusion clearly depicts most of perigastric veins and their relationship with the stomach and perigastric arteries. It can facilitate gastrectomy.

Endovascular stent placement for nutcracker phenomenon.

The nutcracker syndrome is a rare clinic condition associated with severe hematuria and left flank pain due to the entrapment of the left renal vein between the superior mesenteric artery and the aorta. Its diagnostic criteria are not well defined, often causing delayed or misdiagnosis. Although surgical repair has been the standard of care, more recently endovascular stenting of the renal vein has been proposed. We presented six patients (aged 7 to 31 years old; median age, 16.5 years old) with nutcracker syndrome who were endovascularly managed from June 2002 to July 2011. All patients underwent laboratory test and computed tomography (CT) or ultrasound examination before and after endovascular procedures. Self-expandable stents were successfully placed in all cases. The diameter of the left renal vein at aorto-superior mesenteric artery portion significantly increased from 1.88 ± 0.95 mm pre-procedure to 5.24 ± 0.61 mm post-procedure (p< 0.01). Left renal vein pressure significantly decreased from 11.00 ± 4.34 mmHg pre-procedure to 6.00 ± 2.55 mmHg post-procedure (p< 0.01). Severe gross hematuria completely subsided within 2 months to 6 months and left flank pain completely subsided within 7 days to 1 month after treatment. Endovascular therapy provides an alternative therapy with satisfactory long-term clinical and imaging results for symptomatic patients with nutcracker syndrome.

Analysis and hierarchical clustering of infratentorial morphological MRI identifies SCAs phenogroups.

BACKGROUND: Clinical decision-making in spinocerebellar ataxia spectrum diseases (SCAs) has mainly been based on genetic tests, not considering the SCAs' imaging and clinical heterogenicity. OBJECTIVE: To identify SCAs phenogroups by analysis and hierarchical clustering of infratentorial morphological MRI for unveiling pathophysiological differences among common SCA subtypes. METHODS: We prospectively enrolled 119 (62 women; mean age 37 years) genetically diagnosed SCAs (SCA1 n = 21, SCA2 n = 10, symptomatic SCA3 n = 59, presymptomatic SCA3 n = 22, SCA6 n = 7) and 35 healthy controls (HCs). All patients underwent MRI and detailed neurological and neuropsychology examinations. The width of each cerebellar peduncle (CP) and anteroposterior diameter of the spinal cord and pontine were measured. Twenty-five SCAs patients (15 women; mean age 35 years) were followed for at least a year (17 (15, 24) months), whose MRI and the Scale for the Assessment and Rating of Ataxia (SARA) were collected. RESULTS: Infratentorial morphological MRI measurements could significantly discriminate SCAs from HCs, even among SCA subtypes. Two mutually exclusive and clinically distinct phenogroups were identified. Despite similar (CAG)n, phenogroup 1 (n = 66, 55.5%) presented more atrophied infratentorial brain structures and more severe clinical symptoms with older age and earlier age of onset when compared with phenogroup 2. More importantly, all SCA2, most of SCA1 (76%), and symptomatic SCA3 (68%) were classified into phenogroup 1, whereas all SCA6 and all presymptomatic SCA3 were in phenogroup 2. The right middle CP had the highest diagnostic value in predicting phenogroup 2 (AUC = 0.99; P < 0.01) with high specificity (95%). Consistent with the significantly increased SARA (7.5 vs 10, P = 0.021), the bilateral inferior CP, spinal cord, and pontine tegmentum were more atrophy during the follow-up (P < 0.05). CONCLUSION: SCAs were with significant infratentorial brain atrophy than HCs. We identified two different SCAs phenogroups associated with substantial differences in infratentorial brain atrophy, clinical presentation, and may reflect the underlying molecular profiles to some extent, paving the way for a more personalized diagnostic and treatment approach.

Altered large-scale individual-based morphological brain network in spinocerebellar ataxia type 3.

BACKGROUND: Accumulating evidences indicate regional gray matter (GM) morphology atrophy in spinocerebellar ataxia type 3 (SCA3); however, whether large-scale morphological brain networks (MBNs) undergo widespread reorganization in these patients remains unclear. OBJECTIVE: To investigate the topological organization of large-scale individual-based MBNs in SCA3 patients. METHODS: The individual-based MBNs were constructed based on the inter-regional morphological similarity of GM regions. Graph theoretical analysis was taken to assess GM structural connectivity in 76 symptomatic SCA3, 24 pre-symptomatic SCA3, and 54 healthy normal controls (NCs). Topological parameters of the resulting graphs and network-based statistics analysis were compared among symptomatic SCA3, pre-symptomatic SCA3, and NCs groups. The inner association between network properties and clinical variables was further analyzed. RESULTS: Compared to NCs and pre-symptomatic SCA3 patients, symptomatic SCA3 indicated significantly decreased integration and segregation, a shift to "weaker small-worldness", characterized by decreased Cp , lower Eloc, and Eglob (all p < 0.005). Regarding nodal properties, symptomatic SCA3 exhibited significantly decreased nodal profiles in the central executive network (CEN)-related left inferior frontal gyrus, limbic regions involving the bilateral amygdala, left hippocampus, and bilateral pallidum, thalamus; and increased nodal degree, efficiency in bilateral caudate (all pFDR <0.05). Meanwhile, clinical variables were correlated with altered nodal profiles (pFDR ≤0.029). SCA3-related subnetwork was closely interrelated with dorsolateral cortico-striatal circuitry extending to orbitofrontal-striatal circuits and dorsal visual systems (lingual gyrus-striatal). CONCLUSION: Symptomatic SCA3 patients undergo an extensive and significant reorganization in large-scale individual-based MBNs, probably due to disrupted prefrontal cortico-striato-thalamo-cortical loops, limbic-striatum circuitry, and enhanced connectivity in the neostriatum. This study highlights the crucial role of abnormal morphological connectivity alterations beyond the pattern of brain atrophy, which might pave the way for therapeutic development in the future.

Analysis of the Outcomes of 73 Patients with Exogenous Positive Insulin Anti-Body.

Objective: This study aimed to discuss adjusting the treatment plan for patients with type 2 diabetes mellitus (T2DM) who are positive for exogenous insulin antibody (IA). The outcome of patients who are IA-positive with an adjusted treatment plan was considered. Methods: The treatment plan for patients with IA-positive T2DM was adjusted to oral medication or long-acting insulin + oral medication. Insulin antibody, C-peptide, and insulin were re-examined before treatment and at 1, 3, 6, 12, 18, and 24 months after treatment. The time of IA-negative seroconversion and its indexes, including blood glucose, C-peptide, and insulin, were recorded and analyzed. Results: After adjusting the treatment plan for 2 years, in 73 patients, 57 had IA-negative seroconversion, and 16 had positive IA. The blood glucose, C-peptide, insulin, glycosylated hemoglobin (HbA1c), and the daily dose of insulin in the seroconversion group and the non-seroconversion group decreased compared with before the adjustment of the treatment plan (P < 0.05). The negative seroconversion rate within 2 years was related to the insulin concentration before treatment. Conclusion: Patients with IA-positive T2DM need to adjust their treatment plans in time. Even if IA does not turn negative within 2 years after adjusting the treatment plan, the levels of blood glucose, C-peptide, insulin, and HbA1c along with the insulin dosage would be significantly improved, which can benefit patients. The higher the fasting insulin and 2-hour insulin values before adjusting the treatment plan, the longer the time required for IA to turn negative.

Difficult Journey to Find the Best Treatment for Homozygous Familial Hypercholesterolemia: Case Report.

Homozygous familial hypercholesterolemia (HoFH) is a rare autosomal recessive genetic disorder. It is difficult to diagnose and treat it at early stage. We present a nine-year-old boy with HoFH from China. At the beginning, he was misdiagnosed as xanthomatosis in the dermatology department of the local hospital, but the disease did not alleviate after three laser ablation operations. Later, blood lipid monitoring, ultrasound of heart and carotid artery were further added in our hospital, and finally the boy was diagnosed with HoFH by genetic testing. A biallelic mutations was observed in the fourth exon of low density lipoprotein receptor (LDLR): c.418G>A (p.E140K). Our patient achieved a relatively satisfactory therapeutic results after a series of lipid-lowering therapies including atorvastatin monotherapy, lipoprotein apheresis and double-filtration plasma pheresis. We found that LDL-C levels obtained 57% reduction from baseline after atorvastatin combined with double-filtration plasma pheresis (DFPP). It was observed that regression of carotid intima-media thickness (cIMT), valve regurgitation and xanthoma occurred after a series of Intensive lipid-lowering therapy.