Preliminary Feasibility Study on Diffusion Kurtosis Imaging to Monitor the Early Functional Alterations of Kidneys in Streptozocin-Induced Diabetic Rats.

RATIONALE AND OBJECTIVES: The aim of this study was to investigate the potential of diffusion kurtosis imaging (DKI) to assess the early renal functional undulation of diabetic mellitus (DM). MATERIALS AND METHODS: Fifty-seven Sprague-Dawley (SD) rats were randomly divided into two groups and eventually 48 rats were included in this study: the normal control (CON) group and diabetic mellitus (DM) group. Weeks 0, 4, 8, and 12 after the diabetes model was successfully established, all the rats were scanned on the 3.0T MRI. The DKI derived parameters of renal parenchyma, including fractional anisotropy (FAco, FAme), mean diffusivity (MDco, MDme), and mean kurtosis (MKco, MKme) were measured. Their alteration over time was analyzed and then correlated with urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) using Pearson correlation analysis. Finally, hematoxylin and eosin (H&E) staining was performed on the kidneys of the two groups. RESULT: There was a decreasing trend in FA, MK, and MD values over time in diabetic rats. Also, the gradually worsening histological damage of kidneys was noted over time in diabetic rats. The cortical FA and MK values and medullary FA, MK and MD values of diabetic rats were significantly lower than those of controls at most time points after DM induction. In addition, negative correlations were revealed between the BUN and FAco (r = -0.43, p = 0.03) or FAme value (r = -0.49, p = 0.01). The cortical MK value was moderately correlated with UV (r = -0.46, p = 0.03) and BUN (r = -0.55, p = 0.01). CONCLUSION: The preliminary findings suggest that DKI might be an effective and sensitive tool to assess the early changes of renal function impairment in diabetic rats. The FA values of the cortex and medulla and the MK value of the cortex are sensitive markers in detecting renal injury in diabetic rats.

Non-invasive investigation of early kidney damage in streptozotocin-induced diabetic rats by intravoxel incoherent motion diffusion-weighted (IVIM) MRI.

BACKGROUND: The current study investigated the performance of intravoxel incoherent motion diffusion (IVIM) technology in monitoring early renal injury in streptozotocin rats. METHODS: Forty-eight Sprague-Dawley (SD) rats were divided into a control group and a diabetic mellitus (DM) group. Six rats in each group were randomly selected for MR scans at four different time points (0, 4, 8, and 12 weeks). The IVIM-derived parameters (D, D*, f and ADC values) of the renal cortex (CO), outer and inner stripe of the outer medulla (OS, IS), and internal medulla (IM) were acquired. Changes in each IVIM-derived parameter over time were analyzed, and differences between the two groups at each point were assessed. The associations between the IVIM parameters and IV collagen expression, urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) were investigated. RESULTS: The D and D* values of CO and the ADC values of CO, OS, IS and IM displayed significantly different trends between the two groups over time (P<0.05). In addition, significant correlations were discovered between the D* value of CO and UV and BUN (r=0.527, P=0.033; r=0.617, P=0.005), between the ADC value of IM and BUN (r=0.557, P=0.019) and between the f value of IM and BUN (r=0.527, P=0.033). No correlation was found between IVIM parameters and IV collagen expression and Scr. CONCLUSIONS: IVIM is a potential sensitive and noninvasive technology for the simultaneous assessment of early renal cortical and medullary injuries induced by diabetes.

Sirolimus Can Increase the Disappearance Rate of Cardiac Rhabdomyomas Associated with Tuberous Sclerosis: A Prospective Cohort and Self-Controlled Case Series Study.

OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.

Sirolimus improves seizure control in pediatric patients with tuberous sclerosis: A prospective cohort study.

PURPOSE: This study aimed to analyze the therapeutic effect of sirolimus on seizures in pediatric patients with tuberous sclerosis. METHODS: We first compared the efficacy of controlling seizures in all patients after they had taken sirolimus for one year, and then we performed a subgroup analysis based on whether the administered antiepileptic drugs were changed to determine whether the efficacy was associated with changes of antiepileptic drugs. RESULTS: A total of 91 eligible children were enrolled. The response rate was 78.0 % (71/91), and 47.2 % (43/91) of all patients were became seizure-free. The improvement in seizure control before and after treatment with sirolimus was significant (p < 0.001). In the AEDs unaltered group, 34 were responders (34/45, 75.6 %, 95 % CI 17.4-88.3), of which 24 were seizure-free (24/34, 70.6 %). In the AEDs-altered group, 37 were responders (37/46, 80.4 %, 95 % CI 56.7-88.1), of which 19 were seizure-free (19/37, 51.4 %). There was no significant difference between the two groups for reductions in rate of seizure frequency (p = 0.308). In the patients with refractory epilepsy, treatment with sirolimus was also effective (p = 0.01). Logistic regression analysis showed that age was an important factor affecting outcome of epilepsy (p = 0.003, 95 % CI 2.05-38.31). No Grade 3 or 4 adverse events were noted during the follow-up. CONCLUSIONS: Sirolimus has a significant effect on seizures associated with tuberous sclerosis complex (TSC), with no or only moderate adverse events after long-term administration. Sirolimus could be used as the first-line medication for pediatric patients with TSC-associated epilepsy.

Coordinated DNA Methylation and Gene Expression Data for Identification of the Critical Genes Associated with Childhood Atopic Asthma.

Asthma is a chronic inflammatory disorder of airways that involves in many cells and factors. This study aimed to screen critical genes and miRNAs involved in childhood atopic asthma. DNA methylation and gene expression data (access numbers GSE65163 and GSE65204) were downloaded from Gene Expression Omnibus (GEO) database, which included 72 atopic asthmatic subject samples and 69 healthy samples. The differentially expressed genes (DEGs) with DNA methylation changes were identified, followed by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Gene coexpression network and miRNA-target gene regulatory networks were then constructed. Besides, we screened critical drug molecules that have high correlation with atopic asthma in children. A total of 146 critical DEGs with DNA methylation changes were screened from atopic asthmatic samples compared with healthy control samples. GO and KEGG pathway enrichment analysis showed that the critical genes were mainly related to 20 GO terms and 13 KEGG pathways. In the coexpression network, tumor necrosis factor (TNF) and major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) were identified that were significantly related to immune response process. Analysis of miRNA-target gene network showed that hsa-miR-148b had the highest number of target genes(degree = 21). Besides, we found that Alsterpaullone had a correlation value closest to -1 (correlation = -0.884, p = 0.0031), which indicated that the agent might be considered as a potential agent that antagonized to asthma. The dysregulation of TNF, HLA-DPA1, and miR-148b might be related to the immune response of childhood atopic asthma.

Intravoxel incoherent motion (IVIM) at 3.0 T: evaluation of early renal function changes in type 2 diabetic patients.

PURPOSE: The purpose of this study was to evaluate the utility of intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) parameters in identifying early renal function changes in diabetics. METHODS: A total of 40 patients with type 2 diabetes mellitus and 20 healthy control subjects underwent multiple b value DWI. The diabetic patients were stratified into two groups based on albuminuria category: NAU (normal to mildly increased albuminuria; ACR < 30 mg/g) and MAU (moderately increased albuminuria; 30 ≤ ACR < 300 mg/g). The mean cortical and medullary IVIM parameters (D, D*, f, and ADC) were calculated and compared among the different groups, and the correlation of ACR and eGFR was also calculated. RESULTS: The present study revealed the limited water molecule diffusion and hyperperfusion of renal cortex and medulla in diabetic patients before proteinuria detection. Mean cortical and medullary D values negatively correlated with the ACR values in diabetics with 30 ≤ ACR < 300 mg/g, whereas no correlation was found between ACR values and other IVIM parameters. CONCLUSION: IVIM DWI might be helpful in noninvasively identifying early-stage DN. The IVIM parametric values are more sensitive than the ACR in detecting early-stage kidney changes.

Alterations of White Matter Connectivity in Preschool Children with Autism Spectrum Disorder.

Purpose To investigate the topologic architecture of white matter connectivity networks in preschool-aged children with a diagnosis of autism spectrum disorder (ASD) versus typical development (TD). Materials and Methods Forty-two participants were enrolled, including 21 preschool children with ASD (14 male children and seven female children; mean age, 4.56 years ± 0.97 [standard deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13 years ± 0.82). The diagnosis of ASD was determined according to the Diagnostic and Statistical Manual of Mental Disorders Global Assessment of Functioning scores (mean score, 8.00 ± 0.50). All participants underwent diffusion-tensor imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph theoretical analysis was applied to investigate the topologic organization of the brain network including global and local topologic parameters. Statistical analysis was then performed for the comparison between the groups. Results Compared with the TD group, children with ASD demonstrated shortened characteristic path length (t1 = 0.536, t2 = 0.534, t3 = 0.523, t4 = 0.510, and t5 = 0.501; P < .05) and increased global efficiency (t1 = 0.499, t2 = 0.497, t3 = 0.486, t4 = 0.473, and t5 = 0.465; P < .05) and clustering coefficient (t1 = 0.673, t2 = 0.750, t3 = 0.757, t4 = 0.738, and t5 = 0.741; P < .05). Significant increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032, respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P < .01) of the basal ganglia network. Conclusion Significantly altered patterns of global and local brain network topography may underlie the abnormal brain development in preschool children with ASD compared with those who have TD. The identification of altered structural connectivity in basal ganglia and paralimbic-limbic networks may point toward potential imaging biomarkers for preschool-age patients with ASD. © RSNA, 2018.

Two de novo variations identified by massively parallel sequencing in 13 Chinese families with children diagnosed with autism spectrum disorder.

Autism spectrum disorder (ASD) is a genetically heterogeneous neurodevelopmental disorder characterized by impairments in social interaction and communication, and by restricted and repetitive behaviors. The genetic architecture of ASD has been elucidated, including chromosomal rearrangements, de novo or inherited rare variants, and copy number variants. However, the genetic mechanism of Chinese families with ASD children is explored rarely. To identify genetic pathogenesis, we performed massively parallel sequencing on 13 Chinese ASD trio families, and found two de novo variations. The novel de novo splice alteration c.664 + 2T > G in the DEAF1 gene and the novel de novo missense mutation c.95 C > T in the AADAT gene associated with ASD may be important clues for exploring the etiology of this disorder.

Role of quantitative intravoxel incoherent motion parameters in the preoperative diagnosis of nodal metastasis in patients with rectal carcinoma.

PURPOSE: To evaluate the diagnostic value of intravoxel incoherent motion imaging (IVIM) in differentiating metastatic and nonmetastatic lymph nodes in patients with rectal carcinoma. MATERIALS AND METHODS: In all, 68 patients with histologically proven rectal carcinoma underwent an IVIM sequence (b = 0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1000, 1200, 1500, and 2000 s/mm(2) ) on a 3.0T MRI scanner. The IVIM parameters (D, D*, f, and apparent diffusion coefficient [ADC] values) in metastatic and nonmetastatic lymph nodes were measured and calculated. Receiver-operating characteristic (ROC) analyses were conducted to determine the optimal thresholds, the sensitivities, and specificities for differentiation. RESULTS: Mean D, f, and ADC values of metastatic lymph nodes were significantly greater than those of the normal lymph nodes (P < 0.01), whereas the mean D* value of metastatic lymph node was statistically lower (P = 0.03). The AUC, sensitivity, specificity, and the cutoff value, respectively, for differentiating metastatic from nonmetastatic lymph nodes for D, D*, f, and ADC were as follows: D, 0.9460, 89.25%, 91.04%, and 1.14 × 10(-3) mm(2) /s; D*, 0.6930, 64.18%, 82.80%, and 7.02 × 10(-3) mm(2) /s; f, 0.7810, 92.47%, 55.22%, and 0.27%; ADC, 0.8970, 87.10%, 88.06%, and 0.80 × 10(-3) mm(2) /s. The ROC curves demonstrated that the area under the ROC (AUC) of the D, ADC, f, and D* values successively decreased, and D had the highest AUC, with D* values being lowest. CONCLUSION: An IVIM sequence may be helpful in diagnosing metastatic lymph nodes of rectal carcinoma. Average D and ADC values are more sensitive than f and D* values in this differentiation. J. MAGN. RESON. IMAGING 2016;44:1031-1039.

Syndrome of Electrical Status Epilepticus During Sleep: Epileptic Encephalopathy Related to Brain Development.

BACKGROUND: Epileptic encephalopathy with electrical status epilepticus during sleep is an age-related and self-limited disorder. The present study analyzed the etiology, demographics, and pathogenesis of patients with electrical status epilepticus during sleep to provide information on the diagnosis and therapy of this syndrome. METHODS: The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in patients admitted in Chinese People's Liberation Army General Hospital from 2009 to 2014 were retrospectively analyzed. Patients were classified into the genetic, structural-metabolic, and unknown groups according to the etiology. Demographics and clinical characteristics of all the patients were then analyzed and compared among groups. RESULTS: The etiologies of epileptic encephalopathy with electrical status epilepticus during sleep in 75 patients mainly included benign childhood epilepsy with centrotemporal spikes, Landau-Kleffner syndrome, polymicrogyria, and migration disorders. Age at onset of epilepsy did not show a specific pattern, but age at onset of epileptic encephalopathy with electrical status epilepticus during sleep was concentrated at age 6-9 years. The mean age at onset of epilepsy in the genetic group was significantly older than that in the structural-metabolic group (P < 0.05). Age at onset of epileptic encephalopathy with electrical status epilepticus during sleep did not significantly differ between the two groups. CONCLUSIONS: Electrical status epilepticus during sleep is an epileptic encephalopathy related to brain development and presents an age-dependent occurrence.

Efficacy of levetiracetam in electrical status epilepticus during sleep of children: a multicenter experience.

BACKGROUND: Electrical status epilepticus during sleep is characterized by epilepsy, a specific electroencephalographic pattern, and neuropsychological impairment. This study aims to evaluate the efficacy and safety of levetiracetam in treating children with electrical status epilepticus during sleep. METHODS: A multicenter, retrospective, open-label study enrolled 73 children (mean age: 8 years) affected by electrical status epilepticus during sleep. The efficacy was rated according to the seizure frequency and electroencephalography response. RESULTS: After a mean treatment period of 19 months (range: 6 to 24 months), 33 (63.5%) of 52 patients became seizure-free or had experienced remarkable reduction in seizures. The electrical status epilepticus of 41 (56.2%) of 73 patients disappeared off their electroencephalography. The electroencephalography efficacy of levetiracetam treatment was noted in the monotherapy (61.9%) and add-on (53.9%) groups. The clinical (67.7%) and electroencephalography (64.3%) response rates of the idiopathic group were better than those of the symptomatic group (57.1% and 45.2%, respectively). No patient discontinued the trial because of intolerability of side effects. CONCLUSIONS: Levetiracetam is effective in individuals with electrical status epilepticus during sleep with tolerable side effects.