Comparative and expression analyses of AP2/ERF genes reveal copy number expansion and potential functions of ERF genes in Solanaceae.

BACKGROUND: The AP2/ERF gene family is a superfamily of transcription factors that are important in the response of plants to abiotic stress and development. However, comprehensive research of the AP2/ERF genes in the Solanaceae family is lacking. RESULTS: Here, we updated the annotation of AP2/ERF genes in the genomes of eight Solanaceae species, as well as Arabidopsis thaliana and Oryza sativa. We identified 2,195 AP2/ERF genes, of which 368 (17%) were newly identified. Based on phylogenetic analyses, we observed expansion of the copy number of these genes, especially those belonging to specific Ethylene-Responsive Factor (ERF) subgroups of the Solanaceae. From the results of chromosomal location and synteny analyses, we identified that the AP2/ERF genes of the pepper (Capsicum annuum), the tomato (Solanum lycopersicum), and the potato (Solanum tuberosum) belonging to ERF subgroups form a tandem array and most of them are species-specific without orthologs in other species, which has led to differentiation of AP2/ERF gene repertory among Solanaceae. We suggest that these genes mainly emerged through recent gene duplication after the divergence of these species. Transcriptome analyses showed that the genes have a putative function in the response of the pepper and tomato to abiotic stress, especially those in ERF subgroups. CONCLUSIONS: Our findings will provide comprehensive information on AP2/ERF genes and insights into the structural, evolutionary, and functional understanding of the role of these genes in the Solanaceae.

Independent replication of advanced brain age in mild cognitive impairment and dementia: detection of future cognitive dysfunction.

We previously developed a novel machine-learning-based brain age model that was sensitive to amyloid. We aimed to independently validate it and to demonstrate its utility using independent clinical data. We recruited 650 participants from South Korean memory clinics to undergo magnetic resonance imaging and clinical assessments. We employed a pretrained brain age model that used data from an independent set of largely Caucasian individuals (n = 757) who had no or relatively low levels of amyloid as confirmed by positron emission tomography (PET). We investigated the association between brain age residual and cognitive decline. We found that our pretrained brain age model was able to reliably estimate brain age (mean absolute error = 5.68 years, r(650) = 0.47, age range = 49-89 year) in the sample with 71 participants with subjective cognitive decline (SCD), 375 with mild cognitive impairment (MCI), and 204 with dementia. Greater brain age was associated with greater amyloid and worse cognitive function [Odds Ratio, (95% Confidence Interval {CI}): 1.28 (1.06-1.55), p = 0.030 for amyloid PET positivity; 2.52 (1.76-3.61), p < 0.001 for dementia]. Baseline brain age residual was predictive of future cognitive worsening even after adjusting for apolipoprotein E e4 and amyloid status [Hazard Ratio, (95% CI): 1.94 (1.33-2.81), p = 0.001 for total 336 follow-up sample; 2.31 (1.44-3.71), p = 0.001 for 284 subsample with baseline Clinical Dementia Rating ≤ 0.5; 2.40 (1.43-4.03), p = 0.001 for 240 subsample with baseline SCD or MCI]. In independent data set, these results replicate our previous findings using this model, which was able to delineate significant differences in brain age according to the diagnostic stages of dementia as well as amyloid deposition status. Brain age models may offer benefits in discriminating and tracking cognitive impairment in older adults.

Glymphatic system evaluation using diffusion tensor imaging in patients with traumatic brain injury.

PURPOSE: Glymphatic system dysfunction has been reported in animal models of traumatic brain injury (TBI). This study aimed to evaluate the activity of the human glymphatic system using the non-invasive Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS) method in patients with TBI. METHODS: A total of 89 patients with TBI (June 2018 to May 2020) were retrospectively enrolled, and 34 healthy volunteers were included who had no previous medical or neurological disease. Magnetic resonance imaging (MRI) with DTI was performed, and the ALPS index was calculated to evaluate the glymphatic system's activity. Wilcoxon rank-sum test was used to compare the ALPS index between patients with TBI and healthy controls. ANOVA was done to compare the ALPS index among controls and patients with mild/moderate-to-severe TBI. Multivariate logistic regression analyses were used to identify independent clinical and radiological factors associated with the ALPS index. The correlation between Glasgow Coma Scale (GCS) score and the ALPS index was also assessed. RESULTS: The ALPS index was significantly lower in patients with TBI than in healthy controls (median, 1.317 vs. 1.456, P < 0.0001). There were significant differences in the ALPS index between healthy controls and patients with mild/moderate-to-severe TBI (ANOVA, P < 0.001). The presence of subarachnoid hemorrhage (P = 0.004) and diffuse axonal injury (P = 0.001) was correlated with a lower ALPS index in the multivariate analysis. There was a weak positive correlation between the ALPS index and GCS scores (r = 0.242, P = 0.023). CONCLUSIONS: The DTI-ALPS method is useful for evaluating glymphatic system impairment and quantifying its activity in patients with TBI.

De novo phasing resolves haplotype sequences in complex plant genomes.

Genome phasing is a recently developed assembly method that separates heterozygous eukaryotic genomic regions and builds haplotype-resolved assemblies. Because differences between haplotypes are ignored in most published de novo genomes, assemblies are available as consensus genomes consisting of haplotype mixtures, thus increasing the need for genome phasing. Here, we review the operating principles and characteristics of several freely available and widely used phasing tools (TrioCanu, FALCON-Phase, and ALLHiC). An examination of downstream analyses using haplotype-resolved genome assemblies in plants indicated significant differences among haplotypes regarding chromosomal rearrangements, sequence insertions, and expression of specific alleles that contribute to the acquisition of the biological characteristics of plant species. Finally, we suggest directions to solve addressing limitations of current genome-phasing methods. This review provides insights into the current progress, limitations, and future directions of de novo genome phasing, which will enable researchers to easily access and utilize genome-phasing in studies involving highly heterozygous complex plant genomes.

Brain MRI radiomics analysis may predict poor psychomotor outcome in preterm neonates.

OBJECTIVES: This study aimed to apply a radiomics approach to predict poor psychomotor development in preterm neonates using brain MRI. METHODS: Prospectively enrolled preterm neonates underwent brain MRI near or at term-equivalent age and neurodevelopment was assessed at a corrected age of 12 months. Two radiologists visually assessed the degree of white matter injury. The radiomics analysis on white matter was performed using T1-weighted images (T1WI) and T2-weighted images (T2WI). A total of 1906 features were extracted from the images and the minimum redundancy maximum relevance algorithm was used to select features. A prediction model for the binary classification of the psychomotor developmental index was developed and eightfold cross-validation was performed. The diagnostic performance of the model was evaluated using the AUC with and without including significant clinical and DTI parameters. RESULTS: A total of 46 preterm neonates (median gestational age, 29 weeks; 26 males) underwent brain MRI (median corrected gestational age, 37 weeks). Thirteen of 46 (28.3%) neonates showed poor psychomotor outcomes. There was one neonate among 46 with moderate to severe white matter injury on visual assessment. For the radiomics analysis, twenty features were selected for each analysis. The AUCs of prediction models based on T1WI, T2WI, and both T1WI and T2WI were 0.925, 0.834, and 0.902. Including gestational age or DTI parameters did not improve the prediction performance of T1WI. CONCLUSIONS: A radiomics analysis of white matter using early T1WI or T2WI could predict poor psychomotor outcomes in preterm neonates. KEY POINTS: • Radiomics analysis on T1-weighted images of preterm neonates showed the highest diagnostic performance (AUC, 0.925) for predicting poor psychomotor outcomes. • In spite of 45 of 46 neonates having no significant white matter injury on visual assessment, the radiomics analysis of early brain MRI showed good diagnostic performance (sensitivity, 84.6%; specificity, 78.8%) for predicting poor psychomotor outcomes. • Radiomics analysis on early brain MRI can help to predict poor neurodevelopmental outcomes in preterm neonates.

Predicting Endovascular Treatment Outcomes in Acute Vertebrobasilar Artery Occlusion: A Model to Aid Patient Selection from the ASIAN KR Registry.

Background The decision to perform endovascular treatment (EVT) for stroke related to vertebrobasilar occlusion (VBO) remains controversial. Purpose To identify preprocedural predictors of good outcomes and to develop a model to aid patient selection for VBO. Materials and Methods For this retrospective study using a Korean multicenter registry, a predictive model for good outcomes (modified Rankin scale score, 0-2) was generated based on a derivation sample of patients with VBO (January 2011-February 2016). Preprocedural parameters, including onset-to-puncture time, infarct volume, occlusion type as a surrogate marker of intracranial atherosclerotic stenosis-related occlusion or embolic occlusion (truncal-type occlusion vs branching site occlusion), and collateral status, were analyzed. Continuous variables were dichotomized based on receiver operating characteristic analysis. Multiple logistic regression analysis was performed to generate a predictive model. The model was internally validated with the bootstrap method and was externally validated with a single-center sample (April 2016-December 2018). Results A predictive model was generated from 71 patients (mean age, 67 years ± 11 [standard deviation]; 41 [58%] men) and was externally validated in 32 patients (mean age, 72 years ± 13; 19 [59%] men). The composite of initial DW imaging volume of less than 10 mL (odds ratio [OR], 19.3; 95% confidence interval [CI]: 3.0, 126.4; P = .002), onset-to-puncture time of less than 8 hours (OR, 8.7; 95% CI: 1.8, 42.0; P = .007), and branching-site occlusion (OR, 6.1; 95% CI: 1.5, 26.0; P = .01) could be used to predict good outcomes, with a median area under the receiver operating characteristic curve of 0.86 (interquartile range [IQR], 0.77-0.95; bootstrap optimism-corrected C statistic, 0.837) in the derivation sample and 0.78 (IQR, 0.62-0.95) in the validation sample. Results failed to show an association between collateral status and outcome (P = .67). Conclusion When selecting patients with vertebrobasilar occlusion for endovascular treatment, the combination of onset-to-puncture time of less than 8 hours, initial infarct volume of less than 10 mL, and presence of branching-site occlusions is indicative of a good outcome. © RSNA, 2020 Online supplemental material is available for this article.

Texture analysis of deep medullary veins on susceptibility-weighted imaging in infants: evaluating developmental and ischemic changes.

OBJECTIVE: Susceptibility-weighted imaging (SWI) can be used to evaluate deep medullary veins (DMVs). This study aimed to apply texture analysis on SWI to evaluate developmental and ischemic changes of DMV in infants. METHODS: A total of 38 infants with normal brain MRI (preterm [n = 12], term-equivalent age [TEA] [n = 18], and term [n = 8]) and seven infants with ischemic injury (preterm [n = 2], TEA [n = 1], and term [n = 4]) were included. Regions of interests were manually drawn to include DMVs. First-order texture parameters including entropy, skewness, and kurtosis were derived from SWI. The parameters were compared between groups according to age and presence of ischemic injury. A regression analysis was performed to correlate postmenstrual age (PMA) and parameters. A ROC analysis was performed to differentiate ischemic infants from normal infants. RESULTS: Among parameters, entropy showed a significant difference between the age groups (preterm vs. TEA vs. term; 5.395 vs. 4.885 vs. 4.883, p = 0.001). There was a significant positive relationship between PMA and entropy (R square = 0.402, p < 0.001). Skewness was significantly higher in the ischemic group compared with that in the normal group (1.37 vs. 0.70, p = 0.001). The ROC on skewness resulted in an AUC of 0.87 (accuracy, 83.2%) for differentiating infants with ischemic injury. CONCLUSION: A texture analysis of DMVs on SWI showed differences according to age and presence of ischemic injury. The texture parameters can potentially be used as quantitative markers for differentiating infants with ischemic injury through DMV changes. KEY POINTS: • The DMV structure of the infant brain could be quantified on SWI with texture analysis. • Entropy from texture analysis on SWI increased as infants got older. • Normal and ischemic injured infants could be differentiated with a cutoff value of 1.025 for skewness.

Effect of manual aspiration thrombectomy using large-bore aspiration catheter for acute basilar artery occlusion: comparison with a stent retriever system.

BACKGROUND: A large-bore aspiration catheter can be employed for recanalization of acute basilar artery occlusion. Here we compare the results of mechanical thrombectomy using a stent retriever (SR) and manual aspiration thrombectomy (MAT) using a large-bore aspiration catheter system as a first-line recanalization method in acute basilar artery occlusion (BAO). METHODS: The records of 50 patients with acute BAO who underwent mechanical thrombectomy were retrospectively reviewed. Patients were assigned to one of two groups based on the first-line recanalization method. The treatment and clinical outcomes were compared. RESULTS: Sixteen (32%) patients were treated with MAT with a large-bore aspiration catheter and 34 (68%) with a SR as the first-line treatment method. The MAT group had a shorter procedure time (28 vs. 65 min; p = 0.001), higher rate of first-pass recanalization (68.8% vs. 38.2%, p = 0.044), and lower median number of passes (1 vs 2; p = 0.008) when compared with the SR group. There was no significant difference in the incidence of any hemorrhagic complication (6.3% vs. 8.8%; p = 0.754) between the groups. However, there were four cases of procedure-related subarachnoid hemorrhage (SAH) in the SR group and one death occurred due to massive hemorrhage. CONCLUSIONS: Selection of MAT using a large-bore aspiration catheter for acute BAO may be a safe and effective first-line treatment method with higher first-pass recanalization rate and shorter procedure time than SR.

Local tirofiban infusion for remnant stenosis in large vessel occlusion: tirofiban ASSIST study.

BACKGROUND: Compared with embolic occlusions, intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusions (LVOs) often require rescue treatment following mechanical thrombectomy (MT). Herein, we hypothesized that local tirofiban infusion can be effective and safe for remnant stenosis in LVO during endovascular treatment and can improve clinical outcomes. METHODS: This observational multicenter registry study (January 2011 to February 2016) included patients with ICAS who underwent endovascular treatment for LVO within 24 h after stroke onset. An underlying fixed focal stenosis at the occlusion site observed on cerebral angiography during and after MT was retrospectively determined as a surrogate marker of ICAS. Procedural and clinical outcomes were compared between the tirofiban and non-tirofiban groups. RESULTS: Of 118 patients, 59 received local tirofiban infusion. Compared to the non-tirofiban group, patients were older (non-tirofiban group versus tirofiban group; median, 63 years vs. 71 years, p = 0.015) and the onset-to-puncture time was longer (median, 275 min vs. 395 min, p = 0.036) in the tirofiban group. The median percent of residual stenosis prior to rescue treatment tended to be higher in the tirofiban group (80 [71-86] vs. 83 [79-90], p = 0.056). Final reperfusion success (modified Treatment In Cerebral Ischemic 2b-3) was more frequent (42.4%vs. 86.4%, p = 0.016) and post-procedure parenchymal hematoma type 2 and/or thick subarachnoid hemorrhages were less frequent (15.3%vs. 5.1%, p = 0.068) in the tirofiban group. The frequency of favorable outcomes 3 months after endovascular treatment (modified Rankin Scale 0-2) was significantly higher in the tirofiban group (32.2% vs. 52.5%, p = 0.025), and tirofiban administration was an independent predictor of favorable outcomes (odds ratio, 2.991; 95% confidence interval, 1.011-8.848; p = 0.048). CONCLUSIONS: Local tirofiban infusion can be a feasible adjuvant treatment option for patients with ICAS-LVO.

Immediate effects of first-line thrombectomy devices for intracranial atherosclerosis-related occlusion: stent retriever versus contact aspiration.

BACKGROUND: Although stent retriever (SR) is recommended as a frontline device of endovascular treatment (EVT) for embolic large artery occlusion causing acute ischemic stroke, contact aspiration (CA) device showed similar efficacy in the recent trials. However, the efficacy of the both devices as first-line therapy for intracranial atherosclerotic stenosis (ICAS)-related large vessel occlusion has not yet been established. Therefore, we compared the immediate effects and final outcomes of SR and CA as first-line devices for treating ICAS-related occlusions. METHODS: We retrospectively analyzed the data of patients who underwent EVT for acute ischemic stroke from the registry of three Korean hospitals. Patients with ICAS-related occlusion who were treated within 24 h of onset of the symptoms were included. We investigated immediate reperfusion performance, immediate safety outcomes, and 3-month clinical outcomes for the two first-line devices. RESULTS: Of the 720 registered patients, 111 were eligible for this study. Forty-nine patients (44.1%) used SR and 62 (55.9%) used CA as the first-line device. Achieving successful reperfusion immediately after first-line thrombectomy was more frequent in the SR group than that in the CA group (77.6% vs. 43.5%, p = 0.001), with fewer additional rescue treatments (12.2% vs. 59.7%, p < 0.001). The incidence of iatrogenic dissection or rupture was lower in the SR group than that in the CA group (8.2% vs. 29.0%, p = 0.012). After additional rescue treatments, however, the final successful reperfusion rate did not differ between the two groups (SR 87.8% vs. CA 77.4%, p = 0.247), and there was no significant difference in the 3-month good outcomes (modified Rankin Scale, p = 0.524). CONCLUSIONS: First-line SR thrombectomy showed higher immediate reperfusion and less vessel injury for ICAS-related occlusions than CA. However, there was no significant difference in the final reperfusion status or 3-month outcomes from additional rescue treatments.

Differentiation of salivary gland tumors through tumor heterogeneity: a comparison between pleomorphic adenoma and Warthin tumor using CT texture analysis.

PURPOSE: We compared the diagnostic performance of CT texture analysis in single-phase CT scan with that of conventional enhancement pattern analysis in a two-phase CT scan for discrimination of salivary gland tumors, Warthin tumor (WT) from pleomorphic adenoma (PA). METHODS: One hundred seventy-eight patients with PA and 84 patients with WT were selected and CT texture analysis was separately performed on early (40s) and delayed (180s) phases, after injection of the contrast agent, using commercially available software. The attenuation changes and enhancement patterns were visually and quantitatively assessed with Hounsfield units (HU). Differences between PAs and WTs were analyzed using χ2 test and independent t test. Diagnostic performance of texture parameters in single-phase CT was compared with that of dynamic enhancement pattern in two-phase CT using the McNemar test. RESULTS: Ratio of tumoral HU (delayed phase/early phase) was significantly higher in PAs compared with WTs (p < 0.001). Tumor heterogeneity parameters, standard deviation (SD) and entropy, were significantly lower in WTs regardless of the type of filter used (p ≤ 0.001). Mean with coarse filter (AUC = 0.944) on early phase scan and entropy with medium filter (AUC = 0.901) on delayed scan were best discriminators between PAs and WTs. Diagnostic accuracy of mean (90.5%) on early scan and entropy (84.7%) on delayed scan was not significantly different from the accuracy (89.3%) of conventional wash-out pattern for distinguishing WTs from PAs (p = 0.742, p = 0.088, respectively). CONCLUSION: Diagnostic performance of texture parameters was similar to that of quantitative enhancement pattern for differentiating WTs from PAs, with the advantage in lower radiation exposure.

Ischemic Diffusion Lesion Reversal After Endovascular Treatment.

Background and Purpose- Several studies have reported partial reversal of diffusion-weighted imaging (DWI) lesions after acute stroke reperfusion treatment. However, factors associated with DWI reversal have not yet been systematically investigated. We evaluated the factors associated with DWI reversal after endovascular treatment (EVT). Methods- We retrospectively analyzed consecutively encountered patients with acute ischemic stroke who underwent EVT at 3 comprehensive stroke centers in Korea from January 2011 to February 2016. Patients who received EVT within 24 hours of anterior circulation infarction and had both baseline and follow-up DWIs were included. DWI reversal was defined as a decrease in DWI volume from baseline to follow-up. We compared the characteristics and outcomes between patients with and without DWI reversal and assessed independent factors associated with DWI reversal. Results- Of 720 patients encountered during the time period, 404 patients (56.1%) met the study criteria, with 63 patients (15.5%) showing DWI reversal after EVT. The mean time interval between baseline and follow-up DWI was 4.7±2.4 days. Mean baseline DWI volumes of patients with and without DWI reversal were 30.1±36.7 versus 22.0±30.7 mL ( P=0.106), and follow-up DWI volumes were 17.8±24.9 versus 68.7±77.5 mL ( P<0.001). Patients with DWI reversal showed better functional outcomes at 3 months than those without DWI reversal (modified Rankin Scale [interquartile range], 1 [0-3] versus 2 [1-4]; P=0.001). In a multivariate analysis, complete reperfusion (odds ratio, 1.954; 95% CI, 1.063-3.582) and shorter time from baseline DWI to final reperfusion (odds ratio, 0.991; 95% CI, 0.983-0.998) were independently associated with DWI reversal. Conclusions- Complete reperfusion and shorter imaging time to recanalization were independently associated with DWI reversal among patients with acute ischemic stroke who received EVT.

Discrimination of HPV status using CT texture analysis: tumour heterogeneity in oropharyngeal squamous cell carcinomas.

PURPOSE: To evaluate the diagnostic performance of texture analysis for discriminating human papillomavirus (HPV) status in patients with oropharyngeal squamous cell carcinoma (OPSCC) in the primary tumours and metastatic lymph nodes. METHODS: Ninety-five patients with primary tumour and 91 with metastatic lymph nodes with confirmed HPV status, who underwent pretreatment contrast-enhanced CT (CECT), were included as the discovery population. CT texture analysis was performed using commercially available software. Differences between HPV-positive and HPV-negative groups were analysed using the χ2 test (or Mann-Whitney U test) and independent t test (or Fisher's exact test). ROC curve analysis was performed to discriminate HPV status according to heterogeneity parameters. Diagnostic accuracy was evaluated in the separate validation population (n = 36) from an outside hospital. RESULTS: HPV positivity was 52.6% for primary tumours and 56.0% for metastatic lymph nodes. The entropy and standard deviation (SD) values in the HPV-positive group were significantly lower. Entropy using the medium filter was the best discriminator between HPV-positive and HPV-negative primary OPSCCs (AUC, 0.85) and SD without the filter for metastatic lymph nodes (AUC, 0.82). Diagnostic accuracy of entropy for the primary tumour was 80.0% in the discovery group and 75.0% in the validation group. In cases of metastatic lymph node, the accuracy of SD was 79.1% and 78.8%, respectively. CONCLUSION: Significant differences were found in heterogeneity parameters from texture analysis of pretreatment CECT, according to HPV status. Texture analysis could be used as an adjunctive tool for diagnosis of HPV status in clinical practice.

Feasibility of Multiple Burr Hole With Erythropoietin in Acute Moyamoya Patients.

BACKGROUND AND PURPOSE: In patients with acute symptomatic moyamoya (<2 weeks), the feasibility of a combination therapy of multiple burr hole procedure under local anesthesia and intravenous erythropoietin pretreatment was assessed. We also identified the factors associated with transdural revascularization. METHODS: In this prospective single-arm study, perfusion-impaired patients presenting with transient ischemic attack or acute cerebral infarction were assessed. Combination therapy was performed to patients lacking transdural collaterals. Primary outcomes were evaluated clinically with modified Rankin Scale scores and radiologically with revascularization success (transhemispheric, trans-burr hole, and sufficient revascularizations [filling ≥33% of ipsilateral supratentorium]) at 6 months. Treatment-related adverse events were analyzed in 3 phases: pre burr hole, post burr hole, and after-discharge as secondary outcome. Factors associated with sufficient revascularization were investigated. RESULTS: Fifty hemispheres from 37 patients were included. Compared with discharge, modified Rankin Scale score at 6 months significantly improved (2.0 [0.0-5.0] versus 1.0 [0.0-4.0]; P<0.001). Majority had successful revascularization: trans-burr hole arteriogenesis (89.5%), transhemispheric arteriogenesis (98.0%), and sufficient revascularization (52.0%). There was no significant pre burr hole or post burr hole complication. Two (5.4%) transient ischemic attack and 1 (2.7%) cerebral infarction occurred after discharge. Presentation with acute infarction (odds ratio, 4.8; 95% confidence interval, 1.1-21.4), ipsilateral basal moyamoya vessels (odds ratio, 13.9; 95% confidence interval, 1.3-144.2), and delayed mean transit time (odds ratio, 3.9; 95% confidence interval, 1.3-12.2) predicted sufficient revascularization. CONCLUSIONS: Combination therapy allows safe and effective revascularization in moyamoya patients with acute ischemic presentation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03162588.

Feasibility of improved motion-sensitized driven-equilibrium (iMSDE) prepared 3D T1-weighted imaging in the diagnosis of vertebrobasilar artery dissection.

BACKGROUND AND PURPOSE: This study was to evaluate the diagnostic value of improved motion-sensitized driven-equilibrium (iMSDE)-prepared 3D T1-weighted magnetic resonance imaging (MRI) (iMSDE-3DMRI) in intracranial vertebrobasilary dissection (VBD) and to compare iMSDE-3DMRI images with those obtained using 2D high-resolution (HR) MRI with respect to their diagnostic performance in VBD. MATERIALS AND METHODS: We retrospectively reviewed 105 lesions from 102 patients who underwent multimodal imaging and contrast-enhanced iMSDE-3DMRI (CE-iMSDE-3DMRI). The 2D-HRMRI protocol comprised four axial HR images. The CE-iMSDE-3DMRI images were reformatted in the axial, coronal, and sagittal planes. The 2D-HRMRI-based diagnosis was compared with the final diagnosis. The 2D-HRMRI and CE-iMSDE-3DMRI images were examined independently for the diagnosis performance of dissection. RESULTS: VBD was confirmed in 66 lesions in 63 patients; 17 patients had confirmed atherosclerosis, and 22 had no lesions in the vertebrobasilar artery. Diagnostic performances of 2D-HRMRI (AUC, 0.839±0.04; sensitivity, 94.0; specificity, 79.5; diagnostic accuracy, 88.6) CE-iMSDE-3DMRI (AUC, 0.847±0.04; sensitivity, 84.8; specificity, 84.6; diagnostic accuracy, 84.7) and 2D-HRMRI+CE-iMSDE-3DMRI (AUC, 0.893±0.03; sensitivity, 97.0; specificity, 85.0; diagnostic accuracy, 92.5) were good. Comparisons of the diagnostic performance of 2D-HRMRI andCE-iMSDE-3DMRI showed that combined interpretation of 2D-HRMRI and iMSDE-3DMRI yields a significantly higher diagnostic performance than that of 2D-HRMRI (P=0.042). CONCLUSIONS: CE-iMSDE-3DMRI showed good diagnostic performance for the diagnosis of intracranial VBD. These results suggest that CE-iMSDE-3DMRI can be used in combination with 2D-HRMRI for the diagnosis of intracranial VBD.

Quantification of myelin in children using multiparametric quantitative MRI: a pilot study.

PURPOSE: The purpose of this study was to evaluate the usefulness of multiparametric quantitative MRI for myelination quantification in children. METHODS: We examined 22 children (age 0-14 years) with multiparametric quantitative MRI. The total volume of myelin partial volume (Msum), the percentage of Msum within the whole brain parenchyma (Mbpv), and the percentage of Msum within the intracranial volume (Micv) were obtained. Four developmental models of myelin maturation (the logarithmic, logistic, Gompertz, and modified Gompertz models) were examined to find the most representative model of the three parameters. We acquired myelin partial volume values in different brain regions and assessed the goodness of fit for the models. RESULTS: The ranges of Msum, Mbpv, and Micv were 0.8-160.9 ml, 0.2-13%, and 0.0-11.6%, respectively. The Gompertz model was the best fit for the three parameters. For developmental model analysis of myelin partial volume in each brain region, the Gompertz model was the best-fit model for pons (R 2 = 74.6%), middle cerebeller peduncle (R 2 = 76.4%), putamen (R2 = 95.8%), and centrum semiovale (R 2 = 77.7%). The logistic model was the best-fit model for the genu and splenium of the corpus callosum (R 2 = 79.7-93.6%), thalamus (R 2 = 81.7%), and frontal, parietal, temporal, and occipital white matter (R 2 = 92.5-96.5%). CONCLUSIONS: Multiparametric quantitative MRI depicts the normal developmental pattern of myelination in children. It is a potential tool for research studies on pediatric brain development evaluation.

Disrupted short chain specific ß-oxidation and improved synthase expression increase synthesis of short chain fatty acids in Saccharomyces cerevisiae.

Biologically derived fatty acids have gained tremendous interest as an alternative to petroleum-derived fuels and chemical precursors. We previously demonstrated the synthesis of short chain fatty acids in Saccharomyces cerevisiae by introduction of the Homo sapiens fatty acid synthase (hFAS) with heterologous phosphopantetheine transferases and heterologous thioesterases. In this study, short chain fatty acid production was improved by combining a variety of novel enzyme and metabolic engineering strategies. The use of a H. sapiens-derived thioesterase and phosphopantetheine transferase were evaluated. In addition, strains were engineered to disrupt either the full ß-oxidation (by deleting FAA2, PXA1, and POX1) or short chain-specific ß-oxidation (by deleting FAA2, ANT1, and PEX11) pathways. Prohibiting full ß-oxidation increased hexanoic and octanoic acid levels by 8- and 79-fold relative to the parent strain expressing hFAS. However, by targeting only short chain ß-oxidation, hexanoic and octanoic acid levels increased further to 31- and 140-fold over the parent. In addition, an optimized hFAS gene increased hexanoic, octanoic, decanoic and total short chain fatty acid levels by 2.9-, 2.0-, 2.3-, and 2.2-fold, respectively, relative to the non-optimized counterpart. By combining these unique enzyme and metabolic engineering strategies, octanoic acid was increased more than 181-fold over the parent strain expressing hFAS.

Effect of Osteoporosis on Bone Density of Orthognathic Osteotomy Sites in Maxillofacial Region.

OBJECTIVES: The aims of this study were to investigate the availability of Hounsfield unit (HU) measurement of computed tomography (CT) in evaluating the bone density of certain sites by comparing bone density between CT and dual-energy x-ray absorptiometry (DEXA), and to evaluate the effects of osteoporosis on osteotomy sites in orthognathic surgery. METHODS: This retrospective study included 80 patients who had undergone both facial CT and DEXA at our hospital. We selected 7 regions of interest from among the osteotomy sites in bimaxillary orthognathic surgery. The patients were assigned to either the normal (control) group (n = 40) or the abnormal group (n = 40), and HU values were measured in each region of interest. RESULTS: There were statistically significant differences in the mean HU values between 2 groups at all the osteotomy sites in the maxilla and mandible, with the normal group showing higher values than the abnormal group (P < 0.05). In addition, there was a significant positive correlation between T-scores obtained with DEXA and the HU values on CT at the osteotomy sites (P < 0.01). Multiple regression analysis indicated that the abnormal group was more negatively associated with 6 osteotomy sites except for 1 maxillary area, as compared with the normal group. CONCLUSIONS: Measurement of HU values on CT can be valuable in assessing bone density of the maxilla and mandible. It is suggested that osteoporosis may affect bone density at the osteotomy sites in orthognathic surgery, and the preoperative measurement of HU values might be useful in predicting unfavorable fracture or the risks involved in such surgery.

High-resolution magnetic resonance wall imaging findings of Moyamoya disease.

BACKGROUND AND PURPOSE: Diagnosis of Moyamoya disease (MMD) is based on the characteristic angiographic findings. However, differentiating MMD from intracranial atherosclerotic disease (ICAD) is difficult. We compared vessel wall imaging findings on high-resolution magnetic resonance imaging between MMD and ICAD. METHODS: High-resolution magnetic resonance imaging was performed on 32 patients with angiographically proven MMD and 16 patients with acute infarcts because of ICAD. Bilateral internal carotid arteries and steno-occlusive middle cerebral artery were analyzed for wall enhancement and remodeling. RESULTS: Enhancement patterns and distribution were different. Most patients with MMD (90.6%) showed concentric enhancement on distal internal carotid arteries and middle cerebral arteries, whereas focal eccentric enhancement was observed on the symptomatic segment in ICAD. MMD was characterized by middle cerebral artery shrinkage; the remodeling index and wall area were lower in MMD than in ICAD (remodeling index, 0.19±0.11 versus 1.00±0.43; wall area, 0.32±0.22 versus 6.00±2.72; P<0.001). CONCLUSIONS: MMD was characterized by concentric enhancement on bilateral distal internal carotid arteries and shrinkage of middle cerebral artery, regardless of symptoms.

Feasibility of high-resolution MR imaging for the diagnosis of intracranial vertebrobasilar artery dissection.

OBJECTIVES: To evaluate the feasibility of high-resolution MRI (HR-MRI) for diagnosing intracranial vertebrobasilar artery dissection (VBD) and to identify the most useful imaging findings suggesting dissection. METHODS: We retrospectively reviewed 50 patients with suspected intracranial VBDs who underwent HR-MRI. Two neuroradiologists independently reviewed the HR-MR images. The diagnosis based on HR-MRI was compared with the final diagnosis by consensus among the neuroradiologists, neurointerventionist, and neurologist. Two neuroradiologists also sought signs of dissection (mural hematoma, dissection flap, outer-diameter enlargement on T2WI of steno-occlusive lesions). Inter- and intraobserver agreements were analysed. RESULTS: HR-MRI corroborated the final diagnosis in 47 (94%; 31 VBD and 16 non-VBD) patients. A mural haematoma was best detected on T1WI and contrast-enhanced (CE)-T1WI (54.3%). Dissection flaps were observed in almost all cases on CE-T1WI (91.4 %), and then were detected on T2WI (68.6%). Outer-diameter enlargement of the steno-occlusive lesions on angiography was detected in more than half of the cases (62.9%). The two reviewers showed almost perfect agreement for the diagnosis of VBD and detecting dissection signs on every sequence. CONCLUSIONS: HR-MRI can be a useful and non-invasive diagnostic tool for intracranial VBD, and dissection flaps on CE-T1WI are the signs with the greatest diagnostic value. KEY POINTS: Direct imaging findings of dissection were well visualised by HR-MRI. Detection of a dissection flap on CE-T1WI is the most reliable diagnostic finding. HR-MRI could be a useful diagnostic tool for intracranial VBDs.