Microsatellite density landscapes illustrate short tandem repeats aggregation in the complete reference human genome.

BACKGROUND: Microsatellites are increasingly realized to have biological significance in human genome and health in past decades, the assembled complete reference sequence of human genome T2T-CHM13 brought great help for a comprehensive study of short tandem repeats in the human genome. RESULTS: Microsatellites density landscapes of all 24 chromosomes were built here for the first complete reference sequence of human genome T2T-CHM13. These landscapes showed that short tandem repeats (STRs) are prone to aggregate characteristically to form a large number of STRs density peaks. We classified 8,823 High Microsatellites Density Peaks (HMDPs), 35,257 Middle Microsatellites Density Peaks (MMDPs) and 199, 649 Low Microsatellites Density Peaks (LMDPs) on the 24 chromosomes; and also classified the motif types of every microsatellites density peak. These STRs density aggregation peaks are mainly composing of a single motif, and AT is the most dominant motif, followed by AATGG and CCATT motifs. And 514 genomic regions were characterized by microsatellite density feature in the full T2T-CHM13 genome. CONCLUSIONS: These landscape maps exhibited that microsatellites aggregate in many genomic positions to form a large number of microsatellite density peaks with composing of mainly single motif type in the complete reference genome, indicating that the local microsatellites density varies enormously along the every chromosome of T2T-CHM13.

Age-specific optimization of the T2-weighted MRI contrast in infant and toddler brain.

PURPOSE: In 0-2-year-old brains, the T2-weighted (T2w) contrast between white matter (WM) and gray matter (GM) is weaker compared with that in adult brains and rapidly changes with age. This study aims to design variable-flip-angle (VFA) trains in 3D fast spin-echo sequence that adapt to the dynamically changing relaxation times to improve the contrast in the T2w images of the developing brains. METHODS: T1 and T2 relaxation times in 0-2-year-old brains were measured, and several age groups were defined according to the age-dependent pattern of T2 values. Based on the static pseudo-steady-state theory and the extended phase graph algorithm, VFA trains were designed for each age group to maximize WM/GM contrast, constrained by the maximum specific absorption rate and overall signal intensity. The optimized VFA trains were compared with the default one used for adult brains based on the relative contrast between WM and GM. Dice coefficient was used to demonstrate the advantage of contrast-improved images as inputs for automatic tissue segmentation in infant brains. RESULTS: The 0-2-year-old pool was divided into groups of 0-8 months, 8-12 months, and 12-24 months. The optimal VFA trains were tested in each age group in comparison with the default sequence. Quantitative analyses demonstrated improved relative contrasts in infant and toddler brains by 1.5-2.3-fold at different ages. The Dice coefficient for contrast-optimized images was improved compared with default images (p < 0.001). CONCLUSION: An effective strategy was proposed to improve the 3D T2w contrast in 0-2-year-old brains.

Improving Microstructural Estimation in Time-Dependent Diffusion MRI With a Bayesian Method.

BACKGROUND: Accurately fitting diffusion-time-dependent diffusion MRI (td-dMRI) models poses challenges due to complex and nonlinear formulas, signal noise, and limited clinical data acquisition. PURPOSE: Introduce a Bayesian methodology to refine microstructural fitting within the IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) model and optimize the prior distribution within the Bayesian framework. STUDY TYPE: Retrospective. POPULATION: Involving 69 pediatric patients (median age 6 years, interquartile range [IQR] 3-9 years, 61% male) with 41 low-grade and 28 high-grade gliomas, of which 76.8% were identified within the brainstem or cerebellum. FIELD STRENGTH/SEQUENCE: 3 T, oscillating gradient spin-echo (OGSE) and pulsed gradient spin-echo (PGSE). ASSESSMENT: The Bayesian method's performance in fitting cell diameter ( d $$ d $$ ), intracellular volume fraction ( f in $$ {f}_{in} $$ ), and extracellular diffusion coefficient ( D ex $$ {D}_{ex} $$ ) was compared against the NLLS method, considering simulated and experimental data. The tumor region-of-interest (ROI) were manually delineated on the b0 images. The diagnostic performance in distinguishing high- and low-grade gliomas was assessed, and fitting accuracy was validated against H&E-stained pathology. STATISTICAL TESTS: T-test, receiver operating curve (ROC), area under the curve (AUC) and DeLong's test were conducted. Significance considered at P < 0.05. RESULTS: Bayesian methodology manifested increased accuracy with robust estimates in simulation (RMSE decreased by 29.6%, 40.9%, 13.6%, and STD decreased by 29.2%, 43.5%, and 24.0%, respectively for d $$ d $$ , f in $$ {f}_{in} $$ , and D ex $$ {D}_{ex} $$ compared to NLLS), indicating fewer outliers and reduced error. Diagnostic performance for tumor grade was similar in both methods, however, Bayesian method generated smoother microstructural maps (outliers ratio decreased by 45.3% ± 19.4%) and a marginal enhancement in correlation with H&E staining result (r = 0.721 for f in $$ {f}_{in} $$ compared to r = 0.698 using NLLS, P = 0.5764). DATA CONCLUSION: The proposed Bayesian method substantially enhances the accuracy and robustness of IMPULSED model estimation, suggesting its potential clinical utility in characterizing cellular microstructure. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 1.

Automated segmentation and volume prediction in pediatric Wilms' tumor CT using nnu-net.

BACKGROUND: Radiologic volumetric evaluation of Wilms' tumor (WT) is an important indicator to guide treatment decisions. However, due to the heterogeneity of the tumors, radiologists have main-guard differences in diagnosis that can lead to misdiagnosis and poor treatment. The aim of this study was to explore whether CT-based outlining of WT foci can be automated using deep learning. METHODS: We included CT intravenous phase images of 105 patients with WT and double-blind outlining of lesions by two radiologists. Then, we trained an automatic segmentation model using nnUnet. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were used to assess the performance. Next, we optimized the automatic segmentation results based on the ratio of the three-dimensional diameter of the lesion to improve the performance of volumetric assessment. RESULTS: The DSC and HD95 was 0.83 ± 0.22 and 10.50 ± 8.98 mm. The absolute difference and percentage difference in tumor size was 72.27 ± 134.84 cm3 and 21.08% ± 30.46%. After optimization according to our method, it decreased to 40.22 ± 96.06 cm3 and 10.16% ± 9.70%. CONCLUSION: We introduce a novel method that enhances the accuracy of predicting WT volume by integrating AI automated outlining and 3D tumor diameters. This approach surpasses the accuracy of using AI outcomes alone and has the potential to enhance the clinical evaluation of pediatric patients with WT. By intertwining AI outcomes with clinical data, this method becomes more interpretive and offers promising applications beyond Wilms tumor, extending to other pediatric diseases.

Experimental study on the biomechanical stability of complex acetabular fractures in the quadrilateral area: application of a dynamic anterior titanium-plate screw system.

BACKGROUND AND OBJECTIVE: Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. MATERIALS AND METHODS: Eight formal in-preserved cadaveric pelvises aged 30-50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. RESULTS: As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p < 0.05). In the sitting position, the horizontal and longitudinal displacements of the quadrilateral areas were within 0.5 mm in group A and group B, and there was no significant difference between group A and group B (p > 0.05). CONCLUSION: For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.

The epidemiological characteristics of pediatric head injury in Hangzhou, China: a retrospective study based on cranial CT examinations.

PRIMARY OBJECTIVE: This study aims to create a pediatric head injury database based on cranial CT examinations and explore their epidemiologic characteristics. METHODS: Data related to cranial CT examinations of pediatric head injuries from March 2014 to March 2021 were collected at outpatient and emergency department of a pediatric medical center. The causes of injury, observable post-injury symptoms, and cranial injury findings were extracted with the assistance of natural language processing techniques. RESULTS: Reviewing the data from records on 52,821 children with head injuries over a period of 7 years, the most common causes of pediatric head injury were falls (58.3%), traffic accidents (26.0%), smash/crush/strike (13.9%), violence (1.5%) and sports-related incidents (0.3%). Overall, most of those injured were boys which accounting for 62.2% of all cases. Skull fractures most commonly occur in the parietal bone (9.0%), followed by the occipital (5.2%), frontal (3.3%) and temporal bones (3.0%). Most intracranial hemorrhages occurred in epidural (5.8%), followed by subdural (5.1%), subarachnoid (0.9%), intraparenchymal (0.5%) and intraventricular (0.2%) hemorrhages. Spring and autumn showed more events than any other season. CONCLUSIONS: To the best of our knowledge, this is the largest sample of epidemiological study of head injury in the Chinese pediatric population to date.

tert-Butyl Nitrite-Induced Radical Nitrile Oxidation Cycloaddition: Synthesis of Isoxazole/Isoxazoline-Fused Benzo 6/7/8-membered Oxacyclic Ketones.

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia-Ischemia.

BACKGROUND: Diffusion MRI (dMRI) is known to be sensitive to hypoxic-ischemic encephalopathy (HIE). However, existing dMRI studies used simple diffusion tensor metrics and focused only on a few selected cerebral regions, which cannot provide a comprehensive picture of microstructural injury. PURPOSE: To systematically characterize the microstructural alterations in mild, moderate, and severe HIE neonates compared to healthy neonates with advanced dMRI using region of interest (ROI), tract, and fixel-based analyses. STUDY TYPE: Prospective. POPULATION: A total of 42 neonates (24 males and 18 females). FIELD STRENGTH/SEQUENCE: 3-T, diffusion-weighted echo-planar imaging. ASSESSMENT: Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel-based analysis was performed to assess group differences in individual fiber components within a voxel (fixel). STATISTICAL TESTS: One-way analysis of covariance (ANCOVA) to compare dMRI metrics among severe/moderate/mild HIE and control groups and general linear model for fixel-wise group differences (age, sex, and body weight as covariates). Adjusted P value < 0.05 was considered statistically significant. RESULTS: For severe HIE, ROI-based analysis revealed widespread regions, including the deep nuclei and white matter with reduced FA, while in moderate injury, only FC was decreased around the posterior watershed zones. Tract-based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto-occipital fasciculus (IFOF), right inferior longitudinal fasciculus (ILF), and splenium of corpus callosum (SCC) in moderate HIE, and in right IFOF and left anterior thalamic radiation (ATR) in mild HIE. Correspondingly, we found altered fixels in the right middle-posterior IFOF and ILF, and in the central-to-right part of SCC in moderate HIE. DATA CONCLUSION: For severe HIE, extensive microstructural injury was identified. For moderate-mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Automated Measurement of Pancreatic Fat Deposition on Dixon MRI Using nnU-Net.

BACKGROUND: Pancreatic fat accumulation may cause or aggravate the process of acute pancreatitis, ß-cell dysfunction, T2DM disease, and even be associated with pancreatic tumors. The pathophysiology of fatty pancreas remains overlooked and lacks effective imaging diagnostics. PURPOSE: To automatically measure the distribution of pancreatic fat deposition on Dixon MRI in multicenter/population datasets using nnU-Net models. STUDY TYPE: Retrospective. POPULATION: A total of 176 obese/nonobese subjects (90 males, 86 females; mean age, 27.2 ± 19.7) were enrolled, including a training set (N = 132) and a testing set (N = 44). FIELD STRENGTH/SEQUENCE: A 3 T and 1.5 T/gradient echo T1 dual-echo Dixon. ASSESSMENT: The segmentation results of four types of nnU-Net models were compared using dice similarity coefficient (DSC), positive predicted value (PPV), and sensitivity. The ground truth was the manual delineation by two radiologists according to in-phase (IP) and opposed-phase (OP) images. STATISTICAL TESTS: The group difference of segmentation results of four models were assessed by the Kruskal-Wallis H test with Dunn-Bonferroni comparisons. The interobserver agreement of pancreatic fat fraction measurements across three observers and test-retest reliability of human and machine were assessed by intragroup correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: The three-dimensional (3D) dual-contrast model had significantly improved performance than 2D dual-contrast (DSC/sensitivity) and 3D one-contrast (IP) models (DSC/PPV/sensitivity) and had less errors than 3D one-contrast (OP) model according to higher DSC and PPV (not significant), with a mean DSC of 0.9158, PPV of 0.9105 and sensitivity of 0.9232 in the testing set. The test-retest ICC of this model was above 0.900 in all pancreatic regions, exceeded human. DATA CONCLUSION: 3D Dual-contrast nnU-Net aided segmentation of pancreas on Dixon images appears to be adaptable to multicenter/population datasets. It fully automates the assessment of pancreatic fat distribution and has high reliability. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Developmental pattern of association fibers and their interaction with associated cortical microstructures in 0-5-month-old infants.

Association fibers connect the cortical regions and experience rapid development involving myelination and axonal growth during infancy. Yet, the spatiotemporal patterns of microstructural changes along these tracts, as well as the developmental interaction between the white matter (WM) tracts and the cortical gray matter (cGM) connected to them, are mostly unknown during infancy. In this study, we performed a diffusion MRI-based tractography and microstructure study in a cohort of 89 healthy preterm-born infants with gestational age at birth between 28.1∼36.4 weeks and postmenstrual age at scan between 39.9∼59.9 weeks. Results revealed that several C-shaped fibers, such as the arcuate fasciculus, cingulum, and uncinate fasciculus, demonstrated symmetrical along-tract profiles; and the horizontally oriented running fibers, including the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus, demonstrated an anterior-posterior developmental gradient. This study characterized the along-tract profiles using fixel-based analysis and revealed that the fiber cross-section (FC) of all five association fibers demonstrated a fluctuating increase with age, while the fiber density (FD) monotonically increase with age. NODDI was utilized to analyze the microstructural development of cGM and indicated cGM connected to the anterior end of the association fibers developed faster than that of the posterior end during 0-5 months. Notably, a mediation analysis was used to explore the relation between the development of WM and associated cGM, and demonstrated a partial mediation effect of FD in WM on the development of intracellular volume (ICV) in cGM and a full mediation effect of ICV on the growth of FD in most fibers, suggesting a predominant mediation of cGM on the WM development. Furthermore, for assessing whether those results were biased by prematurity, we compared preterm- and term-born neonates with matched scan age, gender, and multiple births from the developing human connectome project (dHCP) dataset to assess the effect of preterm-birth, and the results indicated a similar developmental pattern of the association fibers and their attached cGM. These findings presented a comprehensive picture of the major association fibers during early infancy and deciphered the developmental interaction between WM and cGM in this period.

Growth charts of brain morphometry for preschool children.

Brain development from 1 to 6 years of age anchors a wide range of functional capabilities and carries early signs of neurodevelopmental disorders. However, quantitative models for depicting brain morphology changes and making individualized inferences are lacking, preventing the identification of early brain atypicality during this period. With a sample size of 285, we characterized the age dependence of the cortical thickness and subcortical volume in neurologically normal children and constructed quantitative growth charts of all brain regions for preschool children. While the cortical thickness of most brain regions decreased with age, the entorhinal and parahippocampal regions displayed an inverted-U shape of age dependence. Compared to the cortical thickness, the normalized volume of subcortical regions exhibited more divergent trends, with some regions increasing, some decreasing, and some displaying inverted-U-shaped trends. The growth curve models for all brain regions demonstrated utilities in identifying brain atypicality. The percentile measures derived from the growth curves facilitate the identification of children with developmental speech and language disorders with an accuracy of 0.875 (area under the receiver operating characteristic curve: 0.943). Our results fill the knowledge gap in brain morphometrics in a critical development period and provide an avenue for individualized brain developmental status evaluation with demonstrated sensitivity. The brain growth charts are shared with the public (http://phi-group.top/resources.html).

A comprehensive microsatellite landscape of human Y-DNA at kilobase resolution.

BACKGROUND: Though interest in human simple sequence repeats (SSRs) is increasing, little is known about the exact distributional features of numerous SSRs in human Y-DNA at chromosomal level. Herein, totally 540 maps were established, which could clearly display SSR landscape in every bin of 1 k base pairs (Kbp) along the sequenced part of human reference Y-DNA (NC_000024.10), by our developed differential method for improving the existing method to reveal SSR distributional characteristics in large genomic sequences. RESULTS: The maps show that SSRs accumulate significantly with forming density peaks in at least 2040 bins of 1 Kbp, which involve different coding, noncoding and intergenic regions of the Y-DNA, and 10 especially high density peaks were reported to associate with biological significances, suggesting that the other hundreds of especially high density peaks might also be biologically significant and worth further analyzing. In contrast, the maps also show that SSRs are extremely sparse in at least 207 bins of 1 Kbp, including many noncoding and intergenic regions of the Y-DNA, which is inconsistent with the widely accepted view that SSRs are mostly rich in these regions, and these sparse distributions are possibly due to powerfully regional selection. Additionally, many regions harbor SSR clusters with same or similar motif in the Y-DNA. CONCLUSIONS: These 540 maps may provide the important information of clearly position-related SSR distributional features along the human reference Y-DNA for better understanding the genome structures of the Y-DNA. This study may contribute to further exploring the biological significance and distribution law of the huge numbers of SSRs in human Y-DNA.

Diffusion MRI of the infant brain reveals unique asymmetry patterns during the first-half-year of development.

The human brain demonstrates anatomical and functional lateralization/asymmetry between the left and right hemispheres, and such asymmetry is known to start from the early age of life. However, how the asymmetry changes with brain development during infancy remained unknown. In this study, we aimed to systematically investigate the spatiotemporal pattern of brain asymmetry in healthy preterm-born infants during the first-half-year of development, using high angular resolution diffusion MRI. Sixty-five healthy preterm-born infants (gestational age between 25.3-36.6 weeks) were scanned with postmenstrual age (PMA) ranging from term-equivalent age (TEA) to 6-months. At the regional level, we performed a region-of-interest-based analysis by segmenting the brain into 63 symmetrical pairs of regions, based on which the laterality index was assessed and correlated with PMA. At the voxel level, we performed a fixel-based analysis of each fiber component between the native and left-right flipped data, separately in TEA-1 month, 1-3 months, and 3-6 months groups. The infant brains demonstrated extensive regions with structural asymmetry during their first half-of-year of life. A distinct central-peripheral asymmetry pattern was observed in mean diffusivity, namely, leftward lateralization in the neocortex and rightward asymmetry in the deep brain regions. Besides, the posterior brain demonstrated a higher lateralization index compared with the anterior brain in all metrics, which is congruent with the brain developmental pattern from caudal to rostral. Regionally, language processing regions showed a rightward asymmetry, while visuospatial processing regions exhibited leftward lateralization in fractional anisotropy, fibre density, and fibre cross-section measurements, and most white matter regions were lateralized to the left in these measurements. The laterality index of several regions (12 out 63) demonstrated significant developmental changes in mean diffusivity. At the fixel level, the fiber cross-section of inferior fronto-occipital fasciculus showed significant leftward asymmetry and the extent of asymmetry increased with PMA. In summary, the results revealed unique spatiotemporal patterns of macro- and micro-structural asymmetry in early life, which dynamically changed with age. These findings may contribute to the understanding of brain development during infancy.

The only conserved microsatellite in coding regions of ebolavirus is the editing site.

Lots of viral genomes were found to contain microsatellites (SSRs) including Ebolavirus, and majority of Ebolavirus microsatellite sites are distributed in protein-coding regions of the genomes. Here, we totally identified 212 reserved microsatellite sites in the protein-coding regions of 213 genomic sequences from five Ebolavirus species. In these reserved microsatellite sites, there is only one significantly conserved microsatellite site among the sample Ebolavirus genomic sequences, and this microsatellite is located at RNA editing site of the GP gene, indicating the selective relevance with RNA editing there. This analysis may help to further explore the biological significance of various microsatellites in Ebolavirus genomes.

Frequency-stabilized chemical exchange saturation transfer imaging with real-time free-induction-decay readout.

PURPOSE: To correct the temporal B0 drift in chemical exchange saturation transfer (CEST) imaging in real-time with extra free-induction-decay (FID) readout. THEORY AND METHODS: The frequency stabilization module of the recently proposed frequency-stabilized CEST (FS-CEST) sequence was further simplified by replacing the original three k-space lines of gradient-echo (GRE) readout with a single k-space line of FID readout. The B0 drift was quantified using the phase difference between the odd and even parts of the FID signal in the frequency stabilization module and then used to update the B0 frequency in the succeeding modules. The proposed FS-CEST sequence with FID readout (FID FS-CEST) was validated in phantoms and 16 human subjects on cross-vendor scanners. RESULTS: In the Siemens experiments, the FID FS-CEST sequence successfully corrected the user-induced B0 drift, generating consistent amide proton transfer-weighted (APTw) images and magnetization transfer ratio asymmetry (MTRasym ) spectra with those from the non-frequency-stabilized CEST (NFS-CEST) sequence without B0 drift. In the Philips experiments, the FID FS-CEST sequence produced more stable APTw images and MTRasym spectra than the NFS-CEST sequence in the presence of practical B0 drift. Quantitatively, the SD of the APTw signal values in the deep gray matter from 15 subjects was 0.26% for the FID FS-CEST sequence compared to 1.03% for the NFS-CEST sequences, with the fluctuations reduced by nearly three-quarters. CONCLUSIONS: The proposed FS-CEST sequence with FID readout can effectively correct the temporal B0 drift on cross-vendor scanners.

Differentiation of low- and high-grade pediatric gliomas with amide proton transfer imaging: added value beyond quantitative relaxation times.

OBJECTIVES: To evaluate whether amide proton transfer (APT) MRI can be used to characterize gliomas in pediatric patients and whether it provides added value beyond relaxation times. METHODS: In this prospective study, APT imaging and relaxation time mapping were performed in 203 pediatric patients suspected of gliomas from February 2018 to December 2019. The region of interest (ROI) in the tumor was automatically generated with artifact detection and ROI-shrinking algorithms. Several APT-related metrics (CESTR, CESTRnr, MTRRex, AREX, and APT#) and quantitative T1 and T2 were compared between low-grade and high-grade gliomas using the student's t-test or Mann-Whitney U-test. The performance of these parameters was assessed using the receiver operating characteristic (ROC) analysis. A stepwise multivariate logistic regression model was used to combine the imaging parameters. RESULTS: Forty-eight patients (mean age: 6 ± 4 years; 23 males and 25 females) were included in the final analysis. All the APT-related metrics except APT# had significantly (p < 0.05) higher values in the high-grade group than the low-grade group. Under different ROI-shrinking cutoffs, the quantitative T1 (p = 0.045-0.200) and T2 (p = 0.037-0.171) values of high-grade gliomas were typically lower than those of low-grade ones. The stepwise multivariate logistic regression revealed that CESTRnr and APT# were combined significant predictors of glioma grades (p < 0.05), with an area under the ROC curve (AUC) of 0.86 substantially larger than those of T1 (AUC = 0.69) and T2 (AUC = 0.68). CONCLUSIONS: APT imaging can be used to differentiate high-grade and low-grade gliomas in pediatric patients and provide added value beyond quantitative relaxation times. KEY POINTS: • Amide proton transfer (APT) MRI showed significantly (p < 0.05) higher values in pediatric patients with high-grade gliomas than those with low-grade ones. • The area under the curve was 0.86 for APT MRI to differentiate low-grade and high-grade gliomas in pediatric patients, which was substantially higher than that for quantitative T1 (0.69) and T2 (0.68). • APT MRI demonstrated added value beyond quantitative T1 and T2 mapping in characterizing pediatric gliomas.

Relatively semi-conservative replication and a folded slippage model for short tandem repeats.

BACKGROUND: The ubiquitous presence of short tandem repeats (STRs) in virtually all genomes implicates their functional relevance, while a widely-accepted definition of STR is yet to be established. Previous studies majorly focus on relatively longer STRs, while shorter repeats were generally excluded. Herein, we have adopted a more generous criteria to define shorter repeats, which has led to the definition of a much larger number of STRs that lack prior analysis. Using this definition, we analyzed the short repeats in 55 randomly selected segments in 55 randomly selected genomic sequences from a fairly wide range of species covering animals, plants, fungi, protozoa, bacteria, archaea and viruses. RESULTS: Our analysis reveals a high percentage of short repeats in all 55 randomly selected segments, indicating that the universal presence of high-content short repeats could be a common characteristic of genomes across all biological kingdoms. Therefore, it is reasonable to assume a mechanism for continuous production of repeats that can make the replicating process relatively semi-conservative. We have proposed a folded replication slippage model that considers the geometric space of nucleotides and hydrogen bond stability to explain the mechanism more explicitly, with improving the existing straight-line slippage model. The folded slippage model can explain the expansion and contraction of mono- to hexa- nucleotide repeats with proper folding angles. Analysis of external forces in the folding template strands also suggests that expansion exists more commonly than contraction in the short tandem repeats. CONCLUSION: The folded replication slippage model provides a reasonable explanation for the continuous occurrences of simple sequence repeats in genomes. This model also contributes to the explanation of STR-to-genome evolution and is an alternative model that complements semi-conservative replication.

Age-specific optimization of T1-weighted brain MRI throughout infancy.

The infant brain undergoes drastic morphological and functional development during the first year of life. Three-dimensional T1-weighted Magnetic Resonance Imaging (3D T1w-MRI) is a major tool to characterize the brain anatomy, which however, manifests inherently low and rapidly changing contrast between white matter (WM) and gray matter (GM) in the infant brains (0-12 month-old). Despite the prior efforts made to maximize tissue contrast in the neonatal brains (≤1 months), optimization of imaging methods in the rest of the infancy (1-12 months) is not fully addressed, while brains in the latter period exhibit even more challenging contrast. Here, we performed a systematic investigation to improve the contrast between cortical GM and subcortical WM throughout the infancy. We first performed simultaneous T1 and proton density mapping in a normally developing infant cohort at 3T (n = 57). Based on the evolution of T1 relaxation times, we defined three age groups and simulated the relative tissue contrast between WM and GM in each group. Age-specific imaging strategies were proposed according to the Bloch simulation: inversion time (TI) around 800 ms for the 0-3 month-old group, dual TI at 500 ms and 700 ms for the 3-7 month-old group, and TI around 700 ms for 7-12 month-old group, using a centrically encoded 3D-MPRAGE sequence at 3T. Experimental results with varying TIs in each group confirmed improved contrast at the proposed optimal TIs, even in 3-7 month-old infants who had nearly isointense contrast. We further demonstrated the advantage of improved relative contrast in segmenting the neonatal brains using a multi-atlas segmentation method. The proposed age-specific optimization strategies can be easily adapted to routine clinical examinations, and the improved image contrast would facilitate quantitative analysis of the infant brain development.

Conserved microsatellites may contribute to stem-loop structures in 5', 3' terminals of Ebolavirus genomes.

Microsatellites (SSRs) are ubiquitous in coding and non-coding regions of the Ebolavirus genomes. We synthetically analyzed the microsatellites in whole-genome and terminal regions of 219 Ebolavirus genomes from five species. The Ebolavirus sequences were observed with small intraspecies variations and large interspecific variations, especially in the terminal non-coding regions. Only five conserved microsatellites were detected in the complete genomes, and four of them which well base-paired to help forming conserved stem-loop structures mainly appeared in the terminal non-coding regions. These results suggest that the conserved microsatellites may be evolutionary selected to form conserved secondary structures in 5', 3' terminals of Ebolavirus genomes. It may help to understand the biological significance of microsatellites in Ebolavirus and also other virus genomes.

Improved chemical exchange saturation transfer imaging with real-time frequency drift correction.

PURPOSE: To investigate the effects of frequency drift on chemical exchange saturation transfer (CEST) imaging at 3T, and to propose a new sequence for correcting artifacts attributed to B0 drift in real time. THEORY AND METHODS: A frequency-stabilized CEST (FS-CEST) imaging sequence was proposed by adding a frequency stabilization module to the conventional non-frequency-stabilized CEST (NFS-CEST) sequence, which consisted of a small tip angle radiofrequency excitation pulse and readout of three non-phase-encoded k-space lines. Experiments were performed on an egg white phantom and 26 human subjects on a heavy-duty clinical scanner, in order to compare the difference of FS-CEST and NFS-CEST sequences for generating the z-spectrum, magnetization transfer ratio asymmetry (MTRasym ) spectrum, and amide proton transfer weighted (APTw) image. RESULTS: The B0 drift in CEST imaging, if not corrected, would cause APTw images and MTRasym spectra from both the phantom and volunteers to be either significantly higher or lower than the true values, depending on the status of the scanner. The FS-CEST sequence generated substantially more stable MTRasym spectra and APTw images than the conventional NFS-CEST sequence. Quantitatively, the compartmental-average APTw signals (mean ± standard deviation) from frontal white matter regions of all 26 human subjects were -0.32% ± 2.32% for the NFS-CEST sequence and -0.14% ± 0.37% for the FS-CEST sequence. CONCLUSIONS: The proposed FS-CEST sequence provides an effective approach for B0 drift correction without additional scan time and should be adopted on heavy-duty MRI scanners.