Pituitary MRI Radiomics Improves Diagnostic Performance of Growth Hormone Deficiency in Children Short Stature: A Multicenter Radiomics Study.

RATIONALE AND OBJECTIVES: To develop an efficient machine-learning model using pituitary MRI radiomics and clinical data to differentiate growth hormone deficiency (GHD) from idiopathic short stature (ISS), making the diagnostic process more acceptable to patients and their families. MATERIALS AND METHODS: A retrospective cohort of 297 GHD and 300 ISS children (4-12 years) were enrolled as training and validation cohorts (8:2 ratio). An external cohort from another institution (49 GHD and 51 ISS) was employed as the testing cohort. Radiomics features extracted from the anterior pituitary gland on sagittal T1-weighted image (1.5 T or 3.0 T) were used to develop a radiomics model after feature selection. Hematological biomarkers were selected to create a clinical model and combine with the optimal radiomics features to create a clinical-radiomics model. The area under the receive operating characteristic curve (AUC) and Delong test compared the diagnostic performance of the previously mentioned three models across different validation and testing cohorts. RESULTS: 17 radiomics features were selected for the radiomics model, and total protein, total cholesterol, free triiodothyronine, and triglyceride were utilized for the clinical model. In the training and validation cohorts, the diagnostic performance of the clinical-radiomics model (AUC=0.820 and 0.801) was comparable to the radiomics model (AUC=0.812 and 0.779, both P >0.05), both outperforming the clinical model (AUC=0.575 and 0.593, P <0.001). In the testing cohort, the clinical-radiomics model exhibited the highest AUC of 0.762 than the clinical and radiomics model (AUC=0.604 and 0.741, respectively, P <0.05). In addition, the clinical and radiomics models demonstrated similar diagnostic performance in the testing cohort (P >0.05). CONCLUSION: Integrating radiomics features from conventional pituitary MRI with clinical indicators offers a minimally invasive approach for identifying GHD and shows robustness in a multicenter setting.

Association between paravertebral muscle radiological parameter alterations and non-alcoholic fatty liver disease.

PURPOSE: To assess changes in laboratory indices, paravertebral muscle (PVM) fat infiltration and multi b-value DWI parameters and their potential correlation with NAFLD. METHODS: This retrospective analysis included 178 patients with histopathologically confirmed NAFLD, incluiding 76 with non-alcoholic steatohepatitis (NASH). Differences in PVM fat infiltration ratio (FIR), DWI parameters, and laboratory indices were compared between two groups. The correlation between FIR and NAFLD activity score (NAS) was also analysed. Binary logistic regression was used to identify the independent risk factors for NASH. The clinical utility of PVM fat infiltration, DWI parameters, and laboratory indices for diagnosing NASH in patients with NAFLD was evaluated using receiver operating characteristic (ROC) curves. RESULTS: The FIRs at the L2 and L3 levels were significantly higher in the with NASH group than those in the without NASH group. The heterogeneity index (α) and perfusion fraction (f) values at the L3 level of PVM were lower in the with NASH group. Moreover, the FIR at the L3 level was positively correlated with NAS. FIR at the L3 level was an independent risk factor for NASH along with alanine aminotransferase level. The area under the ROC curve (AUC) using L3 level PVM radiological parameters and laboratory indices for diagnosing NASH in patients with NAFLD was significantly higher than that using the degree of PVM fat infiltration, DWI parameters, or laboratory indices alone. CONCLUSIONS: Radiological parameters of the PVM were correlated with NAFLD. An integrated curve combining PVM radiological parameters may help distinguish NASH from NAFLD, thereby offering novel insights into the diagnosis of NASH.

Quantitative analysis of paravertebral muscle asymmetry and its correlation with spinal deformity in patients with degenerative lumbar scoliosis: a retrospective case-control study.

Background: The degeneration and functional decline of paravertebral muscles (PVMs) are reported to be closely linked to the incidence of degenerative lumbar scoliosis (DLS), a spinal deformity of the mature skeleton. However, the functional role and degeneration of PVMs and their relationship to the development of spinal deformities remain controversial. Therefore, the present study analyzed the morphological changes in the PVMs of patients with DLS, and explored the relationship between PVM degeneration and spinal osseous parameters. Methods: In this retrospective case-control study, we evaluated the PVM parameters of patients with DLS (n=120) and compared them with patients free of DLS (control group, n=120). The cross-sectional area (CSA) and computed tomography (CT) values of the PVM at the lumbar vertebra 1-5 levels were measured. Further, the lumbar scoliosis Cobb, lumbar lordotic, and apical vertebral rotation angles were measured on CT and radiographs in the DLS group, and the relationship between PVM changes and these factors was analyzed. Results: In the control group, the PVM CSA and CT values differed insignificantly between the bilateral sides at all levels (P>0.05). In the DLS group, the CSAs of the multifidus (MF) and erector spinae (ES) were larger on the convex side than the concave side (P>0.05), whereas that of the psoas major (PM) was smaller on the convex side than the concave side (P<0.05). The CT value of the PVM was lower on the convex side at all levels (P<0.05). The CSA and CT values on both sides of the patients were lower in the DLS group than the control group at all levels (P<0.05). Further, the degree of PVM asymmetry at the apical vertebral level was positively correlated with the lumbar scoliosis (P<0.01) and apical vertebral rotation angles (P<0.05), but negatively correlated with the lumbar lordotic angle (P<0.05). Conclusions: Asymmetric degeneration of the PVM was observed bilaterally in DLS patients, and the degeneration was more pronounced on the concave side than the convex side. This asymmetrical degeneration was closely associated with the severity of lumbar scoliosis, vertebral rotation, and loss of lumbar lordosis, and a stronger correlation was observed with the MF and ES than with the PM.

Altered cerebral white matter network topology and cognition in children with obstructive sleep apnea.

OBJECTIVES: The study aimed to explore the underlying mechanisms of OSA-related cognitive impairment by investigating the altered topology of brain white matter networks in children with OSA. METHODS: Graph theory was used to examine white matter networks' network topological properties in 46 OSA and 31 non-OSA children. All participants underwent MRI, polysomnography, and cognitive testing. The effects of the obstructive apnea-hypopnea index (OAHI) on topological properties of white matter networks and network properties on cognition were studied using hierarchical linear regression. Mediation analyses were used to explore whether white matter network properties mediated the effects of OAHI on cognition. RESULTS: Children with OSA had significantly higher assortativity than non-OSA children. Furthermore, OAHI was associated with the nodal properties of several brain regions, primarily in the frontal and temporal lobes. The relationship between OAHI and verbal comprehension index was mediated through clustering coefficients in the right temporal pole of the superior temporal gyrus. CONCLUSIONS: OSA affects the development of white matter networks in children's brains. Besides, the mediating role of white matter network properties between the OAHI and the verbal comprehension index provided neuroimaging evidence of impaired cognitive function in children with OSA.

Gut microbiota moderates multimodal brain structure-function integration and behavioral cognition in growth hormone deficient children.

Background Previous brain studies of growth hormone deficiency (GHD) often used single-mode neuroimaging, missing the complexity captured by multimodal data. Growth hormone affects gut microbiota and metabolism in GHD. However, from a gut-brain axis perspective, the relationship between abnormal GHD brain development and microbiota alterations remains unclear. The ultimate goal is to uncover the manifestations underlying gut-brain axis (GBA) abnormalities in GHD and idiopathic short stature (ISS). Methods Participants included 23 GHD and 25 ISS children. The fusion independent component analysis was applied to integrat multimodal brain datas (high resolution structural, diffusion tensor, and resting state functional MRI) covering regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and White matter fractional anisotropy (FA). Gut microbiome diversity and metabolites were analyzed using 16S sequencing and proton nuclear magnetic resonance (1H-NMR). Associations between multimodal neuroimaging and cognition were assessed using moderation analysis. Results Six components (ReHo, ALFF, and FA) differed significantly between GHD and ISS patients, with three functional components linked to processing speed. GHD individuals showed higher levels of acetate in microbiota metabolism. Higher alpha diversity in GHD strengthened connections between ReHo-IC1, ReHo-IC5, ALFF-IC1, and processing speed, while increasing Agathobacter levels in ISS weakened the link between ALFF-IC1 and speech comprehension. Conclusions Our findings uncover differing brain structure and functional fusion in GHD, alongside microbiota metabolism of short-chain fatty acids. Additionally, microbiome influences connections between neuroimaging and cognition, offering insight into diverse gut-brain axis patterns in GHD and ISS, enhancing our understanding of the disease's pathophysiology and interventions.

Chiral Pyclen-Based Heptadentate Chelates as Highly Stable MRI Contrast Agents.

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.

Impact of different growth hormone levels on gut microbiota and metabolism in short stature.

BACKGROUND: Growth hormone deficiency(GHD) and idiopathic short stature(ISS) are the primary causes of short stature in children. Animal experiments have revealed a link between growth hormone(GH), gut microbiota and metabolism, however, limited information is available from human trials. METHODS: Fecal samples collected from GHD (n = 36), ISS (n = 32) and healthy control (HC) children(n = 16) were subjected to microbiome (16 S rRNA gene sequencing) and metabolome (nuclear magnetic resonance,NMR) analyses. RESULTS: GHD, ISS and HC exhibit distinct differences in beta diversity of gut microbiota.In addition, short stature (GHD and ISS) exhibit higher relative abundance of Prevotellaceae_NK3B31_group at genus level compared to HC, whereas Rodentibacter, Rothia, and Pelomonas showed lower abundance. Additionally,Fusobacterium_mortiferum was identified as the characteristic species of GHD. Moreover, glucose metabolism, pyruvate metabolism and pyrimidine metabolism might play significant roles for distinguishing between GHD and normal GH groups (ISS and HC). Furthermore, a disease prediction model based on differential bacteria and metabolites between GHD and ISS exhibited high diagnostic value. CONCLUSION: These findings highlight the characteristics of different GH levels on the gut microbiota and metabolism in children, providing novel perspectives for early diagnosis and prognostic treatment of short stature with abnormal GH levels. IMPACT: The key message of our study is to identify human-relevant gut microbiota and host metabolic patterns that are interfered with growth hormone levels, and to develop biomarker models to identify short stature associated with growth hormone deficiency. We used idiopathic short stature as a control group for growth hormone deficiency, complementing the absence of height as a factor in the existing literature. Our study ultimately hopes to shed new light on the diagnosis and treatment of short stature children associated with growth hormone deficiency.

A multicenter study of cervical cancer using quantitative diffusion-weighted imaging.

BACKGROUND: Parameters from diffusion-weighted imaging (DWI) have been increasingly used as imaging biomarkers for the diagnosis and monitoring of treatment responses in cancer. The consistency of DWI measurements across different centers remains uncertain, which limits the widespread use of quantitative DWI in clinical settings. PURPOSE: To investigate the consistency of quantitative metrics derived from DWI between different scanners in a multicenter clinical setting. MATERIAL AND METHODS: A total of 193 patients with cervical cancer from four scanners (MRI1, MRI2, MRI3, and MRI4) at three centers were included in this retrospective study. DWI data were processed using the mono-exponential and intravoxel incoherent motion (IVIM) model, yielding the following parameters: apparent diffusion coefficient (ADC); true diffusion coefficient (D); pseudo-diffusion coefficient (D*); perfusion fraction (f); and the product of f and D* (fD*). Various parameters of cervical cancer obtained from different scanners were compared. RESULTS: The parameters D and ADC derived from MRI1 and MRI2 were significantly different from those derived from MRI3 or MRI4 (P <0.01 for all comparisons). However, there was no significant difference in cervical cancer perfusion parameters (D* and fD*) between the different scanners (P >0.05). The P values of comparisons of all DWI parameters (D, D*, fD*, and ADC) between MRI3 and MRI4 (same vendor in different centers) for cervical cancer were all >0.05, except for f (P = 0.05). CONCLUSION: Scanners of the same model by the same vendor can yield close measurements of the ADC and IVIM parameters. The perfusion parameters showed higher consistency among the different scanners.

A Novel Score Based on Controlled Attenuation Parameter Accurately Predicts Hepatic Steatosis in Individuals With Metabolic Dysfunction Associated Steatotic Liver Disease: A Derivation and Independent Validation Study.

INTRODUCTION: In metabolic dysfunction-associated steatotic liver disease, the diagnostic efficacy of controlled attenuation parameter (CAP) was not very accurate in evaluating liver fat content. The aim of this study was to develop a score, based on CAP and conventional clinical parameters, to improve the diagnostic performance of CAP regarding liver fat content. METHODS: A total of 373 participants from 2 independent Chinese cohorts were included and divided into derivation (n = 191), internal validation (n = 75), and external validation (n = 107) cohorts. Based on the significant difference index between the 2 groups defined by the magnetic resonance imaging-proton density fat fraction (MRI-PDFF) in derivation cohort, the optimal model (CAP-BMI-AST score [CBST]) was screened by the number of parameters and the area under the receiver operating characteristic curve (AUROC). In the internal and external validation cohorts, the AUROC and corresponding 95% confidence intervals (CIs) were used to compare the diagnostic performance of CBST with that of CAP. RESULTS: We constructed the CBST = -14.27962 + 0.05431 × CAP - 0.14266 × body mass index + 0.01715 × aspartate aminotransferase. When MRI-PDFF was ≥20%, ≥10%, and ≥5%, the AUROC for CBST was 0.77 (95% CI 0.70-0.83), 0.89 (95% CI 0.83-0.94), and 0.93 (95% CI 0.88-0.98), which was higher than that for CAP respectively. In the internal validation cohort, the AUROC for CBST was 0.80 (95% CI 0.70-0.90), 0.95 (95% CI 0.91-1.00), and 0.98 (95% CI 0.94-1.00). The optimal thresholds of CBST were -0.5345, -1.7404, and -1.9959 for detecting MRI-PDFF ≥20%, ≥10%, and ≥5%, respectively. DISCUSSION: The CBST score can accurately evaluate liver steatosis and is superior to the CAP.

Chiral Gd-DOTA as a Versatile Platform for Hepatobiliary and Tumor Targeting MRI Contrast Agents.

The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.

Genome-wide association study of hippocampal blood-oxygen-level-dependent-cerebral blood flow correlation in Chinese Han population.

Correlation between blood-oxygen-level-dependent (BOLD) and cerebral blood flow (CBF) has been used as an index of neurovascular coupling. Hippocampal BOLD-CBF correlation is associated with neurocognition, and the reduced correlation is associated with neuropsychiatric disorders. We conducted the first genome-wide association study of the hippocampal BOLD-CBF correlation in 4,832 Chinese Han subjects. The hippocampal BOLD-CBF correlation had an estimated heritability of 16.2-23.9% and showed reliable genome-wide significant association with a locus at 3q28, in which many variants have been linked to neuroimaging and cerebrospinal fluid markers of Alzheimer's disease. Gene-based association analyses showed four significant genes (GMNC, CRTC2, DENND4B, and GATAD2B) and revealed enrichment for mast cell calcium mobilization, microglial cell proliferation, and ubiquitin-related proteolysis pathways that regulate different cellular components of the neurovascular unit. This is the first unbiased identification of the association of hippocampal BOLD-CBF correlation, providing fresh insights into the genetic architecture of hippocampal neurovascular coupling.

Longitudinal unraveling: The impact of recombinant human growth hormone on spontaneous brain activity in children with short stature-A resting-state fMRI study.

Recombinant human growth hormone (rhGH) is an approved method to improve the growth and ameliorate behavioral issues in children with short stature. However, the data concerning the effects of rhGH treatment on spontaneous brain activity remains unclear. This study included 35 children with short stature, categorized into two groups: the treated group (n = 14) and the untreated group (n = 21). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological assessments at baseline and at the end of a one-year follow-up. The rs-fMRI based amplitude of low frequency fluctuation (ALFF) analysis method was employed to assess spontaneous brain activity. Interaction effects between rhGH and time on ALFF were detected using a mixed-effects analysis. Additionally, Stepwise regression analysis was conducted to investigate the associations between ALFF values and significant clinical indicators. The treated group exhibited significant improvements in height, weight, insulin-like growth factor-1 (IGF-1) levels, insulin-like growth factor binding protein 3 (IGFBP-3) levels, and processing speed index (PSI) when reevaluated from baseline. The interaction effect of rhGH × time was evident in the right putamen (RPUT), where the ALFF value showed a significant increase following rhGH treatment, while also demonstrating a notable positive correlation with height. Moreover, The main effect of time was manifested as a significant decrease in the ALFF value of the left dorsolateral superior frontal gyrus (LSFG) within the untreated group during the follow-up period, concurrently displaying a positive correlation with age. In conclusion, rhGH treatment not only has a positive effect on the growth, cognition, and behavior of children with short stature, but also improves and normalizes spontaneous brain activity.

Covariation of preadult environmental exposures, adult brain imaging phenotypes, and adult personality traits.

Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity. One model linked greater stress and less support to weaker functional connectivity and activity in the default mode network, stronger activity in subcortical nuclei, greater thickness and volume in the occipital, parietal and temporal cortices, and lower agreeableness, consciousness and extraversion as well as higher neuroticism. The other model linked higher urbanicity and better socioeconomic status to stronger functional connectivity and activity in the sensorimotor network, smaller volume and surface area and weaker functional connectivity and activity in the medial prefrontal cortex, lower white matter integrity, and higher openness to experience. We also conducted mediation analyses to explore the potential bidirectional mediation relationships between adult brain imaging phenotypes and personality traits with the influence of preadult environmental exposures and found both environment-brain-personality and environment-personality-brain pathways. We finally performed moderated mediation analyses to test the potential interactions between macro- and microenvironmental exposures and found that one category of exposure moderated the mediation pathways of another category of exposure. These results improve our understanding of the effects of preadult environmental exposures on the adult brain and personality traits and may facilitate the design of targeted interventions to improve mental health by reducing the impact of adverse environmental exposures.

Disruption of brain regional homogeneity and functional connectivity in male NAFLD: evidence from a pilot resting-state fMRI study.

BACKGROUND: The neurophysiological mechanisms underlying cognitive deficits in non-alcoholic fatty liver disease (NAFLD) remain unknown. Cognitive changes may be caused by brain alterations in neural activity and functional connectivity (FC). AIM: This study aims to investigate the alterations between spontaneous brain neural activity and FC in male NAFLD patients and the relationship of neural activity with cognitive performance. METHODS: In this prospective study, 33 male pre-cirrhosis NAFLD subjects and 20 male controls matched for age, education level, and body mass index. All participants underwent resting-state functional magnetic resonance imaging scans and neuropsychological examinations. Regional homogeneity (ReHo) analysis was used to investigate the brain function in NAFLD, and regions with significantly altered ReHo were selected as seeds for subsequent FC analysis. Partial correlation analysis was used to assess the relationships between altered ReHo measures and cognitive performance indicators. RESULTS: Compared with the controls, the NAFLD patients showed increased ReHo in the opercular part of the right inferior frontal gyrus (IFGoperc) and decreased ReHo in the right middle frontal gyrus (MFG) and left superior parietal gyrus (SPG). The subsequent FC analysis showed increased FC between these regions (right IFGoperc, right MFG, and left SPG) and nodes of the default mode network (DMN) (such as left supraMarginal, left median cingulate and paracingulate gyri, left precuneus, orbital part of left medial frontal gyrus, and bilateral posterior cingulate gyrus). In addition, significant positive correlations were observed between NAFLD patients' clock drawing test scores and altered ReHo in prefrontal cortices (right IFGoperc and right MFG). CONCLUSION: Before developing cirrhosis, NAFLD patients showed altered neural activity in several brain regions and altered FC between the salience network and DMN. These alterations could potentially be a compensatory mechanism to maintain cognitive function in pre-cirrhosis NAFLD patients.

MRI-based radiomics model for distinguishing Stage I endometrial carcinoma from endometrial polyp: a multicenter study.

BACKGROUND: Patients with early endometrial carcinoma (EC) have a good prognosis, but it is difficult to distinguish from endometrial polyps (EPs). PURPOSE: To develop and assess magnetic resonance imaging (MRI)-based radiomics models for discriminating Stage I EC from EP in a multicenter setting. MATERIAL AND METHODS: Patients with Stage I EC (n = 202) and EP (n = 99) who underwent preoperative MRI scans were collected in three centers (seven devices). The images from devices 1-3 were utilized for training and validation, and the images from devices 4-7 were utilized for testing, leading to three models. They were evaluated by the area under the receiver operating characteristic curve (AUC) and metrics including accuracy, sensitivity, and specificity. Two radiologists evaluated the endometrial lesions and compared them with the three models. RESULTS: The AUCs of device 1, 2_ada, device 1, 3_ada, and device 2, 3_ada for discriminating Stage I EC from EP were 0.951, 0.912, and 0.896 for the training set, 0.755, 0.928, and 1.000 for the validation set, and 0.883, 0.956, and 0.878 for the external validation set, respectively. The specificity of the three models was higher, but the accuracy and sensitivity were lower than those of radiologists. CONCLUSION: Our MRI-based models showed good potential in differentiating Stage I EC from EP and had been validated in multiple centers. Their specificity was higher than that of radiologists and may be used for computer-aided diagnosis in the future to assist clinical diagnosis.

Cross-ancestry genome-wide association meta-analyses of hippocampal and subfield volumes.

The hippocampus is critical for memory and cognition and neuropsychiatric disorders, and its subfields differ in architecture and function. Genome-wide association studies on hippocampal and subfield volumes are mainly conducted in European populations; however, other ancestral populations are under-represented. Here we conduct cross-ancestry genome-wide association meta-analyses in 65,791 individuals for hippocampal volume and 38,977 for subfield volumes, including 7,009 individuals of East Asian ancestry. We identify 339 variant-trait associations at P < 1.13 × 10-9 for 44 hippocampal traits, including 23 new associations. Common genetic variants have similar effects on hippocampal traits across ancestries, although ancestry-specific associations exist. Cross-ancestry analysis improves the fine-mapping precision and the prediction performance of polygenic scores in under-represented populations. These genetic variants are enriched for Wnt signaling and neuron differentiation and affect cognition, emotion and neuropsychiatric disorders. These findings may provide insight into the genetic architectures of hippocampal and subfield volumes.

Rational Design of Gd-DOTA-Type Contrast Agents for Hepatobiliary Magnetic Resonance Imaging.

The safety risks of gadolinium (Gd3+)-based contrast agents (GBCAs) arise from their inevitable leakage of Gd3+, and the pursuit of more stable GBCAs for magnetic resonance imaging (MRI) has drawn increasing attention. Yet, Gd-EOB-DTPA and Gd-BOPTA are the only two authorized GBCAs for liver diagnosis in spite of their weak stability. In this study, one of the pendent arms of the most inert commercial Gd-DOTA was decorated with phenyl moieties, in which obvious enhancements of both kinetic and thermodynamic stability were achieved. Gd-L4 with a para-substituted OBn group was observed with ready hepatocellular uptake, with significant contrast provided in diagnosing orthotopic hepatocellular carcinoma, and its hepatobiliary secretion accounted for more than 50% of the injection dose in mice. In this study, Gd-L4 was found with comparable performance in liver MRI diagnosis to that of commercial Gd-EOB-DTPA and was thus deemed as an ideal candidate for further clinical applications.

The impact of pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities in young adults.

BACKGROUND: Urbanicity refers to the conditions that are particular to urban areas and is a growing environmental challenge that may affect hippocampus and neurocognition. This study aimed to investigate the effects of the average pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities as well as the sensitive age windows of the urbanicity effects. PARTICIPANTS AND METHODS: We included 5,390 CHIMGEN participants (3,538 females; age: 23.69 ± 2.26 years, range: 18-30 years). Pre-adulthood urbanicity of each participant was defined as the average value of annual night-time light (NL) or built-up% from age 0-18, which were extracted from remote-sensing satellite data based on annual residential coordinates of the participants. The hippocampal subfield volumes were calculated based on structural MRI and eight neurocognitive measures were assessed. The linear regression was applied to investigate the associations of pre-adulthood NL with hippocampal subfield volumes and neurocognitive abilities, mediation models were used to find the underlying pathways among urbanicity, hippocampus and neurocognition, and distributed lag models were used to identify sensitive age windows of urbanicity effect. RESULTS: Higher pre-adulthood NL was associated with greater volumes in the left (ß = 0.100, 95%CI: [0.075, 0.125]) and right (0.078, [0.052, 0.103]) fimbria and left subiculum body (0.045, [0.020, 0.070]) and better neurocognitive abilities in information processing speed (-0.212, [-0.240, -0.183]), working memory (0.085, [0.057, 0.114]), episodic memory (0.107, [0.080, 0.135]), and immediate (0.094, [0.065, 0.123]) and delayed (0.087, [0.058, 0.116]) visuospatial recall, and hippocampal subfield volumes and visuospatial memory showed bilateral mediations for the urbanicity effects. Urbanicity effects were greatest on the fimbria in preschool and adolescence, on visuospatial memory and information processing from childhood to adolescence and on working memory after 14 years. CONCLUSION: These findings improve our understanding of the impact of urbanicity on hippocampus and neurocognitive abilities and will benefit for designing more targeted intervention for neurocognitive improvement.

Development and Validation of a Combined MRI Radiomics, Imaging and Clinical Parameter-Based Machine Learning Model for Identifying Idiopathic Central Precocious Puberty in Girls.

BACKGROUND: Idiopathic central precocious puberty (ICPP) impairs child development, without early intervention. The current reference standard, the gonadotropin-releasing hormone stimulation test, is invasive which may hinder diagnosis and intervention. PURPOSE: To develop a model for accurate diagnosis of ICPP, by integrating pituitary MRI, carpal bone age, gonadal ultrasound, and basic clinical data. STUDY TYPE: Retrospective. POPULATION: A total of 492 girls with PP (185 with ICPP and 307 peripheral precocious puberty [PPP]) were randomly divided by reference standard into training (75%) and internal validation (25%) data. Fifty-one subjects (16 with ICPP, 35 with PPP) provided by another hospital as external validation. FIELD STRENGTH/SEQUENCE: T1-weighted (spin echo [SE], fast SE, cube) and T2-weighted (fast SE-fat suppression) imaging at 3.0 T or 1.5 T. ASSESSMENT: Radiomics features were extracted from pituitary MRI after manual segmentation. Carpal bone age, ovarian, follicle and uterine volumes and endometrium presence were assessed from radiographs and gonadal ultrasound. Four machine learning methods were developed: a pituitary MRI radiomics model, an integrated image model (with pituitary MRI, gonadal ultrasound and bone age), a basic clinical model (with age and sex hormone data), and an integrated multimodal model combining all features. STATISTICAL TESTS: Intraclass correlation coefficients were used to assess consistency of segmentation. Receiver operating characteristic (ROC) curves and the Delong tests were used to assess and compare the diagnostic performance of models. P < 0.05 was considered statistically significant. RESULTS: The area under of the ROC curve (AUC) of the pituitary MRI radiomics model, integrated image model, basic clinical model, and integrated multimodal model in the training data was 0.668, 0.809, 0.792, and 0.860. The integrated multimodal model had higher diagnostic efficacy (AUC of 0.862 and 0.866 for internal and external validation). CONCLUSION: The integrated multimodal model may have potential as an alternative clinical approach to diagnose ICPP. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Frequency-dependent alterations in regional homogeneity associated with puberty hormones in girls with central precocious puberty: A resting-state fMRI study.

OBJECTIVE: Central precocious puberty (CPP) patients are at significantly higher risk of emotional, mental, and behavioral disorders than those normal pubertal population. However, to date, the definite mechanism of how puberty hormones affect patients with CPP remains unclear. This regional homogeneity (ReHo) study aimed to explore the impact of premature hypothalamus-pituitary-gonadal (HPG) axis activation on brain function alteration in girls with CPP, meanwhile, to explore the relationship between gonadotropin and gonadal hormones levels, abnormal brain activity and cognitive function. METHODS: In this prospective study, a total of 85 girls who were suspected of having CPP were enrolled from the Child Healthcare Department of the Second Affiliated Hospital of Wenzhou Medical University Hospital from June 2018 to May 2021, including 41 CPP girls and 44 non-CPP girls. All participants collected the 0, 30, 60 min blood luteinizing hormone (LH), follicle-stimulating hormone (FSH), 0, 30 min estradiol (E2) and baseline cortisol (COR) and prolactin (PRL) concentrations after gonadotrophin-releasing hormone (GnRH) stimulating test. Resting-state magnetic resonance imaging (rs-MRI) scans were performed for all participants at 2 weeks before the GnRH stimulating test, voxel-wise ReHo was calculated in the standard frequency band (0.01-0.10 Hz), and in slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz). Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) was also collected. Independent-sample t-test or Mann-Whitney U test was used to compare the differences between two groups. The correlation analysis among abnormal brain regions, serum hormone levels and WISC-IV scores were performed by Spearman or partial correlation analysis. RESULTS: Compared to the non-CPP group, the CPP group showed higher regional homogeneity (ReHo) values in the left inferior temporal gyrus (ITG.L), as well as lower ReHo values in left superior temporal gyrus (STG.L), left superior occipital gyrus (SOG.L) and the right middle gyrus (MTG.R) in slow4.in slow5 frequency band, CPP group demonstrated decreased ReHo values in bilateral orbital part of superior frontal gyrus and medial superior frontal gyrus. LIMITATION: Due to the cross-section design of this study, further research is needed to explore the relationships between age, premature activation HPG axis and brain function changes. CONCLUSION: Our findings demonstrate that premature HPG axis activation and alterations in puberty hormones, may lead to changes in brain activity and cognitive function. This rs-fMRI study may enhance our understanding of the neuroendocrine mechanisms of mood, behavior, and cognitive function alterations in patients with CPP.