The characterization of metabolic changes in adipose tissues and muscles due to different exercise intensities by Dixon in healthy young men.

PURPOSE: To delineate the alterations in adipose and muscle tissue composition and functionality among healthy young men across varying exercise intensities, which help to elucidate the impact of exercise intensity on weight management and inform fitness planning. METHOD: 3D Dixon MRI scans were performed on the neck and supraclavicular area in 10 high-intensity exercises (HIE) athletes, 20 moderate intensity exercises (MIE) athletes and 19 low-intensity exercises non-athlete male controls (NCM). Twelve imaging parameters, including the total volume of muscle, white adipose tissue (WAT), brown adipose tissue (BAT), and the mean fat-water fraction (FWF) within these tissues. Additionally, ratios of BAT or WAT to total fat (BATr or WATr) and the proportions of muscle, BAT, or WAT to total tissue volume (Musp, BATp, and WATp) were calculated. Parameters were compared across groups and correlated with Body Mass Index (BMI), waistline, and hipline. RESULTS: The HIE group exhibited the highest total muscle (totalMUS) and brown adipose tissue (totalBAT) volumes among the three groups. Conversely, the NCM group had significantly higher fwfFAT and fwfBAT values. The MUSp was higher in the HIE and MIE groups compared to NCM, while the BATp and WATp were lower. Furthermore, the BATr in HIE and MIE groups were higher than NCM group while the WATr were lower. Significant linear relationships were observed between totalBAT, totalWAT, MUSp, BATr, fwfFAT, and BMI, waistline (P < 0.05) across all groups. CONCLUSIONS: MIE is sufficient for the purpose of weight control, While HIE helps to further increase the muscle mass. All three physical indexes were significantly associated with the image parameters, with waistline emerging as the most effective indicator for detecting metabolic changes across all groups.

Long-term effects of childhood single-parent family structure on brain connectivity and psychological well-being.

The high and increasing proportion of single-parent families is considered a risk factor associated with various childhood trauma experiences. Consequently, concerns have been raised regarding the potential long-term effects of the childhood single-parent family structure. In this study, we employed advanced magnetic resonance imaging technology, including morphometric similarity mapping, functional connectivity density, and network-based analysis, to investigate brain connectivity and behavioral differences among young adults who were raised in single-parent families. Our study also aimed to explore the relationship between these differences and childhood trauma experiences. The results showed that individuals who grew up in single-parent families exhibited higher levels of anxiety, depression, and harm-avoidant personality. The multimodal MRI analysis further showed differences in regional and network-based connectivity properties in the single-parent family group, including increased functional connectivity density in the left inferior parietal lobule, enhanced cortical structural connectivity between the left isthmus cingulate cortex and peri-calcarine cortex, and an increase in temporal functional connectivity. Moreover, elevated levels of anxiety and depression, along with heightened functional connectivity density in the left inferior parietal lobule and increased temporal functional connectivity, were found to be correlated with a greater number of childhood trauma experiences. Through analyzing multiple data patterns, our study provides objective neuropsychobiological evidence for the enduring impact of childhood single-parent family structure on psychiatric vulnerability in adulthood.

Dynamic effective connectivity among large-scale brain networks mediates risk of anxiety.

Anxiety is characterized by altered brain networks. Directional information flows among dynamic brain networks concerning neuropathogenesis of anxiety have not yet been investigated. The role of directional influences between networks in gene-environment effects on anxiety remains to be further elucidated. In a large community sample, this resting-state functional MRI study estimated dynamic effective connectivity among large-scale brain networks based on a sliding-window approach and Granger causality analysis, providing dynamic and directional information for signal transmission in networks. We first explored altered effective connectivity among networks related to anxiety in distinct connectivity states. Due to the potential gene-environment effects on brain and anxiety, we further performed mediation and moderated mediation analyses to investigate the role of altered effective connectivity networks in relationships between polygenic risk scores, childhood trauma, and anxiety. State and trait anxiety scores showed correlations with altered effective connectivity among extensive networks in distinct connectivity states (p < .05, uncorrected). Only in a more frequent and strongly connected state, there were significant correlations between altered effective connectivity networks and trait anxiety (PFDR <0.05). Furthermore, mediation and moderated mediation analyses showed that the effective connectivity networks played a mediating role in the effects of childhood trauma and polygenic risk on trait anxiety. State-dependent effective connectivity changes among brain networks were significantly related to trait anxiety, and mediated gene-environment effects on trait anxiety. Our work sheds novel light on the neurobiological mechanisms underlying anxiety, and provides new insights into early objective diagnosis and intervention evaluation.

Genetic influence on brain volume alterations related to self-reported childhood abuse.

As an important predictor of adulthood psychopathology, self-reported childhood abuse appears heritable and is associated with brain abnormalities. However, the specific genetic mechanisms behind these brain alterations remain largely unknown. This study recruited young adults who reported different degrees of childhood abuse from the community. In order to fully understand the influence of genes on brain changes related to self-reported childhood abuse, various experiments were conducted in this study. Firstly, volume changes of gray matter and white matter related to childhood abuse were investigated by using advanced magnetic resonance imaging techniques. After sequencing the whole exons, we further investigated the relationship between polygenic risk score, brain volume alterations, and childhood abuse score. Furthermore, transcription-neuroimaging association analysis was used to identify risk genes whose expressions were associated with brain volume alterations. The gray matter volumes of left caudate and superior parietal lobule, and white matter volumes of left cerebellum and right temporal lobe-basal ganglia region were significantly correlated with the childhood abuse score. More importantly, brain volume changes mediated the influence of polygenic risk on self-reported childhood abuse. Additionally, transcription-neuroimaging association analysis reported 63 risk genes whose expression levels were significantly associated with childhood abuse-related brain volume changes. These genes are involved in multiple biological processes, such as nerve development, synaptic transmission, and cell construction. Combining data from multiple perspectives, our work provides evidence of brain abnormalities associated with childhood abuse, and further indicates that polygene genetic risk and risk gene expression may affect the occurrence of childhood abuse by brain regulation, which provides insights into the molecularpathology and neuromechanism of childhood adversity. Paying attention to the physical and mental health of high-risk children may be a fundamental way to prevent childhood abuse and promote lifelong mental health.

Contribution of brain network connectivity in predicting effects of polygenic risk and childhood trauma on state-trait anxiety.

BACKGROUND: Anxiety is usually attributed to adverse environmental factors, but it is known as a polygenic inheritance disease. Gene-environment interactions on the occurrence and severity of anxiety are still unclear. The role of brain network connectivity in the gene-environment effects on anxiety has not been explored and may be key to understanding neuropathogenesis and guiding treatment. METHODS: This study recruited 177 young adults from the community that completed functional magnetic resonance imaging, Childhood Trauma Questionnaire (CTQ), state-trait anxiety scores, and whole exome sequencing. We calculated polygenic risk score (PRS) for anxiety and the sum score of CTQ, which are genetic and environmental factors that may affect anxiety, respectively. Abnormal brain network connectivity determined by the gene-environment effects and its associations with anxiety scores were then explored. RESULTS: Except for the main effect of PRS or CTQ on intra-network connectivity, significant interactions were found in intra-network connectivity of visual network, default mode network, self-reference network, and sensorimotor network. Moreover, altered network connectivity was related to anxious tendency. In particular, the effect of CTQ on trait anxiety was mediated by the disrupted sensorimotor network, accompanied by a significant direct effect. However, the PRS influence on anxiety was mainly mediated through sensorimotor network paths, which exceeded the direct influence and was moderated by childhood trauma levels. CONCLUSIONS: These network-specific functional changes related to individual gene-environment risks advance our understanding of psychiatric pathogenesis of anxiety and provide new insights for clinical intervention.

Experience-dependent associations between distinct subtypes of childhood trauma and brain function and architecture.

BACKGROUND: Childhood trauma can alter brain-development trajectories and lead to a greater risk of psychopathology developing in adulthood. For this reason, understanding experience-dependent brain abnormalities associated with different trauma subtypes is crucial for identifying developmental processes disrupted by unfavorable early environments and for proposing early intervention measures to reduce trauma's negative effects. METHODS: This study used multimodal magnetic resonance imaging (MRI) to explore the neural correlates of distinct subtypes of childhood trauma. We recruited a large community sample of young adults (mean age, 24.1, SD 1.9 years) who completed a Childhood Trauma Questionnaire, were given behavioral scores, and underwent multimodal MRI. To quantify brain changes, we used functional connectivity density (FCD) mapping based on whole brain analysis, regions of interest (ROI) analysis, and morphological measurements. Experience-dependent brain abnormalities were identified by multivariable linear regression. RESULTS: We found that diverse brain regions in the FCD mapping were significantly related to 4 trauma subtypes and belonged to different cognitive components used for various behaviors. Experience-related influences on functional circuits and brain morphology were observed in extensive regions, including the sensorimotor, cingulum, accumbens, insula, and frontal-parietal areas, as well as in regions within the default mode network. CONCLUSIONS: Identifying specific regions or systems may be a valid strategy for understanding the pathogenesis and development process of psychiatric disorders in people with different traumatic experiences and may facilitate better-targeted intervention strategies for maltreated children.

Differences in Wall Shear Stress Between High-Risk and Low-Risk Plaques in Patients With Moderate Carotid Artery Stenosis: A 4D Flow MRI Study.

This study aimed to evaluate the difference in wall shear stress (WSS) (axial, circumferential, and 3D) between high-risk and low-risk plaques in patients with moderate carotid artery stenosis and to identify which time points and directions play the dominant roles in determining the risk associated with plaques. Forty carotid arteries in 30 patients were examined in this study. All patients underwent high-resolution vessel wall (HRVW) imaging, diffusion-weighted imaging (DWI), and 4D flow MRI; HRVW imaging and DWI were used to separate low- and high-risk plaque. Twenty-four high-risk plaques and 16 low-risk plaques were enrolled. An independent-sample t-test was used to compare WSS between low- and high-risk plaques in the whole cardiac cycle and at 20 different time points in the cardiac cycle. The study found that patients with high-risk plaques had higher WSS than those with low-risk plaques throughout the entire cardiac cycle (p < 0.05), but the changes varied at the 20 different time points. The number of non-significant differences (p > 0.05) was less in diastole than in systole across different time points. The axial WSS values were higher than the circumferential WSS values; the difference in axial WSS values between high- and low-risk plaques was more significant than the difference in circumferential WSS, whereas 3D WSS values best reflected the difference between high-risk and low-risk plaques because they showed significant differences at every time point. In conclusion, increased WSS, especially during the diastolic period and in the axial direction, may be a signal of a high-risk plaque and may cause cerebrovascular events in patients with moderate carotid artery stenosis. Additionally, WSS can provide hemodynamic information and help clinicians make more appropriate decisions for patients with plaques.

Characterization of microenvironmental changes in the intervertebral discs of patients with chronic low back pain using multiparametric MRI contrasts extracted from Z-spectrum.

PURPOSE: Z-spectral MRI data were analyzed to produce multiparametric metabolic and microenvironmental contrasts for identifying intervertebral discs with/without pain symptom and sore pain. METHODS: Z-spectra data were collected from the lumbar discs of 26 patients with non-specific chronic low bck pain (CLBP) and 21 asymptomatic controls (AC) with a chemical exchange saturation transfer (CEST). Data were fitted to quantify the CEST effects from glycosaminoglycan, amide proton transfer (APT), nuclear Overhauser enhancement (NOE), semi-solid magnetization transfer contrast effects, and the direct saturation of water. Multiparametric maps were computed from the fitted peak amplitudes, and the average values were calculated from all five lumber discs. Those parameters were compared between the CLBP and AC groups and between the subgroups with and without (Nsore) sore pain. RESULTS: The discs in symptomatic patients have lower water content, collagen-bound water and collagen than the discs in AC (P < 0.05). Additionally, Z-sepctral MRI indicated that the discs in the sore subgroup had less water, collagen-bound water and collagen, and likely lower pH compared to the Nsore subgroup (P < 0.05). Lower pH as measured with reduced APT and NOE effects may be an important pathological factor causing sore pain of the back. CONCLUSION: Z-spectral MRI with its multiparametric metabolic and microenvironmental contrasts has been demonstrated to identify discs with and without pain symptom or sore pain, providing more important information of CLBP.

Default Mode Network Alterations Induced by Childhood Trauma Correlate With Emotional Function and SLC6A4 Expression.

As one of the most studied resting-state functional networks, default mode network (DMN) is related to pathogenesis in neuropsychiatry. However, it is unclear whether changed DMN connectivity is transformed into vulnerability to psychopathology in adults who experienced childhood trauma, and what is the underlying genetic basis. Exploring the effect of DMN on environment-behavior pathway and the related genetic modulation mechanisms could further a better understanding of psychiatric pathogenesis and early prevention strategy. Two hundred and sixteen young adults with varying levels of early trauma indexed by the Childhood Trauma Questionnaire (CTQ) were recruited from the community. Static and dynamic functional connectivity based on DMN seeds and independent component analysis based on whole-brain voxels were combined to explore DMN alterations related to the CTQ score. Relationships between CTQ score, DMN connectivity, and behavioral scores were confirmed by mediation effect analysis. Imaging-genomic correlations were further used to identify risk genes whose expression was associated with the DMN changes. Dysregulated DMN connectivity was found both in seed-level and voxel-level analyses. Moreover, the functional disruption in the left temporal pole, right parahippocampal gyrus, and frontoparietal connectivity mediated the effects of childhood trauma on emotional behavior. The serotonin transporter gene was identified and might suggest the biological underpinning of the relationship between childhood trauma, DMN, and emotion regulation. Changed DMN may be useful as biomarkers to provide a powerful supplement to psychological evaluation related to childhood trauma. Combined with gene expression profiles, our findings advance a more integrative understanding of DMN alterations induced by childhood trauma, and clarify its implications for psychiatric pathogenesis and early prevention strategies.

Effects of childhood trauma experience and BDNF Val66Met polymorphism on brain plasticity relate to emotion regulation.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may modulate the link between childhood trauma experience and psychopathology by altering trophic signaling on neuroplasticity. However, few multimodal magnetic resonance imaging (MRI) researches have investigated this gene-environment interaction on both structural and functional plasticity, thereby advancing knowledge about the etiology, prevention, and customized therapeutic directions of mental disease in individuals with childhood trauma experience. We recruited a large non-clinical sample of young adults that completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal MRI scans, and genotyping. Morphometric similarity network (MSN) and independent component analysis were adopted to quantify brain structural and functional changes. Gene-environment-brain-behavior relationships were identified by multiple regression and mediation effect analysis. CTQ score was positively associated with depression and anxiety scores. We found interactions on MSN in sensorimotor, temporal, and orbitofrontal cortex. For intra-network connectivity, significant interaction was noted in clusters within sensorimotor network. For inter-network connectivity, connectivity between dorsal attention network and salience network showed an interactive effect. For mean connectivity strength of each network, we found a main effect of CTQ score on self-reference network that was an outstanding mediator supporting the relationship between CTQ score and anxiety. Our findings demonstrate that childhood trauma and the BDNF Val66Met polymorphism are associated with brain plasticity involving emotion regulation, structurally and functionally, which may contribute to understanding psychotic mechanisms and predicting differential susceptibility. Imaging genetics may be useful as biomarkers to provide early assessment and guide cognitive interventions to avoid or decrease the risk of developing psychopathology.

Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study.

Childhood adversity may act as a stressor to produce a cascade of neurobiological effects that irreversibly alter neural development, setting the stage for developing psychopathology in adulthood. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has received much attention as a candidate gene associated with environmental adversity, modifying risk for psychopathology. In this study, we aim to see how gene × brain × environment models give a more integrative understanding of brain modifications that contribute to predicting psychopathology related to childhood adversity. A large nonclinical sample of young adults completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal magnetic resonance imaging (MRI) scans, and genotyping. We utilized graph-based connectivity analysis in morphometric similarity mapping and resting-state functional MRI to investigate brain alterations. Relationships among COMT genotypes, CTQ score, imaging phenotypes, and behavioral scores were identified by multiple regression and mediation effect analysis. Significant main effect of CTQ score was found in anatomic connectivity of orbitofrontal cortex that was an outstanding mediator supporting the relationship between CTQ score and anxiety/harm-avoiding personality. We also noted the main effect of childhood trauma on reorganization of functional connectivity within the language network. Additionally, we found genotype × CTQ score interactions on functional connectivity of the right frontoparietal network as well as anatomic connectivity of motor and limbic regions. Our data demonstrate childhood adversity and COMT genotypes are associated with abnormal brain connectivity, structurally and functionally. Early identification of individuals at risk, assessment of brain abnormality, and cognitive interventions may help to prevent or limit negative outcomes.

A risk predictor of restenosis after superficial femoral artery stent implantation: relevance of mean platelet volume.

BACKGROUND: To investigate the relationship between an increase in the pre- and post-operative mean platelet volume (MPV) and superficial femoral artery in-stent restenosis (ISR) rate. METHODS AND RESULTS: We recruited patients that underwent superficial femoral artery stenting for lower extremity arteriosclerosis obliterans at our hospital from March 2015 to March 2018. All patients gave venous blood three days before and following implantation. Doppler ultrasound, computed tomography angiography or digital subtraction angiography were used for regular follow-up examination. Logistic regression was used to identify predictors of ISR after superficial femoral artery stenting. We enrolled 173 patients, of which 34 (19.6%) were determined as having ISR for a mean of 8.9 ± 2.7 months (3-12 months). Neutrophil count, neutrophil ratio, lymphocyte ratio and platelet count pre-implantation, and platelet count and MPV after stent implantation, and the pre- and post-operative mean platelet volume difference (MPVD) and mean platelet volume difference ratio (MPVDR) were all statistically different when comparing the ISR and non-restenosis groups (p < 0.05). A positive correlation was found for post-operative MPV and presence of ISR (r = 0.58; P < 0.001). A MPVD not less than 1.5 fL was associated with an odds ratio of 9.17 (95% CI [3.76 to 22.35]; P < 0.001) for presence of ISR. A MPVDR of not less than 17.9% was associated with an odds ratio of 7.68 (95% CI [3.19 to 18.49]; P < 0.001) for occurrence of ISR. CONCLUSIONS: An increase in pre- and post-operative MPV was correlated with the occurrence of superficial femoral artery ISR.

Characterization of brown adipose tissue (BAT) in polycystic ovary syndrome (PCOS) patients by Z-Spectral Imaging (ZSI).

PURPOSE: To characterize brown adipose tissue (BAT) in polycystic ovary syndrome (PCOS) patients in comparison to healthy subjects using Z-spectral imaging (ZSI). METHOD: ZSI data were collected on 19 normal control females (NCF), 17 males (NCM), and 13 PCOS patients. By fitting to multiple Lorentzian functions, ZSI provides fat-water fraction (FWF) of tissue in the supraclavicular area that can be used to differentiate between white adipose tissue (WAT), BAT, and muscle. The fraction of BAT over the total fat depot (BATf) and the average FWF in BAT or FWF(BAT) were then computed, reflecting relative BAT mass and BAT metabolism respectively. The parameters were compared among the three groups, and the correlations to Body Mass Index (BMI) were also quantified. RESULTS: There was an inverse correlation between BATf and BMI in normal subjects. The BATf of the PCOS group was significantly smaller than the NCF (P < 0.001). On the other hand, FWF(BAT) correlated linearly with BMI in healthy subjects. The PCOS group had higher FWF(BAT) than the NCF group (P < 0.001). CONCLUSIONS: Normal subjects with higher BMI show less BATf and have increased FWF(BAT), indicating relatively higher level of metabolic passive WAT depot and relatively reduced metabolism in their BAT depots. PCOS patients have the least BATf and the highest FWF(BAT), suggesting decreased BAT mass and function in PCOS. Novel imaging technique with ZSI for the characterization of BAT mass and function in PCOS may help to monitor treatment responses of PCOS therapies.

Characterization of the microstructure of the intervertebral disc in patients with chronic low back pain by diffusion kurtosis imaging.

PURPOSE: Multivariate analysis of T2-weighted signal, diffusion ADC, and DKI parameters and tractography were used to differentiate chronic non-specific low back pain (CLBP) patients and asymptomatic controls (AC). METHODS: A total of 30 patients with CLBP and 23 AC underwent diffusion kurtosis imaging (DKI) of lumbar spine with a 3T MRI scanner to get the ADC values and seven parameters of DKI in the nucleus pulposus (NP) of the intervertebral disc. The tractography and the tract-related parameters as other parameters were also generated to indicate the intactness of annulus fibrosus (AF). T2-grades of the discs were also quantified based on an eight-grade degeneration grading system. ADC and T2-grades were compared with DKI parameters for the differentiation of CLBP and AC groups. RESULTS: There was no difference in the T2 grades, ADC value, and multiple parameters in DKI of NP between CLBP and AC groups (P > 0.05). The average FA values in NP in AC group were found significantly higher than in the CLBP group (P < 0.05). The scores for the intactness of AF of the intervertebral discs were significantly different in CLBP and AC groups, with 90% of sensitivity and 70% specificity (P < 0.05). Additionally, there were significantly differences in the length and volume values of the AF in CLBP and AC groups (P < 0.05). CONCLUSION: DKI is a good noninvasive method, and it might help to differentiate CLBP from AC. Particularly, the continuation of DKI tractography reflects the presence of annulus fibrosus fissures, an important character in the generation of the low back pain. These slides can be retrieved under Electronic Supplementary Material.

Diffusion kurtosis imaging provides quantitative assessment of the microstructure changes of disc degeneration: an in vivo experimental study.

OBJECTIVE: Our aim was to assess the microstructural changes of intervertebral disc degeneration induced by annulus needle puncture in rats by diffusion kurtosis imaging (DKI). METHODS: Eighteen rats (36 discs) were punctured percutaneously at the intervertebral disc between C6/7, C7/8 (C-coccygeal vertebrae) with a 21-gauge needle. The rats were divided into six groups according to the time after the puncture: 3 h, 48 h, 3 days, 7 days, 10 days and 14 days. There were six discs in three rats in the control group. The rats' tail was imaged at 3T MRI with T2-weighted and diffusion-weighted and diffusion kurtosis imaging (DWI)/DKI sequences. The discs were categorized using a five-grade degeneration system based on the T2 images. The height of the discs and the parameters in DWI/DKI were measured and compared between the different time points. The histological images were also obtained from the discs. RESULTS: The histological study revealed that the discs in the rat of the punctured groups were degenerated. The T2 grades of different groups presented an increasing trend from 7 to 10 days after puncture (R2 = 0.9424, P < 0.001), while the DWI/DKI parameters changes were consistent with the histological changes at the different time points and showed significant differences between the different groups (P < 0.05). CONCLUSIONS: DKI provides quantitative assessment of the microstructure changes of disc degeneration, and it is a non-invasive method. The DKI multi-parameter analysis is sensitive to discs changes caused by puncture. These slides can be retrieved under Electronic Supplementary Material.

The study of the intervertebral disc microstructure in matured rats with diffusion kurtosis imaging.

OBJECTIVES: The aim of this study was to use DKI to detect the microstructural change of the discs in matured normal rats. METHODS: Total 24 normal SD rats (12 males/12 females) underwent DWI/DKI and T2 sequences with a 3T MRI scanner to get the values of ADC, FA, MD, Da, Dr, MK, Ka and Kr. The discs were categorized using a five-grade degeneration grading system in the T2-images. The height of the discs and the parameters in DWI/DKI were measured to compare between the different grades and sexes. The histological images and the images of fiber tracking were also done in the discs. RESULTS: There were 30 Grade 1 and 18 Grade 2 in the discs. Compared with Grade 1, decreased ADC, increased FA and MK values were observed in Grade 2 (P<0.05). By the ROC analysis of grades of the discs, there was low diagnostic accuracy in ADC value, while FA and MK showed higher accuracy. In Grade 1, there were lower ADC value, lower Dr, higher MK, Ka and Kr in male's group than them in female's group. There were no differences in the parameters except the ADC value in the two sexes in Grade 2. The different microstructure of the normal discs in the male and female rats had been proved by the histological images and the images of fiber tracking. CONCLUSION: DKI is a noninvasive and sustainable means to test the changes of intervertebral discs. The discs in Grade 2 were also found in the normal matured SD rat tails. The assessment of the grade of the discs in T2-images should be done before the experimental management. There was microstructural difference in the nucleus pulposus in the discs in Grade 1 and 2. FA and MK showed higher diagnostic accuracy. The laboratory rats should be the same sex because the microstructure of the normal discs weren't the same.