Altered intersubject functional variability of brain white-matter in major depressive disorder and its association with gene expression profiles.

Major depressive disorder (MDD) is a clinically heterogeneous disorder. Its mechanism is still unknown. Although the altered intersubject variability in functional connectivity (IVFC) within gray-matter has been reported in MDD, the alterations to IVFC within white-matter (WM-IVFC) remain unknown. Based on the resting-state functional MRI data of discovery (145 MDD patients and 119 healthy controls [HCs]) and validation cohorts (54 MDD patients, and 78 HCs), we compared the WM-IVFC between the two groups. We further assessed the meta-analytic cognitive functions related to the alterations. The discriminant WM-IVFC values were used to classify MDD patients and predict clinical symptoms in patients. In combination with the Allen Human Brain Atlas, transcriptome-neuroimaging association analyses were further conducted to investigate gene expression profiles associated with WM-IVFC alterations in MDD, followed by a set of gene functional characteristic analyses. We found extensive WM-IVFC alterations in MDD compared to HCs, which were associated with multiple behavioral domains, including sensorimotor processes and higher-order functions. The discriminant WM-IVFC could not only effectively distinguish MDD patients from HCs with an area under curve ranging from 0.889 to 0.901 across three classifiers, but significantly predict depression severity (r = 0.575, p = 0.002) and suicide risk (r = 0.384, p = 0.040) in patients. Furthermore, the variability-related genes were enriched for synapse, neuronal system, and ion channel, and predominantly expressed in excitatory and inhibitory neurons. Our results obtained good reproducibility in the validation cohort. These findings revealed intersubject functional variability changes of brain WM in MDD and its linkage with gene expression profiles, providing potential implications for understanding the high clinical heterogeneity of MDD.

Hippocampal Subregions Volume and Texture for the Diagnosis of Mild Cognitive Impairment.

The aim was to examine the diagnostic efficacy of hippocampal subregions volume and texture in differentiating amnestic mild cognitive impairment (MCI) from normal aging changes. Ninety MCI subjects and eighty-eight well-matched healthy controls (HCs) were selected. Twelve hippocampal subregions volume and texture features were extracted using Freesurfer and MaZda based on T1 weighted MRI. Then, two-sample t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were developed to select a subset of the original features. Support vector machine (SVM) was used to perform the classification task and the area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the diagnostic efficacy of the model. The volume features with high discriminative power were mainly located in the bilateral CA1 and CA4, while texture feature were gray-level non-uniformity, run length non-uniformity and fraction. Our model based on hippocampal subregions volume and texture features achieved better classification performance with an AUC of 0.90. The volume and texture of hippocampal subregions can be utilized for the diagnosis of MCI. Moreover, we found that the features that contributed most to the model were mainly textural features, followed by volume. These results may guide future studies using structural scans to classify patients with MCI.

GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First-Episode and Early-Onset Major Depression Disorder.

BACKGROUND: Glutamate dysregulation is one of the key pathogenic mechanisms of major depressive disorder (MDD), and glutamate chemical exchange saturation transfer (GluCEST) has been used for glutamate measurement in some brain diseases but rarely in depression. PURPOSE: To investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes. STUDY TYPE: Cross-sectional. SUBJECTS: Thirty-two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years). FIELD STRENGTH/SEQUENCE: 3.0 T; magnetization prepared rapid gradient echo (MPRAGE) for three-dimensional T1-weighted images, two-dimensional turbo spin echo GluCEST, and multivoxel chemical shift imaging (CSI) for proton magnetic resonance spectroscopy (1 H MRS). ASSESSMENT: GluCEST data were quantified by magnetization transfer ratio asymmetry (MTRasym ) analysis and assessed by the relative concentration of 1 H MRS-measured glutamate. FreeSurfer was used for hippocampus segmentation. STATISTICAL TESTS: The independent sample t test, Mann-Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant. RESULTS: In the left hippocampus, GluCEST values were significantly decreased in MDD (2.00 ± 1.08 [MDD] vs. 2.62 ± 1.41 [HCs]) and showed a significantly positive correlation with Glx/Cr (r = 0.37). GluCEST values were significantly positively correlated with the volumes of CA1 (r = 0.40), subiculum (r = 0.40) in the left hippocampus and CA1 (r = 0.51), molecular_layer_HP (r = 0.50), GC-ML-DG (r = 0.42), CA3 (r = 0.44), CA4 (r = 0.44), hippocampus-amygdala-transition-area (r = 0.46), and the whole hippocampus (r = 0.47) in the right hippocampus. Hamilton Depression Rating Scale scores showed significantly negative correlations with the volumes of the left presubiculum (r = -0.40), left parasubiculum (r = -0.47), and right presubiculum (r = -0.41). DATA CONCLUSION: GluCEST can be used to measure glutamate changes and help to understand the mechanism of hippocampal volume loss in MDD. Hippocampal volume changes are associated with disease severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Diagnosis of Major Depressive Disorder Using Machine Learning Based on Multisequence MRI Neuroimaging Features.

BACKGROUND: Previous studies have found qualitative structural and functional brain changes in major depressive disorder (MDD) patients. However, most studies ignored the complementarity of multisequence MRI neuroimaging features and cannot determine accurate biomarkers. PURPOSE: To evaluate machine-learning models combined with multisequence MRI neuroimaging features to diagnose patients with MDD. STUDY TYPE: Prospective. SUBJECTS: A training cohort including 111 patients and 90 healthy controls (HCs) and a test cohort including 28 patients and 22 HCs. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted imaging, resting-state functional MRI with echo-planar sequence, and single-shot echo-planar diffusion tensor imaging. ASSESSMENT: Recruitment and integration were used to reflect the dynamic changes of functional networks, while gray matter volume and fractional anisotropy were used to reflect the changes in the morphological and anatomical network. We then fused features with significant differences in functional, morphological, and anatomical networks to evaluate a random forest (RF) classifier to diagnose patients with MDD. Furthermore, a support vector machine (SVM) classifier was used to verify the stability of neuroimaging features. Linear regression analyses were conducted to investigate the relationships among multisequence neuroimaging features and the suicide risk of patients. STATISTICAL TESTS: The comparison of functional network attributes between patients and controls by two-sample t-test. Network-based statistical analysis was used to identify structural and anatomical connectivity changes between MDD and HCs. The performance of the model was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The performance of the RF model integrating multisequence neuroimaging features in the diagnosis of depression was significantly improved, with an AUC of 93.6%. In addition, we found that multisequence neuroimaging features could accurately predict suicide risk in patients with MDD (r = 0.691). DATA CONCLUSION: The RF model fusing functional, morphological, and anatomical network features performed well in diagnosing patients with MDD and provided important insights into the pathological mechanisms of MDD. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Classification of Major Depressive Disorder Based on Integrated Temporal and Spatial Functional MRI Variability Features of Dynamic Brain Network.

BACKGROUND: Characterization of the dynamics of functional brain network has gained increased attention in the study of depression. However, most studies have focused on single temporal dimension, while ignoring spatial dimensional information, hampering the discovery of validated biomarkers for depression. PURPOSE: To integrate temporal and spatial functional MRI variability features of dynamic brain network in machine-learning techniques to distinguish patients with major depressive disorder (MDD) from healthy controls (HCs). STUDY TYPE: Prospective. POPULATION: A discovery cohort including 119 patients and 106 HCs and an external validation cohort including 126 patients and 124 HCs from Rest-meta-MDD consortium. FIELD STRENGTH/SEQUENCE: A 3.0 T/resting-state functional MRI using the gradient echo sequence. ASSESSMENT: A random forest (RF) model integrating temporal and spatial variability features of dynamic brain networks with separate feature selection method (MSFS ) was implemented for MDD classification. Its performance was compared with three RF models that used: temporal variability features (MTVF ), spatial variability features (MSVF ), and integrated temporal and spatial variability features with hybrid feature selection method (MHFS ). A linear regression model based on MSFS was further established to assess MDD symptom severity, with prediction performance evaluated by the correlations between true and predicted scores. STATISTICAL TESTS: Receiver operating characteristic analyses with the area under the curve (AUC) were used to evaluate models' performance. Pearson's correlation was used to assess relationship of predicted scores and true scores. P < 0.05 was considered statistically significant. RESULTS: The model with MSFS achieved the best performance, with AUCs of 0.946 and 0.834 in the discovery and validation cohort, respectively. Additionally, altered temporal and spatial variability could significantly predict the severity of depression (r = 0.640) and anxiety (r = 0.616) in MDD. DATA CONCLUSION: Integration of temporal and spatial variability features provides potential assistance for clinical diagnosis and symptom prediction of MDD. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Individual-level morphological hippocampal networks in patients with Alzheimer's disease.

In patients with Alzheimer's Disease (AD), the hippocampal network has been extensively investigated in previous studies; however, little is known about the morphological network associated with the hippocampus in the AD patients. A total of 68 patients with AD and another 68 gender and age matched healthy subjects were studied. Individual-level morphological hippocampal networks were constructed based on volume and texture features extracted from MRI to study the connections between bilateral hippocampus and 11 other subcortical gray matter structures. The relationship between morphological connections and Mini-Mental State Examination (MMSE) scores was also studied. Connections between bilateral hippocampus and bilateral thalamus, bilateral putamen were significant differences between the AD patients and controls (p < 0.05). There were significantly different in bilateral hippocampal connectivity, and for the left hippocampus, the connection to the right caudate were found to be statistically significant. The morphological connections between left hippocampus and bilateral thalamus (left: R = 0.371, p < 0.001; right: R = 0.411, p < 0.001), bilateral putamen (left: R = 0.383, p < 0.001; right: R = 0.348, p < 0.001), right hippocampus and bilateral thalamus (left: R = 0.370, p < 0.001; right: R = 0.387, p < 0.001), left putamen (R = 0.377, p < 0.001) were significantly positively correlated with the MMSE scores. Similar patterns were observed for left and right hippocampal connectivity and the connections highly associated with MMSE scores were also within the abnormal connections in AD patients.

[A new method for classification of Alzheimer's disease combined with structural magnetic resonance imaging texture features].

In this paper, a new method for the classification of Alzheimer's disease (AD) using multi-feature combination of structural magnetic resonance imaging is proposed. Firstly, hippocampal segmentation and cortical thickness and volume measurement were performed using FreeSurfer software. Then, histogram, gradient, length of gray level co-occurrence matrix and run-length matrix were used to extract the three-dimensional (3D) texture features of the hippocampus, and the parameters with significant differences between AD, MCI and NC groups were selected for correlation study with MMSE score. Finally, AD, MCI and NC are classified and identified by the extreme learning machine. The results show that texture features can provide better classification results than volume features on both left and right sides. The feature parameters with complementary texture, volume and cortical thickness had higher classification recognition rate, and the classification accuracy of the right side (100%) was higher than that of the left side (91.667%). The results showed that 3D texture analysis could reflect the pathological changes of hippocampal structures of AD and MCI patients, and combined with multi-feature analysis, it could better reflect the essential differences between AD and MCI cognitive impairment, which was more conducive to clinical differential diagnosis.

Develop and Validate a Nomogram Combining Contrast-Enhanced Spectral Mammography Deep Learning with Clinical-Pathological Features to Predict Neoadjuvant Chemotherapy Response in Patients with ER-Positive/HER2-Negative Breast Cancer.

RATIONALE AND OBJECTIVES: To develop and validate a nomogram that combines contrast-enhanced spectral mammography (CESM) deep learning with clinical-pathological features to predict neoadjuvant chemotherapy (NAC) response (either low Miller Payne (MP-L) grades 1-2 or high MP (MP-H) grades 3-5) in patients with ER-positive/HER2-negative breast cancer. MATERIALS AND METHODS: In this retrospective study, 265 breast cancer patients were randomly allocated into training and test sets (used for models training and testing, respectively) at a 4:1 ratio. Deep learning models, based on the pre-trained ResNet34 model and initially fine-tuned for identifying breast cancer, were trained using low-energy and subtracted CESM images. The predicted results served as deep learning features for the deep learning-based model. Clinical-pathological features, including age, progesterone receptor (PR) status, estrogen receptor (ER) status, Ki67 expression levels, and neutrophil-to-lymphocyte ratio, were used for the clinical model. All these features contributed to the nomogram. Feature selection was performed through univariate analysis. Logistic regression models were developed and chosen using a stepwise selection method. The deep learning-based and clinical models, along with the nomogram, were evaluated using precision-recall curves, receiver operating characteristic (ROC) curves, specificity, recall, accuracy, negative predictive value, positive predictive value (PPV), balanced accuracy, F1-score, and decision curve analysis (DCA). RESULTS: The nomogram demonstrated considerable predictive ability, with higher area under the ROC curve (0.95, P < 0.05), accuracy (0.94), specificity (0.98), PPV (0.89), and precision (0.89) compared to the deep learning-based and clinical models. In DCA, the nomogram showed substantial clinical value in assisting breast cancer treatment decisions, exhibiting a higher net benefit than the other models. CONCLUSION: The nomogram, integrating CESM deep learning with clinical-pathological features, proved valuable for predicting NAC response in patients with ER-positive/HER2-negative breast cancer. Nomogram outperformed deep learning-based and clinical models.

Altered dynamic and static brain activity and functional connectivity in COVID-19 patients: a preliminary study.

This study aimed to investigate the effects of COVID-19 on brain functional activity through resting-state functional MRI (rs-fMRI). fMRI scans were conducted on a cohort of 42 confirmed COVID-19-positive patients and 46 healthy controls (HCs) to assess brain functional activity. A combination of dynamic and static amplitude of low-frequency fluctuations (dALFF/sALFF) and dynamic and static functional connectivity (dFC/sFC) was used for evaluation. Abnormal brain regions identified were then used as feature inputs in the model to evaluate support vector machine (SVM) capability in recognizing COVID-19 patients. Moreover, the random forest (RF) model was employed to verify the stability of SVM diagnoses for COVID-19 patients. Compared to HCs, COVID-19 patients exhibited a decrease in sALFF in the right lingual gyrus and the left medial occipital gyrus and an increase in dALFF in the right straight gyrus. Moreover, there was a decline in sFC between both lingual gyri and the right superior occipital gyrus and a reduction in dFC with the precentral gyrus. The dynamic and static combined ALFF and FC could distinguish between COVID-19 patients and the HCs with an accuracy of 0.885, a specificity of 0.818, a sensitivity of 0.933 and an area under the curve of 0.909. The combination of dynamic and static ALFF and FC can provide information for detecting brain functional abnormalities in COVID-19 patients.

Multiregional dynamic contrast-enhanced MRI-based integrated system for predicting pathological complete response of axillary lymph node to neoadjuvant chemotherapy in breast cancer: multicentre study.

BACKGROUND: The accurate evaluation of axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) in breast cancer holds great value. This study aimed to develop an artificial intelligence system utilising multiregional dynamic contrast-enhanced MRI (DCE-MRI) and clinicopathological characteristics to predict axillary pathological complete response (pCR) after NAC in breast cancer. METHODS: This study included retrospective and prospective datasets from six medical centres in China between May 2018 and December 2023. A fully automated integrated system based on deep learning (FAIS-DL) was built to perform tumour and ALN segmentation and axillary pCR prediction sequentially. The predictive performance of FAIS-DL was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RNA sequencing analysis were conducted on 45 patients to explore the biological basis of FAIS-DL. FINDINGS: 1145 patients (mean age, 50 years ±10 [SD]) were evaluated. Among these patients, 506 were in the training and validation sets (axillary pCR rate of 40.3%), 127 in the internal test set (axillary pCR rate of 37.8%), 414 in the pooled external test set (axillary pCR rate of 48.8%), and 98 in the prospective test set (axillary pCR rate of 43.9%). For predicting axillary pCR, FAIS-DL achieved AUCs of 0.95, 0.93, and 0.94 in the internal test set, pooled external test set, and prospective test set, respectively, which were also significantly higher than those of the clinical model and deep learning models based on single-regional DCE-MRI (all P < 0.05, DeLong test). In the pooled external and prospective test sets, the FAIS-DL decreased the unnecessary axillary lymph node dissection rate from 47.9% to 6.8%, and increased the benefit rate from 52.2% to 86.5%. RNA sequencing analysis revealed that high FAIS-DL scores were associated with the upregulation of immune-mediated genes and pathways. INTERPRETATION: FAIS-DL has demonstrated satisfactory performance in predicting axillary pCR, which may guide the formulation of personalised treatment regimens for patients with breast cancer in clinical practice. FUNDING: This study was supported by the National Natural Science Foundation of China (82371933), National Natural Science Foundation of Shandong Province of China (ZR2021MH120), Mount Taishan Scholars and Young Experts Program (tsqn202211378), Key Projects of China Medicine Education Association (2022KTM030), China Postdoctoral Science Foundation (314730), and Beijing Postdoctoral Research Foundation (2023-zz-012).

Regional structural-functional connectivity coupling in major depressive disorder is associated with neurotransmitter and genetic profiles.

BACKGROUND: Abnormalities in structural-functional connectivity (SC-FC) coupling have been identified globally in patients with major depressive disorder (MDD). However, investigations have neglected the variability and hierarchical distribution of these abnormalities across different brain regions. Furthermore, the biological mechanisms underlying regional SC-FC coupling patterns are not well understood. METHODS: We enrolled 182 patients with MDD and 157 healthy control (HC) subjects, quantifying the intergroup differences in regional SC-FC coupling. The extreme gradient boosting (XGBoost), support vector machines (SVM) and random forest (RF) models were constructed to assess the potential of SC-FC coupling as biomarkers for MDD diagnosis and symptom prediction. Then, we examined the link between changes in regional SC-FC coupling in patients with MDD, neurotransmitter distributions, and gene expression. RESULTS: We observed increased regional SC-FC coupling in default mode network (T = 3.233) and decreased coupling in frontoparietal network (T = -3.471) in MDD relative to HC. XGBoost (AUC = 0.853), SVM (AUC = 0.832) and RF (p < 0.05) models exhibited good prediction performance. The alterations in regional SC-FC coupling in patients with MDD were correlated with the distributions of four neurotransmitters (p < 0.05) and expression maps of specific genes. These genes were strongly enriched in genes implicated in excitatory neurons, inhibitory neurons, cellular metabolism, synapse function, and immune signaling. These findings were replicated on two brain atlases. CONCLUSIONS: This work enhances our understanding of MDD and pave the way for the development of additional targeted therapeutic interventions.

Dynamic alterations of spontaneous neural activity in post-stroke aphasia: a resting-state functional magnetic resonance imaging study.

Background and purpose: The dynamic alterations in spontaneous neural activity of the brain during the acute phase of post-stroke aphasia (PSA) remain unclear. Therefore, in this study, dynamic amplitude of low-frequency fluctuation (dALFF) was applied to explore abnormal temporal variability in local functional activity of the brain during acute PSA. Materials and methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data from 26 patients with PSA and 25 healthy controls (HCs) were acquired. The sliding window method was used to assess dALFF, with the k-means clustering method used to identify dALFF states. The two-sample t-test was applied to compare differences in dALFF variability and state metrics between the PSA and HC groups. Results: (1) In the PSA group, greater variance of dALFF in the cerebellar network (CBN) and left fronto-temporo-parietal network (FTPN) was observed. (2) Three dALFF states were identified among all subjects. States 1 and 2 were identified in the PSA patients, and the two dALFF states shared a similar proportion. Moreover, the number of transitions between the two dALFF states was higher in the patients compared with that in HCs. Conclusion: The results of this study provide valuable insights into brain dysfunction that occurs during the acute phase (6.00 ± 3.52 days) of PSA. The observed increase in variability of local functional activities in CBN and left FTPN may be related to the spontaneous functional recovery of language during acute PSA, and it also suggests that cerebellum plays an important role in language.

Feasibility of 3.0 T balanced fast field echo non-contrast-enhanced whole-heart coronary magnetic resonance angiography.

Background: Coronary artery disease (CAD) is one of the most common diseases seriously harmful to human health caused by atherosclerosis. Besides coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA), coronary magnetic resonance angiography (CMRA) has become an alternative examination. The purpose of this study was to prospectively evaluate the feasibility of 3.0 T free-breathing whole-heart non-contrast-enhanced coronary magnetic resonance angiography (NCE-CMRA). Methods: After Institutional Review Board approval, the NCE-CMRA data sets of 29 patients acquired successfully at 3.0 T were evaluated independently by two blinded readers for visualization and image quality of coronary arteries using the subjective quality grade. The acquisition times were recorded in the meantime. A part of the patients had undergone CCTA, we represented stenosis by scores and used the Kappa to evaluate the consistency between CCTA and NCE-CMRA. Results: Six patients did not get diagnostic image quality because of severe artifacts. The image quality score assessed by both radiologists is 3.2±0.7, which means the NCE-CMRA can show the coronary arteries excellently. The main vessels of the coronary artery on NCE-CMRA images are considered reliably assessable. The acquisition time of NCE-CMRA, is 8.8±1.2 min. The Kappa of CCTA and NCE-CMRA on detecting stenosis is 0.842 (P<0.001). Conclusions: The NCE-CMRA results in reliable image quality and visualization parameters of coronary arteries within a short scan time. The NCE-CMRA and CCTA have a good agreement for detecting stenosis.

Classification of major depression disorder via using minimum spanning tree of individual high-order morphological brain network.

BACKGROUND: Major depressive disorder (MDD) is an overbroad and heterogeneous diagnosis with no reliable or quantifiable markers. We aim to combine machine-learning techniques with the individual minimum spanning tree of the morphological brain network (MST-MBN) to determine whether the network properties can provide neuroimaging biomarkers to identify patients with MDD. METHOD: Eight morphometric features of each region of interest (ROI) were extracted from 3D T1 structural images of 106 patients with MDD and 97 healthy controls. Six feature distances of the eight morphometric features were calculated to generate a feature distance matrix, which was defined as low-order MBN. Further linear correlations of feature distances between ROIs were calculated on the basis of low-order MBN to generate individual high-order MBN. The Kruskal's algorithm was used to generate the MST to obtain the core framework of individual low-order and high-order MBN. The regional and global properties of the individual MSTs were defined as the feature. The support vector machine and back-propagation neural network was used to diagnose MDD and assess its severity, respectively. RESULT: The low-order and high-order MST-MBN constructed by cityblock distance had the excellent classification performance. The high-order MST-MBN significantly improved almost 20 % diagnostic accuracy compared with the low-order MST-MBN, and had a maximum R2 value of 0.939 between the predictive and true Hamilton Depression Scale score. The different group-level connectivity strength mainly involves the central executive network and default mode network (no statistical significance after FDR correction). CONCLUSION: We proposed an innovative individual high-order MST-MBN to capture the cortical high-order morphological correlation and make an excellent performance for individualized diagnosis and assessment of MDD.

Deep learning-enabled fully automated pipeline system for segmentation and classification of single-mass breast lesions using contrast-enhanced mammography: a prospective, multicentre study.

Background: Breast cancer is the leading cause of cancer-related deaths in women. However, accurate diagnosis of breast cancer using medical images heavily relies on the experience of radiologists. This study aimed to develop an artificial intelligence model that diagnosed single-mass breast lesions on contrast-enhanced mammography (CEM) for assisting the diagnostic workflow. Methods: A total of 1912 women with single-mass breast lesions on CEM images before biopsy or surgery were included from June 2017 to October 2022 at three centres in China. Samples were divided into training and validation sets, internal testing set, pooled external testing set, and prospective testing set. A fully automated pipeline system (FAPS) using RefineNet and the Xception + Pyramid pooling module (PPM) was developed to perform the segmentation and classification of breast lesions. The performances of six radiologists and adjustments in Breast Imaging Reporting and Data System (BI-RADS) category 4 under the FAPS-assisted strategy were explored in pooled external and prospective testing sets. The segmentation performance was assessed using the Dice similarity coefficient (DSC), and the classification was assessed using heatmaps, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. The radiologists' reading time was recorded for comparison with the FAPS. This trial is registered with China Clinical Trial Registration Centre (ChiCTR2200063444). Findings: The FAPS-based segmentation task achieved DSCs of 0.888 ± 0.101, 0.820 ± 0.148 and 0.837 ± 0.132 in the internal, pooled external and prospective testing sets, respectively. For the classification task, the FAPS achieved AUCs of 0.947 (95% confidence interval [CI]: 0.916-0.978), 0.940 (95% [CI]: 0.894-0.987) and 0.891 (95% [CI]: 0.816-0.945). It outperformed radiologists in terms of classification efficiency based on single lesions (6 s vs 3 min). Moreover, the FAPS-assisted strategy improved the performance of radiologists. BI-RADS category 4 in 12.4% and 13.3% of patients was adjusted in two testing sets with the assistance of FAPS, which may play an important guiding role in the selection of clinical management strategies. Interpretation: The FAPS based on CEM demonstrated the potential for the segmentation and classification of breast lesions, and had good generalisation ability and clinical applicability. Funding: This study was supported by the Taishan Scholar Foundation of Shandong Province of China (tsqn202211378), National Natural Science Foundation of China (82001775), Natural Science Foundation of Shandong Province of China (ZR2021MH120), and Special Fund for Breast Disease Research of Shandong Medical Association (YXH2021ZX055).

Decreased Regional Spontaneous Brain Activity and Cognitive Dysfunction in Patients with Coronary Heart Disease: a Resting-state Functional MRI Study.

OBJECTIVES: Chronic coronary heart disease (CHD) is correlated with an increased risk of cognitive impairment (CI), but the mechanisms underlying these changes remain unclear. The aim of the present study was to explore the potential changes in regional spontaneous brain activities and their association with CI, to explore the pathophysiological mechanisms underlying CI in patients with CHD. MATERIALS AND METHODS: A total of 71 CHD patients and 73 matched healthy controls (HCs) were included in this study. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to assess the participants' cognitive functions. Regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation(fALFF) values were calculated to determine regional spontaneous brain activity. Coronary artery calcium (CAC) score provides a measure of the total coronary plaque burden. Mediation analyses were performed to test whether CHD's effects on cognitive decline are mediated by decreased regional spontaneous brain activity. RESULTS: Patients with CHD had significantly lower MMSE and MoCA scores than the HCs. Compared with the HCs, the patients with CHD demonstrated significantly decreased ReHo and fALFF values in the bilateral medial superior frontal gyrus (SFGmed), left superior temporal gyrus (TPOsup) and left middle temporal gyrus (TPOmid). Impaired cognitive performance was positively correlated with decreased activities in the SFGmed. Mediation analyses revealed that the decreased regional spontaneous brain activity in the SFGmed played a critical role in the relationship between the increase in CAC score and the MoCA and MMSE scores. CONCLUSION: The abnormalities of spontaneous brain activity in SFGmed may provide insights into the neurological pathophysiology underlying CHD associated with cognitive dysfunction.

Pregnancy leads to changes in the brain functional network: a connectome analysis.

Pregnancy leads to long-lasting changes in human brain structure; however, little is known regarding alterations in the topological organization of functional networks. In this study, we investigated the effect of pregnancy on human brain function networks. Resting-state fMRI data was collected from eighteen primiparous mothers and twenty-four nulliparous control women of similar age, education level and body mass index (BMI). The functional brain network and topological properties were calculated by using GRETNA toolbox. The demographic data differences between two groups were computed by the independent two sample t-test. We tested group differences in network metrics' area under curve (AUC) using non-parametric permutation test of 1,000 permutations and corrected for false discovery rate (FDR). Differences in regional networks between groups were evaluated using non-parametric permutation tests by network-based statistical analysis (NBS). Compared with the nulliparous control women, a hub node changed from left inferior temporal gyrus to right precentral gyrus in primiparous mothers, while primiparous mothers showed enhanced network global efficiency (p = 0.247), enhanced local efficiency (p = 0.410), larger clustering coefficient (p = 0.410), but shorter characteristic path length (p = 0.247), smaller normalized clustering coefficient (p = 0.111), and shorter normalized characteristic path length (p = 0.705). Although both groups of functional networks have small-world property (σ > 1), the σ values of primiparous mothers were decreased significantly. NBS evaluation showed the majority of altered connected sub-network in the primiparous mothers occurred in the bilateral frontal lobe gyrus (p < 0.05). Altered functional network metrics and an abnormal sub-network were found in primiparous mothers, suggested that pregnancy may lead to changes in the brain functional network.

Altered dynamic amplitude of low-frequency fluctuations in patients with postpartum depression.

BACKGROUND: Postpartum depression (PPD) is a common mood disorder with increasing incidence year by year. However, the dynamic changes in local neural activity of patients with PPD remain unclear. In this study, we utilized the dynamic amplitude of low-frequency fluctuation (dALFF) method to investigate the abnormal temporal variability of local neural activity and its potential correlation with clinical severity in PPD. METHODS: Twenty-four patients with PPD and nineteen healthy primiparous mothers controls (HCs) matched for age, education level and body mass index were examined by resting-state functional magnetic resonance imaging (rs-fMRI). A sliding-window method was used to assess the dALFF, and a k-means clustering method was used to identify dALFF states. Two-sample t-test was used to compare the differences of dALFF variability and state metrics between PPD and HCs. Pearson correlation analysis was used to analyze the relationship between dALFF variability, states metrics and clinical severity. RESULTS: (1) Patients with PPD had lower variance of dALFF than HCs in the cognitive control network, cerebellar network and sensorimotor network. (2) Four dALFF states were identified, and patients with PPD spent more time on state 2 than the other three states. The number of transitions between the four dALFF states increased in the patients compared with that in HCs. (3) Multiple dALFF states were found to be correlated with the severity of depression. The variance of dALFF in the right middle frontal gyrus was negatively correlated with the Edinburgh postnatal depression scale score. CONCLUSION: This study provides new insights into the brain dysfunction of PPD from the perspective of dynamic local brain activity, highlighting the important role of dALFF variability in understanding the neurophysiological mechanisms of PPD.

Mammography-based radiomics for predicting the risk of breast cancer recurrence: a multicenter study.

OBJECTIVE: This study aimed to establish a mammography-based radiomics model for predicting the risk of estrogen receptor (ER)-positive, lymph node (LN)-negative invasive breast cancer recurrence based on Oncotype DX and validated it by using multicenter data. METHODS: A total of 304 potentially eligible patients with pre-operative mammography images and available Oncotype DX score were retrospectively enrolled from two hospitals. The patients were grouped as training set (168 patients), internal test set (72 patients), and external test set (64 patients). Radiomics features were extracted from the mammography images of each patient. Spearman correlation analysis, analysis of variance, and least absolute shrinkage and selection operator regression were performed to reduce the redundant features in the training set, and the least absolute shrinkage and selection operator algorithm was used to construct the radiomics signature based on selected features. Multivariate logistic regression was utilized to construct classification models that included radiomics signature and clinical risk factors to predict low vs intermediate and high recurrence risk of ER-positive, LN-negative invasive breast cancer in the training set. The models were evaluated with the receiver operating characteristic curve in the training set. The internal and external test sets were used to confirm the discriminatory power of the models. The clinical usefulness was evaluated by using decision curve analysis. RESULTS: The radiomics signature consisting of three radiomics features achieved favorable prediction performance. The multivariate logistic regression model including radiomics signature and clinical risk factors (tumor grade and HER 2) showed good performance with areas under the curve of 0.92 (95% confidence interval [CI] 0.86 to 0.97), 0.88 (95% CI 0.75 to 1.00), and 0.84 (95% CI 0.69 to 0.99) in the training, internal and external test sets, respectively. The DCA indicated that when the threshold probability is ranges from 0.1 to 1.0, the radiomics model adds more net benefit than the "treat all" or "treat none" scheme in internal and external test sets. CONCLUSION: As a non-invasive pre-operative prediction tool, the mammography-based radiomics model incorporating radiomics and clinical factors show favorable predictive performance for predicting the risk of ER-positive, LN-negative invasive breast cancer recurrence based on Oncotype DX. ADVANCES IN KNOWLEDGE: The mammography-based radiomics model incorporating radiomics and clinical factors shows favorable predictive performance for predicting the risk of ER-positive, LN-negative invasive breast cancer recurrence.

Altered gray matter structural covariance networks in postpartum depression: a graph theoretical analysis.

BACKGROUND: Postpartum depression (PPD) is a serious postpartum mental health problem worldwide. To date, minimal is known about the alteration of topographical organization in the brain structural covariance network of patients with PPD. This study investigates the brain structural covariance networks of patients with PPD by using graph theoretical analysis. METHODS: High-resolution 3D T1 structural images were acquired from 21 drug-naive patients with PPD and 18 healthy postpartum women. Cortical thickness was extracted from 64 brain regions to construct the whole-brain structural covariance networks by calculating the Pearson correlation coefficients, and their topological properties (e.g., small-worldness, efficiency, and nodal centrality) were analyzed by using graph theory. Nonparametric permutation tests were further used for group comparisons of topological metrics. A node was set as a hub if its betweenness centrality (BC) was at least two standard deviations higher than the mean nodal centrality. Network-based statistic (NBS) was used to determine the connected subnetwork. RESULTS: The PPD and control groups showed small-worldness of group networks, but the small-world network was more evidently in the PPD group. Moreover, the PPD group showed increased network local efficiency and almost similar network global efficiency. However, the difference of the network metrics was not significant across the range of network densities. The hub nodes of the patients with PPD were right inferior parietal lobule (BC = 13.69) and right supramarginal gyrus (BC = 13.15), whereas those for the HCs were left cuneus (BC = 14.96), right caudal anterior-cingulate cortex (BC = 15.51), and right precuneus gyrus (BC = 15.74). NBS demonstrated two disrupted subnetworks that are present in PPD: the first subnetwork with decreased internodal connections is mainly involved in the cognitive-control network and visual network, and the second subnetwork with increased internodal connections is mainly involved in the default mode network, cognitive-control network and visual network. CONCLUSIONS: This study demonstrates the alteration of topographical organization in the brain structural covariance network of patients with PPD, providing in sight on the notion that PPD could be characterized as a systems-level disorder.