Development of a machine learning-based radiomics signature for estimating breast cancer TME phenotypes and predicting anti-PD-1/PD-L1 immunotherapy response.

BACKGROUNDS: Since breast cancer patients respond diversely to immunotherapy, there is an urgent need to explore novel biomarkers to precisely predict clinical responses and enhance therapeutic efficacy. The purpose of our present research was to construct and independently validate a biomarker of tumor microenvironment (TME) phenotypes via a machine learning-based radiomics way. The interrelationship between the biomarker, TME phenotypes and recipients' clinical response was also revealed. METHODS: In this retrospective multi-cohort investigation, five separate cohorts of breast cancer patients were recruited to measure breast cancer TME phenotypes via a radiomics signature, which was constructed and validated by integrating RNA-seq data with DCE-MRI images for predicting immunotherapy response. Initially, we constructed TME phenotypes using RNA-seq of 1089 breast cancer patients in the TCGA database. Then, parallel DCE-MRI images and RNA-seq of 94 breast cancer patients obtained from TCIA were applied to develop a radiomics-based TME phenotypes signature using random forest in machine learning. The repeatability of the radiomics signature was then validated in an internal validation set. Two additional independent external validation sets were analyzed to reassess this signature. The Immune phenotype cohort (n = 158) was divided based on CD8 cell infiltration into immune-inflamed and immune-desert phenotypes; these data were utilized to examine the relationship between the immune phenotypes and this signature. Finally, we utilized an Immunotherapy-treated cohort with 77 cases who received anti-PD-1/PD-L1 treatment to evaluate the predictive efficiency of this signature in terms of clinical outcomes. RESULTS: The TME phenotypes of breast cancer were separated into two heterogeneous clusters: Cluster A, an "immune-inflamed" cluster, containing substantial innate and adaptive immune cell infiltration, and Cluster B, an "immune-desert" cluster, with modest TME cell infiltration. We constructed a radiomics signature for the TME phenotypes ([AUC] = 0.855; 95% CI 0.777-0.932; p < 0.05) and verified it in an internal validation set (0.844; 0.606-1; p < 0.05). In the known immune phenotypes cohort, the signature can identify either immune-inflamed or immune-desert tumor (0.814; 0.717-0.911; p < 0.05). In the Immunotherapy-treated cohort, patients with objective response had higher baseline radiomics scores than those with stable or progressing disease (p < 0.05); moreover, the radiomics signature achieved an AUC of 0.784 (0.643-0.926; p < 0.05) for predicting immunotherapy response. CONCLUSIONS: Our imaging biomarker, a practicable radiomics signature, is beneficial for predicting the TME phenotypes and clinical response in anti-PD-1/PD-L1-treated breast cancer patients. It is particularly effective in identifying the "immune-desert" phenotype and may aid in its transformation into an "immune-inflamed" phenotype.

Noninvasive identification of HER2-low-positive status by MRI-based deep learning radiomics predicts the disease-free survival of patients with breast cancer.

OBJECTIVE: This study aimed to establish a MRI-based deep learning radiomics (DLR) signature to predict the human epidermal growth factor receptor 2 (HER2)-low-positive status and further verified the difference in prognosis by the DLR model. METHODS: A total of 481 patients with breast cancer who underwent preoperative MRI were retrospectively recruited from two institutions. Traditional radiomics features and deep semantic segmentation feature-based radiomics (DSFR) features were extracted from segmented tumors to construct models separately. Then, the DLR model was constructed to assess the HER2 status by averaging the output probabilities of the two models. Finally, a Kaplan‒Meier survival analysis was conducted to explore the disease-free survival (DFS) in patients with HER2-low-positive status. The multivariate Cox proportional hazard model was constructed to further determine the factors associated with DFS. RESULTS: First, the DLR model distinguished between HER2-negative and HER2-overexpressing patients with AUCs of 0.868 and 0.763 in the training and validation cohorts, respectively. Furthermore, the DLR model distinguished between HER2-low-positive and HER2-zero patients with AUCs of 0.855 and 0.750, respectively. Cox regression analysis showed that the prediction score obtained using the DLR model (HR, 0.175; p = 0.024) and lesion size (HR, 1.043; p = 0.009) were significant, independent predictors of DFS. CONCLUSIONS: We successfully constructed a DLR model based on MRI to noninvasively evaluate the HER2 status and further revealed prospects for predicting the DFS of patients with HER2-low-positive status. CLINICAL RELEVANCE STATEMENT: The MRI-based DLR model could noninvasively identify HER2-low-positive status, which is considered a novel prognostic predictor and therapeutic target. KEY POINTS: • The DLR model effectively distinguished the HER2 status of breast cancer patients, especially the HER2-low-positive status. • The DLR model was better than the traditional radiomics model or DSFR model in distinguishing HER2 expression. • The prediction score obtained using the model and lesion size were significant independent predictors of DFS.

Characterizing the temporal dynamics of intrinsic brain activities in depressed adolescents with prior suicide attempts.

Converging evidence has revealed disturbances in the corticostriatolimic system are associated with suicidal behaviors in adults with major depressive disorder. However, the neurobiological mechanism that confers suicidal vulnerability in depressed adolescents is largely unknown. A total of 86 depressed adolescents with and without prior suicide attempts (SA) and 47 healthy controls underwent resting-state functional imaging (R-fMRI) scans. The dynamic amplitude of low-frequency fluctuations (dALFF) was measured using sliding window approach. We identified SA-related alterations in dALFF variability primarily in the left middle temporal gyrus, inferior frontal gyrus, middle frontal gyrus (MFG), superior frontal gyrus (SFG), right SFG, supplementary motor area (SMA) and insula in depressed adolescents. Notably, dALFF variability in the left MFG and SMA was higher in depressed adolescents with recurrent suicide attempts than in those with a single suicide attempt. Moreover, dALFF variability was capable of generating better diagnostic and prediction models for suicidality than static ALFF. Our findings suggest that alterations in brain dynamics in regions involved in emotional processing, decision-making and response inhibition are associated with an increased risk of suicidal behaviors in depressed adolescents. Furthermore, dALFF variability could serve as a sensitive biomarker for revealing the neurobiological mechanisms underlying suicidal vulnerability.

Diffusion basis spectrum imaging detects pathological alterations in substantia nigra and white matter tracts with early-stage Parkinson's disease.

OBJECTIVES: Using diffusion basis spectrum imaging (DBSI) to examine the microstructural changes in the substantia nigra (SN) and global white matter (WM) tracts of patients with early-stage PD. METHODS: Thirty-seven age- and sex-matched patients with early-stage PD and 22 healthy controls (HCs) were enrolled in this study. All participants underwent clinical assessments and diffusion-weighted MRI scans, analyzed by diffusion tensor imaging (DTI) and DBSI to assess the pathologies of PD in SN and global WM tracts. RESULTS: The lower DTI fraction anisotropy (FA) was seen in SN of PD patients (PD: 0.316 ± 0.034 vs HCs: 0.331 ± 0.019, p = 0.015). The putative cells marker-DBSI-restricted fraction (PD: 0.132 ± 0.051 vs HCs: 0.105 ± 0.039, p = 0.031) and the edema/extracellular space marker-DBSI non-restricted-fraction (PD: 0.150 ± 0.052 vs HCs: 0.122 ± 0.052, p = 0.020) were both significantly higher and the density of axons/dendrites marker-DBSI fiber-fraction (PD: 0.718 ± 0.073 vs HCs: 0.773 ± 0.071, p = 0.003) was significantly lower in SN of PD patients. DBSI-restricted fraction in SN was negatively correlated with HAMA scores (r = - 0.501, p = 0.005), whereas DTI-FA was not correlated with any clinical scales. In WM tracts, only higher DTI axial diffusivity (AD) among DTI metrics was found in multiple WM regions in PD, while lower DBSI fiber-fraction and higher DBSI non-restricted-fraction were detected in multiple WM regions. DBSI non-restricted-fraction in both left fornix (cres)/stria terminalis (r = -0.472, p = 0.004) and right posterior thalamic radiation (r = - 0.467, p = 0.005) was negatively correlated with MMSE scores. CONCLUSION: DBSI could potentially detect and quantify the extent of inflammatory cell infiltration, fiber/dendrite loss, and edema in both SN and WM tracts in patients with early-stage PD, a finding remains to be further investigated through more extensive longitudinal DBSI analysis. CLINICAL RELEVANCE STATEMENT: Our study shows that DBSI indexes can potentially detect early-stage PD's pathological changes, with a notable ability to distinguish between inflammation and edema. This implies that DBSI has the potential to be an imaging biomarker for early PD diagnosis. KEY POINTS: • Diffusion basis spectrum imaging detected higher restricted-fraction in Parkinson's disease, potentially reflecting inflammatory cell infiltration. • Diffusion basis spectrum imaging detected higher non-restricted-fraction and lower fiber-fraction in Parkinson's disease, indicating the presence of edema and/or dopaminergic neuronal/dendritic loss. • Diffusion basis spectrum imaging metrics correlated with non-motor symptoms, suggesting its potential diagnostic role to detect early-stage PD dysfunctions.

Abbreviated Versus Full-Protocol MRI for Breast Cancer Neoadjuvant Chemotherapy Response Assessment: Diagnostic Performance by General and Breast Radiologists.

BACKGROUND. Abbreviated protocols could allow wider adoption of MRI in patients undergoing breast cancer neoadjuvant chemotherapy (NAC). However, abbreviated MRI has been explored primarily in screening settings. OBJECTIVE. The purpose of this article was to compare diagnostic performance of abbreviated MRI and full-protocol MRI for evaluation of breast cancer NAC response, stratifying by radiologists' breast imaging expertise. METHODS. This retrospective study included 203 patients with breast cancer (mean age, 52.1 ± 11.2 [SD] years) from two hospitals who underwent MRI before NAC initiation and after NAC completion before surgical resection from March 2017 to April 2021. Abbreviated MRI was extracted from full-protocol MRI and included the axial T2-weighted sequence and precontrast and single early postcontrast T1-weighted sequences. Three general radiologists and three breast radiologists independently interpreted abbreviated and full-protocol MRI in separate sessions, identifying enhancing lesions to indicate residual tumor and measuring lesion size. The reference standard was presence and size of residual tumor on pathologic assessment of post-NAC surgical specimens. RESULTS. A total of 50 of 203 patients had pathologic complete response (pCR). Intraobserver and interobserver agreement for abbreviated and full-protocol MRI for general and breast radiologists ranged from substantial to nearly perfect (κ = 0.70-0.81). Abbreviated MRI compared with full-protocol MRI showed no significant difference for general radiologists in sensitivity (54.7% vs 57.3%, p > .99), specificity (92.8% vs 95.6%, p = .29), or accuracy (83.4% vs 86.2%, p = .30), nor for breast radiologists in sensitivity (60.0% vs 61.3%, p > .99), specificity (94.6% vs 97.4%, p = .22), or accuracy (86.0% vs 88.5%, p = .30). Sensitivity, specificity, and accuracy were not significantly different between protocols for any reader individually (p > .05). Mean difference in residual tumor size on MRI relative to pathology for abbreviated protocol ranged for general radiologists from -0.19 to 0.03 mm and for breast radiologists from -0.15 to -0.05 mm, and for full protocol ranged for general radiologists from 0.57 to 0.65 mm and for breast radiologists from 0.66 to 0.79 mm. CONCLUSION. Abbreviated compared with full-protocol MRI showed similar intraobserver and interobserver agreement and no significant difference in diagnostic performance. Full-protocol MRI but not abbreviated MRI slightly overestimated pathologic tumor sizes. CLINICAL IMPACT. Abbreviated protocols may facilitate use of MRI for post-NAC response assessment by general and breast radiologists.

Optimizing CT and MRI criteria for differentiating intrahepatic mass-forming cholangiocarcinoma and hepatocellular carcinoma.

BACKGROUND: Accurate diagnosis of intrahepatic mass-forming cholangiocarcinoma (IMCC) is crucial with regard to the choice of patient management and treatment options. PURPOSE: To evaluate the feasibility and diagnostic performance of the LI-RADS M (LR-M) targetoid criteria on computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in differentiating IMCC from hepatocellular carcinoma (HCC). MATERIAL AND METHODS: A total of 118 patients with IMCC and HCC were included who underwent CT and EOB-MRI examinations. Multivariate analysis was used to determine the strongest predictors differentiating IMCC from HCC. Using these predictors, a predictive model for differentiating IMCC from HCC was constructed and the performance of the model was confirmed using the receiver operating characteristic curve. RESULTS: Multivariate analyses revealed rim-like arterial phase hyperenhancement (rim APHE) on CT and rim APHE, delayed central enhancement (DCE), and targetoid hepatobiliary phase (HBP) on MRI as independent variables significantly differentiating IMCC from HCC. The multivariate logistic regression model incorporating the three variables on EOB-MRI was constructed with an area under the curve (AUC) of 0.946, sensitivity of 87.80%, specificity of 92.21%, and accuracy of 94.60%. Per the DeLong test, the multivariate logistic regression model showed significantly higher AUC than rim APHE on CT (0.946 vs. 0.871; P = 0.008) and MRI (0.946 vs. 0.876; P = 0.003), whereas rim APHE on CT and MRI did not differ significantly (P = 0.809). CONCLUSION: The multivariate logistic regression model based on rim APHE, DCE, and targetoid HBP on EOB-MRI can effectively distinguish IMCC from HCC and is superior to any other targetoid appearance criterion of LI-RADS on CT and EOB-MRI.

Research on Estimating Rice Canopy Height and LAI Based on LiDAR Data.

Rice canopy height and density are directly usable crop phenotypic traits for the direct estimation of crop biomass. Therefore, it is crucial to rapidly and accurately estimate these phenotypic parameters. To achieve the non-destructive detection and estimation of these essential parameters in rice, a platform based on LiDAR (Light Detection and Ranging) point cloud data for rice phenotypic parameter detection was established. Data collection of rice canopy layers was performed across multiple plots. The LiDAR-detected canopy-top point clouds were selected using a method based on the highest percentile, and a surface model of the canopy was calculated. The canopy height estimation was the difference between the ground elevation and the percentile value. To determine the optimal percentile that would define the rice canopy top, testing was conducted incrementally at percentile values from 0.8 to 1, with increments of 0.005. The optimal percentile value was found to be 0.975. The root mean square error (RMSE) between the LiDAR-detected and manually measured canopy heights for each case was calculated. The prediction model based on canopy height (R2 = 0.941, RMSE = 0.019) exhibited a strong correlation with the actual canopy height. Linear regression analysis was conducted between the gap fractions of different plots, and the average rice canopy Leaf Area Index (LAI) was manually detected. Prediction models of canopy LAIs based on ground return counts (R2 = 0.24, RMSE = 0.1) and ground return intensity (R2 = 0.28, RMSE = 0.09) showed strong correlations but had lower correlations with rice canopy LAIs. Regression analysis was performed between LiDAR-detected canopy heights and manually measured rice canopy LAIs. The results thereof indicated that the prediction model based on canopy height (R2 = 0.77, RMSE = 0.03) was more accurate.

Feasibility of thoracic CT in assessing anemia for aplastic anemia patients undergoing allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Anemia is an important clinical symptom for aplastic anemia (AA) patients who are suffered with peripheral pancytopenia. OBJECTIVE: To evaluate the accuracy of diagnosing anemia with non-invasive chest computed tomography (CT) for AA patients. METHODS: The CT attenuation of left ventricular (LV) cavity and interventricular septum (IVS) on unenhanced thoracic CT images of AA patients are retrospectively analyzed, including 84 AA patients in pre-transplant and 1-month (n = 82), 2-month (n = 72), 3-month (n = 75), 6-month (n = 74) and 12-month (n = 70) followed patients in post-transplant. The difference (IVS-LV) and ratio (LV/IVS) of the CT attenuation between LV cavity and interventricular septum are calculated. Serum hemoglobin is estimated within 24 hours of CT imaging. The CT attenuations of IVS-LV and LV/IVS are correlated with hemoglobin, and their variation tendency is analyzed during the treatment of a-HSCT. A receiver operating characteristic (ROC) curve analysis is then performed for the diagnosis of anemia. RESULTS: The CT attenuations of IVS-LV and LV/IVS well correlate with hemoglobin (r = -0.618 and 0.628, respectively, P <  0.001). The variation tendency of IVS-LV and LV/IVS is similar to that of hemoglobin with opposite directions during one-year follow-up of a-HSCT. When a threshold of CT attenuation of IVS-LV and LV/IVS is set at 11.5HU and 0.77, respectively, both the sensitivity and specificity in diagnosing anemia are good (74.7% and 73.8% in CT attenuation of IVS-LV; 77.4% and 70.4% in LV/LVS, respectively). CONCLUSIONS: Both CT attenuation of LV/IVS and IVS-LV had similar accuracy in diagnosing anemia for AA patients. The non-invasive chest CT can offer a new possibility to complementarily evaluate anemia for AA patients in the diagnostic radiology reports.

Cirrhosis-related Spontaneous Mesocaval Shunt.

Online supplemental material is available for this article.

Evaluation of the Effects of Anti-PD-1 Therapy on Triple-Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced Imaging.

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Fuhrman nuclear grade prediction of clear cell renal cell carcinoma: influence of volume of interest delineation strategies on machine learning-based dynamic enhanced CT radiomics analysis.

OBJECTIVE: To investigate the influence of different volume of interest (VOI) delineation strategies on machine learning-based predictive models for discrimination between low and high nuclear grade clear cell renal cell carcinoma (ccRCC) on dynamic contrast-enhanced CT. METHODS: This study retrospectively collected 177 patients with pathologically proven ccRCC (124 low-grade; 53 high-grade). Tumor VOI was manually segmented, followed by artificially introducing uncertainties as: (i) contour-focused VOI, (ii) margin erosion of 2 or 4 mm, and (iii) margin dilation (2, 4, or 6 mm) inclusive of perirenal fat, peritumoral renal parenchyma, or both. Radiomics features were extracted from four-phase CT images (unenhanced phase (UP), corticomedullary phase (CMP), nephrographic phase (NP), excretory phase (EP)). Different combinations of four-phasic features for each VOI delineation strategy were used to build 176 classification models. The best VOI delineation strategy and superior CT phase were identified and the top-ranked features were analyzed. RESULTS: Features extracted from UP and EP outperformed features from other single/combined phase(s). Shape features and first-order statistics features exhibited superior discrimination. The best performance (ACC 81%, SEN 67%, SPE 87%, AUC 0.87) was achieved with radiomics features extracted from UP and EP based on contour-focused VOI. CONCLUSION: Shape and first-order features extracted from UP + EP images are better feature representations. Contour-focused VOI erosion by 2 mm or dilation by 4 mm within peritumor renal parenchyma exerts limited impact on discriminative performance. It provides a reference for segmentation tolerance in radiomics-based modeling for ccRCC nuclear grading. KEY POINTS: • Lesion delineation uncertainties are tolerated within a VOI erosion range of 2 mm or dilation range of 4 mm within peritumor renal parenchyma for radiomics-based ccRCC nuclear grading. • Radiomics features extracted from unenhanced phase and excretory phase are superior to other single/combined phase(s) at differentiating high vs low nuclear grade ccRCC. • Shape features and first-order statistics features showed superior discriminative capability compared to texture features.

Performance of radiomics models for tumour-infiltrating lymphocyte (TIL) prediction in breast cancer: the role of the dynamic contrast-enhanced (DCE) MRI phase.

OBJECTIVE: To systematically investigate the effect of imaging features at different DCE-MRI phases to optimise a radiomics model based on DCE-MRI for the prediction of tumour-infiltrating lymphocyte (TIL) levels in breast cancer. MATERIALS AND METHODS: This study retrospectively collected 133 patients with pathologically proven breast cancer, including 73 patients with low TIL levels and 60 patients with high TIL levels. The volumes of breast cancer lesions were manually delineated on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and each phase of DCE-MRI, followed by 6250 quantitative feature extractions. The least absolute shrinkage and selection operator (LASSO) method was used to select predictive feature sets for the classifiers. Four models were developed for predicting TILs: (1) single enhanced phase radiomics models; (2) fusion enhanced multi-phase radiomics models; (3) fusion multi-sequence radiomics models; and (4) a combined radiomics-based clinical model. RESULTS: Image features extracted from the delayed phase MRI, especially DCE_Phase 6 (DCE_P6), demonstrated dominant predictive performances over features from other phases. The fusion multi-sequence radiomics model and combined radiomics-based clinical model achieved the highest predictive performances with areas under the curve (AUCs) of 0.934 and 0.950, respectively; however, the differences were not statistically significant. CONCLUSION: The DCE-MRI radiomics model, especially image features extracted from the delayed phases, can help improve the performance in predicting TILs. The radiomics nomogram is effective in predicting TILs in breast cancer. KEY POINTS: • Radiomics features extracted from DCE-MRI, especially delayed phase images, help predict TIL levels in breast cancer. • We developed a nomogram based on MRI to predict TILs in breast cancer that achieved the highest AUC of 0.950.

Alterations of functional connectivity of the lateral habenula in subclinical depression and major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a common cause of disability and morbidity, affecting about 10% of the population worldwide. Subclinical depression (SD) can be understood as a precursor of MDD, and therefore provides an MDD risk indicator. The pathogenesis of MDD and SD in humans is still unclear, and the current diagnosis lacks accurate biomarkers and gold standards. METHODS: A total of 40 MDD, 34 SD, and 40 healthy control (HC) participants matched by age, gender, and education were included in this study. Resting-state functional magnetic resonance images (rs-fMRI) were used to analyze the functional connectivity (FC) of the posterior parietal thalamus (PPtha), which includes the lateral habenula, as the region of interest. Analysis of variance with the post hoc t-test test was performed to find significant differences in FC and clarify the variations in FC among the HC, SD, and MDD groups. RESULTS: Increased FC was observed between PPtha and the left inferior temporal gyrus (ITG) for MDD versus SD, and between PPtha and the right ITG for SD versus HC. Conversely, decreased FC was observed between PPtha and the right middle temporal gyrus (MTG) for MDD versus SD and MDD versus HC. The FC between PPtha and the middle frontal gyrus (MFG) in SD was higher than that in MDD and HC. Compared with the HC group, the FC of PPtha-ITG (left and right) increased in both the SD and MDD groups, PPtha-MTG (right) decreased in both the SD and MDD groups and PPtha-MFG (right) increased in the SD group and decreased in the MDD group. CONCLUSION: Through analysis of FC measured by rs-fMRI, the altered FC between PPtha and several brain regions (right and left ITG, right MTG, and right MFG) has been identified in participants with SD and MDD. Different alterations in FC between PPtha and these regions were identified for patients with depression. These findings might provide insights into the potential pathophysiological mechanisms of SD and MDD, especially related to PPtha and the lateral habenula.

A computed tomography-based radiomic nomogram for predicting lymph node metastasis in patients with early-stage papillary thyroid carcinoma.

BACKGROUND: Accurate assessment of lymph node metastasis (LNM) is important for the selection of the optimal therapeutic strategy in patients with papillary thyroid carcinoma (PTC). PURPOSE: To develop and validate a radiomics nomogram based on computed tomography (CT) for predicting LNM in patients with early-stage PTC. MATERIAL AND METHODS: A total of 92 patients with pathologically confirmed PTC were divided into a training cohort (n = 64) and validation cohort (n = 28). Radiomic features of the tumor and peritumoral interstitium were extracted from contrast-enhanced CT images. The radiomic signature was constructed and the radiomic score (Rad-score) was calculated. Combined with the Rad-score and independent clinical factors, a radiomic nomogram was constructed and its performance was assessed by receiver operating characteristic (ROC) curves and calibration plots. The comparison of ROC curves was performed with DeLong's test. RESULTS: A combined nomogram model of the thyroid tumor and peritumoral interstitium was constructed based on the Rad-score, tumor location, maximum diameter, and T stage, and it had areas under the ROC curve of 0.956 (95% confidence interval [CI] = 0.913-1.000) and 0.876 (95% CI = 0.741-1.000) in the training and validation cohorts, respectively. Decision curve analysis suggested that the combined nomogram model had better clinical usefulness than the other models. CONCLUSION: A CT-based radiomics nomogram incorporating the radiomic signature and the selected clinical predictors can be a reliable approach to preoperatively predict the LNM status in patients with early-stage PTC, which is helpful for treatment decisions and prognosis.

Alterations in resting-state global brain connectivity in bipolar I disorder patients with prior suicide attempt.

BACKGROUND: Bipolar I disorder (BD-I) is associated with a high risk of suicide attempt; however, the neural circuit dysfunction that confers suicidal vulnerability in individuals with this disorder remains largely unknown. Resting-state functional magnetic resonance imaging (rs-fMRI) allows non-invasive mapping of brain functional connectivity. The current study used an unbiased voxel-based graph theory analysis of rs-fMRI to investigate the intrinsic brain networks of BD-I patients with and without suicide attempt. METHODS: A total of 30 BD-I patients with suicide attempt (attempter group), 82 patients without suicide attempt (non-attempter group), and 67 healthy controls underwent rs-fMRI scan, and then global brain connectivity (GBC) was computed as the sum of connections of each voxel with all other gray matter voxels in the brain. RESULTS: Compared with the non-attempter group, we found regional differences in GBC values in emotion-encoding circuits, including the left superior temporal gyrus, bilateral insula/rolandic operculum, and right precuneus (PCu)/cuneus in the bipolar disorder (BD) attempter group, and these disrupted hub-like regions displayed fair to good power in distinguishing attempters from non-attempters among BD-I patients. GBC values of the right PCu/cuneus were positively correlated with illness duration and education in the attempter group. CONCLUSIONS: Our results indicate that abnormal connectivity patterns in emotion-encoding circuits are associated with the increasing risk of vulnerability to suicide attempt in BD patients, and global dysconnectivity across these emotion-encoding circuits might serve as potential biomarkers for classification of suicide attempt in BD patients.

Anomalous static and dynamic functional connectivity of amygdala subregions in individuals with high trait anxiety.

BACKGROUND: Trait anxiety is considered a susceptible factor for stress-related disorders, and is characterized by abnormal brain activity and connectivity in the regions related to emotional processing (e.g., the amygdala). However, only a few studies have examined the static and dynamic changes of functional connectivity in trait anxiety. METHOD: We compared the resting-state static and dynamic functional connectivity (sFC/dFC) in individuals with high trait anxiety (HTA, n = 257) and low trait anxiety (LTA, n = 264) using bilateral amygdala subregions as the seeds, that is, the centromedial amygdala (CMA), basolateral amygdala (BLA), and superficial amygdala (SFA). RESULTS: The CMA, BLA, and SFA all showed reduced sFC with the executive control network (ECN) and anomalous dFC with the default mode network (DMN) in individuals with HTA. The CMA only showed reduced sFC with the ECN and reduced dFC with the DMN in individuals with HTA. The BLA showed reduced sFC with the salience network (mainly in the anterior and median cingulate), and increased dFC between the BLA and the DMN in individuals with HTA compared to those with LTA. Notably, HTA showed widespread anomalous functional connectivity in the SFA, including the visual network, mainly in the calcarine fissure, limbic system (olfactory cortex), and basal ganglia (putamen). CONCLUSION: The anomalous sFC and dFC in individuals with HTA may reflect altered mechanisms in prefrontal control, salient stimuli processing, and amygdaloidal responsivity to potential threats, leading to alterations in associative, attentional, interpretative, and regulating processes that sustain a threat-related processing bias in HTA individuals.

Can Chest CT Features Distinguish Patients With Negative From Those With Positive Initial RT-PCR Results for Coronavirus Disease (COVID-19)?

OBJECTIVE. The purpose of this study was to explore the value of CT in the diagnosis of coronavirus disease (COVID-19) pneumonia, especially for patients who have negative initial results of reverse transcription-polymerase chain reaction (RT-PCR) testing. MATERIALS AND METHODS. Patients with COVID-19 pneumonia from January 19, 2020, to February 20, 2020, were included. All patients underwent chest CT and swab RT-PCR tests within 3 days. Patients were divided into groups with negative (seven patients) and positive (14 patients) initial RT-PCR results. The imaging findings in both groups were recorded and compared. RESULTS. Twenty-one patients with symptoms (nine men, 12 women; age range, 26-90 years) were evaluated. Most of the COVID-19 lesions were located in multiple lobes (67%) in both lungs (72%) in our study. The main CT features were ground-glass opacity (95%) and consolidation (72%) with a subpleural distribution (100%). Otherwise, 33% of patients had other lesions around the bronchovascular bundle. The other CT features included air bronchogram (57%), vascular enlargement (67%), interlobular septal thickening (62%), and pleural effusions (19%). Compared with that in the group with positive initial RT-PCR results, CT of the group with negative initial RT-PCR results was less likely to show pulmonary consolidation (p < 0.05). CONCLUSION. The less pulmonary consolidation found at CT, the greater is the possibility of negative initial RT-PCR results. Chest CT is important in the screening of patients in whom disease is clinically suspected, especially those who have negative initial RT-PCR results.

Altered spontaneous neural activity in the precuneus, middle and superior frontal gyri, and hippocampus in college students with subclinical depression.

BACKGROUND: Subclinical depression (ScD) is a prevalent condition associated with relatively mild depressive states, and it poses a high risk of developing into major depressive disorder (MDD). However, the neural pathology of ScD is still largely unknown. Identifying the spontaneous neural activity involved in ScD may help clarify risk factors for MDD and explore treatment strategies for mild stages of depression. METHODS: A total of 34 ScD subjects and 40 age-, sex-, and education-matched healthy controls were screened from 1105 college students. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of resting-state fMRI were calculated to reveal neural activity. Strict statistical strategies, including Gaussian random field (GRF), false discovery rate (FDR), and permutation test (PT) with threshold-free cluster enhancement (TFCE), were conducted. Based on the altered ALFF and ReHo, resting-state functional connectivity (RSFC) was further analyzed using a seed-based approach. RESULTS: The right precuneus and left middle frontal gyrus (MFG) both showed significantly increased ALFF and ReHo in ScD subjects. Moreover, the left hippocampus and superior frontal gyrus (SFG) showed decreased ALFF and increased ReHo, respectively. In addition, ScD subjects showed increased RSFC between MFG and hippocampus compared to healthy controls, and significant positive correlation was found between the Beck Depression Inventory-II (BDI-II) score and RSFC from MFG to hippocampus in ScD group. CONCLUSION: Spontaneous neural activities in the right precuneus, left MFG, SFG, and hippocampus were altered in ScD subjects. Functional alterations in these dorsolateral prefrontal cortex and default mode network regions are largely related to abnormal emotional processing in ScD, and indicate strong associations with brain impairments in MDD, which provide insight into potential pathophysiology mechanisms of subclinical depression.

[Pharmacokinetic study on five components in phthalide target areas of Chaxiong and its ß-CD inclusion compounds based on UPLC-MS/MS].

This study aims to establish a method for the determination of the concentration of five main components of phthalide target areas of Chaxiong(CPTA) and its inclusion of ß-CD in the plasma of rats, and determine the pharmacokinetic parameters, absolute bioavailability and relative bioavailability of CPTA/ß-CD inclusion compound in vivo. The plasma concentrations of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide were determined with UPLC-MS/MS. The content determination was conducted at the chromatographic conditions as follows: Shim-pack GIST C_(18)-AQ HP column(2.1 mm×100 mm, 3 µm), mobile phase of 0.1% formic acid solution(A)-acetonitrile(B), gradient elution, flow rate of 0.3 mL·min~(-1), column temperature of 35 ℃ and injection volume of 2 µL. The mass spectra were obtained with electrospray ion source(ESI), positive ion mode and multi reaction monitoring. CPTA/ß-CD inclusion compound was prepared by grinding method, DAS 2.0 software was used to model the data, and the absolute bioavailability of CPTA and relative bioavailability of inclusion compound were calculated. Finally, the methods for the determination of five components of senkyunolide A, N-butylphthalide, new osthol lactone, Z-ligustilide and butenyl phthalide in CPTA, were successfully established. The linear relationship among the five components was good within their respective ranges, r>0.99. The absolute bioavailability of the five components in rats was 22.30%, 16.32%, 21.90%, 10.16% and 12.43%, respectively. After CPTA/ß-CD inclusion was prepared, the relative bioavailability of the five components was 138.69%, 198.39%, 218.01%, 224.54% and 363.55%, respectively, significantly improved. This method is rapid, accurate and sensitive, so it is suitable for the pharmacokinetic study of extracts in traditional Chinese medicine and their preparations.

Clear cell renal cell carcinoma: the value of sex-specific abdominal visceral fat measured on CT for prediction of Fuhrman nuclear grade.

OBJECTIVE: To explore whether sex-specific abdominal visceral fat composition on CT can predict the Fuhrman nuclear grade of clear cell renal cell carcinoma (ccRCC). METHODS: One hundred seventy-one patients (123 males and 48 females) from four hospitals (multicentre group) and 159 patients (109 males and 50 females) from the cancer imaging archive (TCIA-KIRC group) with pathologically proven ccRCC (multicentre: 124 low grade and 47 high grade; TCIA-KIRC: 79 low grade and 80 high grade) were retrospectively included. Abdominal fat was segmented into subcutaneous fat area (SFA) and visceral fat area (VFA) on CT using ImageJ. The total fat area (TFA) and relative VFA (rVFA) were then calculated. Clinical characteristics (age, sex, waist circumference and maximum tumour diameter) were also assessed. Univariate and multivariate logistic regression analyses were performed to identify the association between general or sex-specific visceral fat composition and Fuhrman grade. RESULTS: Females with high-grade ccRCC from the multicentre group had a higher rVFA (42.4 vs 31.3, p = 0.001) than those with low-grade ccRCC after adjusting for age. There was no significant difference in males. The rVFA remained a stable and independent predictor for females high-grade ccRCC in both the univariate (multicentre: OR 1.205, 95% CI 1.074-1.352, p = 0.001; TCIA-KIRC: OR 1.171, 95% CI 1.016-1.349, p = 0.029) and multivariate (multicentre: OR 1.095, 95% CI 1.024-1.170, p = 0.003; TCIA-KIRC: OR 1.103, 95% CI 1.024-1.187, p = 0.010) models. CONCLUSIONS: Sex-specific visceral fat composition has different values for predicting high-grade ccRCC and could be used as an independent predictor for females with high-grade ccRCC. KEY POINTS: • Visceral fat measurement (rVFA) as an independent predictor for high-grade ccRCC had good predictive power in females, but not in males. • Sex-specific visceral fat composition was significantly associated with high-grade ccRCC in females only. • The rVFA could be considered one of the risk factors for high-grade ccRCC for females.