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BACKGROUND: MRI-based placental analyses have been used to improve fetal growth restriction (FGR) assessment by complementing ultrasound-based measurements. However, these are still limited by time-consuming manual annotation in MRI data and the lack of mother-based information. PURPOSE: To develop and validate a hybrid model for accurate FGR assessment by automatic placental radiomics on T2-weighted imaging (T2WI) and multifeature fusion. STUDY TYPE: Retrospective. POPULATION: 274 pregnant women (29.5 ± $$ \pm $$ 4.0 years) from two centers were included and randomly divided into training (N = 119), internal test (N = 40), time-independent validation (N = 43), and external validation (N = 72) sets. FIELD STRENGTH/SEQUENCE: 1.5-T, T2WI half-Fourier acquisition single-shot turbo spin-echo pulse sequence. ASSESSMENT: First, the placentas on T2WI were manually annotated, and a deep learning model was developed to automatically segment the placentas. Then, the radiomic features were extracted from the placentas and selected by three-step feature selection. In addition, fetus-based measurement features and mother-based clinical features were obtained from ultrasound examinations and medical records, respectively. Finally, a hybrid model based on random forest was constructed by fusing these features, and further compared with models based on other machine learning methods and different feature combinations. STATISTICAL TESTS: The performances of placenta segmentation and FGR assessment were evaluated by Dice similarity coefficient (DSC) and the area under the receiver operating characteristic curve (AUROC), respectively. A P-value <0.05 was considered statistically significant. RESULTS: The placentas were automatically segmented with an average DSC of 90.0%. The hybrid model achieved an AUROC of 0.923, 0.931, and 0.880 on the internal test, time-independent validation, and external validation sets, respectively. The mother-based clinical features resulted in significant performance improvements for FGR assessment. DATA CONCLUSION: The proposed hybrid model may be able to assess FGR with high accuracy. Furthermore, information complementation based on placental, fetal, and maternal features could also lead to better FGR assessment performance. TECHNICAL EFFICACY: Stage 2.
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INTRODUCTION: Fetal growth restriction (FGR) is associated with placental abnormalities, and its precise diagnosis is challenging. This study aimed to explore the role of radiomics based on placental MRI in predicting FGR. METHODS: A retrospective study using T2-weighted placental MRI data were conducted. A total of 960 radiomic features were automatically extracted. Features were selected using three-step machine learning methods. A combined model was constructed by combining MRI-based radiomic features and ultrasound-based fetal measurements. The receiver operating characteristic curves (ROC) were conducted to assess model performance. Additionally, decision curves and calibration curves were performed to evaluate prediction consistency of different models. RESULTS: Among the study participants, pregnant women who delivered from January 2015 to June 2021 were randomly divided into training (n = 119) and test (n = 40) sets. Forty-three other pregnant women who delivered from July 2021 to December 2021 were used as the time-independent validation set. After training and testing, three radiomic features that were strongly correlated with FGR were selected. The area under the ROC curves (AUCs) of the MRI-based radiomics model reached 0.87 (95% confidence interval [CI]: 0.74-0.96) and 0.87 (95% CI: 0.76-0.97) in the test and validation sets, respectively. Moreover, the AUCs for the model comprising MRI-based radiomic features and ultrasound-based measurements were 0.91 (95% CI: 0.83-0.97) and 0.94 (95% CI: 0.86-0.99) in the test and validation sets, respectively. DISCUSSION: MRI-based placental radiomics could accurately predict FGR. Moreover, combining placental MRI-based radiomic features with ultrasound indicators of the fetus could improve the diagnostic accuracy of FGR.
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Retardo del Crecimiento Fetal , Placenta , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Estudios de Casos y Controles , Factores de Riesgo , Imagen por Resonancia MagnéticaRESUMEN
Intrahepatic cholestasis of pregnancy (ICP) is a common pregnancy-specific disease, characterized by increased bile acid levels and adverse fetal outcomes. We previously reported excessive bile acids led to dysfunction of placental trophoblasts in ICP. However, the detailed mechanism is still unclear. Autophagy is fundamental process for protecting cell survival against adverse conditions. Here, we evaluated the effect of increased concentration of bile acids on autophagy in trophoblasts in vitro and in vivo. First, we demonstrated that the autophagy substrate p62/sequestosome-1 was accumulated in placental tissues from patients with ICP and in human trophoblasts treated with hydrophobic bile acids, including chenodeoxycholic acid and deoxycholic acid. Furthermore, we found that treatment with hydrophobic bile acids impaired autophagic flux in both time- and concentration-dependent manners, by suppressing the AMP-activated protein kinase/unc-51-like kinase 1 autophagic signaling pathway. Notably, trophoblasts were prone to apoptotic cell death upon starvation along with bile-acids treatment in vitro or in an ICP mouse model in vivo. Additionally, we revealed mitochondrial dysfunction was the predominant biological process in excessive bile acids induced trophoblast impairment under starvation by proteomic assay. Collectively, our study proposed a complex interaction of excessive bile acids induced autophagic flux, mitochondrial dysfunction, and cellular apoptosis in placental trophoblasts may play a critical role in the pathogenesis of ICP.
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Placenta , Trofoblastos , Animales , Apoptosis , Autofagia , Ácidos y Sales Biliares/farmacología , Colestasis Intrahepática , Femenino , Humanos , Ratones , Mitocondrias , Placenta/metabolismo , Embarazo , Complicaciones del Embarazo , Proteómica , Trofoblastos/metabolismoRESUMEN
Importance: Bile acids play essential roles in metabolic modulation. Excessive serum total bile acid (sTBA) levels during pregnancy are associated with adverse perinatal outcomes; however, their association with the risk of intrauterine growth restriction (IUGR) remains unclear. Objective: To investigate the association between maternal sTBA concentration during pregnancy and the risk of IUGR. Design, Setting, and Participants: This retrospective cohort study included pregnant individuals who delivered live singleton neonates and had regular antenatal examination records available at a hospital-based center in Shanghai, China, from 2014 to 2018. Data were analyzed from July to November 2020. Exposures: Maternal sTBA concentration during pregnancy. Main Outcomes and Measures: Fetal birth weight and probability of low birth weight (LBW) and IUGR. Results: This study included 68â¯245 singleton pregnancies with live births for analysis. The mean (SD) age of the pregnant individuals was 30.5 (3.8) years, 67â¯168 patients (98.4%) were Han, and 50â¯155 (73.5%) were nulliparous. Nonlinear regression models suggested that there was an inverted J-shaped association between maternal sTBA level during pregnancy and fetal birth weight, with a steep decrease in birth weight at high sTBA levels (estimated mean [SE] birth weight for sTBA of 40.8 ug/mL, 2879 [39.9] g) and greater birth weights at lower sTBA levels (estimated mean [SE] birth weight for sTBA 0.4 µg/mL, 3290 [3.9] g; and for 4.1 µg/mL, 3334 [1.6] g). Lower birth weight and a higher incidence of IUGR were observed in patients with gestational hypercholanemia (sTBA ≥4.08 µg/mL) compared with those without gestational hypercholanemia (birth weight: estimated adjusted mean [SE], 3309 [3.32] vs 3338 [0.80] g; P = .005; incidence of IUGR: 62 of 4467 [1.4%] vs 312 of 63â¯778 [0.5%]; P < .001). Moreover, compared with patients with sTBA concentrations of less than 4.08 µg/mL, those with gestational hypercholanemia had an increased risk of LBW (adjusted odds ratio [aOR], 1.29; 95% CI, 1.09-1.53) and IUGR (aOR, 2.18; 95% CI, 1.62-2.91). In addition, there was an additive interaction between hypertensive disorders in pregnancy (HDP) and hypercholanemia on LBW and IUGR risk. The highest risks of LBW and IUGR were found in pregnant individuals with both HDP and hypercholanemia compared with those with normotensive pregnancies with sTBA concentrations less than 4.08 µg/mL (LBW: aOR, 9.13; 95% CI, 6.88-12.12; IUGR: aOR, 19.14; 95% CI, 12.09-30.28). Conclusions and Relevance: This study found that gestational hypercholanemia was associated with an increased risk of LBW and IUGR, especially in pregnant individuals with HDP. Therefore, it would be meaningful to monitor sTBA concentration during the follow-up of pregnancies with potential IUGR.
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Ácidos y Sales Biliares/sangre , Retardo del Crecimiento Fetal/sangre , Recién Nacido de Bajo Peso , Pruebas de Detección del Suero Materno/estadística & datos numéricos , Complicaciones del Embarazo/sangre , Adulto , Peso al Nacer , China , Femenino , Peso Fetal , Humanos , Hipertensión Inducida en el Embarazo/sangre , Recién Nacido , Embarazo , Análisis de Regresión , Estudios RetrospectivosRESUMEN
Carcinoma in situ (CIS) of the uterine cervix is a precursor to cervical carcinoma. However, hysterectomy can be avoided in patients who can be treated by cone biopsy. Previous studies have shown that imaging-based approaches allow for the noninvasive visualization of cervical cancer, and radiomics has high accuracy in classifying cancer and predicting treatment outcome for different cancer types. To develop a magnetic resonance (MR)-based radiomics model for identifying residual disease in patients with CIS after cervical conization. Patients who had CIS after conization and finally underwent hysterectomy were collected to comprise a database to establish an imaging model for predicting the residual status after conization. Then, patients who opted for uterine preservation were classified as high-risk or low-risk patients according to the model. The disease-free survival was compared between the different risk groups using the Kaplan-Meier curve. The model built with the Boruta features outperformed the random forest model. Further validation with patients with uterine preservation showed that the patients classified as high risk were more likely to have tumor recurrence/residual disease in the follow-up period. In conclusion, radiomics can be used to identify residual disease in patients with CIS after cervical conization and could have the potential to predict recurrence in patients who opt for uterine preservation.
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Carcinoma in Situ/patología , Conización/métodos , Histerectomía/métodos , Imagen por Resonancia Magnética/métodos , Neoplasia Residual/patología , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Carcinoma in Situ/cirugía , Femenino , Humanos , Persona de Mediana Edad , Neoplasia Residual/cirugía , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/cirugía , Adulto Joven , Displasia del Cuello del Útero/cirugíaRESUMEN
We report a dual-tasked methylation that is based on cooperative palladium/norbornene catalysis. Readily available (hetero)aryl halides (39 iodides and 4 bromides) and inexpensive MeOTs or trimethylphosphate are utilized as the substrates and methylating reagent, respectively. Six types of "ipso" terminations can modularly couple with this "ortho" C-H methylation to constitute a versatile methylation toolbox for preparing diversified methylated arenes. This toolbox features inexpensive methyl sources, excellent functional-group tolerance, simple reaction procedures, and scalability. Importantly, it can be uneventfully extended to isotope-labeled methylation by switching to the corresponding reagents CD3OTs or 13CH3OTs. Moreover, this toolbox can be applied to late-stage modification of biorelevant substrates with complete stereoretention. We believe these salient and practical features of our dual-tasked methylation toolbox will be welcomed by academic and industrial researchers.
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Placental insufficiency is a major cause of intrauterine growth restriction (IUGR) and seriously affects fetal development. When placental insufficiency happened, the diffusion of water molecule was restricted and the metabolic balance was destroyed in the placenta. In this prospective study, we aimed to evaluate the diagnostic value of diffusion-weighted imaging (DWI) in combination with proton magnetic resonance spectroscopy (1H MRS) for placental insufficiency in IUGR. The apparent diffusion coefficient (ADC) values were calculated using DWI, and the metabolism of N-acetylaspartate (NAA), choline, and lipid and their ratios in the placenta were calculated using 1H MRS. Data were statistically analyzed by receiver operating characteristic (ROC) curves and logistic regression analysis. The NAA and choline peaks were decreased in IUGR placentas compared with normal placentas, while lipid peaks showed an opposite trend. The average ADC value and the NAA/lipid and choline/lipid ratios were lower in the IUGR group than in the normal group ( P < .01). Logistic regression with multiple parameters showed that combination of the ADC value and choline/lipid ratio was more favorable than either parameter alone in analyzing placental insufficiency of IUGR ( P < .05). The area under the ROC curve for the combination was 0.939, indicating reasonably good discrimination. We concluded that reduced ADC and NAA/lipid and choline/lipid ratios could serve as potential markers for placental insufficiency of IUGR. Furthermore, the combination of ADC value and choline/lipid ratio greatly improved the diagnostic value.