Activation of hepatic acetyl-CoA carboxylase by S-nitrosylation in response to diet.

Nitric oxide (NO), produced primarily by nitric oxide synthase enzymes, is known to influence energy metabolism by stimulating fat uptake and oxidation. The effects of NO on de novo lipogenesis (DNL), however, are less clear. Here we demonstrate that hepatic expression of endothelial nitric oxide synthase is reduced following prolonged administration of a hypercaloric high-fat diet. This results in marked reduction in the amount of S-nitrosylation of liver proteins including notably acetyl-CoA carboxylase (ACC), the rate-limiting enzyme in DNL. We further show that ACC S-nitrosylation markedly increases enzymatic activity. Diminished endothelial nitric oxide synthase expression and ACC S-nitrosylation may thus represent a physiological adaptation to caloric excess by constraining lipogenesis. Our findings demonstrate that S-nitrosylation of liver proteins is subject to dietary control and suggest that DNL is coupled to dietary and metabolic conditions through ACC S-nitrosylation.

A Hybrid Model for Fetal Growth Restriction Assessment by Automatic Placental Radiomics on T2-Weighted MRI and Multifeature Fusion.

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.

An enzyme that selectively S-nitrosylates proteins to regulate insulin signaling.

Acyl-coenzyme A (acyl-CoA) species are cofactors for numerous enzymes that acylate thousands of proteins. Here, we describe an enzyme that uses S-nitroso-CoA (SNO-CoA) as its cofactor to S-nitrosylate multiple proteins (SNO-CoA-assisted nitrosylase, SCAN). Separate domains in SCAN mediate SNO-CoA and substrate binding, allowing SCAN to selectively catalyze SNO transfer from SNO-CoA to SCAN to multiple protein targets, including the insulin receptor (INSR) and insulin receptor substrate 1 (IRS1). Insulin-stimulated S-nitrosylation of INSR/IRS1 by SCAN reduces insulin signaling physiologically, whereas increased SCAN activity in obesity causes INSR/IRS1 hypernitrosylation and insulin resistance. SCAN-deficient mice are thus protected from diabetes. In human skeletal muscle and adipose tissue, SCAN expression increases with body mass index and correlates with INSR S-nitrosylation. S-nitrosylation by SCAN/SNO-CoA thus defines a new enzyme class, a unique mode of receptor tyrosine kinase regulation, and a revised paradigm for NO function in physiology and disease.

White matter injury detection based on preterm infant cranial ultrasound images.

Introduction: White matter injury (WMI) is now the major disease that seriously affects the quality of life of preterm infants and causes cerebral palsy of children, which also causes periventricular leuko-malacia (PVL) in severe cases. The study aimed to develop a method based on cranial ultrasound images to evaluate the risk of WMI. Methods: This study proposed an ultrasound radiomics diagnostic system to predict the WMI risk. A multi-task deep learning model was used to segment white matter and predict the WMI risk simultaneously. In total, 158 preterm infants with 807 cranial ultrasound images were enrolled. WMI occurred in 32preterm infants (20.3%, 32/158). Results: Ultrasound radiomics diagnostic system implemented a great result with AUC of 0.845 in the testing set. Meanwhile, multi-task deep learning model preformed a promising result both in segmentation of white matter with a Dice coefficient of 0.78 and prediction of WMI risk with AUC of 0.863 in the testing cohort. Discussion: In this study, we presented a data-driven diagnostic system for white matter injury in preterm infants. The system combined multi-task deep learning and traditional radiomics features to achieve automatic detection of white matter regions on the one hand, and design a fusion strategy of deep learning features and manual radiomics features on the other hand to obtain stable and efficient diagnostic performance.

Fetal-placental MR angiography at 1.5 T and 3 T.

OBJECTIVES: The objective of this work was to investigate the application of 2D Time-of-Flight (TOF) magnetic resonance angiography (MRA) to observe the placental vasculature at both 1.5 T and 3 T. METHODS: Fifteen appropriate for gestational age (AGA) (GA: 29.7 ± 3.4 weeks; GA range: 23 and 6/7 weeks to 36 and 2/7 weeks) and eleven patients with an abnormal singleton pregnancy (GA: 31.4 ± 4.4 weeks; GA range: 24 weeks to 35 and 2/7 weeks) were recruited in the study. Three AGA patients were scanned twice at different gestational ages. Patients were scanned either at 3 T or 1.5 T using both T2-HASTE and 2D TOF to image the entire placental vasculature. RESULTS: The umbilical, chorionic vessels, stem vessels, arcuate arteries, radial arteries, and spiral arteries were shown in most of the subjects. Hyrtl's anastomosis was found in two subjects in the 1.5 T data. The uterine arteries were observed in more than half of the subjects. For those patients scanned twice, the same spiral arteries were identified in both scans. CONCLUSIONS: 2D TOF is a technique that can be applied in studying the fetal-placental vasculature at both 1.5 T and 3 T.

Predicting the risk of fetal growth restriction by radiomics analysis of the placenta on T2WI: A retrospective case-control study.

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.

Transition of ovarian granulosa cell tumor from a solid mass to a cystic mass in two months on MR imaging in an adult woman: A case report.

Ovarian granulosa cell tumor (OGCT) is a relatively rare ovarian tumor originating from ovarian sex cord-stromal cells. It is generally believed that the tumor is mainly a solid mass in the early stage, and with the volume increasing, the tumor would undergo multiple cystic changes. But few such cases have been reported. This article reports a case of transition of ovarian granulosa cell tumor from a solid mass to a cystic mass in 2 months on MR imaging in an adult woman. In this case, a 55-year-old postmenopausal woman underwent MR imaging for irregular vaginal bleeding in March 2022, during which a 6-cm cystic-solid mass was detected in the right ovary with iso-hypo intensity on T1WI, iso-hyper intensity on T2WI, and hyper intensity on DWI. After injection of the contrast medium, the mass displayed progressive and obvious enhancement, which was diagnosed as OGCT. Due to the COVID-19 pandemic, the patient was unable to receive surgery in time. Two months later, the patient returned to the hospital and underwent MRI again, when a 20-cm cyst mass was detected in the pelvis, which contained little solid component at the edge. The patient was admitted and underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The postoperative pathology confirmed the diagnosis of adult type stage IC1 OGCT. This finding may be precious in that it could help understand the initiation and progression of OGCT.

A multienzyme S-nitrosylation cascade regulates cholesterol homeostasis.

Accumulating evidence suggests that protein S-nitrosylation is enzymatically regulated and that specificity in S-nitrosylation derives from dedicated S-nitrosylases and denitrosylases that conjugate and remove S-nitrosothiols, respectively. Here, we report that mice deficient in the protein denitrosylase SCoR2 (S-nitroso-Coenzyme A Reductase 2; AKR1A1) exhibit marked reductions in serum cholesterol due to reduced secretion of the cholesterol-regulating protein PCSK9. SCoR2 associates with endoplasmic reticulum (ER) secretory machinery to control an S-nitrosylation cascade involving ER cargo-selection proteins SAR1 and SURF4, which moonlight as S-nitrosylases. SAR1 acts as a SURF4 nitrosylase and SURF4 as a PCSK9 nitrosylase to inhibit PCSK9 secretion, while SCoR2 counteracts nitrosylase activity by promoting PCSK9 denitrosylation. Inhibition of PCSK9 by an NO-based drug requires nitrosylase activity, and small-molecule inhibition of SCoR2 phenocopies the PCSK9-mediated reductions in cholesterol observed in SCoR2-deficient mice. Our results reveal enzymatic machinery controlling cholesterol levels through S-nitrosylation and suggest a distinct treatment paradigm for cardiovascular disease.

S-nitrosylation is required for ß2AR desensitization and experimental asthma.

The ß2-adrenergic receptor (ß2AR), a prototypic G-protein-coupled receptor (GPCR), is a powerful driver of bronchorelaxation, but the effectiveness of ß-agonist drugs in asthma is limited by desensitization and tachyphylaxis. We find that during activation, the ß2AR is modified by S-nitrosylation, which is essential for both classic desensitization by PKA as well as desensitization of NO-based signaling that mediates bronchorelaxation. Strikingly, S-nitrosylation alone can drive ß2AR internalization in the absence of traditional agonist. Mutant ß2AR refractory to S-nitrosylation (Cys265Ser) exhibits reduced desensitization and internalization, thereby amplifying NO-based signaling, and mice with Cys265Ser mutation are resistant to bronchoconstriction, inflammation, and the development of asthma. S-nitrosylation is thus a central mechanism in ß2AR signaling that may be operative widely among GPCRs and targeted for therapeutic gain.

Optimized S-nitrosohemoglobin Synthesis in Red Blood Cells to Preserve Hypoxic Vasodilation Via ßCys93.

Classic physiology links tissue hypoxia to oxygen delivery through control of microvascular blood flow (autoregulation of blood flow). Hemoglobin (Hb) serves both as the source of oxygen and the mediator of microvascular blood flow through its ability to release vasodilatory S-nitrosothiol (SNO) in proportion to degree of hypoxia. ß-globin Cys93Ala (ßCys93Ala) mutant mice deficient in S-nitrosohemoglobin (SNO-Hb) show profound deficits in microvascular blood flow and tissue oxygenation that recapitulate microcirculatory dysfunction in multiple clinical conditions. However, the means to replete SNO in mouse red blood cells (RBCs) to restore RBC function is not known. In particular, although methods have been developed to selectively S-nitrosylate ßCys93 in human Hb and intact human RBCs, conditions have not been optimized for mouse RBCs that are used experimentally. Here we show that loading SNO onto Hb in mouse RBC lysates can be achieved with high stoichiometry and ß-globin selectivity. However, S-nitrosylation of Hb within intact mouse RBCs is ineffective under conditions that work well with human RBCs, and levels of metHb are prohibitively high. We developed an optimized method that loads SNO in mouse RBCs to maintain vasodilation under hypoxia and shows that loss of SNO loading in ßCys93Ala mutant RBCs results in reduced vasodilation. We also demonstrate that differences in SNO/met/nitrosyl Hb stoichiometry can account for differences in RBC function among studies. RBCs loaded with quasi-physiologic amounts of SNO-Hb will produce vasodilation proportionate to hypoxia, whereas RBCs loaded with higher amounts lose allosteric regulation, thus inducing vasodilation at both high and low oxygen level. SIGNIFICANCE STATEMENT: Red blood cells from mice exhibit poor hemoglobin S-nitrosylation under conditions used for human RBCs, frustrating tests of vasodilatory activity. Using an optimized S-nitrosylation protocol, mouse RBCs exhibit hypoxic vasodilation that is significantly reduced in hemoglobin ßCys93Ala mutant RBCs that cannot carry S-nitrosothiol allosterically, providing genetic validation for the role of ßCys93 in oxygen delivery.

Detecting abnormal placental microvascular flow in maternal and fetal diseases based on flow-compensated and non-compensated intravoxel incoherent motion imaging.

INTRODUCTION: Intravoxel Incoherent Motion (IVIM) imaging has been used to assess placental microcirculatory flows. We proposed a joint analysis of flow-compensated (FC) and non-compensated (NC) diffusion MRI to estimate the fraction and velocity of ballistic microcirculatory flow (fb and vb), and evaluated the diagnostic performance of the new markers in maternal and fetal disorders. METHODS: Gestational diabetes mellitus (GDM, n = 15) pregnancies and fetal growth restriction (FGR, n = 12), along with gestational age matched normal controls (n = 19 for GDM and 15 for FGR) underwent FC and NC-encoded IVIM scans at 1.5 T. fb and vb obtained from a FC-NC joint model, along with the conventional IVIM indices, were compared between patient groups for whole-placenta and maternal/fetal sides of the placenta. A linear support vector machine (SVM) was used to classify the GDM, FGR and controls. RESULTS: vb of whole-placenta were significantly lower in both GDM (p = 0.017) and FGR (p = 0.043), compared with their controls, and the differences were more evident in the fetal side (p = 0.010 for GDM and p = 0.042 for FGR). fb and fFC showed group differences in the fetal side and DFC showed differences in whole-placenta for GDM patients. In the classification task, vb showed the highest diagnostic accuracy of 70.6% for GDM and 63.0% for FGR, and the combination of fb and vb further improved the detection accuracy to 73.5% and 66.7% for GDM and FGR, respectively. DISCUSSION: vb showed superior performance in the diagnosis of GDM and FGR, indicating the potential of the joint FC-NC IVIM method for placenta examinations.

Hypoxic vasodilatory defect and pulmonary hypertension in mice lacking hemoglobin ß-cysteine93 S-nitrosylation.

Systemic hypoxia is characterized by peripheral vasodilation and pulmonary vasoconstriction. However, the system-wide mechanism for signaling hypoxia remains unknown. Accumulating evidence suggests that hemoglobin (Hb) in RBCs may serve as an O2 sensor and O2-responsive NO signal transducer to regulate systemic and pulmonary vascular tone, but this remains unexamined at the integrated system level. One residue invariant in mammalian Hbs, ß-globin cysteine93 (ßCys93), carries NO as vasorelaxant S-nitrosothiol (SNO) to autoregulate blood flow during O2 delivery. ßCys93Ala mutant mice thus exhibit systemic hypoxia despite transporting O2 normally. Here, we show that ßCys93Ala mutant mice had reduced S-nitrosohemoglobin (SNO-Hb) at baseline and upon targeted SNO repletion and that hypoxic vasodilation by RBCs was impaired in vitro and in vivo, recapitulating hypoxic pathophysiology. Notably, ßCys93Ala mutant mice showed marked impairment of hypoxic peripheral vasodilation and developed signs of pulmonary hypertension with age. Mutant mice also died prematurely with cor pulmonale (pulmonary hypertension with right ventricular dysfunction) when living under low O2. Altogether, we identify a major role for RBC SNO in clinically relevant vasodilatory responses attributed previously to endothelial NO. We conclude that SNO-Hb transduces the integrated, system-wide response to hypoxia in the mammalian respiratory cycle, expanding a core physiological principle.

A Combined Nomogram Model to Predict Disease-free Survival in Triple-Negative Breast Cancer Patients With Neoadjuvant Chemotherapy.

Background: To investigate whether the radiomics signature (Rad-score) of DCE-MRI images obtained in triple-negative breast cancer (TNBC) patients before neoadjuvant chemotherapy (NAC) is associated with disease-free survival (DFS). Develop and validate an intuitive nomogram based on radiomics signatures, MRI findings, and clinicopathological variables to predict DFS. Methods: Patients (n = 150) from two hospitals who received NAC from August 2011 to May 2017 were diagnosed with TNBC by pathological biopsy, and follow-up through May 2020 was retrospectively analysed. Patients from one hospital (n = 109) were used as the training group, and patients from the other hospital (n = 41) were used as the validation group. ROIs were drawn on 1.5 T MRI T1W enhancement images of the whole volume of the tumour obtained with a 3D slicer. Radiomics signatures predicting DFS were identified, optimal cut-off value for Rad-score was determined, and the associations between DFS and radiomics signatures, MRI findings, and clinicopathological variables were analysed. A nomogram was developed and validated for individualized DFS estimation. Results: The median follow-up time was 53.5 months, and 45 of 150 (30.0%) patients experienced recurrence and metastasis. The optimum cut-off value of the Rad-score was 0.2528, which stratified patients into high- and low-risk groups for DFS in the training group (p<0.001) and was validated in the external validation group. Multivariate analysis identified three independent indicators: multifocal/centric disease status, pCR status, and Rad-score. A nomogram based on these factors showed discriminatory ability, the C-index of the model was 0.834 (95% CI, 0.761-0.907) and 0.868 (95% CI, 0.787-949) in the training and the validation groups, respectively, which is better than clinicoradiological nomogram(training group: C-index = 0.726, 95% CI = 0.709-0.743; validation group: C-index = 0.774,95% CI = 0.743-0.805). Conclusion: The Rad-score derived from preoperative MRI features is an independent biomarker for DFS prediction in patients with TNBC to NAC, and the combined radiomics nomogram improved individualized DFS estimation.

Age-specific structural fetal brain atlases construction and cortical development quantification for chinese population.

In magnetic resonance imaging (MRI) studies of fetal brain development, structural brain atlases usually serve as essential references for the fetal population. Individual images are usually normalized into a common or standard space for analysis. However, the existing fetal brain atlases are mostly based on MR images obtained from Caucasian populations and thus are not ideal for the characterization of the fetal Chinese population due to neuroanatomical differences related to genetic factors. In this paper, we use an unbiased template construction algorithm to create a set of age-specific Chinese fetal atlases between 21-35 weeks of gestation from 115 normal fetal brains. Based on the 4D spatiotemporal atlas, the morphological development patterns, e.g., cortical thickness, cortical surface area, sulcal and gyral patterns, were quantified. The fetal brain abnormalities were detected when referencing the age-specific template. Additionally, a direct comparison of the Chinese fetal atlases and Caucasian fetal atlases reveals dramatic anatomical differences, mainly in the medial frontal and temporal regions. After applying the Chinese and Caucasian fetal atlases separately to an independent Chinese fetal brain dataset, we find that the Chinese fetal atlases result in significantly higher accuracy than the Caucasian fetal atlases in guiding brain tissue segmentation. These results suggest that the Chinese fetal brain atlases are necessary for quantitative analysis of the typical and atypical development of the Chinese fetal population in the future. The atlases with their parcellations are now publicly available at https://github.com/DeepBMI/FBA-Chinese.

Ultrasound-Guided High-Intensity Focused Ultrasound for Devascularization of Uterine Fibroid: A Feasibility Study.

This study aimed to establish the feasibility of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for devascularization of uterine fibroids. Ultrasound color Doppler flow imaging (CDFI) and B-mode imaging were used to target fibroid vascularity. The vessels were covered and ablated by high-intensity focused ultrasound spots. In this study, 42 fibroids with a volume of 66.98 ± 4.00 cm3 were treated. No blood flow was detected by post-treatment CDFI in 40 fibroids. The 6-mo non-perfusion volume rate was 75.23% ± 34.77% (n = 40). The mean shrinkage in fibroid volume was 38.20% and 43.89%, respectively, at 1 and 6 mo after treatment (p < 0.001). The uterine fibroid symptom and quality of life scores were reduced by 9.43% at 1 mo and 26.66% at 6-mo after treatment (p < 0.001). No serious adverse event was observed. This study demonstrates the feasibility of USgHIFU-induced fibroid devascularization, and more studies are required for the evaluation of safety and efficacy.

Estimating cerebral venous oxygenation in human fetuses with ventriculomegaly using quantitative susceptibility mapping.

RATIONALE AND OBJECTIVES: The goal of this study was to estimate venous blood oxygen saturation (SvO2) in the superior sagittal sinus (SSS) in fetal brains with ventriculomegaly (VM) using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: A radiofrequency spoiled gradient echo sequence was used to evaluate data on 19 fetuses with VM (gestational age(GA): median = 29.9 weeks (range 23 to 37.3 weeks)) and 20 healthy fetuses (GA: median = 30.9 (range 22.7 to 38.7 weeks)) at 1.5 T. Susceptibility weighted images encompassing the entire fetal brain were acquired within 1 min. An iterative, geometry constraint-based thresholded k-space division algorithm was used for generating QSM data of the fetal brain. The venous oxygen saturation was calculated using the magnetic susceptibility of the SSS obtained from the QSM data. Mixed-model analysis of variance and interobserver variability assessment were used to analyze the results. RESULTS: The median SvO2 values in the entire VM cohort as well as for second and third trimester fetuses (with interquartile range) were: 67.8% (63.2%, 73.6%), 73.1% (69.1%, 77.3%) and 63.8% (59.4%, 68.1%), respectively. The corresponding median SvO2 value in the healthy control group was: 65.3% (58.3%, 68.2%), 67.5% (61.7%, 69.2%) and 60.8% (53.6%, 68.2%), respectively. However, the difference of SvO2 between VM and control groups was not significant at the p = 0.05 level (p = 0.076). The SvO2 was found decreasing significantly with GA in the healthy control group (p < 0.05). CONCLUSIONS: We report for the first time the estimation of cerebral SvO2 in human fetuses with VM using QSM. This measure of oxygen saturation might be beneficial in assessing and monitoring the metabolic status of the fetus in various clinical conditions.

Abdominopelvic leiomyoma with large ascites: A case report and review of the literature.

BACKGROUND: Leiomyoma of the uterus is relatively common, but uterine leiomyoma of the greater omentum is rare. CASE SUMMARY: Here, we report the case of a 22-year-old woman who presented with a 3 mo history of progressive abdominal distension and a hypervascular abdominopelvic mass. Due to a high serum concentration of CA125, the preoperative diagnosis was unclear. During surgery, 5 L of ascites was removed. An 18.8 cm solid mass, which was pedunculated from the uterine fundus and exhibited complex adhesion to the greater omentum, was removed. The CA125 level was reduced postoperatively, and a pathologic study confirmed that the mass was a leiomyoma that originated in the uterus. CONCLUSION: Uterine leiomyoma can share vessels with the greater omentum. This case highlights the difficulty of diagnosing pseudo-Meigs syndrome and the importance of imaging and laboratory examinations.

Fetal brain tissue characterization at 1.5 T using STrategically Acquired Gradient Echo (STAGE) imaging.

OBJECTIVES: To estimate human fetal brain MRI tissue properties including apparent T1 (T1app) and apparent proton density (PDapp) by using a rapid multi-contrast acquisition protocol called STrategically Acquired Gradient Echo (STAGE) imaging. METHODS: STAGE data were collected using two flip angles (15° and 60°, with a TR = 600 ms) for 30 pregnant women at 1.5 T (15 healthy controls: gestational age (GA) range 19 + 1/7 weeks to 34 + 5/7 weeks; 11 abnormal subjects with ventriculomegaly: GA range 21 + 5/7 weeks to 31 + 5/7 weeks; 4 subjects with other abnormalities). Both T1app and PDapp maps of the fetal brain were calculated from the STAGE data. A region-of-interest-based approach was used to measure T1app and PDapp in the subplate/intermediate zone (SP/IZ), cortical plate (CP), and cerebrospinal fluid (CSF) in the fetal brain. RESULTS: The ratios of T1appSP/IZ/T1appCP and PDappSP/IZ/PDappCP were larger than unity while T1appSP/IZ/T1appCSF and PDappSP/IZ/PDappCSF were both less than unity. CONCLUSIONS: STAGE imaging provides a potential practical approach to estimate multi-parametric properties of the human fetal brain. KEY POINTS: • STAGE is feasible in measuring fetal brain tissue properties. • Water content in cortical plate and subplate/intermediate zone approaches that of cerebrospinal fluid in early gestational ages.

Probing the ballistic microcirculation in placenta using flow-compensated and non-compensated intravoxel incoherent motion imaging.

PURPOSE: Intravoxel incoherent motion (IVIM) imaging is widely used to evaluate microcirculatory flow, which consists of diffusive and ballistic flow components. We proposed a joint use of flow-compensated (FC) and non-compensated (NC) diffusion gradients to probe the fraction and velocity of ballistic flow in the placenta. METHODS: Forty pregnant women were included in this study and scanned on a 1.5T clinical scanner. FC and NC diffusion MRI (dMRI) sequences were achieved using a pair of identical or mirrored bipolar gradients. A joint FC-NC model was established to estimate the fraction (fb ) and velocity (vb ) of the ballistic flow. Conventional IVIM parameters (f, D, and D*) were obtained from the FC and NC data, separately. The vb and f·D*, as placental flow velocity measurements, were correlated with the umbilical-artery Doppler ultrasound indices and gestational ages. RESULTS: The ballistic flow component can be observed from the difference between the FC and NC dMRI signal decay curves. vb fitted from the FC-NC model showed strong correlations with umbilical-artery impedance indices, the systolic-to-diastolic (SD) ratio and pulsatility index (PI), with correlation coefficients of 0.65 and 0.62. The f·D* estimated from the NC data positively correlated with SD and PI, while the FC-based f·D* values showed weak negative correlations. Significant gestational-age dependence was also found in the flow velocity measurements. CONCLUSION: Our results demonstrated the feasibility of using FC and NC dMRI to noninvasively measure ballistic flow velocity in the placenta, which may be used as a new marker to evaluate placenta microcirculation.