Is the rabbit a natural model of fetal growth restriction? Morphological and functional characterization study using diffusion-weighted MRI and stereology.

INTRODUCTION: Rabbits are routinely used as a natural model of fetal growth restriction (FGR); however, no studies have confirmed that rabbits have FGR. This study aimed to characterize the fetoplacental unit (FPU) in healthy pregnant rabbits using diffusion-weighted MRI and stereology. A secondary objective of the study was to describe the associations among findings from diffusion-weighted MRI (DW-MRI), fetal weight measurement and histological analysis of the placenta. METHODS: Pregnant rabbits underwent DW-MRI under general anesthesia on embryonic day 28 of pregnancy. MR imaging was performed at 3.0 T. The apparent diffusion coefficient (ADC) values were calculated for the fetal brain, liver, and placenta. The placenta was analyzed by stereology (volume density of trophoblasts, the maternal blood space and fetal vessels). Each fetus and placenta were weighed. Two groups of fetuses were defined according to the position in the uterine horn (Cervix group versus Ovary group). RESULTS: We analyzed 20 FPUs from 5 pregnant rabbits. Fetuses and placentas were significantly lighter in the Cervix group than in the Ovary group (34.7 ± 3.7 g vs. 40.2 ± 5.4 g; p = 0.02). Volume density analysis revealed that the percentage of fetal vessels, the maternal blood space and trophoblasts was not significantly affected by the position of the fetus in the uterine horn. There was no difference in ADC values according to the position of the fetus in the uterine horn, and there was no correlation between ADC values and fetal weight. DISCUSSION: The findings of a multimodal evaluation of the placenta in a rabbit model of FGR suggested is not a natural model of fetal growth restriction.

From the Clinical to the Bench: Exploring the Insulin Modulation Effects of Tacrolimus and Belatacept.

Calcineurin inhibitors (CNIs) are critical in preventing rejection posttransplantation but pose an increased risk of post-transplant diabetes (PTD). Recent studies show that late conversion from CNIs to belatacept, a costimulation blocker, improves HbA1c in kidney transplant recipients with PTD or de novo diabetes. This study investigates whether the observed effects on PTD stem solely from CNI withdrawal or if belatacept influences PTD independently. The study assessed the impact of tacrolimus and belatacept on insulin secretion in MIN6 cells (a beta cell line) and rat islets. Tacrolimus and belatacept were administered to the cells and islets, followed by assessments of cell viability and insulin secretion. Tacrolimus impaired insulin secretion without affecting cell viability, while belatacept showed no detrimental effects on either parameter. These findings support clinical observations of improved HbA1c upon switching from tacrolimus to belatacept. Belatacept holds promise in islet or pancreas transplantation, particularly in patients with unstable diabetes. Successful cases of islet transplantation treated with belatacept without severe hypoglycemia highlight its potential in managing PTD. Further research is needed to fully understand the metabolic changes accompanying the transition from CNIs to belatacept. Preserving insulin secretion emerges as a promising avenue for investigation in this context.

Role of aldosterone in mid- and long-term left ventricular remodelling after acute myocardial infarction: The REMI study.

AIMS: Whether aldosterone levels after myocardial infarction (MI) are associated with mid- and long-term left ventricular (LV) remodelling in the era of systematic use of renin-angiotensin system inhibitors is uncertain. We prospectively investigated the relationship between aldosterone levels and mid- and long-term LV remodelling in patients with acute MI. METHODS AND RESULTS: Plasma aldosterone was measured in 119 patients successfully treated by primary percutaneous coronary angioplasty for a first acute ST-elevation MI (STEMI) 2-4 days after the acute event. LV volumes were assessed by cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) in the same timeframe and 6 months later. LV assessment was repeated by TTE 3-9 years after MI (n = 80). The median aldosterone level at baseline was 23.1 [16.8; 33.1] pg/ml. In the multivariable model, higher post-MI aldosterone concentration was significantly associated with more pronounced increase in LV end-diastolic volume index (TTE: ß ± standard error [SE]: 0.113 ± 0.046, p = 0.015; CMR: ß ± SE: 0.098 ± 0.040, p = 0.015) and LV end-systolic volume index (TTE: ß ± SE: 0.083 ± 0.030, p = 0.008; CMR: ß ± SE: 0.064 ± 0.032, p = 0.048) at 6-month follow-up, regardless of the method of assessment. This result was consistent also in patients with a LV ejection fraction (LVEF) >40%. The association between baseline plasma aldosterone and adverse LV remodelling did not persist at the 3-9-year follow-up evaluation. CONCLUSION: Aldosterone concentration in the acute phase was associated with adverse LV remodelling in the medium term, even in the subgroup of patients with LVEF >40%, suggesting a potential role of the mineralocorticoid system in post-MI adverse remodelling. Plasma aldosterone was no longer associated with LV remodelling in the long term (NCT01109225).

Contribution of contrast-enhanced ultrasound in the diagnosis of adnexal torsion (AGATA): protocol for a prospective comparative study.

INTRODUCTION: Adnexal torsion is a surgical emergency and its prognosis depends on the time elapsed prior to treatment. The diagnosis relies on pelvic ultrasound in which sensitivity remains low and may lead to misdiagnosis.The primary objective is to evaluate the diagnostic performance of contrast-enhanced ultrasound for the diagnosis of adnexal torsion in women with suspected adnexal torsion. The secondary objectives are: (1) to describe the perfusion parameters of the ovaries by contrast-enhanced ultrasound, (2) to compare diagnostic performance of contrast ultrasound with bidimensional (2D) Doppler for the detection of adnexal torsion, (3) to describe the perfusion parameters of the ovarian as a function of the degree of adnexal torsion, (4) to compare perfusion parameters before and after ovarian detorsion and (5) to describe perfusion parameters of the ovarian by using MicroVascular Flow technique. METHODS AND ANALYSIS: This is a monocentric, prospective comparative, non-randomised, open and interventional study. We hypothesise to include 30 women: 20 positive cases compared with 10 control cases. Women are informed and recruited in the emergency ward, over a period of 36 months.The primary endpoint is the signal intensity measurement to assess sensitivity, specificity, positive and negative predictive values of contrast-enhanced ultrasound for detection of adnexal torsion in women with suspected adnexal torsion. The presence or absence of adnexal torsion is confirmed during the surgical intervention. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee, the CPP (Comité de Protection des Personnes) OUEST I on 3 July 2020 with reference number 2020T1-16. The results of this study will be published in a peer-reviewed journal and will be presented at relevant conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT04522219); EudraCT registry (2020-000993-27).

Machine Learning-Based Phenogrouping in MVP Identifies Profiles Associated With Myocardial Fibrosis and Cardiovascular Events.

BACKGROUND: Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in patients with mitral valve prolapse (MVP). In this setting, it is likely that an unsupervised approach using machine learning may improve their risk assessment. OBJECTIVES: This study used machine learning to improve the risk assessment of patients with MVP by identifying echocardiographic phenotypes and their respective association with myocardial fibrosis and prognosis. METHODS: Clusters were constructed using echocardiographic variables in a bicentric cohort of patients with MVP (n = 429, age 54 ± 15 years) and subsequently investigated for their association with myocardial fibrosis (assessed by cardiac magnetic resonance) and cardiovascular outcomes. RESULTS: Mitral regurgitation (MR) was severe in 195 (45%) patients. Four clusters were identified: cluster 1 comprised no remodeling with mainly mild MR, cluster 2 was a transitional cluster, cluster 3 included significant left ventricular (LV) and left atrial (LA) remodeling with severe MR, and cluster 4 included remodeling with a drop in LV systolic strain. Clusters 3 and 4 featured more myocardial fibrosis than clusters 1 and 2 (P < 0.0001) and were associated with higher rates of cardiovascular events. Cluster analysis significantly improved diagnostic accuracy over conventional analysis. The decision tree identified the severity of MR along with LV systolic strain <21% and indexed LA volume >42 mL/m2 as the 3 most relevant variables to correctly classify participants into 1 of the echocardiographic profiles. CONCLUSIONS: Clustering enabled the identification of 4 clusters with distinct echocardiographic LV and LA remodeling profiles associated with myocardial fibrosis and clinical outcomes. Our findings suggest that a simple algorithm based on only 3 key variables (severity of MR, LV systolic strain, and indexed LA volume) may help risk stratification and decision making in patients with MVP. (Genetic and Phenotypic Characteristics of Mitral Valve Prolapse, NCT03884426; Myocardial Characterization of Arrhythmogenic Mitral Valve Prolapse [MVP STAMP], NCT02879825).

Magnetic Resonance Imaging Angiography of Physiological and Pathological Pregnancy Placentas Ex Vivo: Protocol for a Prospective Pilot Study.

BACKGROUND: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are 2 major pregnancy complications due to abnormal placental vasculogenesis. Data on whole fetoplacental vasculature are still missing; hence, these pathologies are not well understood. Ex vivo magnetic resonance imaging (MRI) angiography has been developed to characterize the human placental vasculature by injecting a contrast agent within the umbilical cord. OBJECTIVE: The primary objective of this study is to compare the placental vascular architecture between normal and pathological pregnancies. This study's secondary objectives are to (1) compare texture features on MRI between groups (normal and pathological), (2) quantitatively compare the vascular architecture between both pathological groups (pathological IUGR, and pathological PE), (3) evaluate the quality of the histological examination in injected placentas, and (4) compare vascularization indices to histological characteristics. METHODS: This is a prospective controlled study. We expect to include 100 placentas: 40 from normal pregnancies and 60 from pathological pregnancies (30 for IUGR and 30 for PE). Ex vivo MR image acquisition will be performed shortly after delivery and with preparation by injection of a contrast agent in the umbilical cord. The vascular architecture will be quantitatively described by vascularization indices measured from ex vivo MRI angiography data. Comparisons of vascularization indices and texture features in accordance with the group and within comparable gestational age will be also performed. After MR image acquisition, placental histopathological analysis will be performed. RESULTS: The enrollment of women began in November 2019. In view of the recruitment capacity of our institution and the availability of the MRI, recruitment should be completed by March 2022. As of November 2021, we enrolled 70% of the intended study population. CONCLUSIONS: This study protocol aims to provide information about the fetal side of placental vascular architecture in normal and pathological placenta through MRI. TRIAL REGISTRATION: Clinicaltrials.gov NCT04389099; https://clinicaltrials.gov/ct2/show/NCT04389099. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35051.

Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study.

BACKGROUND: This translational study explores multi-tracer PET imaging for the non-invasive detection of the IDH1 mutation which is a positive prognostic factor in glioma. METHODS: U87 human high-grade glioma (HGG) isogenic cell lines with or without the IDH1 mutation (CRISP/Cas9 method) were stereotactically grafted into rat brains, and examined, in vitro, in vivo and ex vivo. PET imaging sessions, with radiotracers specific for glycolytic metabolism ([18F]FDG), amino acid metabolism ([18F]FDopa), and inflammation ([18F]DPA-714), were performed sequentially during 3-4 days. The in vitro radiotracer uptake was expressed as percent per million cells. For each radiotracer examined in vivo, static analyses included the maximal and mean tumor-to-background ratio (TBRmax and TBRmean) and metabolic tumor volume (MTV). Dynamic analyses included the distribution volume ratio (DVR) and the relative residence time (RRT) extracted from a reference Logan model. Ex vivo analyses consisted of immunological analyses. RESULTS: In vitro, IDH1+ cells (i.e. cells expressing the IDH1 mutation) showed lower levels of [18F]DPA-714 uptake compared to IDH1- cells (p < 0.01). These results were confirmed in vivo with lower [18F]DPA-714 uptake in IDH+ tumors (3.90 versus 5.52 for TBRmax, p = 0.03). Different values of [18F]DPA-714 and [18F] FDopa RRT (respectively 11.07 versus 22.33 and 2.69 versus - 1.81 for IDH+ and IDH- tumors, p < 0.02) were also observed between the two types of tumors. RRT [18F]DPA-714 provided the best diagnostic performance to discriminate between the two cell lines (AUC of 100%, p < 0.01). Immuno-histological analyses revealed lower expression of Iba-1 and TSPO antibodies in IDH1+ tumors. CONCLUSIONS: [18F]DPA-714 and [18F] FDopa both correlate with the presence of the IDH1 mutation in HGG. These radiotracers are therefore good candidates for translational studies investigating their clinical applications in patients.

Comparison of T2 Quantification Strategies in the Abdominal-Pelvic Region for Clinical Use.

OBJECTIVES: The aim of the study was to compare different magnetic resonance imaging (MRI) acquisition strategies appropriate for T2 quantification in the abdominal-pelvic area. The different techniques targeted in the study were chosen according to 2 main considerations: performing T2 measurement in an acceptable time for clinical use and preventing/correcting respiratory motion. MATERIALS AND METHODS: Acquisitions were performed at 3 T. To select sequences for in vivo measurements, a phantom experiment was conducted, for which the T2 values obtained with the different techniques of interest were compared with the criterion standard (single-echo SE sequence, multiple acquisitions with varying echo time). Repeatability and temporal reproducibility studies for the different techniques were also conducted on the phantom. Finally, an in vivo study was conducted on 12 volunteers to compare the techniques that offer acceptable acquisition time for clinical use and either address or correct respiratory motion. RESULTS: For the phantom study, the DESS and T2-preparation techniques presented the lowest precision (ρ2 = 0.9504 and ρ2 = 0.9849 respectively), and showed a poor repeatability/reproducibility compared with the other techniques. The strategy relying on SE-EPI showed the best precision and accuracy (ρ2 = 0.9994 and Cb = 0.9995). GRAPPATINI exhibited a very good precision (ρ2 = 0.9984). For the technique relying on radial TSE, the precision was not as good as GRAPPATINI (ρ2 = 0.9872). The in vivo study demonstrated good respiratory motion management for all of the selected techniques. It also showed that T2 estimate ranges were different from one method to another. For GRAPPATINI and radial TSE techniques, there were significant differences between all the different types of organs of interest. CONCLUSIONS: To perform T2 measurement in the abdominal-pelvic region, one should favor a technique with acceptable acquisition time for clinical use, with proper respiratory motion management, with good repeatability, reproducibility, and precision. In this study, the techniques relying respectively on SE-EPI, radial TSE, and GRAPPATINI appeared as good candidates.

Replacement Myocardial Fibrosis in Patients With Mitral Valve Prolapse: Relation to Mitral Regurgitation, Ventricular Remodeling, and Arrhythmia.

BACKGROUND: Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders, and death. Left ventricular (LV) replacement myocardial fibrosis, a marker of maladaptive remodeling, has been described in patients with MVP, but the implications of this finding remain scarcely explored. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance in patients with MVP. METHODS: Four hundred patients (53±15 years of age, 55% male) with MVP (trace to severe MR by echocardiography) from 2 centers, who underwent a comprehensive echocardiography and LGE cardiac magnetic resonance, were included. Correlates of replacement myocardial fibrosis (LGE+), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events (cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, and life-threatening ventricular arrhythmia). RESULTS: Replacement myocardial fibrosis (LGE+) was observed in 110 patients (28%; 91 with myocardial wall including 71 with basal inferolateral wall, 29 with papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate MR, and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45% versus 26%, P<0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass (odds ratio, 1.01 [95% CI, 1.002-1.017], P=0.009) and moderate-severe MR (odds ratio, 2.28 [95% CI, 1.21-4.31], P=0.011). LGE+ was associated with worse 4-year cardiovascular event-free survival (49.6±11.7 in LGE+ versus 73.3±6.5% in LGE-, P<0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ (hazard ratio, 2.6 [1.4-4.9], P=0.002) were associated with poor outcome. CONCLUSIONS: LV replacement myocardial fibrosis is frequent in patients with MVP; is associated with mitral valve apparatus alteration, more dilated LV, MR grade, and ventricular arrhythmia; and is independently associated with cardiovascular events. These findings suggest an MVP-related myocardial disease. Last, cardiac magnetic resonance provides additional information to echocardiography in MVP.

In vivo characterization of physiological and metabolic changes related to isocitrate dehydrogenase 1 mutation expcression by multiparametric MRI and MRS in a rat model with orthotopically grafted human-derived glioblastoma cell lines.

The physiological mechanism induced by the isocitrate dehydrogenase 1 (IDH1) mutation, associated with better treatment response in gliomas, remains unknown. The aim of this preclinical study was to characterize the IDH1 mutation through in vivo multiparametric MRI and MRS. Multiparametric MRI, including the measurement of blood flow, vascularity, oxygenation, permeability, and in vivo MRS, was performed on a 4.7 T animal MRI system in rat brains grafted with human-derived glioblastoma U87 cell lines expressing or not the IDH1 mutation by the CRISPR/Cas9 method, and secondarily characterized with additional ex vivo HR-MAS and histological analyses. In univariate analyses, compared with IDH1-, IDH1+ tumors exhibited higher vascular density (p < 0.01) and better perfusion (p = 0.02 for cerebral blood flow), but lower vessel permeability (p < 0.01 for time to peak (TTP), p = 0.04 for contrast enhancement) and decreased T1 map values (p = 0.02). Using linear discriminant analysis, vascular density and TTP values were found to be independent MRI parameters for characterizing the IDH1 mutation (p < 0.01). In vivo MRS and ex vivo HR-MAS analysis showed lower metabolites of tumor aggressiveness for IDH1+ tumors (p < 0.01). Overall, the IDH1 mutation exhibited a higher vascularity on MRI, a lower permeability, and a less aggressive metabolic profile. These MRI features may prove helpful to better pinpoint the physiological mechanisms induced by this mutation.

Relationship Between Left Ventricular Ejection Fraction Variation and Systemic Vascular Resistance: A Prospective Cardiovascular Magnetic Resonance Study.

Introduction: This cardiovascular magnetic resonance (CMR) study aims to determine whether changes in systemic vascular resistance (SVR), obtained from CMR flow sequences, might explain the significant long-term changes in left ventricular (LV) ejection fraction (EF) observed in subjects with no cardiac disease history. Methods: Cohort subjects without any known cardiac disease but with high rates of hypertension and obesity, underwent CMR with phase-contrast sequences both at baseline and at a median follow-up of 5.2 years. Longitudinal changes in EF were analyzed for any concomitant changes in blood pressure and vascular function, notably the indexed SVR given by the formula: mean brachial blood pressure / cardiac output x body surface area. Results: A total of 118 subjects (53 ± 12 years, 52% women) were included, 26% had hypertension, and 52% were obese. Eighteen (15%) had significant EF variations between baseline and follow-up (7 increased EF and 11 decreased EF). Longitudinal changes in EF were inversely related to concomitant changes in mean and diastolic blood pressures (p = 0.030 and p = 0.027, respectively) and much more significantly to SVR (p < 0.001). On average, these SVR changes were -8.08 ± 9.21 and +8.14 ± 8.28 mmHg.min.m2.L-1, respectively, in subjects with significant increases and decreases in EF, and 3.32 ± 7.53 mmHg.min.m2.L-1 in subjects with a stable EF (overall p < 0.001). Conclusions: Significant EF variations are not uncommon during the long-term CMR follow-up of populations with no evident health issues except for uncomplicated hypertension and obesity. However, most of these variations are linked to SVR changes and may therefore be unrelated to any intrinsic change in LV contractility. This underscores the benefits of specifically assessing LV afterload when EF is monitored in populations at risk of vascular dysfunction. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01716819 and NCT02430805.

Assessing the neuroanatomy knowledge and spatial ability of radiotherapy technologist undergraduates using an interactive volumetric simulation tool-the RadioLOG project.

OBJECTIVE: To assess the use of a volumetric image display simulation tool (VDST) for the evaluation of applied radiological neuroanatomy knowledge and spatial understanding of radiotherapy technologist (RTT) undergraduates. METHODS: Ninety-two third-year RTT students from three French RTT schools took an examination using software that allows visualization of multiple volumetric image series. To serve as a reference, 77 first- and second-year undergraduates, as well as ten senior neuroradiologists, took the same examination. The test included 13 very-short-answer questions (VSAQ) and 21 exercises in which examinees positioned markers onto preloaded brain MR images from a healthy volunteer. The response time was limited. Each correct answer scored 100 points, with a maximum possible test score of 3,400 (VSAQ = 1,300; marker exercise = 2,100). Answers were marked automatically for the marker positioning exercise and semi-automatically for the VSAQs against prerecorded expected answers. RESULTS: Overall, the mean test score was 1,787 (150-3,300) and the standard deviation was 781. Scores were highly significantly different between all evaluated groups (p < 0.001). The interoperator reproducibility was 0.90. All the evaluated groups could be discriminated by VSAQ, marker, and overall total scores independently (p ≤ 0.0001 to 0.001). The test was able to discriminate between the three schools either by VSAQ scores (p < 0.001 to 0.02) or by overall total score (p < 0.001 to 0.05). CONCLUSION: This software is a high-quality evaluation tool for the assessment of radiological neuroanatomy knowledge and spatial understanding in RTT undergraduates. KEY POINTS: • This VDST allows volumetric image analysis of MR studies. • A high reliability test could be created with this tool. • Test scores were strongly associated with the examinee expertise level.

Birth experience during COVID-19 confinement (CONFINE): protocol for a multicentre prospective study.

INTRODUCTION: The absence of companionship during childbirth is known to be responsible for negative emotional birth experience, which can increase the risk of postpartum depression and post-traumatic stress disorder. The context of COVID-19 epidemic and the related confinement could increase the rate of negative experience and mental disorders. The main objective is to compare, in immediate post partum, the maternal sense of control during childbirth between a group of women who gave birth during confinement ('confinement' group) versus a group of women who gave birth after confinement but in the context of epidemic ('epidemic' group) versus a group of control women ('control' group; excluding confinement and epidemic context). METHODS AND ANALYSIS: This is a national multicentre prospective cohort study conducted in four French maternity units. We expect to include 927 women in a period of 16 months. Women will be recruited immediately in post partum during three different periods constituting the three groups: 'confinement'; 'epidemic' and 'control' group. The maternal sense of control will be evaluated by the Labour Agentry Scale questionnaire completed immediately in post partum. Postnatal depression (Edinburgh Postnatal Depression Scale), post-traumatic stress disorder (Impact of Event Scale-Revised) and breast feeding (evaluative statement) will be evaluated at 2 months post partum. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee, the CPP (Comité de Protection des Personnes) SUD OUEST ET OUTRE-MER IV on 16th of April 2020 with reference number CPP2020-04-040. The results of this study will be published in a peer-reviewed journal and will be presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT04348929.

First trimester screening for pre-eclampsia and intrauterine growth restriction using three-dimensional Doppler angiography (SPIRIT): protocol for a multicentre prospective study in nulliparous pregnant women.

INTRODUCTION: Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are two major pregnancy complications, related to chronic uteroplacental hypoperfusion. Nowadays, there is no screening or diagnostic test for uteroplacental vascularisation deficiency in pregnant women. Since 2004, 3 three-imensional power Doppler (3DPD) angiography has been used for the evaluation of uteroplacental vascularisation and three vascular indices are usually calculated: Vascularisation Index (VI), Flow Index (FI) and vascularisation-FI (VFI). A high intraobserver and interobserver reproducibility and a potential interest for placental function study were reported by our team and others.The main objective of our study is to determine differences in 3DPD indices at first trimester between pregnancies defined at their outcome as uncomplicated pregnancy, PE (mild and severe) and IUGR in nulliparous women. METHODS AND ANALYSIS: This is a national multicentre prospective cohort study conducted in four French maternity units. We expect to include 2200 women in a period of 36 months. The nulliparous pregnant women will be recruited during their first trimester consultation (11-13+6 gestation week (GW)).The 3DPD and uterine artery Doppler acquisition will be included in the current routine 11-13+6 GW ultrasound. Also, additional blood samples will be taken for biomarker analysis (PAPP-A and P1GF) and biological collection. Uteroplacental VIs (FI and VFI) will be measured. For each subgroup (uncomplicated pregnancy, PE and IUGR), mean values in 3DPD indices will be computed and compared using a pairwise t test with a Bonferroni correction p value adjustment. ETHICS AND DISSEMINATION: The study was approved by the French Ethics Committee, the Comité de Protection des Personnes SUD MEDITERRANEE IV on 13 February 2018 with reference number 17 12 03. The results of this study will be published in a peer-reviewed journal and will be presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT03342014; Pre-results. PHRCN-16-0567.

Optimization of Fetal Biometry With 3D Ultrasound and Image Recognition (EPICEA): protocol for a prospective cross-sectional study.

CONTEXT: Variability in 2D ultrasound (US) is related to the acquisition of planes of reference and the positioning of callipers and could be reduced in combining US volume acquisitions and anatomical structures recognition. OBJECTIVES: The primary objective is to assess the consistency between 3D measurements (automated and manual) extracted from a fetal US volume with standard 2D US measurements (I). Secondary objectives are to evaluate the feasibility of the use of software to obtain automated measurements of the fetal head, abdomen and femur from US acquisitions (II) and to assess the impact of automation on intraobserver and interobserver reproducibility (III). METHODS AND ANALYSIS: 225 fetuses will be measured at 16-30 weeks of gestation. For each fetus, six volumes (two for head, abdomen and thigh, respectively) will be prospectively acquired after performing standard 2D biometry measurements (head and abdominal circumference, femoral length). Each volume will be processed later by both a software and an operator to extract the reference planes and to perform the corresponding measurements. The different sets of measurements will be compared using Bland-Altman plots to assess the agreement between the different processes (I). The feasibility of using the software in clinical practice will be assessed through the failure rate of processing and the score of quality of measurements (II). Interclass correlation coefficients will be used to evaluate the intraobserver and interobserver reproducibility (III). ETHICS AND DISSEMINATION: The study and related consent forms were approved by an institutional review board (CPP SUD-EST 3) on 2 October 2018, under reference number 2018-033 B. The study has been registered in https://clinicaltrials.gov registry on 23 January 2019, under the number NCT03812471. This study will enable an improved understanding and dissemination of the potential benefits of 3D automated measurements and is a prerequisite for the design of intention to treat randomised studies assessing their impact. TRIAL REGISTRATION NUMBER: NCT03812471; Pre-results.

Benefit from revascularization after thrombectomy according to FLAIR vascular hyperintensities-DWI mismatch.

OBJECTIVES: We tested whether FLAIR vascular hyperintensities (FVH)-DWI mismatch could identify candidates for thrombectomy most likely to benefit from revascularization. METHODS: We retrospectively reviewed 100 patients with proximal MCA occlusion from 18 stroke centers randomized in the IV-thrombolysis plus mechanical thrombectomy arm of the THRACE trial (2010-2015). We tested the associations between successful revascularization on digital subtraction angiography (modified Thrombolysis in Cerebral Infarction 2b/3) and 3-month favorable outcome (modified Rankin Scale score ≤ 2), stratified on FVH-DWI mismatch status, with secondary analyses adjusted on National Institutes of Health Stroke Scale (NIHSS) and DWI lesion volume. RESULTS: FVH-DWI mismatch was present in 79% of patients, with a similar prevalence at 1.5 T (80%) and 3 T (78%). Successful revascularization (74%) was more frequent in patients with FVH-DWI mismatch (63/79, 80%) than in patients without (11/21, 52%), p = 0.01. The OR of favorable outcome for revascularization were 15.05 (95% CI 3.12-72.61, p < 0.001) in patients with FVH-DWI mismatch and 0.83 (95% CI 0.15-4.64, p = 0.84) in patients without FVH-DWI mismatch (p = 0.011 for interaction). Similar results were observed after adjustment for NIHSS (OR = 12.73 [95% CI 2.69-60.41, p = 0.001] and 0.96 [95% CI 0.15-6.30, p = 0.96]) or for DWI volume (OR = 12.37 [95% CI 2.76-55.44, p = 0.001] and 0.91 [95% CI 0.16-5.33, p = 0.92]) in patients with and without FVH-DWI mismatch, respectively. CONCLUSIONS: The FVH-DWI mismatch identifies patients likeliest to benefit from revascularization, irrespective of initial DWI lesion volume and clinical stroke severity, and could serve as a useful surrogate marker for penumbral evaluation. KEY POINTS: • The FVH-DWI mismatch, defined by FLAIR vascular hyperintensities (FVH) located beyond the boundaries of the DWI lesion, is associated with large penumbra. • Among stroke patients with proximal middle cerebral artery occlusion referred for thrombectomy, those with FVH-DWI mismatch are most likely to benefit from revascularization. • FVH-DWI mismatch provides an alternative to PWI-DWI mismatch in order to select patients who are candidates for thrombectomy.

Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke.

Importance: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. Objective: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. Design, Setting, and Participants: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. Main Outcome and Measure: The 90-day functional outcome via the modified Rankin Scale (mRS). Results: Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P = .007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. Conclusions and Relevance: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.