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.

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.

Validation of overestimation ratio and TL-SVS as imaging biomarker of cardioembolic stroke and time from onset to MRI.

OBJECTIVE: We aimed to determine in the "THRACE" trial, the clinical and MRI technical parameters associated with the two-layered susceptibility vessel sign (TL-SVS) and the overestimation ratio (overR). MATERIALS AND METHODS: Patients with pre-treatment brain gradient echo (GRE) sequence and an etiological work-up were identified. Two readers reviewed TL-SVS, i.e., a SVS with a linear low-intense signal core surrounded by a higher intensity and measured the overR as the width of SVS divided by the width of the artery. Binomial and ordinal logistic regression respectively tested the association between TL-SVS and quartiles of overR with patient characteristics, cardioembolic stroke (CES), time from onset to imaging, and GRE sequence parameters (inter slice gap, slice thickness, echo time, flip angle, voxel size, and field strength). RESULTS: Among 258 included patients, 102 patients were examined by 3 Tesla MRI and 156 by 1.5 Tesla MRI. Intra- and inter-reader agreements for quartiles of overR and TL-SVS were good to excellent. The median overR was 1.59 (IQR, 1.30 to 1.86). TL-SVS was present in 101 patients (39.2%, 95%CI, 33.1 to 45.1%). In multivariate analysis, only CES was associated with overR quartiles (OR, 1.83; 95%CI, 1.11 to 2.99), and every 60 min increase from onset to MRI time was associated with TL-SVS (OR, 1.72; 95%CI, 1.10 to 2.67). MRI technical parameters were statistically associated with neither overR nor TL-SVS. CONCLUSION: Independent of GRE sequence parameters, an increased overR was associated to CES, while the TL-SVS is independently related to a longer time from onset to MRI. KEY POINTS: • An imaging biomarker would be useful to predict the etiology of stroke in order to adapt secondary prevention of stroke. • The two-layered susceptibility vessel sign and the overestimation ratio are paramagnetic effect derived markers that vary according to the MRI machines and sequence parameters. • Independent of sequence parameters, an increased overestimation ratio was associated to cardioembolic stroke, while the two-layered susceptibility vessel sign is independently related to a longer time from onset to MRI.

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.

Impact of microvascular obstruction on left ventricular local remodeling after reperfused myocardial infarction.

PURPOSE: To evaluate by cardiac magnetic resonance imaging (MRI) the impact of microvascular obstruction (MVO) on regional left ventricular (LV) wall characteristics and local remodeling after acute myocardial infarction (AMI). MATERIALS AND METHODS: In all, 114 AMI patients underwent cardiac MRI at 3T within 2-4 days (baseline) and at 6 months (follow-up) after reperfusion. Late gadolinium enhancement and cine sequences were performed. The impact of MVO (ie, presence and extent) on regional wall thickening (WT, %), end-diastolic wall thickness (EDWT, mm), and local cavity change (mm) of LV were quantitatively analyzed. Local cavity change, calculated as surface-to-surface distance from registered endocardial surface meshes of cine imaging datasets acquired initially and at follow-up, was used to assess local remodeling. RESULTS: MVO was detected in 69 patients (60.5%). WT was significantly lower when MVO was present (P < 0.05); and it was inversely related to MVO transmural extent (P < 0.0001). WT improvement was significantly worsened when MVO was present in segments with infarct transmural extent exceeding 50%. Significant wall thinning occurred at follow-up in segments with infarct transmural extent >75% with further thinning by MVO presence; and EDWT decreased with increasing MVO transmural extent (P < 0.0001). LV cavity shrank in patients without MVO, whereas it dilated in those with MVO. Local cavity changes were not significantly different by a region-to-region analysis throughout the LV within each group (P = 0.57 and 0.74, respectively). CONCLUSION: MVO has a significant adverse effect on LV wall characteristics and LV remodeling. Postinfarct remodeling seems to be globally mediated rather than locally mediated during the first 6 months. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:499-510.

Contrast-Enhanced 3-T Perfusion MRI With Quantitative Analysis for the Characterization of Musculoskeletal Tumors: Is It Worth the Trouble?

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of quantitative perfusion parameters in 3-T MRI for benign-malignant differentiation in musculoskeletal tumors. SUBJECTS AND METHODS: Ninety-five patients with histologically proven musculoskeletal tumors were prospectively included in this study. All patients underwent 3-T contrast-enhanced perfusion MRI with T1 mapping. The extended Tofts pharmacokinetic model was used to obtain four semiquantitative and four quantitative perfusion parameters for each tumor. Two radiologists evaluated all images and manually placed the ROIs in consensus. RESULTS: The 95 patients had 57 (59%) benign and 38 (41%) malignant tumors. Thirty-seven (39%) were bone and 58 (61%) were soft-tissue tumors. No significant differences were found in the perfusion parameters of benign and malignant tumors (p = 0.105-0.609). The best performance for benign-malignant differentiation was found for fractional volume of the extravascular extracellular space, which yielded 79% and 38% sensitivity and specificity. When soft-tissue tumors were considered, the transfer constant from plasma to the extravascular extracellular space exhibited a significant difference (p = 0.028) and had 79% and 27% sensitivity and specificity. CONCLUSION: Quantitative perfusion MRI had fair sensitivity and poor specificity for benign-malignant differentiation, which was similar to that obtained with semiquantitative parameters.

Impact of denoising on precision and accuracy of saturation-recovery-based myocardial T1 mapping.

PURPOSE: To evaluate the impact of a novel postprocessing denoising technique on accuracy and precision in myocardial T1 mapping. MATERIALS AND METHODS: This study introduces a fast and robust denoising method developed for magnetic resonance T1 mapping. The technique imposes edge-preserving regularity and exploits the co-occurence of spatial gradients in the acquired T1 -weighted images. The proposed approach was assessed in simulations, ex vivo data and in vivo imaging on a cohort of 16 healthy volunteers (12 males, average age 39 ± 8 years, 62 ± 9 bpm) both in pre- and postcontrast injection. The method was evaluated in myocardial T1 mapping at 3T with a saturation-recovery technique that is accurate but sensitive to noise. ROIs in the myocardium and left-ventricle blood pool were analyzed by an experienced reader. Mean T1 values and standard deviation were extracted and compared in all studies. RESULTS: Simulations on synthetic phantom showed signal-to-noise ratio and sharpness improvement with the proposed method in comparison with conventional denoising. In vivo results demonstrated that our method preserves accuracy, as no difference in mean T1 values was observed in the myocardium (precontrast: 1433/1426 msec, 95%CI: [-40.7, 55.9], p = 0.75, postcontrast: 766/759 msec, 95%CI: [-60.7, 77.2], p = 0.8). Meanwhile, precision was improved with standard deviations of T1 values being significantly decreased (precontrast: 223/151 msec, 95%CI: [27.3, 116.5], p = 0.003, postcontrast: 176/135 msec, 95%CI: [5.5, 77.1], p = 0.03). CONCLUSION: The proposed denoising method preserves accuracy and improves precision in myocardial T1 mapping, with the potential to offer better map visualization and analysis. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1377-1388.

Contrast-enhanced 3T MR Perfusion of Musculoskeletal Tumours: T1 Value Heterogeneity Assessment and Evaluation of the Influence of T1 Estimation Methods on Quantitative Parameters.

OBJECTIVE: To evaluate intra-tumour and striated muscle T1 value heterogeneity and the influence of different methods of T1 estimation on the variability of quantitative perfusion parameters. MATERIAL AND METHODS: Eighty-two patients with a histologically confirmed musculoskeletal tumour were prospectively included in this study and, with ethics committee approval, underwent contrast-enhanced MR perfusion and T1 mapping. T1 value variations in viable tumour areas and in normal-appearing striated muscle were assessed. In 20 cases, normal muscle perfusion parameters were calculated using three different methods: signal based and gadolinium concentration based on fixed and variable T1 values. RESULTS: Tumour and normal muscle T1 values were significantly different (p = 0.0008). T1 value heterogeneity was higher in tumours than in normal muscle (variation of 19.8% versus 13%). The T1 estimation method had a considerable influence on the variability of perfusion parameters. Fixed T1 values yielded higher coefficients of variation than variable T1 values (mean 109.6 ± 41.8% and 58.3 ± 14.1% respectively). Area under the curve was the least variable parameter (36%). CONCLUSION: T1 values in musculoskeletal tumours are significantly different and more heterogeneous than normal muscle. Patient-specific T1 estimation is needed for direct inter-patient comparison of perfusion parameters. KEY POINTS: • T1 value variation in musculoskeletal tumours is considerable. • T1 values in muscle and tumours are significantly different. • Patient-specific T1 estimation is needed for comparison of inter-patient perfusion parameters. • Technical variation is higher in permeability than semiquantitative perfusion parameters.

Cardiac remodeling following reperfused acute myocardial infarction is linked to the concomitant evolution of vascular function as assessed by cardiovascular magnetic resonance.

BACKGROUND: Left ventricular (LV) remodeling following acute myocardial infarction (MI) is difficult to predict at an individual level although a possible interfering role of vascular function has yet to be considered to date. This study aimed to determine the extent to which this LV remodeling is influenced by the concomitant evolution of vascular function and LV loading conditions, as assessed by phase-contrast Cardiovascular Magnetic Resonance (CMR) of the ascending aorta. METHODS: CMR was performed in 121 patients, 2-4 days after reperfusion of a first ST-segment elevation myocardial infarction and 6 months thereafter. LV remodeling was: (i) assessed by the 6-month increase in end-diastolic volume (EDV) and/or ejection fraction (EF) and (ii) correlated with the indexed aortic stroke volume (mL.m-2), determined by a CMR phase-contrast sequence, along with derived functional vascular parameters (total peripheral vascular resistance (TPVR), total arterial compliance index, effective arterial elastance). RESULTS: At 6 months, most patients were under angiotensin enzyme converting inhibitors (86%) and beta-blockers (84%) and, on average, all functional vascular parameters were improved whereas blood pressure levels were not. An increase in EDV only (EDV+/EF-) was documented in 17% of patients at 6 months, in EF only (EDV-/EF+) in 31%, in both EDV and EF (EDV+/EF+) in 12% and neither EDV nor EF (EDV-/EF-) in 40%. The increase in EF was mainly and independently linked to a concomitant decline in TPVR (6-month change in mmHg.min.m2.L-1, EDV-/EF-: +1 ± 8, EDV+/EF-: +3 ± 9, EDV-/EF+: -7 ± 6, EDV+/EF+: -15 ± 20, p < 0.001) while the absence of any EF improvement was associated with high persisting rates of abnormally high TPVR at 6 months (EDV-/EF-: 31%, EDV+/EF-: 38%, EDV-/EF+: 5%, EDV+/EF+: 13%, p = 0.007). By contrast, the 6-month increase in EDV was mainly dependent on cardiac as opposed to vascular parameters and particularly on the presence of microvascular obstruction at baseline (EDV-/EF-: 37%, EDV+/EF-: 76%, EDV-/EF+: 38%, EDV+/EF+: 73%, p = 0.003). CONCLUSION: LV remodeling following reperfused MI is strongly influenced by the variable decrease in systemic vascular resistance under standard care vasodilating medication. The CMR monitoring of vascular resistance may help to tailor these medications for improving vascular resistance and consequently, LV ejection fraction. TRIAL REGISTRATION: NCT01109225 on ClinicalTrials.gov site (April, 2010).

Myocardial infarct sizing by late gadolinium-enhanced MRI: Comparison of manual, full-width at half-maximum, and n-standard deviation methods.

PURPOSE: To compare three widely used methods for myocardial infarct (MI) sizing on late gadolinium-enhanced (LGE) magnetic resonance (MR) images: manual delineation and two semiautomated techniques (full-width at half-maximum [FWHM] and n-standard deviation [SD]). MATERIALS AND METHODS: 3T phase-sensitive inversion-recovery (PSIR) LGE images of 114 patients after an acute MI (2-4 days and 6 months) were analyzed by two independent observers to determine both total and core infarct sizes (TIS/CIS). Manual delineation served as the reference for determination of optimal thresholds for semiautomated methods after thresholding at multiple values. Reproducibility and accuracy were expressed as overall bias ± 95% limits of agreement. RESULTS: Mean infarct sizes by manual methods were 39.0%/24.4% for the acute MI group (TIS/CIS) and 29.7%/17.3% for the chronic MI group. The optimal thresholds (ie, providing the closest mean value to the manual method) were FWHM30% and 3SD for the TIS measurement and FWHM45% and 6SD for the CIS measurement (paired t-test; all P > 0.05). The best reproducibility was obtained using FWHM. For TIS measurement in the acute MI group, intra-/interobserver agreements, from Bland-Altman analysis, with FWHM30%, 3SD, and manual were -0.02 ± 7.74%/-0.74 ± 5.52%, 0.31 ± 9.78%/2.96 ± 16.62% and -2.12 ± 8.86%/0.18 ± 16.12, respectively; in the chronic MI group, the corresponding values were 0.23 ± 3.5%/-2.28 ± 15.06, -0.29 ± 10.46%/3.12 ± 13.06% and 1.68 ± 6.52%/-2.88 ± 9.62%, respectively. A similar trend for reproducibility was obtained for CIS measurement. However, semiautomated methods produced inconsistent results (variabilities of 24-46%) compared to manual delineation. CONCLUSION: The FWHM technique was the most reproducible method for infarct sizing both in acute and chronic MI. However, both FWHM and n-SD methods showed limited accuracy compared to manual delineation. J. Magn. Reson. Imaging 2016;44:1206-1217.

Advanced Techniques in Musculoskeletal Oncology: Perfusion, Diffusion, and Spectroscopy.

The imaging characterization of musculoskeletal tumors can be challenging, and a significant number of lesions remain indeterminate when conventional imaging protocols are used. In recent years, clinical availability of functional imaging methods has increased. Functional imaging has the potential to improve tumor detection, characterization, and follow-up. The most frequently used functional methods are perfusion imaging, diffusion-weighted imaging (DWI), and MR proton spectroscopy (MRS). Each of these techniques has specific protocol requirements and diagnostic pitfalls that need to be acknowledged to avoid misdiagnoses. Additionally, the application of functional methods in the MSK system has various technical issues that need to be addressed to ensure data quality and comparability. In this article, the application of contrast-enhanced perfusion imaging, DWI, and MRS for the evaluation of bone and soft tissue tumors is discussed, with emphasis on acquisition protocols, technical difficulties, and current clinical indications.

3D myocardial T1 mapping at 3T using variable flip angle method: pilot study.

PURPOSE: Myocardial T1 mapping is an emerging technique that could improve cardiovascular magnetic resonance diagnostic accuracy. In this study, a variable flip angle approach with B1 correction is proposed at 3T on the myocardium, employing standard 3D spoiled fast gradient echo and echo planar imaging sequences. METHODS: The method was tested on phantoms to determine the set of standard 3D spoiled fast gradient echo angles adapted to myocardial T1 measurements and was compared to the inversion-recovery spin-echo reference T1 method. Seven volunteers underwent magnetic imaging resonance to acquire myocardial T1 maps and T1 values of the human heart. RESULTS: This original method demonstrated good reproducibility in phantoms and a significant correlation between variable flip angle T1 values and reference inversion-recovery spin-echo T1 values. It yielded myocardial T1 values consistent with expected T1 and an increasing homogenization of myocardial segments owing to B1 correction. The mean myocardial T1 value was 1341 ± 42 ms. CONCLUSION: Myocardial 3D T1 mapping using the variable flip angle approach can potentially be useful for evaluating fibrosis on the entire myocardium using a standard clinical sequence.

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.

Dynamic MR imaging of osteoid osteomas: correlation of semiquantitative and quantitative perfusion parameters with patient symptoms and treatment outcome.

OBJECTIVE: To evaluate the relationship between multiple MR perfusion parameters and symptoms of patients with osteoid osteomas after percutaneous laser therapy. METHODS: MR perfusion studies of 20 patients diagnosed with an osteoid osteoma, treated with CT-guided percutaneous laser therapy, were retrospectively evaluated. Multiple perfusion parameters correlated with the treatment outcome and the presence of osteoid osteoma-related symptoms. RESULTS: There were 16 successful treatments, 6 recurrences and a significant difference in the perfusion parameters of these groups (P < 0.0001). Patients with successful treatment demonstrated delayed progressive enhancement or no enhancement (mean time to peak = 182 s, mean delay to the arterial peak = 119.3 s). Patients with treatment failure demonstrated an early and steep enhancement (mean time to peak = 78 s and mean delay to the arterial peak = 24 s). Plasmatic volume and transfer constant values significantly changed after successful treatment (P < 0.008). MR perfusion has a sensitivity and a specificity higher than 90 % in the detection of recurrent osteoid osteomas. CONCLUSION: The identification of an early and steep enhancement with short time to peak and a short delay between the arterial and nidus peaks on MR perfusion in the postoperative setting is highly indicative of an osteoid osteoma recurrence. Key points • Magnetic resonance perfusion is becoming widely used for several tumours. • MR perfusion measurements correlate well with osteoid osteoma-related symptoms. • MR perfusion has high diagnostic performance for osteoid osteoma recurrence. • MR perfusion can improve the diagnostic confidence of osteoid osteoma recurrence.

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).

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).

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).

Diffusion tensor imaging of diffuse axonal injury in a rat brain trauma model.

Diffusion tensor imaging (DTI) was used to study traumatic brain injury. The impact-acceleration trauma model was used in rats. Here, in addition to diffusivities (mean, axial and radial), fractional anisotropy (FA) was used, in particular, as a parameter to characterize the cerebral tissue early after trauma. DTI was implemented at 7 T using fast spiral k-space sampling and the twice-refocused spin echo radiofrequency sequence for eddy current minimization. The method was carefully validated on different phantom measurements. DTI of a trauma group (n = 5), as well as a sham group (n = 5), was performed at different time points during 6 h following traumatic brain injury. Two cerebral regions, the cortex and corpus callosum, were analyzed carefully. A significant decrease in diffusivity in the trauma group versus the sham group was observed, suggesting the predominance of cellular edema in both cerebral regions. No significant FA change was detected in the cortex. In the corpus callosum of the trauma group, the FA indices were significantly lower. A net discontinuity in fiber reconstructions in the corpus callosum was observed by fiber tracking using DTI. Histological analysis using Hoechst, myelin basic protein and Bielschowsky staining showed fiber disorganization in the corpus callosum in the brains of the trauma group. On the basis of our histology results and the characteristics of the impact-acceleration model responsible for the presence of diffuse axonal injury, the detection of low FA caused by a drastic reduction in axial diffusivity and the presence of fiber disconnections of the DTI track in the corpus callosum were considered to be related to the presence of diffuse axonal injury.