The development of sensitive multimodal contrast agents is a key issue to provide better global, multi-scale images for diagnostic or therapeutic purposes. Here we present the synthesis of ...Zn-Cu-In-(S, Se)/Zn(1-x)Mn(x)S core-shell quantum dots (QDs) that can be used as markers for both near-infrared fluorescence imaging and magnetic resonance imaging (MRI). We first present the synthesis of Zn-Cu-In-(S, Se) cores coated with a thick ZnS shell doped with various proportions of Mn. Their emission wavelengths can be tuned over the NIR optical window suitable for deep tissue imaging. The incorporation of manganese ions (up to a few thousand ions per QD) confers them a paramagnetic character, as demonstrated by structural analysis and electron paramagnetic resonance spectroscopy. These QDs maintain their optical properties after transfer to water using ligand exchange. They exhibit T1-relaxivities up to 1400 mM(-1) QD s(-1) at 7 T and 300 K. We finally show that these QDs are suitable multimodal in vivo probes and demonstrate MRI and NIR fluorescence detection of regional lymph nodes in mice.
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).
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
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.
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.
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.
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 (
FFDG), amino acid metabolism (
FFDopa), and inflammation (
FDPA-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 (TBR
and TBR
) 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.
In vitro, IDH1+ cells (i.e. cells expressing the IDH1 mutation) showed lower levels of
FDPA-714 uptake compared to IDH1- cells (p < 0.01). These results were confirmed in vivo with lower
FDPA-714 uptake in IDH+ tumors (3.90 versus 5.52 for TBR
, p = 0.03). Different values of
FDPA-714 and
F 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
FDPA-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.
18FDPA-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.
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
Right ventricular (RV) dysfunction after acute myocardial infarction (AMI) is frequent and associated with poor prognosis. The complex anatomy of the right ventricle makes its echocardiographic ...assessment challenging. Quantification of RV deformation by speckle-tracking echocardiography is a widely available and reproducible technique that readily provides an integrated analysis of all segments of the right ventricle. The aim of this study was to investigate the accuracy of conventional echocardiographic parameters and speckle-tracking echocardiographic strain parameters in assessing RV function after AMI, in comparison with cardiac magnetic resonance imaging (CMR).
A total of 135 patients admitted for AMI (73 anterior, 62 inferior) were prospectively studied. Right ventricular function was assessed by echocardiography and CMR within 2 to 4 days of hospital admission. Right ventricular dysfunction was defined as CMR RV ejection fraction < 50%. Right ventricular global peak longitudinal systolic strain (GLPSS) was calculated by averaging the strain values of the septal, lateral, and inferior walls.
Right ventricular dysfunction was documented in 20 patients. Right ventricular GLPSS was the best echographic correlate of CMR RV ejection fraction (r = -0.459, P < .0001) and possessed good diagnostic value for RV dysfunction (area under the receiver operating characteristic curve AUROC, 0.724; 95% CI, 0.590-0.857), which was comparable with that of RV fractional area change (AUROC, 0.756; 95% CI, 0.647-0.866). In patients with inferior myocardial infarctions, the AUROCs for RV GLPSS (0.822) and inferolateral strain (0.877) were greater than that observed for RV fractional area change (0.760) Other conventional echocardiographic parameters performed poorly (all AUROCs < 0.700).
After AMI, RV GLPSS is the best correlate of CMR RV ejection fraction. In patients with inferior AMIs, RV GLPSS displays even higher diagnostic value than conventional echocardiographic parameters.
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.
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
), 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).
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.m
.L
, 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).
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.
NCT01109225 on ClinicalTrials.gov site (April, 2010).
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.
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.
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 (
= 0.030 and
= 0.027, respectively) and much more significantly to SVR (
< 0.001). On average, these SVR changes were -8.08 ± 9.21 and +8.14 ± 8.28 mmHg.min.m
.L
, respectively, in subjects with significant increases and decreases in EF, and 3.32 ± 7.53 mmHg.min.m
.L
in subjects with a stable EF (overall
< 0.001).
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.
ClinicalTrials.gov, identifier: NCT01716819 and NCT02430805.
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