Influence of portal vein occlusion on portal flow and liver elasticity in an animal model

Hepatic fibrosis causes an increase in liver stiffness, a parameter measured by elastography and widely used as a diagnosis method. The concomitant presence of portal vein thrombosis (PVT) implies a change in hepatic portal inflow that could also affect liver elasticity. The main objective of this study is to determine the extent to which the presence of portal occlusion can affect the mechanical properties of the liver and potentially lead to misdiagnosis of fibrosis and hepatic cirrhosis by elastography. Portal vein occlusion was generated by insertion and inflation of a balloon catheter in the portal vein of four swines. The portal flow parameters peak flow (PF) and peak velocity magnitude (PVM) and liver mechanical properties (shear modulus) were then investigated using 4D-flow MRI and MR elastography, respectively, for progressive obstructions of the portal vein. Experimental results indicate that the reduction of the intrahepatic venous blood flow (PF/PVM decreases of 29.3%/8.5%, 51.0%/32.3% and 83.3%/53.6%, respectively) measured with 50%, 80% and 100% obstruction of the portal vein section results in a decrease of liver stiffness by $0.8\%\pm0.1\%$, $7.7\%\pm0.4\%$ and $12.3\%\pm0.9\%$, respectively. While this vascular mechanism does not have sufficient influence on the elasticity of the liver to modify the diagnosis of severe fibrosis or cirrhosis (F4 METAVIR grade), it may be sufficient to attenuate the increase in stiffness due to moderate fibrosis (F2-F3 METAVIR grades) and consequently lead to false-negative diagnoses with elastography in the presence of PVT

Characterization of susceptibility artifacts in magnetic resonance thermometry images during laser interstitial thermal therapy: dimension analysis and temperature error estimation

Objective: Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to treat a lesion through light irradiation and consequent temperature increase. Magnetic Resonance Thermometry Imaging (MRTI) provides a multidimensional measurement of the temperature inside the target thus enabling accurate monitoring of the zone of damage during the procedure. In proton resonance frequency shift-based thermometry, artifacts in the images may strongly interfere with the estimated temperature maps. In our work, after noticing the formation of the dipolar-behavior artifact linkable to magnetic susceptibility changes during in vivo LITT, an investigation of susceptibility artifacts in tissue-mimicking phantoms was implemented. Approach: The artifact was characterized: (i) by measuring the area and total volume of error regions and their evolution during the treatment; and (ii) by comparison with temperature reference provided by three temperature sensing needles. Lastly, a strategy to avoid artifacts formation was devised by using the temperature-sensing needles to implement a temperature-controlled LITT. Main results: The artifact appearance was associated with gas bubble formation and with unwanted treatment effects producing magnetic susceptibility changes when 2 W laser power was set. The analysis of the artifact's dimension demonstrated that in the sagittal plane the dipolar-shape artifact may consistently spread following the temperature trend until reaching a volume 8 times bigger than the ablated one. Also, the artifact shape is quite symmetric with respect to the laser tip. An absolute temperature error showing a negative Gaussian profile in the area of susceptibility artifact with values up to 64.4 °C was estimated. Conversely, a maximum error of 2.8 °C is measured in the area not-affected by artifacts and far from the applicator tip. Finally, by regulating laser power, susceptibility artifacts formation was avoided, and appreciable thermal damage was induced. Significance: Such findings may help in improving the MRTI-based guidance of thermal therapies

Magnetic Resonance Elastography and Portal Hypertension: Influence of the Portal Venous Flow on the Liver Stiffness

International audienceThe invasive measurement of the hepatic venous pressure gradient is still considered as the reference method to assess the severity of portal hypertension. Even though previous studies have shown that the liver stiffness measured by elastography could predict portal hypertension in patients with chronic liver disease, the mechanisms behind remain today poorly understood. The main reason is that the liver stiffness is not specific to portal hypertension and is also influenced by concomitant pathologies, such as cirrhosis. Portal hypertension is also source of a vascular incidence, with a substantial diversion of portal venous blood to the systemic circulation, bypassing the liver. This study focuses on this vascular effect of portal hypertension. We propose to generate and control the portal venous flow (to isolate the modifications in the portal venous flow as single effect of portal hypertension) in an anesthetized pig and then to quantify its implications on liver stiffness by an original combination of MRE and 4D-Flow Magnetic Resonance Imaging (MRI). A catheter balloon is progressively inflated in the portal vein and the peak flow, peak velocity magnitude and liver stiffness are quantified in a 1.5T MRI scanner (AREA, Siemens Healthcare, Erlangen, Germany). A strong correlation is observed between the portal peak velocity magnitude, the portal peak flow or the liver stiffness and the portal vein intraluminal obstruction. Moreover, the comparison of mechanical and flow parameters highlights a correlation with the possibility of identifying linear relationships. These results give preliminary indications about how liver stiffness can be affected by portal venous flow and, by extension, by hypertension

RMN d’émulsions fluorées : développements méthodologiques et application à l’évaluation de l’oxymétrie et de la biodistribution dans le foie et la rate, et à la détection de l’angiogenèse tumorale dans le cerveau du rongeur

This study aimed at developing a method for detection of brain tumors at 7 teslas thanks to 19F MRI contrast agents. We particularly assessed the potential of this method to highlight tumor angiogenesis with RGD-functionalized contrast agents targeting ανβ3 integrin, a biomarker over-expressed at the surface of new capillary blood vessels. Owing to low local concentrations in contrast agent, the first step consisted in optimizing a multi spin echo sequence dedicated to a well-known biocompatible perfluorocarbon, perfluorooctylbromide (PFOB). We show that careful adjustment of sequence parameters allows cancellation of J-modulation and T2 enhancement, and yields an excellent sensitivity in vitro. Our sequence was then tested for oxygenation measurements in the mouse liver and spleen after injection of a PFOB emulsion. The results demonstrate very good accuracy of the measurements after one single infusion of emulsion. We also perform a dynamic biodistribution study in order to monitor emulsion nanoparticle uptake in the liver and spleen. Moreover, we show that stealth of emulsions grafted with different quantities of polyethylene glycol (PEG) can be assessed by fitting experimental data with a pharmacokinetic empirical model. Our sequence was finally used to visualize ανβ3-targeted nanoparticles in a U87 glioblastoma mouse model. Concentrations found in tumors after injection of an RGD-functionalized emulsion and a control emulsion are compared. Concentrations are found to be significantly higher with the RGD emulsion than with the control emulsion, suggesting specific binding of functionalized nanoparticles with ανβ3 integrin. The last part is dedicated to a new diffusion-weighted 19F NMR spectroscopy sequence. This method aims at suppressing vascular signal coming from circulating PFOB nanoparticles in order to evaluate signal coming from bound nanoparticles only.L’objectif ici était de développer une méthode de détection des tumeurs cérébrales via des agents de contraste pour l’IRM du 19F à 7 teslas. Nous évaluons en particulier le potentiel de cette méthode à mettre en évidence l’angiogenèse tumorale à l’aide d’agents de contraste fonctionnalisés avec le peptide RGD et ciblant l’intégrine ανβ3, biomarqueur surexprimé à la surface des néo-vaisseaux irriguant la tumeur. Du fait des basses concentrations locales en agent de contraste, les efforts portent dans un premier temps sur l’optimisation d’une séquence multi échos de spin dédiée à l’imagerie du PFOB (perfluorooctyl bromure), perfluorocarbure biocompatible choisi pour constituer la base de nos agents de contraste. Nous montrons qu’un paramétrage minutieux de cette séquence permet la suppression de la J-modulation et un rehaussement du T2, conduisant à une excellente sensibilité in vitro. La séquence est ensuite testée pour des mesures d’oxygénation dans le foie et la rate chez la souris, après injection d’une émulsion de PFOB. Les résultats indiquent une très bonne précision des mesures après injection d’une seule dose d’émulsion. Notre séquence est également utilisée pour réaliser une étude de biodistribution dynamique, permettant de suivre l’accumulation des nanoparticules d’émulsion dans le foie et la rate juste après injection. Nous montrons par ailleurs qu’il est possible d’évaluer la furtivité d’émulsions contenant différentes quantités de PEG (Poly Ethylène Glycol) en ajustant les données expérimentales sur un modèle pharmacocinétique empirique. La séquence est enfin utilisée pour détecter des nanoparticules d’émulsions fonctionnalisées pour cibler l’intégrine ανβ3 dans un modèle souris U87 de glioblastome. Nous comparons les concentrations en agent de contraste obtenues dans la tumeur avec une émulsion contenant le peptide RGD, et une émulsion contrôle. Les résultats indiquent des concentrations significativement plus élevées avec l’émulsion RGD qu’avec l’émulsion contrôle, supposant un ciblage spécifique d’ανβ3 par les nanoparticules fonctionnalisées. Un dernier chapitre est dédié à une nouvelle méthode de spectroscopie de diffusion en 19F, dont le but est d’éliminer le signal vasculaire provenant des nanoparticules de PFOB circulantes afin d’évaluer le signal ne provenant que des particules liées

NMR of 19F emulsions : methodological developments and application to evaluation of oximetry and dynamic biodistribution in the liver and spleen and to detection of tumor angiogenesis in the rodent brain

L’objectif ici était de développer une méthode de détection des tumeurs cérébrales via des agents de contraste pour l’IRM du 19F à 7 teslas. Nous évaluons en particulier le potentiel de cette méthode à mettre en évidence l’angiogenèse tumorale à l’aide d’agents de contraste fonctionnalisés avec le peptide RGD et ciblant l’intégrine ανβ3, biomarqueur surexprimé à la surface des néo-vaisseaux irriguant la tumeur. Du fait des basses concentrations locales en agent de contraste, les efforts portent dans un premier temps sur l’optimisation d’une séquence multi échos de spin dédiée à l’imagerie du PFOB (perfluorooctyl bromure), perfluorocarbure biocompatible choisi pour constituer la base de nos agents de contraste. Nous montrons qu’un paramétrage minutieux de cette séquence permet la suppression de la J-modulation et un rehaussement du T2, conduisant à une excellente sensibilité in vitro. La séquence est ensuite testée pour des mesures d’oxygénation dans le foie et la rate chez la souris, après injection d’une émulsion de PFOB. Les résultats indiquent une très bonne précision des mesures après injection d’une seule dose d’émulsion. Notre séquence est également utilisée pour réaliser une étude de biodistribution dynamique, permettant de suivre l’accumulation des nanoparticules d’émulsion dans le foie et la rate juste après injection. Nous montrons par ailleurs qu’il est possible d’évaluer la furtivité d’émulsions contenant différentes quantités de PEG (Poly Ethylène Glycol) en ajustant les données expérimentales sur un modèle pharmacocinétique empirique. La séquence est enfin utilisée pour détecter des nanoparticules d’émulsions fonctionnalisées pour cibler l’intégrine ανβ3 dans un modèle souris U87 de glioblastome. Nous comparons les concentrations en agent de contraste obtenues dans la tumeur avec une émulsion contenant le peptide RGD, et une émulsion contrôle. Les résultats indiquent des concentrations significativement plus élevées avec l’émulsion RGD qu’avec l’émulsion contrôle, supposant un ciblage spécifique d’ανβ3 par les nanoparticules fonctionnalisées. Un dernier chapitre est dédié à une nouvelle méthode de spectroscopie de diffusion en 19F, dont le but est d’éliminer le signal vasculaire provenant des nanoparticules de PFOB circulantes afin d’évaluer le signal ne provenant que des particules liées.This study aimed at developing a method for detection of brain tumors at 7 teslas thanks to 19F MRI contrast agents. We particularly assessed the potential of this method to highlight tumor angiogenesis with RGD-functionalized contrast agents targeting ανβ3 integrin, a biomarker over-expressed at the surface of new capillary blood vessels. Owing to low local concentrations in contrast agent, the first step consisted in optimizing a multi spin echo sequence dedicated to a well-known biocompatible perfluorocarbon, perfluorooctylbromide (PFOB). We show that careful adjustment of sequence parameters allows cancellation of J-modulation and T2 enhancement, and yields an excellent sensitivity in vitro. Our sequence was then tested for oxygenation measurements in the mouse liver and spleen after injection of a PFOB emulsion. The results demonstrate very good accuracy of the measurements after one single infusion of emulsion. We also perform a dynamic biodistribution study in order to monitor emulsion nanoparticle uptake in the liver and spleen. Moreover, we show that stealth of emulsions grafted with different quantities of polyethylene glycol (PEG) can be assessed by fitting experimental data with a pharmacokinetic empirical model. Our sequence was finally used to visualize ανβ3-targeted nanoparticles in a U87 glioblastoma mouse model. Concentrations found in tumors after injection of an RGD-functionalized emulsion and a control emulsion are compared. Concentrations are found to be significantly higher with the RGD emulsion than with the control emulsion, suggesting specific binding of functionalized nanoparticles with ανβ3 integrin. The last part is dedicated to a new diffusion-weighted 19F NMR spectroscopy sequence. This method aims at suppressing vascular signal coming from circulating PFOB nanoparticles in order to evaluate signal coming from bound nanoparticles only

Interprofessional survey on knowledge and attitudes of midwives regarding oral health, in France

Introduction Oral health is essential for psychosocial well-being and general health. For expectant mothers, pregnancy increases the risk of oral diseases and has a subsequent impact on the oral health of a child once born. Midwives are in charge of pregnancy monitoring, childbirth and newborns’ first days of life. They could have an important role in prevention. However, limited studies evaluating the knowledge, attitudes and practices on oral health among midwives have been conducted in Europe. Methods We performed a cross-sectional study using a self-administered questionnaire. Two local midwifery associations sent out the questionnaire by email and social media networks to all registered midwives and practicing in the department of Herault (n=613), between April and May 2022. Statistical analyses on quantitative data and descriptive analyses of qualitative free-text responses were performed. Results In total, 167 midwives were included. We found a lack of knowledge on many oral health topics and this was stated as the main reason that only 29% of midwives provided oral health information to their patients. Only 30% of the midwives had a training module on oral health during their initial training, and less than half of them considered the training adequate. To improve their lack of knowledge, participants expressed a preference for digital communication methods for themselves; however, they favored in-person interaction for public interventions. Conclusions This study showed a lack of training and knowledge about oral health among midwives and a lack of oral health discussion with expectant mothers who are a high-risk population for oral diseases

MAGNETIC RESONANCE ELASTOGRAPHY: INFLUENCE OF THE PORTAL VENOUS FLOW ON THE LIVER STIFFNESS

International audienceBackground: This presentation aims not only to present the base concepts of Magnetic Resonance Elastography (MRE), but also to present a specific in vivo application to link the liver elasticity measurement to the hepatic vascular flow (as described below). Aims: The invasive measurement of the hepatic venous pressure gradient (HVPG) is still considered as the reference method to assess the degree of Portal Hypertension (PH) [Boleslawski et al. 2012]. Even though previous studies have shown that the liver stiffness (LS) measured by elastography could predict PH in patients with chronic liver disease [Ipek-Ugay et al. 2016] the mechanisms behind remain today poorly understood. The main reason is that the LS is not specific to PH and is also influenced by concomitant pathologies, such as cirrhosis [Bavu et al. 2011; Ferraioli et al. 2012]. PH is also source of a substantial diversion of portal venous blood to the systemic circulation, bypassing the liver [Berzigotti et al. 2013]. This study focuses on this effect of PH. Methods: We propose to generate and control the portal venous flow (PVF) (to isolate the modifications in the PVF as single effect of PH) in two pigs and then to quantify its implications on LS by an original combination of MRE and 4D-Flow Magnetic Resonance Imaging (MRI), respectively. A catheter balloon is progressively inflated in the portal vein (Fig.(A)) and the following parameters are quantified in a 1.5T MRI scanner (AREA, Siemens Healthcare, Erlangen, Germany): (1) the peak flow (PF) and the peak velocity magnitude (PVM) (4D-Flow, Fig.(B)); (2) the LS µ (MRE, Fig.(C)). Results: A strong correlation appears between both the PVM, PF or the LS and the inflation state of the balloon. Moreover, the comparison of LS with PVM or PF highlights a strong correlation of these parameters with the possibility of identifying linear relationships (Fig.(D)). Conclusions: These results are thought to give indications about how LS can be affected by PH. Otherwise, this study provides unprecedented information for the mechanical modeling of the liver (including mechanical properties and vascular flows) dedicated to computer-assisted surgery. Fig. A catheter balloon is successively inflated in the portal vein (A). The flow (B) and mechanical (C) parameters are successively measured. LS is shown as correlated to PVM and PF (D). Acknowledgements: This work has benefitted from support of the ANR (Agence Nationale de la Recherche) by the French national program "Investissements d'Avenir" (IHU, ANR-10-IAHU-02)

Investigation of PVC plastisol tissue-mimicking phantoms for MR-and ultrasound-elastography

International audienceObjective: Realistic tissue-mimicking phantoms are essential for the development, the investigation and the calibration of medical imaging techniques and protocols. Because it requires taking both mechanical and imaging properties into account, the development of robust, calibrated phantoms is a major challenge in elastography. Soft polyvinyl chloride gels in a liquid plasticizer (plastisol or PVCP) have been proposed as soft tissue-mimicking phantoms (TMP) for elasticity imaging. PVCP phantoms are relatively low-cost and can be easily stored over long time periods without any specific requirements. In this work, the preparation of a PVCP gel phantom for both MR and ultrasoundelastography is proposed and its acoustic, NMR and mechanical properties are studied.Material and methods: The acoustic and magnetic resonance imaging properties of PVCP are measured for different mass ratios between ultrasound speckle particles and PVCP solution, and between resin and plasticizer. The linear mechanical properties of plastisol samples are then investigated over time using not only indentation tests, but also MR and ultrasound-elastography clinical protocols. These properties are compared to typical values reported for biological soft tissues and to the values found in the literature for PVCP gels.Results and conclusions: After a period of two weeks, the mechanical properties of the plastisol samples measured with indentation testing are stable for at least the following 4 weeks (end of follow-up period 43 days after gelation-fusion). Neither the mechanical nor the NMR properties of plastisol gels were found to be affected by the addition of cellulose as acoustic speckle. Mechanical properties of the proposed gels were successfully characterized by clinical, commercially-available MR Elastography and sonoelastography protocols. PVCP with a mass ratio of ultrasound speckle particles of 0.6% to 0.8% and a mass ratio between resin and plasticizer between 50 and 70% appears as a good TMP candidate that can be used with both MR and ultrasound-based elastography methods

Investigation of PolyVinyl Chloride Plastisol Tissue-Mimicking Phantoms for MR- and Ultrasound-Elastography

Objective: Realistic tissue-mimicking phantoms are essential for the development, the investigation and the calibration of medical imaging techniques and protocols. Because it requires taking both mechanical and imaging properties into account, the development of robust, calibrated phantoms is a major challenge in elastography. Soft polyvinyl chloride gels in a liquid plasticizer (plastisol or PVCP) have been proposed as soft tissue-mimicking phantoms (TMP) for elasticity imaging. PVCP phantoms are relatively low-cost and can be easily stored over long time periods without any specific requirements. In this work, the preparation of a PVCP gel phantom for both MR and ultrasound-elastography is proposed and its acoustic, NMR and mechanical properties are studied.Materials and methods: The acoustic and magnetic resonance imaging properties of PVCP are measured for different mass ratios between ultrasound speckle particles and PVCP solution, and between resin and plasticizer. The linear mechanical properties of plastisol samples are then investigated over time using not only indentation tests, but also MR and ultrasound-elastography clinical protocols. These properties are compared to typical values reported for biological soft tissues and to the values found in the literature for PVCP gels.Results and conclusions: After a period of two weeks, the mechanical properties of the plastisol samples measured with indentation testing are stable for at least the following 4 weeks (end of follow-up period 43 days after gelation-fusion). Neither the mechanical nor the NMR properties of plastisol gels were found to be affected by the addition of cellulose as acoustic speckle. Mechanical properties of the proposed gels were successfully characterized by clinical, commercially-available MR Elastography and sonoelastography protocols. PVCP with a mass ratio of ultrasound speckle particles of 0.6%–0.8% and a mass ratio between resin and plasticizer between 50 and 70% appears as a good TMP candidate that can be used with both MR and ultrasound-based elastography methods