Suivi par élastographie ultrasonore après réparation endovasculaire d’anévrisme aorto-iliaque : étude de faisabilité in vivo

Les maladies cardiovasculaires sont la première cause de mortalité dans le monde et les anévrismes de l’aorte abdominale (AAAs) font partie de ce lot déplorable. Un anévrisme est la dilatation d’une artère pouvant conduire à la mort. Une rupture d’AAA s’avère fatale près de 80% du temps. Un moyen de traiter les AAAs est l’insertion d’une endoprothèse (SG) dans l’aorte, communément appelée la réparation endovasculaire (EVAR), afin de réduire la pression exercée par le flux sanguin sur la paroi. L’efficacité de ce traitement est compromise par la survenue d’endofuites (flux sanguins entre la prothèse et le sac anévrismal) pouvant conduire à la rupture de l’anévrisme. Ces flux sanguins peuvent survenir à n’importe quel moment après le traitement EVAR. Une surveillance par tomodensitométrie (CT-scan) annuelle est donc requise, augmentant ainsi le coût du suivi post-EVAR et exposant le patient à la radiation ionisante et aux complications des contrastes iodés. L’endotension est le concept de dilatation de l’anévrisme sans la présence d’une endofuite apparente au CT-scan. Après le traitement EVAR, le sang dans le sac anévrismal coagule pour former un thrombus frais, qui deviendra progressivement un thrombus plus fibreux et plus organisé, donnant lieu à un rétrécissement de l’anévrisme. Il y a très peu de données dans la littérature pour étudier ce processus temporel et la relation entre le thrombus frais et l’endotension. L’étalon d’or du suivi post-EVAR, le CT-scan, ne peut pas détecter la présence de thrombus frais. Il y a donc un besoin d’investir dans une technique sécuritaire et moins coûteuse pour le suivi d’AAAs après EVAR. Une méthode récente, l’élastographie dynamique, mesure l’élasticité des tissus en temps réel. Le principe de cette technique repose sur la génération d’ondes de cisaillement et l’étude de leur propagation afin de remonter aux propriétés mécaniques du milieu étudié. Cette thèse vise l’application de l’élastographie dynamique pour la détection des endofuites ainsi que de la caractérisation mécanique des tissus du sac anévrismal après le traitement EVAR. Ce projet dévoile le potentiel de l’élastographie afin de réduire les dangers de la radiation, de l’utilisation d’agent de contraste ainsi que des coûts du post-EVAR des AAAs. L’élastographie dynamique utilisant le « Shear Wave Imaging » (SWI) est prometteuse. Cette modalité pourrait complémenter l’échographie-Doppler (DUS) déjà utilisée pour le suivi d’examen post-EVAR. Le SWI a le potentiel de fournir des informations sur l’organisation fibreuse du thrombus ainsi que sur la détection d’endofuites. Tout d’abord, le premier objectif de cette thèse consistait à tester le SWI sur des AAAs dans des modèles canins pour la détection d’endofuites et la caractérisation du thrombus. Des SGs furent implantées dans un groupe de 18 chiens avec un anévrisme créé au moyen de la veine jugulaire. 4 anévrismes avaient une endofuite de type I, 13 avaient une endofuite de type II et un anévrisme n’avait pas d’endofuite. Des examens échographiques, DUS et SWI ont été réalisés à l’implantation, puis 1 semaine, 1 mois, 3 mois et 6 mois après le traitement EVAR. Une angiographie, un CT-scan et des coupes macroscopiques ont été produits au sacrifice. Les régions d’endofuites, de thrombus frais et de thrombus organisé furent identifiées et segmentées. Les valeurs de rigidité données par le SWI des différentes régions furent comparées. Celles-ci furent différentes de façon significative (P < 0.001). Également, le SWI a pu détecter la présence d’endofuites où le CT-scan (1) et le DUS (3) ont échoué. Dans la continuité de ces travaux, le deuxième objectif de ce projet fut de caractériser l’évolution du thrombus dans le temps, de même que l’évolution des endofuites après embolisation dans des modèles canins. Dix-huit anévrismes furent créés dans les artères iliaques de neuf modèles canins, suivis d’une endofuite de type I après EVAR. Deux gels embolisants (Chitosan (Chi) ou Chitosan-Sodium-Tetradecyl-Sulfate (Chi-STS)) furent injectés dans le sac anévrismal pour promouvoir la guérison. Des examens échographiques, DUS et SWI ont été effectués à l’implantation et après 1 semaine, 1 mois, 3 mois et 6 mois. Une angiographie, un CT-scan et un examen histologique ont été réalisés au sacrifice afin d’évaluer la présence, le type et la grosseur de l’endofuite. Les valeurs du module d’élasticité des régions d’intérêts ont été identifiées et segmentées sur les données pathologiques. Les régions d’endofuites et de thrombus frais furent différentes de façon significative comparativement aux autres régions (P < 0.001). Les valeurs d’élasticité du thrombus frais à 1 semaine et à 3 mois indiquent que le SWI peut évaluer la maturation du thrombus, de même que caractériser l’évolution et la dégradation des gels embolisants dans le temps. Le SWI a pu détecter des endofuites où le DUS a échoué (2) et, contrairement au CT-scan, détecter la présence de thrombus frais. Finalement, la dernière étape du projet doctoral consistait à appliquer le SWI dans une phase clinique, avec des patients humains ayant déjà un AAA, pour la détection d’endofuite et la caractérisation de l’élasticité des tissus. 25 patients furent sélectionnés pour participer à l’étude. Une comparaison d’imagerie a été produite entre le SWI, le CT-scan et le DUS. Les valeurs de rigidité données par le SWI des différentes régions (endofuite, thrombus) furent identifiées et segmentées. Celles-ci étaient distinctes de façon significative (P < 0.001). Le SWI a détecté 5 endofuites sur 6 (sensibilité de 83.3%) et a eu 6 faux positifs (spécificité de 76%). Le SWI a pu détecter la présence d’endofuites où le CT-scan (2) ainsi que le DUS (2) ont échoué. Il n’y avait pas de différence statistique notable entre la rigidité du thrombus pour un AAA avec endofuite et un AAA sans endofuite. Aucune corrélation n’a pu être établie de façon significative entre les diamètres des AAAs ainsi que leurs variations et l’élasticité du thrombus. Le SWI a le potentiel de détecter les endofuites et caractériser le thrombus selon leurs propriétés mécaniques. Cette technique pourrait être combinée au suivi des AAAs post-EVAR, complémentant ainsi l’imagerie DUS et réduisant le coût et l’exposition à la radiation ionisante et aux agents de contrastes néphrotoxiques.Cardiovascular diseases are the leading cause of death worldwide. Abdominal aortic aneurysms (AAAs) are part of these horrible diseases. An aneurysm is a dilatation of an artery that can lead to death. A rupture of an AAA can lead to death nearly 80% of the time. One way to treat AAAs is the insertion of a stent-graft (SG) in the aorta in order to reduce the pressure on the wall, commonly known as endovascular repair (EVAR). Endoleak, defined as persistent blood flow within the aneurysm sac and outside the SG, is the main complication of EVAR. This phenomenon increases the risk of rupture and can develop at any time after EVAR. A life-long surveillance follow-up with computed tomography (CT-scan) is required to detect endoleak, increasing the cost of EVAR, exposing patient to ionizing radiation and nephrotoxic contrast agent. Aneurysm growth without evidence of endoleak on CT-scan is called endotension. After SG delivery, the blood is trapped between the SG and aneurysm wall. If there is no residual flow (endoleak), the blood will coagulate to form fresh thrombus that will progressively organize to become a fibrous thrombus leading to aneurysm shrinkage. There is little data in the literature to study the timing of this process and the relationship between thrombus organization and aneurysm shrinkage. The gold-standard of post-EVAR surveillance, the CT-scan, cannot detect the presence of fresh thrombus. There is a clear need to invest in a safe and cost effective technique for post-EVAR surveillance. A recent method, dynamic elastography, measures the elasticity of tissues in real time. The principle of this technique is based on the generation of shear waves and studies their propagations for the determination of elastic properties (stiffness) of tissues. This thesis aims the application of dynamic elastography for the detection of endoleak and to characterize mechanical properties of AAAs tissues after EVAR. This project reveals the potential of elastography to reduce costs, exposure to ionizing radiation and nephrotoxic contrast agents in CT-scan follow-up of AAAs post-EVAR. Dynamic elastography using the shear wave imaging (SWI) is promising and can complement the Doppler ultrasound (DUS), which is already used in post-EVAR follow-up. SWI has the potential to get information from thrombus organization and to detect endoleak. The first objective of this thesis was to test the SWI on AAAs in canines models for the detection of endoleak and the characterization of thrombus. SGs were implanted in 18 dogs after surgical creation of type I endoleaks (4 AAAs), type II endoleaks (13 AAAs) and no endoleaks (1 AAA). DUS and SWI were engaged before (baseline) and 7, 30, 90 and 180 days (sacrifice) after SG implantation. Digital subtraction angiography, CT-scan and macroscopic tissue sections were analyzed at sacrifice. Endoleak and thrombus areas were identified and segmented. Elasticity (Young's) moduli were measured in different regions of interest (endoleaks, fresh and organized thrombi) after registration of pathological findings. Rigidity values of the regions of interest were significantly different (P < 0.001). SWI was able to detect endoleaks where CT-scan (1) and DUS (3) failed. The second objective of this project was to characterize the evolution of the thrombus in time, also as the endotension after endoleak embolization in canines models. EVAR was done with creation of type I endoleak in 18 aneurysms created in nine dogs (common iliacs arteries). Two embolization gels (Chitosan (Chi) or Chitosan-Sodium-Tetradecyl-Sulfate (Chi-STS)) were injected in the sac to seal the endoleak and promote healing. SWI and DUS were performed at baseline (implantation, 1 week, 1 month, 3 months) whereas angiography and CT-scan were performed at sacrifice to evaluate the presence and type of the endoleak. Macroscopic and histopathological analyses were processed to identify and segment five different regions of interest (ROIs) (endoleak, fresh or organized thrombus, Chi or Chi-STS). Elasticity values of endoleak and fresh thrombus areas were significantly lower than organized thrombus, Chi and Chi-STS areas (P < 0.001). Elasticity values of fresh thrombus at 1 week and at 3 months indicated that SWI can evaluate thrombus maturation. It can also characterize embolization agents degradation. SWI was able to detect endoleak where DUS failed (2) and distinguish fresh thrombi which cannot be detected on CT-scan. Finally, the last step of the doctoral project was to apply the SWI in a clinical phase with humans with an AAA for the detection of endoleak and characterizing elasticity of tissues. 25 patients were selected to participate in the study. Comparison of SWI, CT-scan and DUS images was conducted. Rigidity values by SWI of regions of interest (endoleak, thrombus) were identified and segmented. These were significantly different (P < 0.001). SWI detected 5 endoleaks on 6 (sensitivity of 83.3%) and had 6 false positives (specificity of 76%). SWI detected endoleaks where CT-scan (2) and DUS (2) failed. No statistical difference was found in elasticity between thrombus with an AAA with endoleak and thrombus with an AAA without endoleak. Also, no correlation was found between AAA diameter or its variation over time and thrombus elasticity. SWI has the potential to detect endoleaks and characterize thrombus. The approach could be combined with DUS surveillance of AAAs after EVAR, which is currently widely practiced to reduce the cost of AAA follow-up and exposure to ionizing radiation and contrast agents

Feasibility of shear wave sonoelastography to detect endoleak and evaluate thrombus organization after endovascular repair of abdominal aortic aneurysm

Purpose To investigate the feasibility of shear wave sonoelastography (SWS) for endoleak detection and thrombus characterization of abdominal aortic aneurysm (AAA) after endovascular repair (EVAR). Materials and methods Participants who underwent EVAR were prospectively recruited between November 2014 and March 2016 and followed until March 2019. Elasticity maps of AAA were computed using SWS and compared to computed tomography angiography (CTA) and color Doppler ultrasound (CDUS). Two readers, blinded to the CTA and CDUS results, reviewed elasticity maps and B-mode images to detect endoleaks. Three or more CTAs per participant were analyzed: pre-EVAR, baseline post-EVAR, and follow-ups. The primary endpoint was endoleak detection. Secondary endpoints included correlation between total thrombus elasticity, proportion of fresh thrombus, and aneurysm growth between baseline and reference CTAs. A 3-year follow-up was made to detect missed endoleaks, EVAR complication, and mortality. Data analyses included Cohen’s kappa; sensitivity, specificity, and positive predictive value (PPV); Pearson coefficient; and Student’s t tests. Results Seven endoleaks in 28 participants were detected by the two SWS readers (k = 0.858). Sensitivity of endoleak detection with SWS was 100%; specificity and PPV averaged 67% and 50%, respectively. CDUS sensitivity was estimated at 43%. Aneurysm growth was significantly greater in the endoleak group compared to sealed AAAs. No correlation between growth and thrombus elasticity or proportion of fresh thrombus in AAAs was found. No new endoleaks were observed in participants with SWS negative studies. Conclusion SWS has the potential to detect endoleaks in AAA after EVAR with comparable sensitivity to CTA and superior sensitivity to CDUS

Intracapsular pressures in the flexion-abduction-external rotation and flexion-adduction-internal rotation tests and their comparison with classic hip range of motion : a cadaveric assessment

Background Flexion-Abduction-External-Rotation and Flexion-Adduction-Internal-Rotation tests are used to reproduce pain at the hip during clinical assessment. As pain can be elicited by high intracapsular pressure, no information has been provided regarding intracapsular pressure during these pain provocative tests. Methods Eight hip joints from four cadaveric specimens (78.5 ± 7.9 years) were assessed using intra-osseous tunnels reaching the lateral and acetabular compartments. To simulate synovial liquid, 2.7 ml of liquid were inserted in both compartments using adaptor injectors. Optic pressure transducers were used to measure pressure variations. Pressures were compared between compartments in each test and between tests for each compartment. Both tests were compared with uniplanar movements. Findings The Flexion-Adduction-Internal-Rotation test showed a significant difference between pressure measured in the lateral (27.17 ± 42.63 mmHg) and acetabular compartment (−26.80 ± 29.26 mmHg) (P < 0.006). The pressure measured in the lateral compartment during the Flexion-Adduction-Internal-Rotation test (27.17 ± 42.63 mmHg) was significantly higher than in the Flexion-Abduction-External-Rotation test (−8.09 ± 15.09 mmHg) (P < 0.010). The pressure measured in the lateral compartment in the Flexion-Abduction-External-Rotation test was significantly lower than during internal rotation (P = 0.011) and extension (P = 0.006). Interpretation High intracapsular pressure is correlated with greater pain at the hip. Clinicians should assess pain with caution during the Flexion-Adduction-Internal-Rotation test as this test showed high intracapsular pressures in the lateral compartment. The Flexion-Abduction-External-Rotation is not influenced by high intra-capsular pressures

Glenohumeral joint capsular tissue tension loading correlates moderately with shear wave elastography: a cadaveric investigation

Purpose The purpose of this study was to investigate changes in the mechanical properties of capsular tissue using shear wave elastography (SWE) and a durometer under various tensile loads, and to explore the reliability and correlation of SWE and durometer measurements to evaluate whether SWE technology could be used to assess tissue changes during capsule tensile loading. Methods The inferior glenohumeral joint capsule was harvested from 10 fresh human cadaveric specimens. Tensile loading was applied to the capsular tissue using 1-, 3-, 5-, and 8-kg weights. Blinded investigators measured tissue stiffness and hardness during loading using SWE and a durometer, respectively. Intraobserver reliability was established for SWE and durometer measurements using intraclass correlation coefficients (ICCs). The Pearson product-moment correlation was used to assess the associations between SWE and durometer measurements. Results The ICC3,5 for durometer measurements was 0.90 (95% confidence interval [CI], 0.79 to 0.96; P<0.001) and 0.95 (95% CI, 0.88 to 0.98; P<0.001) for SWE measurements. The Pearson correlation coefficient values for 1-, 3-, and 5-kg weights were 0.56 (P=0.095), 0.36 (P=0.313), and -0.56 (P=0.089), respectively. When the 1- and 3-kg weights were combined, the ICC3,5 was 0.72 (P<0.001), and it was 0.62 (P<0.001) when the 1-, 3-, and 5-kg weights were combined. The 8-kg measurements were severely limited due to SWE measurement saturation of the tissue samples. Conclusion This study suggests that SWE is reliable for measuring capsular tissue stiffness changes in vitro at lower loads (1 and 3 kg) and provides a baseline for the non-invasive evaluation of effects of joint loading and mobilization on capsular tissues in vivo

Visualization of mouse neuronal ganglia infected by Herpes Simplex Virus 1 (HSV-1) using multimodal non-linear optical microscopy.

International audienceHerpes simplex virus 1 (HSV-1) is a neurotropic virus that causes skin lesions and goes on to enter a latent state in neurons of the trigeminal ganglia. Following stress, the virus may reactivate from latency leading to recurrent lesions. The in situ study of neuronal infections by HSV-1 is critical to understanding the mechanisms involved in the biology of this virus and how it causes disease; however, this normally requires fixation and sectioning of the target tissues followed by treatment with contrast agents to visualize key structures, which can lead to artifacts. To further our ability to study HSV-1 neuropathogenesis, we have generated a recombinant virus expressing a second generation red fluorescent protein (mCherry), which behaves like the parental virus in vivo. By optimizing the application of a multimodal non-linear optical microscopy platform, we have successfully visualized in unsectioned trigeminal ganglia of mice both infected cells by two-photon fluorescence microscopy, and myelinated axons of uninfected surrounding cells by coherent anti-Stokes Raman scattering (CARS) microscopy. These results represent the first report of CARS microscopy being combined with 2-photon fluorescence microscopy to visualize virus-infected cells deep within unsectioned explanted tissue, and demonstrate the application of multimodal non-linear optical microscopy for high spatial resolution biological imaging of tissues without the use of stains or fixatives

Interferometric Second Harmonic Generation microscopy for tissue imaging

Second Harmonic Generation (SHG) microscopy is used to image tissues rich in noncentrosymmetric proteins such as collagen [1]. Two identical noncentrosymmetric structures with opposite orientation will emit a π phase shifted SHG signal because their second order nonlinear susceptibility tensors (χ(2)) are inverted. This can be exploited to obtain additional information about the orientation of noncentrosymmetric structures in a sample by measuring the phase of the SHG signal generated in an area scanned with SHG microscopy

Imaging the noncentrosymmetric structural organization of tissues with Interferometric Second Harmonic Generation microscopy

We image the relative orientation of organized groups of noncentrosymmetric molecules (like collagen or myosin) at the micron scale in biological tissues by combining interferometry and Second Harmonic Generation (SHG) microscopy

Scoping review on the treatment of radiodermatitis secondary to radiotherapy treatment of head and neck, and breast cancer

Purpose : Almost 95% of patients undergoing radiotherapy treatments will develop a form of radiodermatitis. Despite this prevalence, treatment recommendations lack consensus, and clinical practices differ. The purpose of this scoping review is to examine the literature for radiodermatitis treatment options occurring in persons with head and neck, as well as breast, cancer and to report the pain felt by these populations after receiving radiotherapy. Methods : A scoping review based on the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA_Sc-R) checklist was performed. To identify the sources of evidence, the MEDLINE, CINAHL, Cochrane, LiSSA and Google Scholar databases were searched. All available articles published in the French and English languages were included. Results : Two hundred fifty-five studies met the inclusion criteria. The included studies demonstrated heterogeneous results, owing to significant variations in the interventions, the controls and the assessment tools. The quality of the evidence was found to be low and at high risk for biases. Conclusion : This scoping review provides a broad overview of the available data and highlights the paucity of highquality evidence to guide therapeutic interventions for the optimal management of radiodermatitis. Since radiodermatitis is a common injury of radiotherapy for breast cancer and head and neck cancer, more research is needed to guide the prevention and treatment of radiodermatitis for patients suffering from this complication

Identification of cells infected by vUs7-8mCherry in histological sections.

<p>(A) Eyes of mice infected with vUs7-8mCherry-a were harvested at 2 days p.i., and analyzed by standard confocal microscopy. Structures of the eye are indicated by the white arrows. The red arrow indicates a group of cells infected by vUs7-8mCherry-a. (B) TG of mice infected with vUs7-8mCherry were harvested at 3 days p.i.; an infected neuron is visualized by confocal microscopy using the red field. (C) Merge image showing the autofluorescence of the TG in green field and the red field showing an infected cell. The white dashed line outlines an infected neuron.</p