Shear Wave Elastography (SWE) is an ultrasound based technique which is able to measure tissue stiffness through the speed of induced shear waves. Tissue stiffness is often related to pathological conditions and detecting mechanical changes can help the recognition of potential diseases. The clinical use of SWE is limited to isotropic tissue due to the difficulty in assessing a theoretical model for more complex tissue and this project therefore aimed to evaluate the possibility of obtaining a full mechanical characterization of a transversely isotropic (TI) phantom with dual-probe SWE. A TI hydrogel phantom was developed and mechanical tests were performed to verify its anisotropy and determine the elastic moduli in both the perpendicular and longitudinal directions. Shear moduli were estimated using conventional and dual-probe SWE comparing the results to theoretical pure-transverse (PT) and quasi-transverse (QT) wave propagation modes. Both mechanical and SWE tests showed that the phantoms were transversely isotropic ET/EL=0.81. Moreover, multiple wave propagation modes calculated with dual-probe SWE showed a good agreement with the theoretical curves and indicated the possibility of measuring all the elasticity constants needed to fully characterize an incompressible, TI tissue with dual-probe SWE.

Yes / In recent years, imaging has played an increasing role in the clinical management of patients with rheumatic diseases with respect to aiding diagnosis, guiding therapy and monitoring disease progression. These roles have been underpinned by research which has enhanced our understanding of disease pathogenesis and pathophysiology of rheumatology conditions, in addition to their key role in outcome measurement in clinical trials. However, compared to joints, imaging research of muscles is less established, despite the fact that muscle symptoms are very common and debilitating in many rheumatic diseases. Recently, it has been shown that even though patients with rheumatoid arthritis may achieve clinical remission, defined by asymptomatic joints, many remain affected by lingering constitutional systemic symptoms like fatigue, tiredness, weakness and myalgia, which may be attributed to changes in the muscles. Recent improvements in imaging technology, coupled with an increasing clinical interest, has started to ignite new interest in the area. This perspective discusses the rationale for using imaging, particularly ultrasound and MRI, for investigating muscle pathology involved in common inflammatory rheumatic diseases. The muscles associated with rheumatic diseases can be affected in many ways, including myositis—an inflammatory muscle condition, and myopathy secondary to medications, such as glucocorticoids. In addition to non-invasive visual assessment of muscles in these conditions, novel imaging techniques like shear wave elastography and quantitative MRI can provide further useful information regarding the physiological and biomechanical status of the muscle. / This research is funded by the NIHR infrastructure at Leeds.

Notre objectif était de rechercher une méthode d’évaluation musculaire afin de déterminer des facteurs de non réponse tissulaire à une injection de toxine botulique (TB) dans un muscle spastique, chez l’adulte post AVC et chez l’enfant paralysé cérébral (PC). Une étude de reproductibilité et 3 revues systématiques de la littérature ont été réalisées. Les mesures échographiques de l’épaisseur et de l’angle des pennation des fibres du muscle gastrocnémien médial en 2D sont reproductibles. La mesure du module d’élasticité par Shear Wave Ultrasound Elastography délivre une information fiable sur la rigidité du muscle gastrocnémien médial spastique au repos.L’analyse du devenir du muscle post-injection rapporte que la TB participe au remodelage du muscle spastique avec une atrophie persistante, répétition d’injections dépendante.L’étude de l’impact des traitements adjuvants à la TB chez l’enfant PC montre que le renforcement musculaire intensif, y compris des muscles injectés, permet de lutter contre l’atrophie sans renforcer la spasticité. Les plâtres d’allongement permettent d’optimiser le fonctionnement articulaire mais les preuves sur la diminution de la raideur musculaire restent faibles. Dans la description des facteurs pronostics d’efficacité, plus de la moitié des patients identifiés comme secondairement non-répondeurs à la TB dans la spasticité des membres ne sont pas immunisés contre la TB. Les anticorps neutralisants ne sont donc pas la principale cause de non-réponse secondaire. Une évaluation de la qualité musculaire échographique comme facteur pronostic de réponse à la TB et pour mesurer l’impact des traitements adjuvants devrait être réalisée régulièrement afin de déterminer à quel moment ces traitements ne sont plus favorables au système musculaire. / The aim was to investigate a muscle evaluation method to determine tissue factors leading to non-responsiveness to an injection of botulinum toxin (BTX) into a spastic muscle in adult post stroke and children with cerebral palsy (CP). A reproducibility study and 3 systematic literature reviews were carried out. 2D ultrasound measurements of thickness and pennation angle of medialis gastrocnemius muscle fibers are reproducible. Measurement of the modulus of elasticity by shear wave ultrasound elastography provides a reliable information about the rigidity of the spastic medial gastrocnemius muscle at rest.Analysis of the post-injection muscle fate found that BTX participates in the remodeling of the spastic muscle with persistent atrophy that is dependent on the repetition of the injections.Analysis of the impact of BTX adjuvant therapies in CP children showed that intensive muscle strengthening, including of the injected muscles, may help combat atrophy without increasing spasticity. Stretching casts are used to optimize joint function, but there is little evidence for a reduction in muscle stiffness. In the description of prognostic efficacy factors, more than half of patients identified as secondariy non-responders to BTX in limb spasticity tests were not immunized against BTX. Neutralizing antibodies were therefore not the main cause for secondary non-responsiveness. An ultrasound evaluation of muscle quality as a prognostic factor for BTX response and to measure the impact of adjuvant treatments must be regularly performed to determine when these treatments are no longer favourable for the muscle system.

Understanding cardiac pumping function is crucial to guiding diagnosis, predicting outcomes of interventions, and designing medical devices that interact with the cardiovascular system.  Computer simulations of hemodynamics can show how the complex cardiovascular system is influenced by changes in single or multiple parameters and can be used to test clinical hypotheses. In addition, methods for the quantification of important markers such as elevated arterial stiffness would help reduce the morbidity and mortality related to cardiovascular disease. The general aim of this thesis work was to improve understanding of cardiovascular physiology and develop new methods for assisting clinicians during diagnosis and follow-up of treatment in cardiovascular disease. Both computer simulations and medical imaging were used to reach this goal. In the first study, a cardiac model based on piston-like motions of the atrioventricular plane was developed. In the second study, the presence of the anatomical basis needed to generate hydraulic forces during diastole was assessed in heathy volunteers. In the third study, a previously validated lumped-parameter model was used to quantify the contribution of arterial and cardiac changes to blood pressure during aging. In the fourth study, in-house software that measures arterial stiffness by ultrasound shear wave elastography (SWE) was developed and validated against mechanical testing. The studies showed that longitudinal movements of the atrioventricular plane can well explain cardiac pumping and that the macroscopic geometry of the heart enables the generation of hydraulic forces that aid ventricular filling. Additionally, simulations showed that structural changes in both the heart and the arterial system contribute to the progression of blood pressure with age. Finally, the SWE technique was validated to accurately measure stiffness in arterial phantoms. / <p>QC 20161115</p>

Breast cancer is the most common cancer in women worldwide. In 2009, a novel imaging modality called Shear Wave Elastography (SWE), an ultrasound technique visualising the elasticity of tissue, was introduced to the field of clinical breast imaging. Because malignant tissues are generally stiffer than benign tissues, SWE supports the differentiation of benign / malignant solid breast lesions. However, no standard has yet been defined for the application and the evaluation of results. Furthermore, image evaluation has to be carried out directly from the ultrasound system, complicating long-term and multi-centre studies. This PhD thesis investigated the influences from the imaging process and image evaluation on SWE measurements. Various parameters were appraised with regard to their diagnostic performance, in order to define the best clinical standard. To define more complex image analysis, taking the parameters investigated into account, algorithms were devised to enable automatic assessment of B-mode and SWE images. In this work, influences from the imaging process and image evaluation on the SWE measurements were demonstrated. The influences investigated included: the impact from the region of interest and the imaging plane used; the individual variation in breast composition; the number of images considered and the pressure applied during imaging. The algorithms described within this work achieved a diagnostic accuracy similar to that of manual assessment by a radiology expert. This thesis demonstrated influences from the imaging process and image evaluation on the SWE measurements obtained. Taking these influences into consideration would complicate the clinical application of SWE imaging. However, automatic image evaluation as presented here would overcome this issue. Using the guidelines defined in this PhD thesis also allows for comparison of results taken from different imaging sites.

Les maladies chroniques du foie constituent un problème majeur de santé publique. L’évaluation précise du degré de fibrose hépatique apporte au clinicien une estimation du pronostic dès la prise en charge initiale de ces patients, mais permet également la réalisation d’une surveillance évolutive, et intervient dans la décision et le choix d’un traitement. L’évaluation noninvasive de la fibrose hépatique par élastographie a permis de révolutionner la prise en charge des malades atteints d’une maladie chronique du foie. L’objectif de notre travail est d’évaluer les performances diagnostiques d’une nouvelle technique d’élastographie hépatique, appelée « Supersonic ShearImaging » (SSI), et d’analyser sa plus-value dans l’évaluation non-invasive des maladies chroniques du foie.Dans une première étude, nous avons prospectivement analysé et comparé les performances diagnostiques de l’élastographie SSI par rapport au FibroScan et l’ARFI pour le staging de la fibrose hépatique sur une série de 349 patients avec une maladie chronique du foie diagnostiquée et gradée par ponction-biopsiehépatique.Dans une seconde étude, nous avons prospectivement étudié l’impact diagnostique de l’élastographie SSIsur le foie et la rate chez une population de 401 patients avec cirrhose pour l’évaluation de la gravité de la maladie cirrhotique.Dans une troisième étude, nous avons réalisé une analyse prospective bicentrique (Angers et Bordeaux)de la performance diagnostique de l’élastographie SSI par rapport au FibroScan et l’ARFI dans l’évaluation non invasive de la fibrose hépatique sur une série de 291 patients avec stéatopathie non-alcoolique et ponction-biopsiehépatique. / Abstract :The management and the prognosis for chronic liver diseases are widely based on the presence and the development of a liver fibrosis. The progressive worsening of liver fibrosis leads in a certain number of patients to the development of cirrhosis and its complications. Thus, the development of non-invasive diagnostic tools for the diagnosis and the monitoring of the liver fibrosis is of crucial interest. Liver elastography is one of the most promising techniques that have recently emerged in the field of chronic liver diseases. In this study, we aim to assess the diagnostic accuracy of a new elastography technique, named “Supersonic Shear Imaging” (SSI), and toanalyse its added value in the non invasive diagnosis of chronic liver diseases.In a first study, we prospectively analysed and compared the diagnostic performances of SSI elastography versus FibroScan and ARFI for the staging of liver fibrosis in a cohort of 349 patients with chronic liver diseases that consecutively underwent a liver biopsy. In a second study, we prospectively analysed the impact of liver and spleen SSI elastography in a cohortof 401 cirrhotic patients for the non invasive diagnosis of cirrhosis severity and oesophageal varices.In a third study, we assessed the clinical use of liver stiffness measurement evaluated by SSI, FibroScan,and ARFI in a cohort of nonalcoholic fatty liver disease patients who underwent liver biopsy. A total of 291 NAFLD patients were prospectively enrolled at 2 French university hospitals (Angers and Bordeaux).

Each year million of babies are born pre-term, some of these pre-term births occur due to the motherhaving a too soft cervix which can not withstand the forces the baby exposes it to. The aim of thisstudy was to implement and evaluate a programmable shear wave elastography ultrasound system forcervical applications and investigate the optimal settings of shear wave elastography push voltage andshear wave elastography push focus depth. Shear wave elastography is an ultrasound based imagingmodality aiming to evaluate the tissue elasticity by using acoustic radiation forces to induce shear waves.The propagation of the shear waves through the tissue is then tracked in order to calculate the shearwave velocity which is related to the tissue elasticity. B-mode imaging, pushing sequence and planewave imaging have been implemented and measurements have been conducted on four cervical polyvinylalcohol phantoms. The acquired data has been post-processed using Loupas 2D-autocorrector to gainthe axial displacement and enabling tracking of the shear waves to allow evaluation and optimizationof the implemented method. The implemented shear wave technique showed to be able to distinguishcervical phantoms of dierent elasticity and a high pushing voltage and shallow focus push depth havebeen found to produce the most reliable results.

Shear wave elastography is a medical imaging modality in which tissue elasticity is estimated by measuring the speed of ultrasound-induced shear waves. This study aimed to implement four shear wave generating pushes and compare their performance according to chosen metrics. The focused push, unfocused push, unfocused comb push and line push were implemented on a Verasonics ultrasound system and tested on a polyvinyl alcohol phantom. Shear wave propagation was imaged using angle-compounded ultrafast imaging. Axial particle velocities were estimated using a 2D autocorrelator and then cross-correlated to obtain local shear wave speed estimates. The focused push and line push were found to generate shear waves with 1--3 times higher peak axial particle velocity, implying better signal-to-noise ratios. The focused push, unfocused push and line push were found to exhibit areas 7 mm wide around the pushing beams in which shear wave speed cannot be estimated, whereas the unfocused comb push has no such blind area.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第21042号 / 人健博第58号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 坪山 直生, 教授 黒木 裕士, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

In the past decade there has been a significant increase in focus on the effect upper body vibration (UBV) has on the recovery of skeletal muscle after exercise-induced muscle damage. Recovery can be defined and investigated using a wide variety of methods. This study used three different measurements to track muscle recovery over 7 days following an exercise muscle damage protocol and applied vibration to a mathematical model. A visual analog scale (VAS) was used to measure muscle pain, a strain gauge was used to obtain maximum voluntary isometric contraction (MVIC) strength measurements, and shear wave elastography (SWE) represented muscle stiffness over the 7-day experiment. Thirty-three participants were divided into three groups. The first was a control group (C) that experienced no exercise and no therapy. The no vibration group (NV) performed the damage an exercise protocol but received no therapy. The vibration group (V) performed the same exercise protocol but also received vibration therapy. The exercise protocol consisted of 100 dumbbell curls at starting at 50% of their MVIC with one minute of rest after each set of ten. The data provided convincing evidence (27.2%, p < 0.0001) that group NV was not back to its normal stiffness after 7 days unlike group V, which was shown not to be any different from its baseline at the end of the week (9.15%, p = 0.137). Three vibration factors (����1, ����2, ����3) were added to a skeletal muscle regeneration model (SK) to simulate how vibration affects muscle regeneration. The three factors were determined by analyzing previous research to understand how vibration affects cells in the regeneration process. Adding these into SK decreased the time to recovery from about 13 days to about 7 days. Recovery was defined by reaching 10% of the original number of myofibers within the damaged muscle.