Le rythme thêta est un rythme cérébral associé à l’activité locomotrice et au sommeil paradoxal. Bien que son implication dans la communication entre régions du cerveau et processus mnésiques ait largement été démontrée, il persiste un manque de données extensives dû à la difficulté d’imager l’ensemble de l’activité cérébrale dans des conditions naturelles de locomotion et d’exploration. Dans cette thèse, j’ai développé une approche qui combine l’enregistrement des potentiels de champs locaux à l’imagerie ultrasonore fonctionnelle (fUS) sur l’animal en mouvement libre. Pour la première fois, j’ai pu révéler les réponses hémodynamiques associées au rythme thêta dans la plupart des structures du système nerveux central avec de bonnes résolutions spatiale (100 x 100 x 400 μm) et temporelle (200 ms). Pendant la locomotion et le sommeil, les variations hémodynamiques de l’hippocampe, du thalamus dorsal et du cortex (rétrosplenial, somatosensoriel) corrèlent fortement avec la puissance instantanée du signal thêta hippocampique, avec un décalage temporel variant de 0.7 s à 2.0 s selon les structures. De manière intéressante, les rythmes gamma hippocampiques moyen (55-95 Hz) et rapide (100-150 Hz) expliquent la variance des signaux hémodynamiques mieux que le seul rythme thêta, alors que le rythme gamma lent (30-50 Hz) est non pertinent. L’hyperémie fonctionnelle de l’hippocampe suit séquentiellement la boucle tri-synaptique (gyrus denté - région CA3 - région CA1) et se renforce considérablement à mesure que la tâche progresse. Lors du sommeil paradoxal, j’ai observé une hyperémie tonique globale ainsi que des activations phasiques de grande amplitude initiées dans le thalamus et terminant dans les aires corticales, que nous avons appelées “poussées vasculaires”. De fortes bouffées d’activité gamma rapide (100-150 Hz) précèdent de manière robuste ces poussées vasculaires, l’inverse n’étant pas vrai. Dans l’ensemble, ces résultats révèlent la dynamique spatio-temporelle des signaux hémodynamiques associés à la locomotion et au sommeil paradoxal et suggèrent un lien fort entre rythmes thêta, gamma rapide et activité vasculaire globale / Theta rhythm is a prominent oscillatory pattern of EEG strongly associated with active locomotion and REM sleep. While it has been shown to play a crucial role in communication between brain areas and memory processes, there is a lack of extensive data due to the difficulty to image global brain activity during locomotion behavior. In this thesis, I developed an approach that combines local field potential recordings (LFP) and functional ultrasound imaging (fUS) to unrestrained rats. For the first time, I could image the hemodynamic responses associated with theta rhythm in most central nervous system (CNS) structures, with high spatial (100 x 100 x 400 μm) and temporal (200 ms) resolutions. During running and REM sleep, hemodynamic variations in the hippocampus, dorsal thalamus and cortices (S1BF, retrosplenial) correlated strongly with instantaneous theta power, with a delay ranging from 0.7 to 2.0 s after theta peak. Interestingly, mid (55-95 Hz) and high gamma (100-150 Hz) instantaneous power better explained hemodynamic variations than mere theta activity, while low-gamma (30-50 Hz) did not. Hippocampal hyperaemia followed sequentially the trisynaptic circuit (dentate gyrus - CA3 region - CA1 region) and was considerably strengthened as the task progressed. REM sleep revealed brain-wide tonic hyperaemia, together with phasic high-amplitude vascular activation starting in the dorsal thalamus and fading in cortical areas, which we referred to as “vascular surges”. Strong bursts of hippocampal high gamma (100-150 Hz) robustly preceded these surges, while the opposite was not true. Taken together, these results reveals the spatio-temporal dynamics of hemodynamics associated with locomotion and REM sleep and suggest a strong link between theta, high-gamma rhythms and brain-wide vascular activity.

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The harmonic generation due to the nonlinear behavior of Ultrasound Contrast Agents (UCAs) must be exploited for improved efficiency when imaging vascular targets in the neighborhood of highly echogenic tissue. One may even further improve the efficiency by focusing on the subharmonic generation of the UCAs, which is an even more exclusive property than the generation of higher harmonics, for improved Contrast-to-Tissue ratio (CTR). The aim of this work was first, the design of a set-up for nonlinear imaging of Poly-Vinyl Alcohol (PVA) based UCAs on The Verasonics Research System with special focus on nondestructive Subharmonic Imaging. The second part of the work addressed the evaluation of the subharmonic response provided by the agents in the developed setup. Six different imaging techniques were developed. These were Fundamental B-mode imaging (FB), Pulse Inversion imaging (PI), and a Contrast Pulse Sequence based on three pulses (CPS3), with and without a focus on the subharmonic component by the implementation of a Linear Bandpass Filter (LBF). Experiments were performed on a tissue mimicking flow phantom and the performance of the agents for each technique was determined in terms of CTR and CNR. The PVA agents provided a backscattering enhancement of the order of 23 dB through FB imaging. However, the performance of the FB technique was unsatisfactory in terms of CTR. The CPS3 sequence performed best of the six techniques with an improvement of 14 dB and 13 dB in CTR and CNR, respectively, compared with the FB technique. Combining the LBF around the subharmonic component with the multi-pulse techniques of PI and CPS3 resulted in a degraded CTR performance due to significant amount of signals from tissue around the subharmonic component and insufficient subharmonic detection from the PVA agents.

In the past decade, the application of adaptive beamforming methods to medical ultrasound imaging has become a field of increased interest, due to their ability to achieve superior ultrasound image quality. Such enhancements, however, come at a high computational cost. This thesis attempts to address the following simple question: Can we maintain a superior image quality while reducing the computational cost of adaptive beamforming? Our goal is to effectively combine low-complexity nonadaptive beamforming, such as the Delay-and-Sum (DAS) technique, with high-complexity adaptive beamforming, such as the Minimum variance Distortionless Response (MVDR) technique, implemented using the Generalized Sidelobe Canceller (GSC), to obtain high-quality images at low computational cost. We propose a simple two-pass beamforming scheme for that purpose. During the first pass, our scheme processes buffered input vectors using the inexpensive DAS method and computes the corresponding envelope. Based on that envelope information, selected outputs may be recomputed during the second pass (to improve beamforming performance) using the expensive GSC beamforming method. The purpose of the first pass is to identify which nonadaptively beamformed outputs can be spared from a heavy computational load of adaptive beamforming taking place in the second pass. We have evaluated our scheme using simulated ultrasound images of a 12-point phantom and a point-scatterer-cyst phantom, achieving substantial threshold-dependent computational savings without significant degradation in image resolution and contrast, compared to pure GSC beamforming. / Graduate / rehoumahichem@gmail.com

High Intensity Focused Ultrasound (HIFU) is a promising technique for the treatment of localized cancers. The ability to focus ultrasound precisely on a predetermined volume allows the possibility of selective tissue destruction at this position without damage to surrounding tissues. However, many difficulties remain in the treatment of deep-seated tumors. In this thesis, new therapeutic and monitoring techniques are proposed to address these problems, by using phased arrays of ultrasound transducers. Two monitoring techniques based on the detection of the displacements of the ultrasonic speckle are developed, and allowed us to image the changes in the temperature and the shear modulus during HIFU therapy. In-vitro ultrasound-guided experiments are performed. Secondly, the problem of organs motion during the treatment is addressed. A method for real-time tracking the 3D motion of tissues is combined with a 2D High Intensity Focused Ultrasound multi-channel system in order to correct the respiratory motion during HIFU therapies. In the last section of this thesis, a high power ultrasonic system is developed for transcranial HIFU brain therapy. The skulls aberrations are corrected using a time reversal mirror thanks to an implanted hydrophone. In-vivo experiments are conducted on 22 sheep with minimally invasive surgery. Finally, a non-invasive protocol based on CT scans of the entire skull is developed and allows the prediction of the skulls aberrations and the skull overheating.

Regenerative medicine is an interdisciplinary field which has advanced with the use of biotechnologies related to biomaterials, growth factors, and stem cells to replace or restore damaged cells, tissues, and organs. Among various therapeutic approaches, cell-based therapy is most challenging and exciting for both scientists and clinicians pursuing regenerative medicine. Specifically, stem cells, including mesenchymal stem cells and adipose-derived stem cells, are promising candidate cell types for cell-based therapy because they can differentiate into multiple cell types for tissue regeneration and stimulate other cells through neovascularization or paracrine signaling. Also, for effective treatment using stem cells, the tissue engineered constructs, such as bioactive degradable scaffolds, that provide the physical and chemical cues to guide their differentiation are incorporated with stem cells before implantation. Also, it was previously demonstrated that tissue-engineered matrices can promote tubulogenesis and differentiation of stem cells to vascular cell phenotypes. Hence, during tissue regeneration after stem cell therapy, there are numerous factors that need to be monitored. As a result, imaging-based stem cell tracking is essential to evaluate the distribution of stem cells as well as to monitor proliferation, differentiation, and interaction with the microenvironment. Therefore, there is a need for a stem cell imaging technique that is not only noninvasive, sensitive, and easy to operate, but also capable of quantitatively assessing stem cell behaviors in the long term with high spatial resolution. Therefore, the overall goal of this research is to demonstrate a novel imaging method capable of continuous in vitro assessment of stem cells as prepared with tissue engineered constructs and noninvasive longitudinal in vivo monitoring of stem cell behaviors and tissue regeneration after stem cell implantation. In order to accomplish this, gold nanoparticles are demonstrated as photoacoustic imaging contrasts to label stem cells. In addition, ultrasound and photoacoustic imaging was utilized to monitor stem cells and neovascularization in the injured rat tissue. Therefore, using these methods, tissue regeneration can be promoted and noninvasively monitored, resulting in a better understanding of the tissue repair mechanisms following tissue injury. / text

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The purposes of this dissertation were to determine: 1) the relationship betweenmuscle thickness change (MTC) as measured by rehabilitative ultrasound imaging(RUSI) and EMG activity in the lumbar multifidus (LM), 2) if motor control changesproduced by experimentally induced pain are measurable with RUSI, 3) if a differenceexists in MTC between subjects with low back pain (LBP) classified in the treatmentbasedclassification system (TBC) system and controls, 4) if MTC improves followingintervention.Current literature suggests sub-groups of patients with LBP exist and responddifferently to treatment, challenging whether the majority of LBP is "nonspecific". TheTBC system categorizes subjects into one of four categories (stabilization, mobilization,direction specific exercise, or traction). Currently, only stabilization subjects receive anintervention emphasizing stability. Because recent research has demonstrated that motorcontrol impairments of lumbar stabilizing muscles are present in most subjects with LBP,it is hypothesized that impairments may be present across the TBC classifications.Study 1: Established the relationship between MTC as measured by RUSI andEMG in the LM. Study 2: Assessed MTC of the LM during control and painfulconditions to determine if induced pain changes in LM and transverse abdominis (TrA)are measurable with RUSI. Study 3: Measured MTC of the LM and TrA in subjects withLBP classified in the TBC system and 20 controls. Subjects completed a stabilizationprogram and were re-tested.The inter-tester reliability of the RUSI measurements was excellent (ICC3,3 =.91,SEM=3.2%). There was a curvilinear relationship (r = .79) between thickness changeand EMG activity. There was a significant difference (p andlt; .01) between control andpainful conditions on 4 of the 5 LM tasks tested and on the TrA task. There was adifference in MTC between subjects and controls on the loaded LM test which varied bylevel and category. All categories were different from control on the TrA. Followingintervention the TrA MTC improved (p andlt; .01). The LM MTC did not (p values from .13-.86).These findings suggest MTC can be clinically measured and that deficits existwithin TBC system. Significant disability and pain reduction were measured.

The role rehabilitation plays in the management of patients with lateral epicondylalgia (LE) remains elusive secondary to high recurrence rates. Addressing scapular muscle deficits may be important in the rehabilitation of patients with LE. However, it is unknown if scapular muscle impairments exist in a working population of patients with LE. The purpose of this dissertation was to assess scapular muscle strength and endurance in a working population of patients with LE. Clinical scapular muscle assessment tools are limited in their ability to isolate specific muscles. Rehabilitative ultrasound imaging (RUSI) is a potentially useful tool but few studies have investigated its utility. Absolute muscle thickness measurements were obtained on healthy individuals for the lower trapezius (LT) and serratus anterior (SA) under three conditions (arm at rest, arm elevated with a low load, arm elevated with a high load). For both the LT and SA, a significant distinction could be made in muscle thickness between rest and a loaded condition but not between the two load conditions. Furthermore, excellent reliability was demonstrated for both muscles. It is unknown whether arm dominance plays a role in scapular muscle assessments. Therefore, healthy individuals between the ages of 30 and 65 were recruited to compare the effect of arm dominance on scapular muscle strength, endurance, and change in thickness measured by RUSI. Results indicate that arm dominance does significantly affect some measures of scapular muscle strength and endurance. However, the differences between the dominant and non-dominant limbs were not beyond measurement error. Scapular muscle strength, endurance, and change in muscle thickness of the LT and SA were assessed in 28 patients presenting with signs and symptoms consistent with LE. LT strength, SA strength, middle trapezius strength, endurance, and change in SA thickness were significantly less in patients with LE compared to matched controls. SA and LT strength were significantly less in the involved limb compared to the uninvolved limb in patients with LE. The results suggest that assessing scapular muscle endurance as well as LT and SA strength is indicated when evaluating patients with LE, and the results should be compared to normative data.

Ultrasound has been widely used in medical diagnostic imaging to image soft tissues. Compared with other methods, ultrasound is superior with no ionizing-radiation, easy portability, low cost, and the capability to provide elasticity information. Conventional ultrasound images provide distorted image information when the ultrasound beam is not normal to the bone structures. In this thesis, we present two imaging algorithms: reverse time migration (RTM) and split-step Fourier migration (SSFM), to image long bones using ultrasound. The methods are tested using simulated data sets. The reconstructed images show accurate cortical thickness measurement and provide the correct fracture dip. The images also clearly illustrate the healing process of a 1-mm wide crack with different in-filled tissue velocities simulating fracture healing. Two in-vitro examples using fractured bones are also presented. The study has showed that the migration methods have great potential to quantify bone fractures and monitor the fracture healing process.