<p>Several groups have proposed classifying atherosclerotic disease by using acoustic radiation</p><p>force (ARF) elasticity methods to estimate the mechanical and material</p><p>properties of plaque. However, recent evidence suggests that cardiovascular disease</p><p>(CVD), in addition to involving pathological changes in arterial tissue, is also a</p><p>hemodynamic remodeling problem. As a result, integrating techniques that can</p><p>estimate localized hemodynamics relevant to CVD remodeling with existing ARF based</p><p>elastography methods may provide a more complete assessment of CVD.</p><p>This thesis describes novel imaging approaches for combining clinically-accepted,</p><p>ultrasound-based flow velocity estimation techniques (color-flow Doppler and spectral-</p><p>Doppler imaging) with ARF-based elasticity characterization of vascular tissue. Techniques</p><p>for integrating B-mode, color-flow Doppler, and ARFI imaging were developed</p><p>(BACD imaging), validated in tissue-mimicking phantoms, and demonstrated for in</p><p>vivo imaging. The resulting system allows for the real-time acquisition (< 20 Hz) of</p><p>spatially registered B-mode, flow-velocity, and ARFI displacement images of arterial</p><p>tissue throughout the cardiac cycle. ARFI and color-flow Doppler imaging quality,</p><p>transducer surface heating, and tissue heating were quantified for different frame-rate</p><p>and scan-duration configurations. The results suggest that BACD images can be acquired</p><p>at high frame rates with minimal loss of imaging quality for approximately</p><p>five seconds, while staying beneath suggested limits for tissue and transducer surface</p><p>heating.</p><p>Because plaque-burden is potentially a 3D problem, techniques were developed</p><p>to allow for the 3D acquisition of color-flow Doppler and ARFI displacement data</p><p>using a stage-controlled, freehand scanning approach. The results suggest that a</p><p>40mm x 20mm x 25mm BACD volume can be acquired in approximately three seconds.</p><p>Jitter, SNR, lesion CNR, soft-plaque detectability, and flow-area assessment were</p><p>quantified in tissue mimicking phantoms with a range of elastic moduli relevant</p><p>to ARFI imaging applications. Results suggest that both jitter and SNR degrade</p><p>with increased sweep velocity, and that degradation is worse when imaging stiffer</p><p>materials. The results also suggest that a transition between shearing-dominated</p><p>jitter and motion-dominated jitter occurs sooner with faster sweep speeds and in</p><p>stiffer materials. These artifacts can be reduced with simple, linear filters. Results</p><p>from plaque mimicking phantoms suggest that the estimation of soft-plaque area</p><p>and flow area, both important tasks for CVD imaging, are only minimally affected</p><p>at faster sweep velocities.</p><p>Current clinical assessment of CVD is guided by spectral Doppler velocity methods.</p><p>As a result, novel imaging approaches (SAD-SWEI, SAD-GATED) were developed</p><p>for combining spectral Doppler methods with existing ARF-based imaging</p><p>techniques to allow for the combined assessment of cross-luminal velocity profiles,</p><p>wall-shear rate (WSR), ARFI displacement and ARF-induced wave velocities. These</p><p>techniques were validated in controlled phantom experiments, and show good agreement</p><p>between previously described ARF-techniques and theory. Initial in vivo feasibility</p><p>was then evaluated in five human volunteers. Results show that a cyclic</p><p>variability in both ARFI displacement and ARF-generated wave velocity occurs during</p><p>the cardiac cycle. Estimates of WSR and peak velocity show good agreement</p><p>with previous ultrasonic-based assessments of these metrics. In vivo ARFI and Bmode/</p><p>WSR images of the carotid vasculature were successfully formed using ECG gating</p><p>techniques.</p><p>This thesis demonstrates the potential of these methods for the combined assessment</p><p>of vascular hemodynamics and elasticity. However, continued investigation</p><p>into optimizing sequences to reduce transducer surface heating, removing the angle</p><p>dependency of the SAD-SWEI/SAD-GATED methods, and decreasing processing</p><p>time will help improve the clinical viability of the proposed imaging techniques.</p> / Dissertation

<p>This dissertation investigates the use of intraprocedure acoustic radiation force impulse (ARFI) imaging for visualization of radiofrequency ablation (RFA) lesions during cardiac transcatheter ablation (TCA) procedures. Tens of thousands of TCA procedures are performed annually to treat atrial fibrillation (AF) and other cardiac arrhythmias. Despite the use of sophisticated electroanatomical mapping (EAM) techniques to validate the modification of the electrical substrate, post-procedure arrhythmia recurrence is common due to incomplete lesion delivery and electrical conduction through lesion line discontinuities. The clinical demand for an imaging modality that can visually confirm the presence and completeness of RFA lesion lines motivated this research.</p><p>ARFI imaging is an ultrasound-based technique that transmits radiation force impulses to locally displace tissue and uses the tissue deformation response to generate images of relative tissue stiffness. RF-induced heating causes irreversible tissue necrosis and contractile protein denaturation that increases the stiffness of the ablated region. Preliminary in vitro and in vivo feasibility studies determined RF ablated myocardium appears stiffer in ARFI images.</p><p>This thesis describes results for ARFI imaging of RFA lesions for three research milestones: 1) an in vivo experimental verification model, 2) a clinically translative animal study, and 3) a preliminary clinical feasibility trial in human patients. In all studies, 2-D ARFI images were acquired in normal sinus rhythm and during diastole to maximize the stiffness contrast between the ablated and unablated myocardium and to minimize the bulk cardiac motion during the acquisition time.</p><p>The first in vivo experiment confirmed there was a significant decrease in the measured ARFI-induced displacement at ablation sites during and after focal RFA; the displacements in the lesion border zone and the detected lesion area stabilized over the first several minutes post-ablation. The implications of these results for ARFI imaging methods and the clinical relevance of the findings are discussed.</p><p>The second and third research chapters of this thesis describe the system integration and implementation of a multi-modality intracardiac ARFI imaging-EAM system for intraprocedure lesion evaluation. EAM was used to guide the 2-D ARFI imaging plane to targeted ablation sites in the canine right atrium (RA); the presence of EAM lesions markers and conduction disturbances in the local activation time (LAT) maps were used to find the sensitivity and specificity of predicting the presence of RFA lesion with ARFI imaging. The contrast and contrast-to-noise ratio between RFA lesion and unablated myocardium were calculated for ARFI and conventional ICE images. The opportunities and potential developments for clinical translation are discussed. </p><p>The last research chapter in this thesis describes a feasibility study of intracardiac ARFI imaging of RFA lesions in clinical patients. ARFI images of clinically relevant ablation sites were acquired, and this pilot study determined ARFI-induced displacements in human myocardium decreased at targeted ablation sites after RF-delivery. The challenges and successes of this pilot study are discussed.</p><p>This work provides evidence that intraprocedure ARFI imaging is a promising technology for the visualization of RFA lesions during cardiac TCA procedures. The clinical significance of this research is discussed, as well as challenges and considerations for future iterations of this technology aiming for clinical translation.</p> / Dissertation

Small-amplitude, high-frequency (ultrasound) forcing of fluid/particle systems is being used in a number of applications associated with non-destructive fluid mixing and the movement/manipulation of particles in suspension. Of most importance in this context are the second-order, steady, effects arising from the nonlinear interaction of a leading-order oscillatory field with itself. In this thesis we consider some of these steady effects in both incompressible and compressible fluids. We first consider the axisymmetric steady streaming generated in an incompressible, viscous fluid contained between two (radially) infinite parallel plates, each oscillating in a direction normal to its own plane. In the limit of small-amplitude, high-frequency oscillations, we show that the steady-streaming flow in the fluid bulk is driven by thin streaming sublayers at the plates, at which the normal velocity is zero and the radial velocity varies linearly with distance from the axis of rotational symmetry. Effectively, in the bulk flow, the bounding plates appear as (no-slip) impermeable walls that stretch radially. This bulk-flow problem is extended to allow for the analogous steady flow of two immiscible, incompressible, viscous fluids, each undergoing a radial-stretching motion appropriate to high-frequency steady streaming. For a flat interface between the fluids, a self-similar solution reduces the Navier--Stokes equations to a nonlinear boundary-value problem, the solution of which exhibits an interesting structure in the limit of large Reynolds number. In this limit, solutions can be found using matched asymptotic expansions, but the location of the interface between the fluids can only be determined if terms that are exponentially small in the Reynolds number are included. It is shown that for fluids of almost-equal densities, exponentially-small differences can have a leading-order effect on the observed flow. The second part of the thesis is concerned with the (steady) acoustic radiation force on a rigid sphere submerged in a compressible, inviscid fluid, when the wavelength of the incident acoustic field is large compared to the radius of the sphere. In this limit, a matched asymptotic expansion method is used to derive an expression for the acoustic radiation force, on both fixed and free rigid spheres, due to a range of incident fields. For incident acoustic fields that are appropriate to planar and circular waveguides/channels, expressions are derived for the scattered field and the radiation force on a rigid sphere in the long-wavelength limit. Fixed and free spheres located both on and off the axis of symmetry of these incident fields are considered. This is an extension to the current literature, in which numerical methods are used to examine the scattering from spheres in an off-axis position, and problems are restricted to the consideration of fixed spheres only. It is shown that there are stable and unstable positions within the waveguide where any off-axis acoustic radiation force vanishes, leaving only an along-channel component. For free spheres, these positions are shown to be dependent on the relative particle density and it is suggested that this may allow for a mechanism to sort such small particles radially in a circular waveguide, if secondary scattering effects are neglected.

Die vorliegende medizinische Dissertation untersucht nicht-invasive bildgebende Verfahren wie die konventionelle Sonographie, die Acoustic radiation force impulse (ARFI)-Elastographie sowie die Transiente Elastographie (TE) zur Detektion von Komplikationen in der Frühphase nach allogener Stammzelltransplantation. Dem kurativen Therapieansatz der Stammzelltransplantation steht ein hohes Komplikationspotential gegenüber. Besonders hepatobiliär treten Graft-versus-host Erkrankungen (GvHD) sowie Gefäßkomplikationen (VOD) auf. Der bisherige diagnostische Goldstandard, die Leberbiopsie, ist als invasives Verfahren mit einer hohen Intra- und Inter-Untersucher-Variabilität sowie der geringen Repräsentativität als Screeningmethode ungeeignet. Die Elastographieverfahren ARFI und TE als nicht-invasive Alternativen ermitteln die Lebergewebesteifigkeit als Surrogatparameter fibrotischer Veränderungen und wurden bereits in zahlreichen Studien als geeignete Diagnoseverfahren für Leberfibrose und -zirrhose unterschiedlicher Ätiologie definiert. Ziel dieser prospektiven Pilotstudie war die Evaluation der genannten Methoden zur Detektion von Frühkomplikationen nach allogener Stammzelltransplantation. Die Ergebnisse der Studie zeigen, dass sowohl die konventionelle Sonographie als auch die Transiente Elastographie pathologische Organveränderungen vor allem des hepatobiliären Systems detektieren können. Allerdings erscheinen diese Veränderungen unspezifisch. Es bestehen keine signifikanten Unterschiede zwischen Patienten mit und ohne Komplikationen. Anders bei der ARFI-Elastographie. Hier zeigten die Messwerte im linken Leberlappen signifikant höhere Werte bei Patienten mit Komplikationen. Zusammenfassend ist die ARFI-Elastographie zur Prädiktion möglicher Komplikationen nach allogener Stammzelltransplantation geeignet, sollte allerdings mit anderen diagnostischen Verfahren ergänzt werden.

A primary purpose of elasticity imaging, commonly known as elastography, is to extract the viscoelastic properties of a medium (including soft tissue) from the displacement caused by a stress field. Dynamic elastography methods that use the acoustic radiation force of ultrasound have several advantages, such as, non-invasiveness, low cost, and ability to produce a highly localized force field. A method for remotely generating localized low frequency shear waves in soft tissue is investigated, by using the modulated radiation force resulting from two intersecting quasi-CW confocal ultrasound beams of slightly different frequencies. In contrast to most radiation force-based methods previously presented, such shear waves are narrowband rather than broadband. As they propagate within a viscoelastic medium, different frequency-dependent effects will not significantly affect their spectrum, thereby providing a means for measuring the shear attenuation and speed as a function of frequency. Furthermore, to improve the detection signal-to-noise-ratio (SNR), increased acoustic pressure conditions may be needed, causing higher harmonics to be generated due to nonlinear propagation effects. Shear-wave propagation at harmonic modulation frequencies does not appear to have been previously discussed in the elastography literature. The properties of the narrowband shear wave propagation in soft tissue are studied by using the Voigt viscoelastic model and Green’s functions. In particular, the manner in which the characteristics of the viscoelastic medium affect their evolution under both low-amplitude (linear) and high-amplitude (nonlinear) source excitation and conditions that conform to human safety standards. It is shown that an exact solution of the viscoelastic Green’s function is needed to properly represent the propagation in higher-viscosity media, such as soft tissue, at frequencies much beyond a few hundred hertz. Methods for estimating the shear modulus and viscosity in viscoelastic media are developed based on both the fundamental and harmonic shear components.

<p>Implemented on an intracardiac echocardiography transducer, acoustic radiation force methods may provide a useful means of characterizing the heart's elastic properties. Elasticity imaging may be of benefit for diagnosis and characterization of infarction and heart failure, as well as for guidance of ablation therapy for the treatment of arrhythmias. This thesis tests the hypothesis that with appropriately designed imaging sequences, intracardiac acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) are viable tools for quantification of myocardial elasticity, both temporally and spatially. Multiple track location SWEI (MTL-SWEI) is used to show that, in healthy in vivo porcine ventricles, shear wave speeds follow the elasticity changes with contraction and relaxation of the myocardium, varying between 0.9 and 2.2 m/s in diastole and 2.6 and 5.1 m/s in systole. Infarcted tissue is less contractile following infarction, though not unilaterally stiffer. Single-track-location SWEI (STL-SWEI) is proven to provide suppression of speckle noise and enable improved resolution of structures smaller than 2 mm in diameter compared to ARFI and MTL-SWEI. Contrast to noise ratio and lateral edge resolution are shown to vary with selection of time step for ARFI and arrival time regression filter size for STL-SWEI and MTL-SWEI. </p><p>In 1.5 mm targets, STL-SWEI achieves alternately the tightest resolution (0.3 mm at CNR = 3.5 for a 0.17 mm filter) and highest CNR (8.5 with edge width = 0.7 mm for a 0.66 mm filter) of the modalities, followed by ARFI and then MTL-SWEI.</p><p>In larger, 6 mm targets, the CNR-resolution tradeoff curves for ARFI and STL-SWEI overlap for ARFI time steps up to 0.5 ms and kernels $\leq$1 mm for STL-SWEI. STL-SWEI can operate either with a 25 dB improvement over MTL-SWEI in CNR at the same resolution, or with edge widths 5$\times$ as narrow at equivalent CNR values, depending on the selection of regression filter size. Ex vivo ablations are used to demonstrate that ARFI, STL-SWEI and MTL-SWEI each resolve ablation lesions between 0.5 and 1 cm in diameter and gaps between lesions smaller than 5 mm in 3-D scans. Differences in contrast, noise, and resolution between the modalities are discussed. All three modalities are also shown to resolve ``x''-shaped ablations up to 22 mm in depth with good visual fidelity and correspondence to surface photographs, with STL-SWEI providing the highest quality images. Series of each type of image, registered using 3-D data from an electroanatomical mapping system, are used to build volumes that show ablations in in vivo canine atria. In vivo images are shown to be subject to increased noise due to tissue and transducer motion, and the challenges facing the proposed system are discussed. Ultimately, intracardiac acoustic radiation force methods are demonstrated to be promising tools for characterizing dynamic myocardial elasticity and imaging radiofrequency ablation lesions.</p> / Dissertation

O objetivo deste trabalho é estudar o fenômeno da força de radiação acústica produzida por ondas progressivas e estacionárias. Neste trabalho o estudo da força produzida por ondas estacionárias é aplicado na análise de um levitador acústico e o estudo da força de radiação acústica por ondas progressivas é feito visando a futura construção de um separador acústico. Neste trabalho é utilizado o método dos elementos finitos para simular o comportamento de um levitador acústico. Primeiramente, é feita a simulação de um levitador acústico que consiste de um transdutor de Langevin com uma face de emissão plana que opera na freqüência de aproximadamente 20 kHz e um refletor plano. O método dos elementos finitos é utilizado para determinar o deslocamento da face do transdutor e o potencial acústico que atua numa esfera pequena. O deslocamento da face do transdutor obtido numericamente é comparado com o medido experimentalmente por um vibrômetro de fibra ótica e o potencial acústico determinado pelo método dos elementos é verificado experimentalmente colocando pequenas esferas de isopor no levitador. Depois de verificar o modelo numérico, o método dos elementos finitos é utilizado na otimização de um levitador acústico composto de um refletor côncavo e um transdutor com face de emissão côncava. Os resultados numéricos mostram que a força de radiação acústica no novo levitador é aumentada em 604 vezes quando comparada com o levitador composto de um transdutor com face plana e refletor plano. Este trabalho também apresenta um modelo numérico para determinar a trajetória de partículas esféricas na presença de uma onda de ultra-som progressiva. O modelo assume que as seguintes forças atuam na partícula: gravidade, empuxo, forças viscosas e força de radiação acústica devido a uma onda progressiva. Com o objetivo de não restringir o tamanho das partículas que podem ser utilizadas no modelo é empregada uma equação empírica do coeficiente de arrasto, válida para uma grande faixa de número de Reynolds. O modelo proposto requer a distribuição de pressão gerada pelo transdutor de ultra-som. A distribuição de pressão é medida experimentalmente utilizando um hidrofone calibrado. A verificação do modelo é feita soltando-se pequenas esferas de vidro (com diâmetros da ordem de 500 m) em frente a um transdutor de ultra-som de 1 MHz e 35 mm de diâmetro. / The objective of this work is to study the acoustic radiation force produced by progressive and standing waves. In this work, the studies related to the acoustic radiation force generated by ultrasonic standing waves are applied in the analysis of an acoustic levitator and the studies involving the acoustic radiation force generated by progressive waves are conducted aiming the design of acoustic separators. In this work, the finite element method is used to simulate an acoustic levitator. First, an acoustic levitator consisting of a 20 kHz Langevin ultrasonic transducer with a plane radiating surface and a plane reflector is simulated by the finite element method. The finite element method is used to determine the transducer face displacement and the acoustic radiation potential that acts on a small sphere. The numerical displacement is compared with that obtained by a fiber-optic vibration sensor and the acoustic radiation potential determined by the finite element method is verified experimentally by placing small Styrofoam spheres in the levitator. After verifying the numerical method, the finite element method was used to optimize an acoustic levitator consisting of a concave-faced transducer and a curved reflector. The numerical results show that the acoustic radiation force in the new levitator is enhanced 604 times compared with the levitator consisting of a plane transducer and a plane reflector. This work also presents a numerical model to determine the trajectory of sphere particles when submitted to ultrasonic progressive waves. This model assumes that the following forces act on the particle: gravity, buoyancy, viscous forces and acoustic radiation force due to the progressive wave. In order not to restrict the model to a small particle size range, the viscous forces that act on the sphere are modeled by an empirical relationship of drag coefficient that is valid for a wide range of Reynolds numbers. The numerical model requires the pressure field radiated by the ultrasonic transducer. The pressure field is obtained experimentally by using a calibrated needle hydrophone. The numerical model validation is done by dropping small glass spheres (on the order of 500 m diameter) in front of a 1-MHz 35-mm diameter ultrasonic transducer.

<p>Cardiovascular disease is the leading cause of death for developed countries, including the United States. In order to diagnose and detect certain cardiac diseases, it is necessary to assess myocardial performance and function. One mechanical property that has been shown to reflect myocardial performance is myocardial stiffness. Acoustic radiation force impulse (ARFI) imaging has been demonstrated to be capable of visualizing variations in local stiffness within soft tissue. </p><p>In this thesis, the initial investigations into the visualization of myocardial performance with ARFI imaging are presented. <italic>In vivo</italic> ARFI images were acquired with a linear array placed on exposed <italic>canine</italic> hearts. When co-registered with the electrocardiogram (ECG), ARFI images of the heart reflected the expected changes in myocardial stiffness through the cardiac cycle. With the implementation of a quadratic motion filter, motion artifacts within the ARFI images were reduced to below 1.5 &mu m at all points of the cardiac cycle. The inclusion of pre-excitation displacement estimates in the quadratic motion filter further reduced physiological motion artifacts at all points of the cardiac cycle to below 0.5 &mu m. </p><p>In order for cardiac ARFI imaging to more quantitatively assess myocardial performance, novel ARFI imaging sequences and methods were developed to address challenges specifically related to cardiac imaging. These improvements provided finer sampling and improved spatial and temporal resolution within the ARFI images. <italic>In vivo</italic> epicardial ARFI images of an <italic>ovine</italic> heart were formed using these sequences, and the quality and utility of the resultant ARFI-induced displacement curves were examined.</p><p><italic>In vivo</italic> cardiac ARFI images were formed of <italic>canine</italic> left ventricular free walls while the hearts were externally paced by one of two electrodes positioned epicardially on either side of the imaging plane. Directions and speeds of myocardial stiffness propagation were measured within the ARFI imaging field of view. In all images, the myocardial stiffness waves were seen to be traveling away from the stimulating electrode. The stiffness propagation velocities were also shown to be consistent with propagation velocities measured from elastography and tissue velocity imaging as well as the local epicardial ECG.</p><p>ARFI-induced displacement curves of an <italic>ovine</italic> heart were formed and temporally registered with left ventricular pressure and volume measurements. From these plots, the synchronization of myocardial stiffening and relaxation with the four phases (isovolumic contraction, ejection, isovolumic relaxation, and filling) of the cardiac cycle was determined. These ARFI imaging sequences were also used to correlate changes in left ventricular performance with changes in myocardial stiffness. These preliminary results indicated that changes in the ARFI imaging-derived stiffnesses were consistent with those predicted by current, clinically accepted theories of myocardial performance and function.</p><p>These results demonstrate the ability of ARFI imaging to visualize changes in myocardial stiffness through the cardiac cycle and its feasibility to provide clinically useful insight into myocardial performance.</p> / Dissertation

<p>Acoustic radiation force impulses (ARFI) have been used to generated transverse-traveling mechanical waves in various biological tissues. The velocity of these waves is related to a medium's stiffness and thus can offer useful diagnostic information. Consequently, shear wave velocimetry has the potential to investigate cardiac disease states that manifest themselves as changes in tissue stiffness (e.g., ischemia).</p><p> The work contained herein focuses on employing ARFI-based shear wave velocimetry techniques, similar to those previously utilized on other organs (e.g., breast, liver), for the investigation of cardiac tissue. To this end, ARFI excitations were used to generate slow-moving (under 3 m/s) mechanical waves in exposed myocardium (with access granted through a thoracotomy); these waves were then tracked with ultrasonic methods. Imaging techniques to increase frame-rate, decrease transducer/tissue heating, and reduce the effects of physiological motion were developed. These techniques, along with two shear wave velocimetry methods (i.e., the Lateral Time-to-Peak and Radon sum transformation algorithms), were utilized to successfully track shear wave propagation through the mid-myocardial layer <italic>in vitro</italic> and <italic>in vivo</italic>. <italic>In vitro</italic> experiments focused on the investigation of a shear wave anisotropy through the myocardium. This experimentation suggests a moderate shear wave velocity anisotropy through regions of the mid-myocardial layer. <italic>In vivo</italic> experiments focused on shear wave anisotropy (which tend to corroborate the aforementioned <italic>in vitro</italic> results), temporal/spatial stability of shear wave velocity estimates, and estimation of wave velocity through the cardiac cycle. Shear wave velocity was found to cyclically vary through the cardiac cycle, with the largest estimates occurring during systole and the smallest occurring during diastole. This result suggests a cyclic stiffness variation of the myocardium through the cardiac cycle. A novel, on-axis technique, the displacement ratio rate (DRR) method, was developed and compared to conventional shear wave velocitmetry and ARFI imaging results; all three techniques suggest a similar cyclic stiffness variation.</p><p> Shear wave velocimetry shows promise in future investigations of myocardial elasticity. The DRR method may offer a means for transthoracic characterization of myocardial stiffness. Additionally, the future use of transesophageal and catheter-based transducers presents a way of generating and tracking shear waves in a clinical setting (i.e., when epicardial imaging is not feasible). Lastly, it is hoped that continued investigations into the physical basis of these ARFI-generated mechanical waves may further clarify the relationship between their velocity in myocardium and material stiffness.</p> / Dissertation

This dissertation introduces a new approach to measure the mechanical properties of soft tissues. A laser-induced microbubble, created by focusing a single nanosecond laser pulse with a custom-made objective lens, was created at desired locations inside a tissue sample. An acoustic radiation force was generated by a low frequency transducer to displace the microbubble. A custom-built high pulse repetition frequency (PRF) ultrasound system, consisting of two 25 MHz single element transducers, was used to track the dynamics of the microbubble. Reconstruction of the mechanical properties at the specific location in a tissue sample was performed using a theoretical model, which calculated the dynamics of a microbubble under an externally applied force in a viscoelastic medium. The theoretical model and the high PRF ultrasound system were successfully validated in both gelatin phantoms and ex vivo bovine crystalline lenses. Age-related sclerosis of the crystalline lenses from bovine was clearly detected, which might be linked to changes in the crystalline. Location-dependent variation explained that the outer cortex and the inner nucleus had different mechanical properties. In the old and young porcine vitreous humors, age-related changes were not found. However, local variations of the mechanical properties were discovered, which may coincide with the different distributions of the molecular compositions. The laser-induced microbubble approach shows potential for future research into the origin of physiological phenomena and the development of inherent disorders in the eye. I hope that further studies – in the development of a more suitable theoretical model for the microbubble dynamics, in extension to in vivo applications, and in defining the relationship of the mechanical properties to molecular components in the eye – may provide a plan for the therapeutic treatment of eye-related diseases. / text