Flow velocity mapping using contrast enhanced high-frame-rate plane wave ultrasound and image tracking: methods and initial in vitro and in vivo evaluation

Ultrasound imaging is the most widely used method for visualising and quantifying blood flow in medical practice, but existing techniques have various limitations in terms of imaging sensitivity, field of view, flow angle dependence, and imaging depth. In this study, we developed an ultrasound imaging velocimetry approach capable of visualising and quantifying dynamic flow, by combining high-frame-rate plane wave ultrasound imaging, microbubble contrast agents, pulse inversion contrast imaging and speckle image tracking algorithms. The system was initially evaluated in vitro on both straight and carotid-mimicking vessels with steady and pulsatile flows and in vivo in the rabbit aorta. Colour and spectral Doppler measurements were also made. Initial flow mapping results were compared with theoretical prediction and reference Doppler measurements and indicate the potential of the new system as a highly sensitive, accurate, angle-independent and full field-of-view velocity mapping tool capable of tracking and quantifying fast and dynamic flows

Noninvasive Thrombolysis using Microtripsy

Thrombosis refers to blood clot formation and when pathological, is the cause of many vascular diseases. For example, deep vein thrombosis (DVT), which affects three million Americans per year, is the formation of clots in the deep veins of the legs. Current clinical treatments include thrombolytic drugs and catheter-based surgical procedures. Both methods have significant drawbacks, such as excessive bleeding, invasiveness, and long treatment time. Ultrasound has been combined with thrombolytic drugs and/or microbubbles to enhance drug delivery. However, these methods are still quite slow and share the drawbacks of thrombolytic drugs. Histotripsy is a tissue ablation method that mechanically fractionates soft tissue via well-controlled acoustic cavitation generated by microsecond-long, high-pressure ultrasound pulses. The initial feasibility and safety of using histotripsy as a noninvasive, drug-free, and image-guided thrombolysis technique has been demonstrated both in vitro and in vivo. The overriding goal of this dissertation is clinical translation of histotripsy thrombolysis. First, an integrated image-guided histotripsy thrombolysis system suitable for clinical DVT treatment are designed and constructed. Second, the recently discovered technical innovations, microtripsy and bubble-induced color Doppler (BCD), are investigated for histotripsy thrombolysis application to further improve treatment efficacy. Microtripsy is a new histotripsy approach and uses an intrinsic threshold mechanism to generate more reproducible and predictable cavitation via a single ultrasound pulse, which can minimize vessel damage by confining cavitation within vessel lumen and eliminate cavitation on vessel wall. BCD is developed to monitor tissue motion induced by histotripsy pulses and investigated as a real-time quantitative feedback for histotripsy thrombolysis. Finally, a comprehensive pre-clinical study in a large animal DVT model is conducted to validate the safety and efficacy of this clinically designed system incorporating these technical innovations. It is our hope that this dissertation work will establish a foundation for the translation of this noninvasive thrombolysis technology into relevant clinical applications.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/135813/1/xizh_1.pd

Boosting transducer matrix sensitivity for 3D large field ultrasound localization microscopy using a multi-lens diffracting layer: a simulation study

Mapping blood microflows of the whole brain is crucial for early diagnosis of cerebral diseases. Ultrasound localization microscopy (ULM) was recently applied to map and quantify blood microflows in 2D in the brain of adult patients down to the micron scale. Whole brain 3D clinical ULM remains challenging due to the transcranial energy loss which significantly reduces the imaging sensitivity. Large aperture probes with a large surface can increase both resolution and sensitivity. However, a large active surface implies thousands of acoustic elements, with limited clinical translation. In this study, we investigate via simulations a new high-sensitive 3D imaging approach based on large diverging elements, combined with an adapted beamforming with corrected delay laws, to increase sensitivity. First, pressure fields from single elements with different sizes and shapes were simulated. High directivity was measured for curved element while maintaining high transmit pressure. Matrix arrays of 256 elements with a dimension of 10x10 cm with small ( $\lambda$ /2), large (4 $\lambda$ ), and curved elements (4 $\lambda$ ) were compared through point spread functions analysis. A large synthetic microvessel phantom filled with 100 microbubbles per frame was imaged using the matrix arrays in a transcranial configuration. 93% of the bubbles were detected with the proposed approach demonstrating that the multi-lens diffracting layer has a strong potential to enable 3D ULM over a large field of view through the bones

Contrast echocardiography for cardiac quantifications

The indicator-dilution-theory for cardiac quantifications has always been limited in practice by the invasiveness of the available techniques. However, the recent introduction of stable ultrasound contrast agents opens new possibilities for indicator dilution measurements. This study describes a new and successful approach to overcome this invasiveness issue. We show a novel approach for minimally invasive quantification of several cardiac parameters based on the dilution of ultrasound contrast agents. A single peripheral injection of an ultrasound contrast agent bolus can result in the simultaneous assessment of cardiac output, pulmonary blood volume, and left and right ventricular ejection fraction. The bolus passage in different sites of the central circulation is detected by an ultrasound transducer. The detected acoustic (or video) intensities are processed and several indicator dilution curves are measured simultaneously. To this end, we exploit that for low concentrations the relation between contrast concentration and acoustic backscatter is approximately linear. The Local Density Random Walk Model is used to fit and interpret the indicator dilution curves for cardiac output, pulmonary blood volume, and ejection fraction measurements. Two fitting algorithms based either on a multiple linear regression in the logarithmic domain or on the solution of the moment equations are developed. The indicator dilution system can be also interpreted as a linear system and, therefore, characterized by an impulse response function. An adaptive Wiener deconvolution filter is implemented for robust dilution system identification. For ejection fraction measurements, the atrial and ventricular indicator dilution curves are measured and processed by the deconvolution filter, resulting in the estimate of the left ventricle dilution-system impulse response. This curve can be fitted and interpreted by a mono-compartment exponential model for the ejection fraction assessment. The proposed deconvolution filter is also used for the identification of the dilution system between right ventricle and left atrium. The Local Density Random Walk Model fit of the estimated impulse response allows the pulmonary blood volume assessment. Both cardiac output and pulmonary blood volume measurements are validated in vitro with accurate results (correlation coefficients larger than 0.99). The Pulmonary blood volume measurement feasibility is also tested in humans with promising results. The ejection fraction measurement is validated in-vivo. The impulse response approach allows accurate left ventricle ejection fraction estimates. Comparison with echocardiographic bi-plane measurements shows a correlation coefficient equal to 0.93. A dedicated image segmentation algorithm for videodensitometry has also been developed for automating the determination of regions of interest. The resulting algorithm has been integrated with the indicator dilution analysis system. The automatic determination of the measurement region results in improved dilution-curve signal-to-noise ratios. In conclusion, this study proves that quantification of cardiac output, pulmonary blood volume, and left and right ventricular ejection fraction by dilution of ultrasound contrast agents is feasible and accurate. Moreover, the proposed methods are applicable in different contexts (e.g., magnetic resonance imaging) and for different types of measurements, leading to a broad range of applications