<p>Phase correction has the potential to increase the image quality of real-time 3D (RT3D) ultrasound, especially for transcranial ultrasound. Such improvement would increase the diagnostic utility of transcranial ultrasound, leading to improvements in stroke diagnosis, treatment, and monitoring. This work describes the implementation of the multi-lag least-squares cross-correlation and partial array speckle brightness methods for static and moving targets and the investigation of contrast-enhanced (CE) RT3D transcranial ultrasound.</p><p>The feasibility of using phase aberration correction with 2D arrays and RT3D ultrasound was investigated. Using the multi-lag cross-correlation method on electronic and physical aberrators, we showed the ability of 3D phase aberration correction to increase anechoic cyst identification, image brightness, contrast-to-noise ratio (CNR), and, in 3D color Doppler experiments, the ability to visualize flow. With a physical aberrator, CNR increased by 13%, while the number of detectable cysts increased from 4.3 to 7.7.</p><p>We performed an institutional review board (IRB) approved clinical trial to assess the ability of a novel ultrasound technique, namely RT3D CE transcranial ultrasound. Using micro-bubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and 9 via the sub-occipital window and report our detection rates for the major cerebral vessels. In 82% of subjects, we identified the ipsilateral circle of Willis from the temporal window, and in 65% we imaged the entire circle of Willis. From the sub-occipital window, we detected the entire vertebrobasilar circulation in 22% of subjects, and in 50% the basilar artery. </p><p>We then compared the performance of the multi-lag cross-correlation method with partial array reference on static and moving targets for an electronic aberrator. After showing that the multi-lag method performs better, we evaluated its performance with a physical aberrator. Using static targets, the correction resulted in an average contrast increase of 22.2%, compared to 13.2% using moving targets. The CNR increased by 20.5% and 12.8%, respectively. Doppler signal strength and number of Doppler voxels increased, by 5.6% and 14.4%, respectively, for the static method, and 9.3% and 4.9% for moving targets. </p><p>We performed two successful in vivo aberration corrections. We used this data and measure the isoplanatic patch size to be an average of 10.1°. The number of Doppler voxels increased by 38.6% and 19.2% for the two corrections. In both volunteers, correction enabled the visualization of a vessel not present in the uncorrected volume. These results are promising, and could potentially have a significant impact on public health.</p><p>Lastly, we show preliminary work testing the feasibility of a unique portable dedicated transcranial ultrasound system capable of simultaneous scanning from all three acoustic windows. Such a system would ideally be used in a preclinical setting, such as an ambulance.</p> / Dissertation