Browsing by Author "Smith, Stephen W"

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.

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.

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.

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.

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.

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.

In this work, I examine the problem of rapid imaging of stroke and present ultrasound-based approaches for addressing it. Specifically, this dissertation discusses aberration and attenuation due to the skull as sources of image degradation and presents a prototype system for simultaneous 3D bilateral imaging via both temporal acoustic windows. This system uses custom sparse array transducers built on flexible multilayer circuits that can be positioned for simultaneous imaging via both temporal acoustic windows, allowing for registration and fusion of multiple real-time 3D scans of cerebral vasculature. I examine hardware considerations for new matrix arrays--transducer design and interconnects--in this application. Specifically, it is proposed that signal-to-noise ratio (SNR) may be increased by reducing the length of probe cables. This claim is evaluated as part of the presented system through simulation, experimental data, and in vivo imaging. Ultimately, gains in SNR of 7 dB are realized by replacing a standard probe cable with a much shorter flex interconnect; higher gains may be possible using ribbon-based probe cables. In vivo images are presented depicting cerebral arteries with and without the use of microbubble contrast agent that have been registered and fused using a search algorithm which maximizes normalized cross-correlation.

The scanning geometry of a brain helmet-type system is also utilized to allow each matrix array to serve as a correction source for the opposing array. Aberration is estimated using cross-correlation of RF channel signals followed by least mean squares solution of the resulting overdetermined system. Delay maps are updated and real-time 3D scanning resumes. A first attempt is made at using multiple arrival time maps to correct multiple unique aberrators within a single transcranial imaging volume, i.e. several isoplanatic patches. This adaptive imaging technique, which uses steered unfocused waves transmitted by the opposing or "beacon" array, updates the transmit and receive delays of 5 isoplanatic patches within a 64°×64° volume. In phantom experiments, color flow voxels above a common threshold have increased by an average of 92% while color flow variance decreased by an average of 10%. This approach has been applied to both temporal acoustic windows of two human subjects, yielding increases in echo brightness in 5 isoplanatic patches with a mean value of 24.3 ± 9.1%, suggesting such a technique may be beneficial in the future for improving image quality in non-invasive 3D color flow imaging of cerebrovascular disease including stroke.

Acoustic window failure and the possibility of overcoming it using a low frequency, large aperture array are also examined. In performing transcranial ultrasound examinations, 8-29% of patients in a general population may present with window failure, in which it is not possible to acquire clinically useful sonographic information through the temporal acoustic window. The incidence of window failure is higher in the elderly and in populations of African descent, making window failure an important concern for stroke imaging through the intact skull. To this end, I describe the technical considerations, design, and fabrication of low-frequency (1.2 MHz), large aperture (25.3 mm) sparse matrix array transducers for 3D imaging in the event of window failure. These transducers are integrated into the existing system for real-time 3D bilateral transcranial imaging and color flow imaging capabilities at 1.2 MHz are directly compared with arrays operating at 1.8 MHz in a flow phantom with approximately 47 dB/cm0.8/MHz0.8 attenuators. In vivo contrast-enhanced imaging allowed visualization of the arteries of the Circle of Willis in 5 of 5 subjects and 8 of 10 sides of the head despite probe placement outside of the acoustic window. Results suggest that the decrease from approximately 2 to 1 MHz for 3D transcranial ultrasound may be sufficient to allow acquisition of useful images either in individuals with poor windows or outside of the temporal acoustic window by untrained operators in the field.

Each year, over 13,000 people in the United States die from a primary malignant brain tumor. Currently, primary BTs are treated most commonly by surgery, radiotherapy, and systemic chemotherapy, though each of these methods carries a risk of complications or acute side effects.

Ultrasound hyperthermia has been investigated as way to open the blood-brain barrier for improved chemotherapeutic drug delivery, but previous methods have involved either invasively removing skull bone via surgery or non-invasively dealing with the high ultrasound attenuation, reflection, and phase aberration resulting from the skull and its variable thickness. Dual-mode ultrasound transducers for image-guided therapy have also been investigated for several applications; in some instances, phased arrays are ideal, allowing control over the ultrasound energy deposition pattern and inherent spatial registration between imaging, treatment, and monitoring.

Additionally, thermosensitive liposomes can be configured to encapsulate drugs and actively target regions of tumor angiogenesis. When used in combination with localized hyperthermia, thermosensitive liposomes can provide targeted control of drug release that may enhance chemotherapeutic efficacy in many clinical settings. Meanwhile, catheter devices and endovascular techniques are used by interventional neuroradiologists to treat various intracranial diseases, including intracranial aneurysm and dural venous sinus thrombosis. These procedures can be extended to the treatment of intracranial tumors (advancement of a 5 Fr catheter as far as the frontal portion of the superior sagittal sinus has been demonstrated).

The objective of the work presented in this dissertation was the realization of a dual-mode catheter transducer for a minimally-invasive, vascular approach to deliver localized, image-guided ultrasound hyperthermia to an intracranial tumor target. Toward this end, a series of prototype ultrasound transducers were designed, simulated, built, and tested for imaging and therapeutic potential.

Two 14-Fr phased-array prototypes were built with PZT-5H ceramic and tested for real-time 3D intracranial imaging and focused-beam hyperthermia capability. These were able to visualize the lateral ventricles and Circle of Willis in a canine model, and generate a temperature rise over 4°C at a 2-cm focal distance in excised tissue.

Single-channel intravascular ultrasound (IVUS) coronary imaging catheters as small as 3.5 Fr were then considered as a construction template; several possible transducer apertures were simulated before fabricating prototypes with PZT-4. The transducers exhibited a dual-frequency response, due to the presence of thickness-mode and width-mode resonances. A thermal model was developed to estimate the +4°C thermal penetration depth for a given transducer aperture, predicting an effective therapeutic range of up to 12 mm with a 5 × 0.5 mm aperture.

A 3.5-Fr commercial mechanical IVUS catheter was retrofitted with a PZT-4 transducer and tested for 9-MHz imaging performance in several animal studies, successfully visualizing anatomical structures in the brain and navigating a minimally-invasive vascular pathway toward the brain. An identical PZT-4 transducer was used to build a 3.3-MHz therapy prototype, which produced a temperature rise of +13.5°C at a depth of 1.5 mm in live xenograft brain tumor tissue in the mouse model.

These studies indicate that a minimally-invasive catheter transducer can be made capable of visualizing brain structures and generating localized hyperthermia to trigger drug release from thermosensitive liposomes in brain tumor tissue.