Дисертації з теми "Biomedical Ultrasound Imaging"

The diminutive size of microrobots makes them advantageous for minimally invasive operations and precise, localized treatment. One such application is aiding in localized drug delivery for colorectal cancer as microrobots could offer reduced patient trauma, lower risk of side effects, and higher drug retention rates. In this study, we evaluate the abilities of a magnetic microrobot in a variety of conditions using a high frequency ultrasound system. Under the influence of an external rotating magnetic field, the microrobot tumbles end-over-end to propel itself forward. Cytotoxicity tests demonstrated the constituent materials of polydimethylsiloxane (PDMS) and SU-8 were nontoxic to murine fibroblasts. Then, we quantified robot locomotion in an ex vivo porcine colon, testing the materials, the tumbling orientation, and three magnet rotation frequencies. Significant differences were found between materials and tumbling orientation, revealing that SU-8 lengthwise microrobots were the fastest with an average velocity of 2.12±0.25mm/s at a frequency of 1Hz. With this finding, the next tests were completed at 1Hz frequency with SU-8 lengthwise microrobots. We used in vitro agarose gels to maneuver the robot through a variety of trajectories, tested the microrobots in situ and in vivo murine colons as well. Average velocities were calculated for all tests with the in vivo murine colon tests finding an average velocity of 2.07±0.05mm/s. Finally, the microrobots were coated with a fluorescein payload and were shown to release a payload over a one-hour time period. These findings suggest microrobots are promising for targeted drug delivery and other in vivo biomedical applications.

Piezoelectric micromachined ultrasound transducer (pMUT) two-dimensional (2D) arrays have been proposed as an alternative to conventional bulk-PZT thickness-mode transducers for high frequency, forward-looking, catheter-based ultrasound imaging of the cardiovascular system. The appeal of pMUTs is based on several key advantages over conventional transducer technologies, including high operational frequencies, small element size, and low cost due to their microelectromechanical system (MEMS) silicon-based fabrication. While previous studies have demonstrated acoustic performance characteristics suitable for ultrasound image formation, pulse-echo B-mode imaging of tissue and tissue-like phantoms using 2D pMUT arrays small enough for forward-looking catheter-based applications have been demonstrated only at Duke University by Dausch et al.

Having demonstrated the suitability of 2D pMUT arrays for tissue imaging, an important step is to demonstrate effective design control. The frequency of operation is a fundamental component of transducer design. Previous modeling efforts for pMUT vibration have used classical/Kirchoff thin plate theory (CPT) or Mindlin thick plate theory, however pMUTs with geometric dimensions similar to those explored here, have not been modeled with experimental comparison to physical devices.

It is hypothesized that the frequency of vibration of pMUTs can be predictively modeled based on experimental data from various pMUT configurations. Experimental frequency results were acquired and used to develop an empirical model based on a modified Mindlin thick plate theory. This dissertation presents the development of the frequency design theory culminating in a set of predictive design equations for the frequency of vibration of 2D pMUT arrays aimed at improving their use in high-frequency, forward-looking, catheter-based ultrasound imaging applications.

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.

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 the United States, heart failure is a leading cause of hospitalization. The medical industry places great emphasis on diagnosing heart disease through cardiac metrics like ejection fraction. Left ventricular ejection fraction is a commonly used diagnostic indicator for heart efficiency and is measured with echocardiography through different volume calculation techniques. However, ejection fraction results can drastically vary from one examiner to another. Generally cardiologists still give ejection fraction measurements a plus or minus 10 percent error range.

A program developed at Duke called 4DViz is robust enough for users to process 3D ultrasound data. 4DViz allows examiners to determine heart chamber volumes by constructing a surface model over an imaged heart chamber with many mouse click inputs. Through 4DViz programming, a viable approach for calculating ejection fraction is attempted in this thesis. Using feature tracking, surface drawing, and voxel filling, the new approach aims to reduce examiner input and improve ejection fraction consistency. Water filled balloons were used to calibrate the algorithm's parameters. In testing, several volunteers were asked to use the 4DViz. Their results are compared to volume measurements where user input was standard. The results show promise and may remove some of the inconsistency behind ejection fraction measurements.

Prostate cancer (PCa) is the most common non-cutaneous cancer in men with an estimated almost 30,000 deaths occurring in the United States in 2014. Currently, the most widely utilized methods for screening men for prostate cancer include the digital rectal exam and prostate specific antigen analysis; however, these methods lack either high sensitivity or specificity, requiring needle biopsy to confirm the presence of cancer. The biopsies are conventionally performed with only B-mode ultrasound visualization of the organ and no targeting of specific regions of the prostate, although recently, multi-parametric magnetic resonance imaging has shown promise for targeting biopsies. Earlier work has demonstrated the feasibility of acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) to visualize cancer in the prostate, however multiple challenges with both methods have been identified.

The aim of this thesis is to contribute to both the technical development and clinical applications of ARFI and SWEI imaging using the latest advancements in ultrasound imaging technology.

The introduction of the Siemens Acuson SC2000 provided multiple technological improvements over previous generations of ultrasound scanners, including: an improved power supply, arbitrary waveform generator, and additional parallel receive beamforming. In this thesis, these capabilities were utilized to improve both ARFI and SWEI imaging and reduce acoustic exposure and acquisition duration. However, the SC2000 did not originally have radiation force imaging capabilities; therefore, a new tool set for prototyping these sequences was developed along with rapid data processing and display code. These tools leveraged the increasing availability of general purpose computing on graphics processing units (GPUs) to significantly reduce the data processing time, facilitating real-time display for ultrasonic research systems.

These technical developments for both acquisition and processing were applied to investigate new methods for ARFI and SWEI imaging. Specifically, the power supply on the SC2000 allowed for a new type of multi-focal zone ARFI images to be acquired, which are shown to provide improved image quality over an extended depth of field. Additionally, a new algorithm for SWEI image processing was developed using an adaptive filter based on a maximum a posteriori estimator, demonstrating increases in the contrast to noise ratio of lesion targets upwards of 50%.

Finally, the optimized ARFI imaging methods were integrated with a transrectal ultrasound transducer to acquire volumetric in vivo data in patients undergoing robotic radical prostatectomy procedures in an ongoing study. When the study was initiated, it was recognized that the technological improvements of Siemens Acuson SC2000 allowed for the off-axis response to the radiation force excitation to be concurrently recorded without impacting ARFI image quality. This volumetric SWEI data was reconstructed retrospectively using the approaches developed in this thesis, but the images were low quality. A further investigation identified multiple challenges with the SWEI sequence, which should be addressed in future studies. The ARFI image volumes were very high quality and are currently being analyzed to assess the accuracy of ARFI to visualize prostate anatomy and clinically significant prostate cancer tumors. After a blinded evaluation of the ARFI image volumes for suspicion of prostate cancer, three readers correctly identified 63% of all clinically significant tumors and 74% of clinically significant tumors in the posterior region, showing great promise for using ARFI in the context of prostate cancer visualization for targeting biopsies, focal therapy, and watchful waiting.