Browsing by Subject "ARFI"

Heart Failure (HF) is a major cause of morbidity and mortality in the world. This disorder is characterized by compromised systolic and/or diastolic function of the myocardium that reduces the pumping and/or filling efficiency resulting in diminished cardiac output. Cardiovascular researchers have been attempting to develop tools for assessment of cardiac function for decades. Evaluating cardiac function helps clinicians to diagnose and to follow the progress of HF patients.

The gold standard technique for cardiac functional assessment, including systolic and diastolic function, is the pressure-volume (PV) loop measurement; however, this measurement is not typically used clinically due to the invasiveness of the technique. PV loop measurement requires the introduction of a pressure or pressure-volume catheter into the left ventricle. Cardiovascular researchers have been attempting to develop non-invasive tools for assessment of cardiac function primarily by measuring surrogates of ventricular contractility and compliance.

These measures are based on imaging and include Ejection Fraction and Doppler and ultrasound strain imaging. These measurements are indirect measures that rely on cardiac motion or volume changes. The measurements are load dependent and could be affected by the heart rhythm and valvular disorders. Despite research toward this goal, there is no clinically accepted noninvasive technique to provide a direct myocardial measurement of cardiac function.

Acoustic radiation force (ARF) based ultrasound elastography techniques were developed in early 2000s and have been used to measure the static stiffness of tissue. These techniques are being used in the clinic for diagnosis of disorders and malignancies in tissues such as liver. When applied to the heart, it was shown that dynamic changes in the stiffness of the myocardium during the cardiac cycle could be recorded using modified versions of these static techniques.

This had the potential to be a direct measure of the time-varying elastance measured during the cardiac cycle using pressure-volume measurements. The question arose as to whether these ARF based measurements of dynamic stiffness could be used for cardiac functional assessments during systole and diastole; and if so, what the relationship is between these measurements and the gold standard method. The goal of this research was to assess the ability of ARF based measurements of cardiac dynamic stiffness to provide meaningful indices of cardiac function.

In this dissertation both acoustic radiation force impulse (ARFI) and shear wave elasticity imaging (SWEI) ultrasound elastography techniques were studied. These are qualitative and quantitative measures of stiffness, respectively. While the focus of the studies was more on SWEI due to its quantitative nature, ARFI measurements of cardiac function were also investigated and compared to SWEI.

The studies were performed in isolated rabbit hearts in Langendorff or working modes because the preparation has several significant advantages. 1) Parameters including preload, afterload, and coronary perfusion can be accurately controlled. 2) The heart’s left ventricular free wall can be easily imaged from multiple angles. 3) Confounding neurohormonal reflexes of the body can be eliminated.

SWEI measurements of stiffness were used to characterize changes in contractility induced using the Gregg effect. The Gregg effect is the active effect of coronary perfusion on cardiac contractility. It was shown that SWEI measurements of stiffness could detect the changes in contractility induced by this known effect and that the effect was blocked using a Ca channel blocker.

The relationship between ARFI and SWEI measurements was characterized and the possibility of deriving functional indices such as systolic/diastolic ratio and isovolumic relaxation time constant (τ) using either of these techniques was evaluated. It was shown that in the same imaging configuration, the measurements of ARFI and SWEI are linearly related to one another. This could be important, as the ARFI technique will likely be the first cardiac elastography measurement technique to be implemented using transthoracic ultrasound throughout the cardiac cycle.

The Garden Hose effect was used to investigate SWEI’s ability to measure cardiac compliance. SWEI was used to detect the passive effect of coronary perfusion on cardiac compliance and the relationship between perfusion pressure and stiffness was characterized. Finally, SWEI derived measurements of diastolic function were compared to the gold standard PV measurements of cardiac diastolic function including end diastolic stiffness and the relaxation time constant. It was shown that SWEI could detect the changes in cardiac stiffness after induction of global ischemia. These changes were similar to the changes in the PV measure of diastolic stiffness. Furthermore, the results indicated that SWEI could be used to derive the relaxation time constant similar to the relaxation constant derived from intra-ventricular pressure recordings.

In summary, the results of the studies presented in this thesis illustrate the assessments of systolic and diastolic function using ARFI and SWEI ultrasound based elastography. It is concluded that these measurements can be used to derive cardiac functional indices that would have the advantages of an ultrasound based technique; they would be noninvasive, less expensive and could be widely applied outside of the cath lab.

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.

Every day, 1,300 children in the U.S. and an additional 34,000 children worldwide are born prematurely. This study acts as a feasibility study for a proposed ultrasonic technique for the identification of preterm birth risk factors using an acoustic technique known as Acoustic Radiation Force Impulse (ARFI) imaging. A 3D finite element model was constructed to optimize transducer ARFI parameters in a layered cervix structure prior to clinical evaluation. The transducer model optimized in this study was the AcuNav^TM (Siemens Medical Solutions, Mountain View, CA). Cervix model structural geometry and material properties were varied according to anticipated pregnancy induced property fluctuation. Transmitted ARFI acoustic fields were generated by applying a Field II derived pulse to the 3D model[15]. Optimization procedures were performed in the following order: focal depth evaluation, transmit frequency optimization, effect of material property variation and the application of ARFI shear wave speed calculation algorithms to a layered cervical structure. Results indicated that ARFI evaluation of a layered cervix structure was most feasible using an 8MHz transmit frequency in the focal range of 5-10mm axial depth. It was observed that material property estimation errors were most likely when ARFI excitations were focused near a material boundary. A phenomenon was noted where shear waves initiated in stiffer media were slowed as a function of their relative proximity to a more compliant medium. Overall, these simulation studies demonstrate that ARFI shear wave imaging in the cervix is feasible; a model has been developed that can be used to evaluate the accuracy of shear stiffness estimates in the cervix to help address the important clinical problem of premature cervical ripening.

This dissertation investigates the feasibility of a real-time transthoracic Acoustic Radiation Force Impulse (ARFI) imaging system to measure myocardial function non-invasively in clinical setting. Heart failure is an important cardiovascular disease and contributes to the leading cause of death for developed countries. Patients exhibiting heart failure with a low left ventricular ejection fraction (LVEF) can often be identified by clinicians, but patients with preserved LVEF might be undetected if they do not exhibit other signs and symptoms of heart failure. These cases motivate development of transthoracic ARFI imaging to aid the early diagnosis of the structural and functional heart abnormalities leading to heart failure.

M-Mode ARFI imaging utilizes ultrasonic radiation force to displace tissue several micrometers in the direction of wave propagation. Conventional ultrasound tracks the response of the tissue to the force. This measurement is repeated rapidly at a location through the cardiac cycle, measuring timing and relative changes in myocardial stiffness. ARFI imaging was previously shown capable of measuring myocardial properties and function via invasive open-chest and intracardiac approaches.

The prototype imaging system described in this dissertation is capable of rapid acquisition, processing, and display of ARFI images and shear wave elasticity imaging (SWEI) movies. Also presented is a rigorous safety analysis, including finite element method (FEM) simulations of tissue heating, hydrophone intensity and mechanical index (MI) measurements, and thermocouple transducer face heating measurements. For the pulse sequences used in later animal and clinical studies, results from the safety analysis indicates that transthoracic ARFI imaging can be safely applied at rates and levels realizable on the prototype ARFI imaging system.

Preliminary data are presented from in vivo trials studying changes in myocardial stiffness occurring under normal and abnormal heart function. Presented is the first use of transthoracic ARFI imaging in a serial study of heart failure in a porcine model. Results demonstrate the ability of transthoracic ARFI to image cyclically-varying stiffness changes in healthy and infarcted myocardium under good B-mode imaging conditions at depths in the range of 3-5 cm. Challenging imaging scenarios such as deep regions of interest, vigorous lateral motion and stable, reverberant clutter are analyzed and discussed.

Results are then presented from the first study of clinical feasibility of transthoracic cardiac ARFI imaging. At the Duke University Medical Center, healthy volunteers and patients having magnetic resonance imaging-confirmed apical infarcts were enrolled for the study. The number of patients who met the inclusion criteria in this preliminary clinical trial was low, but results showed that the limitations seen in animal studies were not overcome by allowing transmit power levels to exceed the FDA mechanical index (MI) limit. The results suggested the primary source of image degradation was clutter rather than lack of radiation force. Additionally, the transthoracic method applied in its present form was not shown capable of tracking propagating ARFI-induced shear waves in the myocardium.

Under current instrumentation and processing methods, results of these studies support feasibility for transthoracic ARFI in high-quality B-Mode imaging conditions. Transthoracic ARFI was not shown sensitive to infarct or to tracking heart failure in the presence of clutter and signal decorrelation. This work does provide evidence that transthoracic ARFI imaging is a safe non-invasive tool, but clinical efficacy as a diagnostic tool will need to be addressed by further development to overcome current challenges and increase robustness to sources of image degradation.