Browsing by Subject "Elasticity"

Prostate cancer (PCa) is the most common non-cutaneous cancer in men in the United States. Early detection of PCa is essential for improving treatment outcomes and survival rates. However, diagnosis of PCa at an early stage is challenged by the lack of an imaging method that can accurately visualize PCas. Because pathological processes change the mechanical properties of the tissue, elasticity imaging methods have the potential to differentiate PCas from other prostatic tissues. Acoustic radiation force impulse (ARFI) imaging is a relatively new elasticity imaging method that visualizes the local stiffness variations inside soft tissue.

The work presented in this dissertation investigates the feasibility of prostate ARFI imaging. Volumetric ARFI data acquisition and display methods were developed to visualize anatomic structures and pathologies in ex vivo human prostates. The characteristic appearances of various prostatic tissues in ARFI images were identified by correlating ARFI images with McNeal's zonal anatomy and the correlated histological slides, in which prostatic pathologies were delineated by a pathologist blinded to the ARFI images. The results suggest ARFI imaging is able to differentiate anatomic structures and identify suspicious PCa regions in the prostate.

To investigate the correlation between ARFI displacement amplitudes and the underlying tissue stiffness in the prostate ARFI images, the mechanical properties of prostatic tissues were characterized using a quantitative method, based upon shear wave elasticity imaging (SWEI). Co-registered ARFI and SWEI datasets were acquired in excised prostate specimens to reconstruct the shear moduli of prostatic tissues. The results demonstrated that variations in ARFI displacement amplitudes were inversely related to the underlying tissue stiffness; and the reconstructed shear moduli of prostatic tissues had good agreements with those reported in literature. The study suggests the matched ARFI and SWEI datasets provide complementary

information about tissue's elasticity.

To increase the efficiency of the data acquisition, a novel imaging sequence was developed to acquired matched ARFI-SWEI datasets without increasing the number of excitations compared to a conventional ARFI imaging sequence. Imaging parameters were analyzed both theoretically and experimentally. An analytical model was derived to quantify the fundamental accuracy limit in the reconstructed shear modulus, and demonstrated good agreement with the experimental data. The novel sequence was demonstrated in tissue-mimicking phantoms.

Finally, ARFI imaging sequences were developed in a transrectal probe, and ARFI images were presented from in vivo data acquired in patients under radical prostatectomy. The in vivo ARFI images demonstrated decreased contrast and resolution as compared to the matched ex vivo ARFI data. However, prostate anatomy and some PCa were successfully visualized in the in vivo ARFI images. Thus, we conclude that ARFI imaging has the potential to provide image guidance for locating cancerous regions during PCa diagnosis and treatment.

Implemented on an intracardiac echocardiography transducer, acoustic radiation force methods may provide a useful means of characterizing the heart's elastic properties. Elasticity imaging may be of benefit for diagnosis and characterization of infarction and heart failure, as well as for guidance of ablation therapy for the treatment of arrhythmias. This thesis tests the hypothesis that with appropriately designed imaging sequences, intracardiac acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI) are viable tools for quantification of myocardial elasticity, both temporally and spatially. Multiple track location SWEI (MTL-SWEI) is used to show that, in healthy in vivo porcine ventricles, shear wave speeds follow the elasticity changes with contraction and relaxation of the myocardium, varying between 0.9 and 2.2 m/s in diastole and 2.6 and 5.1 m/s in systole. Infarcted tissue is less contractile following infarction, though not unilaterally stiffer. Single-track-location SWEI (STL-SWEI) is proven to provide suppression of speckle noise and enable improved resolution of structures smaller than 2 mm in diameter compared to ARFI and MTL-SWEI. Contrast to noise ratio and lateral edge resolution are shown to vary with selection of time step for ARFI and arrival time regression filter size for STL-SWEI and MTL-SWEI.

In 1.5 mm targets, STL-SWEI achieves alternately the tightest resolution (0.3 mm at CNR = 3.5 for a 0.17 mm filter) and highest CNR (8.5 with edge width = 0.7 mm for a 0.66 mm filter) of the modalities, followed by ARFI and then MTL-SWEI.

In larger, 6 mm targets, the CNR-resolution tradeoff curves for ARFI and STL-SWEI overlap for ARFI time steps up to 0.5 ms and kernels $\leq$1 mm for STL-SWEI. STL-SWEI can operate either with a 25 dB improvement over MTL-SWEI in CNR at the same resolution, or with edge widths 5$\times$ as narrow at equivalent CNR values, depending on the selection of regression filter size. Ex vivo ablations are used to demonstrate that ARFI, STL-SWEI and MTL-SWEI each resolve ablation lesions between 0.5 and 1 cm in diameter and gaps between lesions smaller than 5 mm in 3-D scans. Differences in contrast, noise, and resolution between the modalities are discussed. All three modalities are also shown to resolve ``x''-shaped ablations up to 22 mm in depth with good visual fidelity and correspondence to surface photographs, with STL-SWEI providing the highest quality images. Series of each type of image, registered using 3-D data from an electroanatomical mapping system, are used to build volumes that show ablations in in vivo canine atria. In vivo images are shown to be subject to increased noise due to tissue and transducer motion, and the challenges facing the proposed system are discussed. Ultimately, intracardiac acoustic radiation force methods are demonstrated to be promising tools for characterizing dynamic myocardial elasticity and imaging radiofrequency ablation lesions.

Tissue stiffness can be an indicator of various types of ailments. However, no standard diagnostic imaging modality has the capability to depict the stiffness of tissue. To overcome this deficiency, various elasticity imaging methods have been proposed over the past 20 years. A promising technique for elasticity imaging is acoustic radiation force impulse (ARFI) based shear wave imaging. Spatially localized acoustic radiation force excitation is applied impulsively to generate shear waves in tissue and its stiffness is quantified by measuring the shear wave speed (SWS).

The aim of this thesis is to contribute to both the clinical application of ARFI shear wave imaging and its technical development using the latest advancements in ultrasound imaging capabilities.

To achieve the first of these two goals, a pilot imaging study was conducted to evaluate the suitability of ARFI shear wave imaging for the assessment of liver fibrosis using a rodent model of the disease. The stiffness of severely fibrotic rat livers were found to be significantly higher than healthy livers. In addition, liver stiffness was correlated with fibrosis as quantified using collagen content.

Based on these findings, an imaging study was conducted on patients undergoing liver biopsy at the Duke University Medical Center. A robust SWS estimation algorithm was implemented to deal with noisy patient shear wave data using the random sample consensus (RANSAC) approach. RANSAC estimated liver stiffness was found to be higher in severely fibrotic and cirrhotic livers, suggesting that ARFI shear wave imaging may potentially be useful for the staging of severe

fibrosis in humans.

To achieve the second aim of this thesis, a system capable of monitoring ARFI induced shear wave propagation in 3D was implemented using a 2D matrix array transducer. This capability was previously unavailable with conventional 1D arrays. This system was used to study the precision of time-of-flight (TOF) based SWS estimation. It was found that by placing tracking beam locations at the edges of the SWS measurement region of interest using the 2D matrix array, TOF SWS precision could be improved in a homogeneous medium.

The 3D shear wave imaging system was also used to measure the SWS in muscle, which does not conform to the isotropic mechanical behavior usually assumed for tissue, due to the parallel arrangement of muscle fibers. It is shown that the SWS along and across the fibers, as well as the 3D fiber orientation can be estimated from a single 3D shear wave data-set. In addition, these measurements can be made independent of the probe orientation relative to the fibers. This suggests that 3D shear wave imaging can be useful for characterizing anisotropic mechanical properties of tissue.

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.