Liang Zhai

An Integrated Indenter-ARFI Imaging System for Tissue Stiffness Quantification

The goal of this work is to develop and characterize an integrated indenter-ARFI (acoustic radiation force impulse) imaging system. This system is capable of acquiring matched datasets of ARFI images and stiffness profiles from ex vivo tissue samples, which will facilitate correlation of ARFI images of tissue samples with independently-characterized material properties. For large and homogeneous samples, the indenter can be used to measure the Youngs moduli by using Boussinesqs solution for a load on the surface of a semi-infinite isotropic elastic medium. Experiments and finite element method (FEM) models were designed to determine the maximum indentation depth and minimum sample size for accurate modulus reconstruction using this solution. Applying these findings, indentation measurements were performed on three calibrated commercial tissue-mimicking phantoms and the results were in good agreement with the calibrated stiffness. For heterogeneous tissue samples, indentation can be used independently to characterize relative stiffness variation across the sample surface, which can then be used to validate the stiffness variation in registered ARFI images. Tests were performed on heterogeneous phantoms and freshly-excised colon cancer specimens to detect the relative stiffness and lesion sizes using the combined system. Normalized displacement curves across the lesion surface were calculated and compared. Good agreement of the lesion profiles was observed between indentation and ARFI imaging.

Acoustic radiation force impulse (ARFI) imaging of the gastrointestinal tract.

The evaluation of lesions in the gastrointestinal (GI) tract using ultrasound can suffer from poor contrast between healthy and diseased tissue. Acoustic Radiation Force Impulse (ARFI) imaging provides information about the mechanical properties of tissue using brief, high-intensity, focused ultrasound to generate radiation force and ultrasonic correlation-based methods to track the resulting tissue displacement. Using conventional linear arrays, ARFI imaging has shown improved contrast over B-mode images when applied to solid masses in the breast and liver. The purpose of this work is to (1) investigate the potential for ARFI imaging to provide improvements over conventional B-mode imaging of GI lesions and (2) demonstrate that ARFI imaging can be performed with an endocavity probe. ARFI images of an adenocarcinoma of the gastroesophageal (GE) junction, status-post chemotherapy and radiation treatment, demonstrate better contrast between healthy and fibrotic/malignant tissue than standard B-mode images. ARFI images of healthy gastric, esophageal, and colonic tissue specimens differentiate normal anatomic tissue layers (i.e., mucosal, muscularis and adventitial layers), as confirmed by histologic evaluation. ARFI imaging of ex vivo colon and small bowel tumors portray interesting contrast and structure that are not as well defined in B-mode images. An endocavity probe created ARFI images to a depth of over 2 cm in tissue-mimicking phantoms, with maximum displacements of 4 μm. These findings support the clinical feasibility of endocavity ARFI imaging to guide diagnosis and staging of disease processes in the GI tract.

Acoustic Radiation Force Impulse Imaging of Human Prostates Ex Vivo

It has been challenging for clinicians using current imaging modalities to visualize internal structures and detect lesions inside human prostates. Lack of contrast among prostatic tissues and high false positive or negative detection rates of prostate lesions have limited the use of current imaging modalities in the diagnosis of prostate cancer. In this study, acoustic radiation force impulse (ARFI) imaging is introduced to visualize the anatomical and abnormal structures in freshly excised human prostates. A modified Siemens Antares ultrasound scanner (Siemens Medical Solutions USA Inc., Malvern, PA) and a Siemens VF10-5 linear array were used to acquire ARFI images. The transducer was attached to a three-dimensional (3-D) translation stage, which was programmed to automate volumetric data acquisition. A depth dependent gain (DDG) method was developed and applied to 3-D ARFI datasets to compensate for the displacement gradients associated with spatially varying radiation force magnitudes as a function of depth. Nine human prostate specimens were collected and imaged immediately after surgical excision. Prostate anatomical structures such as seminal vesicles, ejaculatory ducts, peripheral zone, central zone, transition zone and verumontanum were visualized with high spatial resolution and in good agreement with McNeals zonal anatomy. The characteristic appearance of prostate pathologies, such as prostate cancerous lesions, benign prostatic hyperplasia, calcified tissues and atrophy were identified in ARFI images based upon correlation with the corresponding histologic slides. This study demonstrates that ARFI imaging can be used to visualize internal structures and detecting suspicious lesions in the prostate and appears promising for image guidance of prostate biopsy.

Characterizing stiffness of human prostates using acoustic radiation force.

Acoustic Radiation Force Impulse (ARFI) imaging has been previously reported to portray normal anatomic structures and pathologies in ex vivo human prostates with good contrast and resolution. These findings were based on comparison with histological slides and McNeals zonal anatomy. In ARFI images, the central zone (CZ) appears darker (smaller displacement) than other anatomic zones and prostate cancer (PCa) is darker than normal tissue in the peripheral zone (PZ). Since displacement amplitudes in ARFI images are determined by both the underlying tissue stiffness and the amplitude of acoustic radiation force that varies with acoustic attenuation, one question that arises is how the relative displacements in prostate ARFI images are related to the underlying prostatic tissue stiffness. In linear, isotropic elastic materials and in tissues that are relatively uniform in acoustic attenuation (e.g., liver), relative displacement in ARFI images has been shown to be correlated with underlying tissue stiffness. However, the prostate is known to be heterogeneous. Variations in acoustic attenuation of prostatic structures could confound the interpretation of ARFI images due to the associated variations in the applied acoustic radiation force. Therefore, in this study, co-registered three-dimensional (3D) ARFI datasets and quantitative shear wave elasticity imaging (SWEI) datasets were acquired in freshly-excised human prostates to investigate the relationship between displacement amplitudes in ARFI prostate images and the matched reconstructed shear moduli. The lateral time-to-peak (LTTP) algorithm was applied to the SWEI data to compute the shear-wave speed and reconstruct the shear moduli. Five types of prostatic tissue (PZ, CZ, transition zone (TZ) and benign prostatic hyperplasia (BPH), PCa and atrophy) were identified, whose shearmoduli were quantified to be 4.1±0.8 kPa, 9.9±0.9 kPa, 4.8±0.6 kPa, 10.0±1.0 kPa and 8.0 kPa, respectively. Linear regression was per formed to compare ARFI displacement amplitudes and the inverse of the corresponding reconstructed shear moduli at multiple depths. The results indicate an inverse relation between ARFI displacement amplitude and reconstructed shear modulus at all depths. These findings support the conclusion that ARFI prostate images portray underlying tissue stiffness variations.

4K-5 Shear Wave Velocity Estimation Using Acoustic Radiation Force Impulsive Excitation in Liver In Vivo

Acoustic radiation force can be used to mechanically excite tissue in remote, focused locations, and the tissue response can be monitored using ultrasonic correlation based methods. The speed with which the resulting shear waves propagate away from the focal region can be estimated and used to quantify the material shear modulus, as originally proposed by Sarvazyan et. al. (1998). This imaging approach has been implemented by Bercoff et. al. (2004), using a highly parallel custom ultrasound system, and Helmholtz reconstructions. We have developed a system that is implemented on a commercial scanner using 4:1 parallel processing, and a new algorithm for estimating shear wave speed, which does not require 2nd order temporal and spatial differentiation of displacement data. The method is robust and generates consistent measurements over multiple acquisitions. The goal of our work is to develop this system for the purpose of staging liver fibrosis. The method was used to measure elastic moduli of liver in vivo in healthy human volunteers, and in a rat model, and the moduli obtained with this method are consistent with those reported in the literature

Acoustic radiation force impulse (ARFI) imaging of the gastrointestinal tract

Currently, the evaluation of lesions in the gastrointestinal (GI) tract using ultrasound suffers from poor contrast between healthy and diseased tissue. Acoustic radiation force impulse (ARFI) imaging provides information about the mechanical properties of tissue using brief, high-intensity, focused ultrasound to generate radiation force, and conventional, ultrasonic correlation-based methods to track tissue displacement. Using conventional linear arrays, ARFI imaging has shown improved contrast over B-mode images when applied to solid masses in the breast and liver. The purpose of this work is to (1) demonstrate that ARFI imaging can be performed with an endocavity probe, and (2) demonstrate that ARFI imaging can provide improvements over conventional B-mode imaging of GI lesions. An EC94, 6.2 MHz, endocavity probe was modified to perform ARFI imaging in tissue-mimicking phantoms using a Siemens SONOLINE Antares/spl trade/ scanner. ARFI imaging was performed on fresh, surgically excised, GI lesions using a 75L40, 7.2 MHz. linear array on a modified Siemens SONOLINE Elegra/spl trade/ scanner. The endocavity probe created ARFI images to a depth of over 2 cm in tissue-mimicking phantoms, with maximum displacements of 5 /spl mu/m. The endocavity probe did not heat appreciably during ARFI imaging, demonstrating that the probes small size will not limit in vivo ARFI imaging. ARFI images of an adenocarcinoma of the gastroesophageal (GE) junction status post chemotherapy and radiation treatment, demonstrate better contrast between healthy and fibrotic/malignant tissue than standard B-mode images. ARFI images of healthy gastric, esophageal, and colonic tissue specimens differentiate normal anatomic tissue planes (i.e., mucosal, muscularis, and adventitial layers), as confirmed by histologic evaluation. ARFI imaging of an ex vivo colon cancer portrays interesting contrast and structure not present in B-mode images. These findings support the clinical feasibility of endoscopic ARFI imaging to guide diagnosis and staging of disease processes in the GI tract.

Correlation between SWEI and ARFI image findings in ex vivo human prostates

Acoustic Radiation Force Impulse (ARFI) imaging has previously been used to visualize normal anatomic structures and pathologies in both ex vivo and in vivo human prostates. Based on the relative displacement amplitudes in ARFI images and comparison with histological slides and McNeals zonal anatomy, it seems that the central zone (CZ) is stiffer than other anatomic zones, and prostate cancer (PCa) is stiffer than normal tissue in the peripheral zone and benign prostatic hyperplasia (BPH). Since displacement amplitudes in ARFI images are determined by both the underlying tissue stiffness and the amplitude of acoustic radiation force, one question that arises is: how are the relative displacements in ARFI images related to the underlying tissue stiffness? In this study, co-registered three-dimensional (3D) ARFI datasets and shear wave elasticity imaging (SWEI) datasets were acquired to investigate the relationship between displacement amplitudes in ARFI images and the underlying tissue stiffness. Six freshly excised human prostates were collected and imaged. The lateral time-to-peak (TTP) algorithm was used to reconstruct the tissue stiffness. Linear regression was performed between ARFI displacement amplitudes and the inverse of the corresponding reconstructed shear moduli. Five types of prostatic tissues were identified in ARFI images, and their stiffnesses were quantified.

Three-dimensional acoustic radiation force impulse (ARFI) imaging of human prostates in vivo

We are investigating utilizing ARFI imaging to guide prostate needle biopsy. Our previous ex vivo study demonstrated that ARFI imaging using a VF10-5 linear array was able to visualize the internal anatomy and suspicious lesions in the prostate, which may help improve the diagnostic accuracy of prostate needle biopsy. The objective of this study is to implement ARFI techniques on a 3D wobbler rectal probe and image human prostates in vivo. Three patients were imaged. The initial in vivo results are reported.

Acoustic radiation force based quantification of tissue shear modulus within the region of excitation

The speed of shear wave propagation in tissue is directly related to the tissues shear modulus. Shear waves can be generated in tissue using focused, impulsive, acoustic radiation force excitations. Shear modulus reconstruction has typically been performed by monitoring shear wave propagation in regions that are spatially offset from the region of excitation (ROE), but such methods require greater radiation forces than methods that work within the ROE. Previously validated 3D FEM models of soft tissue response to impulsive radiation force excitations, coupled with Field II simulations of ultrasonic displacement tracking, were utilized for this work. Simulations were performed for a given focal geometry (Siemens CH41 transducer) for a range of tissue stiffnesses (mu = 1-15 kPa). Linear, elastic, isotropic material properties were assumed, making the time-to-peak (TTP) displacements along the axis of symmetry in the ROE proportional to the tissues shear wave speed and the excitation beam geometry. Lookup tables specific to an excitation/tracking focal configuration were generated from simulated data, and stiffness estimates as a function of depth were possible using experimental data in calibrated phantoms and soft tissues in vivo. These stiffness estimates were compared with estimates using our previously validated Lateral TTP method. Simulation data indicate that the reconstructed shear moduli are independent of variations in tissue attenuation that impact the spatial distribution of radiation force in the ROE. Phantom reconstructions yielded ROE TTP shear modulus estimates within 0.15 kPa to those using the Lateral TTP method. The axial ROI for each method is similar, but the lateral ROI is ~30times smaller for the ROE TTP method (0.2 vs. 6 mm). The ROE TTP algorithm applied to in vivo data yielded similar mean shear stiffness estimates (mu = 1.7 kPa), but with increased variance (0.9 vs. 0.2 kPa) compared to the Lateral TTP algorithm. Greater displacement magnitudes are present within the ROE compared with spatially-offset locations, producing greater displacement SNR and reducing the acoustic energy needed to generate accurate displacement estimates. Reduced acoustic output leads to decreased transducer and tissue heating. Measuring TTP values within the ROE, instead of at multiple offset locations, also reduces data acquisition times, limiting displacement motion artifacts. The ROE TTP precision is jitter dependent; material shear moduli can be reconstructed within <0.5 kPa.

Ultrasonic imaging of the mechanical properties of tissues using localized, transient acoustic radiation force

Acoustic radiation force impulse (ARFI) imaging utilizes brief, high energy, focused acoustic pulses to generate radiation force in tissue, and ultrasonic correlation-based methods to detect the resulting tissue displacements in order to image the relative mechanical properties of tissue. The magnitude and spatial extent of the applied force is dependent upon the transmit beam parameters and the tissue attenuation. Forcing volumes are on the order of 5 mm/sup 3/, pulse durations are less than 1 msec, and tissue displacements are typically several microns. Displacement is quantified using interpolation and cross-correlation methods. Noise reduction is accomplished by adaptively filtering the temporal response, and median filters are applied to the resulting images. Images of tissue displacement reflect local tissue stiffness, with softer tissues (e.g. fat) displacing farther than stiffer tissues (e.g. muscle). Parametric images of maximum displacement, time to peak displacement, and recovery time provide information about tissue material properties and structure. In both in vivo and ex vivo data, structures shown in matched B-mode images are in good agreement with those shown in ARFI images, with comparable resolution. Potential clinical applications under investigation include: soft tissue lesion characterization, assessment of focal atherosclerosis, and imaging of thermal lesion formation during tissue ablation procedures. Results from ongoing studies are presented.