Kristin Frinkley

Quantifying Hepatic Shear Modulus In Vivo Using Acoustic Radiation Force

The speed at which shear waves propagate in tissue can be used to quantify the shear modulus of the tissue. As many groups have shown, shear waves can be generated within tissues using focused, impulsive, acoustic radiation force excitations, and the resulting displacement response can be ultrasonically tracked through time. The goals of the work herein are twofold: (i) to develop and validate an algorithm to quantify shear wave speed from radiation force-induced, ultrasonically-detected displacement data that is robust in the presence of poor displacement signal-to-noise ratio and (ii) to apply this algorithm to in vivo datasets acquired in human volunteers to demonstrate the clinical feasibility of using this method to quantify the shear modulus of liver tissue in longitudinal studies. The ultimate clinical application of this work is noninvasive quantification of liver stiffness in the setting of fibrosis and steatosis. In the proposed algorithm, time-to-peak displacement data in response to impulsive acoustic radiation force outside the region of excitation are used to characterize the shear wave speed of a material, which is used to reconstruct the materials shear modulus. The algorithm is developed and validated using finite element method simulations. By using this algorithm on simulated displacement fields, reconstructions for materials with shear moduli (mu) ranging from 1.3-5 kPa are accurate to within 0.3 kPa, whereas stiffer shear moduli ranging from 10-16 kPa are accurate to within 1.0 kPa. Ultrasonically tracking the displacement data, which introduces jitter in the displacement estimates, does not impede the use of this algorithm to reconstruct accurate shear moduli. By using in vivo data acquired intercostally in 20 volunteers with body mass indices ranging from normal to obese, liver shear moduli have been reconstructed between 0.9 and 3.0 kPa, with an average precision of +/-0.4 kPa. These reconstructed liver moduli are consistent with those reported in the literature (mu = 0.75-2.5 kPa) with a similar precision (+/-0.3 kPa). Repeated intercostal liver shear modulus reconstructions were performed on nine different days in two volunteers over a 105-day period, yielding an average shear modulus of 1.9 +/- 0.50 kPa (1.3-2.5 kPa) in the first volunteer and 1.8 +/- 0.4 kPa (1.1-3.0 kPa) in the second volunteer. The simulation and in vivo data to date demonstrate that this method is capable of generating accurate and repeatable liver stiffness measurements and appears promising as a clinical tool for quantifying liver stiffness.

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.

Experimental Studies of the Thermal Effects Associated with Radiation Force Imaging of Soft Tissue

Many groups are studying acoustic radiation force-based imaging modalities to determine the mechanical properties of tissue. Acoustic Radiation Force Impulse (ARFI) imaging is one of these modalities that uses standard diagnostic ultrasound scanners to generate localized, impulsive, acoustic radiation force in tissue. This radiation force generates tissue displacements that are tracked using conventional correlation-based ultrasound methods. The dynamic response of tissue to this impulsive radiation force provides information about the mechanical properties of the tissue. The generation of micron-scale displacements using acoustic radiation force in tissue requires the use of high-intensity acoustic beams, and the soft tissue heating associated with these high-intensity beams must be evaluated to ensure safety when performing ARFI imaging in vivo. Experimental studies using thermocouples have validated Finite Element Method (FEM) models that simulate the heating of soft tissue during ARFI imaging. Spatial maps of heating measured with the thermocouples are in good agreement with FEM model predictions, with cooling time constants measured and modeled to be on the order of several seconds. Transducer heating during ARFI imaging has been measured to be less than 1 °C for current clinical implementations. These validated FEM models can now be used to simulate soft tissue heating associated with different transducers, beam spacing, focal configurations and thermal material properties. These experiments confirm that ARFI imaging of soft tissue is safe, although thermal response must be monitored when developing ARFI beam sequences for specific tissue types and organ systems.

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

Imaging tissue mechanical properties using impulsive acoustic radiation force

Acoustic radiation force impulse (ARFI) imaging utilizes brief, high energy, focused acoustic pulses to generate radiation force in tissue, and conventional diagnostic ultrasound methods to detect the resulting tissue displacements in order to image the relative mechanical properties of tissue. Parametric images of maximum displacement, the time the tissue takes to reach its peak displacement, and tissue recovery time provide information about tissue material properties and structure. FEM simulations have been developed and validated of tissue mechanical and thermal response to ARFI excitation. Potential clinical applications under investigation include: soft tissue lesion characterization, assessment of diffuse and focal atherosclerosis, and imaging of thermal lesion formation during tissue ablation procedures. In both in vivo and ex vivo data, structures shown in matched B-mode images are in good agreement with those shown in ARFI displacement images. In ex vivo tissue ablation studies (HIFU and RF-ablation), thermal lesion size correlates well with matched pathology images. In vivo breast studies, palpable breast masses exhibit smaller displacements (i.e. they are stiffer) than surrounding tissues. Some malignant masses appear larger in ARFI displacement images than in matched B-mode images, consistent with a desmoplastic reaction; however, this is not the case for all malignant breast masses that have been studied. Benign fibroadenomas, in general, exhibit less contrast than malignant masses in ARFI displacement images. Results from ongoing studies will be presented.

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.

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.

ON THE POTENTIAL FOR GUIDANCE OF ABLATION THERAPY USING ACOUSTIC RADIATION FORCE IMPULSE IMAGING

Acoustic radiation force imaging methods utilize acoustic radiation force to mechanically excite tissue, and the tissue response is monitored with conventional imaging methods. Radiation force based methods comprise a subset of elasticity imaging, in which images reflect relative differences in tissue stiffness. Acoustic radiation force impulse (ARFI) imaging is one such method that is implemented on a modified diagnostic ultrasound scanner, using the same transducer for the excitation and monitoring of the tissue response. ARFI imaging is under investigation for its potential to monitor thermal ablation procedures because thermal lesions are associated with considerable (> 4 times) stiffness increases as compared to viable tissue. Applications include monitoring radiofrequency ablation procedures in the liver, kidney, and heart, and monitoring focused ultrasound ablation procedures. We present results from ongoing studies in these areas

Controlled spatio-temporal heating patterns using a commercial, diagnostic ultrasound system

Thermal ultrasound therapy is being investi- gated as a non-invasive surgical tool with applications in soft tissue tumor and cardiac ablation; as a method for hemostasis; and in the control of thermally-activated drug delivery vehicles. The success of localized ultrasonic thermal therapy depends on image guidance, typically done with a separate imaging transducer, but alignment of these trans- ducers is challenging. A system capable of both functions would be ideal. However, the inherent tradeoff between image quality and power output presents a challenge for dual- function probe design. A Siemens Antares TM scanner and CH62 transducer (fc=4.4 MHz) were employed to investigate the feasibility of using a modified, commercial diagnostic ultrasound system to combine B-mode, Doppler guidance, ARFI imaging, and therapeutic thermal applications. Custom pulse sequences were designed to transmit high intensity pulses down a single line of flight using different pulse lengths, amplitudes, PRFs, and F/#s for therapeutic purposes. These sequences were delivered to ex vivo porcine muscle through a waterpath to the focal point, where a type T thermocouple was positioned at the water/muscle interface. Transducer surface heating was monitored in separate experiments for these sequences by centering a thermocouple on the surface of the transducer. The porcine measurements were compared with analytic solutions to the bio-heat transfer equation and FEM models. Transmit parameters were evaluated to determine the optimal sequencing approach for different thermal therapies. Temperature rises of 28.6 ± 1.2 ◦ Cf or∼50 ms were regularly achieved on the surface of the porcine muscle with damage to the transducer only after several repetitions. Temperature measurements at the focus were made for increasing durations of insonification and were consistent with the bio-heat transfer equation solution (neglecting perfusion). These temperature rises suggest the feasibility of using this system for creating HIFU lesions and aiding in drug therapy treatments. However, these experiments do not incorporate perfusion effects or, more significantly, attenuation of intervening tissue which will be encountered for most in vivo applications and will therefore require increased acoustic output. Thus, passive cooling mod- ifications are being explored to decrease transducer heating while maintaining good image quality.

Image processing and data acquisition optimization for acoustic radiation force impulse imaging of in vivo breast masses

Acoustic radiation force impulse (ARFI) imaging utilizes brief, high energy, focused acoustic pulses to generate radiation force in tissue, and conventional ultrasonic correlation-based methods to track the resulting tissue displacements in order to image the relative mechanical properties of tissue. In an ongoing clinical study, ARFI datasets from in vivo breast masses are acquired prior to core biopsy. Matched B-mode and ARFI images are generated for each mass. Data sets are divided based upon biopsy results, and images are evaluated for differentiating features. The purpose of this study is to acquire in vivo ARFI datasets in real-time, and to identify differentiable features between benign and malignant breast masses in the ARFI images. A modified Siemens SONOLINE Antares/spl trade/ scanner and a VF10-5 probe were programmed to implement ARFI imaging in a multi-focal zone configuration. Under an IRB approved protocol. patients scheduled for breast core biopsy were recruited for participation. Data was acquired in real-time and processed offline. Matched B-mode and ARFI images were evaluated concurrently. To date, 27 masses have been imaged under this experimental protocol. In addition, single focal zone ARFI data acquired from 52 masses with a Siemens SONOLINE Elegra/spl trade/ scanner and a 75L40 transducer were evaluated for consistency of the differentiating features. Of the 27 masses interrogated via multi-focal-zone ARFI, 9 were malignant, 9 were benign fibroadenomas, 4 were cysts, and the rest were other benign masses (i.e. lymph nodes, fat necrosis, etc.) Structures in matched B-mode images are in good agreement with those in ARFI displacement images, with both modalities demonstrating comparable resolution. In general ARFI displacement images of malignant breast masses exhibit increased contrast and improved margin definition over matched B-mode images. Cancers displace less (i.e. they are stiffer) than the surrounding tissue, and generally appear larger than in matched B-mode images. In addition, some malignant masses exhibit a slower recovery time, which has not been observed with benign masses. The cysts and fibroadenomas, in general, exhibit less contrast in ARFI images than in matched B-mode images. In many cases, fibroadenomas are not clearly distinguished from the surrounding tissues in ARFI displacement images, and can appear either stiffer or softer than the surrounding tissue. Acoustic streaming is observed in cyst fluid in response to ARFI excitation. ARFI displacement images portray different, complementary information than matched B-mode images. Some possible differentiating features between malignant and benign breast masses have been identified by this pilot study. Promising features include: differences in B-mode and ARFI lesion size. displacement magnitude, recovery time, and image contrast. These results encourage further study of breast mass characterization using ARFI imaging.