Jeremy J. Dahl

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.

Chemostratigraphic reconstruction of biofacies: Molecular evidence linking cyst-forming dinoflagellates with pre-Triassic ancestors

New data from numerous detailed mass-spectrometric studies have detected triaromatic dinosteroids in Precambrian to Cenozoic rock samples. Triaromatic dinosteroids are organic geochemicals derived from dinosterols, compounds known in modern organisms to be the nearly exclusive widely occurring products of dinoflagellates. We observed the ubiquitous occurrence of these dinosteroids in 49 Late Triassic through Cretaceous marine source rocks and the absence of them in 13 Permian-Carboniferous source rocks synergistic with the dinoflagellate cyst record. However, finding dinosteroids in lower Paleozoic and Precambrian strata presents challenging results for molecular paleontologists, evolutionary biologists, palynologists, and especially for those concerned with the food web at various times of biological crisis. Other than the few species known as parasites and symbionts, many other dinoflagellate species are important as primary producers. The presence of Precambrian to Devonian triaromatic dinosteroids gives chemostratigraphic evidence of dinoflagellates (or other organisms with similar chemosynthetic capabilities) in rocks significantly older than the oldest undisputed dinoflagellate fossils (dinoflagellate cysts from the Middle Triassic, ∼ 240 Ma), and older than the putative Silurian ∼ 420 Ma) dinocyst, Arpylorus antiquus (Calandra) Sargent, from Tunisia. This systematic chemostratigraphic approach can shed light not only on lineages of dinoflagellates and their precursors, but potentially on many other lineages, especially bacteria, algae, plants, and possibly some metazoans.

A parallel tracking method for acoustic radiation force impulse imaging

Radiation force-based techniques have been developed by several groups for imaging the mechanical properties of tissue. Acoustic radiation force impulse (ARFI) imaging is one such method that uses commercially available scanners to generate localized radiation forces in tissue. The response of the tissue to the radiation force is determined using conventional B-mode imaging pulses to track micron-scale displacements in tissue. Current research in ARFI imaging is focused on producing real-time images of tissue displacements arid related mechanical properties. Obstacles to producing a real-time ARFl imaging modality include data acquisition, processing power, data transfer rates, heating of the transducer, and patient safety concerns. We propose a parallel receive beamforming technique to reduce transducer heating and patient acoustic exposure, and to facilitate data acquisition for real-time ARFI imaging. Custom beam sequencing was used with a commercially available scanner to track tissue displacements with parallel-receive beamforming in tissue-mimicking phantoms. Using simulations, the effects of material properties on parallel tracking are observed. Transducer and tissue heating for parallel tracking are compared to standard ARFI beam sequencing. The effects of tracking beam position and size of the tracked region are also discussed in relation to the size and temporal response of the region of applied force, and the impact on ARFI image contrast arid signal-to-noise ratio are quantified

Short-lag spatial coherence of backscattered echoes: imaging characteristics

Conventional ultrasound images are formed by delay-and-sum beamforming of the backscattered echoes received by individual elements of the transducer aperture. Although the delay-and-sum beamformer is well suited for ultrasound image formation, it is corrupted by speckle noise and challenged by acoustic clutter and phase aberration. We propose an alternative method of imaging utilizing the short-lag spatial coherence (SLSC) of the backscattered echoes. Compared with matched B-mode images, SLSC images demonstrate superior SNR and contrast-to-noise ratio in simulated and experimental speckle-generating phantom targets, but are shown to be challenged by limited point target conspicuity. Matched B-mode and SLSC images of a human thyroid are presented. The challenges and opportunities of real-time implementation of SLSC imaging are discussed.

A heterogeneous nonlinear attenuating full- wave model of ultrasound

A full-wave equation that describes nonlinear propagation in a heterogeneous attenuating medium is solved numerically with finite differences in the time domain (FDTD). Three-dimensional solutions of the equation are verified with water tank measurements of a commercial diagnostic ultrasound transducer and are shown to be in excellent agreement in terms of the fundamental and harmonic acoustic fields and the power spectrum at the focus. The linear and nonlinear components of the algorithm are also verified independently. In the linear nonattenuating regime solutions match results from Field II, a well established software package used in transducer modeling, to within 0.3 dB. Nonlinear plane wave propagation is shown to closely match results from the Galerkin method up to 4 times the fundamental frequency. In addition to thermoviscous attenuation we present a numerical solution of the relaxation attenuation laws that allows modeling of arbitrary frequency dependent attenuation, such as that observed in tissue. A perfectly matched layer (PML) is implemented at the boundaries with a numerical implementation that allows the PML to be used with high-order discretizations. A -78 dB reduction in the reflected amplitude is demonstrated. The numerical algorithm is used to simulate a diagnostic ultrasound pulse propagating through a histologically measured representation of human abdominal wall with spatial variation in the speed of sound, attenuation, nonlinearity, and density. An ultrasound image is created in silico using the same physical and algorithmic process used in an ultrasound scanner: a series of pulses are transmitted through heterogeneous scattering tissue and the received echoes are used in a delay-and-sum beam-forming algorithm to generate a images. The resulting harmonic image exhibits characteristic improvement in lesion boundary definition and contrast when compared with the fundamental image. We demonstrate a mechanism of harmonic image quality improvement by showing that the harmonic point spread function is less sensitive to reverberation clutter.

Acoustic Radiation Force Impulse Imaging for Noninvasive Characterization of Carotid Artery Atherosclerotic Plaques: A Feasibility Study

Atherosclerotic disease in the carotid artery is a risk factor for stroke. The susceptibility of atherosclerotic plaque to rupture, however, is challenging to determine by any imaging method. In this study, acoustic radiation force impulse (ARFI) imaging is applied to atherosclerotic disease in the carotid artery to determine the feasibility of using ARFI to noninvasively characterize carotid plaques. ARFI imaging is a useful method for characterizing the local mechanical properties of tissue and is complementary to B-mode imaging. ARFI imaging can readily distinguish between stiff and soft regions of tissue. High-resolution images of both homogeneous and heterogeneous plaques were observed. Homogeneous plaques were indistinguishable in stiffness from vascular tissue. However, they showed thicknesses much greater than normal vascular tissue. In heterogeneous plaques, large and small soft regions were observed, with the smallest observed soft region having a diameter of 0.5 mm. A stiff cap was observed covering the large soft tissue region, with the cap thickness ranging from 0.7-1.3 mm.

An ultrasound research interface for a clinical system

Under a contract with the National Cancer Institute, we have developed a research interface to an ultrasound system. This ultrasound research interface (URI) is an optional feature providing several basic capabilities not normally available on a clinical scanner. The URI can store high-quality beamformed radio-frequency data to file for off-line processing. Also, through an integrated user interface, the user is provided additional control over the B-mode receive aperture and color flow ensemble size. A third major capability is the ability to record and playback macro files. In this paper, we describe the URI and illustrate its use on three research examples: elastography, computed tomography, and spatial compounding.

Errata - An ultrasound research interface for a clinical system

Under a contract with the National Cancer Institute, we have developed a research interface to an ultrasound system. This ultrasound research interface (URI) is an optional feature providing several basic capabilities not normally available on a clinical scanner. The URI can store high-quality beamformed radio-frequency data to file for off-line processing. Also, through an integrated user interface, the user is provided additional control over the B-mode receive aperture and color flow ensemble size. A third major capability is the ability to record and playback macro files. In this paper, we describe the URI and illustrate its use on three research examples: elastography, computed tomography, and spatial compounding

Lesion Detectability in Diagnostic Ultrasound with Short-Lag Spatial Coherence Imaging

We demonstrate a novel imaging technique, named short-lag spatial coherence (SLSC) imaging, which uses short distance (or lag) values of the coherence function of backscattered ultrasound to create images. Simulations using Field II are used to demonstrate the detection of lesions of varying sizes and contrasts with and without acoustical clutter in the backscattered data. B-mode and SLSC imaging are shown to be nearly equivalent in lesion detection, based on the contrast-to-noise ratio (CNR) of the lesion, in noise-free conditions. The CNR of the SLSC image, however, can be adjusted to achieve an optimal value at the expense of image smoothness and resolution. In the presence of acoustic clutter, SLSC imaging yields significantly higher CNR than B-mode imaging and maintains higher image quality than B-mode with increasing noise. Compression of SLSC images is shown to be required under high-noise conditions but is unnecessary under no- and low-noise conditions. SLSC imaging is applied to in vivo imaging of the carotid sheath and demonstrates significant gains in CNR as well as visualization of arterioles in the carotid sheath. SLSC imaging has a potential application to clutter rejection in ultrasonic imaging.

Image quality, tissue heating, and frame rate trade-offs in acoustic radiation force impulse imaging

The real-time application of acoustic radiation force impulse (ARFI) imaging requires both short acquisition times for a single ARFI image and repeated acquisition of these frames. Due to the high energy of pulses required to generate appreciable radiation force, however, repeated acquisitions could result in substantial transducer face and tissue heating. We describe and evaluate several novel beam sequencing schemes which, along with parallel-receive acquisition, are designed to reduce acquisition time and heating. These techniques reduce the total number of radiation force impulses needed to generate an image and minimize the time between successive impulses. We present qualitative and quantitative analyses of the trade-offs in image quality resulting from the acquisition schemes. Results indicate that these techniques yield a significant improvement in frame rate with only moderate decreases in image quality. Tissue and transducer face heating resulting from these schemes is assessed through finite element method modeling and thermocouple measurements. Results indicate that heating issues can be mitigated by employing ARFI acquisition sequences that utilize the highest track-to-excitation ratio possible.