Stephen Rosenzweig

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.

Derivation and analysis of viscoelastic properties in human liver: impact of frequency on fibrosis and steatosis staging

Commercially-available shear wave imaging systems measure group shear wave speed (SWS) and often report stiffness parameters applying purely elastic material models. Soft tissues, however, are viscoelastic, and higher-order material models are necessary to characterize the dispersion associated with broadband shear waves. In this paper, we describe a robust, model-based algorithm and use a linear dispersion model to perform shear wave dispersion analysis in traditionally difficult-to-image subjects. In a cohort of 135 non-alcoholic fatty liver disease patients, we compare the performance of group SWS with dispersion analysis-derived phase velocity c(200 Hz) and dispersion slope dc/df parameters to stage hepatic fibrosis and steatosis. Area under the ROC curve (AUROC) analysis demonstrates correlation between all parameters [group SWS, c(200 Hz), and, to a lesser extent dc/df ] and fibrosis stage, whereas no correlation was observed between steatosis stage and any of the material parameters. Interestingly, optimal AUROC threshold SWS values separating advanced liver fibrosis (≥F3) from mild-to-moderate fibrosis (≤F2) were shown to be frequency-dependent, and to increase from 1.8 to 3.3 m/s over the 0 to 400 Hz shear wave frequency range.

Contrast‐enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood‐brain barrier with ultrasound

The use of contrast agents for neuroimaging is limited by the blood‐brain barrier (BBB), which restricts entry into the brain. To administer imaging agents to the brain of rats, intracarotid infusions of hypertonic mannitol have been used to open the BBB. However, this technically challenging approach is invasive, opens only a limited region of the BBB, and is difficult to extend to mice. In this work, the BBB was opened in mice, using unfocused ultrasound combined with an injection of microbubbles. This technique has several notable features: it (a) can be performed transcranially in mice; (b) takes only 3 min and uses only commercially available components; (c) opens the BBB throughout the brain; (d) causes no observed histologic damage or changes in behavior (with peak‐negative acoustic pressures of 0.36 MPa); and (e) allows recovery of the BBB within 4 h. Using this technique, Gadopentetate Dimeglumine (Gd‐DTPA) was administered to the mouse brain parenchyma, thereby shortening T1 and enabling the acquisition of high‐resolution (52 × 52 × 100 micrometers3) images in 51 min in vivo. By enabling the administration of both existing anatomic contrast agents and the newer molecular/sensing contrast agents, this technique may be useful for the study of mouse models of neurologic function and pathology with MRI. Magn Reson Med, 2010.

Single- and Multiple-Track-Location Shear Wave and Acoustic Radiation Force Impulse Imaging: Matched Comparison of Contrast, Contrast-to-Noise Ratio and Resolution

Acoustic radiation force impulse imaging and shear wave elasticity imaging (SWEI) use the dynamic response of tissue to impulsive mechanical stimulus to characterize local elasticity. A variant of conventional, multiple-track-location SWEI, denoted single-track-location SWEI, offers the promise of creating speckle-free shear wave images. This work compares the three imaging modalities using a high push and track beam density combined acquisition sequence to image inclusions of different sizes and contrasts. Single-track-location SWEI is found to have a significantly higher contrast-to-noise ratio than multiple-track-location SWEI, allowing for operation at higher resolution. Acoustic radiation force impulse imaging and single-track-location SWEI perform similarly in the larger inclusions, with single-track-location SWEI providing better visualization of small targets ≤ 2.5 mm in diameter. The processing of each modality introduces different trade-offs between smoothness and resolution of edges and structures; these are discussed in detail.

Analysis of rapid multi-focal-zone ARFI imaging

Acoustic radiation force impulse (ARFI) imaging has shown promise for visualizing structure and pathology within multiple organs; however, because the contrast depends on the push beam excitation width, image quality suffers outside of the region of excitation. Multi-focal-zone ARFI imaging has previously been used to extend the region of excitation (ROE), but the increased acquisition duration and acoustic exposure have limited its utility. Supersonic shear wave imaging has previously demonstrated that through technological improvements in ultrasound scanners and power supplies, it is possible to rapidly push at multiple locations before tracking displacements, facilitating extended depth of field shear wave sources. Similarly, ARFI imaging can utilize these same radiation force excitations to achieve tight pushing beams with a large depth of field. Finite element method simulations and experimental data are presented, demonstrating that single- and rapid multi-focal-zone ARFI have comparable image quality (less than 20% loss in contrast), but the multi-focal-zone approach has an extended axial region of excitation. Additionally, as compared with single-push sequences, the rapid multi-focalzone acquisitions improve the contrast-to-noise ratio by up to 40% in an example 4-mm-diameter lesion.

RSNA QIBA ultrasound shear wave speed Phase II phantom study in viscoelastic media

Using ultrasonic shear wave speed (SWS) estimates has become popular to noninvasively evaluate liver fibrosis, but significant inter-system variability in liver SWS measurements can preclude meaningful comparison of measurements performed with different systems. The RSNA Quantitative Imaging Biomarker Alliance (QIBA) ultrasound SWS committee has been developing elastic and viscoelastic (VE) phantoms to evaluate system dependencies of SWS estimates. The objective of this study is to compare SWS measurements between commercially-available systems using phantoms that have viscoelastic properties similar to those observed in normal and fibrotic liver. CIRS, Inc. fabricated three phantoms using a proprietary oil-water emulsion infused in a Zerdine® hydrogel that were matched in viscoelastic behavior to healthy and fibrotic human liver data. Phantoms were measured at academic, clinical, government and vendor sites using different systems with curvilinear arrays at multiple focal depths (3.0, 4.5 & 7.0 cm). The results of this study show that current-generation ultrasound SWS measurement systems are able to differentiate viscoelastic materials that span healthy to fibrotic liver. The deepest focal depth (7.0 cm) yielded the greatest inter-system variability for each phantom (maximum of 17.7%) as evaluated by IQR. Inter-system variability was consistent across all 3 phantoms and was not a function of stiffness. Median SWS estimates for the greatest outlier system for each phantom/focal depth combination ranged from 12.7-17.6%. Future efforts will include performing more robust statistical analyses of these data, comparing these phantom data trends with viscoelastic digital phantom data, providing vendors with study site data to refine their systems to have more consistent measurements, and integrating these data into the QIBA ultrasound shear wave speed measurement profile.

Analyzing the Impact of Increasing Mechanical Index and Energy Deposition on Shear Wave Speed Reconstruction in Human Liver

Shear wave elasticity imaging (SWEI) has found success in liver fibrosis staging. However, technical failure and unreliable shear wave speed (SWS) estimation have been reported to increase both with elevated patient body mass index (BMI) and in the presence of significant hepatic fibrosis. Elevated BMI results in a significant amount of subcutaneous fat which attenuates acoustic radiation force (ARF) and abberates tracking beams. Advanced fibrosis results in small displacement amplitudes in stiff livers. This work evaluates hepatic SWEI measurement success as a function of push pulse energy using 2 Mechanical Index (MI) values (1.6 and 2.2) over a range of pulse durations. The rate of successful SWS estimation for 8 repeated measurements is linearly proportional to the push energy level. As expected, elevated push energy in SWEI measurements results in higher displacement signal-to-noise ratio (SNR). SWEI measurements with elevated push energy are successful in patients for whom standard push energy levels failed. Deep liver capsule is shown to be an indicator for lower yield of SWS estimation. Patients with deep liver capsules are likely to benefit from elevated push energies. We conclude that there is clinical benefit to using elevated acoustic output for hepatic SWS measurement in “difficult to image” patients.

Acoustic Radiation Force Impulse (ARFI) Imaging-Based Needle Visualization

Ultrasound-guided needle placement is widely used in the clinical setting, particularly for central venous catheter placement, tissue biopsy and regional anesthesia. Difficulties with ultrasound guidance in these areas often result from steep needle insertion angles and spatial offsets between the imaging plane and the needle. Acoustic Radiation Force Impulse (ARFI) imaging leads to improved needle visualization because it uses a standard diagnostic scanner to perform radiation force based elasticity imaging, creating a displacement map that displays tissue stiffness variations. The needle visualization in ARFI images is independent of needle-insertion angle and also extends needle visibility out of plane. Although ARFI images portray needles well, they often do not contain the usual B-mode landmarks. Therefore, a three-step segmentation algorithm has been developed to identify a needle in an ARFI image and overlay the needle prediction on a coregistered B-mode image. The steps are: (1) contrast enhancement by median filtration and Laplacian operator filtration, (2) noise suppression through displacement estimate correlation coefficient thresholding and (3) smoothing by removal of outliers and best-fit line prediction. The algorithm was applied to data sets from horizontal 18, 21 and 25 gauge needles between 0–4 mm offset in elevation from the transducer imaging plane and to 18G needles on the transducer axis (in plane) between 10° and 35° from the horizontal. Needle tips were visualized within 2 mm of their actual position for both horizontal needle orientations up to 1.5 mm offset in elevation from the transducer imaging plane and on-axis angled needles between 10°–35° above the horizontal orientation. We conclude that segmented ARFI images overlaid on matched B-mode images hold promise for improved needle visibility in many clinical applications.

Identifying Clinically Significant Prostate Cancers using 3-D In Vivo Acoustic Radiation Force Impulse Imaging with Whole-Mount Histology Validation.

Overly aggressive prostate cancer (PCa) treatment adversely affects patients and places an unnecessary burden on our health care system. The inability to identify and grade clinically significant PCa lesions is a factor contributing to excessively aggressive PCa treatment, such as radical prostatectomy, instead of more focal, prostate-sparing procedures such as cryotherapy and high-dose radiation therapy. We have performed 3-D in vivo B-mode and acoustic radiation force impulse (ARFI) imaging using a mechanically rotated, side-fire endorectal imaging array to identify regions suspicious for PCa in 29 patients being treated with radical prostatectomies for biopsy-confirmed PCa. Whole-mount histopathology analyses were performed to identify regions of clinically significant/insignificant PCa lesions, atrophy and benign prostatic hyperplasia. Regions of suspicion for PCa were reader-identified in ARFI images based on boundary delineation, contrast, texture and location. These regions of suspicion were compared with histopathology identified lesions using a nearest-neighbor regional localization approach. Of all clinically significant lesions identified on histopathology, 71.4% were also identified using ARFI imaging, including 79.3% of posterior and 33.3% of anterior lesions. Among the ARFI-identified lesions, 79.3% corresponded to clinically significant PCa lesions, with these lesions having higher indices of suspicion than clinically insignificant PCa. ARFI imaging had greater sensitivity for posterior versus anterior lesions because of greater displacement signal-to-noise ratio and finer spatial sampling. Atrophy and benign prostatic hyperplasia can cause appreciable prostate anatomy distortion and heterogeneity that confounds ARFI PCa lesion identification; however, in general, ARFI regions of suspicion did not coincide with these benign pathologies.

B-Mode and Acoustic Radiation Force Impulse (ARFI) Imaging of Prostate Zonal Anatomy Comparison with 3T T2-Weighted MR Imaging

Prostate cancer (PCa) is the most common non-cutaneous malignancy among men in the United States and the second leading cause of cancer-related death. Multi-parametric magnetic resonance imaging (mpMRI) has gained recent popularity to characterize PCa. Acoustic Radiation Force Impulse (ARFI) imaging has the potential to aid PCa diagnosis and management by using tissue stiffness to evaluate prostate zonal anatomy and lesions. MR and B-mode/ARFI in vivo imaging datasets were compared with one another and with gross pathology measurements made immediately after radical prostatectomy. Images were manually segmented in 3D Slicer to delineate the central gland (CG) and prostate capsule, and 3D models were rendered to evaluate zonal anatomy dimensions and volumes. Both imaging modalities showed good correlation between estimated organ volume and gross pathologic weights. Ultrasound and MR total prostate volumes were well correlated (R2 = 0.77), but B-mode images yielded prostate volumes that were larger (16.82% ± 22.45%) than MR images, due to overestimation of the lateral dimension (18.4% ± 13.9%), with less significant differences in the other dimensions (7.4% ± 17.6%, anterior-to-posterior, and −10.8% ± 13.9%, apex-to-base). ARFI and MR CG volumes were also well correlated (R2 = 0.85). CG volume differences were attributed to ARFI underestimation of the apex-to-base axis (−28.8% ± 9.4%) and ARFI overestimation of the lateral dimension (21.5% ± 14.3%). B-mode/ARFI imaging yielded prostate volumes and dimensions that were well correlated with MR T2-weighted image (T2WI) estimates, with biases in the lateral dimension due to poor contrast caused by extraprostatic fat. B-mode combined with ARFI imaging is a promising low-cost, portable, real-time modality that can complement mpMRI for PCa diagnosis, treatment planning, and management.