Sound Speed Estimation for Distributed Aberration Correction in Laterally Varying Media

Spatial variation in sound speed causes aberration in medical ultrasound imaging. Although our previous work has examined aberration correction in the presence of a spatially varying sound speed, practical implementations were limited to layered media due to the sound speed estimation process involved. Unfortunately, most models of layered media do not capture the lateral variations in sound speed that have the greatest aberrative effect on the image. Building upon a Fourier split-step migration technique from geophysics, this work introduces an iterative sound speed estimation and distributed aberration correction technique that can model and correct for aberrations resulting from laterally varying media. We first characterize our approach in simulations where the scattering in the media is known a-priori. Phantom and in-vivo experiments further demonstrate the capabilities of the iterative correction technique. As a result of the iterative correction scheme, point target resolution improves by up to a factor of 4 and lesion contrast improves by up to 10.0 dB in the phantom experiments presented

Merging single-track location Elastographic imaging with the frequency shift method improves shear wave attenuation measurements

The frequency shift (FS) method is emerging as the standard approach for estimating shear wave attenuation coefficient (SWA). However, measurement noise can negatively impact the FS method’s accuracy, especially when employed in vivo. We hypothesized that combining plane wave single-track location shear wave elastography imaging with the FS method would reduce this problem. To test our hypothesis, we performed studies on calibrated phantoms and two groups of in vivo murine liver: control and obese mice. We evaluated the performance of various SWA methods, including the plane wave single-track location frequency shift (pSTL-FS) method that we recently developed, the original FS method, and the attenuation-measuring-shear-wave ultrasound elastography (AMUSE) method. We also assessed the effectiveness of assuming a Gaussian distribution versus a Gamma distribution for the shear wave spectrum when estimating SWA coefficients with the pSTL-FS and FS methods. The actual SWA coefficients of the phantoms were determined by performing independent mechanical testing on representative samples. The accuracy incurred when estimating SWA ranged from 84.69% to 97.55% for pSTL-FS (Gamma), 51.37%–72.18% for pSTL-FS (Gaussian), 40.33%–57.00% for FS (Gamma), 39.33%–55.37% for FS (Gaussian), and 59.25%–99.22% for AMUSE. The results of studies performed on murine livers (n = 10) revealed that assuming a Gaussian distribution during pSTL-FS imaging resulted in lower attenuation values than when a Gamma distribution was assumed. We also observed that pSTL-FS (Gamma) resulted in the highest significant difference between control and obese mice than all other approaches (p-value <0.0001). We also observed that the standard FS method with either Gamma or Gaussians produced lower attenuation estimates than pSTL-FS, AMUSE and mechanical testing. The mean attenuation coefficients of the murine livers measured with the pSTL-FS (Gamma and Gaussian functions) methods were consistently higher than those computed with the standard FS methods but lower than those computed with the AMUSE method. Our results demonstrated that combining the pSTL method with FS method provided more robust estimates of the SWA coefficient. For the murine livers, a Gamma distribution is more representative of the shear wave frequency spectrum than a Gaussian distribution

Collagen Complexity Spatially Defines Microregions of Total Tissue Pressure in Pancreatic Cancer.

The poor efficacy of systemic cancer therapeutics in pancreatic ductal adenocarcinoma (PDAC) is partly attributed to deposition of collagen and hyaluronan, leading to interstitial hypertension collapsing blood and lymphatic vessels, limiting drug delivery. The intrinsic micro-regional interactions between hyaluronic acid (HA), collagen and the spatial origins of mechanical stresses that close off blood vessels was investigated here. Multiple localized pressure measurements were analyzed with spatially-matched histochemical images of HA, collagen and vessel perfusion. HA is known to swell, fitting a linear elastic model with total tissue pressure (TTP) increasing above interstitial fluid pressure (IFP) directly with collagen content. However, local TTP appears to originate from collagen area fraction, as well as increased its entropy and fractal dimension, and morphologically appears to be maximized when HA regions are encapsulated by collagen. TTP was inversely correlated with vascular patency and verteporfin uptake, suggesting interstitial hypertension results in vascular compression and decreased molecular delivery in PDAC. Collagenase injection led to acute decreases in total tissue pressure and increased drug perfusion. Large microscopic variations in collagen distributions within PDAC leads to microregional TPP values that vary on the hundred micron distance scale, causing micro-heterogeneous limitations in molecular perfusion, and narrows viable treatment regimes for systemically delivered therapeutics

Elastographic imaging of pancreatic cancer tumor microenvironment

Thesis (Ph. D.)--University of Rochester. Department of Electrical and Computer Engineering, 2019.Pancreatic ductal adenocarcinoma (PDAC) is a common and aggressive malignancy with a 5-year survival rate of less than 5%. Surgical resection with targeted neoadjuvant therapy remains the most effective treatment plan available. Despite extensive research, targeted therapies have made incremental improvement in efficacy for PDAC patients. The unique abnormal PDAC tumor microenvironment has been postulated to promote tumor growth and inhibit drug delivery. The role of the dense stroma contents and high interstitial pressure are under active investigation regarding their role in vascular compression. An imaging technique that can measure the tumor stroma stiffness would provide crucial information on how the tumor microenvironment changes during different therapies. Contrast agent-based computed tomography, and magnetic resonance imaging modalities are faced with contrast pooling and poor contrast delivery, also a result of the abnormal tumor microenvironment. The objective of this thesis is to establish shear modulus as a surrogate biomarker for tissue pressure in pancreatic tumors using ultrasound elastography including model-based iterative reconstruction schemes and shear wave elasticity imaging. To achieve this goal, the following objectives are to be satisfied: (1) establish the relationship between shear modulus and stromal components of the pancreatic cancer tumor microenvironment; (2) investigate how shear modulus impacts drug delivery and vascular patency in pancreatic tumors; (3) assess the effects of radiotherapy and immunotherapy on shear modulus and the underlying tissue components. The results of these studies showed that the shear modulus is an excellent surrogate imaging biomarker for tissue pressure in pancreatic tumors. We demonstrated through three animal studies that shear modulus is inversely related to drug delivery in pancreatic adenocarcinoma tumors. Shear modulus also changes in response to modifications in tumor stroma attributes due to emerging treatment regimens such as immunotherapy and stereotactic body radiation therapy

Acoustic characterization and nonlinear imaging of ultrasound contrast agents for intravascular assessment of atherosclerosis

Thesis (Ph. D.)--University of Rochester. Dept. of Electrical and Computer Engineering, 2014.Cardiovascular disease kills more Americans than all cancers combined, and is estimated to cost over 300 billion dollars annually. The majority of these deaths are caused when the rupture of atherosclerotic plaques triggers life-threatening conditions such as myocardial infarction and stroke. Although the histopathological features of life-threatening plaques are known, detecting them in vivo is challenging. The abnormal proliferation of the adventitial vasa vasorum, the microvessels that nourish arterial walls, may destabilize atherosclerotic plaques. Therefore, visualizing the vasa vasorum could help assess atherosclerotic plaques. Contrast-enhanced ultrasound can characterize the neovascular vasa vasorum in atherosclerotic arteries. However, the translation of vasa vasorum imaging to the clinic is hampered by the absence of techniques capable of reliably detecting microbubble contrast agents. The goal of the research reported in this thesis is to develop methods for the intravascular detection of the vasa vasorum. To achieve this goal, we conducted physical characterization and imaging studies with Targestar-P®, a commercial contrast agent. Specifically, we 1)investigated the impact of the size distribution of the agent on its nonlinear response; 2) discovered that temporal changes in the agent can be harnessed to enhance nonlinear emissions; 3) demonstrated using numerical simulations and acoustic measurements that chirp-coded pulsing can substantially enhance the nonlinear response of microbubbles; and 4) developed a prototype intravascular ultrasound system for vasa vasorum imaging. We validated the vasa vasorum imaging system by conducting experiments with hydrogelow phantoms. Further, we compared the performance achievable with this system in subharmonic and ultraharmonic imaging modes. The findings reported in this thesis could accelerate the development of efficacious contrast agents for intravascular ultrasound imaging. The vasa vasorum imaging system developed in this work can be useful in preclinical research and clinical imaging | for improving our understanding of the pathophysiology of atherosclerosis, evaluating new therapies, and assessing cardiovascular risk

Principal strain vascular elastography for imaging the carotid artery

Thesis (Ph. D.)--University of Rochester. Department of Electrical and Computer Engineering, 2017.Atherosclerosis kills more Americans than all forms of cancer combined. The onset of the disease is characterized by thickening and stiffening of the arterial wall, and in advanced stages it leads to formation of life-threatening plaques. Rupture of these advanced plaques can lead to myocardial or cerebral infarction, and the propensity of the plaques to rupture is governed by their composition and structure. Vascular elastography can visualize the strain distribution in the carotid artery, and serve as a useful screening tool to assess the stiffness of the arterial wall – for early detection of major cardiovascular and cerebrovascular diseases, and to assess plaque composition. Currently available vascular elastography techniques visualize polar strains across the transverse cross-section, and axial strain across the sagittal cross- section. It is difficult to produce reliable transverse polar strain elastograms (radial and circumferential) because the center of the carotid artery is typically unknown. Further, axial strain estimated along the sagittal plane can only measure a component of the radial strain in the vessel. In this thesis, we hypothesized that principal strain imaging can overcome these limitations, provided reliable estimates of lateral displacements were available. To enable high quality estimation of lateral displacements, multi-element synthetic aperture (MSA) vascular elastography was developed. The phantom and in vivo experiments demonstrated that MSA imaging can produce high quality axial and lateral strain estimates. Compared with synthetic aperture (SA) imaging and compounded plane wave (CPW) imaging, MSA imaging improved the elastographic contrast-to-noise ratio of the vascular elastograms by over 15 dB and 12 dB, respectively. Subsequently, it was demonstrated that principal strains reduced artifacts incurred when polar strains were computed with imprecise estimates of the vessel center. The feasibility of using principal strain imaging in characterizing transversely isotropic mechanical behavior of the carotid artery was also established. Further, principal strain imaging addressed the issue of dependency of axial strain on the geometry of the vessel, when imaging across the sagittal cross-section. More specifically, principal strain imaging enabled estimation of arterial strain in the radial direction, independent of the angle between the transducer and the vessel, which is typically governed by the geometry and anatomy of the vessel, and varies across subjects. The results obtained from this thesis suggest that principal strain imaging can be a very useful tool for translation of vascular elastography to the clinic. Future studies should involve the assessment of the mechanical properties of the carotid artery using principal strain elastography, and compare it to conventional markers of subclinical atherosclerosis