@article{anand_gallippi_2022, title={4D Cardiac Gated Vector Flow Imaging Accurately Measures WSS in a Pressurized Closed-Loop System}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958037}, abstractNote={Wall shear stress plays a critical role in atherosclerotic plaque remodeling and risk of rupture. High framerate volumetric imaging is required to capture potentially malignant hemodynamic forces on the plaque. We show that accurate volumetric wall shear stress estimation over time is feasible by sweeping a linear array transmitting plane wave vector Doppler sequences, with gated acquisitions. Pulsatile flow in a pressurized straight tube CIRS peripheral vascular phantom generated mimicked “end diastolic” and “peak systolic” wall shear stresses of 0.26 Pa and 1.63 Pa, respectively. The 4D vector flow imaging overall tracked changes in WSS along the tube with <15% error relative to the analytical ground truth, with slightly more underestimation near the sides of the tube. Together, the results demonstrate that, despite the poor elevational resolution of a linear array, volumetric WSS can be measured throughout the cardiac cycle. This approach may be relevant to volumetric evaluation of WSS in human carotid arteries, with extension to incorporating volumetric interrogation of plaque composition and structure.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Anand, Keerthi S. and Gallippi, Caterina M.}, year={2022} }
 @article{phillips_torres_steed_caughey_merhout_kirk_hartman_kuzmiak_ray_gallippi_2022, title={Breast Lesion Diameter in VisR Imaging Differs Between Malignant and Benign Masses in Women}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958080}, abstractNote={The specificity of current clinical screening for identifying malignant breast lesions is as low as 65%, requiring costly and invasive additional tests to rule out false positives [1]. Ultrasound elastography is increasingly being used to augment diagnosis by measuring mechanical properties of the tissue. For this purpose, we investigate the E/B ratio, which compares lesion size on an elastogram to lesion size on B-mode and is reported to be >1 in malignant cases and <1 in benign cases. The E/B ratio is typically measured from stiffness estimate images that are based on tissue displacement after mechanical excitation, like SE or SWE. These stiffness estimation methods fail to account for viscosity, which is diagnostically relevant for breast cancer and can also bias stiffness estimates. We improve on these previous methods by measuring E/B ratio from both stiffness and viscosity VisR images. We found that E/B ratio measured from VisR relative elasticity (RE) and relative viscosity (RV) statistically separated benign and malignant breast lesions and improved AUC and sensitivity compared to E/B ratio measured from ARFI peak displacement.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Phillips, Anna V. and Torres, Gabriela and Steed, Doreen and Caughey, Melissa C. and Merhout, Jasmin and Kirk, Shanah R. and Hartman, Terry S. and Kuzmiak, Cherie M. and Ray, Emily M. and Gallippi, Caterina M.}, year={2022} }
 @article{muhtadi_haque_gallippi_2022, title={Combined B-mode and Nakagami Images for Improved Discrimination of Breast Masses using Deep Learning}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9957624}, abstractNote={Although ultrasound has become an important screening tool for the non-invasive diagnosis of breast cancer, it is limited by intra- and inter-observer variability, and subjectivity in diagnosis. On the other hand, deep learning-based approaches have the potential for objective and automated diagnosis in a manner that is efficient and reproducible. In this study, we propose a deep learning methodology for the classification of benign and malignant breast lesions based on combined ultrasound B-mode and Nakagami images. We hypothesize that combining the images, which contain complementary information, will provide better classification performance in a deep learning framework than using the images by themselves. The study included 230 patients who had 152 benign and 78 malignant masses. Nakagami images were formed using a sliding window applied to the envelope data of each patient. A superposition approach was adopted to form fused images, where Nakagami images and B-mode images were superimposed onto each other at differing weights. A modified VGG-16 network was trained on the resulting images, and performance was evaluated on a separate test dataset containing 50 images. Models trained using fused images outperformed models trained using individual B-mode and Nakagami images. Furthermore, the AVCs obtained by models trained on fused images were found to be statistically significantly higher than models trained on individual images. The obtained results demonstrate the feasibility of combining information from Nakagami and B-mode images, and its potential to provide improved diagnosis for breast cancer.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Muhtadi, Sabiq and Haque, Syed Tousiful and Gallippi, Caterina M.}, year={2022} }
 @article{anand_kolahdouz_homeister_smith_griffith_gallippi_2022, title={Concurrent ARFI Plaque Imaging and Wall Shear Stress Measurement in Human Carotid Artery, with Validation by Fluid Structure Interaction Models}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958828}, abstractNote={The rupture potential of an atherosclerotic plaque is dependent on both the plaque's composition and the shear stresses it encounters from blood flow. Because plaques move and deform throughout the cardiac cycle, resulting in changes to plaque position and shape as well as to the encountered shear stresses, concurrent imaging of both risk factors over time is required to accurately predict plaque vulnerability. To evaluate the potential to achieve as much, multi-angle plane wave (PW) ARFI and least-squares vector Doppler data were acquired in a calibrated flow phantom with channels of 4–8 mm diameters and flow rates of 100–600 ml/min. The wall shear stress (WSS) was measured to within 15% of the ground-truth analytical solutions. The same methods were then implemented in an excised human cadaveric carotid with a x% stenotic plaque. ARFI VoA detected plaque regions of calcium and intraplaque hemorrhage that were validated by spatially-matched histology. Concurrent vector Doppler yielded a peak WSS of 5.2 Pa on the plaque shoulder, which was consistent with the 6.4 Pa WSS predicted by an immersed interface fluid-solid interation (FSI) model developed using the specific geometry of the examined cadaveric carotid. Overall our results demonstrate the feasibility of concurrent imaging of carotid plaque composition by ARFI VoA, vector flow, and WSS to better assess stroke risk.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Anand, Keerthi S. and Kolahdouz, Ebrahim M. and Homeister, Jonathon and Smith, Margaret-Anne and Griffith, Boyce E. and Gallippi, Caterina M.}, year={2022} }
 @article{czernuszewicz_aji_moore_montgomery_velasco_torres_anand_johnson_deal_zuki_et al._2022, title={Development of a Robotic Shear Wave Elastography System for Noninvasive Staging of Liver Disease in Murine Models}, ISSN={["2471-254X"]}, DOI={10.1002/hep4.1912}, abstractNote={Shear wave elastography (SWE) is an ultrasound-based stiffness quantification technology that is used for noninvasive liver fibrosis assessment. However, despite widescale clinical adoption, SWE is largely unused by preclinical researchers and drug developers for studies of liver disease progression in small animal models due to significant experimental, technical, and reproducibility challenges. Therefore, the aim of this work was to develop a tool designed specifically for assessing liver stiffness and echogenicity in small animals to better enable longitudinal preclinical studies. A high-frequency linear array transducer (12-24 MHz) was integrated into a robotic small animal ultrasound system (Vega; SonoVol, Inc., Durham, NC) to perform liver stiffness and echogenicity measurements in three dimensions. The instrument was validated with tissue-mimicking phantoms and a mouse model of nonalcoholic steatohepatitis. Female C57BL/6J mice (n = 40) were placed on choline-deficient, L-amino acid-defined, high-fat diet and imaged longitudinally for 15 weeks. A subset was sacrificed after each imaging timepoint (n = 5) for histological validation, and analyses of receiver operating characteristic (ROC) curves were performed. Results demonstrated that robotic measurements of echogenicity and stiffness were most strongly correlated with macrovesicular steatosis (R2 = 0.891) and fibrosis (R2 = 0.839), respectively. For diagnostic classification of fibrosis (Ishak score), areas under ROC (AUROCs) curves were 0.969 for ≥Ishak1, 0.984 for ≥Ishak2, 0.980 for ≥Ishak3, and 0.969 for ≥Ishak4. For classification of macrovesicular steatosis (S-score), AUROCs were 1.00 for ≥S2 and 0.997 for ≥S3. Average scanning and analysis time was <5 minutes/liver. Conclusion: Robotic SWE in small animals is feasible and sensitive to small changes in liver disease state, facilitating in vivo staging of rodent liver disease with minimal sonographic expertise.}, journal={HEPATOLOGY COMMUNICATIONS}, author={Czernuszewicz, Tomasz J. and Aji, Adam M. and Moore, Christopher J. and Montgomery, Stephanie A. and Velasco, Brian and Torres, Gabriela and Anand, Keerthi S. and Johnson, Kennita A. and Deal, Allison M. and Zuki, Dzenan and et al.}, year={2022}, month={Feb} }
 @article{hossain_gallippi_2022, title={Quantitative Estimation of Mechanical Anisotropy Using Acoustic Radiation Force (ARF)-Induced Peak Displacements (PD): In Silico and Experimental Demonstration}, volume={41}, ISSN={["1558-254X"]}, DOI={10.1109/TMI.2022.3141084}, abstractNote={Elastic degree of anisotropy (DoA) is a diagnostically relevant biomarker in muscle, kidney, breast, and other organs. Previously, elastic DoA was qualitatively assessed as the ratio of peak displacements (PD) achieved with the long-axis of a spatially asymmetric Acoustic Radiation Force Impulse (ARFI) excitation point spread function (PSF) aligned along versus across the axis of symmetry (AoS) in transversely isotropic materials. However, to better enable longitudinal and cross-sectional analyses, a quantitative measure of elastic DoA is desirable. In this study, qualitative ARFI PD ratios are converted to quantitative DoA, measured as the ratio of longitudinal over transverse shear elastic moduli, using a model empirically derived from Field II and finite element method (FEM) simulations. In silico, the median absolute percent error (MAPE) in ARFI-derived shear moduli ratio (SMR) was 1.75%, and predicted SMRs were robust to variations in transverse shear modulus, Young's moduli ratio, speed of sound, attenuation, density, and ARFI excitation PSF dimension. Further, ARFI-derived SMRs distinguished two materials when the true SMRs of the compared materials differed by as little as 10%. Experimentally, ARFI-derived SMRs linearly correlated with the corresponding ratios measured by Shear Wave Elasticity Imaging (SWEI) in excised pig skeletal muscle ( [Formula: see text], MAPE = 13%) and in pig kidney, in vivo ( [Formula: see text], MAPE = 5.3%). These results demonstrate the feasibility of using the ARFI PD to quantify elastic DoA in biological tissues.}, number={6}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Hossain, Md Murad and Gallippi, Caterina M.}, year={2022}, month={Jun}, pages={1468–1481} }
 @article{yokoyama_nichols_gallippi_2022, title={Quantitative Estimation of Shear Elastic Heterogeneity and Anisotropy in Excised Canine Kidneys using Double Profile Intersection (DoPIo) Ultrasound}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9957981}, abstractNote={Quantitative elastography methods based on dis-placement measurements coaxial to ARFI excitations are ad-vantageous over shear wave-based approaches in heterogeneous and anisotropic tissues, such as kidney, that confound or limit shear wave propagation. Double-Profile Intersection (DoPIo) elastography quantifies shear elasticity by tracking ARF -induced displacements using two different focal configurations, identifying the time at which the profiles intersect, and then estimating modulus from times intersect via FEM-derived models. We demonstrate herein quantitative estimates of shear modulus, elastic regional ratios (RR) between anatomical features, and elastic degree of anisotropy (DoA) using DoPIo ultrasound in dog kidneys. Three ex vivo canine kidney with no known pathologies were imaged, shear elastic modulus was estimated in the renal cortex, medulla, and crest, and DoA and RR were measured in each region and compared against ARFI peak displacements (PD). DoPIo distinguished differences in elasticity between the cortex (median and MAD <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\boldsymbol{9.3\pm 3.1\ \mathbf{kPa}}$</tex> ) and inner parenchymal structures <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$(\boldsymbol{4.8 \pm 0.9}\ \mathbf{kPa};\ \boldsymbol{p\leq 0.0077})$</tex> , and DoPIo-based DoA indicated higher shear elasticity along nephrons versus across them in the renal crest in a consistent manner as PD. Thus, DoPIo may be relevant to on-axis measurement of shear elasticity, elastic RR, and elastic DoA in heterogeneous and anisotropic kidneys.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Yokoyama, Keita A. and Nichols, Timothy C. and Gallippi, Caterina M.}, year={2022} }
 @article{richardson_gallippi_2022, title={Quantitative Viscoelastic Response (QVisR) Domain Adaption with Fine Tuning}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9957979}, abstractNote={Quantitative Viscoelastic Response (QVisR) ultrasound uses in silico on -axis VisR displacement profiles to estimate the elastic and viscous moduli of an interrogated material. This work fine-tunes QVisR models with scanner data acquired in a CIRS elasticity phantom to adapt the modulus estimation domain from simulation to phantom. Before fine-tuning, QVisR is able to distinguish material property relative to others within the same image, however it fails to estimate the actual moduli of the materials within reasonable bounds. After fine-tuning, QVisR much more closely estimates the CIRS phantom moduli while still showing the correct relative trends within images. These results suggest fine tuning can be used to adapt simulation trained Q VisR models to more realistic imaging environments with a small, labeled dataset.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Richardson, Joseph B. and Gallippi, Caterina M.}, year={2022} }
 @article{yokoyama_hossain_caughey_fisher_detweiler_chang_gallippi_2022, title={in vivo VisR Measurements of Viscoelasticity and Viscoelastic Anisotropy in Human Allografted Kidneys Differentiate Interstitial Fibrosis and Graft Rejection}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958358}, abstractNote={Assessment of renal transplant failure typically in-volves nonspecific biomarkers or invasive biopsies, presenting a clinical need for noninvasive imaging modalities that can identify pathologic changes in renal allografts. One approach is Viscoelastic Response (VisR) ultrasound, an acoustic radiation force (ARF)-based imaging method that qualitatively evaluates, relative to the applied ARF amplitude, tissue elasticity (RE) and viscosity (RV). We hypothesize that, by measuring the RE and RV degree of anisotropy (DoA) along versus across nephrons in the cortex and the regional ratio (RR) of RE and RV in the outer versus inner cortex, VisR can discriminate transplanted kidneys with fibrosis and rejection in humans in vivo. VisR imaging was performed in renal transplant patients from 3 to 36 months after transplantation at 3 mo. (quarterly) intervals, coincident with routine clinic visits. RE and RV-based DoA in outer and inner cortices were significantly different between patients with and without biopsy-confirmed interstitial fibrosis up to 4 quarters before the time of clinically indicated biopsies. VisR RE-based RR had similar performance but also differentiated rejected from fibrotic kidney. These results suggest that noninvasive VisR imaging is relevant to early detection of transplant kidney fibrosis and rejection, which could enable timely interventions that extend graft life.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Yokoyama, Keita A. and Hossain, Md. Murad and Caughey, Melissa C. and Fisher, Melrose W. and Detweiler, Randal K. and Chang, Emily H. and Gallippi, Caterina M.}, year={2022} }
 @article{wu_hossain_kim_gallippi_jiang_2021, title={A 1.5-D Array for Acoustic Radiation Force (ARF)-Induced Peak Displacement-Based Tissue Anisotropy Assessment With a Row-Column Excitation Method}, volume={68}, ISSN={["1525-8955"]}, url={https://doi.org/10.1109/TUFFC.2020.3030040}, DOI={10.1109/TUFFC.2020.3030040}, abstractNote={Many biological tissues, including muscle or kidney, are mechanically anisotropic, and the degree of anisotropy (DoA) in mechanical properties is diagnostically relevant. DoA can be assessed either using the ratio of shear wave velocities (SWVs) or acoustic radio forced impulse (ARFI)-induced peak displacements (PD) measured longitudinal over transverse orientations. Whether using SWV or PD as a basis, DoA expressed as the ratio of values requires 90° transducer rotation when a linear array is employed. This large rotation angle is prone to misalignment errors. One solution is the use of a fully sampled matrix array for electronic rotation of point spread function (PSF). However, the challenges of matrix array are its high fabrication cost and complicated fabrication procedures. The cheaper and simpler alternative of matrix array is the use of a row-column array. A 3×64 elements 1.5-D array with a row-column excitation mode is proposed to assess DoA in mechanical properties using the PD ratio. Different numbers of elements in elevational and lateral directions were selected to have orthogonal ARFI excitation beams without rotating the transducer. A custom-designed flex circuit was used to fabricate the array with a simpler electrode connection than a fully sampled matrix array. The performance of the array was evaluated in Field II simulation and experiment. The output pressure was 0.57-MPa output under a 40- [Formula: see text] excitation with a -6-dB point spread dimension of 14×4 mm2 in orthogonal directions. The PD was measured to be [Formula: see text] in an isotropic elastic phantom with Young's modulus of 5.4 kPa. These results suggest that the array is capable of assessing DoA using PD ratio without physical rotation of the transducer. The array has the potential to reduce the misalignment errors for DoA assessment.}, number={4}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, publisher={Institute of Electrical and Electronics Engineers (IEEE)}, author={Wu, Huaiyu and Hossain, Md Murad and Kim, Howuk and Gallippi, Caterina M. and Jiang, Xiaoning}, year={2021}, month={Apr}, pages={1278–1287} }
 @article{phillips_torres_steed_caughey_merhout_kirk_hartman_kuzmiak_ray_gallippi_2021, title={ARFI Variance of Acceleration for Diagnostic Breast Cancer Imaging in Women, in vivo}, ISSN={["1948-5719"]}, DOI={10.1109/IUS52206.2021.9593527}, abstractNote={Early detection of breast cancer greatly aids survival. However, the specificity of current screening methods for identifying malignancy is poor, requiring costly and invasive additional tests and causing anxiety for the patient. Although some ultrasound methods have used mechanical properties to discriminate benign and malignant lesions, they are complicated by tissue features like fluid and necrosis. We propose a new metric, ΔLog(VoA), which can be calculated from ARFI ultrasound data and incorporates the mechanical and acoustic properties of tissue into one parameter. ΔLog(VoA) is statistically significantly lower in fluid- and necrosis-containing masses than solid ones (Wilcoxin, p<0.006). ΔLog(VoA) does not significantly differ between malignant and benign masses. However, it is significantly lower in the surrounding tissue of malignant masses than in the surrounding tissue of benign ones (Wilcoxin, p<0.02). These results suggest that ΔLog(VoA) can differentiate clinically relevant lesion features such as fluid and necrosis, and detect tissue characteristics that coincide with malignancy.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Phillips, Anna V and Torres, Gabriela and Steed, Doreen and Caughey, Melissa C. and Merhout, Jasmin and Kirk, Shanah R. and Hartman, Terry S. and Kuzmiak, Cherie M. and Ray, Emily M. and Gallippi, Caterina M.}, year={2021} }
 @article{yokoyama_anand_gallippi_2021, title={Assessing the Impact of ARF Excitation Beam Width and Tracking Beam Concurrency on DoPIo Imaging Performance in a Calibrated Phantom}, ISSN={["1948-5719"]}, DOI={10.1109/IUS52206.2021.9593658}, abstractNote={Double-profile intersection (DoPIo) ultrasound combines two displacement profiles capturing identical tissue motion following an acoustic radiation force (ARF) push to estimate shear elastic modulus via an empirically derived model. However, the displacement-tracking scheme may be impacted by differences in focal configurations for both the push and track beams. A wider push beam imparts a more uniform displacement gradient than narrow ARF pushes for on-axis tracking beams, while the simultaneous formation of two displacement profiles from a single, wide transmit pulse enables the tracking of identical scatterer distributions at the cost of diminished differences between the two displacement profiles. In silico experiments suggested that DoPIo acquisitions performed using a wide ARF push beam and simultaneous tracking provided the most accurate and precise elasticity estimates. While all four combinations of parameters enabled the differentiation of a soft inclusion within a stiff background in vitro, elasticity estimates on a commercially calibrated phantom were consistently overestimated.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Yokoyama, Keita A. and Anand, Keerthi S. and Gallippi, Caterina M.}, year={2021} }
 @article{torres_caughey_anand_huang_lee_zamora_hung_merricks_ezzell_homeister_et al._2021, title={Atherosclerotic Plaque Characterization in Humans with ARFI Variance of Acceleration: Blinded Reader Study}, ISSN={["1948-5719"]}, DOI={10.1109/IUS52206.2021.9593630}, abstractNote={Stroke is commonly caused by thromboembolic events originating from atherosclerotic plaques in the carotid vasculature. To improve stroke risk prediction by delineating vulnerable plaque features, our group has developed ARFI Variance of Acceleration log(VoA) imaging. We herein evaluate the ability of trained, blinded readers to interpret in vivo ARFI log(VoA) images of human carotid plaques, with validation by matched histology. Patients undergoing carotid endarterectomy were imaged using a Siemens S3000 and a 9L4 transducer. From 21 plaques, one was excluded due to specimen damage during surgery. Parametric 2D images of ARFI log(VoA) were rendered and evaluated by 3 neuroradiologists, 1 abdominal radiologist, 1 sonographer, and 1 pathologist, all blinded to the histological gold standard. Receiver operating characteristic (ROC) curve analysis was performed, and area under the curve (AUC) was taken as a metric of performance for detecting lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Reader log(VoA) outcomes were compared to those achieved using ARFI peak displacement (PD) in a comparable prior study. Average AUC performance for plaque features were as follows: CAL, 0.77; COL, 0.76; LRNC, 0.79; IPH, 0.82. Grouping the stiff (COL and CAL) and soft (LRNC and IPH) features together increased average AUCs to 0.86 for stiff and 0.87 for soft. These log(VoA) AUC outcomes were higher than those achieved by blinded readers evaluating ARFI PD images. This study shows the relevance of ARFI log(VoA) imaging, as interpreted by trained, blinded readers, to delineating the structure and composition of carotid atherosclerotic plaque in humans, in vivo.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Torres, Gabriela and Caughey, Melissa C. and Anand, Keerthi and Huang, Benjamin Y. and Lee, Ellie R. and Zamora, Carlos A. and Hung, Sheng-Che and Merricks, Elizabeth and Ezzell, J. Ashley and Homeister, Jonathon W. and et al.}, year={2021} }
 @article{torres_caughey_anand_homeister_farber_gallippi_2021, title={Automatic Classification of Human Carotid Plaque Features, In Vivo, Using Multiple Forms of ARFI Data}, ISSN={["1948-5719"]}, DOI={10.1109/IUS52206.2021.9593467}, abstractNote={Rupture potential of atherosclerotic plaques in carotid arteries is conferred by both composition and structure of plaques. Previous studies have shown that from in vivo collected data, carotid plaque components such as collagen, calcium, necrotic core and intraplaque hemorrhage can be automatically detected by an ARFI imaging-derived machine learning classifier. Automatic classification considered normalized cross-correlation measurements of ARFI-induced displacement, signal-to-noise ratio and cross-correlation coefficients from an on-axis ARFI acquisition. We now extend our prior work by hypothesizing that using multiple ARFI data forms improves plaque feature detection and FC thickness measurement in human carotid plaques, relative to a single form of ARFI data. Carotid plaques were imaged in vivo prior to surgery in 20 patients undergoing carotid endarterectomy (CEA), and extracted plaque specimens were harvested after CEA for histological processing. ARFI data were acquired with cardiac gating to diastole with push (DP) and to systole without push (SNP) using fundamental low (FL), fundamental high (FH), and harmonic (H) tracking frequencies. Combinations of the resulting displacement profiles were used as inputs to the SVM classifier. The classifier was evaluated by 5-fold cross-validation, with the histological samples acting as gold standards. From the output SVM likelihood matrices, ROC curves were calculated for separating collagen from calcium and lipid-rich necrotic core from intraplaque hemorrhage. For all examined plaques, DP+FH+H achieved the highest average AUC of 0.926 (Sensitivity = 0.932, Specificity = 0.915) but required 2 acquisitions. The best data combination requiring only one acquisition (DP+FH) achieved an AUC of 0.917 (Sensitivity = 0.902, Specificity = 0.880). These results suggest that using multiple forms of frequency and gating of ARFI data as inputs to an automatic classifier improves discrimination of carotid plaque components, relevant for rupture vulnerability assessment.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Torres, Gabriela and Caughey, Melissa C. and Anand, Keerthi and Homeister, Jonathon W. and Farber, Mark A. and Gallippi, Caterina M.}, year={2021} }
 @article{richardson_gallippi_2021, title={Effect of SNR on Quantitative Viscoelastic Response (QVisR) Ultrasound in silico}, ISSN={["1948-5719"]}, DOI={10.1109/IUS52206.2021.9593924}, abstractNote={Quantitative Viscoelastic Response (QVisR) ultrasound uses in silico on-axis VisR displacement profiles to estimate the elastic and viscous moduli of an interrogated material. This work studies the effect of varying the radio frequency (RF) data signal-to-noise ratio (SNR) on QVisR's estimates. White Gaussian noise was added to the RF data of simulated viscoelastic materials subject to a VisR beamsequence with SNRs from 0-50dB in steps of 10dB. Tracked displacements were used as features for a neural network model to estimate elastic and viscous moduli. Predicted elastic moduli RMSE was smaller than the simulated material elastic step size down to 20dB SNR and viscous moduli RMSE was smaller than the viscous step size down to 40dB SNR. These findings suggest QVisR can be used to estimate viscoelastic moduli in noisy environments that more closely model non-simulation data acquisitions.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Richardson, Joseph B. and Gallippi, Caterina M.}, year={2021} }
 @article{hossain_gallippi_2021, title={Electronic Point Spread Function Rotation Using a Three-Row Transducer for ARFI-Based Elastic Anisotropy Assessment: In Silico and Experimental Demonstration}, volume={68}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2020.3019002}, abstractNote={Degree of anisotropy (DoA) of mechanical properties has been assessed as the ratio of acoustic radiation force impulse (ARFI)-induced peak displacements (PDs) achieved using spatially asymmetric point spread functions (PSFs) that are rotated 90° to each other. Such PSF rotation has been achieved by manually rotating a linear array transducer, but manual rotation is cumbersome and prone to misalignment errors and higher variability in measurements. The purpose of this work is to evaluate the feasibility of electronic PSF rotation using a three-row transducer, which will reduce variability in DoA assessment. A Siemens 9L4, with 3×192 elements, was simulated in Field II to generate spatially asymmetric ARFI PSFs that were electronically rotated 63° from each other. Then, using the finite element method (FEM), PD due to the ARFI excitation PSFs in 42 elastic, incompressible, transversely isotropic (TI) materials with shear moduli ratios of 1.0-6.0 were modeled. Finally, the ratio of PDs achieved using the two rotated PSFs was evaluated to assess elastic DoA. DoA increased with increasing shear moduli ratios and distinguished materials with 17% or greater difference in shear moduli ratios (Wilcoxon, ). Experimentally, the ratio of PDs achieved using ARFI PSF rotated 63° from each other distinguished the biceps femoris muscle from two pigs, which had median shear moduli ratios of 4.25 and 3.15 as assessed by shear wave elasticity imaging (SWEI). These results suggest that ARFI-based DoA assessment can be achieved without manual transducer rotation using a three-row transducer capable of electronically rotating PSFs by 63°. It is expected that electronic PSF rotation will facilitate data acquisitions and improve the reproducibility of elastic anisotropy assessments.}, number={3}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Hossain, Md Murad and Gallippi, Caterina M.}, year={2021}, month={Mar}, pages={632–646} }
 @article{anand_gallippi_2021, title={Multiangle PW Compounding Supports ARFI Variance of Acceleration (VoA) Carotid Plaque Imaging for Integration with Vector Doppler}, ISSN={["1948-5719"]}, DOI={10.1109/IUS52206.2021.9593578}, abstractNote={Acoustic Radiation Force Impulse (ARFI) Log Variance of Acceleration (log(VoA)) was previously demonstrated with a single ARFI excitation and plane wave (PW) tracking to detect plaque structure and composition. However, a separate multi-angle sequence was required to enable simultaneous display of 2-D vector-Doppler (VD) and plaque morphology. This paper evaluates the performance of various multi-angle compounded PW implementations of log(VOA). Experiments were conducted in a CIRS elastic phantom and in an excised human cadaveric carotid. In phantoms, increasing SNR by way of compounding increased inclusion SNR and CNR. Increasing the angle range over which PWs were steered decreased SNR, but did not appreciably change CNR. When applied to the ex vivo carotid, an angle range of 10° best predicted calcium area (as validated by spatially-aligned, expert-segmented histology), and higher number of angles spanning 10° improved delineation of plaque boundaries. These results suggest that, compared to an unsteered PW sequence, a multi-angle compounded PW sequence improves log(VoA) performance, suggesting the potential for extension to implementation with concurrent vector Doppler imaging.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Anand, Keerthi S. and Gallippi, Caterina M.}, year={2021} }
 @article{torres_czernuszewicz_homeister_farber_caughey_gallippi_2020, title={Carotid Plaque Fibrous Cap Thickness Measurement by ARFI Variance of Acceleration: In Vivo Human Results}, volume={39}, ISSN={["1558-254X"]}, DOI={10.1109/TMI.2020.3019184}, abstractNote={This study evaluates the performance of an acoustic radiation force impulse (ARFI)-based outcome parameter, the decadic logarithm of the variance of acceleration, or log(VoA), for measuring carotid fibrous cap thickness. Carotid plaque fibrous cap thickness measurement by log(VoA) was compared to that by ARFI peak displacement (PD) in patients undergoing clinically indicated carotid endarterectomy using a spatially-matched histological validation standard. Fibrous caps in parametric log(VoA) and PD images were automatically segmented using a custom clustering algorithm, and a pathologist with expertise in atherosclerosis hand-delineated fibrous caps in histology. Over 10 fibrous caps, log(VoA)-derived thickness was more strongly correlated to histological thickness than PD-derived thickness, with Pearson correlation values of 0.98 for log(VoA) compared to 0.89 for PD. The log(VoA)-derived cap thickness also had better agreement with histology-measured thickness, as assessed by the concordance correlation coefficient (0.95 versus 0.62), and, by Bland-Altman analysis, was more consistent than PD-derived fibrous cap thickness. These results suggest that ARFI log(VoA) enables improved discrimination of fibrous cap thickness relative to ARFI PD and further contributes to the growing body of evidence demonstrating ARFI's overall relevance to delineating the structure and composition of carotid atherosclerotic plaque for stroke risk prediction.}, number={12}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Torres, Gabriela and Czernuszewicz, Tomasz J. and Homeister, Jonathon W. and Farber, Mark A. and Caughey, Melissa C. and Gallippi, Caterina M.}, year={2020}, month={Dec}, pages={4383–4390} }
 @article{hossain_gallippi_2020, title={Viscoelastic Response Ultrasound Derived Relative Elasticity and Relative Viscosity Reflect True Elasticity and Viscosity: In Silico and Experimental Demonstration}, volume={67}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2019.2962789}, abstractNote={Viscoelastic response (VisR) ultrasound characterizes the viscoelastic properties of tissue by fitting acoustic radiation force (ARF)-induced displacements in the region of ARF excitation to a 1-D mass-spring-damper (MSD) model. Elasticity and viscosity are calculated separately but relative to the applied ARF amplitude. We refer to these parameters as "relative elasticity (RE)" and "relative viscosity (RV)." We herein test the hypothesis that RE and RV linearly correlate to true elasticity and viscosity in tissue. VisR imaging was simulated in 144 homogeneous viscoelastic materials with varying elasticities and viscosities. Derived RE linearly correlated with material elasticity and varied by an average of 2.52% when the material viscosity changed from 0.1 to 1.3 Pa · s. Derived RV linearly correlated with material viscosity but varied by an average of 102.5% when material elasticity changed from 3.33 to 20 kPa. The effect of elasticity on RV measurement was compensated using the slope of the linear relationship between RV and natural frequency ( ωtextn ). After compensation, RV [Formula: see text] (elasticity compensated RV) linearly correlated with material viscosity and varied by less than 1.00% on average when the modeled shear elastic modulus changed from 3.3 to 20 kPa. In addition to elasticity compensation, variation in ARF amplitude over depth was compensated, yielding REDC and [Formula: see text]. REDC and [Formula: see text] successfully contrasted elastic and viscous inclusions, respectively, in three simulated phantoms. Experimentally, in the homogeneous oil-in-gelatin phantoms and excised livers, REDC linearly correlated with shear wave dispersion ultrasound vibrometry (SDUV) derived shear elastic modulus, and [Formula: see text] linearly correlated with SDUV-derived shear viscosity. In excised livers containing viscoelastic oil-in-gelatin inclusions, the inclusions were successfully contrasted from the liver background by both REDC and [Formula: see text]. These results suggest that RE and RV are relevant for qualitatively assessing the elastic and viscous properties of tissue.}, number={6}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Hossain, Md Murad and Gallippi, Caterina M.}, year={2020}, month={Jun}, pages={1102–1117} }
 @article{torres_czernuszewicz_homeister_caughey_huang_lee_zamora_farber_marston_huang_et al._2019, title={Delineation of Human Carotid Plaque Features In Vivo by Exploiting Displacement Variance}, volume={66}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2019.2898628}, abstractNote={While in vivo acoustic radiation force impulse (ARFI)-induced peak displacement (PD) has been demonstrated to have high sensitivity and specificity for differentiating soft from stiff plaque components in patients with carotid plaque, the parameter exhibits poorer performance for distinguishing between plaque features with similar stiffness. To improve discrimination of carotid plaque features relative to PD, we hypothesize that signal correlation and signal-to-noise ratio (SNR) can be combined, outright or via displacement variance. Plaque feature detection by displacement variance, evaluated as the decadic logarithm of the variance of acceleration and termed “log(VoA),” was compared to that achieved by exploiting SNR, cross correlation coefficient, and ARFI-induced PD outcome metrics. Parametric images were rendered for 25 patients undergoing carotid endarterectomy, with spatially matched histology confirming plaque composition and structure. On average, across all plaques, log(VoA) was the only outcome metric with values that statistically differed between regions of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Further, log(VoA) achieved the highest contrast-to-noise ratio (CNR) for discriminating between LRNC and IPH, COL and CAL, and grouped soft (LRNC and IPH) and stiff (COL and CAL) plaque components. More specifically, relative to the previously demonstrated ARFI PD parameter, log(VoA) achieved 73% higher CNR between LRNC and IPH and 59% higher CNR between COL and CAL. These results suggest that log(VoA) enhances the differentiation of LRNC, IPH, COL, and CAL in human carotid plaques, in vivo, which is clinically relevant to improving stroke risk prediction and medical management.}, number={3}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Torres, Gabriela and Czernuszewicz, Tomasz J. and Homeister, Jonathon W. and Caughey, Melissa C. and Huang, Benjamin Y. and Lee, Ellie R. and Zamora, Carlos A. and Farber, Mark A. and Marston, William A. and Huang, David Y. and et al.}, year={2019}, month={Mar}, pages={481–492} }
 @article{hossain_detwiler_chang_caughey_fisher_nichols_merricks_raymer_whitford_bellinger_et al._2019, title={Mechanical Anisotropy Assessment in Kidney Cortex Using ARFI Peak Displacement: Preclinical Validation and Pilot In Vivo Clinical Results in Kidney Allografts}, volume={66}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2018.2865203}, abstractNote={The kidney is an anisotropic organ, with higher elasticity along versus across nephrons. The degree of mechanical anisotropy in the kidney may be diagnostically relevant if properly exploited; however, if improperly controlled, anisotropy may confound stiffness measurements. The purpose of this study is to demonstrate the clinical feasibility of acoustic radiation force (ARF)-induced peak displacement (PD) measures for both exploiting and obviating mechanical anisotropy in the cortex of human kidney allografts, in vivo. Validation of the imaging methods is provided by preclinical studies in pig kidneys, in which ARF-induced PD values were significantly higher ( , Wilcoxon) when the transducer executing asymmetric ARF was oriented across versus along the nephrons. The ratio of these PD values obtained with the transducer oriented across versus along the nephrons strongly linearly correlated ( R2 = 0.95 ) to the ratio of shear moduli measured by shear wave elasticity imaging. On the contrary, when a symmetric ARF was implemented, no significant difference in PD was observed ( p > 0.01 ). Similar results were demonstrated in vivo in the kidney allografts of 14 patients. The symmetric ARF produced PD measures with no significant difference ( p > 0.01 ) between along versus across alignments, but the asymmetric ARF yielded PD ratios that remained constant over a six-month observation period post-transplantation, consistent with stable serum creatinine level and urine protein-to-creatinine ratio in the same patient population ( p > 0.01 ). The results of this pilot in vivo clinical study suggest the feasibility of 1) implementing symmetrical ARF to obviate mechanical anisotropy in the kidney cortex when anisotropy is a confounding factor and 2) implementing asymmetric ARF to exploit mechanical anisotropy when mechanical anisotropy is a potentially relevant biomarker.}, number={3}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Hossain, Md Murad and Detwiler, Randal K. and Chang, Emily H. and Caughey, Melissa C. and Fisher, Melrose W. and Nichols, Timothy C. and Merricks, Elizabeth P. and Raymer, Robin A. and Whitford, Margaret and Bellinger, Dwight A. and et al.}, year={2019}, month={Mar}, pages={551–562} }
 @article{selzo_moore_hossain_palmeri_gallippi_2019, title={On the Quantitative Potential of Viscoelastic Response (VisR) Ultrasound Using the One-Dimensional Mass-Spring-Damper Model (vol 63, pg 1276, 2016)}, volume={66}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2018.2883811}, abstractNote={In the original publication of this paper [1], equation (3) contained sign errors for the amplitude of the third and fourth Heaviside functions. The corrected equation is shown in the following: [Formula: see text].}, number={1}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Selzo, Mallory R. and Moore, Christopher J. and Hossain, Md Murad and Palmeri, Mark L. and Gallippi, Caterina M.}, year={2019}, month={Jan}, pages={251–251} }
 @article{hossain_gallippi_2019, title={On the feasibility of quantifying mechanical anisotropy in transversely isotropic elastic materials using acoustic radiation force (ARF)-induced displacements}, volume={10955}, ISSN={["1996-756X"]}, DOI={10.1117/12.2511765}, abstractNote={Many soft tissues, including skeletal muscle and kidney, can be modeled astransversely isotropic (TI) materials defined by an axis of symmetry (AoS) perpendicular to a plane of isotropy. In such materials, mechanical properties differ along versus across the AoS. The degree of mechanical anisotropy in TI materials was previously assessed as the ratio of peak displacement (PD) achieved when the long axis of an asymmetric acoustic radiation force (ARF) excitation point spread function (PSF) was aligned along versus across the material’s AoS, but the measurement was qualitative. The objectives of this work were: (i) to derive an empirical model describing the relationship between the PD ratio and shear moduli ratio; (ii) to investigate the impact of ARF excitation PSF aberration due to speed of sound (c), attenuation (α), and dimension of ARF excitation PSF on the empirical model; and (iii) to estimate mechanical anisotropy in excised pig biceps femoris muscles and in vivo pig kidney using the empirical model. The empirical model was derived by simulating ARF Impulse (ARFI) imaging of ‘train’ TI materials (shear moduli ratios varying from 1.0 to 10 in steps of 0.75) and validated on ‘test’ materials (shear moduli ratios varying from 1.25 to 8.75 in steps of 0.75) using finite element method (FEM) models. Siemens VF73 transducer parameter with lateral F/1.5 was simulated for ARFI imaging. The speed of sound and attenuation was set to1540 ms-1 and 0.5 dB/cm/MHZ, respectively for train materials and was set to1540 or 1620 ms-1 and 0.5 or 1.0 dB/cm/MHZ, respectively for test materials. To find the impact of ARF excitation PSF dimension, a matrix array was simulated and the lateral and elevational F/# was set to 2.0 and 3.4, respectively for train materials and was set to 2.0 or 3.0 and 3.4 or 5.1, respectively for test materials. Ultrasound tracking of FEM displacements was performed in Field II with an SNR of 30 dB. The average absolute percent error in predicting shear moduli ratio of all ‘test’ materials was 1.6%. The empirical model was not impacted by the deviation from expected attenuation, sound speed, and ARF excitation PSF dimension. Shear moduli ratios derived using the empirical model matched those derived from shear wave elasticity imaging (SWEI) in pig muscle (model: 4.44 ± 0.47 and SWEI: 4.38 ± 0.27), renal medulla (model: 1.31 ± 0.07 and SWEI: 1.32 ± 0.04) and renal cortex (model: 2.0 ± 0.19 and SWEI: 1.99 ± 0.06). These results suggest the feasibility of using the PD empirical model to quantify mechanical anisotropy in biological tissues.}, journal={MEDICAL IMAGING 2019: ULTRASONIC IMAGING AND TOMOGRAPHY}, author={Hossain, Md Murad and Gallippi, Caterina M.}, year={2019} }
 @article{gallippi_dahl_2019, title={Special Issue on Pilot Clinical Translation of New Medical Ultrasound Methodologies}, volume={66}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2019.2902085}, abstractNote={Ultrasound imaging is uniquely relevant in the modern era of clinical medicine. While the fundamental platform remains low-cost and portable, meeting demands for cost-efficient diagnostic and therapeutic options in the context of constrained medical resources, technology development races forward to achieve applications that were not possible just years ago. A vital first step to translating these cutting-edge ultrasound methods to clinical implementation is performing pilot studies in humans, in vivo. Initial human studies are critical because they demonstrate the feasibility of new methodologies in the context of complex tissue environments with unknown parameters and when penetration requirements and complicated noise sources interfere with signal detection. Furthermore, developing methods for validating outcome measures in the complex and unknown in vivo human setting is difficult. Finally, the logistics associated with obtaining regulatory approval for conducting human studies, the time required to recruit subjects, and the associated expenses compound the technical challenges.}, number={3}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Gallippi, Caterina M. and Dahl, Jeremy J.}, year={2019}, month={Mar}, pages={423–424} }
 @article{hossain_levy_thapa_oldenburg_gallippi_2018, title={Blind Source Separation-Based Motion Detector for Imaging Super-Paramagnetic Iron Oxide (SPIO) Particles in Magnetomotive Ultrasound Imaging}, volume={37}, ISSN={["1558-254X"]}, DOI={10.1109/TMI.2018.2848204}, abstractNote={In magnetomotive ultrasound (MMUS) imaging, an oscillating external magnetic field displaces tissue loaded with super-paramagnetic iron oxide (SPIO) particles. The induced motion is on the nanometer scale, which makes its detection and its isolation from background motion challenging. Previously, a frequency and phase locking (FPL) algorithm was used to suppress background motion by subtracting magnetic field off ( -off) from on ( -on) data. Shortcomings to this approach include long tracking ensembles and the requirement for -off data. In this paper, a novel blind source separation-based FPL (BSS-FPL) algorithm is presented for detecting motion using a shorter ensemble length (EL) than FPL and without -off data. MMUS imaging of two phantoms containing an SPIO-laden cubical inclusion and one control phantom was performed using an open-air MMUS system. When background subtraction was used, contrast and contrast to noise ratio (CNR) were, respectively, 1.20±0.20 and 1.56±0.34 times higher in BSS-FPL as compared to FPL-derived images for EL < 3.5 s. However, contrast and CNR were similar for BSS-FPL and FPL for EL ≥ 3.5 s. When only -on data was used, contrast and CNR were 1.94 ± 0.21 and 1.56 ± 0.28 times higher, respectively, in BSS-FPL as compared to FPL-derived images for all ELs. Percent error in the estimated width and height was 39.30% ± 19.98% and 110.37% ± 6.5% for FPL and was 7.30% ± 7.6% and 16.21% ± 10.29% for BSS-FPL algorithm. This paper is an important step toward translating MMUS imaging to in vivo application, where long tracking ensembles would increase acquisition time and -off data may be misaligned with -on due to physiological motion.}, number={10}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Hossain, Md Murad and Levy, Benjamin E. and Thapa, Diwash and Oldenburg, Amy L. and Gallippi, Caterina M.}, year={2018}, month={Oct}, pages={2356–2366} }
 @article{hossain_selzo_hinson_baggesen_detwiler_chong_burke_caughey_fisher_whitehead_et al._2018, title={EVALUATING RENAL TRANSPLANT STATUS USING VISCOELASTIC RESPONSE (VISR) ULTRASOUND}, volume={44}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2018.03.016}, abstractNote={Chronic kidney disease is most desirably and cost-effectively treated by renal transplantation, but graft survival is a major challenge. Although irreversible graft damage can be averted by timely treatment, intervention is delayed when early graft dysfunction goes undetected by standard clinical metrics. A more sensitive and specific parameter for delineating graft health could be the viscoelastic properties of the renal parenchyma, which are interrogated non-invasively by Viscoelastic Response (VisR) ultrasound, a new acoustic radiation force (ARF)-based imaging method. Assessing the performance of VisR imaging in delineating histologically confirmed renal transplant pathologies in vivo is the purpose of the study described here. VisR imaging was performed in patients with (n = 19) and without (n = 25) clinical indication for renal allograft biopsy. The median values of VisR outcome metrics (τ, relative elasticity [RE] and relative viscosity [RV]) were calculated in five regions of interest that were manually delineated in the parenchyma (outer, center and inner) and in the pelvis (outer and inner). The ratios of a given VisR metric for all possible region-of-interest combinations were calculated, and the corresponding ratios were statistically compared between biopsied patients subdivided by diagnostic categories versus non-biopsied, control allografts using the two-sample Wilcoxon test (p <0.05). Although τ ratios non-specifically differentiated allografts with vascular disease, tubular/interstitial scarring, chronic allograft nephropathy and glomerulonephritis from non-biopsied control allografts, RE distinguished only allografts with vascular disease and tubular/interstitial scarring, and RV distinguished only vascular disease. These results suggest that allografts with scarring and vascular disease can be identified using non-invasive VisR RE and RV metrics.}, number={8}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Hossain, Md Murad and Selzo, Mallory R. and Hinson, Robert M. and Baggesen, Leslie M. and Detwiler, Randal K. and Chong, Wui K. and Burke, Lauren M. and Caughey, Melissa C. and Fisher, Melrose W. and Whitehead, Sonya B. and et al.}, year={2018}, month={Aug}, pages={1573–1584} }
 @article{moore_caughey_meyer_emmett_jacobs_chopra_howard_gallippi_2018, title={IN VIVO VISCOELASTIC RESPONSE (VISR) ULTRASOUND FOR CHARACTERIZING MECHANICAL ANISOTROPY IN LOWER-LIMB SKELETAL MUSCLES OF BOYS WITH AND WITHOUT DUCHENNE MUSCULAR DYSTROPHY}, volume={44}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2018.07.004}, abstractNote={Our group has previously found that in silico, mechanical anisotropy may be interrogated by exciting transversely isotropic materials with geometrically asymmetric acoustic radiation force excitations and then monitoring the associated induced displacements in the region of excitation. We now translate acoustic radiation force-based anisotropy assessment to human muscle in vivo and investigate its clinical relevance to monitoring muscle degeneration in Duchenne muscular dystrophy (DMD). Clinical anisotropy assessments were performed using Viscoelastic Response ultrasound, with a degree of anisotropy reflected by the ratios of Viscoelastic Response relative elasticity (RE) or relative viscosity (RV) measured with the asymmetric radiation force oriented parallel versus perpendicular to muscle fiber alignment. In vivo results from rectus femoris and gastrocnemius muscles of boys aged ∼7.9–10.4 y indicate that RE and RV anisotropy ratios in rectus femoris muscles of boys with DMD were significantly higher than those of healthy control boys (RE: DMD = 1.51 ± 0.87, control = 0.99 ± 0.69, p = 0.04, Wilcoxon rank sum test; RV: DMD = 1.04 ± 0.71, control = 0.74 ± 0.22, p = 0.02). In the gastrocnemius muscle, only the RV anisotropy ratio was significantly higher in dystrophic than control patients (DMD = 1.23 ± 0.35, control = 0.88 ± 0.31, p = 0.04). In the dystrophic rectus femoris muscle, the RE anisotropy ratio was inversely correlated (slope = –0.03/lbf, r = –0.43, p = 0.07, Pearson correlation) with quantitative muscle testing functional output measures but was not correlated with quantitative muscle testing in the dystrophic gastrocnemius. These results suggest that Viscoelastic Response RE and RV measures reflect differences in mechanical anisotropy associated with functional impairment with dystrophic degeneration that are relevant to monitoring DMD clinically.}, number={12}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Moore, Christopher J. and Caughey, Melissa C. and Meyer, Diane O. and Emmett, Regina and Jacobs, Catherine and Chopra, Manisha and Howard, James F., Jr. and Gallippi, Caterina M.}, year={2018}, month={Dec}, pages={2519–2530} }
 @inproceedings{torres_czernuszewicz_homeister_farber_gallippi_2017, title={ARFI variance of acceleration (VoA) for noninvasive characterization of human carotid plaques in vivo}, DOI={10.1109/embc.2017.8037484}, abstractNote={Rather than degree of stenosis, assessing plaque structure and composition is relevant to discerning risk for plaque rupture with downstream ischemic event. The structure and composition of carotid plaque has been assessed noninvasively using Acoustic Radiation Force Impulse (ARFI) ultrasound imaging. In particular, ARFI-derived peak displacement (PD) estimations have been demonstrated for discriminating soft (lipid rich necrotic core (LRNC) or intraplaque hemorrhage (IPH)) from stiff (collagen (COL) or calcium (CAL)) plaque features; however, PD did not differentiate LRNC from IPH or COL from CAL. The purpose of this study is to evaluate a new ARFI-based measurement, the variance of acceleration (VoA), for differentiating among soft and stiff plaque components. Both PD and VoA results were obtained in vivo for a human carotid plaque acquired in a previous study and matched to a histological standard analyzed by a pathologist. With VoA, plaque feature contrast was increased by an average of 60% in comparison to PD.}, booktitle={Proceedings of annual international conference of the ieee engineering}, author={Torres, G. and Czernuszewicz, T. J. and Homeister, J. W. and Farber, M. A. and Gallippi, C. M.}, year={2017}, pages={2984–2987} }
 @article{hossain_moore_gallippi_2017, title={Acoustic Radiation Force Impulse-Induced Peak Displacements Reflect Degree of Anisotropy in Transversely Isotropic Elastic Materials}, volume={64}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2017.2690223}, abstractNote={In transversely isotropic (TI) materials, mechanical properties (Young's modulus, shear modulus, and Poisson's ratio) are different along versus across the axis of symmetry (AoS). In this work, the feasibility of interrogating such directional mechanical property differences using acoustic radiation force impulse (ARFI) imaging is investigated. We herein test the hypotheses that 1) ARFI-induced peak displacements (PDs) vary with TI material orientations when an asymmetrical ARFI excitation point spread function (PSF) is used, but not when a symmetrical ARFI PSF is employed; and 2) the ratio of PDs induced with the long axis of an asymmetrical ARFI PSF oriented along versus across the material's AoS is related to the degree of anisotropy of the material. These hypotheses were tested in silico using finite element method (FEM) models and Field II. ARFI excitations had F/1.5, 3, 4, or 5 focal configurations, with the F/1.5 and F/5 cases having the most asymmetrical and symmetrical PSFs at the focal depth, respectively. These excitations were implemented for ARFI imaging in 52 different simulated TI materials with varying degrees of anisotropy, and the ratio of ARFI-induced PDs was calculated. The change in the ratio of PDs with respect to the anisotropy of the materials was highest for the F/1.5, indicating that PD was most strongly impacted by the material orientation when the ARFI excitation was the most asymmetrical. On the contrary, the ratio of PDs did not depend on the anisotropy of the material for the F/5 ARFI excitation, suggesting that PD did not depend on material orientation when the ARFI excitation was symmetrical. Finally, the ratio of PDs achieved using asymmetrical ARFI PSF reflected the degree of anisotropy in TI materials. These results support that symmetrical ARFI focal configurations are desirable when the orientation of the ARFI excitation to the AoS is not specifically known and measurement standardization is important, such as for longitudinal or cross-sectional studies of anisotropic organs. However, asymmetrical focal configurations are useful for exploiting anisotropy, which may be diagnostically relevant. Feasibility for future experimental implementation is demonstrated by simulating ultrasonic displacement tracking and by varying the ARF duration.}, number={6}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Hossain, Md Murad and Moore, Christopher J. and Gallippi, Caterina M.}, year={2017}, month={Jun}, pages={989–1001} }
 @article{czernuszewicz_homeister_caughey_wang_zhu_huang_lee_zamora_farber_fulton_et al._2017, title={Performance of acoustic radiation force impulse ultrasound imaging for carotid plaque characterization with histologic validation}, volume={66}, ISSN={["0741-5214"]}, DOI={10.1016/j.jvs.2017.04.043}, abstractNote={ObjectiveStroke is commonly caused by thromboembolic events originating from ruptured carotid plaque with vulnerable composition. This study assessed the performance of acoustic radiation force impulse (ARFI) imaging, a noninvasive ultrasound elasticity imaging method, for delineating the composition of human carotid plaque in vivo with histologic validation.MethodsCarotid ARFI images were captured before surgery in 25 patients undergoing clinically indicated carotid endarterectomy. The surgical specimens were histologically processed with sectioning matched to the ultrasound imaging plane. Three radiologists, blinded to histology, evaluated parametric images of ARFI-induced peak displacement to identify plaque features such as necrotic core (NC), intraplaque hemorrhage (IPH), collagen (COL), calcium (CAL), and fibrous cap (FC) thickness. Reader performance was measured against the histologic standard using receiver operating characteristic curve analysis, linear regression, Spearman correlation (ρ), and Bland-Altman analysis.ResultsARFI peak displacement was two-to-four-times larger in regions of NC and IPH relative to regions of COL or CAL. Readers detected soft plaque features (NC/IPH) with a median area under the curve of 0.887 (range, 0.867-0.924) and stiff plaque features (COL/CAL) with median area under the curve of 0.859 (range, 0.771-0.929). FC thickness measurements of two of the three readers correlated with histology (reader 1: R2 = 0.64, ρ = 0.81; reader 2: R2 = 0.89, ρ = 0.75).ConclusionsThis study suggests that ARFI is capable of distinguishing soft from stiff atherosclerotic plaque components and delineating FC thickness.}, number={6}, journal={JOURNAL OF VASCULAR SURGERY}, author={Czernuszewicz, Tomasz J. and Homeister, Jonathon W. and Caughey, Melissa C. and Wang, Yue and Zhu, Hongtu and Huang, Benjamin Y. and Lee, Ellie R. and Zamora, Carlos A. and Farber, Mark A. and Fulton, Joseph J. and et al.}, year={2017}, month={Dec}, pages={1749-+} }
 @article{zhang_yu_wang_hanne_cui_qian_wang_xin_cole_gallippi_et al._2017, title={Thrombin-responsive transcutaneous patch for auto-anticoagulant regulation}, volume={29}, DOI={10.1002/adma.201770028}, abstractNote={A thrombin-responsive microneedle-based transcutaneous patch is developed by C. M. Gallippi, Y. Zhu, Z. Gu, and co-workers, as demonstrated in article 1604043. The anticoagulant drug heparin is loaded into the hyaluronic acid needles through a thrombin cleavable peptide linker. This heparin patch can sense the thrombin level in blood vessels and autoregulate blood coagulation in a long-term manner. Cover design credit: Yuqi Zhang.}, number={4}, journal={Advanced Materials}, author={Zhang, Y. Q. and Yu, J. C. and Wang, J. Q. and Hanne, N. J. and Cui, Z. and Qian, C. G. and Wang, C. and Xin, H. L. and Cole, Jacqueline and Gallippi, C. M. and et al.}, year={2017} }
 @inproceedings{czernuszewicz_homeister_caughey_huang_lee_zamora_farber_fulton_ford_marston_et al._2016, title={Carotid plaque characterization with ARFI imaging: Blinded reader study}, DOI={10.1109/ultsym.2016.7728873}, abstractNote={Stroke is commonly caused by thromboembolic events originating from vulnerable atherosclerotic plaque in the carotid vasculature. The purpose of this study was to evaluate the ability of acoustic radiation force impulse (ARFI) imaging, a noninvasive elastography imaging technique, to assess the composition of carotid artery plaques using histologic examination as the gold standard. Twenty-five patients undergoing carotid endarterectomy (CEA) were enrolled and imaged with ARFI. After surgery, extracted specimens were histologically processed and matched to the ultrasound imaging plane. Parametric 2D ARFI images of peak displacement (PD) were evaluated by three radiologists blinded to the histology result. Receiver operating characteristic (ROC) curve analysis was performed, and area under the ROC curve (AUC) was taken as a metric of performance for detecting plaque features such as necrotic core (NC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Additionally, linear regression was performed on fibrous cap (FC) thickness measurements. Areas of plaque with NC and IPH were observed to have substantially increased ARFI PD (2× to 4×) compared to areas of plaque with COL or CAL. Median AUC for detecting soft plaque features (NC/IPH) was 0.887 (range: 0.867 – 0.924) and stiff plaque features (COL/CAL) was 0.859 (range: 0.771 – 0.929). FC thickness measured by two of the three radiologists matched closely with histology (reader 1: R2 = 0.64; reader 2: R2 = 0.89). This study suggests that ARFI is capable of distinguishing soft from stiff compositional elements of atherosclerotic plaques and may be relevant to improving plaque risk assessment.}, booktitle={2016 ieee international ultrasonics symposium (ius)}, author={Czernuszewicz, T. J. and Homeister, J. W. and Caughey, M. C. and Huang, B. Y. and Lee, E. R. and Zamora, C. A. and Farber, M. A. and Fulton, J. J. and Ford, P. F. and Marston, W. A. and et al.}, year={2016} }
 @inproceedings{moore_selzo_caughey_meyer_emmett_howard_chopra_gallippi_2016, title={Cross-sectional comparison of in vivo viscoelastic response (VisR) ultrasound in lower limb muscles of boys with and without Duchenne muscular dystrophy}, DOI={10.1109/ultsym.2016.7728722}, abstractNote={Duchenne muscular dystrophy (DMD) is a genetic disorder that causes progressive muscle degeneration involving necrosis and inflammation, with subsequent replacement of muscle fibers by fibrosis and fatty tissue. These compositional changes underlie mechanical property alterations in affected muscles, which may be assessed using Viscoelastic Response (VisR) ultrasound. We hypothesize that VisR will delineate differences in the viscoelastic properties of lower limb skeletal muscles in boys with versus without DMD. VisR imaging was performed in the vastus intermedius (VI), rectus femoris (RF), sartorius (SM) and gastrocnemius (GM) muscles of seven boys (4 DMD, 3 control) aged 7.9 – 10.4 years. Parametric images of relative elasticity (RE) and relative viscosity (RV) were rendered. From the parametric images, percent muscle area with relatively high RE or RV value was calculated and compared (Wilcoxon rank-sum) between DMD and control on a per-muscle basis. In the VI, RF and SM, percent muscle with relatively high RV was larger (VI: 17.7% v. 13.1% RF: 98.9% v. 93.7%, SM: 43.2% v. 40.6% p < 0.05) in DMD than control muscles. In the VI, percent muscle with relatively high RE was larger (32.8% v. 29.5%, p < 0.05) in DMD muscles. No significant differences were observed in the GM between DMD and control. VisR results were consistent with temporally-matched functional testing using a hand-held dynamometer, which showed 40.5% to 70.0% lower force output in DMD RF, VL and SM - and only 21.8% lower force output in DMD GM - relative to the corresponding control muscles. These results suggest that VisR imaging is relevant to delineating viscoelastic property alterations that are associated with dystrophic muscle degeneration in boys with DMD, in vivo.}, booktitle={2016 ieee international ultrasonics symposium (ius)}, author={Moore, C. J. and Selzo, M. R. and Caughey, M. C. and Meyer, D. O. and Emmett, R. and Howard, J. F. and Chopra, M. and Gallippi, C. M.}, year={2016} }
 @article{wang_li_czernuszewicz_gallippi_liu_geng_jiang_2016, title={Design, Fabrication, and Characterization of a Bifrequency Colinear Array}, volume={63}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2015.2506000}, abstractNote={Ultrasound imaging with high resolution and large penetration depth has been increasingly adopted in medical diagnosis, surgery guidance, and treatment assessment. Conventional ultrasound works at a particular frequency, with a - 6-dB fractional bandwidth of ~ 70% , limiting the imaging resolution or depth of field. In this paper, a bifrequency colinear array with resonant frequencies of 8 and 20 MHz was investigated to meet the requirements of resolution and penetration depth for a broad range of ultrasound imaging applications. Specifically, a 32-element bifrequency colinear array was designed and fabricated, followed by element characterization and real-time sectorial scan (S-scan) phantom imaging using a Verasonics system. The bifrequency colinear array was tested in four different modes by switching between low and high frequencies on transmit and receive. The four modes included the following: 1) transmit low, receive low; 2) transmit low, receive high; 3) transmit high, receive low; and 4) transmit high, receive high. After testing, the axial and lateral resolutions of all modes were calculated and compared. The results of this study suggest that bifrequency colinear arrays are potential aids for wideband fundamental imaging and harmonic/subharmonic imaging.}, number={2}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Wang, Zhuochen and Li, Sibo and Czernuszewicz, Tomasz J. and Gallippi, Caterina M. and Liu, Ruibin and Geng, Xuecang and Jiang, Xiaoning}, year={2016}, month={Feb}, pages={266–274} }
 @article{czernuszewicz_gallippi_2016, title={On the Feasibility of Quantifying Fibrous Cap Thickness With Acoustic Radiation Force Impulse (ARFI) Ultrasound}, volume={63}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2016.2535440}, abstractNote={Acute cerebrovascular accidents are associated with the rupture of vulnerable atherosclerotic plaques in the carotid arteries. Fibrous cap (FC) thickness has been shown to be an important predictor of plaque rupture but has been challenging to measure accurately with clinical noninvasive imaging modalities. The goals of this investigation were first, to evaluate the feasibility of using transcutaneous acoustic radiation force impulse (ARFI) ultrasound to quantify FC thickness and second, to optimize both imaging and motion-tracking parameters to support such measurements. FCs with varying thickness (0.1-1.0 mm) were simulated using a simple-layered geometry, and their mechanical response to an impulse of radiation force was solved using finite-element method (FEM) modeling. Ultrasound tracking of FEM displacements was performed in Field II utilizing three center frequencies (6, 9, and 12 MHz) and eight motion-tracking kernel lengths ( 0.5λ-4λ). Additionally, FC thickness in two carotid plaques imaged in vivo was measured with ARFI and compared to matched histology. The results of this study demonstrate that 1) tracking pulse frequencies around 12 MHz are necessary to resolve caps around 0.2 mm; 2) large motion-tracking kernel sizes introduce bias into thickness measurements and overestimate the true cap thickness; and 3) color saturation settings on ARFI peak displacement images can impact thickness measurement accuracy substantially.}, number={9}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Czernuszewicz, Tomasz J. and Gallippi, Caterina M.}, year={2016}, month={Sep}, pages={1262–1275} }
 @article{selzo_moore_hossain_palmeri_gallippi_2016, title={On the Quantitative Potential of Viscoelastic Response (VisR) Ultrasound Using the One-Dimensional Mass-Spring-Damper Model}, volume={63}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2016.2539323}, abstractNote={Viscoelastic response (VisR) ultrasound is an acoustic radiation force (ARF)-based imaging method that fits induced displacements to a one-dimensional (1-D) mass-spring-damper (MSD) model to estimate the ratio of viscous to elastic moduli, τ, in viscoelastic materials. Error in VisR τ estimation arises from inertia and acoustic displacement underestimation. These error sources are herein evaluated using finite-element method (FEM) simulations, error correction methods are developed, and corrected VisR τ estimates are compared with true simulated τ values to assess VisR's relevance to quantifying viscoelasticity. With regard to inertia, adding a mass term in series with the Voigt model, to achieve the MSD model, accounts for inertia due to tissue mass when ideal point force excitations are used. However, when volumetric ARF excitations are applied, the induced complex system inertia is not described by the single-degree-of-freedom MSD model, causing VisR to overestimate τ. Regarding acoustic displacement underestimation, associated deformation of ARF-induced displacement profiles further distorts VisR τ estimates. However, median error in VisR τ is reduced to approximately -10% using empirically derived error correction functions applied to simulated viscoelastic materials with viscous and elastic properties representative of tissue. The feasibility of corrected VisR imaging is then demonstrated in vivo in the rectus femoris muscle of an adult with no known neuromuscular disorders. These results suggest VisR's potential relevance to quantifying viscoelastic properties clinically.}, number={9}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Selzo, Mallory R. and Moore, Christopher J. and Hossain, Md. Murad and Palmeri, Mark L. and Gallippi, Caterina M.}, year={2016}, month={Sep}, pages={1276–1287} }
 @inproceedings{hossain_moore_gallippi_2016, title={On the quantitative potential of viscoelastic response (VisR) ultrasound using matrix array transducers: In silico demonstration}, DOI={10.1109/ultsym.2016.7728878}, abstractNote={VisR ultrasound is an acoustic radiation force (ARF)-based imaging method that fits induced displacements to a 1D mass-spring-damper (MSD) model to estimate the ratio of viscous to elastic moduli, τ, in viscoelastic materials. A source of error in VisR τ estimation is complex and interrelated 3D system inertia. We hypothesize that error due to system inertia may be reduced by minimizing the volumetric extent of the employed ARF excitations, i.e. by reducing elevational and lateral F/#s using a matrix array transducer. This hypothesis was tested in silico using finite element method (FEM) models and Field II simulating homogeneous viscoelastic materials and viscoelastic materials with inclusions. In homogeneous viscoelastic materials, decreasing the elevational F/# from 5.0 to 0.75 yielded 62.5%, 96.7%, and 223.69% decreases in the median percent error in VisR τ estimates in materials with Young's modulus of 10, 50, and 100 kPa, respectively. In viscoelastic materials with inclusions, the elevational F/0.75 focal configuration better delineated inclusion borders in comparison to F/5.0, and measured contrast was closer to the true contrast. The CNRs achieved using elevational F/0.75 was 1.25 – 5.0 times higher than those from F/5.0. These results show that as the volumetric extent of ARF excitations decreases by reducing the elevational F/#, VisR τ estimates more closely approximate the true material τ. These results suggest that error in quantitative VisR τ estimates would be reduced by using a transducer capable of elevational focusing.}, booktitle={2016 ieee international ultrasonics symposium (ius)}, author={Hossain, M. M. and Moore, C. and Gallippi, C.}, year={2016} }
 @article{wang_jiang_czernuszewicz_gallippi_2015, title={Dual-frequency IVUS transducer for acoustic radiation force impulse (ARFI) imaging}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2015.0119}, abstractNote={Coronary atherosclerotic disease is the major cause of mortality in the United States. Elasticity imaging techniques such as acoustic radiation force impulse (ARFI) imaging using intravascular ultrasound (IVUS) transducers can be used to characterize coronary plaque. Conventional IVUS transducers with frequencies of 20 MHz – 60 MHz are not optimized for high-voltage, long-duration pulses required for ARFI imaging. In this work, a dual-frequency IVUS transducer, consisting of a 6.5 MHz “pushing” element and a 26 MHz “tracking” element, was designed and fabricated for ARFI application. In ARFI testing with a 160 V, 1000-cycle burst excitation, a displacement of 12.3 µm was detected in a phantom with a Young's modulus of 10 kPa at an axial depth of 3.5 mm. The result of this study suggests great potential of this dual-frequency IVUS transducer for intravascular ARFI imaging.}, journal={2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Wang, Zhuochen and Jiang, Xiaoning and Czernuszewicz, Tomasz J. and Gallippi, Caterina M.}, year={2015} }
 @article{czernuszewicz_homeister_caughey_farber_fulton_ford_marston_vallabhaneni_nichols_gallippi_2015, title={NON-INVASIVE IN VIVO CHARACTERIZATION OF HUMAN CAROTID PLAQUES WITH ACOUSTIC RADIATION FORCE IMPULSE ULTRASOUND: COMPARISON WITH HISTOLOGY AFTER ENDARTERECTOMY}, volume={41}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2014.09.016}, abstractNote={Ischemic stroke from thromboembolic sources is linked to carotid artery atherosclerotic disease with a trend toward medical management in asymptomatic patients. Extent of disease is currently diagnosed by non-invasive imaging techniques that measure luminal stenosis, but it has been suggested that a better biomarker for determining risk of future thromboembolic events is plaque morphology and composition. Specifically, plaques that are composed of mechanically soft lipid/necrotic regions covered by thin fibrous caps are the most vulnerable to rupture. An ultrasound technique that non-invasively interrogates the mechanical properties of soft tissue, called acoustic radiation force impulse (ARFI) imaging, has been developed as a new modality for atherosclerotic plaque characterization using phantoms and atherosclerotic pigs, but the technique has yet to be validated in vivo in humans. In this preliminary study, in vivo ARFI imaging is presented in a case study format for four patients undergoing clinically indicated carotid endarterectomy and compared with histology. In two type Va plaques, characterized by lipid/necrotic cores covered by fibrous caps, mean ARFI displacements in focal regions were high relative to the surrounding plaque material, suggesting soft features were covered by stiffer layers within the plaques. In two type Vb plaques, characterized by heavy calcification, mean ARFI peak displacements were low relative to the surrounding plaque and arterial wall, suggesting stiff tissue. This pilot study illustrates the feasibility and challenges of transcutaneous ARFI for characterizing the material and structural composition of carotid atherosclerotic plaques via mechanical properties, in humans, in vivo.}, number={3}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Czernuszewicz, Tomasz J. and Homeister, Jonathon W. and Caughey, Melissa C. and Farber, Mark A. and Fulton, Joseph J. and Ford, Peter F. and Marston, William A. and Vallabhaneni, Raghuveer and Nichols, Timothy C. and Gallippi, Caterina M.}, year={2015}, month={Mar}, pages={685–697} }
 @article{moore_selzo_caughey_meyer_emmett_howard_chopra_gallippi_2015, title={Viscoelastic Response (VisR) Assessment of Longitudinal Dystrophic Degeneration in Clinical Duchenne Muscular Dystrophy}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2015.0225}, abstractNote={Viscoelastic Response (VisR) imaging is an acoustic radiation force (ARF)-based ultrasonic technique for estimating the viscoelastic properties of tissue. It has been proposed as a method for monitoring degeneration in the skeletal muscles of boys with Duchenne muscular dystrophy (DMD). DMD causes progressive inflammation, necrosis, fibrosis and fatty deposition in muscle, all of which will alter the elasticity and viscosity of the tissue. The motivation of this work is to investigate VisR's potential as method for monitoring dystrophic muscle degeneration, in vivo, in boys with DMD. In an ongoing longitudinal clinical study, muscles in the lower limbs of boys affected with DMD and age-matched healthy control boys are imaged using VisR thrice yearly for four years. A case study of serial imaging results in the Medial Gastrocnemius (GM) muscle of one boy with DMD is herein presented. Beginning at age 6.2 years, parametric VisR images of τ, or the ratio of viscosity to elasticity, show a growing region of high τ (>1.2 ms) over the span of one year. This result is consistent with expected progressive inflammation and fatty deposition early in the GM's degenerative cycle. Over the course of the next four months, the area of high τ decreases, which is in agreement with the expected onset of muscle fibrosis. Then, at age 8.3 years, small and diffusely distributed high τ regions are observed in the muscle, consistent with expected distributed fatty depositions. These results suggest that VisR, a noninvasive ultrasound imaging method, may be clinically viable for monitoring local muscular compositional and structural changes associated with dystrophic degeneration, in vivo.}, journal={2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Moore, Christopher J. and Selzo, Mallory R. and Caughey, Melissa C. and Meyer, Diane O. and Emmett, Regina and Howard, James F., Jr. and Chopra, Manisha and Gallippi, Caterina M.}, year={2015} }
 @article{czernuszcwicz_gallippi_wang_ma_jiang_2014, title={Acoustic radiation force (ARF) generation with a novel dual-frequency intravascular transducer.}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0569}, abstractNote={Atherosclerosis and coronary artery disease remain the leading cause of death in the US. Coronary plaque is visualized with intravascular ultrasound (IVUS) and is typically implemented with high center frequencies (>20 MHz) for superior spatial resolution. Coronary plaque characterization may be improved by implementing elasticity imaging techniques such as acoustic radiation force impulse (ARFI) imaging using IVUS transducers. In this work we propose to extend ARFI imaging to a novel, dual-frequency small-aperture transducer design that includes a low-frequency “pushing” element and a high-frequency “tracking” element. A 40 MHz element (0.6 mm × 0.6 mm) was integrated onto a 5 MHz element (0.6 mm × 3 mm). Both elements of the transducer were fabricated from single crystal PMN-PT and the whole transducer was mounted on a 20 gauge needle tip. ARF-induced motion from the low-frequency element was quantified using optical tracking methods in a translucent phantom (∼8 kPa) containing embedded graphite microparticles. Displacements induced by ARF excitations with 300, 600, 900, and 1200 cycles (5 MHz, 190 V) were captured and compared to baseline. Median (inter-quartile range) peak displacements for 300, 600, 900, and 1200 cycles were 0.33 (0.27 – 0.39) µm, 0.72 (0.62 – 0.87) µm, 1.1 (1.0 – 1.3) µm, and 1.6 (1.43 – 1.75) µm, respectively. In another phantom, 40 MHz pulse/echo RF lines were captured to demonstrate backscatter sensitivity. The results of this study show that ARF generation and high-resolution tracking is feasible on a small-aperture transducer fit for IVUS implementation.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Czernuszcwicz, Tomasz J. and Gallippi, Caterina M. and Wang, Zhuochen and Ma, Jianguo and Jiang, Xiaoning}, year={2014}, pages={2284–2287} }
 @article{selzo_czernuszewicz_gallippi_2014, title={Displacement Underestimation Correction Using Shear Waves in VisR Ultrasound}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0261}, abstractNote={We have previously proposed an imaging technique called Viscoelastic Response (VisR) ultrasound that uses acoustic radiation force (ARF) impulses to assess the viscoelastic properties of tissue. Using two successive ARF impulses in the same region of excitation and monitoring the induced deformation, VisR fits displacements to the mass-spring-damper mechanical model to measure the relaxation time constant, τ. In this method, ARF pulses are generated by the same transducer that is used to track motion and thus, the tracked displacements are susceptible to underestimation. Displacement underestimation introduces error into measurement of τ. It is hypothesized that by utilizing shear waves to generate displacement and monitoring tissue displacement outside the region of excitation we can better estimate axial displacements and generate τ measurements that more closely represent the material. We demonstrate displacement underestimation in, versus outside of, the ROE and the associated impact on VisR-derived τ using FEM simulations and experimentally using optical tracking in a translucent tissue-mimicking phantom.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Selzo, Mallory R. and Czernuszewicz, Tomasz J. and Gallippi, Caterina M.}, year={2014}, pages={1065–1068} }
 @article{selzo_gallippi_2014, title={Distinguishing Viscous from Elastic Properties in Viscoelastic Response (VisR) Ultrasound}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0274}, abstractNote={Viscoelastic Response (VisR) ultrasound is an acoustic radiation force (ARF)-based imaging method for noninvasively interrogating the viscoelastic properties of tissue. ViSR ultrasound uses two successive ARF impulses delivered to a single region of excitation (ROE) and tracks the micrometer-scale induced displacements. We have previously demonstrated that tracked displacements can be fit to the mass-spring-damper model in order to measure the relaxation time constant, τ, given by the ratio of viscosity to elasticity. Because it is a ratio, we cannot determine a change in τ is due to changes in elasticity, viscosity, or both. However, elasticity and viscosity may be evaluated uniquely by VisR if considered relative to the magnitude of the forcing function. It is hypothesized that their separation enhances discrimination of viscoelastic materials in VisR ultrasound. We demonstrate that VisR is able to isolate elasticity and viscosity from τ in FEM simulated data and experimentally in a gelatin phantom with a soft inclusion.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Selzo, Mallory R. and Gallippi, Caterina M.}, year={2014}, pages={1117–1120} }
 @article{geist_gallippi_nichols_merricks_caughey_2014, title={In Vivo ARFI Surveillance of Subcutaneous Hemorrhage (ASSH) for Monitoring rcFVIII Dose Response in Hemophilia A Dogs}, ISSN={["1948-5719"]}, DOI={10.1109/ultsym.2014.0572}, abstractNote={Acoustic Radiation Force Impulse (ARFI) ultrasound is used in ARFI Surveillance of Subcutaneous Hemorrhage (ASSH), a new in vivo hemostasis assay, to assess bleeding response in hemophilia A dogs. ASSH bleeding parameters were calculated from a small dose response study with 7 hemostatically normal dogs and 7 dogs exhibiting severe hemophilia A. Hemophilia A dogs were imaged in the naive state and/or when prophylactically treated with different levels of recombinant canine FVIII before bleeding was induced. A standardized injury of a 1-2mm vein by needle puncture induced subcutaneous bleeding in soft tissue. Bleeding was monitored by ASSH for 60 minutes. There was a significant difference (p<;0.05, Wilcoxon ranksum) in ASSH bleeding rate (BR) and a 34.8% reduction in occurrence of abnormal ASSH time to hemostasis (TTH) between naive hemophilia A and hemophilia A treated to 100% rcFVIII cohorts. These data indicate that ASSH could be relevant in differentiating bleeding responses to different levels of rcFVIII treatment.}, journal={2014 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS)}, author={Geist, Rebecca E. and Gallippi, Catcrina M. and Nichols, Timothy C. and Merricks, Elizabeth P. and Caughey, Melissa C.}, year={2014}, pages={2296–2299} }
 @article{behler_czernuszewicz_wu_nichols_zhu_homeister_merricks_gallippi_2013, title={Acoustic Radiation Force Beam Sequence Performance for Detection and Material Characterization of Atherosclerotic Plaques: Preclinical, Ex Vivo Results}, volume={60}, ISSN={["1525-8955"]}, DOI={10.1109/tuffc.2013.2847}, abstractNote={This work presents preclinical data demonstrating performance of acoustic radiation force (ARF)-based elasticity imaging with five different beam sequences for atherosclerotic plaque detection and material characterization. Twelve trained, blinded readers evaluated parametric images taken ex vivo under simulated in vivo conditions of 22 porcine femoral arterial segments. Receiver operating characteristic (ROC) curve analysis was carried out to quantify reader performance using spatially-matched immunohistochemistry for validation. The beam sequences employed had high sensitivity (sens) and specificity (spec) for detecting Type III+ plaques (sens: 85%, spec: 79%), lipid pools (sens: 80%, spec: 86%), fibrous caps (sens: 86%, spec: 82%), calcium (sens: 96%, spec: 85%), collagen (sens: 78%, spec: 77%), and disrupted internal elastic lamina (sens: 92%, spec: 75%). 1:1 single-receive tracking yielded the highest median areas under the ROC curve (AUC), but was not statistically significantly higher than 4:1 parallel-receive tracking. Excitation focal configuration did not result in statistically different AUCs. Overall, these results suggest ARF-based imaging is relevant to detecting and characterizing plaques and support its use for diagnosing and monitoring atherosclerosis.}, number={12}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Behler, Russell H. and Czernuszewicz, Tomasz J. and Wu, Chih-Da and Nichols, Timothy C. and Zhu, Hongtu and Homeister, Jonathon W. and Merricks, Elizabeth P. and Gallippi, Caterina M.}, year={2013}, month={Dec}, pages={2471–2487} }
 @article{czernuszewicz_streeter_dayton_gallippi_2013, title={Experimental Validation of Displacement Underestimation in ARFI Ultrasound}, volume={35}, ISSN={["1096-0910"]}, DOI={10.1177/0161734613493262}, abstractNote={Acoustic radiation force impulse (ARFI) imaging is an elastography technique that uses ultrasonic pulses to displace and track tissue motion. Previous modeling studies have shown that ARFI displacements are susceptible to underestimation due to lateral and elevational shearing that occurs within the tracking resolution cell. In this study, optical tracking was utilized to experimentally measure the displacement underestimation achieved by acoustic tracking using a clinical ultrasound system. Three optically translucent phantoms of varying stiffness were created, embedded with subwavelength diameter microspheres, and ARFI excitation pulses with F/1.5 or F/3 lateral focal configurations were transmitted from a standard linear array to induce phantom motion. Displacements were tracked using confocal optical and acoustic methods. As predicted by earlier finite element method studies, significant acoustic displacement underestimation was observed for both excitation focal configurations; the maximum underestimation error was 35% of the optically measured displacement for the F/1.5 excitation pulse in the softest phantom. Using higher F/#, less tightly focused beams in the lateral dimension improved accuracy of displacements by approximately 10 percentage points. This work experimentally demonstrates limitations of ARFI implemented on a clinical scanner using a standard linear array and sets up a framework for future displacement tracking validation studies.}, number={3}, journal={ULTRASONIC IMAGING}, author={Czernuszewicz, Tomasz J. and Streeter, Jason E. and Dayton, Paul A. and Gallippi, Caterina M.}, year={2013}, month={Jul}, pages={196–213} }
 @article{behler_nichols_zhu_merricks_gallippi_2009, title={ARFI IMAGING FOR NONINVASIVE MATERIAL CHARACTERIZATION OF ATHEROSCLEROSIS PART II: TOWARD IN VIVO CHARACTERIZATION}, volume={35}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2008.08.015}, abstractNote={Seventy percent of cardiovascular disease (CVD) deaths are attributed to atherosclerosis. Despite their clinical significance, nonstenotic atherosclerotic plaques are not effectively detected by conventional atherosclerosis imaging methods. Moreover, conventional imaging methods are insufficient for describing plaque composition, which is relevant to cardiovascular risk assessment. Atherosclerosis imaging technologies capable of improving plaque detection and stratifying cardiovascular risk are needed. Acoustic radiation force impulse (ARFI) ultrasound, a novel imaging method for noninvasively differentiating the mechanical properties of tissue, is demonstrated for in vivo detection of nonstenotic plaques and plaque material assessment in this pilot investigation. In vivo ARFI imaging was performed on four iliac arteries: (1) of a normocholesterolemic pig with no atherosclerosis as a control, (2) of a familial hypercholesterolemic pig with diffuse atherosclerosis, (3) of a normocholesterolemic pig fed a high-fat diet with early atherosclerotic plaques and (4) of a familial hypercholesterolemic pig with diffuse atherosclerosis and a small, minimally occlusive plaque. ARFI results were compared with spatially matched immunohistochemistry, showing correlations between elastin and collagen content and ARFI-derived peak displacement and recovery time parameters. Faster recoveries from ARFI-induced peak displacements and smaller peak displacements were observed in areas of higher elastin and collagen content. Importantly, spatial correlations between tissue content and ARFI results were consistent and observable in large and highly evolved as well as small plaques. ARFI imaging successfully distinguished nonstenotic plaques, while conventional B-mode ultrasound did not. This work validates the potential relevance of ARFI imaging as a noninvasive imaging technology for in vivo detection and material assessment of atherosclerotic plaques. (E-mail: [email protected] )}, number={2}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Behler, Russell H. and Nichols, Timothy C. and Zhu, Hongtu and Merricks, Elizabeth P. and Gallippi, Caterina M.}, year={2009}, month={Feb}, pages={278–295} }
 @article{mauldin_zhu_behler_nichols_gallippi_2008, title={Robust principal component analysis and clustering methods for automated classification of tissue response to ARFI excitation}, volume={34}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2007.07.019}, abstractNote={We introduce a new method for automatic classification of acoustic radiation force impulse (ARFI) displacement profiles using what have been termed "robust" methods for principal component analysis (PCA) and clustering. Unlike classical approaches, the robust methods are less sensitive to high variance outlier profiles and require no a priori information regarding expected tissue response to ARFI excitation. We first validate our methods using synthetic data with additive noise and/or outlier curves. Second, the robust techniques are applied to classifying ARFI displacement profiles acquired in an atherosclerotic familial hypercholesterolemic (FH) pig iliac artery in vivo. The in-vivo classification results are compared with parametric ARFI images showing peak induced displacement and time to 67% recovery and to spatially correlated immunohistochemistry. Our results support that robust techniques outperform conventional PCA and clustering approaches to classification when ARFI data are inclusive of low to relatively high noise levels (up to 5 dB average signal-to-noise [SNR] to amplitude) but no outliers: for example, 99.53% correct for robust techniques vs. 97.75% correct for the classical approach. The robust techniques also perform better than conventional approaches when ARFI data are inclusive of moderately high noise levels (10 dB average SNR to amplitude) in addition to a high concentration of outlier displacement profiles (10% outlier content): for example, 99.87% correct for robust techniques vs. 33.33% correct for the classical approach. This work suggests that automatic identification of tissue structures exhibiting similar displacement responses to ARFI excitation is possible, even in the context of outlier profiles. Moreover, this work represents an important first step toward automatic correlation of ARFI data to spatially matched immunohistochemistry.}, number={2}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Mauldin, F. William, Jr. and Zhu, Hongtu T. and Behler, Russell H. and Nichols, Timothy C. and Gallippi, Caterina M.}, year={2008}, month={Feb}, pages={309–325} }