@article{richardson_moore_gallippi_2024, title={Quantitative Viscoelastic Response (QVisR): Direct Estimation of Viscoelasticity With Neural Networks}, volume={71}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2024.3404457}, abstractNote={We present a machine learning method to directly estimate viscoelastic moduli from displacement time-series profiles generated by viscoelastic response (VisR) ultrasound excitations. VisR uses two colocalized acoustic radiation force (ARF) pushes to approximate tissue viscoelastic creep response and tracks displacements on-axis to measure the material relaxation. A fully connected neural network is trained to learn a nonlinear mapping from VisR displacements, the push focal depth, and the measurement axial depth to the material elastic and viscous moduli. In this work, we assess the validity of quantitative VisR (QVisR) in simulated materials, propose a method of domain adaption to phantom VisR displacements, and show in vivo estimates from a clinically acquired dataset.}, number={7}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Richardson, Joseph B. and Moore, Christopher J. and Gallippi, Caterina M.}, year={2024}, month={Jul}, pages={910–923} }
 @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{rojas_joiner_velasco_bautista_aji_moore_beaumont_pylayeva-gupta_dayton_gessner_et al._2022, title={Validation of a combined ultrasound and bioluminescence imaging system with magnetic resonance imaging in orthotopic pancreatic murine tumors}, volume={12}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-021-03684-z}, abstractNote={AbstractPreclinical mouse solid tumor models are widely used to evaluate efficacy of novel cancer therapeutics. Recent reports have highlighted the need for utilizing orthotopic implantation to represent clinical disease more accurately, however the deep tissue location of these tumors makes longitudinal assessment challenging without the use of imaging techniques. The purpose of this study was to evaluate the performance of a new multi-modality high-throughput in vivo imaging system that combines bioluminescence imaging (BLI) with robotic, hands-free ultrasound (US) for evaluating orthotopic mouse models. Long utilized in cancer research as independent modalities, we hypothesized that the combination of BLI and US would offer complementary advantages of detection sensitivity and quantification accuracy, while mitigating individual technological weaknesses. Bioluminescent pancreatic tumor cells were injected into the pancreas tail of C57BL/6 mice and imaged weekly with the combination system and magnetic resonance imaging (MRI) to serve as a gold standard. BLI photon flux was quantified to assess tumor activity and distribution, and US and MRI datasets were manually segmented for gross tumor volume. Robotic US and MRI demonstrated a strong agreement (R2 = 0.94) for tumor volume measurement. BLI showed a weak overall agreement with MRI (R2 = 0.21), however, it offered the greatest sensitivity to detecting the presence of tumors. We conclude that combining BLI with robotic US offers an efficient screening tool for orthotopic tumor models.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Rojas, Juan D. and Joiner, Jordan B. and Velasco, Brian and Bautista, Kathlyne Jayne B. and Aji, Adam M. and Moore, Christopher J. and Beaumont, Nathan J. and Pylayeva-Gupta, Yuliya and Dayton, Paul A. and Gessner, Ryan C. and et al.}, year={2022}, month={Jan} }
 @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={<h2>Abstract</h2> Our group has previously found that <i>in silico,</i> 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 <i>in vivo</i> 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. <i>In vivo</i> 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, <i>p</i> = 0.04, Wilcoxon rank sum test; RV: DMD = 1.04 ± 0.71, control = 0.74 ± 0.22, <i>p</i> = 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, <i>p</i> = 0.04). In the dystrophic rectus femoris muscle, the RE anisotropy ratio was inversely correlated (slope = –0.03/lbf, <i>r</i> = –0.43, <i>p</i> = 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} }
 @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_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 paper, 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} }
 @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{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{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} }