Research

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Improved estimation of quantitative ultrasound features

Work on improving the accuracy and precision of quantitative ultrasound technique never ends (constantly evolving?)! As we expand the application of these techniques to different body parts and different diseases, new challenges and sources of errors arise. Thus, we are continuously working to improve these techniques from the physical basis to more advanced signal processing and problem inversion methods.  In the field of pulse-echo quantitative ultrasound, have partnered with Dr. Hassan Rivaz (Concordia University), to find ways to improve the accuracy and precision of estimates of quantitative features by using novel regularization approaches and deep learning. In the field of strain imaging, we are collaborating with the group of Dr. Paul Barbone (Boston University) and Assad Oberai (USC)  to improve motion tracking over large deformations as well as elastic modulus reconstructions to provide better estimates of tissue stiffness, like breast.

Recent publications:

  • Rosen DP, Nayak R, Wang Y, Gendin D, Larson NB, Fazzio RT, Oberai AA, Hall TJ, Barbone PE, Alizad A, Fatemi M. A Force-Matched Approach to Large-Strain Nonlinearity in Elasticity Imaging for Breast Lesion Characterization. IEEE Transactions on Biomedical Engineering. 2023 Aug 17. 10.1109/TBME.2023.3305986
  • Jafarpisheh N, Castaneda-Martinez L, Whitson H, Rosado-Mendez IM, Rivaz H. Physics-Inspired Regularized Pulse-Echo Quantitative Ultrasound: Efficient Optimization with ADMM. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. 2023 (in press) 10.1109/TUFFC.2023.3321250
  • Tehrani AK, Rosado-Mendez IM, Rivaz H. Homodyned K-distribution: parameter estimation and uncertainty quantification using Bayesian neural networks. In 2023 IEEE 20th International Symposium on Biomedical Imaging (ISBI) 2023 Apr 18 (pp. 1-4). IEEE. 1109/ISBI53787.2023.10230797
  • Tehrani AK, Rosado-Mendez IM, Rivaz H. Robust scatterer number density segmentation of ultrasound images. IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. 2022 Jan 19;69(4):1169-80. 1109/TUFFC.2022.3144685
  • Jafarpisheh N, Hall TJ, Rivaz H, Rosado-Mendez IM. Analytic global regularized backscatter quantitative ultrasound. IEEE transactions on ultrasonics, ferroelectrics, and frequency control. 2020 Dec 7;68(5):1605-17. 10.1109/TUFFC.2020.3042942
  • Wang Y, Bayer M, Jiang J, Hall TJ. Large-strain 3-D in vivo breast ultrasound strain elastography using a multi-compression strategy and a whole-breast scanning system. Ultrasound in medicine & biology. 2019 Dec 1;45(12):3145-59. https://doi.org/10.1016/j.ultrasmedbio.2019.08.013
  • Wang Y, Bayer M, Jiang J, Hall TJ. An improved region-growing motion tracking method using more prior information for 3-D ultrasound elastography. IEEE transactions on ultrasonics, ferroelectrics, and frequency control. 2019 Oct 24;67(3):580-97. 10.1109/TUFFC.2019.2948984

Sources of funding

  • NIH grants:
  • Other sources of funding: Universidad Nacional Autonoma de Mexico
  • Industrial Support: Siemens Healthineers

Quantitative imaging biomarker of cervical remodeling during pregnancy

[SHG image of an NHP cervix?]

The complex and poorly understood physiology of pregnancy and birth underlies obstetrical practice today, which remains anchored in practices introduced in the early to mid 1900s. This complexity is exacerbated by the simultaneous physiological processes occurring in reproductive tissues during pregnancy, as well as in the developing fetus. In partnership with Dr. Helen Feltovich (Mt. Sinai Health System) and Dr. Kristin Myers (Columbia University), we are devising ways to use ultrasound to simultaneously quantify biomarkers describing different aspects of tissue remodeling. Our current focus is on the cervix, which plays a key role in supporting pregnancy and allowing for vaginal delivery. We have made significant progress in developing shear wave elastography and backscatter-based quantitative ultrasound to assess different aspects of cervical remodeling, like softening and collagen reorganization. These biomarkers will be fundamental to a kit of tools to identify and address PTB, ultimately leading to tailored interventions based on a patient-specific biomarker “fingerprint” of pregnancy.

  • Santoso AP, Rosado-Mendez I, Guerrero QW, Hall TJ. A Geometric Model of Ultrasound Backscatter to Describe Microstructural Anisotropy of Tissue. Ultrasonic Imaging. 2023 Jul;45(4):206-14. https://doi.org/10.1177/01617346231171147
  • Torres A, Palmeri ML, Feltovich H, Hall TJ, Rosado-Mendez IM. Shear wave dispersion as a potential biomarker for cervical remodeling during pregnancy: evidence from a non-human primate model. Frontiers in physics. 2021 Feb 15;8:606664. https://doi.org/10.3389/fphy.2020.606664
  • Carlson LC, Hall TJ, Rosado-Mendez IM, Mao L, Feltovich H. Quantitative assessment of cervical softening during pregnancy with shear wave elasticity imaging: an in vivo longitudinal study. Interface focus. 2019 Oct 6;9(5):20190030. https://doi.org/10.1098/rsfs.2019.0030
  • Guerrero QW, Feltovich H, Rosado-Mendez IM, Santoso AP, Carlson LC, Zea R, Hall TJ. Quantitative ultrasound parameters based on the backscattered echo power signal as biomarkers of cervical remodeling: a longitudinal study in the pregnant rhesus macaque. Ultrasound in medicine & biology. 2019 Jun 1;45(6):1466-74. https://doi.org/10.1016/j.ultrasmedbio.2018.12.004

Sources of funding

  • NIH grants: R01HD072077, R01HD096361, R21HD063031, R21HD61896, F31HD082911
  • Other sources of funding: Biomarkers of Uterine and Cervical Change (BOUNCE) funded by Intermountain Research and Medical Foundation
  • Industrial Support: Equipment loans and technical support from Siemens Healthineers ultrasound division

Multiscale imaging: Linking quantitative ultrasound to mesoscale tissue properties

Backscatter-based quantitative ultrasound has the potential to bridge the link between macroscopic imaging (resolutions >1mm) and microscopic imaging (resolutions <1um). This is because the frequency dependence of the backscatter coefficient carries information about the organization of tissue at the mesoscale. In order to validate this hypothesis, we have partnered with Dr. Kevin Eliceiri (UW-Madison) to develop a multiscale imaging system that combines a programable Verasonics Vantage 256 scanner with an optical microscopy setup able to perform second-harmonic generation microscopy, optical coherent tomography, and enhanced backscatter microcopy.  This system will open the door to many research studies focusing on understanding the relationship between imaging biomarkers extracted from the analysis of the backscatter coefficient and different features of the tissue microstructure.

Recent publications:

  • Pinkert MA, Hall TJ, Eliceiri KW. Challenges of conducting quantitative ultrasound with a multimodal optical imaging system. Physics in Medicine & Biology. 2021 Jan 22;66(3):035008. 10.1088/1361-6560/abc93c
  • Pinkert MA, Cox BL, Dai B, Hall TJ, Eliceiri KW. 3-D-Printed registration phantom for combined ultrasound and optical imaging of biological tissues. Ultrasound in medicine & biology. 2020 Jul 1;46(7):1808-14. https://doi.org/10.1016/j.ultrasmedbio.2020.03.010
  • Pinkert MA, Hall TJ, Eliceiri KW. Challenges of conducting quantitative ultrasound with a multimodal optical imaging system. Physics in Medicine & Biology. 2021 Jan 22;66(3):035008. https://doi.org/10.1364/BOE.383248

Sources of funding

  • NIH grants:
  • Other sources of funding:
  • Industrial Support:

Non-invasive detection of neonatal brain damage

[Image]

There is an urgent need for non-invasive, practical methods to evaluate the damage in the brain of neonates that result from perinatal asphyxia, ischemia, hemorrhagic stroke, among other issues. In partnership with Dr. Chris Ikonomidou (UW-Madison), we developed a Rhesus macaque model to investigate the potential of backscatter-based quantitative ultrasound to detect microstructural changes in the thalamus induced by long exposures to anesthesia. We have demonstrated a strong correlation of changes in the effective scatterer diameter with the level of expression of caspase 3, a protein related to the induction of apoptosis. We have also observed significant reductions in the effective scatterer size in rhesus macaques exposed to 5 hours of sevoflurane with respect to a control group. We are currently translating these techniques to human application and refining them to assess the complex three-dimensional architecture of the brain microstructure.

[Publications]

  • Castañeda-Martinez L, Noguchi KK, Ikonomidou C, Zagzebski JA, Hall TJ, Rosado-Mendez IM. Optimization of ultrasound backscatter spectroscopy to assess neurotoxic effects of anesthesia in the newborn non-human primate brain. Ultrasound in medicine & biology. 2020 Aug 1;46(8):2044-56. https://doi.org/10.1016/j.ultrasmedbio.2020.04.004
  • Rosado-Mendez IM, Noguchi KK, Castañeda-Martinez L, Kirvassilis G, Wang SH, Manzella F, Swiney BS, Masuoka K, III SC, Brunner KG, Crosno K. Quantitative ultrasound and apoptotic death in the neonatal primate brain. Neurobiology of disease. 2019 Jul 1;127:554-62. https://doi.org/10.1016/j.nbd.2019.03.032

Sources of funding

  • NIH grants:
  • Other sources of funding: Department of Radiology (seed funds to I. Rosado-Mendez)
  • Industrial Support: Siemens Healthineers

 

Validation of microvascular imaging

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Recent developments in microvascular ultrasound imaging, like Super-Resolution UltraSound and microvascular Doppler, provide improved sensitivity to slow flow from the blood microvasculature compared to conventional Doppler techniques. We are currently funded by the Wisconsin Parthership Program to build a reference standard to evaluate the performance of these techniques and understand their advantages and limitations. We are also developing in vivo models to validate these techniques.

[Publications]

Sources of funding

  • NIH grants:
  • Other sources of funding: Wisconsin Partnership Program, School of Medicine and Public Health
  • Industrial Support: Siemens Healthineers

Quantitative biomarkers for diffuse liver disease

Ultrasound plays an important role in the evaluation of diffuse liver disease, like the deposit of fat in hepatocytes (steatosis) or the deposition of fibrous tissue (fibrosis). As these problems become more common due to the increasing prevalence of overweight and obesity, reliance on ultrasound for patient management become more important due to its widespread availability. However, conventional B-mode imaging is highly operator and observer dependent and is not sensitive to initial stages of the disease. Working with Dr. Scott Reeder (UW-Madison) and Dr. Claude Sirlin (University of California, San Diego), we are exploring the value of quantitative ultrasound and shear wave elastography to provide biomarkers of liver steatosis and fibrosis in patients undergoing bariatric surgery. In parallel, as part of our contribution to the Quantitative Imaging Biomarkers Alliance, we are helping develop standardized guides for implementing these techniques in clinical practice, in order to ensure their successful translation.

Recent publications

Fetzer DT, Rosado-Mendez IM, Wang M, Robbin ML, Ozturk A, Wear KA, Ormachea J, Stiles TA, Fowlkes JB, Hall TJ, Samir AE. Pulse-echo quantitative US biomarkers for liver steatosis: toward technical standardization. Radiology. 2022 Nov;305(2):265-76.

Sources of funding and technical support

  • NIH grants:
  • Other sources of funding: UW-Madison Radiology R&D
  • Industrial Support: Pfeizer, Siemens Healthineers, GE Healthcare

Quantitative ultrasound for the characterization of solid breast lesions

[Image]

Ultrasound imaging plays a key role in the detection and management of breast cancer. Once a lesion is detected, ultrasound can help determine if that lesion is cancer. However, the sensitivity of ultrasound to finding abnormalities comes at the expense of a limited ability to separate those lesions that are not cancer, a.k.a., benign lesions. During the past decade, our lab focused on applying quantitative ultrasound to provide radiologists with objective assessments of the (subjective) visual features that they assess as part of the routine evaluation of breast sonograms. For example, the backscatter coefficient can be used as a surrogate to the relative echogenicity (brightness) of the lesion compared to the surrounding adipose tissue, while the attenuation coefficient can be used as a surrogate for the presence of posterior features (shadows, zones of enhancement). After demonstrating this relationship between visual features and quantitative ultrasound features, we provided preliminary evidence of the possibility of differentiating between benign and malignant lesions with features backscatter quantitative ultrasound. With sight on an extended clinical application, in collaboration with the Instituto de Fisica, UNAM and the Instituto Nacional de Cancerologia in Mexico City, we investigated how the experience of the probe operator affected the variability of the backscatter coefficient of breast masses. We are now investigating the relationship between quantitative ultrasound and different molecular and histological features of different types of breast lesions.

[Publications]

  • Argueta‐Lozano AK, Castañeda‐Martinez L, Bass V, Mateos MJ, Castillo‐López JP, Perez‐Badillo MP, Aguilar‐Cortazar LO, Porras‐Reyes F, Sollozo‐Dupont MI, Torres‐Robles F, Márquez‐Flores J. Inter‐and Intra‐Operator Variability of Regularized Backscatter Quantitative Ultrasound for the Characterization of Breast Masses. Journal of Ultrasound in Medicine. 2023 Jul 25. https://doi.org/10.1002/jum.16292
  • Nasief HG, Rosado-Mendez IM, Zagzebski JA, Hall TJ. A quantitative ultrasound-based multi-parameter classifier for breast masses. Ultrasound in medicine & biology. 2019 Jul 1;45(7):1603-16. https://doi.org/10.1016/j.ultrasmedbio.2019.02.025
  • Nasief HG, Rosado-Mendez IM, Zagzebski JA, Hall TJ. Acoustic properties of breast fat. Journal of Ultrasound in Medicine. 2015 Nov;34(11):2007-16. https://doi.org/10.7863/ultra.14.07039
  • Nam K, Zagzebski JA, Hall TJ. Quantitative assessment of in vivo breast masses using ultrasound attenuation and backscatter. Ultrasonic imaging. 2013 Apr;35(2):146-61. https://doi.org/10.1177/0161734613480281

Sources of funding

  • NIH grants:
  • Other sources of funding: Consejo Nacional de Ciencia y Tecnología, Mexico
  • Industrial Support: Siemens Healthineers