scholarly journals Ultrasound-Based Molecular Imaging of Tumors with PTPmu Biomarker-Targeted Nanobubble Contrast Agents

2021 ◽  
Vol 22 (4) ◽  
pp. 1983
Author(s):  
Mette L. Johansen ◽  
Reshani Perera ◽  
Eric Abenojar ◽  
Xinning Wang ◽  
Jason Vincent ◽  
...  
Keyword(s):  
Contrast Agents ◽  
Ultrasound Imaging ◽  
Imaging Modality ◽  
Tyrosine Phosphatase ◽  
Receptor Protein ◽  
Contrast Enhanced Ultrasound ◽  
Core Lipid ◽  
Contrast Enhanced

Ultrasound imaging is a widely used, readily accessible and safe imaging modality. Molecularly-targeted microbubble- and nanobubble-based contrast agents used in conjunction with ultrasound imaging expand the utility of this modality by specifically targeting and detecting biomarkers associated with different pathologies including cancer. In this study, nanobubbles directed to a cancer biomarker derived from the Receptor Protein Tyrosine Phosphatase mu, PTPmu, were evaluated alongside non-targeted nanobubbles using contrast enhanced ultrasound both in vitro and in vivo in mice. In vitro resonant mass and clinical ultrasound measurements showed gas-core, lipid-shelled nanobubbles conjugated to either a PTPmu-directed peptide or a Scrambled control peptide were equivalent. Mice with heterotopic human tumors expressing the PTPmu-biomarker were injected with PTPmu-targeted or control nanobubbles and dynamic contrast-enhanced ultrasound was performed. Tumor enhancement was more rapid and greater with PTPmu-targeted nanobubbles compared to the non-targeted control nanobubbles. Peak tumor enhancement by the PTPmu-targeted nanobubbles occurred within five minutes of contrast injection and was more than 35% higher than the Scrambled nanobubble signal for the subsequent two minutes. At later time points, the signal in tumors remained higher with PTPmu-targeted nanobubbles demonstrating that PTPmu-targeted nanobubbles recognize tumors using molecular ultrasound imaging and may be useful for diagnostic and therapeutic purposes.

scholarly journals Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
John R. Eisenbrey ◽  
Anush Sridharan ◽  
Ji-Bin Liu ◽  
Flemming Forsberg
Keyword(s):  
Contrast Agents ◽  
Tumor Imaging ◽  
Three Dimensional ◽  
Ultrasound Contrast Agents ◽  
Surrounding Tissue ◽  
Contrast Enhanced Ultrasound ◽  
Ultrasound Contrast ◽  
Contrast Enhanced ◽  
Subharmonic Response

Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imagingin vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging.

scholarly journals Window-Modulated Compounding Nakagami Parameter Ratio Approach for Assessing Muscle Perfusion with Contrast-Enhanced Ultrasound Imaging

Sensors ◽  
2020 ◽  
Vol 20 (12) ◽  
pp. 3584
Author(s):  
Huang-Chen Lin ◽  
Shyh-Hau Wang
Keyword(s):  
Contrast Agents ◽  
Ultrasound Imaging ◽  
Ultrasound Contrast Agents ◽  
Muscle Disease ◽  
Contrast Enhanced Ultrasound ◽  
Time Intensity Curve ◽  
Muscle Perfusion ◽  
Ultrasound Contrast ◽  
Parameter Ratio ◽  
Contrast Enhanced

The assessment of microvascular perfusion is essential for the diagnosis of a specific muscle disease. In comparison with the current available medical modalities, the contrast-enhanced ultrasound imaging is the simplest and fastest means for probing the tissue perfusion. Specifically, the perfusion parameters estimated from the ultrasound time-intensity curve (TIC) and statistics-based time–Nakagami parameter curve (TNC) approaches were found able to quantify the perfusion. However, due to insufficient tolerance on tissue clutters and subresolvable effects, these approaches remain short of reproducibility and robustness. Consequently, the window-modulated compounding (WMC) Nakagami parameter ratio imaging was proposed to alleviate these effects, by taking the ratio of WMC Nakagami parameters corresponding to the incidence of two different acoustic pressures from an employed transducer. The time–Nakagami parameter ratio curve (TNRC) approach was also developed to estimate perfusion parameters. Measurements for the assessment of muscle perfusion were performed from the flow phantom and animal subjects administrated with a bolus of ultrasound contrast agents. The TNRC approach demonstrated better sensitivity and tolerance of tissue clutters than those of TIC and TNC. The fusion image with the WMC Nakagami parameter ratio and B-mode images indicated that both the tissue structures and perfusion properties of ultrasound contrast agents may be better discerned.

scholarly journals Contrast-Enhanced Ultrasound Imaging and in Vivo Circulatory Kinetics with Low-Boiling-Point Nanoscale Phase-Change Perfluorocarbon Agents

2015 ◽  
Vol 41 (3) ◽  
pp. 814-831 ◽  
Author(s):  
Paul S. Sheeran ◽  
Juan D. Rojas ◽  
Connor Puett ◽  
Jordan Hjelmquist ◽  
Christopher B. Arena ◽  
...  
Keyword(s):  
Phase Change ◽  
Ultrasound Imaging ◽  
Boiling Point ◽  
Contrast Enhanced Ultrasound ◽  
Contrast Enhanced

scholarly journals Dynamic Interaction of PTPμ with Multiple Cadherins In Vivo

1998 ◽  
Vol 141 (1) ◽  
pp. 287-296 ◽  
Author(s):  
Susann M. Brady-Kalnay ◽  
Tracy Mourton ◽  
Joseph P. Nixon ◽  
Gregory E. Pietz ◽  
Michael Kinch ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
Tyrosine Phosphatase ◽  
Cross Reactivity ◽  
Receptor Protein ◽  
Temperature Sensitive ◽  
Mutant Form ◽  
Cell Biol ◽  
E Cadherin

There is a growing body of evidence to implicate reversible tyrosine phosphorylation as an important mechanism in the control of the adhesive function of cadherins. We previously demonstrated that the receptor protein tyrosine phosphatase PTPμ associates with the cadherin–catenin complex in various tissues and cells and, therefore, may be a component of such a regulatory mechanism (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977– 986). In this study, we present further characterization of this interaction using a variety of systems. We observed that PTPμ interacted with N-cadherin, E-cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We observed a direct interaction between PTPμ and E-cadherin after coexpression in Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v-Src, the complex between PTPμ and E-cadherin was dynamic, and conditions that resulted in tyrosine phosphorylation of E-cadherin were associated with dissociation of PTPμ from the complex. Furthermore, we have demonstrated that the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was required for association with PTPμ in WC5 cells. Zondag et al. (Zondag, G., W. Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513–1517) have asserted that the association we observed between PTPμ and the cadherin–catenin complex in immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity between BK2, our antibody to PTPμ, and cadherins. In this study we have confirmed our initial observation and demonstrated the presence of cadherin in immunoprecipitates of PTPμ obtained with three antibodies that recognize distinct epitopes in the phosphatase. In addition, we have demonstrated directly that the anti-PTPμ antibody BK2 that we used initially did not cross-react with cadherin. Our data reinforce the observation of an interaction between PTPμ and E-cadherin in vitro and in vivo, further emphasizing the potential importance of reversible tyrosine phosphorylation in regulating cadherin function.

scholarly journals Functions of the Ectodomain and Cytoplasmic Tyrosine Phosphatase Domains of Receptor Protein Tyrosine Phosphatase Dlar In Vivo

2003 ◽  
Vol 23 (19) ◽  
pp. 6909-6921 ◽  
Author(s):  
Neil X. Krueger ◽  
R. Sreekantha Reddy ◽  
Karl Johnson ◽  
Jack Bateman ◽  
Nancy Kaufmann ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
P Element ◽  
Receptor Protein ◽  
Loss Of Function ◽  
Protein Tyrosine ◽  
Receptor Protein Tyrosine Phosphatase ◽  
Catalytically Active

ABSTRACT The receptor protein tyrosine phosphatase (PTPase) Dlar has an ectodomain consisting of three immunoglobulin (Ig)-like domains and nine fibronectin type III (FnIII) repeats and a cytoplasmic domain consisting of two PTPase domains, membrane-proximal PTP-D1 and C-terminal PTP-D2. A series of mutant Dlar transgenes were introduced into the Drosophila genome via P-element transformation and were then assayed for their capacity to rescue phenotypes caused by homozygous loss-of-function genotypes. The Ig-like domains, but not the FnIII domains, are essential for survival. Conversely, the FnIII domains, but not the Ig-like domains, are required during oogenesis, suggesting that different domains of the Dlar ectodomain are involved in distinct functions during Drosophila development. All detectable PTPase activity maps to PTP-D1 in vitro. The catalytically inactive mutants of Dlar were able to rescue Dlar −/− lethality nearly as efficiently as wild-type Dlar transgenes, while this ability was impaired in the PTP-D2 deletion mutants DlarΔPTP-D2 and Dlarbypass . Dlar-C1929S, in which PTP-D2 has been inactivated, increases the frequency of bypass phenotype observed in Dlar −/− genotypes, but only if PTP-D1 is catalytically active in the transgene. These results indicate multiple roles for PTP-D2, perhaps by acting as a docking domain for downstream elements and as a regulator of PTP-D1.

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