An official website of the United States government
Abstract Ultrasound localization microscopy (ULM) enables deep tissue microvascular imaging by localizing and tracking intravenously injected microbubbles circulating in the bloodstream. However, conventional localization techniques require spatially isolated microbubbles, resulting in prolonged imaging time to obtain detailed microvascular maps. Here, we introduce LOcalization with Context Awareness (LOCA)-ULM, a deep learning-based microbubble simulation and localization pipeline designed to enhance localization performance in high microbubble concentrations. In silico, LOCA-ULM enhanced microbubble detection accuracy to 97.8% and reduced the missing rate to 23.8%, outperforming conventional and deep learning-based localization methods up to 17.4% in accuracy and 37.6% in missing rate reduction. In in vivo rat brain imaging, LOCA-ULM revealed dense cerebrovascular networks and spatially adjacent microvessels undetected by conventional ULM. We further demonstrate the superior localization performance of LOCA-ULM in functional ULM (fULM) where LOCA-ULM significantly increased the functional imaging sensitivity of fULM to hemodynamic responses invoked by whisker stimulations in the rat brain.
more »
« less
Singular value decomposition and 2D crosscorrelation based localization of gas vesicles for super-resolution ultrasound imaging
We report the potentials of nanometer-sized contrast agents which are called gas vesicles (GVs) for super-resolution ultrasound (SRUS) imaging to diagnose of vasculature deep inside tissue. Thus, we developed the GVs and ultrasound localization microscopy (ULM) based on singular value decomposition and 2D cross-correlation techniques. Furthermore, the SRUS imaging of the vessel-mimicking phantom with the GVs was performed. These results demonstrate that GVs could have potentials as novel contrast agents at nanoscale for implementing the SRUS imaging, thus indicating that ULM with GVs would be used for better visualization of micro-vasculature in vivo.
more »
« less
- Award ID(s):
- 1943852
- PAR ID:
- 10321178
- Date Published:
- Journal Name:
- 2020 IEEE International Ultrasonics Symposium (IUS)
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Magnetic nanoparticles are robust contrast agents for MRI and often produce particularly strong signal changes per particle. Leveraging these effects to probe cellular- and molecular-level phenomena in tissue can, however, be hindered by the large sizes of typical nanoparticle contrast agents. To address this limitation, we introduce single-nanometer iron oxide (SNIO) particles that exhibit superparamagnetic properties in conjunction with hydrodynamic diameters comparable to small, highly diffusible imaging agents. These particles efficiently brighten the signal in T 1 -weighted MRI, producing per-molecule longitudinal relaxation enhancements over 10 times greater than conventional gadolinium-based contrast agents. We show that SNIOs permeate biological tissue effectively following injection into brain parenchyma or cerebrospinal fluid. We also demonstrate that SNIOs readily enter the brain following ultrasound-induced blood–brain barrier disruption, emulating the performance of a gadolinium agent and providing a basis for future biomedical applications. These results thus demonstrate a platform for MRI probe development that combines advantages of small-molecule imaging agents with the potency of nanoscale materials.more » « less
-
Abstract A promising new field of genetically encoded ultrasound contrast agents in the form of gas vesicles has recently emerged, which could extend the specificity of medical ultrasound imaging. However, given the delicate genetic nature of how these genes are integrated and expressed, current methods of producing gas vesicle‐expressing mammalian cell lines requires significant cell processing time to establish a clonal/polyclonal line that robustly expresses the gas vesicles sufficiently enough for ultrasound contrast. Here, we describe an inducible and drug‐selectable acoustic reporter gene system that can enable gas vesicle expression in mammalian cell lines, which we demonstrate using HEK293T cells. Our drug‐selectable construct design increases the stability and proportion of cells that successfully integrate all plasmids into their genome, thus reducing the amount of cell processing time required. Additionally, we demonstrate that our drug‐selectable strategy forgoes the need for single‐cell cloning and fluorescence‐activated cell sorting, and that a drug‐selected mixed population is sufficient to generate robust ultrasound contrast. Successful gas vesicle expression was optically and ultrasonically verified, with cells expressing gas vesicles exhibiting an 80% greater signal‐to‐noise ratio compared to negative controls and a 500% greater signal‐to‐noise ratio compared to wild‐type HEK293T cells. This technology presents a new reporter gene paradigm by which ultrasound can be harnessed to visualize specific cell types for applications including cellular reporting and cell therapies.more » « less
-
There is a long-existing trade-off between the imaging resolution and penetration depth in acoustic imaging caused by the diffraction limit. Most existing approaches addressing this trade-off require controlled “labels,” i.e., metamaterials or contrast agents, to be deposited close to the objects and to either remain static or be tracked precisely during imaging. We propose a “blind-label” approach for acoustic subwavelength imaging. The blind labels are randomly distributed acoustic scatterers with deep-subwavelength sizes whose exact locations and trajectories are not necessary information in image reconstruction. The proposed method achieves the resolution of 0.24 wavelengths in ultrasound imaging experiments and 0.2 wavelengths in simulations, providing over 10 times improvement compared to the diffraction limit. We also elucidate the influence of scatterer size and concentration on imaging performance. The proposed “blind-label” approach relaxes the restrictions of existing acoustic subwavelength imaging technologies relying on controlled labels, therefore substantially improving the practicality of acoustic subwavelength imaging in biomedical ultrasound imaging, sonar, and nondestructive testing.more » « less
-
Macrophages are specialized phagocytes that play central roles in immunity and tissue repair. Their diverse functionalities have led to an evolution of new allogenic and autologous macrophage products. However, realizing the full therapeutic potential of these cell‐based therapies requires development of imaging technologies that can track immune cell migration within tissues in real‐time. Such innovations will not only inform treatment regimens and empower interpretation of therapeutic outcomes but also enable prediction and early intervention during adverse events. Here, phase‐changing nanoemulsion contrast agents are reported that permit real‐time, continuous, and high‐fidelity ultrasound imaging of macrophages in situ. Using a de novo designed peptide emulsifier, liquid perfluorocarbon nanoemulsions are prepared and show that rational control over interfacial peptide assembly affords formulations with tunable acoustic sensitivity, macrophage internalization, and in cellulo stability. Imaging experiments demonstrate that emulsion‐loaded macrophages can be readily visualized using standard diagnostic B‐mode and Doppler ultrasound modalities. This allows on‐demand and long‐term tracking of macrophages within porcine coronary arteries, as an exemplary model. The results demonstrate that this platform is poised to open new opportunities for non‐invasive, contrast‐enhanced imaging of cell‐based immunotherapies in tissues, while leveraging the low‐cost, portable, and safe nature of diagnostic ultrasound.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1109/IUS46767.2020.9251651
