Ultrafast amplitude modulation for molecular and hemodynamic ultrasound imaging

Ultrasound is playing an emerging role in molecular and cellular imaging thanks to new micro- and nanoscale contrast agents and reporter genes. Acoustic methods for the selective in vivo detection of these imaging agents are needed to maximize their impact in biology and medicine. Existing ultrasound pulse sequences use the nonlinearity in contrast agents’ response to acoustic pressure to distinguish them from mostly linear tissue scattering. However, such pulse sequences typically scan the sample using focused transmissions, resulting in a limited frame rate and restricted field of view. Meanwhile, existing wide-field scanning techniques based on plane wave transmissions suffer from limited sensitivity or nonlinear artifacts. To overcome these limitations, we introduce an ultrafast nonlinear imaging modality combining amplitude-modulated pulses, multiplane wave transmissions and selective coherent compounding. This technique achieves contrast imaging sensitivity comparable to much slower gold-standard amplitude modulation sequences and enables the acquisition of larger and deeper fields of view, while providing a much faster imaging framerate of 3.2kHz. Additionally, it enables simultaneous nonlinear and linear image formation, and allows concurrent monitoring of phenomena accessible only at ultrafast framerates, such as blood volume variations. We demonstrate the performance of this ultrafast amplitude modulation (uAM) technique by imaging gas vesicles, an emerging class of genetically encodable biomolecular contrast agents, in several in vitro and in vivo contexts. These demonstrations include the rapid discrimination of moving contrast agents and the real-time monitoring of phagolysosomal function in the mouse liver

Chapter 7 - Work and Kinetic Energy

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Chapter 13 - Gravitation

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The reported durations of GOES Soft X-Ray flares in different solar cycles

The Geostationary Orbital Environmental Satellites (GOES) Soft X-ray (SXR) sensors have provided data relating to, inter alia, the time, intensity and duration of solar flares since the 1970s. The GOES SXR Flare List has become the standard reference catalogue for solar flares and is widely used in solar physics research and space weather. We report here that in the cur- rent version of the list there are significant differences between the mean du- ration of flares which occurred before May 1997 and the mean duration of flares thereafter. Our analysis shows that the reported flare timings for the pre-May 1997 data were not based on the same criteria as is currently the case. This finding has serious implications for all those who used flare duration (or fluence, which depends on the chosen start and end times) as part of their analysis of pre-May 1997 solar events, or statistical analyses of large sam- ples of flares, e.g. as part of the assessment of a Solar Energetic Particle fore- casting algorithm

Biomolecular Ultrasound Imaging of Phagolysosomal Function

Phagocytic clearance and lysosomal processing of pathogens and debris are essential functions of the innate immune system. However, the assessment of these functions in vivo is challenging because most nanoscale contrast agents compatible with noninvasive imaging techniques are made from nonbiodegradable synthetic materials that do not undergo regular lysosomal degradation. To overcome this challenge, we describe the use of an all-protein contrast agent to directly visualize and quantify phagocytic and lysosomal activities in vivo by ultrasound imaging. This contrast agent is based on gas vesicles (GVs), a class of air-filled protein nanostructures naturally expressed by buoyant microbes. Using a combination of ultrasound imaging, pharmacology, immunohistology, and live-cell optical microscopy, we show that after intravenous injection, GVs are cleared from circulation by liver-resident macrophages. Once internalized, the GVs undergo lysosomal degradation, resulting in the elimination of their ultrasound contrast. By noninvasively monitoring the temporal dynamics of GV-generated ultrasound signal in circulation and in the liver and fitting them with a pharmacokinetic model, we can quantify the rates of phagocytosis and lysosomal degradation in living animals. We demonstrate the utility of this method by showing how these rates are perturbed in two models of liver dysfunction: phagocyte deficiency and nonalcoholic fatty liver disease. The combination of proteolytically degradable nanoscale contrast agents and quantitative ultrasound imaging thus enables noninvasive functional imaging of cellular degradative processes

Ultrasound Technologies for Imaging and Modulating Neural Activity

Visualizing and perturbing neural activity on a brain-wide scale in model animals and humans is a major goal of neuroscience technology development. Established electrical and optical techniques typically break down at this scale due to inherent physical limitations. In contrast, ultrasound readily permeates the brain, and in some cases the skull, and interacts with tissue with a fundamental resolution on the order of 100 μm and 1 ms. This basic ability has motivated major efforts to harness ultrasound as a modality for large-scale brain imaging and modulation. These efforts have resulted in already-useful neuroscience tools, including high-resolution hemodynamic functional imaging, focused ultrasound neuromodulation, and local drug delivery. Furthermore, recent breakthroughs promise to connect ultrasound to neurons at the genetic level for biomolecular imaging and sonogenetic control. In this article, we review the state of the art and ongoing developments in ultrasonic neurotechnology, building from fundamental principles to current utility, open questions, and future potential

Ultrasound Technologies for Imaging and Modulating Neural Activity

Visualizing and perturbing neural activity on a brain-wide scale in model animals and humans is a major goal of neuroscience technology development. Established electrical and optical techniques typically break down at this scale due to inherent physical limitations. In contrast, ultrasound readily permeates the brain, and in some cases the skull, and interacts with tissue with a fundamental resolution on the order of 100 μm and 1 ms. This basic ability has motivated major efforts to harness ultrasound as a modality for large-scale brain imaging and modulation. These efforts have resulted in already-useful neuroscience tools, including high-resolution hemodynamic functional imaging, focused ultrasound neuromodulation, and local drug delivery. Furthermore, recent breakthroughs promise to connect ultrasound to neurons at the genetic level for biomolecular imaging and sonogenetic control. In this article, we review the state of the art and ongoing developments in ultrasonic neurotechnology, building from fundamental principles to current utility, open questions, and future potential

Self-assembly of protein superstructures by physical interactions under cytoplasm-like conditions

The structure-driven assembly of multimeric protein complexes and the formation of intracellular phase-like protein condensates have been the subject of intense research. However, the assembly of larger superstructures comprising cellular components, such as protein nanoparticles driven by general physical rather than specific biochemical interactions, remains relatively uncharacterized. Here, we use gas vesicles (GVs)—genetically encoded protein nanoparticles that form ordered intracellular clusters—as a model system to study the forces driving multiparticle assembly under cytoplasm-like conditions. Our calculations and experimental results show that the ordered assembly of GVs can be achieved by screening their mutual electrostatic repulsion with electrolytes and creating a crowding force with dissolved macromolecules. The precise balance of these forces results in different packing configurations. Biomacromolecules such as polylysine and DNA are capable of driving GV clustering. These results provide basic insights into how physically driven interactions affect the formation of protein superstructures, offer guidance for manipulating nanoparticle assembly in cellular environments through synthetic biology methods, and inform research on the biotechnology applications of GVs