Ultraharmonic VUS Imaging of Microvascularization

The coronary arteries are major blood vessels branching along the heart surface to convey nutrients and oxygen carried in the blood to the heart muscle cells. In turn, the heart ensures the perpetual transportation of blood throughout the other organs of the circulatory system. Coronary arteries comprise the right and left coronary artery. Both originate from the root of the aorta. The left main coronary artery (LCA) gives off the left circumflex artery (LCX) and continues its descent as the left anterior descending coronary artery (LAD). The LCX runs around the left border of the heart to reach the posterior surface where it supplies the left ventricle muscle. The LAD and its branches supply two thirds of the anterior heart surface. The right coronary artery (RCA) descends along the border of the right atrium and the right ventricle to supply the right ventricle muscle. A simplified representation of the coronary artery anatomy is represented in Figure 1

Ada style guide (version 1.1)

Ada is a programming language of considerable expressive power. The Ada Language Reference Manual provides a thorough definition of the language. However, it does not offer sufficient guidance on the appropriate use of Ada's powerful features. For this reason, the Goddard Space Flight Center Ada User's Group has produced this style guide which addresses such program style issues. The guide covers three areas of Ada program style: the structural decomposition of a program; the coding and the use of specific Ada features; and the textural formatting of a program

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

Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function

Most cellular phenomena of interest to mammalian biology occur within the context of living tissues and organisms. However, today’s most advanced tools for observing and manipulating cellular function, based on fluorescent or light-controlled proteins, work best in cultured cells, transparent model species, or small, surgically accessed anatomical regions. Their reach into deep tissues and larger animals is limited by photon scattering. To overcome this limitation, we must design biochemical tools that interface with more penetrant forms of energy. For example, sound waves and magnetic fields easily permeate most biological tissues, allowing the formation of images and delivery of energy for actuation. These capabilities are widely used in clinical techniques such as diagnostic ultrasound, magnetic resonance imaging, focused ultrasound ablation, and magnetic particle hyperthermia. Each of these modalities offers spatial and temporal precision that could be used to study a multitude of cellular processes in vivo. However, connecting these techniques to cellular functions such as gene expression, proliferation, migration, and signaling requires the development of new biochemical tools that can interact with sound waves and magnetic fields as optogenetic tools interact with photons. Here, we discuss the exciting challenges this poses for biomolecular engineering and provide examples of recent advances pointing the way to greater depth in in vivo cell biology