[This entry is marked for removal.]

From POINT Biomedical Corp
BiSphere™ is a technology for drug delivery applications by ultrasound. BiSpheres™ consists of microparticles comprising a shell of an outer layer of a biologically compatible material and an inner layer of biodegradable polymer. The core of the microbubbles contains a filling gas, liquid, or solid for use in drug delivery or as a contrast agent for ultrasonic contrast imaging. The contrast agent particles are capable of passing through the capillary systems of a subject. The drug-loaded biSpheres™ would be administered intravenously and freely circulate throughout the body, while the drug encapsulated within would remain biologically unavailable. The drug would only be released when the biSpheres become flooded when passing through an externally directed ultrasound field.
The use of biSpheres™ to transport agents to specific sites within the body is expected to substantially increase local efficacy while decreasing systemic side effects or adverse reactions. The biSpheres™ may also serve to protect labile agents from metabolism or degradation. The noninvasive release of a protected, encapsulated agent can be controlled by ultrasound imaging to a depth of 20-30 cm from the skin surface.
The flexibility in size control in the biSphere™ technology has enabled the construction of submicron ultrasound contrast agents suitable for lymphatic imaging, with a diameter in the submicron range. This agent, while much smaller in size than CardioSphere®, is based on the BiSphere configuration: a shell within a shell enclosing a gas. The inner layer, made from a biodegradable polymer, provides the physical structure and controls the acoustic response. The outer layer functions as the biological interface. Each of these layers has been independently tailored to fulfill the specific requirements for lymphatic imaging.

Cavitation is any activity of highly compressible transient or stable microbubbles of gas and/or vapour, generated by ultrasonic power in the propagation medium. Cavitation can be described as inertial or non-inertial. Inertial cavitation has the most potential to damage tissue and occurs when a gas-filled cavity grows, during pressure rarefaction of the ultrasound pulse, and contracts, during the compression phase. Collapses of bubbles can generate local high temperatures and pressures. Transient cavitation can cause tissue damage.
The threshold for cavitation is high and does not occur at current levels of diagnostic ultrasound. The introduction of contrast agents leads to the formation of microbubbles that potentially provide gas nuclei for cavitation. The use of contrast agents can lower the threshold at which cavitation occurs.

Types of cavitation:

Microbubbles filled with air or inert gases are used as contrast agents in ultrasound imaging. Compression and rarefaction created by an ultrasound wave insonating a gas-filled microbubble along with the mechanical index of the ultrasonic beam lead to volume pulsations of the bubbles, and it is this change that results in the signal enhancement.
Microbubbles have diameters from 1 μm to 10 μm and a thin flexible or rigid shell composed of albumin, lipid, or polymer confining a gas such as nitrogen, or a perfluorocarbon. These microbubbles can cross the pulmonary capillaries and have a serum half-life of a few minutes. Microbubbles in the 1-10 μm range have their resonance at the frequencies used in diagnostic ultrasound (1−15MHz). Smaller bubbles resonate at higher frequencies. Caused by this coincidence, they are such effective reflectors.
The intrinsic compressibility of microbubbles is approximately 17,000 times more than water, and they are very strong scatterers of ultrasound. Under acoustic pressure the vibrating bubble radius may have a conventional linear response or a harmonic non-linear response. Microbubbles usually increase the Doppler signal amplitude by up to 30 dB.

The definition of imaging is the visual representation of an object. Medical imaging is a broad term that encompasses various imaging modalities and techniques used in the field of medicine to visualize and study the body's anatomy and physiology. It includes both diagnostic and non-diagnostic imaging procedures, where diagnostic imaging specifically refers to the subset of medical imaging techniques that are primarily focused on diagnosing diseases or conditions. Medical imaging techniques are employed to obtain images or visual representations of the internal organs, tissues, and structures, aiding in the diagnosis, treatment, and monitoring of medical conditions.
The field of medical imaging has significantly evolved since the discovery of X-rays by Konrad Roentgen in 1896. Initially, radiological imaging involved focusing X-rays on the body and capturing the images on a single piece of film within a specialized cassette. Subsequent advancements introduced the use of fluorescent screens and special glasses for real-time visualization of X-ray images.
A significant breakthrough came with the application of contrast agents, enhancing image contrast and improving organ visualization. In the 1950s, nuclear medicine studies utilizing gamma cameras demonstrated the uptake of low-level radioactive chemicals in organs, enabling the observation of biological processes in vivo. Currently, positron emission tomography (PET) and single photon emission computed tomography (SPECT) technologies play pivotal roles in clinical research and the diagnosis of biochemical and physiological processes. Additionally, the advent of the x-ray image intensifier in 1955 facilitated the capture and display of x-ray movies.
In the 1960s, diagnostic imaging incorporated the principles of sonar, using ultrasonic waves generated by a quartz crystal. These waves, reflecting at the interfaces between different tissues, were received by ultrasound machines and translated into images through computer algorithms and reconstruction software. Ultrasound (ultrasonography) has become an indispensable diagnostic tool across various medical specialties, with immense potential for further advancements such as targeted contrast imaging, real-time 3D or 4D ultrasound, and molecular imaging. The first use of ultrasound contrast agents (USCA) dates back to 1968.
Digital imaging techniques were introduced in the 1970s, revolutionizing conventional fluoroscopic image intensifiers. Godfrey Hounsfield's pioneering work led to the development of the first computed tomography (CT) scanner. Digital images are now electronic snapshots represented as grids of dots or pixels. X-ray CT brought about a breakthrough in medical imaging by providing cross-sectional images of the human body with high contrast between different types of soft tissue. These advancements were made possible by analog-to-digital converters and computers. The introduction of multislice spiral CT technology dramatically expanded the clinical applications of CT scans.
The first magnetic resonance imaging (MRI) devices were tested on clinical patients in 1980. With technological improvements, such as higher field strength, more open MRI magnets, faster gradient systems, and novel data-acquisition techniques, MRI has emerged as a real-time interactive imaging modality capable of providing detailed structural and functional information of the body.
Today, imaging in medicine offers a wide range of modalities, including:

These imaging modalities have become integral components of modern healthcare. With the rapid advancement of digital imaging, efficient management has become important, leading to the expansion of radiology information systems (RIS) and the adoption of Picture Archiving and Communication Systems (PACS) for digital image archiving. In telemedicine, real-time transmission of all medical image modalities from MRI to X-ray, CT and ultrasound has become the standard. The field of medical imaging continues to evolve, promising further innovations and advancements in the future, ultimately contributing to improved patient care and diagnostics.

See also History of Ultrasound Contrast Agents, and History of Ultrasound.

The earliest introduction of vascular ultrasound contrast agents (USCA) was by Gramiak and Shah in 1968, when they injected agitated saline into the ascending aorta and cardiac chambers during echocardiographic to opacify the left heart chamber. Strong echoes were produced within the heart, due to the acoustic mismatch between free air microbubbles in the saline and the surrounding blood.