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History of Ultrasound Contrast Agents
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.
The disadvantage of this microbubbles produced by agitation, was that the air quickly leak from the thin bubble shell into the blood, where it dissolved. In addition, the small bubbles that were capable of traversing the capillary bed did not survive long enough for imaging because the air quickly dissipated into the blood. Aside from agitated saline, also hydrogen peroxide, indocyanine green dye, and iodinated contrast has been tested. The commercial development of contrast agents began in the 1980s with greatest effort to the stabilization of small microbubbles.

The development generations by now:
first generation USCA = non-transpulmonary vascular;;
second generation USCA = transpulmonary vascular, with short half-life (less than 5 min);
third generation USCA = transpulmonary vascular, with longer half-life (greater than 5 min).

To pass through the lung capillaries and enter into the systemic circulation, microspheres should be less than 10 μm in diameter. Air bubbles in that size range persist in solution for only a short time; too short for systemic vascular use.
The first developed agent was Echovist (1982), which enabled the enhancement of the right heart. The second generation of echogenic agents, sonicated 5% human albumin-containing air bubbles (Albunex), were capable of transpulmonary passage but often failed to produce adequate imaging of the left heart. Both Albunex and Levovist utilize air as the gas component of the microbubble.
In the 1990s newer developed agents with fluorocarbon gases and albumin, surfactant, lipid, or polymer shells have an increased persistence of the microspheres. This smaller, more stable microbubble agents, and improvements in ultrasound technology, have resulted in a wider range of application including myocardial perfusion.

See also First Generation USCA, Second Generation USCA, and Third Generation USCA.
Medical Imaging
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:
X-ray projection imaging;
Fluoroscopy;
Computed tomography (CT / CAT);
Single photon emission computed tomography (SPECT);
Positron emission tomography (PET);
Mammography.

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.
Stress Echocardiogram
Stress echocardiograms are used for detection of coronary artery disease, or to determine the cardiac performance. Stress echocardiograms are less performed to evaluate pulmonary artery pressures, pulmonary hypertension or the significance of valvular heart disease.
Stress increases the degree to which the heart contracts. After a myocardial infarction there will be a region of the heart muscle that contracts abnormal at rest. This area may worsen with stress. A coronary artery blockage most often do not impairs the function of the heart at rest. With stress, a region of the heart does not receive enough blood to work effectively and wall motion abnormalities occur. The echocardiographer compares rest and exercise and can determine the presence and severity of a coronary artery blockage.

Stress echocardiograms involve:
A bicycle stress echocardiogram involves transthoracic echocardiography performed at the rest baseline and after or during different stages of physical exercise.
A dobutamine stress echocardiography uses the drug dobutamine instead physical exercise.
Transthoracic echocardiograms are routinely performed during stress and rest.
Cardiovascular stress represents a minimal risk to the patient.

See also Transesophageal Echocardiography, Echocardiography, M-Mode, Curved Transducer, Doppler Ultrasound, History of Ultrasound and History of Ultrasound Contrast Agents.
Third Generation USCA
The third generation ultrasound contrast agents (UCA/USCA) are more echogenic and stable, and are able to enhance the echogenicity of parenchyma on B-mode images. These microbubbles may thus show perfusion, even in such a difficult region as the myocardium.

See also History of Ultrasound Contrast Agents.
Lantheus Medical Imaging
www.lantheus.com Lantheus Medical Imaging, Inc. engages in discovering, developing, and marketing medical imaging agents. Lantheus Medical Imaging has headquarters in North Billerica, Massachusetts, and offices in Puerto Rico, Canada, and Australia. During its history, the company launched the products Cardiolite (Technetium Tc99m Sestamibi Preparation Kit), which has become the gold standard for use in myocardial perfusion imaging, and Definity (perflutren lipid microsphere) for use in suboptimal echocardiograms.
From 2001 to 2008 Lantheus was part of the Bristol-Myers Squibb Medical Imaging, Inc. group.

Ultrasound Contrast Agents:
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Lantheus Medical Imaging
Bldg. 200-2
331 Treble Cove Rd.
N. Billerica, MA 01862
USA
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