GLOSSARY OF TERMS
Accuracy: A measure of the percentage of patients in which an imaging test is correct relative to a truth standard. It is the sum of the number of true positives plus true negatives divided by the sum of the true positives plus true negatives plus false positives plus false negatives.
Acute systemic inflammation response: The body’s natural system for reacting quickly to foreign stimuli/agents, such as the presence of bacteria, virus particles etc.
Adenosine: Adenosine is a naturally occurring chemical present in all tissues and has many functions. Adenosine causes dilation of the coronary arteries, increasing blood flow to the heart muscle, and so mimics the effect of exercise. Other agents such as dipyridamole, which works by increasing the amount of free adenosine in the blood, also acts as pharmacologic stressors, and are used in imaging tests when patients cannot exercise adequately.
Angiography: Angiography or arteriography is a medical imaging technique to visualize blood in the inside, or lumen, of arteries. It can therefore detect the presence of flow limiting blockages. Coronary angiography is a highly invasive technique involving the puncturing of an artery, usually in the groin, threading a thin tube through the arterial system into the arteries supplying blood to the heart muscle and injecting a dye which shows up using X-rays. The film or image of the arteries is called an angiogram.
Agreement: A measure of the percentage of patients in which the test is correct relative to a standard.
Aggressive readers: Cardiologists who interpret images (nuclear or ultrasound) with minor irregularities in perfusion or wall motion as being abnormal, and therefore diagnose the patients as having coronary artery disease.
Apex: Region of the left ventricle, the main pumping chamber of the heart, which is at the tip of the heart, closest to the chest wall.
Attenuation: An artifact that results from the ultrasound contrast agent causing a shadow on an adjacent area that obscures that part of the image. This phenomenon results from the contrast agent absorbing too much of the ultrasound beam instead of reflecting it. The shadowing occurs when a large amount of contrast agent is directly between the ultrasound energy source and the region of the heart being studied. This is a common phenomenon with injection of early ultrasound contrast agents like Definity® or Optison®.
Baseline wall motion (BWM): Ultrasound study of heart wall motion without using contrast, often used as a reference standard for comparing the effect of adding a contrast agent.
Blinded readers: Cardiologists, with expertise in reading stress echo images (echo blinded reader) or nuclear stress images (nuclear blinded reader), who have access to no clinical information about the patient, and so have to make their diagnoses solely on the images they see. Blinded reading is much more difficult than reading in the normal clinical setting, where physicians have access to patient history, symptoms and other test results.
Blood pool imaging: Imaging of the large, blood containing chambers of the heart, particularly the left ventricle. Bradycardia: Slow heart rate, typically defined as being under 60 beats per minute, though seldom symptomatic until the rate drops below 50 beat/min. Resting bradycardia is often considered normal if the individual has no other symptoms such as fatigue, weakness, dizziness, lightheadedness, fainting, chest discomfort, palpitations or shortness of breath associated with it.
CABG: Coronary artery bypass grafting, an open heart surgical procedure performed to relieve angina and reduce the risk of death from coronary artery disease. Arteries or veins from elsewhere in the patient's body are grafted to the coronary arteries to bypass blockages and improve the blood supply to the heart muscle.
CI: Confidence Interval is the range of values for a measurement within which the true value will likely fall. It is based on statistical calculations, which depend on the number of data points and the level of certainty that is required (for clinical applications, this is usually 95%).
Conservative readers: Cardiologists who interpret images (nuclear or ultrasound) with minor irregularities in perfusion or wall motion as being normal, and therefore diagnose the patients as not having coronary artery disease.
Continuous imaging: Standard method of acquiring 2-dimensional ultrasound images which enables a moving object, such as the beating heart, to be visualized in motion (real time).
Cyanosis: Blue coloration of the skin due to a lack of oxygen in blood vessels near the skin surface. It occurs when the overall oxygen level (referred to as oxygen saturation or SaO2) in the blood falls below 85-90%.
Dipyridamole: An approved IV drug used to cause vasodilatation of the coronary arteries. It simulates the effects of exercise stress on blood flow to the heart muscle, and is a common agent used in nuclear perfusion studies of the heart when patients cannot exercise adequately.
Dobutamine: Dobutamine is an IV drug which speeds up the heart rate, just like exercise. It is commonly used in stress ultrasound imaging of the heart to mimic the effects of exercise in patients who cannot exercise adequately.
Echocardiography: Ultrasound study of the heart.
Hyperlipidemia: The presence of raised or abnormal levels of lipids and/or lipoproteins in the blood.
Hypertension: Abnormally high blood pressure.
Hypotension: Abnormally low blood pressure.
Inducible ischemia: Inadequate blood flow to parts of the heart muscle under stress conditions, but normal at rest. This indicates that the coronary artery supplying the area is obstructed.
Ischemia: Inadequate blood flow to the heart muscle.
Lateral wall: Region of the wall of the left ventricle that is furthest away from the right ventricle.
Left ventricular opacification (LVO): The ability of an ultrasound contrast agent to highlight the blood pool inside the left ventricle and so help delineate the borders of the inside wall of the ventricle. This improves image quality of a wall motion study and is the indication for current approved ultrasound contrast agents.
Leukocytosis: A transient increase in the number of leukocytes (white blood cells) in the blood.
Lymphocyte: Type of white blood cell in the immune system. Lymphocytes play an important and integral role in the body's defenses.
MAA: Marketing Authorization Application seeking regulatory approval in the European Union to market and sell a new drug such as Imagify. It is the European equivalent of an NDA which is submitted in the U.S. to the FDA.
Macrophages: Cells within the tissues that engulf and then digest cellular debris and microparticles (such as bacteria) and stimulate lymphocytes and other immune cells to respond to the potentially harmful agents.
MIBI: Abbreviation for the generic name (sestamibi) of Cardiolite®, the global leading radiopharmaceutical used in nuclear imaging to detect myocardial perfusion.
Microbubble: Thin shelled, gas filled bubbles whose average diameter is in the micrometer (millionth of a meter) range. The current FDA approved microbubble ultrasound contrast agents are indicated for use in certain patients with suboptimal echocardiograms. These products are used to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.
Microsphere: Spherical particles composed of various natural and synthetic materials with diameters in the micrometer range.
mITT: Modified intent to treat. The Intent-to-Treat population in a clinical trial is based upon all randomized patients who receive the drug under study. Usually some patients are allowed to be excluded from final data analysis due to pre-specified criteria (such as missing truth standard or comparator data), leaving a smaller group known as mITT.
Monocyte: Type of leukocyte, part of the body's immune system.
Myocardial perfusion: Blood flow in the heart muscle.
NDA: New Drug Application seeking U.S. regulatory approval to market and sell a new drug such as Imagify.
Neutrophil count: Measure of the number of neutrophil granulocytes present in the blood. Neutrophils are a type of white blood cell that fights against infection.
Non-inferiority: A statistical type of trial analysis, which is designed to show that one test or product, has similar performance to another test, within a certain statistical margin of error.
P value: A statistical measure which is the probability that the particular result obtained in a trial could have happened by random chance. Parasternals: One of the standard views of the heart muscle during echocardiography which enable the cardiologist to see all the regions of the wall of the left ventricle.
Perflubutane: A colorless, water insoluble gas.
RAMP-1 and RAMP-2: Two pivotal Phase 3 trials conducted by Acusphere to assess the safety and efficacy of Imagify. The purpose of these trials is to demonstrate that stress echo with Imagify is non-inferior to nuclear stress testing. RAMP is an abbreviation for Real-time Assessment of Myocardial Perfusion with echocardiography.
Reticuloendothial systems: Often abbreviated as RES, they are part of the immune system. One function of the RES is to clear particles from the blood.
Rigors: Trembling or shaking that often occurs during fever.
Sensitivity: Ability of an imaging technique, expressed as a percentage, to detect disease in comparison to a standard. It is the number of true positives divided by the sum of the true positives plus the false negatives.
Septal wall: Region of the heart muscle which separates the left and right ventricles.
Specificity: Ability of an imaging technique, expressed as a percentage, to detect normalcy in comparison to a standard. It is the number of true negatives divided by the sum of the true negatives plus the false positives.
SPECT: Abbreviation for Single Photon Emission Computed Tomography, which is the state-of-the-art technique of acquiring nuclear perfusion images.
Stress echo: Ultrasound study of the heart which compares wall motion at rest to wall motion under exercise or pharmacologic stress.
Stress perfusion imaging: Study which compares blood flow in the muscle of the left ventricle at rest compared to stress (exercise or pharmacologic). Absence of perfusion in the same area at rest and stress indicates the presence of dead tissue from an old heart attack; absence of perfusion at stress, with normal perfusion at rest, indicates inducible ischemia.
Territorial vascular bed scores: The images of the heart (SPECT nuclear and Imagify echo) are divided up into multiple segments, with each segment being scored individually by the blinded readers as having normal or abnormal perfusion and/or wall motion. These individual segments were then collapsed into three major territories, which represent the areas of the heart muscle which are supplied by each of the 3 major coronary arteries. This allows the cardiologist to potentially identify which coronary artery is blocked and causing the perfusion/wall motion defect.
Triggered imaging: Sometimes called intermittent imaging, this is a method of ultrasound imaging which relies on short pulses of ultrasound energy delivered every few seconds, typically timed to coincide with a particular point in the cardiac cycle. In this technique, the image of the moving heart is frozen in place as a still frame until the next ultrasound pulse is delivered and a new updated stationary image replaces it. This is one of the ways to capture perfusion information, but does not allow for simultaneous assessment of wall motion.
Vasovagal syncope: Fainting or feeling like you are going to faint. This is a set of conditions commonly encountered when patients have IV injections, blood drawn, or are giving blood donation.
Wall motion: The ability of the heart muscle in the left ventricle to contract and therefore efficiently pump blood. Dead heart muscle resulting from an old heart attack, or ischemic heart muscle resulting from an obstructed coronary artery causes the absent or diminished wall motion.