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Radionuclide angiography is an area of
nuclear medicine Nuclear medicine or nucleology is a medical specialty involving the application of radioactive substances in the diagnosis and treatment of disease. Nuclear imaging, in a sense, is "radiology done inside out" because it records radiation emitting ...
which specialises in imaging to show the
functionality Function or functionality may refer to: Computing * Function key, a type of key on computer keyboards * Function model, a structured representation of processes in a system * Function object or functor or functionoid, a concept of object-oriente ...
of the right and left ventricles of the
heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...
, thus allowing informed diagnostic intervention in
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
. It involves use of a
radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is ...
, injected into a patient, and a
gamma camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
for acquisition. A MUGA scan (multigated acquisition) involves an acquisition triggered (gated) at different points of the
cardiac cycle The cardiac cycle is the performance of the human heart from the beginning of one heartbeat to the beginning of the next. It consists of two periods: one during which the heart muscle relaxes and refills with blood, called diastole, following ...
. MUGA scanning is also called equilibrium radionuclide angiocardiography, radionuclide ventriculography (RNVG), or gated blood pool imaging, as well as SYMA scanning (synchronized multigated acquisition scanning). This mode of imaging uniquely provides a
cine Ciné film or cine film is the term commonly used in the UK and historically in the US to refer to the 8 mm, Super 8, 9.5 mm, and 16 mm motion picture film formats used for home movies. It is not normally used to refer ...
type of image of the beating heart, and allows the interpreter to determine the efficiency of the individual
heart valve A heart valve is a one-way valve that allows blood to flow in one direction through the chambers of the heart. Four valves are usually present in a mammalian heart and together they determine the pathway of blood flow through the heart. A heart v ...
s and
chambers Chambers may refer to: Places Canada: *Chambers Township, Ontario United States: *Chambers County, Alabama * Chambers, Arizona, an unincorporated community in Apache County * Chambers, Nebraska * Chambers, West Virginia * Chambers Township, Hol ...
. MUGA/Cine scanning represents a robust adjunct to the now more common
echocardiogram An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in th ...
. Mathematics regarding acquisition of
cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: t ...
(''Q'') is well served by both of these methods as well as other inexpensive models supporting
ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, ventricle, gall bladder, ...
as a product of the heart/myocardium in
systole Systole ( ) is the part of the cardiac cycle during which some chambers of the heart contract after refilling with blood. The term originates, via New Latin, from Ancient Greek (''sustolē''), from (''sustéllein'' 'to contract'; from ''sun ...
. The advantage of a MUGA scan over an echocardiogram or an
angiogram Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is performe ...
is its accuracy. An echocardiogram measures the shortening fraction of the ventricle and is limited by the user's ability. Furthermore, an angiogram is invasive and, often, more expensive. A MUGA scan provides a more accurate representation of cardiac ejection fraction.


History

The MUGA scan was first introduced in the early 1970s and quickly became accepted as the preferred technique for measurement of left ventricular ejection fraction (LVEF) with a high degree of accuracy. Several early studies demonstrated an excellent correlation of MUGA-derived LVEF with values obtained by cardiac catheterization contrast ventriculography.


Purpose

Radionuclide ventriculography is done to evaluate
coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
(CAD),
valvular heart disease Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These ...
,
congenital heart disease A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
s,
cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
, and other
cardiac disorder Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
s. MUGA is typically ordered for the following patients: * With known or suspected
coronary artery disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...
, to diagnose the disease and predict outcomes * With
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...
s in their
heart valve A heart valve is a one-way valve that allows blood to flow in one direction through the chambers of the heart. Four valves are usually present in a mammalian heart and together they determine the pathway of blood flow through the heart. A heart v ...
s * With
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
* Who have undergone
percutaneous transluminal coronary angioplasty Percutaneous coronary intervention (PCI) is a non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The process involves combining coronary angioplasty with stenting, which is the i ...
,
coronary artery bypass graft Coronary artery bypass surgery, also known as coronary artery bypass graft (CABG, pronounced "cabbage") is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pai ...
surgery, or medical therapy, to assess the efficacy of the treatment * With low
cardiac output In cardiac physiology, cardiac output (CO), also known as heart output and often denoted by the symbols Q, \dot Q, or \dot Q_ , edited by Catherine E. Williamson, Phillip Bennett is the volumetric flow rate of the heart's pumping output: t ...
after open-heart surgery * Who are undergoing
cardiotoxic Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by chemotherapy (a usual example is th ...
drug agents such as in
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
e.g., with
doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used togeth ...
or
immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
(
herceptin Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wi ...
) * Who have had a
cardiac transplant A heart transplant, or a cardiac transplant, is a surgical transplant procedure performed on patients with end-stage heart failure or severe coronary artery disease when other medical or surgical treatments have failed. , the most common proce ...
Radionuclide ventriculography gives a much more precise measurement of left ventricular ejection fraction (LVEF) than a transthoracic echocardiogram (TTE). Transthoracic echocardiogram is highly operator dependant, therefore radionuclide ventriculography is a more reproducible measurement of LVEF. Its primary use today is in monitoring cardiac function in patients receiving certain chemotherapeutic agents (anthracyclines: doxorubicin or daunorubicin) which are cardiotoxic. The chemotherapy dose is often determined by the patient's cardiac function. In this setting, a much more accurate measurement of ejection fraction, than a transthoracic echocardiogram can provide, is necessary.


Procedure

The MUGA scan is performed by labeling the patient's red blood pool with a radioactive tracer,
technetium Technetium is a chemical element with the symbol Tc and atomic number 43. It is the lightest element whose isotopes are all radioactive. All available technetium is produced as a synthetic element. Naturally occurring technetium is a spontaneous ...
-99m-
pertechnetate The pertechnetate ion () is an oxyanion with the chemical formula . It is often used as a convenient water-soluble source of isotopes of the radioactive element technetium (Tc). In particular it is used to carry the 99mTc isotope (half-life 6 hou ...
(Tc-99m), and measuring radioactivity over the anterior chest as the radioactive blood flows through the large vessels and the heart chambers. The introduction of the radioactive marker can either take place ''
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' or ''
in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...
''. In the in vivo method, stannous (
tin Tin is a chemical element with the symbol Sn (from la, stannum) and atomic number 50. Tin is a silvery-coloured metal. Tin is soft enough to be cut with little force and a bar of tin can be bent by hand with little effort. When bent, t ...
) ions are injected into the patient's bloodstream. A subsequent intravenous injection of the
radioactive Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is consid ...
substance,
technetium Technetium is a chemical element with the symbol Tc and atomic number 43. It is the lightest element whose isotopes are all radioactive. All available technetium is produced as a synthetic element. Naturally occurring technetium is a spontaneous ...
-99m-
pertechnetate The pertechnetate ion () is an oxyanion with the chemical formula . It is often used as a convenient water-soluble source of isotopes of the radioactive element technetium (Tc). In particular it is used to carry the 99mTc isotope (half-life 6 hou ...
, labels the red blood cells ''
in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
''. With an administered activity of about 800
MBq ''MBQ'' is an original English-language manga created by Tokyopop's Rising Stars of Manga second-place winner Felipe Smith. ''MBQ'' is an expansion of his second-place winning entry in the third Rising Stars competition. It is the story of a you ...
, the
effective radiation dose Effective dose is a dose quantity in the International Commission on Radiological Protection (ICRP) system of radiological protection.ICRP publication, 103 para 103 It is the tissue-weighted sum of the equivalent doses in all specified tissues and ...
is about 6
mSv mSv or MSV may refer to: * Maize streak virus, a plant disease * Medium-speed vehicle, US category * Medium Systems Vehicle, a class of fictional artificially intelligent starship in The Culture universe of late Scottish author Iain Banks * Mill ...
. In the ''in vitro'' method, some of the patient's blood is drawn and the stannous ions (in the form of
stannous chloride Tin(II) chloride, also known as stannous chloride, is a white crystalline solid with the formula . It forms a stable dihydrate, but aqueous solutions tend to undergo hydrolysis, particularly if hot. SnCl2 is widely used as a reducing agent (in acid ...
) are injected into the drawn blood. The technetium is subsequently added to the mixture as in the ''in vivo'' method. In both cases, the stannous chloride reduces the technetium ion and prevents it from leaking out of the red blood cells during the procedure. The ''in vivo'' technique is more convenient for the majority of patients since it is less time-consuming and less costly and more than 80 percent of the injected radionuclide usually binds to red blood cells with this approach. Red blood cell binding of the radioactive tracer is generally more efficient than ''in vitro'' labeling, and it is preferred in patients with indwelling intravenous catheters to decrease the adherence of Tc-99m to the catheter wall and increase the efficiency of blood pool labeling. The patient is placed under a
gamma camera A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
, which detects the low-level 140
keV Kev can refer to: Given name * Kev Adams, French comedian, actor, screenwriter and film producer born Kevin Smadja in 1991 * Kevin Kev Carmody (born 1946), Indigenous Australian singer-songwriter * Kev Coghlan (born 1988), Scottish Grand Prix motor ...
gamma Gamma (uppercase , lowercase ; ''gámma'') is the third letter of the Greek alphabet. In the system of Greek numerals it has a value of 3. In Ancient Greek, the letter gamma represented a voiced velar stop . In Modern Greek, this letter re ...
radiation being given off by
Technetium-99m Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical ra ...
(99mTc). As the gamma camera images are acquired, the patient's heart beat is used to 'gate' the acquisition. The final result is a series of images of the heart (usually sixteen), one at each stage of the
cardiac cycle The cardiac cycle is the performance of the human heart from the beginning of one heartbeat to the beginning of the next. It consists of two periods: one during which the heart muscle relaxes and refills with blood, called diastole, following ...
. Depending on the objectives of the test, the doctor may decide to perform either a resting or a stress MUGA. During the resting MUGA, the patient lies stationary, whereas during a stress MUGA, the patient is asked to exercise during the scan. The stress MUGA measures the heart performance during exercise and is usually performed to assess the impact of a suspected coronary artery disease. In some cases, a
nitroglycerin Nitroglycerin (NG), (alternative spelling of nitroglycerine) also known as trinitroglycerin (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless, oily, explosive liquid most commonly produced by nitrating g ...
MUGA may be performed, where nitroglycerin (a
vasodilator Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...
) is administered prior to the scan. The resulting images show that the
volumetric Volume is a measure of occupied three-dimensional space. It is often quantified numerically using SI derived units (such as the cubic metre and litre) or by various imperial or US customary units (such as the gallon, quart, cubic inch). The defi ...
ally derived blood pools in the chambers of the heart and timed images may be computationally interpreted to calculate the
ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, ventricle, gall bladder, ...
and
injection fraction An ejection fraction (EF) is the volumetric fraction (mathematics), fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or cardiac cycle, heartbeat). It can refer to the card ...
of the heart. The Massardo method can be used to calculate ventricle volumes. This nuclear medicine scan yields an accurate, inexpensive and easily reproducible means of measuring and monitoring the ejection and injection fractions of the ventricles, which are one of many of the important clinical metrics in assessing global heart performance.


Radiation exposure

It exposes patients to less radiation than do comparable
chest x-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most common film taken in med ...
studies. However, the radioactive material is retained in the patient for several days after the test, during which sophisticated radiation alarms may be triggered, such as in airports.Merck manuals > Radionuclide Imaging
Last full review/revision May 2009 by Michael J. Shea, MD. Content last modified May 2009
Radionuclide ventriculography has largely been replaced by
echocardiography An echocardiography, echocardiogram, cardiac echo or simply an echo, is an ultrasound of the heart. It is a type of medical imaging of the heart, using standard ultrasound or Doppler ultrasound. Echocardiography has become routinely used in t ...
, which is less expensive, and does not require radiation exposure.


Results


Normal results

In normal subjects, the left ventricular ejection fraction (LVEF) should be about 50%(range, 50-80%). There should be no area of abnormal wall motion ( hypokinesis, akinesis or dyskinesis). Abnormalities in cardiac function may be manifested as a decrease in LVEF and/or the presence of abnormalities in global and regional wall motion. For normal subjects, peak filling rates should be between 2.4 and 3.6
end diastolic volume In cardiovascular physiology, end-diastolic volume (EDV) is the volume of blood in the right or left ventricle at end of filling in diastole which is ammount of blood present in ventricle at the end of diastole systole. Because greater EDVs cause g ...
(EDV) per second, and the time to peak filling rate should be 135-212 ms.


Abnormal results

An uneven distribution of technetium in the heart indicates that the patient has coronary artery disease, a
cardiomyopathy Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
, or blood shunting within the heart. Abnormalities in a resting MUGA usually indicate a heart attack, while those that occur during exercise usually indicate
ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
. In a stress MUGA, patients with coronary artery disease may exhibit a decrease in ejection fraction. For a patient that has had a heart attack, or is suspected of having another disease that affects the heart muscle, this scan can help pinpoint the position in the heart that has sustained damage as well as assess the degree of damage. MUGA scans are also used to evaluate heart function prior to and while receiving certain chemotherapies (e.g. doxorubicin (Adriamycin)) or immunotherapy (specifically,
herceptin Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together wi ...
) that have a known effect on heart function.


Massardo method

The Massardo method is one of a number of approaches for estimating the volume of the ventricles and thus ultimately the ejection fraction. Recall that a MUGA scan is a nuclear imaging method involving the injection of a radioactive isotope (
Tc-99m Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical r ...
) that acquires gated 2D images of the heart using a
SPECT Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
scanner. The pixel values in such an image represent the number of counts (nuclear decays) detected from within that region in a given time interval. The Massardo method enables a 3D volume to be estimated from such a 2D image of decay counts via: V = 1.38 M^3 r^ , where M is the pixel dimension and r is the ratio of total counts within the ventricle to the number of counts within the brightest (hottest) pixel. The Massardo method relies on two assumptions: (i) the ventricle is spherical and (ii) the radioactivity is homogeneously distributed. The
ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, ventricle, gall bladder, ...
, E_f , can then be calculated: E_f(\%) = \frac \times 100 , where the EDV (end-diastolic volume) is the volume of blood within the ventricle immediately before a contraction and the ESV (end-systolic volume) is the volume of blood remaining in the ventricle at the end of a contraction. The ejection fraction is hence the fraction of the end-diastolic volume that is ejected with each beat. The Siemens Intevo
SPECT Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
scanners employ the Massardo method in their MUGA scans. Other methods for estimating ventricular volume exist, but the Massardo method is sufficiently accurate and simple to perform, avoiding the need for blood samples, attenuation corrections or decay corrections.


Derivation

Define the ratio r as the ratio of counts within the chamber of the heart to the counts in the hottest pixel: r = \frac = \frac . Assuming that the activity is homogeneously distributed, the total count is proportional to the volume. The maximum pixel count is thus proportional to the length of the longest axis perpendicular to the collimator, D_m, times the cross-sectional area of a pixel, M^2. We can thus write: N_m = K M^2 D_m , where K is some constant of proportionality with units counts/cm^3. The total counts, N_t, can be written N_t = K V_t where V_t is the volume of the ventricle and K is the same constant of proportionality since we are assuming a homogeneous distribution of activity. The Massardo method now makes the simplification that the ventricle is spherical in shape, giving N_t = K \left( \frac \right) D^3 , where D is the diameter of the sphere and is thus equivalent to D_m above. This allows us to express the ratio r as r = \frac = \frac , finally giving the diameter of the ventricle in terms of r, i.e. counts, alone: D^2 = \left( \frac \right) M^2 r . From this, the volume of the ventricle in terms of counts alone is simply V_t = \sqrt M^3 r^ \approx 1.38 M^3 r^ .


References


External links

* {{Medical imaging 2d nuclear medical imaging Cardiovascular physiology Cardiac imaging