Cardiovascular System :Cardiovascular System Radionuclide studies of the cardiovascular system are primarily used to detect and characterize acquired heart diseases such as coronary artery disease or CAD, cardiotoxicity of anti-cancer drugs, and congestive heart failure (CHF). both SPECT and PET are utilized; PET has higher spatial resolution than SPECT and can be used to acquire data on myocardial perfusion, ventricular function, and viability in similar fashion to those obtained with SPECT cameras 1


Slide 2:Statistics Approximately 71 million people in United States have one or more forms of heart or blood vessel disease. 65 million Americans have hypertension CAD is present in 13.2 million Americans CHF in approximately 4.9 million and stroke and 4.4 million CAD caused about 500,000 deaths in United States in 2002 making it the number one killer in the U.S. About 1.2 million people will suffer a new or recurrent heart attack each year 550,000 new cases of heart failure occur each year (the inability of the heart to pump sufficient blood to meet the demand of the body occur) 2


Slide 3:Cardiomyopathy, a disorder of the heart muscle has two major forms: 1. Abnormal increase in the thickness of the myocardium; 2. Poor contractibility of the myocardium results in thinning of the muscle and dilation of the chambers Myocardial ischemia is a reversible condition caused by temporary deficiency in the supply of oxygen to the myocardium, usually as a result of narrowing of a coronary artery. Myocardial infarction is irreversible damage to myocardium caused by lack of blood supply as a result of occluded arteries; early ID important; restoration of blood flow within six hours often results in preservation of myocardium and improved function Disease progression: Fatty streaks which began around puberty progress to raised lesions that intrude in the arterial lumen over about 30 to 50 years. 3


Slide 4:Diabetes, elevated cholesterol, elevated homocysteine levels, and diets rich in saturated/trans fats accelerate the progression of CAD Narrowing of >=70% of the lumen often result in symptoms Ischemia is associated with decreased tissue perfusion and decreased contraction in the affected area; these changes can be readily detected by radionuclide imaging studies. Anatomy Review The adult heart holds around 500 mL of blood The heart is actually two pumps, right heart and left heart, operating in parallel to eject the same amount of blood with each beat The right heart accepts blood from the body and pumps this blood to the lungs, where it is oxygenated 4


Slide 5:The left heart accepts blood returning from the lungs and pumps it to the body Each side has two chambers, a thin walled atrium which holds about 100 mL and a more muscular ventricle with a capacity of about 150 mL Atria serve as temporary reservoirs for blood returned to the heart and the ventricles do the major work of pumping the blood away from the heart The right atrium accepts the deoxygenated blood returning to the heart from the body through the superior and inferior vena cava The right atrium pumps blood into the right ventricle, which in turn pumps the blood to the lungs, where it is oxygenated before returning to the left atrium Left atrium pumps oxygenated blood to the left ventricle, which pumps the oxygenated blood to the body 5


Slide 6:Right and left atrium are separated by a thin, muscular wall- the interatrial septum; ventricles are separated by the thicker, muscular interventricular septum Valves prevent blood from flowing backwards Valve separate the atria from the ventricles and the ventricles from the arteries The tricuspid valve separates the right atrium from the right ventricle The mitral valve separates the left atrium from the left ventricle The pulmonary valve separates the right ventricle from the pulmonary artery They are aortic valve separates the left ventricle from the aorta The myocardium or heart muscle needs blood and nutrients to supply its own needs, which it gets via coronary arteries 6


Slide 7:7


Slide 8:The left main coronary artery divides into two main branches: left anterior descending artery supplies oxygen and nutrition to the interventricular septum and the anterior wall of the left ventricle The left circumflex artery supplies the left atrium and posterior and lateral walls of the left ventricle the right coronary artery supplies the inferior wall of the left ventricle, the free wall of the right ventricle, and the right atrium blood drains from the heart muscle via coronary veins which run long alongside coronary arteries and terminate in the coronary sinus of the right atrium, where this deoxygenated blood mixes with blood from the vena cava 8


Slide 9:9


Slide 10:Mechanical Activity of the Heart: Each cardiac cycle consists of systole- the period of ventricular contraction and diastole-the period of ventricular relaxation; the two sides of the heart contract in unison. The quantity of blood in the ventricle at the end of diastole is called end diastolic volume, which is about 150 mL in an average adult. During systole, the myofibrils of the ventricular myocardium shorten, and the left ventricle pressure rises causing the mitral valve to close The aortic valve opens and ventricular ejection begins; blood is also returned to the left atrium 10


Slide 11:11


Slide 12:At the conclusion of left ventricular ejection, the myofibrils rapidly relax, left ventricular pressure falls, the aortic valve closes, mitral valve opens, and the ventricle starts to fill with blood from the atria The amount of blood ejected from the left ventricle over a one minute interval is called cardiac output. The amount of blood ejected in a single beat is the stroke volume; normal adult stroke volume is approximately 80 to 100 mL the sinoatrial node is a small mass of specialized cells embedded in the walls of the right atrium near the entrance of the superior vena cava; it serves as the impulse generator for the remainder of the heart. The wave of electrical depolarization spreads to the surrounding atrial muscle cells and stimulates mechanical contraction 12


Slide 13:The electrocardiogram or ECG reflects electrical activity of the heart. It consists of a P wave, QRS complex, and T-wave. The P-wave is the electrical signal that starts atrial contraction; the QRS complex serves the same function in the ventricles, and the T-wave identifies an electrical reset of the ventricles for the next cardiac cycle. box 16 – 1 page 484 Imaging: SPECT cardiac images are recorded at 3 to 6° steps in an arc spanning at least 180°, beginning at 30° RAO and moving to 30° LPO Digital image data are typically recorded in a 64 x 64 matrix for standard FOV detector or a 128 x 128 matrix for a large FOV detector. The individual projections are reconstructed into a series of transverse slices through the image of the volume. The transverse slices are reoriented along the long axis of the left ventricle. 13


Slide 14:14 ECG


Slide 15:The reoriented images are then reconstructed into the three standard cardiac views: vertical long axis which corresponds to coronal images; vertical long axis images slice the volume from the anterior lateral wall to the inferior wall Horizontal long axis which corresponds to transverse sections; horizontal long axis images depict the right ventricle, septum, and posterior wall Short axis which corresponds to the sagittal views; short axis depicts the myocardium from apex to base Reconstruction is done using either filtered back projection or iterative algorithms 15


Slide 16:16


Slide 17:Although motion correction software is available, the corrections are often incomplete and may result in artifacts in the reconstructed data. Multiple episodes of motion or movement >2 pixels, or loss of >1 set of projection data creates significant artifacts that can lead to erroneous interpretation and the acquisition should be repeated (when possible). To record the 180° arc around the patient, a dual detector system with the detectors oriented 90° to each other is preferable because the detectors are closest to the heart for each image; is often called cardiac 90 mode 180° limited imaging reduces both the noise that comes from recording highly attenuated data from the patient’s back which is far from the heart, and the attenuation artifacts that may be caused by the spine. 17


Slide 18:High-resolution collimators should be used Data is collected for 15 to 60 seconds at each step; angular sampling of about 3° or continuous data acquisition is recommended; step and shoot mode (stops at each position) has greater resolution due to no detector motion blurring but an acquisition requires more time Common angular projections for imaging range from 30 to 64 Elliptical orbits have better resolution but are more complicated; a circular orbit generally is used During a 20 to 30 minute acquisition the patient lies supine with the left arm above the head Prone is sometimes used to minimize attenuation from the diaphragm at a cost of decreased patient comfort. 18


Slide 19:19 Top: cardiac 90 mode Right: SPECT acquisition


Slide 20:SPECT imaging should begin about 10 minutes after high-level exercise to avoid the phenomenon of myocardial motion caused by change in the degree of diaphragmatic excursion as the patient’s respiration returns to normal (post exercise) This phenomenon has been referred to as myocardial creep or upward creep and is seen mostly in patients who achieve high levels of exercise It typically results in an artifactual lesion in the inferior or inferoseptal regions of the left ventricle 20 FIGURE 1.  (A) Projection images derived from stress SPECT. (B and C) Thirty-second frame is last projection image of detector 2 (B), and 33rd frame is first projection image of detector 1 (C). Upward creep of heart can easily be detected by comparing distance between lower edge of image and lowest part of heart silhouette on these consecutive images.


Slide 21:Gated acquisition is possible to show regional wall motion and ejection fraction utilizing the patient’s cardiac cycle; technetium agents give better image quality for gated SPECT Attenuation correction: the soft tissue the chest musculature, breast and diaphragm are known to cause attenuation of the signal and lead to artifacts that resemble perfusion defects; this is usually worse for thallium and less significant for Tc99m agents Attenuation can be corrected by measuring the attenuation coefficient using a transmission source or using the x-ray beams from a SPECT CT machine Information is incorporated in the reconstruction data to compensate for the attenuation Gadolinium 153 or Cobalt 57 are used for Tc99m; Americium 241 is used for Tl-201attenuation correction 21


Slide 22:22 Examples of AC


Slide 23:The rod source itself can cause artifacts by scatter of emission data into the attenuation window and insufficient photon flux for the attenuation images caused by very obese patients or weak sources Myocardial Perfusion Imaging (MPI) As the heart does more work, the amt of oxygen delivered to the myocardium must increase When the myocardium O2 demand increases the coronary arteries dilate and artery blood flow increases 3x-5x With stenosis of >50%, blood flow cannot increase sufficiently to meet the maximum demand for oxygen. When myocardium oxygen demand exceeds oxygen supply, ischemia results 23


Slide 24:The inadequately perfused zone of myocardium stops or reduces contracting within a few seconds causing regional wall motion abnormality on images recorded during ischemia Perfusion imaging is performed to detect myocardial ischemia/infarct and determine its location and extent Thallium 201 a nuclide with biological properties similar to potassium and a mercury x-ray of 80 KeV is well suited to the scintillation camera; thallium was approved for myocardial perfusion evaluation in 1974 has been widely used since then; 2 Tc 99m labeled agents tetrofosmin and sestamibi have also been approved as tracers for MPI The shorter physical half-life of the Tc agents results in lower radiation burden allowing administration up to 30 mCi per examination. 24


Slide 25:Thallium 201 is a radiopharmaceutical with biological behavior similar to that of potassium 43; it is produced by proton bombardment of thallium 203 in a cyclotron. An intermediate product Pb-201 is produced which decays to Tl-201. Tl-201 has a physical half-life of 74 hours and decays by e- capture, with a production of mercury x-rays of about 80 KeV and gamma photons of 135 and 167 KeV It has a long biological half-life; about 3.5% of the injected dose localizes in the myocardium In myocardium that is ischemic, immediately after injection the relative amount of thallium in the zone of diminished perfusion is lower than that of normally perfused zone; this is in direct proportion to the difference in tissue blood flow to the two regions 25


Slide 26:If serial images are recorded over several hours, the relative loss of Tl-201 from the normally perfused zone is greater than that to the ischemic zone. In images recorded 4-24 hours after injection, the relative concentration of thallium in the two areas may appear similar. This phenomenon called redistribution makes thallium very useful for identifying ischemic myocardium. an effective half-life of 57 hours results in a dose limited to about 4 mCi Technetium cardiac agents are teboroxime, sestamibi, and tetrofosmin; only sestamibi and tetrofosmin are in wide clinical use; these agents have lower myocardial extraction than thallium and slightly slower blood clearance than thallium, making it important to continue exercise for two minutes after injection instead of 1 minute usually used for thallium 26


Slide 27:27 Tl 201 redistribution


Slide 28:Lower radiation dose allows administration up to 30 mCi; first pass and gated data is possible Technetium agents do not redistribute; therefore separate injections are required to depict perfusion at rest and with stress Both agents have a biological half-life of >5 hrs in myocardium, allowing images to be recorded up to 90 minutes after injection Imaging protocols: see chart in Christian p.489 When thallium is used alone, stress injection is given first with redistribution imaging at 3-4 hours later; 24-hour imaging may be done for additional information about ischemic yet viable myocardium The technetium labeled tracers can be done with either a 1 or 2 day protocol 28


Slide 29:In the two-day protocol, the rest and stress examinations are done on separate days, each with a dose of 20 to 30 mCi For the one-day study, patients can have either the rest are stress study performed first, typically with a dose of 10 mCi. Then, a four to six hours delay permits physical and biological decay from the myocardium; then a rest or stress examination at a dose of 20 to 30 mCi is done Patient can be injected first at rest and then at stress, or vice versa, with a larger dose of tracer used for the second study A dual isotope technique uses thallium for rest and technetium agents for the stress imaging; this is an effective, time efficient one day protocol. (usually 3 mCi Tl-201 rest 1st and 25 mCi sestamibi or tetrofosmin stress 2nd) 29


Slide 30:The advantage of this approach is that thallium imaging at rest provides information to detect viable myocardium and the stress test can be performed at the conclusion of rest imaging, thus eliminating the waiting time needed to image with a single isotope The technetium labeled agents are somewhat less sensitive than thallium for the detection of ischemic myocardium; this may relate to lack of redistribution which occurs with Tl-201; in cases of severe stenosis, the dual isotope study may be useful Techniques may vary from clinic to clinic: check with your chief technologist or NM physician to clarify details of MPI procedures 30


Slide 31:Cardiac Stress Test Overview: A treadmill is usually used for exercise; patient’s heart rate, EKG, BP, and symptoms are continuously monitored Perfusion tracers are administered at the peak of exercise; patient continues exercising for 1-2 addl min; perfusion images are acquired after injection of tracer uniform pattern of perfusion makes it unlikely the patient has significant risk of sudden death or MI within the next 2 years An abnormal scan at stress and normal scan with injection at rest suggests myocardial ischemia An abnormality on both rest and stress scans suggests myocardial scarring which is less likely to be a significant event than ischemia 31


Slide 32:32 ISCHEMIA: = The top strip of the tomos (stress images) are abnormal. They show dark colors in the inferior wall and apex (VLA view), apex and lateral wall in the HSA view and the lower lateral wall in the SA view. Thus, there is evidence of reduced blood flow to the inferior, apex and lateral walls. In comparison, the rest images show near normalization of all three segments (which regain brighter colors). This is a typical finding in a patient with ischemia or reversible stress-induced reduction of blood supply to the LV.


Slide 33:33 HEART ATTACK: = The top strip of the tomo slices (stress images) show that the inferior, apex and lower lateral walls of the LV have dark colors. It also appears thinner than the normal walls because of reduced blood flow and consequent decrease in tracer uptake. Notice that these findings persist in the rest or lower strips. In other words, there is no reversibility of flow in the Rest images. Such findings indicate a previous heart attack. Also, in the absence of reversibility there is no evidence of additional threatened or jeopardized heart muscle.


Slide 34:Stress testing: Treadmill exercise is usually done using the standard Bruce protocol which consists of 7 stages of exercise, with a duration of three minutes each, and gradually increasing speed and treadmill grade or elevation 34 Ischemia bullseye


Slide 35:For exercise test to be adequate, the patient should achieve at least 85% of the maximum heart rate which is 220-the patient’s age in yrs; otherwise suboptimal The patient should be continuously monitored with a 12 lead ECG recorded every minute and BP recorded at least every 3 minutes Radiopharmaceutical should be administered at the peak of exercise and exercise should continue for additional one to two minutes, to permit the tracer to clear from the blood and localize in the myocardium in proportion to perfusion at the peak of exercise Injection of tracer is followed by flush of 10 mL of saline: important if saline bag and IV tubing used After exercise the patient is placed supine on imaging table, ECG, and BP monitoring continue until normal cardiac rhythm and BP is achieved 35


Slide 36:Imaging should commence within 10 minutes of injection of thallium and within 15 minutes for sestamibi and tetrofosmin If thallium is the only tracer used for recording MPI, the stress examination is performed first followed by immediate imaging; because TL redistributes, delayed images are obtained 3-4 hours later; eating carbs should be avoided which accelerates the rate of thallium 201 clearance from normal and ischemic myocardium (masks ischemia) Occasionally to improve cts, an additional one mCi dose of thallium is administered at rest before the delayed images are recorded; in the case of rejection the tracer measures the regional distribution of perfusion at rest 36


Slide 37:Pharmacological Stress Testing: Some patients cannot exercise for various reasons: in these patients myocardial blood flow may be increased by using drugs to cause vasodilation of the coronary arteries or to increase myocardial oxygen demand The vasodilator method is used more often; although dipyridamole (Persantine) or adenosine (Adenocard) can be used, adenosine is preferred because of a short biological half-life; both agents cause relaxation of precapillary sphincters in the arterioles resulting in marked decrease in peripheral resistance and increase in regional blood flow to the myocardium=“simulated exercise” Dipyridamole reduces the metabolism of endogenously produced adenosine by inhibiting an enzyme called adenosine deaminase: increases “natural” adenosine 37


Slide 38:Adenosine which is infused, however, exerts a direct effect by occupying the adenosine receptors; dipyridamole last for several hours after administration, whereas adenosine has a biological half-life of only 10 seconds When the drugs are infused, coronary arteries dilate to increase myocardial blood flow to all areas of the myocardium uniformly; if tracer is administered at the time of maximum effect of the drug, all normal areas of the myocardium show normal uptake If a vessel is markedly narrowed, flowed distal to the narrowing does not increase to the same degree as that supplied by normal coronary arteries; then, areas of below normal uptake can be seen 38


Slide 39:The effects of both drugs may be reversed by aminophylline Because of the vasodilator properties both drugs result in decreased BP; patient should be there lying supine or performing low-level exercise; BP and ECG should be monitored continuously; in the unlikely event that a patient desert develops serious complications such as third-degree heart block or severe hypotension aminophylline should be available and given; adenosine is usually very short lived; stopping infusion usually decreases symptoms instantly Serious side effects such as arrhythmias, severe hypotension, cerebral ischemia, stroke and death have been reported with pharmacological stress tests 39


Slide 40:If the patient has asthma, the tests are contraindicated with either dipyridamole or adenosine; patient should prepare for the test by fasting for at least 4 hours and refraining from food or beverages containing caffeine for lease 24 hours; discontinue all xanthine containing medications for 36 hours before the study; caffeine and xanthine reduced the effectiveness of the vasodilator and may produce a false negative test; pt prep crucial Blood-pressure, ECG must be monitored throughout the procedure; the drugs are given intravenously using infusion pump Dipyridamole dosing is 0.56 mg/kg over four minutes while adenosine is 0.140 mg/kg/minute for 6 minutes The perfusion tracer is administered approximately 3-4 minutes after conclusion of the dipyridamole infusion or during the 3rd minute of adenosine infusion 40


Slide 41:Recent studies suggest that the interval of adenosine infusion can be reduced to a total of 4 minutes with a perfusion tracer injected at 2 minutes; this results in fewer side effects Both drugs may produce a pounding headache, heaviness in the chest, nausea, and a feeling of shortness of breath Adenosine may be combined with a low-level exercise protocol to minimize side effects and improve image quality Alternative Pharmacological Test Dobutamine increases the heart rate and BP. This agent increases myocardial work and hence the need for increased flow in the coronary arteries; Dobutamine may be used when a pt has asthma or severe COPD, takes theophylline, or has ingested anything with caffeine, or has 2nd or 3rd degree AV block 41


Slide 42:Dobutamine has a low incidence of cardiac arrhythmia and a half life of 1-2 minutes=limited duration; monitor pt vitals The drug causes increased oxygen consumption and can cause ischemia similar to exercise; see Christian p. 495 for dosing/procedure Testing with Nitrates Nitroglycerin is often used to relieve myocardial ischemia. The drug works by causing both venodilation and arterial dilation. Venodilation decreases the amt of blood returning to the heart thereby decreasing myocardial O2 requirements Arterial dilation results in increased blood flow to the myocardium; in severe CAD with 95-99% stenosis, administration of nitroglycerin enhances detection of viable but ischemic myocardial tissue in 10 to 15% of patients 42


Slide 43:0.4 mg sublingual tablet about two minutes before the rest tracer injection is utilized Gated SPECT Imaging: Gated perfusion SPECT is typically recorded using 8 frames per cardiac cycle; the slices are usually displayed as multiple cine loops on the screen for visual assessment; ejection fraction and ventricular volume may be calculated; the technetium agents are best suited for gated SPECT=high photon yield and increased counts Analysis of Data From MPI Myocardial perfusion data are of evaluated by viewing the images to detect zones of diminished tracer localization and by quantification of the relative regional distribution of the agent 43


Slide 44:Data are quantified by the automated ROI analysis to express the regional concentration of tracer in the myocardium SPECT images may be quantified by stacking the short axis slices onto a bull’s-eye display where the apex is at the center in the basal slice is at the periphery The basis of interpretation is that perfusion abnormalities that appear less severe on rest or delayed images than they do on stress indicate areas of stress induced myocardial ischemia; those that remained fixed on delay imaging most likely reflect sites of myocardial scarring Images are presented in short axis (SA), vertical long axis (VLA), and horizontal long axis (HLA) slices Artifacts can occur as a result of attenuation from adjacent tissues such as the breast or stomach or intense areas of adjacent activity such as liver or bowel 44


Slide 45:45


Slide 46:PET Myocardial Perfusion Tracers Rubidium-82 chloride is FDA approved and is available from a strontium-82 generator; it has a physical half-life of 75 seconds and behaves similar to TL-201; it is concentrated in the myocardium initially in proportion to regional myocardial perfusion; accumulation depends on the metabolic state of myocardium; short physical half-life of this tracer permits repeat imaging Nitrogen 13 ammonia is produced by deuteron bombardment of oxygen-16 in a cyclotron; localizes in the myocardium in proportion to regional perfusion; has a 9.9 minute half-life 46


Slide 47:Oxygen 15 is cyclotron produced and has a half-life of 122 seconds; used to label water Because water is freely diffusible into myocytes or heart cells, extraction into myocardial tissue is nearly 100% and does not depend on the flow rate; is metabolically inert therefore accumulation in the myocardium does not depend on the metabolic state of the tissue Because O-15 water resides in both the tissue and blood pool, a second tracer, usually O-15 carbon monoxide, is inhaled by the patient and must be administered to permit image correction for O-15 water photons emanating from the intravascular compartment. Pharmacological stress testing is possible using PET isotopes and either dipyridamole or adenosine 47


Slide 48:Because PET has higher energy annihilation radiation and improved correction for attenuation, its specificity tends to be 10 to 15% higher than that of SPECT Sensitivity: true positive fraction=% of patients who really have disease who have a positive PET scan Specificity: true negative fraction=% of patients who really do not have disease who have a negative PET scan PET Cardiac Imaging Perfusion: PET myocardial perfusion imaging can be performed with either N-13 ammonia (cyclotron-produced) with 9.9 min half-life, or rubidium-82 chloride (generator-produced) with 75 second half-life. Both localize in the myocardium relative to blood flow. Advantages of PET vs. Nuclear SPECT include higher spatial resolution, better attenuation correction, reduced radiation, and higher accuracy. 48


Slide 49:PET perfusion studies can be performed with pharmacologic stress (e.g., adenosine, dipyridamole, or dobutamine), and can be completed on modern PET/CT systems in less than 30 minutes. Two images (rest and stress) are required to detect ischemia-reduced blood flow to heart at stress. Viability: The heart uses fatty acids first for energy; when blood flow is reduced and ischemia results, glucose becomes the preferred energy source. PET utilizing 18-fluorodeoxyglucose (FDG), is a well-recognized method to assess myocardial viability and hibernating myocardium ; FDG uptake =viability, and as many as 30%-50% of regions felt to be dead tissue by standard nuclear tests are found to be viable with PET. These patients would be likely to benefit from bypass surgery to restore blood to a portion of the heart. FDG PET of the heart (left), with stress tetrofosmin (SPECT) study on the right. Viable, but ischemic myocardium uses glucose metabolism and FDG will accumulate in this myocardium. This same region will demonstrate a defect on the conventional perfusion study (thallium, 99mTc-sestamibi or 99mTc-tetrofosmin). The difference in distribution indicates viability.


Slide 50:50


Slide 51:Radionuclide Evaluation of Ventricular Function: In blood pool imaging, direct assessment of activity within the heart cavity between diastole and systole allows assessment of ejection fraction and wall motion There are 2 approaches to evaluating ventricular function with tracers in the blood pool: first pass and equilibrium (also stress MUGAs possible) Equilibrium Gated Blood Pool Studies: The equilibrium technique analyzes the heart at rest although a stress study is also possible which is usually done with either bicycle ergometer or dobutamine Red blood cells must be labeled with pertechnetate Three different methods are available 51


Slide 52:In vivo labeling: give stannous pyrophosphate IV 10 mg/kg weight, wait 15 to 30 minutes; inject 20 mCi of pertechnetate; overall poor for labeling with an efficiency of 60 to 90% 52 In vitro/in vitro method Ultratag Kits 1. To vial containing Sn2+ compound, add 3-5 ml of anticoagulated blood 2. Incubate 15 min 3. add 25 mCi Tc-99m pertechnetate 4. add Na hypochlorite (NaClO) to destroy extracellular Sn2+ ion 5. Add Citrate Buffer 6. incubate 20 min. Expected labeling efficiency >98%


In vitro/in vitro (Ultratag): Advantages/disadvantages :In vitro/in vitro (Ultratag): Advantages/disadvantages Advantages: quick, simple, inexpensive method; achieves higher labeling efficiency than in vivo/in vivo technique since incubation with RBC is extracorporeal. Ideally suited for GI Bleeding Studies; produces excellent delayed images. Disadvantage: takes extra tech time; slight potential for breaking sterility


Slide 54:Modified in vivo labeling: inject cold PYP IV; wait 15 to 30 minutes; withdraw 1-5 mL of blood into a heparin syringe with 20 mCi of pertechnetate. Mix. Incubate syringe 10 minutes at room temperature; reinject whole blood; labeling=90-95% Because multiple points of the cardiac cycle are recorded, the technique is often called multiple gated acquisition or MUGA After the tracer has equilibrated in the blood pool, about 5-10 minutes after administration of the labeled RBCs, data are recorded in synchrony with the patient’s cardiac cycle The R-wave of the patient’s electrocardiogram is used as a marker for the end of diastole The length of the cardiac cycle is usually divided into 16 frames 54


Slide 55:The computer is programmed to record data from the first portion of the cardiac cycle in the first frame, second portion of the cardiac cycle in the second frame, and so on, until the last frame is reached or the next R wave is sensed. This resets the recording to the first frame to repeat the process Data from 500 to 1000 cycles are added to obtain an average cardiac cycle Planar Acquisition: the planar views are usually recorded in three views: anterior, 45° LAO, either left lateral or LPO The LAO is optimized to separate the right and left ventricle and determine the timing and motion of the anterior wall, posterior wall, and motion and thickening of the septum of the left ventricle 55


Slide 56:Gated blood pool SPECT has the advantage of viewing the heart from 180° or 360°. This eliminates the anatomic overlap that occurs in planar imaging; reconstructed data is possible and assessment of regional wall motion is better Patient prep: electrocardiogram electrodes should be placed and a baseline recording is obtained; usually four electrodes are placed Data Analysis: The planar LAO view or best septal view is analyzed to calculate ejection fraction (EF) of the total counts in the left ventricle at end systole and end diastole; ROIs can be drawn over the left ventricle automatically using either a second derivative or threshold algorithm or manually. 56


Slide 57:the background subtraction step is crucial to the subsequent calculation of EF; subtraction too much background results in a falsely elevated EF; subtraction of too little produces a falsely depressed EF The total background corrected counts in left ventricle on each frame are then normalized to the counts in the end diastolic frame and the time activity curve from the left ventricle ROI is displayed; normal values of LVEF range from 50 to 75% and are about 5% higher in women than men, because female hearts are slightly smaller; in addition to the EF, the time of filling and emptying and the ejection and filling rates of ventricles can be readily computed from these curves 57


Slide 58:58 MUGA processing and beating heart with normal EF Left=poor EF, dyskinesis


Slide 59:59


Slide 60:Regional wall motion left and right ventricles can be readily appreciated from visual assessment of the cinematic display A major application of MUGAs is evaluation of chemotherapy pts; many cancer agents are cardiotoxic; 5% or > drop in EF or LVEF<50%= neg cardiac reaction to agents Gated blood pool stress is possible using a bicycle ergometer exercise; starts with workload of 20-25 W with increments every 3 minutes, planar LAO views are obtained during the last 2 minutes of each stage; the images may be count poor because of short acquisition time of 2 minutes; a combination of low counts and pt motion make edge detection difficult and limits the assessment of small reductions in wall motion; assessment of EF however is reliable 60


Slide 61:Exercises increases in 25 W increments every two minutes; the ECG is monitored continuously and BPs recorded at least once/stage throughout the procedure Normal subjects should have at least a 5% increase in EF from rest to maximum level exercise If the patient cannot exercise a dobutamine MUGA may be performed First Pass Studies: First pass studies are used to examine right ventricular function and are based upon recording data (20 to 50 ms per frame) with ECG synchronization during the first passage of the radiopharmaceutical through the heart The study is complete within 30 to 60 seconds of injection 61


Slide 62:If the tracer is cleared rapidly from the blood, repeat studies can be easily acquired in the same imaging session if necessary First pass studies are performed with an injection of about 20 mCi of activity with a peak photon flux through a high-resolution collimator of about 83,000 cts/sec; Tc DTPA commonly used= rapid clearance=mult studies possible Most scintillation cameras can image maximum count rates of more than 100,000 counts/second with dead time losses <20% and no image distortion Images are recorded in the anterior or 45° LAO position; recording is started at 25 ms per frame just prior to injection and continued for total one minute with approximately 2400 frames of overall data 62


Slide 63:A small volume bolus injection followed by a flush of 10 to 20 mL saline should be used and external jugular vein or basilic vein is the preferred site of injection Data identifies transit of rphx. through the superior vena cava, right ventricle, lungs, left ventricle and aorta; ROIs are drawn over the ventricles to generate time activity curves The FWHM transit time of activity through the superior vena cava should be < 2.5 seconds Right ventricle EF is counted with following formula: EF=(ED cts=ES cts)/ED cts 63


Slide 64:MI Necrosis Imaging using Rphxs 2 agents are used for acute myocyte necrosis: Tc99m pyrophosphate and In-111 antimyosin Myocardial infarction is irreversible damage to the heart muscle due lack of O2 > 15 min; ECG changes, elevations of cardiac enzymes= typical symptoms Method of localization: damaged cells have increase permeability of cell membrane with leakage outward of substances and allowance of normally excluded substances to enter cell. Cell cannot regulate amt of calcium and excess calcium enters the cell; if Tc-PYP is injected at this time, it localizes in area of necrosis; occurs within hrs of occlusion and continues for 8-10 days 64


Slide 65:Another approach is to use an antibody against cardiac myosin, a key heart contractile protein; myosin usually not soluble; loss of cell membrane in damaged cells permits antimyosin antibody to enter inside the cell where it combines with the antigen resulting in localization in areas of dead tissue; the antibody is labeled with In-111 and uptake occurs within hrs of event and within 10-14 days of event; 2 mCi used These approaches have been mostly replaced by serial EKGs and serum enzymes; Tc PYP=20 mCi 12 hrs-10 days post MI; wait 4-6 hrs post inj; planar and SPECT useful 65