Myocardial Perfusion Scintigraphy OverviewDr. Mustafa SayedProf . Of Nuclear MedicineAsyut University , Egypt.Myocardial perfusion scintigraphy descrip sequential physiological events: -First, the materials(radiopharmacuticals) must be delivered to the myocardium. -Second, a viable metabolically active myocardial cell must be present to extract this material. -Finally, a significant amount of the material must remain within the cell to allow for imaging. The scintigraphic images are a map of regional myocardial perfusion. If a patient has reduced regional perfusion as a result of hemodynamically significant (CAD) or a loss of cell viability as a result of myocardial infarction, a perfusion defect or cold region is seen on the images. All diagnostic patterns in the many diverse applications follow from these observationsThe radiopharmaceutical is a combination of radioactive material used alone or mixed with inert kits. These materials have selective affinity to target cell components.These radiopharmaceuticals emit gamma rays which are collected by special instrumentations called gamma camera which has different types.These types include multi view planar imaging which was followed by single-photon emission tomography (SPECT), gated SPECT, SPECT/CT, then positron emission tomography (PET),and PET/CT.

The RadiopharmaceuticalsSuch radipharmaceuticals are injected under stress as well as resting conditions, and images are obtained to define the regional distribution of radioactivity within the myocardium.1- Thallium-201 Chloride: First used for myocardial scintigraphy in the mid-1970s, it was the only perfusion agent available until the 1990s, when Tc-99mlabeled radiotracers were introduced. Tl-201 is less commonly used today because of its poorer image quality. At some imaging clinics it is used for the rest study in dual-isotope studies or for viability studiesMechanism of Localization and Pharmacokinetics:After intravenous injection, Tl-201 blood clearance is rapid. It is transported across the myocardial cell membrane via the Na+/K+ ATPase pump. More than 85% is extracted by the myocardial cell on first pass through the coronary capillary circulation . Peak myocardial uptake occurs by 10 minutes. Approximately 3% of the administered dose localizes in the myocardium.Extraction is proportional to relative regional perfusion over a range of flow rates. At high flow rates, extraction efficiency decreases; at low rates, it increases. It can only be extracted by viable myocardium, but not in regions of infarction or scar.2- Technetium-99m labelled compounds:Tc-99m is the radiotracer which emits gamma rays and can be labelled with different materials.= Technetium-99m MIBI: approved by the (FDA) for clinical use in 1990. Generic Tc-99m sestamibi became available late (chemical name: hexakis 2-Methoxy Iso Butyl Isonitrile).Mechanism of Localization and Uptake: Because it is lipid soluble, Tc-99m mibi diffuses from the blood into the myocardial cell. It is retained intracellular in the mitochondria because of its negative transmembrane potential. First-pass extraction fraction is 60% . Extraction is proportional to coronary blood flow.= Technetium-99m Tetrofosmin:Tc-99m tetrofosmin (Myoview) was approved by the FDA in 1996. An advantage over Tc-99m mibi is its more rapid liver clearance.Mechanism of Localization and Uptake: Similar to mibi, Tc-99m tetrofosmin is a lipophilic cation that localizes inside mitochondria in the myocardial cell and remains fixed at that site. First-pass extraction is slightly less than that of mibi (50% vs. 60%). Extraction is proportional to blood flow, but underestimated at high flow rates. It is widely used nowadays.

Imaging MethadologySingle Photon Emission Computed Tomography:SPECT is the standard method for myocardial perfusion scintigraphy. The cross-sectional images have high contrast resolution and are displayed three-dimension along the short and long axis of the heart providing good delineation of the various regional myocardial perfusion beds supplied by their individual coronary arteries.The diagram shows a photon reaching the NaI crystal through the collimator and undergoing photoelectric absorption. The photomultiplier tubes (PMTs) are optically coupled to the NaI crystal. The electrical outputs from the respective PMTs are further processed through positioning circuitry to calculate (x, y) coordinates and through addition circuitry to calculate the deposited energy of the pulse. The energy signal passes through the pulse height analyzer. If the event is accepted, it is recorded spatially in the location determined by the (x,y) positioning pulses to form the image.

Cardiac SPECT software: reconstructs cross-sectional cardiac images along the short and long axes of the heart , that is, transaxial (short axis), coronal (horizontal long axis), and sagittal (vertical long axis) .The SPECT cross-sectional images descrip the regional perfusion of the myocardium as it relates to the coronary artery supplying blood to that region and permits visual estimation of the degree and extent of the perfusion abnormalityCardiac SPECT cross-sectional images with corresponding anatomy. The slices are cut along the short and long axis of the heart: top (short-axis), middle (vertical long axis), bottom (horizontal long axis). The left ventricle is best seen because of its greater myocardial mass; the right ventricle is normally much less well seen. Atria are never visualized.

Stress Myocardial Perfusion ScintigraphyCardiac stress testing with ECG monitoring has long been used to diagnose ischemic coronary artery diseases.Cardiac stress can be physical by graded treadmill or pharmacological with specific drugs. The SPECT imaging provides valuable information on the extent and severity of coronary artery disease which is useful for risk assessment, prognosis, and patient management.

The patients must be fasting for 4 to 6 hours before the test to prevent stress-induced gastric distress and minimize splanchnic blood distribution.Cardiac medications may be held depending on the indication for the stress testthat is, whether for diagnosis or to determine the effectiveness of therapy and type of stress. Beta blockers may prevent achievement of maximum heart rate. Nitrates and calcium channel blockers may mask or prevent cardiac ischemia,so limiting the tests diagnostic value. Assessment of drug therapy effectiveness requires the patient to remain on medication. Thyophylline and caffeine also held before pharmacological test. Drugs That Interfere with Stress Testing: Recommended Withdrawal IntervalWithdrawal interval Drugs 48 hours24 hours (also with pharma.)24 hours (also with pharma.)

24 hours24 hoursIn EXERCISbeta blockersCalcium channel blockersNitrates

In PHARMACOLOGICALThyophylline derivativesCaffeine

MPI with Exercise StressIn addition to a standard 12-lead baseline ECG, an intravenous line is kept open. The patient is continuously monitored during the study. Graded treadmill exercise is performed according to a standardized Bruce protocol. When the patient has achieved maximal exercise or peak patient tolerance the radio-pharmaceutical is injected. The adequacy of exercise is judged by the degree of cardiac work. Patients achieving more than 85% of the age-predicted maximum heart rate (220 age = maximum predicted heart rate) are considered to have achieved adequate exercise, stress metabolic equivalents (METS) also can be used to judge the adequacy of exercise. Failure to achieve adequate exercise is the most common reason for a false negative stress test result.Exercise is continued for another 1 minute after injection of radiotracer to ensure adequate uptake. Early discontinuation of exercise may result in tracer distribution reflecting perfusion at sub maximal exercise levels.MPI with Pharmacological Stress1- Coronary Vasodilating Drugs: Dipyridamole, Adenosine, and Regadenoson. Dipyridamole (Persantine) and adenosine (Adenoscan) are coronary vasodilating drugs that have long been used for stress myocardial perfusion imaging. Regadenoson (Lexiscan) was approved by the FDA in 2009 but dipyridamole is the widely used . The vasodilators increase coronary blood flow in normal vessels 3 to 5 times. Because coronary arteries with significant stenoses cannot increase blood flow to the same degree as normal vessels, vasodilator stress results in vascular regions of relative hypoperfusion on myocardial perfusion scintigraphy similar to that seen with exercise-induced ischemia.Dipyridamole injection protocol:Dose 0.56 mg / Kg diluted in 50 ml normal saline and given as infusion for 4 minutes.The radiopharmaceutical should be injected after 2-4 minutes after completion of infusion.It is contraindicated in bronchial asthma and preferred in LBBB cases.- Heart rate, blood pressure and ECG should be measured and recorded at baseline and every 2 minutes during the infusion until stress-induced haemodynamic changes are improving and the patient regains baseline status.2- Inotropic Drugs: Dobutamine is a synthetic catecholamine that acts on alpha- and beta-adrenergic receptors producing inotropic and chronotropic effects that increase cardiac work. In normal coronary arteries, increased blood flow is the result. In the face of significant stenosis, regional flow does not increase, producing scintigraphic patterns similar to that seen with ischemia .Dobutamine injection protocol: Initial infusion rate is 5 g/kg/min over 3 minutes, then increased to 10 g/kg/min for another 3 minutes and further increased by that amount every 10 minutes until a maximum of 40 g/kg/min is achieved. The radiopharmaceutical is injected after the maximal tolerable dose reaching the target heart rate and the dobutamine infusion is continue for 1 minute.

Technetium-99m labelled compounds two-Day Patient Imaging Protocol

Rest Stress 25 m Ci 25 m Ci Radiopharmaceutical doseSupine or prone

45-60 min.Supine or prone

20 30 min with exercise45-60 min with drugsPatient position

Injection - Imaging Time

Acquisition camera SPECT study:

Dual head gamma camera moves around the patient viewing the heart in 180 degrees in 64 steps for 25 second per step ,starts from 45 degree RAO to 135 degree LPO. Image acquisition with standard SPECT systems requires 20 to 30 minutes

Again ,Cardiac SPECT cross-sectional images with corresponding anatomy. The slices are cut along the short and long axis of the heart: top (short-axis), middle (vertical long axis), bottom (horizontal long axis). The left ventricle is best seen because of its greater myocardial mass; the right ventricle is normally much less well seen. Atria are never visualized.

Short ,horizontal long and vertical long axis of L.V. Walls with corresponding Coronary arteries.

Standardization of SPECT myocardial segments. This method divides the myocardium into 17 regions and has been recommended for all cardiac imaging. The diagram also correlates coronary artery anatomy with regional perfusion. Some computer software systems use a different number of regions. LAD, Left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery

Diagnostic Patterns in Coronary Artery DiseaseAfter initial assessment of the presence or absence of perfusion defects, a complete evaluation of the stress study includes assessment of the location, size, severity, and likely vascular distribution of the visualized abnormalities. A true perfusion defect should be seen on more than one cross-sectional slice and in other cross-section planes. Certainty increases with lesion size and the degree or severity of photon deficiency.Diagnostic patterns of MPI

Visual scoring of severity

Normal myocardial SPECT perfusion study. Top two rows display the short-axis transaxial images (stress above, rest below), third and fourth rows display the horizontal long-axis (sagittal) stress and rest views, and the bottom rows display the vertical long-axis (coronal) views.

Single vessel disease (LAD): In stress images there is large sever perfusion defect at anterior and anterolateral wall. Rest images show partial reversibility of perfusion. Mixed infarction and ischemia.

Multiple Perfusion Defects:Perfusion defects in more than one coronary artery distribution area indicate multiple vessel disease. Prognosis worsens with increasing number and size of perfusion defects . Not all significant coronary artery stenoses are always seen on stress perfusion scans. N.B. Stress-induced ischemia of the most severe stenotic lesion limits further exercise, and thus other stenoses may not be seen and multiple vessel disease may be underestimated.Multi vessel disease Dipyridamole (Persantine) stress images show moderate reduced perfusion of the lateral wall and sever reduced perfusion to the inferior wall. Rest images show improvement in the lateral wall but no improved perfusion to the inferior wall.(lateral wall ischemia and inferior wall infarction) .

Transient Ischemic Dilation (TID)The normal cardiac response is to dilate mildly during stress and return to normal size promptly with cessation of exercise. Post stress significant ventricular dilation is abnormal and suggests multi vessel disease. One explanation for this finding is myocardial stunning during stress ,another is widespread subendocardial ischemia.Myocardial perfusion Scintigraphy in multi vessel disease. The stress study shows sever large hypoperfusion ofthe anterolateral, lateral, inferlateral, and inferior walls. The rest study shows normal perfusion.( Large sever ischemia).In comparison with rest, stress images suggest TID.

Attenuation ArtifactsThe effects of soft tissue attenuation can be seen on most cardiac images and are worse with large patients. Males typically have decreased activity in the inferior wall .This is called diaphragmatic attenuation, meaning attenuation by subdiaphragmatic organs interpositioned between the heart and gamma camera. The amount of attenuation effect is dependenton patient size, shape, and internal anatomy.Inferior wall attenuation correction. Dipyridamole (Persantine) stress and rest SPECT/CT study. Non corrected (NAC) stress and rest images and the attenuation-corrected images (AC). Note the improvement in inferior wall perfusion with attenuation correction.

Women often have relatively decreased activity in the anterior wall, apex, or anterior lateral portion of the heart, secondary to breast attenuation, depending on the size and position of the breasts. Women also may have sub diaphragmatic attenuation, but breast attenuation is dominant and most commonly noted. The cinematic rotating raw data should be reviewed for the presence of attenuation and motion. If the breasts are in different positions for the two studies, this could be misinterpreted as ischemia

Breast attenuation. A, Single projection image from a cinematic display at stress (left) and rest (right) illustrates breast attenuation artifacts. Note the decreased activity in the upper portion of the heart. B, The patients SPECT slices show reduced activity in the anterior wall, best seen in the short axis and sagittal views and likely due to attenuation.

LBBBExercise-induced reversible hypo perfusion of the septum can be seen in patients with left bundle branch block (LBBB) in the absence of coronary disease. Typically, the apex and anterior wall are not involved, as would be expected with left anterior descending (LAD) coronary artery disease.The stress-induced decreased septal blood flow is thought to be caused by asynchronous relaxation of the septum, which is out of phase with diastolic filling of the remainder of the ventricle when coronary perfusion is maximal. This scan abnormality is less seen with pharmacological stress, and thus the latter is indicated in patients with LBBB or ventricular pacemakers.A figure demonstrates a perfusion defect in the septum in a 74-y-old woman ,she has a LBBB as shown on her ECG ,we note that the apex and anterior wall perfusion is within normal.

Gated SPECT StudyECG is acquired at the time of the SPECT acquisition for simultaneous assessment of perfusion and function of the left ventricle in one examination. Evaluation of regional wall motion and systolic thickening of the left ventricular walls .

Left ventricular end-diastolic volume, end-systolic volume, stroke volume and ejection fraction may be calculated automatically, although the values obtained should be checked against initial qualitative assessment

We obtain myocardial perfusion images within one representative cardiac cycle : from end-diastole through end-systole to end-diastole of next cardiac cycle

The computer software calculate the EF,EDV,ESV and SV by using the end diastolic and end systolic images.

At the end ,some limitations of cardiac MPI SPECTDecreased sensitivity and specificity in single vessel CAD ( 60 76% )Diffuse disease in all three vessels (Balanced ischemia)Diffuse disease without segmental stenosis (Vulnerable for plaque rupture and coronary events)Early disease identificationArtifacts Non uniform attenuationRelative low efficiency of Gamma cameraLonger acquisition protocols

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