Fundamentals of PET CT Cardiac Imaging

Fundamentals of PET CT Cardiac Imaging • Identify basic cardiac structures and coronary circulation By the end of this course you will be able to: • List the various types of coronary diseases and how they affect coronary physiology • Describe the various types of PET cardiac imaging • List the isotopes and radiopharmaceuticals that are used in PET cardiac imaging • Describe the protocols that are commonly used • Describe the procedure and how to evaluate myocardial blood flow • Describe the procedure used to evaluate calcium scoring Cardiac Anatomy & Physiology                                          Chambers Blood Flow Valves Cardiac Output 4 Cardiac Chambers Atria •  Upper chambers •  Collect blood that enters the heart and pushes it into the ventricles             Ventricles •  Lower chambers •  Push blood out of the heart and into the arteries O2 poor blood from upper body returns through Superior Vena Cava O2 poor blood from lower body returns through Inferior Vena Cava Right Atrium collects O2 poor blood returning from body & pushes it through Tricuspid Valve into Right Ventricle Right Ventricle collects O2 poor blood from Right Atrium and pushes it through Pulmonary Valve to the lungs Pulmonary Arteries carry blood from heart to lungs to pick up O2 Pulmonary Veins carry O2 rich blood from lungs to the heart Left Atrium collects O2 rich blood returning from lungs through Mitral Valve into Left Ventricle Left Ventricle pushes O2 rich blood through Aortic Valve to the Aorta Aorta carries O2 rich blood to rest of the body Cardiac Output (CO) • Volume of blood that heart pumps per minute • Function of the volume of the blood pumped per stroke (SV) and the heart rate (HR) • CO = SV x HR > Average SV in males at rest = 8 ml/min > Average HR in males at rest = 70 bpm > Average CO in males at rest = 5,600 ml/min (~1.5 gallons) Cardiac Index (CI) • Comparison of the CO to the total body surface area (BSA) to be perfused • CI = CO/BSA > Typical CI for 70 kg male is 3.0 liters/min/sq. meter Aortic valve Tricuspid valve Pulmonary valve Mitral valve Bicuspid Valve in Systolic Phase   Images courtesy of Siemens' TDC • Double walled sac containing heart and great vessels • Fluid between layers provide lubrication for heart motion •  Coronary Circulation •  Planes Right Coronary Artery Aorta Left Coronary Artery RCA Image courtesy of Siemens' TDC Aorta Right Coronary Artery Left Coronary Artery Circumflex Artery Left Anterior Descending Artery Circumflex Artery Left Anterior Descending Artery Left Coronary Artery Aorta Right Coronary Artery Supplies: •  Interventricular Septum •  Apex •  LV Anterior Wall •  Left Bundle of His Images Courtesy Massachusetts General Hospital, U.S.A Images Courtesy of Siemens' TDC Cardiac Physiology & Disease                                          • Failure of coronary circulation to supply adequate oxygenated blood to the cardiac muscle and surrounding tissue • Most common cause of death in affluent countries Tunica Media (smooth muscle) Atherosclerotic Artery Cross-Section Tunica Adventitia (collagen) Tunica Intima (severely thickened) This lumen is 25-35% of its original size Atheromatous Plaque • Atheroma is a nodular accumulation of soft, flaky, yellowish material at the center of a plaque • Underlying areas composed of WBCs • Calcification at the outer base of older/advanced lesions Initial lesion •  histologically "normal" •  macrophage infiltration •  isolated foam cells Fatty streak •  mainly intracellular lipd •  accumulation Intermediate lesion •  Intracellular lipid accumulation •  small extracellular lipid pools Atheroma •  intracellular lipid accumulation •  core of extracellular lipid Fibroatheroma •  single or multiple lipid cores •  fibrotic/calcific layers Complicated lesion •  surface defect •  hematoma-hemorrhage •  thrombosis   Atheromatous Plaques • Artery enlargement • Leads to aneurysm • May rupture, forming a clot • Further limits blood flow to cardiac muscle • Infarction can occur in <5 minutes • Signs and symptoms typically noted in advanced disease state • Typical first sign is myocardial ischemia Depends upon: • Location and severity of stenosis • Presence or absence of collateral vessels • Demands of myocardium • Coexistence of various risk factors (HTN, diabetes, high LDL) Coronary circulation is inadequate for myocardial O2 demands. Can result in: • Angina • MI • Sudden death Images courtesy of Siemens' TDC Site • Discomfort beneath upper sternum • Radiation down arms (typically left) • Radiation to neck, jaw, or lower back Character • Squeezing, crushing, strangling, tightness, pressure, heaviness, or "funny feeling" Exertion • Typical onset Duration • Typically 2-10 minutes • Can be up to 30 minutes     Features of clinical syndrome resulting from transient and reversible ischemia include: Types: Transmural • Involves the entire thickness of the myocardium Subendocardial • Involves only a portion of the myocardium • Cardiac tissue death resulting from total coronary occlusion • Dead tissue no longer contributes to ventricle's pumping action • Offloads greater burden to remaining viable myocardium • Irreversible only in the center of the infarcted area Transmural Infarction Subendocardial Infarction • Initial lack of blood flow • Collateral blood seeps through infarcted area • Infarcted area overfills with stagnant blood • Myocardium uses remaining O2 in the blood, turning hemoglobin dark blue • Vessels become highly permeable, begin leaking fluid • Tissue becomes edematous and cardiac muscle begins to swell • Cellular death over 24 hours Cardiac Arrhythmias • Developed in 75% of patients within 72 hours • 50% develop potentially lethal ventricular arrhythmias Pulmonary Edema • Blood accumulates in pulmonary circulation due to weakening of the left ventricle • Incomplete emptying of the heart • Increased venous volume, decreased arterial volume   >  Decreasing arterial volume = kidneys producing aldosterone     –  Retention of sodium and water     – Increases total blood volume     – Fluid shifts from capillaries to tissues Cardiogenic Shock • Decrease cardiac output due to inadequate tissue perfusion Ventricular Aneurysm • Akinetic infarcted area can form an aneurysm Mitral Insufficiency • Caused by infarction or rupture of the papillary muscles Ventricular Septal Defect • An MI can weaken septum to the point of rupture Cardiac Rupture • Caused by a large transmural infarct Types of PET Cardiac Imaging Procedures                                              Evaluates: • Myocardial blood flow • Coronary blood flow reserve • Myocardial ischemia • CAD risk   -  Degree -  Location -  Extent Provides similar information as a cardiac catheterization • Less invasive • Less costly Images courtesy of Siemens' TDC SPECT MPI PET MPI Sensitivity - 81% Sensitivity - 95% Specificity - 67% Specificity - 95%* Diagnostic Accuracy - 68% Diagnostic Accuracy - 93%** Procedure Length   Tc99m - 2-3 hours   TI201 - 4-24 hours Procedure Length   N13 - 65-90 minutes   Rb82 - 28-32 minutes Exercise and Pharmacological Pharmacological only Less costly More costly Less accurate 3 vessel disease detection Accurate 3 vessel disease detection No cardiac blood flow reserve evaluation Cardiac blood flow reserve evaluation Spatial resolution 7.5 mm FWHM Spatial resolution 4.7 mm FWHM+ Less number of counts collected Greater number of counts collected *http://www.cardiogen.com/cardiogen-82/faq.html ** 2009 study reported 96% diagnostic certainty + HIRez processing       Absolute Contraindications Relative Contraindications Acute MI Severe mitral stenosis Unstable angina Arterial hypertension (>180/100) Sever pulmonary hypertension Arterial hypotension (<90 mm systolic) Obstructive hypertrophic cardiomyopathy Tachycardia (>120 bpm) Pregnancy   Sever reaction to stress pharmaceutical   Second or third degree AV block (adenossine stress)   Cardiac Metabolism Facts: • Perfusion, contractility and metabolism are closely interrelated • Fasting heart will metabolize fatty acids • Glucose-loaded state heart will metabolize sugar • Ischemia   -  Low perfusion -  Myocardial cells shift from fatty acid to glucose metabolism Adenosine Triphosphate (ATP): • Provides cardiac cells energy for metabolism of proteins Adenosine Diphosphate (ADP): • Produced by the hydrolysis of ATP • Involved in energy metabolism Acetyl Coenzyme A (Acetyl CoA): • Conveys carbon atoms to be used in the Kreb's cycle Isotopes & Stress Pharmaceuticals Used in PET Cardiac Imaging                                              Advantages: • Exhibits rapid blood clearance • Can perform exercise testing • Bolus injection • Relatively high uptake retention (~83%) • Quantification (CBR) • Cyclotron produced • Half-life:  10 minutes • Energy 1.19 MeV Disadvantages: • Cyclotron produced • Longer T1/2   -  Decreased throughput when compared to Rb82 • High initial cost • Marked lung uptake in smokers • Low uptake in lateral/posterolateral wall in some normals • Excess lung and liver uptake in some patients Images courtesy of Siemens' TDC Advantages: • K+ analog • Generator produced • Lower cost than 13NH3 • Short T 1/2 (75 seconds) • Repeat scans quicker • Low technologist exposure • Generator produced • Half-life:  75 seconds • Energy:  3.35 MeV Image courtesy of the University of Michigan Disadvantages: • Administered as a long infusion, no bolus • Higher monthly costs • Higher energy 3.35 MeV • Lower resolution • Scatter from 700 keV gamma 3rd particle (10-15% total activity) • Lower uptake and retention than NH3 • Image quality affected by:   -  BMI   -  Pulmonary HTN   -  LVH • Can only do pharmacologic stress • Image quality declines over generator life • Cyclotron produced • Half-life:  110 minutes • Energy:  0.6335 MeV FDG PET for follow-up of apical MI Stress Pharmaceuticals                                             Vasodilators • Cause the heart and blood vessels to mimic the effects of exercise • Dilation of the coronary vessels • Indirect coronary vasodilator • Infused IV -  142 µg/kg/min over 4 minutes • Hyperemia lasts > 15 minutes • Peak hyperemia at 2-3 minutes • Plasma T 1/2 = 30 minutes • Aminophylline is given if the patient is symptomatic or if there are signs of ischemia • Direct coronary vasodilator • Activates A2 receptors • Infused IV at 140 µg/kg/min • Peak hyperemia at 1-2 minutes • Rapid return to baseline after ceasing administration Contraindications Potential Side Effects Uncontrolled asthma Chest pain Greater than 1st degree AV block Dyspnea Systolic BP less than 90 mm Dizziness Taking dipyridamole or aminophylline in last 24 hours Nausea Caffeine in last 12 hours Hypotension Profound sinus bradycardia AV block Known hypersensitivity to dipyridamole or aminophylline ST depression Unstable acute MI   Acute coronary syndrome   Inotropic Agent • Increases the force of the energy of the cardiac muscular contractility, heart rate, and blood pressure • Synthetic catecholamine • Plasma T 1/2 = 2 minutes • Infused at 2-3 minute increments starting at 10 μg/kg/min and increasing to 40 to 50 μg/kg/min • Radiopharmaceutical is injected at 1 minute into the highest dose infusion Dobutamine Use: • Must be off beta blockers • Patient does not have to be off caffeine • Better for patients with asthma and breathing problems • Not for patients with pace makers • Atropine can greatly increase HR • Need to reach at least 85% of peak Contraindications Potential Side Effects Known hypersensitivity Ectopic heart beats Idiopathic hypertrophic subaortic stenosis (IHSS) Chest pain Sodium bisulfate allergy Palpitations Previous MI Nausea Atrial fibrillation Headache   Vomiting   Leg cramps   Dyspnea • Newer vasodilator agent • Selective A2A inhibitor • Adenosine receptor agonist • Low affinity and binds less tightly to its receptor • Disassociates quickly • Physiological response that terminates rapidly • 2 to 3 minute biological half-life • Can be used as a single bolus injection • Comes in preloaded syringes of 0.4 mg/5 mL • Not dependent on patient's weight • Not affected by the presence of beta blockers Intracoronary Blood Flow Effect: • 2.5 x over baseline sustained for over 2 minutes • Decreases to less than twice the baseline within 10 minutes Contraindications Potential Side Effects Known hypersensitivity Ectopic heart beats Idiopathic hypertrophic subaortic stenosis (IHSS) Chest pain Sodium bisulfate allergy Palpitations Previous MI Nausea Atrial fibrillation Headache   Vomiting   Leg cramps   Dyspnea Protocol Examples                                          CT Topogram CT Rest Scan for AC Injection of 13NH3 20-25 mCi Wait 1.5-3 mins PET resting list mode image for 10-15 mins CT Wait 20-25 mins between injections Stress drug injection Wait 3 mins Injection of 13NH3 2-25 mCi Wait 3-5 mins PET stress list mode image for 10-15 mins CT stress scan for AC PET resting list mode image for 10-15 mins Oral Glucose Loading Protocol 1. Patient should be fasting for 6-12 hours 2. Check blood glucose level (BGL)   a.  If BGL is <250 mg/dl ⇒ administer oral glucose of 25-100 g b.  If BGL is >250 mg/dl ⇒ no glucose loading necessary 3. Proceed with insulin administration (see next slide) 4. Administer 5-15 mCi of FDG if BGL is >150 mg/dl BGL at 45-90 Minutes After Administration Possible Restorative Measures 130-140 mg/dl 1 unit of regular insulin IV 140-180 mg/dl 2 units of regular insulin IV 160-180 mg/dl 3 units of regular insulin IV 180-200 mg/dl 5 units of regular insulin IV >200 mg/dl Notify physician IV Glucose Loading Protocol 1. Patient should be fasting for 6-12 hours prior to the procedure 2. Check blood glucose level (BGL)   a.  Fasting BGL is <150 mg/dl ⇒ administer 125 g D-50-W       -  Add 20 mg hydrocortisone to D-50-W to minimize pain at injection site b.  Fasting BGL is between 125 and 225 mg/dl ⇒ administer 12 g D-50-W c.  Fasting BGL is >225 mg/dl ⇒ administer insulin using the following formula      -  (BGL-50)/25 d.  After 30-60 minutes, if BGL is < 150 mg/dl ⇒ administer 5-15 mCi FDG intravenously e.  After 30-60 minutes, if BGL is > 150 mg/dl ⇒ administer more regular insulin until BGL is <150 mg/dl before administering FDG f.  Uptake time is 45-60 minutes Data courtesy of Emory University - Crawford Long Memorial Hospital Injection of 5-15 mCi F18 FDG Wait 45-60 minutes CT Topogram CT scan for AC PET static or list mode image 10-30 minutes Myocardial Blood Flow Imaging & Evaluation                                             Epicardial Coronary Vessels • Vessels that run along the outer surface of the heart • Remain patient during systole Subendocardial Coronary Vessels • Vessels that enter the myocardium • Compressed during systole • Blood flow to subendocardium stops during systole • Most myocardial perfusion during diastole Auto-regulation is mediated by the vascular resistance of vessels • Precapillary arterioles (Diameter <100 µm) • Pre-arterioles (Diameter of 100 - 500  µm) Resting State • This resistance is normal and constant Exercise State • Increases myocardial demand • Increased HR, contractility and blood pressure • Decrease in precapillary arteriole resistance   -  Arteriolar vasodilation   -  Increase myocardial blood flow to meet O2 demands Resting Coronary Blood Flow Reserve • Measurement of the ability of the myocardium to increase blood flow in response to maximal exercise     Flow Reserve • Ration of the myocardial blood flow at peak stress (maximum vasodilation) to flow at rest • Normal adults = 2.0 or higher Images courtesy of Cardiovascular Imaging Technologies, St. Luke’s Hospital, Kansas City, MO Multivessel CAD • Detection of subnormal flow in arteries with low level of stenosis • Appear normal on visual evaluation in the presence of arteries with more severe defects Multivessel Exclusion of CAD in Symptomatic Patients • Normal MPI study Balanced Multivessel CAD • Similar level of stenosis in all 3 vessels • Similar ischemia throughout the LV • Appearance of being normal Microvascular Disease • Abnormal flow reserve can define microvascular disease • Diabetes, hypercholesterolemia, and cardiomyopathies Post Revascularization • Flow estimation for evaluation of the effect of revascularization Severe Stenosis and Diffuse Coronary Artery Disease • Cause low flow of circulation even at rest • Inadequate O2 demand Hibernating Myocardium • Low resting flow • Intact cellular integrity • Chronic but reversible LV dysfunction • Improvement after revascularization • MBF can be used to determine hibernating vs. infarcted myocardium 13NH3 study with reversible inferior wall defect 13NH3 study with apical wall defect Image courtesy of Siemens Whitepaper “Validation of syngo.PET Myocardial Blood Flow” Calcium Scoring                                             Non-Invasive • Identifies the presence, location, and extent of calcified plaque in coronary arteries Calcified Plaques • Result from buildup of fat and other substances under the inner layer of the artery • Material can calcify, signaling the presence of atherosclerosis Normal Early Lipid Rich Internal Rupture Calcified Shell Calcified Plaque Vulnerable Rupture Thrombus Myocardial Infarction Obstructive Fatty streaks White blood cells Calcium Lipid rich plaque Red blood cells   Scar White blood cells Platelets & fibrin Inflammation & calcification Scar development with calcification Calcium Score Presence of CAD 0 No evidence 1-10 Minimal evidence 11-110 Mild evidence 101-400 Moderate evidence Over 400 Extensive evidence Data courtesy of CardiacHealth.org Quantification of calcified coronary lesions based on low dose CT acquisition • ECG triggered sequence • Retrospective gated spiral scans Multiple Scans • Can be used to follow changes in the coronary calcium load Features and Benefits • Accurate visualization and quick quantification of calcified coronary lesions • Scoring facilitated by automatic selection • Region growing tools for defining lesions in the main coronary branches (RCA, LM, LAD, CX) • Possibility of freehand ROI definition of lesions in addition to the seeding method Indications & Usage Fludeoxyglucose F18 injection (18F FDG) is indicated for positron emission tomography (PET) imaging in the following settings: Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer. Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging. Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.   Important Safety Information Radiation Risk: Radiation-emitting products, including Fludeoxyglucose F 18 Injection, may increase the risk for cancer, especially in pediatric patients. Use the smallest dose necessary for imaging and ensure safe handling to protect the patient and health care worker. Blood Glucose Abnormalities: In the oncology and neurology setting, suboptimal imaging may occur in patients with inadequately regulated blood glucose levels. In these patients, consider medical therapy and laboratory testing to assure at least two days of normoglycemia prior to Fludeoxyglucose F 18 Injection administration. Adverse Reactions: Hypersensitivity reactions with pruritus, edema and rash have been reported; have emergency resuscitation equipment and personnel immediately available. Dosage Forms and Strengths Multiple-dose 30 mL and 50 mL glass vial containing 0.74 to 7.40 GBq/mL (20 to 200 mCi/mL) of Fludeoxyglucose F 18 injection and 4.5 mg of sodium chloride with 0.1 to 0.5% w/w ethanol as a stabilizer (approximately 15 to 50 mL volume) for intravenous administration. Fludeoxyglucose F 18 injection is manufactured by Siemens’ PETNET Solutions, 810 Innovation Drive, Knoxville, TN 39732   Kreb's Cycle • Complex series of chemical reactions • Produces CO2 and ATP • Occurs in all cells that utilize O2 • CO2 is produced • Creates energy and DNA replication Fatty Acid Metabolism Glucose Metabolism Fatty Acid β-Oxidation Spiral Acetyl CoA Kreb's Cycle Glucose (FDG) Glycolysis Pyruvate or Lactic Acid Pyruvate or Lactic Dehydrogenase Acetyl CoA Why PET Myocardial Viability Scanning? • Permanent damage vs. viable heart muscle tissue • Determines if heart can recover if blood supply is restored • FDG - form of glucose • Heart has to demonstrate ability to metabolize glucose Permanent Damage • No glucose metabolism • No benefit from revascularization • 35% of bypass or angioplasty patients do not show improvement in cardiac function No Permanent Damage • Heart able to metabolize glucose • Possible benefit from revascularization Contraindications Potential Side Effects Uncontrolled asthma Flushing Greater than 1st degree AV block Chest pain Systolic BP less than 90 mm Headache Taking dipyridamole or aminophylline in last 24 hours Dizziness Caffeine in last 12 hours AV block Profound sinus bradycardia   Known hypersensitivity to dipyridamole or aminophylline   Unstable acute MI   Acute coronary syndrome   • Identify basic cardiac structures and coronary circulation By the end of this course you will be able to: • List the various types of coronary diseases and how they affect coronary physiology • Describe the various types of PET cardiac imaging • List the isotopes and radiopharmaceuticals that are used in PET cardiac imaging • Describe the protocols that are commonly used • Describe the procedure and how to evaluate myocardial blood flow • Describe the procedure used to evaluate calcium scoring Circumflex Artery Left Anterior Descending Artery Left Coronary Artery Aorta Right Coronary Artery Supplies: •  Sino-Atrial Node in some of the population •  Left Bundle of His CT Topogram CT Rest Scan for AC Injection of Rb82 20-60 mCi Wait 60-90 secs PET resting list mode image for 8 mins Injection of Rb82 20-60 mCi Stress drug injection Wait 60-90 secs PET stress list mode image for 8 mins CT stress scan for AC