Presented By:Michael MalloInstructor:NMT1713 Tim Marshel :Presented By:Michael MalloInstructor:NMT1713 Tim Marshel Cardiac PET Imaging


Objectives :Objectives Explain PET Instrumentation. Detector Configuration. PET Quantification. Image Reconstruction, Data Processing, and Attenuation Correction. Discuss Myocardial Metabolism. Carbohydrate Metabolism. Fatty Acid Metabolism. Substrate Utilization. Describe PET imaging agents. Perfusion-Related Tracers. Carbohydrate Metabolism-Related Tracers. Fatty Acid Metabolism-Related Tracers. Discuss Advantages/Disadvantages of PET. Overview Clinical PET Applications. Positron Imaging. Evaluation of Myocardial Perfusion in CAD. Viability Detection.


PET Instrumentation :PET Instrumentation PET systems are designed to detect the two 511-keV photons emitted from the nucleus of positron-emitting radionuclide. Most PET systems consist of rings of hundreds of pairs of solid-state detectors, such as bismuth germinate (BGO) or other detector materials, which surround the patient and their internal radiation source. This configuration permits exclusion of events from outside the ROI and permits electronic collimation and localization of events. This in turn allows three-dimensional reconstruction of tracer activity. Positron emissions can be efficiently counted and localized by pairs of detectors that are aligned 180° apart. Only photons that impinge upon both detectors, located at 180° angles to each other, at virtually the same time, coincidences, are included as true counts.


Pet quantification :Pet quantification Spatial resolution affects the quantification of image data because it relates to the smallest object size one can reliably analyze. A measured image value will underestimate the true tissue concentration of a radiopharmaceutical if the region analyzed is less than about twice the FWHM resolution limit and the background activity level is low. The geometry of the detector configuration in ring-type PET systems as compared to single or multiple detector gamma camera systems also affects quantification of the image data. Algorithms utilized in the reconstruction of cross-sectional images for PET, require at least 180° of data around a given plane in order to reconstruct the corresponding cross-sectional image through that plane. Ring-type systems have a fundamentally better temporal resolution than single or multihead gamma camera systems which must orbit the patient to acquire the 180-360° angular data used in reconstruction.


PET Image Reconstruction and Data Processing :PET Image Reconstruction and Data Processing In current PET devices, multiple adjacent detector rings produce 15-50 contiguous tomographic slices. Some time-of-flight systems which utilize detectors with an intrinsically faster decay time, such as CsF, permit binning the events as a function of time. The event data collected by the PET system are then reconstructed into cross-sectional images utilizing standard image reconstruction methods such as filtered-back projections (FBP). The in plane (x-y plane) resolution may therefore be better than the axial (z-axis) resolution. However, most modern PET systems produce multiple simultaneous axial images with z-axis resolution nearly comparable to the x-y resolution. Myocardial PET scans are usually reconstructed obliquely from the acquired dataset rather than in a strictly transaxial mode. Orientation is based on the long-axis of the heart (similar to SPECT) with reconstruction of short-axis, vertical and horizontal long-axis images.


PET Attenuation Correction :PET Attenuation Correction Attenuation correction it is critically important to PET evaluation. Attenuation correction of PET data can be either calculated or measured directly utilizing a transmission source. If structures are imaged which have relatively uniform attenuation characteristics, such as the head, then calculated attenuation correction methods may be used as an approximation based on assumption of the standard value for the linear attenuation coefficient. In the thorax, this approach does not work because of the large differential in attenuation profiles between lung (primarily air) and the heart (primarily soft-tissue density. Transmission source must be used which produces the equivalent of a relatively low resolution CT image of the patient from a line or ring of activity, often in the form of 68Ge.


AN OVERVIEW OF MYOCARDIAL metabolism :AN OVERVIEW OF MYOCARDIAL metabolism The ability to assess the myocardial utilization of a variety of substrates with PET (using a host of positron-emitting radiotracers) and SPECT (using a few single-photon emitting tracers) has made some aspects of myocardial metabolism a part of the nuclear cardiology curriculum. These techniques are increasingly used for clinical decision making, it is critical that myocardial metabolism be better understood by clinicians.


Substrate Utilization :Substrate Utilization The myocardium can utilize a variety of substrates, including free fatty acids, carbohydrates, lactate, ketone bodies and amino acids. Myocardial metabolic utilization of various substrates depends on their relative abundance in plasma and in cells, the hormonal mileau, patterns of perfusion, oxygen availability, enzyme activity and the degree of cardiac work. In the presence of adequate oxygen supply, free fatty acids are the preferred substrate, accounting for 60%-80% of the energy production of the heart. Shortly after a high carbohydrate meal, insulin levels are increased, plasma fatty acid levels are depressed and glucose utilization increases. All substrates are metabolized oxidatively through the tricarboxylic (citric) acid (TCA), or Krebs cycle, with acetyl Co-A.


Carbohydrate Metabolism :Carbohydrate Metabolism Only the brain surpasses the heart (myocardium) in its role as an obligatory aerobic organ. The heart, unlike the brain, has the ability to alternate between fatty acid and glucose metabolism for energy production. Under normal conditions, glucose stands with fatty acids and a host of other substrates as fuel for the cardiac myocyte. However, this changes with ischemia. The fatty acid metabolism will be the predominant energy-producing substrate for myocardial metabolism in a fasting state, while in a postprandial state, the heart will preferentially metabolize glucose. Energy can be derived from glucose metabolism an aerobically by glycolysis, which produces lactate, or aerobically by glycolysis, the citric acid cycle, and the respiratory chain. the amount of energy (ATP) generated anaerobically is very small and, although it may maintain cellular viability for short intervals, anaerobic glycolysis cannot sustain mechanical function for any substantial interval. Oxidative glucose metabolism is an important component of normal cardiac metabolic balance. Glucose enters the myocyte by carrier-mediated facilitated diffusion. The glucose transporter demonstrates stereo specificity and can translocate from a microsommal pool to the sarcolemmal membrane in the presence of increased cardiac work, plasma glucose or insulin levels.


Fatty Acid Metabolism :Fatty Acid Metabolism Fatty acids comprise the predominant myocardial substrate under most conditions and are albumin-bound. Their extraction depends upon the plasma concentration and the molar ratio of free fatty acids to albumin. Free fatty acid uptake and oxidation vary with fatty acid chain length and the degree of saturation. Once fatty acids are extracted into myocytes, they are transported to the mitochondria for beta oxidation. During ischemia, beta oxidation is significantly decreased. At advanced stages of ischemia, there is reduced esterification and storage of free fatty acids as triglycerides. During ischemia, accumulated intermediates of fatty acid metabolism further impairs cellular function.


PET IMAGING AGENTS :PET IMAGING AGENTS Radionuclides such as, carbon-11 (11Q, 13N and oxygen-15 (15O), are organic in nature or participate in the formulation of PET radiopharmaceuticals for rapid, repeatable and reproducible monitoring of physiologic, and often metabolic, processes with a small related radiation exposure. Dynamic acquisition and application of a biologic model, data extracted from PET agent localization can be used to quantitate absolute flow and metabolic rates. A variety of positron-emitting radiopharmaceuticals have been developed for and used in a variety of myocardial metabolic processes, including nC-acetate to evaluate oxidative metabolism and nC-palmitate for fatty acid metabolism. Fluorine-18 substitutes for hydrogen in organic materials. Fluoro-deoxyglucose (FDG) is an analog of glucose that is taken up by the myocardium. Myocardial glucose metabolic evaluation uses FDG which is the primary PET metabolic tracer in clinical studies.


Perfusion-Related Tracers :Perfusion-Related Tracers Rubidium-82 is a positron-emitting cation that can be obtained from a strontium-82 (82Sr) generation. The tracer is taken up by the myocardium and distributed intracellularly, in relation to perfusion, in a manner similar to potassium and 201T1. Uptake of 82Rb is linearly related to blood flow measured by microspheres up to approximately two times normal resting levels. The extraction fraction is 50%-60% on the first pass. Similar to other diffusable perfusion agents, uptake begins to plateau at higher flow rates because of decreased fractional extraction related to a reduction in residence time


Perfusion-Related Tracers :Nitrogen-13-ammonia is a particularly well extracted, diffusible tracer that has been used to estimate regional myocardial perfusion. Nitrogen-13-ammonia permits both PET imaging and quantification of myocardial blood flow (MBF). The technique has been validated in animals and humans. Appropriate one and two compartment tracer kinetic models have produced estimates of MBF with 13N-ammonia that are in good agreement with microsphere measurements. Lipid-soluble 13N-ammonia diffuses passively across both cell and capillary membranes and is then converted to 13N-glutamine by the glutamate-glutamine reaction and the alpha-ketoglutarte-glutamate reactions. Perfusion-Related Tracers


Carbohydrate Metabolism-Related Tracers :Most metabolic imaging of carbohydrate metabolism has been accomplished with 18F-2-fluoro-2-deoxyglucose (18FDG). FDG is an analog of glucose that is transported across the sarcolemma in proportion to glucose transport from plasma to tissue by the same carrier protein as glucose. FDG, like, and in competition with, glucose, is then phosphorylated by hexokinase to FDG-6-PO4, but, unlike glucose, it is not metabolized further. FDG-6-PO4 does not diffuse out of the myocyte and the 18F tissue signal accumulates in proportion to glucose metabolism. In normal subjects and patients, 18FDG is extracted by the myocardium with facilitated diffusion of the unaltered tracer, which competes with phosphorylation by hexokinase to 18FDG-6 PO4. The uptake of 18FDG is markedly affected by the dietary state of the patient. Uptake of 18FDG is low during the fasted state and has been associated with regional differences in 18FDG uptake unaccompanied by regional alterations in myocardial perfusion. Carbohydrate Metabolism-Related Tracers


Fatty Acid Metabolism-Related Tracers :Fatty Acid Metabolism-Related Tracers Carbon- 11-palmitate is a medium-chain length fatty acid whose clearance can be used to assess beta oxidation of fatty acids, the predominant aerobic substrate of the myocardium. This technique is dependent on activation of the tracer to its fatty acyl CoA derivative, which is trapped in the myocardial cell unless it is metabolized. Carbon-11-palmitate has been used with PET to assess myocardial oxidative metabolism. The rate of clearance from the rapidly clearing pool is accelerated by increased cardiac work and decreased in zones of ischemia or infarction. The uptake and clearance of uC-palmitate is dependent on the substrate environment, mandating that studies be performed in a fasting state.


ADVANTAGES OF PET :ADVANTAGES OF PET Positron decay and PET are intrinsically tomographic. PET provides homogeneous high efficiency event detection. This increases the modality's speed and temporal resolution. PET provides better intrinsic spatial resolution independent of depth and approaching 3 mm, which is far less than that of conventional scintillation cameras. The high energy of positron emission reduces but does not eliminate tissue attenuation of conventional low-energy emitters. Attenuation correction of PET data, benefited by real physical advantages, is perfected, routine and superior to that of SPECT. Many PET tracers are participants in basic body processes and can image physiology and biochemistry favorably. The physical precision of PET, together with tracer kinetic models, facilitates numerical descriptions of cardiac biological processes in physiologic unit quantitation.


Advantages / Disadvantages :Advantages / Disadvantages


CLINICAL PET APPLICATIONS :CLINICAL PET APPLICATIONS PET is an important physiologic complement to the exquisite anatomic imaging methods of US, CT and MRI. It also promises to complement imaging with conventional single-photon emitters. Cardiac PET studies have focused on physiologic measurements, such as myocardial perfusion, as well as biochemical processes, such as glucose and fatty acid metabolism. The most widespread clinical applications of cardiac PET studies include identification of coronary artery disease with perfusion imaging techniques utilizing 13N-ammonia, 150-water, 82Rb and other tracers, and, possibly more im­portantly, assessment of myocardial viability. PET perfusion studies are based on the same principles as myocardial SPECT perfusion studies. rest defects suggest scar and stress-induced perfusion deficits relate to abnormalities of CFR in locations of myocardium that suggest specific diseased coronary arteries.


Viability detection :PET myocardial viability assessment maps the uncoupling of flow and metabolism by combined flow/metabolism studies that characterize dysfunctional but viable myocardial segments. Myocardial segments with low flow at rest (or with stress) and high glucose utilization rates. Viability assessment has a strong and growing effect on the clinical management of coronary patients with extensive dysfunctional myocardium and heart failure, where it plays a large and increasing role in the decision to revascularize or refer patients for heart transplantation. PET viability assessment has become the gold standard for other noninvasive imaging methods which seek to identify viable but dysfunctional myocardium. Viability detection


Evaluation of Myocardial Perfusion in Coronary Artery Disease :Evaluation of Myocardial Perfusion in Coronary Artery Disease Myocardial blood flow is affected by a variety of factors, including the presence of atherosclerotic stenoses, coronary perfusion pressure, the state of the coronary microcirculation and intramyocardial pressure. The small coronary arterioles, below 450 microns in diameter, account for the majority of coronary vascular resistance but cannot be visualized with anatomic contrast techniques such as angiography. The goal of PET perfusion imaging is to produce images reflective of perfu­sion as well as quantitative perfusion measurements in physiologic units such as milliliters per minute per gram (ml/min/g). SPECT myocardial perfusion studies effectively image relative regional MBF patterns, but, because of imprecise attenuation correction methods, they do not result in quantitative measures of MBF in absolute units of flow. The ratio of MBF at maximum dilation compared to baseline, the coronary flow reserve (CFR), is calculated with the MBF measurement in units of flow during coronary dilation and at rest. Most PET studies of MBF have used the vasodilating agents adenosine or dipyridamole to test CFR because exercise is incompatible with the logistics related to the short tracer half-life.


C.a.d diagnostic :C.a.d diagnostic


N-13 ammonia vs. f-18 deoxyglucose :N-13 ammonia vs. f-18 deoxyglucose


COST-EFFECTIVENESS :COST-EFFECTIVENESS Current and earlier research and the more widespread commercial availability of perfusion and metabolic PET imaging agents and devices make PET the next important clinical breakthrough in noninvasive cardiac imaging. PET's expense, particularly in the current increasingly restricted funding environment, and the success of less expensive conventional techniques, necessitate careful evaluation of PET's relative diagnostic accuracy, clinical efficacy and cost-effectiveness. Selected applications of diagnostic PET methods have been advocated as cost-effective when performed in association with, or in place of, conventional methods to evaluate cardiac symptomatology or pathophysiology. PET requires expensive equipment and additional personnel and space, factors that may make the use of PET perfusion imaging in the initial examination to diagnose coronary disease appear costly. When evaluating multiple noninvasive diagnostic methods, PET may be most cost-effective in diagnosing coronary disease because of its great accuracy.


SUMMARY :SUMMARY PET provides a noninvasive method to quantitate chemistry in vivo, yielding information in humans akin to autoradiography in tissue slices. It promises to be the most accurate noninvasive analytic method for coronary diagnosis, prognosis and viability evaluation, with important implications for clinical management. There are now more than 150 PET centers active or planned in the U.S. and over 250 worldwide. While many of these facilities are primarily committed to research activities, they are increasingly accommodating growing clinical needs and primary clinical centers are also proliferating. This trend can be expected to increase dramatically with approval of PET reimbursement. For PET to succeed, its technology has to be simplified with: user friendly software, automation of scanner and cyclotron, simplification of PET interpretation, availability of PET radiopharmaceuticals and trained personnel, and cost reduction. As these issues are addressed, PET can indeed lead imaging specialties into their roles in the "molecular medicine" of the future.


References :References Society of Nuclear Medicine. (1998). Nuclear Medicine CARDIOLOGY, Cardiac PET Imaging. Reston, Virginia: Library of Congress Catalog in Publication Data.


Slide 26:Cardiac PET Imaging