CT Basics: PET-CT Essentials Module 6N PDF

Module 6N For educational and institutional use. This transcript is licensed for noncommercial, educational in- house or online educational course use only in educational and corporate institutions. Any broadcast, d...

Module 6N For educational and institutional use. This transcript is licensed for noncommercial, educational in- house or online educational course use only in educational and corporate institutions. Any broadcast, duplication, circulation, public viewing, conference viewing or Internet posting of this product is strictly prohibited. Purchase of the product constitutes an agreement to these terms. In return for the licensed use, the Licensee hereby releases, and waives any and all claims and/or liabilities that may arise against ASRT as a result of the product and its licensing.  CT Basics: PET-CT Essentials Module 6N 1. Title Slide Module 6N: PET-CT Essentials 2. License Agreement 3. Objectives After completing this module, you will be able to: 1. Discuss the history and evolution of PET-CT. 2. Name the major components of a PET-CT system. 3. Describe the scientific principles associated with PET-CT. 4. Discuss PET-CT patient preparation and imaging indications. 5. List the safety and quality requirements for PET-CT. 6. Discuss the requirements for performing PET-CT scans in cardiology, neurology and oncology. 4. History of PET-CT Positron emission tomography, or PET, relies on the action of positively and negatively charged electrons that destroy each other to create 2 powerful photons, each traveling 180 degrees from each other. We’ll discuss this action, known as the annihilation reaction, in greater detail later in this module. PET is a relative newcomer to the list of medical imaging modalities, yet its origins go back to the early part of the 20th century. The development of the cyclotron in the 1930s made it possible to create the radiotracers needed for PET. It was not until 1953, however, that Gordon Brownell and W.H. Sweet of Massachusetts General Hospital constructed the precursor to the modern PET scanner. This positron annihilation-based detector used copper 64 and arsenic 75 to diagnose brain tumors. 5. History of PET-CT In the 1960s the first single-plane PET scanner was developed at Brookhaven National Laboratory on Long Island, New York. It was used to measure cerebral blood flow. These scanners’ initial images were crude, yet the algorithms developed by Sir Godfrey Hounsfield, the developer of the computed tomography (CT) scanner, could be used with PET scanning to reconstruct images. 6. Early PET The first commercial PET scanner was created by EG&G ORTEC in Oak Ridge, Tennessee, and was called the ECAT II. ECAT stood for emission computed axial tomography. The first ECAT II was acquired by the University of California Los Angeles in 1976. PET imaging has continued to evolve through the use of new radiotracers, new crystalline detectors and improved reconstruction algorithms. ©2014 ASRT. All rights reserved. CT Basics: Module 6N  Passage of the FDA Reform Bill in 1997 also contributed to the development of PET imaging by making PET procedures reimbursable under Medicare, first for lung cancer and cardiovascular disease examinations, and in 1999 for lymphoma, melanoma and colon cancer. 7. PET-CT Beginnings When the functional images of PET are fused with the anatomical images of CT, PET becomes a powerful tool in the fight against cancer and other diseases. PET-CT was invented by Ron Nutt and David Townsend and was named the Invention of the Year by Time Magazine in 2000. In 2001 commercial PET-CT scanners were released by GE and Siemens; Philips Medical Systems followed suit in 2003. 8. PET-CT Uses Today PET-CT is used for a variety of reasons, such as evaluating cardiac disease and the effects of a heart attack, but mostly to help with cancer detection and monitoring. PET-CT images help pinpoint areas of cancerous activity in the body and distinguish between malignant and benign tissue, grade and stage cancerous lesions and identify new areas of cancerous activity in patients with a previously diagnosed cancer. PET images also assist clinicians in planning cancer treatments and monitoring the effectiveness of treatment. 9. PET Scanner First-generation PET scanners used rod or pin sources for attenuation correction. Attenuation correction measures and corrects for attenuation from tissues within the body. Each bed position could take 15 minutes or more to acquire. Technologists had to acquire separate emission and transmission scans per bed position, loading and parking the sources after every other movement. Patient motion was a common problem with first-generation scanners because scan times often lasted more than an hour. All tumor imaging was performed in 2-D mode with no fusion display easily available. Most PET-only systems used bismuth germinate (BGO) crystals, and some used sodium iodide crystals. 10. First-generation PET-CT First-generation PET-CT greatly reduced scan times and provided the first real-time fusion imaging. Although the scan times were nearly halved to about 30 minutes, the PET scanner technology remained the same, using 2-D imaging and BGO crystals. The pin sources remained in the PET camera for quality control (QC). The CT-generated attenuation correction map was generated in seconds instead of several minutes and was superior to rod or pin source maps. Attenuation coefficients generated from the CT were applied to the PET data during reconstruction. The CT scanner was placed in front of the PET scanner. The image on the slide is a first-generation GE PET-CT scanner that is a fused GE Discovery Light Speed CT scanner and GE Advance PET Scanner. The CT scanner was a 4-slice system used for attenuation correction and fusion. The bore of the CT scanner was 70 cm and the bore of the PET scanner was only 55 cm. The entire length of the system was 4.5 feet. 11. Second-generation PET-CT Second-generation scanners provided a constant bore diameter throughout the scanner, which increased patient comfort and helped ease patients’ claustrophobia. Scan time ©2014 ASRT. All rights reserved. CT Basics: Module 6N remained about the same as the first-generation scanner, at 20 to 30 minutes. Crystal technology improved with the availability of lutetium oxyorthosilicate (LSO) or lutetium-yttrium oxyorthosilicate (LYSO) crystals. However, BGO crystals were still the most common crystal type. Cameras using LSO crystals could cut down scan time further by imaging in 3-D. Faster CT technology also reduced CT scan time. Second-generation PET-CT used a faster, 16-slice CT scanner with a bore diameter of 70 cm. The bore length also was shorter than first-generation scanners, measuring 3.5 feet. 12. Third-generation PET-CT Current scanner technology uses a 64-slice CT scanner with a 70-cm bore and a bore length of 3.5 feet. These scanners incorporate time-of-flight PET imaging, which considers the time it takes for each gamma ray to reach the detector. Time-of-flight imaging can increase the signal-to-noise ratio and image resolution. Scanners with LSO and LYSO crystals are widely available. Imaging in 3-D is the new standard, and is the only imaging mode available with some newer PET systems. 3-D imaging reduces scan times, depending on department protocols. BGO crystal scanners still are available and widely used, and pin sources remain for QC imaging. 13. Positron Annihilation As we discussed earlier, PET scanning is possible because of annihilation reactions involving protons. PET uses proton-rich radionuclides. As they decay, the radionuclides emit positively charged electrons known as positrons, along with neutrinos. The emitted positrons interact with negatively charged electrons. The distance traveled by the positrons generally is very small but can be affected by the type of isotope used, which affects the image resolution. A positron with higher energy travels a greater distance. As the positron almost comes to a rest, both the positron and the electron are annihilated. This process produces 2 photons of 511 kiloelectron volts (keV) that are emitted 180° from each other and are collected by the PET scanner’s detectors. 14. Coincidence Detection The 2 photons emitted from the annihilation process are detected by the PET camera’s crystal matrix. A timing and energy window determines a true coincidence of events. If 2 separate events are recorded within the timing window (t), then they are counted as a coincidence event and a line of response is created within the field of view. Errors occur when scattered or single photons are incorrectly identified as a coincidence pair with another photon, thus adding noise to the image. This also can occur when 2 single photons are identified as a coincidence pair by the PET detectors. Various methods are used to correct for this problem. Because photons created by the annihilation reaction contain 511 keV, it’s assumed that coincidence rates at photon energies below 511 keV must be scattered photons and should be ignored. These methods require increased processing capacity and can add noise to the final image. Most scatter correction in the clinical setting is performed with theoretical models. Algorithms used today are based mostly on single-scatter approximation. 15. PET-CT Components PET-CT uses a standard CT scanner with an x-ray tube and a detector array. The x-ray tube and detectors rotate around the patient inside the gantry as the table system moves the patient through the detector. The CT system uses an adjustable peak kilovoltage (kVp) and ©2014 ASRT. All rights reserved. CT Basics: Module 6N milliamperage per second (mAs) to adjust the x-ray beam to the desired power. Collimation and pitch are used to determine slice thickness. State law determines whether a technologist must have CT certification to operate the CT portion of the PET-CT scanner. Certification also may be required if the CT portion of the PET- CT scanner is used to perform diagnostic CT examinations. Nondiagnostic CT can be performed to acquire the attenuation map and fusion image, which substantially lowers radiation dose from CT scanning. Contrast-enhanced PET-CT is possible with both intravenous (IV) and oral contrast. However, contrast can cause PET image artifacts. 16. PET Scanner The PET camera consists of a ring of detectors. The detectors are made up of a crystal matrix with stopping power and light-emitting properties. Some PET cameras are equipped with septa, or collimators that allow the camera to operate in 2-D mode. These collimators are in front of the crystal blocks and shield the detectors, reducing scatter and random coincidence events. Most modern PET scanners have 3-D cameras only, which means they do not have septa. Photomultiplier tubes located behind the crystal block detectors amplify the light from the crystals to create an electric pulse. The pulse is sent to the coincidence processing unit where the sinogram data is generated and sent for image reconstruction. 17. Crystal Types Crystals used in PET detectors have unique properties because PET detectors operate much more efficiently than the detectors used in gamma cameras. The ideal PET crystal must be very dense and convert most of the absorbed annihilation energy to light. Current crystals have excellent properties, but also have limitations. Today’s PET scanners use either BGO or LSO crystals. LYSO crystals also are available and their properties are similar to those of LSO crystals, but LYSO crystals contain a small amount of yttrium. Both crystal types are rugged and nonhygroscopic, which means they do not absorb moisture from the atmosphere. 18. BGO Use of BGO crystals was standard in PET imaging for years before the development of LSO-based detectors. The density of BGO makes it a good choice for stopping 511 keV photons. As the crystal absorbs the photon, it converts a fraction of the energy to light. This process takes time. The BGO decay time of 300 nanoseconds is good, but not ideal for 3-D imaging. Decay time means that it takes 300 nanoseconds for BGO to recover and then absorb a photon to emit light again. Light output from BGO is not optimal, but its high density and stopping power make it a good choice for PET. Its high singles efficiency also makes BGO a good scintillator for PET. BGO with a thickness of 25 mm will detect 91% of incoming photons. 19. LSO/LYSO Crystals LSO characteristics are much better than BGO’s, and LSO now is the preferred crystal for PET imaging. Because of its much shorter decay time and higher light output, LSO performs very well for 3-D imaging. 20. 2-D Imaging Septa rings are lead or tungsten collimators designed to shield the detectors from scattered photons during image acquisition. When imaging in 2-D, the septa rings are installed in front of the crystal matrix. This separates each crystal ring with lead or tungsten and ensures ©2014 ASRT. All rights reserved. CT Basics: Module 6N recording of coincidence events only between the same or directly adjacent rings. The septa ring blocks recording of data from events in other detector rings. This affects the system’s sensitivity because the septa rings have a shadowing effect on the crystals. Lower scatter fraction is a benefit of using septa rings with 2-D imaging. Only the scatter events that take place within the plane of each detector ring can be detected. It is possible to detect photons with much greater scatter angles with the septa removed. 21. 3-D Imaging The septa rings are removed for 3-D imaging. With the septa removed, all rings are exposed to detection coincidental events. All angles of photon detection are available, which increases sensitivity. As mentioned earlier, this also increases scattered photon detection. Removing the septa rings increases the field of view for detecting single events. This increases the probability of random coincidence events formed by 2 single photons. Algorithms are used in reconstructing the images to correct for these sources of error. This method of acquiring PET data now is used widely and has helped shorten scan times significantly. 22. Emission Scanning Emission scanning consists of capturing the annihilation photons coming from the source within the field of view in the PET camera. Emission data are separate from CT data because the data sets are acquired independently. Emission data are acquired in a step-and- shoot or dynamic manner, depending on the anatomical structure of interest. Each bed position is acquired for a set time, according to department protocol. The time per bed position movement usually is 2 to 3 minutes for 3-D imaging. When 2-D imaging is used, more time per bed position is added because of the limited sensitivity resulting from the septa ring. Technologists reconstruct emission data using iterative or filtered back projection methods. The system’s electronics sort true coincident events from scatter and single events. Modern 3-D systems must handle count rates of more than1 million counts per second. 23. Transmission Scanning Transmission scanning is performed in 2 ways. PET-only systems use pin sources made of germanium 68 or cesium 137. These sources are rotated around the patient to generate an attenuation map of that section of the patient’s anatomy. The map is acquired in a step-and- shoot manner. First-generation PET scanners used this method of attenuation correction. The scan started with an emission acquisition of about 5 minutes. The system then switched to transmission mode and acquired the transmission map of that section of the body. The bed would move to the next position and acquire the transmission map of that section of the body. The system would then switch to emission mode, and so on. These scans took as long as 1 hour or more to complete. Modern PET-CT systems use CT as the source for the transmission map. The CT scan generates the attenuation coefficients needed to correct the emission data. The CT scan is far superior to using rod or pin sources and can be acquired in seconds, compared with several minutes. An anatomical image is generated for fusion display. The use of 3-D PET imaging has further reduced scanning times dramatically. 24. Germanium 68 ©2014 ASRT. All rights reserved. CT Basics: Module 6N  Germanium 68 rod sources are the most common rod source used in transmission and QC scanning. Germanium decays to gallium 68, which then decays by positron emission. The sources have half-lives of 280 days, and should be replaced every year. The decay product of gallium 68 provides the correct energy photon for the needs of the transmission map and QC data. 25. Cesium 137 Cesium also is used for transmission sources. Its decay product, barium, produces a 662 keV gamma ray needed for PET imaging. Cesium 137 is not seen very often in scanning hardware because it has an extremely long half-life of 30 years. Disposal of used cesium 137 can be a problem. Both germanium 68 and cesium 137 are used as transmission sources. 26. Knowledge Check 27. Knowledge Check 28. Knowledge Check 29. Principles of PET-CT PET-CT provides the clinician with unique information. PET displays glucose metabolism within the body, which is a valuable tool in cancer imaging. Most, but not all, tumors take up sugar heavily. Staging disease before treatment helps clinicians determine how best to approach treatment and can help in surgical decision making. PET also can help physicians determine whether a tumor is viable after chemotherapy treatment and gauge treatment response by displaying glucose metabolism. Monitoring the effectiveness of treatment can be challenging with anatomical imaging such as CT or MR. PET is the only modality that can demonstrate whether the tissue is alive or necrosed through sugar metabolism. Using standardized uptake values, PET can gauge how a lesion is responding to radiation or chemotherapy by quantifying metabolism. 30. Principles of PET-CT Mathematically, the standardized uptake value is equal to concentration at acquisition time within the region of interest divided by the product of injected dose, divided by patient weight in kilograms. Standardized uptake value offers a semiquantitative analysis of the region of interest. It is a ratio of tissue radioactivity concentration at time (t). The time point must be the same for both scans to gauge treatment response using standardized uptake values. This method has limitations caused by changes in the patient’s metabolic state. Scanner calibration and image noise also can affect standardized uptake values. 31. Uses of PET-CT In addition to its many oncologic uses, PET imaging also is used for brain scanning. Patients undergoing clinical assessment and diagnosis of dementia can benefit from PET brain imaging with fluoro-2-deoxy-D-glucose (FDG). Physicians evaluate the pattern of cerebral FDG uptake to differentiate among various types of dementia. The most common types of dementia imaged by PET are Alzheimer disease and frontotemporal dementia. Brain scanning with fluorine F18 flourodopa also can be used in diagnosing and assessing treatment response of ©2014 ASRT. All rights reserved. CT Basics: Module 6N Parkinson disease. Although less common, FDG-PET brain scanning also can be used to differentiate scar tissue from malignant brain tumors. Heart disease also is evaluated with PET imaging. Coronary artery disease is assessed by observing functional flow. Blood perfusion to the myocardium is displayed on the scan. Vessels with significant narrowing show less tracer uptake in the myocardium than vessels with no narrowing. The 2 widely used radiopharmaceuticals for PET perfusion imaging are N 13 ammonia and Rb 82 chloride. Metabolic imaging to distinguish viable myocardia from infarcted or dead myocardia also is performed using FDG and is considered the gold standard for this type of imaging. 32. PET Radiopharmaceuticals PET radiopharmaceuticals offer a range of clinical and research uses. Most facilities that use FDG as the primary radiopharmaceutical use PET for oncology imaging. FDG offers providers flexibility for unit dose shipments from centrally located cyclotrons whereas larger facilities that conduct research and have high patient volumes might purchase their own cyclotrons. Isotopes with short half-lives such as oxygen 15 require the use of a cyclotron during the isotopes’ administration. With a half-life of about 2 minutes, oxygen 15 obviously cannot be shipped. Instead, it is delivered directly from the cyclotron to the patient using special equipment. The field of PET radiopharmaceutical research is very active and many new tracers are in development. 33. The Cyclotron A negatively charged ion is subjected to a strong magnetic and electric field within the cyclotron to accelerate the ion between 2 plates called dees. The ion is accelerated to a very high energy and then stripped of its electrons to make a positively charged proton. The proton is diverted to the target where it reacts with oxygen 18, forming fluorine 18. The fluorine 18 then is separated from the aqueous solvent in an ion exchange column and bound to the glucose molecule in commercially available cassettes within the hot cell. Different target materials produce different isotopes for clinical and research purposes. Quality control is performed on the final product before it is injected into a patient. Cyclotrons come as self-shielding units or unshielded units. A self-shielding unit is larger and might not be a practical choice for many PET providers. A vault must be built to shield unshielded cyclotrons. 34. Common PET Radiopharmaceuticals As we discussed previously, FDG is by far the most common tracer used in the clinical setting today and the only tracer that shows metabolism. Other tracers with their specific uses are also listed on this page. Observing metabolism helps to gauge treatment response and, therefore, treatment accuracy. Clinicians can assess whether a particular medication is effective by imaging patients early in their treatment using FDG. If FDG-PET imaging shows signs of reduced tumor metabolism, the treatment likely continues. Using FDG to gauge metabolism is a powerful tool in cardiology and neurology as well. Perfusion agents such as nitrogen 13 ammonia and rubidium 82 also are commonly used in PET cardiology. 35. Radiopharmaceutical Administration ©2014 ASRT. All rights reserved. CT Basics: Module 6N  It is common to use manual injection methods for administering FDG and other radiopharmaceuticals in PET imaging. First, the technologist puts in an intravenous (IV) catheter or uses a butterfly needle injection set. Then the technologist injects the tracer into the patient using a saline push and a shielded FDG syringe. Lead and tungsten shields are large and heavy, making direct injection with a shielded syringe difficult. The technologist must record the dose amount and time before injection. The injection time must be recorded along with a measurement of the residual FDG to calculate the actual dose injected. The injection time also is used to accurately gauge uptake time. 36. Flow-rate Controlled Injection Flow-rate controlled injection is a pump-driven system that infuses 18F-FDG in very precise amounts. The technologist places an IV in the patient’s arm and the patient is connected to the pump in the cart that has a disposable injection set. The first controlled flow-rate system for PET was the Intego system from MEDRAD (Warrendale, Pennsylvania). The technologist can adjust dose amount via Intego’s touch screen. The dose is administered with a saline push through the system’s controlled administration. The system administration set is controlled with a one-way valve to ensure no back flow into the system. The Intego system is self-shielding, which reduces the technologist’s radiation exposure during administration of FDG. The system prints out the injected dose when completed. 37. Research Injection Systems Oxygen 15 water and gas is used for blood flow and gas exchange research. Research drug delivery systems are used with various PET radiopharmaceuticals. Short-lived isotopes usually are injected with a system connected directly to the cyclotron. Oxygen 15 has a very short half-life of 2 minutes, making unit dose delivery through special research drug delivery systems necessary. Institutions with a cyclotron that are participating in research using these tracers are the only places that currently use this type of equipment, and commercial production of these systems is very limited. A direct connection to the cyclotron generally is created through a floor or wall conduit, depending on the location of the cyclotron and camera. These conduits must be shielded for safety. The cyclotron is calibrated to deliver the correct dose. Once ready, the cyclotron delivers a constant supply of oxygen 15 and the oxygen 15 water is delivered to the patient through a collection device. The camera is ready to acquire PET images before injection begins and the patient is injected while positioned in the camera unit. 38. Oncology In the next several pages we will be exploring the use of PET/CT in oncology diagnosis and monitoring. 39. Oncology As we have discussed previously, PET-CT is often used in oncology diagnosis and monitoring. Patient preparation is essential to a quality scan in PET using FDG. Because the scan relies on metabolism, it is critical that patients fast. ©2014 ASRT. All rights reserved. CT Basics: Module 6N  If the patient has eaten within 4 hours of the scan, the scan should be rescheduled because the insulin released after ingesting food drives glucose into the liver and muscles. This is a normal response to increased blood sugar levels. When a patient is injected during this insulin phase, the injected glucose is pushed into the liver and muscles, which decreases the scan’s sensitivity. Strenuous activity has a similar effect on the recovery phase of the muscles used. Scan quality is not affected as much as in a nonfasting state. Only the muscles used will typically be seen. Typically, patients are advised to eat a low-carbohydrate diet the night before the exam, along with fasting the day of the scan, to ensure a favorable metabolic state. Adequate hydration helps provide favorable target-to- background ratio because hydration helps to clear soft tissues of free FDG. Once injected, the patient should rest for about 1 hour for oncology studies, depending on department protocol. The patient should be kept warm and relaxed during uptake to provide the best environment for proper uptake of the FDG. Sedatives can be used to help the patient relax during uptake and scanning. 40. Patients With Diabetes Diabetes presents metabolic challenges for many patients. PET departments should set guidelines to deal with patients who have diabetes and establish glucose limits to help technologists working with these patients. Fasting can cause problems for patients who have diabetes, which can affect insulin injection times and types. Fast- and slow-acting insulin can change the injection time for a patient. If the patient’s blood sugar is too high upon arrival, he or she can receive fast-acting insulin to lower the glucose to within department-set limits. Technologists also should be aware that low blood sugar in a patient might lead to cancellation of an FDG-PET examination for the patient’s safety. Patients on steroids for chemotherapy treatment can have elevated blood sugar. All of these situations should be considered and proper protocols put in place to deal with them. 41. Inpatients Hospital inpatients often present different imaging challenges than outpatients. Communication with staff on the patient’s floor is important to ensure proper patient preparation. A check of all IV solutions must be made before injecting FDG to ensure that the patient is receiving no insulin or dextrose. Solutions containing dextrose are common and can affect FDG-PET scan quality. If an insulin or dextrose solution is circulating during injection and uptake, it causes increased muscle uptake results on the scan. Sensitivity can be compromised and confidence in scan results decreases dramatically. Attention to matters such as IV solutions can prevent repeat exams. Inpatients’ mobility needs also must also be considered, and a slider board or patient lift might be needed to transfer the patient to a gurney for the trip to the nuclear medicine department. 42. Indications As we have seen, cancer is the primary indication for FDG scanning. Most tumor types take up FDG readily. Because FDG uptake is based on metabolism, faster growing tumors have a higher affinity for FDG. The list of tumor types now reimbursable under Medicare for PET imaging continues to grow. Initial staging and post-treatment restaging are the most common indications for oncology. Medication treatment response also can be gauged with FDG. If it is ©2014 ASRT. All rights reserved. CT Basics: Module 6N found that the current treatment is not effective based on standardized uptake value analysis or generalized decreased metabolism, clinicians can make adjustments during the early stages of treatment. 43. Contraindications PET scanning is a very safe procedure and FDG has no known side effects when injected with normal saline. High blood sugar due to diabetes or chemotherapy can delay the procedure or result in its cancellation, as can low blood sugar. High blood sugar should be lowered to meet department guidelines before beginning a PET scan with FDG. Patients with low blood sugar can receive juice 30 to 60 minutes after FDG injection if it is determined to be safe per department guidelines. Other contraindications for PET scanning include pregnancy, extreme obesity that prevents the patient from fitting into the scanner and failure to fast according to instructions. 44. Positioning Technologists should emphasize comfort when positioning patients. This helps ensure good image quality. Some patients have shoulder pain that prevents them from putting their arms above their head easily, so putting the patient’s arms down and strapping them by the patient’s side may be more practical. Common sense should be used when positioning a patient. Positioning the patient on his or her side may make the difference in helping the patient get through the scan. Depending on the specific protocol, the catheter placement and landmarks used to start the scan should be adjusted accordingly. Good communication with patients and listening to patients’ needs is essential for good quality images. 45. Artifacts Image artifacts are a common problem in PET-CT. Metal objects on or in a patient create reconstruction artifacts because of the CT attenuation map. Patient motion causes mismatched fusion display and scatter correction artifacts. Some scatter correction problems can be fixed by turning the scatter correction off as a component of the reconstruction algorithm. Doing so negates the validity of standard uptake values, however, and can necessitate reimaging of the patient. Patient comfort on the imaging table is very important to avoid some common motion artifacts. Injection site artifacts can be avoided by imaging the patient with the affected arm out of the field of view if possible. 46. Oncology Scan Walk-through When a patient enters the PET-CT scanning department, imaging staff should obtain some basic information, including patient identification, fasting status, height, weight and whether the patient has diabetes. If the patient meets the fasting requirements, a blood sugar test should be administered. Individual departments set blood sugar limits that technologists always should follow. An IV should then be started in the patient’s arm and the FDG injected. FDG dose amounts also are determined per department protocol. Common dose amounts are 10 to 20 millicurie FDG. The patient should be made comfortable and kept warm during the uptake phase. A 60-minute uptake is common for scanning of tumors. The patient should empty his or ©2014 ASRT. All rights reserved. CT Basics: Module 6N her bladder before the scan so that the radiologist can better evaluate the pelvis. The patient is positioned on the scanner and the scan is started. 47. Knowledge Check 48. Knowledge Check 49. Knowledge Check 50. Neurology In the next several pages we will be exploring the use of PET/CT in neurology. 51. Brain Scan Preparation Preparation for brain scanning is similar to tumor scanning, except for injection and uptake. Sedatives should not be used if possible. FDG is the most common tracer used, so the procedure generally follows the same fasting and diabetic restrictions as oncology scanning. During injection, the patient should close his or her eyes to reduce light stimulation to the brain. Uptake time usually is only 30 minutes. The patient should be kept in a dark, quiet environment during uptake, and should not listen to music. The technologist should encourage the patient to avoid falling asleep during the 30 minutes. Tracers other than FDG that have other methods of action do not require such restrictions. 52. Indications Most PET brain scanning is performed using FDG. Because brain metabolism is altered in many neurological conditions, changes in metabolism can be detected early in the disease process using FDG. The brain has high glucose uptake under normal circumstances, so FDG-PET usually is not used to diagnose or stage brain tumors, but FDG is used to evaluate treatment response and to differentiate scar tissue from malignant tissue in some cases. PET scanning with 18 F dopa can image dopamine receptors in the brains of patients suspected of having Parkinson disease, along with gauging treatment response in these patients. Alzheimer disease and other dementias are the most common indications for PET brain scanning. Early diagnosis is critical to effective treatment and new drugs are in development to help diagnose these diseases at earlier stages of development. 53. Contraindications PET brain scanning has the same contraindications as scanning for tumors if the scans involve FDG. Scanning with 18F dopa has no fasting or blood sugar restrictions. The patient may need to receive carbidopa before18F-fluorodopa is injected. Carbidopa inhibits the enzyme decarboxylase, which increases the bioavailability of F-Dopa. Patients undergoing metabolic brain scans with FDG should not be sedated, and if a patient has taken a sedative, this should be noted before injecting FDG. Sedatives used for anxiety can alter the brain’s metabolism. 54. Positioning Positioning for PET brain scanning requires centering the head in the camera bore. The ideal position for scanning is supine, although comfort is important to minimize patient motion. Scan time usually is shorter than with body scanning, and scan times of 5 to 10 minutes are common with modern 3-D cameras. If the patient is considered at high risk for motion, such as a patient with dementia, the technologist should consider using dynamic scanning. ©2014 ASRT. All rights reserved. CT Basics: Module 6N 55. Artifacts Brain imaging artifacts usually are caused by patient motion. Metal implants infrequently cause artifacts, but patients should remove hearing aids and jewelry if the items might interfere with imaging. Imaging patients with Alzheimer disease or other dementias can present additional challenges because the patient’s mental status can lead to motion artifacts. Dynamic imaging can help to minimize motion artifacts. 56. PET-CT Brain Scan Walk-through Let’s briefly walk through a PET brain scan procedure. The patient arrives at the nuclear medicine department after fasting for at least 4 hours, but drinking enough water to be well hydrated. After a successful blood glucose check, the patient is injected with FDG at a dose set by department protocol. The patient is placed in a comfortable position to rest in a dimly lit room for 30 minutes and then positioned on the imaging table using appropriate landmarks. A CT scout scan is performed, and PET acquisition parameters are prescribed from the scout scan. The CT scan is then performed, followed by PET acquisition. 57. Cardiology Cardiac disease is the leading cause of death in both men and women. The most common disease of the heart is coronary artery disease (CAD). CAD is a narrowing of arterial vessels that supply the heart muscle with blood and oxygen. This narrowing results in insufficient oxygen delivery to the heart muscle, also known as ischemia. If not detected and corrected, this condition can lead to myocardial infarction, or death of cardiac muscle. Cardiac PET scanning is not a direct measure of the degree of vessel wall narrowing, but instead demonstrates the functional significance of the disease. Cardiac angiography is considered the standard imaging method for direct measurement, but carries certain risks. PET scanning is less invasive and shows function rather than anatomy. 58. Patient Preparation Technologists should obtain the patient’s cardiac history before proceeding with cardiac procedures. This includes cardiac-related symptoms and previous cardiac events or procedures. The presence or history of diabetes also should be noted for certain PET procedures. The patient must fast and refrain from ingesting caffeine, smoking and taking certain medications that can counteract the effects of pharmacologic stress testing. This testing is an essential part of coronary flow reserve PET imaging. Cardiac viability imaging also can be compromised by improper patient preparation. 59. Coronary Flow Reserve PET cardiac flow reserve imaging includes 2 components: imaging at rest and imaging during stress. Rest imaging shows baseline blood perfusion of the myocardium; stress imaging shows the amount of vascular narrowing that may only be evident at high flow rates. The technologist injects radiotracers with myocardial localization properties. Blood vessel limitations can be evaluated by the degree of radiotracer uptake in the myocardium. The physician determines which myocardial wall is affected and the vessels that supply the wall. Interpretation is based on the intensity and distribution of tracer in the myocardium in 3 imaging planes: short, horizontal long and vertical long axes. Images at rest (or baseline) and ©2014 ASRT. All rights reserved. CT Basics: Module 6N stress images in all axes are compared. If images are acquired in a gated mode, the wall motion and ejection fraction also can be evaluated. 60. Normal Coronary Flow Reserve Scan These images demonstrate a normal cardiac PET scan with images taken in 3 planes under stress and at rest. 61. Positive Coronary Flow Reserve Scan When the stress images show a mismatch or low myocardial perfusion uptake compared with normal rest images, the physician diagnoses ischemia. The arrows in the image on the right indicate an area of low myocardial perfusion uptake. This is seen on multiple slices and in the different projections. In this short axis image projection, all walls of the left ventricle can be seen at rest but not during stress. 62. Patient Preparation The patient must have an IV in place for radiotracer and pharmacological stress agent infusion. Ideally, one IV line is placed for each agent to prevent bolus of pharmacological stress agent. Stress testing requires that the patient be monitored at all times. A 12-lead electrocardiogram (EKG) and blood pressure monitoring take place throughout the procedure. 63. Coronary Flow Reserve Radioisotopes The 2 most common radiopharmaceuticals for PET cardiac imaging are nitrogen 13 ammonia and rubidium 82. Use of N 13 ammonia results in better resolution because of a low kinetic energy during decay and thus shorter positron range. Because nitrogen 13 ammonia is cyclotron produced and has a short half-life of about 10 minutes, it is not easy for most facilities to obtain. Rubidium 82 has a higher kinetic energy and a lower spatial resolution but is more readily available and affordable for facilities that do not have cyclotrons. Instead, rubidium 82 is generator produced and purchased as a cart with monthly generator exchanges. 64. Stress Test Unlike traditional nuclear medicine cardiac imaging, the stress induced for PET imaging is created using pharmacology instead of physical exercise on a treadmill. Radiotracers have relatively short half-lives, and it takes time to complete the treadmill portion of conventional stress tests and then transfer and position the patient for imaging. Instead, technologists can induce stress using drugs such as dipyridamole, adenosine, regadenoson and dobutamine. Pharmacologic stress testing is performed on the imaging table with the patient positioned for imaging. This allows for immediate imaging at the optimal time during stress response. Another reason to use pharmacologic rather than treadmill-induced stress testing is that after an exercise test on a treadmill, the patient’s breathing pattern changes from the initial images throughout the acquisition. The patient begins with deep breaths and returns to baseline breathing patterns. This can cause motion artifacts on acquisitions using a source for transmission (PET only) and even more so on those acquired with PET-CT. 65. Stress Techniques ©2014 ASRT. All rights reserved. CT Basics: Module 6N  Stress testing is an important component of the coronary flow reserve study. A physician with experience in pharmacological stress and advanced life support always should be present to supervise the entire stress test. Proper stress response is essential in coronary flow reserve imaging to obtain optimal results. Generally speaking, use of a dynamic stress test such as a treadmill is the best choice for patients who are physically able to complete the test. Using the dynamic method in PET imaging can be a difficult transition, however, and may result in suboptimal imaging. The safest and most effective stress test is chosen for each patient after careful evaluation of the patient’s cardiac and overall health history. 66. Dipyridamole Procedure One common pharmacological stress agent is dipyridamole. Dipyridamole acts indirectly by blocking the transport of endogenous adenosine into the cells, which increases the levels of adenosine locally that can interact with the A2A receptors on smooth muscle cells. This results in vasodilation. Dipyridamole is infused intravenously at the rate of 0.14 mg/kg/min over 4 minutes. The radiopharmaceutical agent should be injected 3 to 4 minutes after completion of the dipyridamole injection. It is very common to have side effects from the dipyridamole injection, including flushing, headache, nausea and chest discomfort. Dipyridamole is not always an ideal choice for PET stress testing because it has a tendency to cause side effects that last throughout the examination. This makes it hard for the patient to lie still for imaging and for the staff to return the patient to a resting state while imaging is in progress and the patient is positioned in the camera. If symptoms become severe or troublesome, they can be reversed with IV administration of 100 to 200 mg aminophylline, but only after radiopharmaceutical injection. 67. Adenosine Procedure Another common pharmacological stress agent is adenosine. Adenosine administration results in direct stimulation of the adenosine receptor A2A in the smooth muscle cells. This causes the conversion of adenosine triphosphate (ATP) to active adenosine triphosphate (cATP), which results in vasodilation. Adenosine is administered at the rate of 0.14 mg/kg/min over a 6- minute period. Adenosine has a short biological effect of about 10 seconds, so it is important to continue the infusion while the radiotracer is being localized in the myocardium. The radiotracer is administered at the 3-minute mark, halfway into the pharmacological infusion. Side effects from the adenosine infusion include shortness of breath, flushing and chest pain. Atrioventricular block also can occur, so close monitoring of the patient’s EKG is vital. Because of its short biological effect, the effects of adenosine can be reversed quickly if needed by stopping the infusion. This characteristic allows imaging to begin before the patient’s side effects interfere with the examination. 68. Regadenoson Procedure Regadenoson is the newest pharmacological agent used for stress testing. It only has been approved by the FDA since 2008, so clinicians have less experience with this medication than with others. Regadenoson administration results in direct stimulation of the adenosine receptor A2A in the smooth muscle cells. This causes the conversion of adenosine triphosphate ©2014 ASRT. All rights reserved. CT Basics: Module 6N (ATP) to active adenosine triphosphate (cATP), which results in vasodilation. Regadenoson is administered rapidly in a single dose of 0.40 mg over 10 seconds. The regadenoson infusion is followed by a saline flush, and the radiopharmaceutical follows 10 to 20 seconds after the saline flush. The side effects and contraindications from regadenoson, although rare, are almost identical to those of adenosine. Regadenoson is a selective agent that binds primarily to A2A receptors of the capillary walls, thus avoiding most of the side effects related to agents that bind to multiple adenosine receptors, such as adenosine. 69. Dobutamine Procedure Dobutamine, a synthetic catecholamine, is a sympathomimetic stress agent that has a high affinity to adrenergic B1 receptors. It causes secondary coronary vasodilation by increasing myocardial oxygen demand. Dobutamine is administered slowly using a titration method that starts at 0.005 to 0.01 mg/kg/min and increases in increments of.010 mg/kg/min to achieve the patient’s target heart rate (calculated as a cardiac double product) to a maximum dose of 0.05 mg/kg/min. Once the desired heart rate is reached, the radioisotope is injected. Atropine can safely be added to help reach the desired peak heart rate. The pharmaceutical infusion is stopped 1 to 2 minutes after the radioactive tracer is injected. The patient’s heart rate returns to baseline during recovery. Side effects can include a pounding feeling in the chest and ectopy. A beta blocker such as esmolol can be given to reverse ectopy side effects if necessary. 70. Walk-through of Coronary Flow Reserve Procedure Because of the short half-life of PET cardiac perfusion tracers, the patient is prepared for a stress test and positioned on the camera for initial resting imaging, directly followed by stress test and post-stress imaging. With use of nitrogen 13 ammonia, there is typically a delay for decay of at least 45 minutes between the 2 injections. EKG and blood pressure readings are obtained at baseline and then monitored throughout the stress test. Once the appropriate level of stress is achieved, the technologist injects the tracer at the optimal time for the designated stress agent. The stress imaging starts promptly after stress test completion, and recovery continues during this imaging procedure. The rest and stress PET image is a 1-bed acquisition lasting approximately 10 minutes. These images can be static or dynamic at rest and typically gated at stress. A second transmission scan can be done at the end, following the stress emission images, so that the patient can be moved out of the scanner for the stress test and repositioned for the stress images. This also helps to avoid patient motion artifacts even if the patient remains in the same bed location for the entire procedure. If this transmission scan is acquired following the stress images, a transmission/emission acquisition must be obtained when using nitrogen 13 ammonia. This consists of a 2-minute static acquisition that will correct for the activity remaining from the N13 injection within the transmission scan. Transmission scans with rod or pin sources are most commonly used for cardiac PET. These transmission scans are used for positioning and attenuation correction in cardiac PET. When using CT for attenuation correction there are often artifacts caused by cardiac motion. 71. Myocardial Viability Study ©2014 ASRT. All rights reserved. CT Basics: Module 6N  When perfusion PET imaging reveals decreased or absent uptake on both rest and stress images, the finding typically is due to myocardial infarction. Angiography or PET perfusion imaging may not be able to differentiate between very low flow and cell death, thus metabolic PET imaging with 18F-FDG is ideal. Metabolic imaging displays mismatched uptake that can indicate presence of an underlying viable myocardium. A hibernating myocardium can reliably be differentiated from scar tissue and thus help plan a patient’s treatment strategy. A perfusion study is performed first, and then the patient is prepared for the FDG injection. The myocardium uses fatty acid as its primary energy source, so it is necessary to convert the myocardium from free fatty acid metabolism to glucose metabolism to better display the heart on an FDG-PET scan. This is done by prepping the patient with oral glucose and insulin administration or by using the hyperinsulinemic euglycemic clamp. The latter is a lengthy and cumbersome procedure but results in the most reliable myocardial FDG uptake. It also may be the only way to control the blood glucose levels in patients with diabetes. This preparation can be lengthy and varies from patient to patient, which makes scheduling of camera time difficult. There is no way to predict at what time the patient will be ready for the 18F-FDG injection. The nursing staff may have to hold the clamp for varying periods of time for proper timing of the injection, followed by the scan approximately 60 minutes later. Coronary flow reserve procedures have little uptake time. Ideally, the imaging is started as soon as possible after radioisotope injection. Cardiac viability imaging is similar to tumor imaging with FDG. Once the patient is injected with the FDG, uptake time is 60 to 90 minutes before imaging begins. 72. Positioning The patient is positioned in the scanner feet first for PET-only imaging so that the head is outside of the scanner. This positioning is essential for communication during the stress test and so that all patient monitoring equipment is accessible. It is very important to make the patient as comfortable as possible to minimize patient motion during scanning. The patient’s arms are placed up and out of the field of view for less attenuation and to allow access to IV lines and the blood pressure cuff. In PET-only imaging, the transmission and emission scans are in the exact same position in the scanner. To make the patient more comfortable during stress testing, the table can be moved out slightly just for the stress test and then moved into the scanner as imaging begins. In this case, the emission scan is started immediately for optimal count rate followed by the transmission scan. This also requires a transmission/emission acquisition when using NITROGEN 13 ammonia. PET-CT imaging requires the patient be positioned in the scanner head first. The position of the patient is different in the scanner for the PET and CT imaging sets. The PET scanner is positioned in the back of the CT scanner, although theoretically the scanners are in the same position for image acquisition. The patient must be moved from CT position to PET position. Monitoring the patient during recovery can be more challenging with PET-CT because the patient is positioned through the back of the scanner at this point. 73. Contraindications The patient’s inability to lie flat or still throughout the procedure is a contraindication to PET-CT. Some patients have claustrophobic issues because of the equipment’s size; these ©2014 ASRT. All rights reserved. CT Basics: Module 6N patients may refuse the exam. Some patients cannot fit into the scanner’s bore because of their size. Some form of pharmacological stress usually is appropriate and possible, but there are many contraindications to stress tests. These include asthma, atrioventricular block, abnormal blood pressure, unstable angina, recent heart attack and ingestion of caffeine or certain medications before the examination. Again, patients should be evaluated for these potential contraindications before proceeding with PET-CT. 74. Artifacts Mispositioning of a patient within the scanner can lead to various forms of artifacts. Notice the mismatch between the CT and PET images above. The PET image is shifted to the left. This can happen when the patient moves slightly between the CT and PET image acquisitions. This image cannot be used for diagnostic assessment. Motion correction can help negate the artifact in mild cases. 75. Quality Control This image shows a bad detector block. Notice the missing lines through the sonogram. Service is required to determine the reason for the bad detector. 76. Knowledge Check 77. Knowledge Check 78. Knowledge Check 79. PET Camera PET camera QC is performed each morning before patient imaging begins. Modern PET- CT systems perform multiple self-checks on the detectors and electronics. QC checks are done on coincidence events, singles, dead time, timing and energy windows. The results are compared with a baseline prepared after a calibration has been performed. Monthly and quarterly checks and calibrations can be done per manufacturer recommendations or department guidelines. 80. Daily QC Daily QC is performed each morning before the camera is used for patient imaging. The system uses a transmission source to check multiple aspects of system performance. The results usually are compared with a baseline created during a quarterly calibration. 81. CT Scanner QC CT scanner QC is performed each morning before patient scanning to ensure normal equipment function and to catch potential hardware and software problems. A tube warm-up brings the tube slowly to normal operating temperature to prevent thermal cracking or arcing. Daily air calibration adjusts detector gains to achieve a uniform response. The water phantom is used to check for artifacts caused by nonuniformities in detector response, such as ring and streak artifacts. 82. Weekly QC ©2014 ASRT. All rights reserved. CT Basics: Module 6N  Weekly system QC is performed to compensate for photomultiplier tube gain drift due to room temperature fluctuations, along with aging detector blocks and electronics. QC also should be performed whenever maintenance has been performed on the camera detectors. Coincidence-timing calibration adjusts for the time delay between detector blocks. The calibration time stamps all detector blocks as equal. 83. Quarterly QC Quarterly QC usually is performed by a service person or physics consultant. Normalization is a uniformity correction for efficiency variations in lines of response for each slice. A normalization also should be performed after system maintenance. The crystal-map calibration maps the position of a detected event to a specific crystal. Again, this should be performed after detector maintenance. Well-counter calibration is performed with a phantom with a known concentration of 18F-FDG. The calibration ensures accurate standard uptake value data. 84. Radiopharmaceutical QC Once the 18F is bound to the sugar molecule and delivered to a vial, it must be checked before injection into a patient. QC ensures that the product is safe. Character is determined by visual inspection of the agent. If it is not clear and colorless, it should not be used. Identity ensures that the agent actually is FDG. The pH is checked to ensure it is correct before injection. Purity and sterility are checked, as well as a check to ensure there are no traces of residual organic volatile solvents, to ensure patient safety. State laws may require that additional tests be carried out before the radiopharmaceutical is released for clinical use. 85. Radiation Safety Handling 18F-FDG around patients presents a higher exposure risk because of the higher energy of 18F. The patient is the highest source of a technologist’s exposure to radiation in PET imaging. Basic safety precautions should be taken by all personnel working with FDG. Technologists should decrease their time with patients, increase distance from patients and use the appropriate shielding to minimize exposure during the scanning process. Of course, patient safety should never be compromised. 86. Patient Preparation The technologist also is at risk of exposure when injecting radiopharmaceuticals. Tungsten is the most commonly used type of manual injection shielding. Its high density makes it ideal compared with lead. Tungsten has a density almost twice that of lead at 18.6 g/cc vs 10 g/cc. Tungsten also is environmentally friendly, compared with lead’s toxicity. The commercially available injection cart is an alternative to manual injection and can reduce exposure significantly. By housing a vial in a shielded cart and injecting with a pump, technologists put some distance between themselves and patients during injections. Uptake space should be shielded or away from the technologist. Alarm systems can be used so that the patient can notify technologists if anything is needed; these allow technologists to increase their distance from the injection. 87. Future of PET-CT The future is bright for PET-CT imaging. A commercially available PET-MR scanner also is on the market. New crystal technology increases sensitivity and decreases PET acquisition times. ©2014 ASRT. All rights reserved. CT Basics: Module 6N The future will bring new agents to image different diseases and diagnose earlier stages in the disease process. Pittsburgh Compound B, or PiB, is a new PET tracer in clinical trials that is used to image amyloid plaque in the brain or body. Brain imaging with PiB could help diagnose Alzheimer disease at an earlier stage. Labeled peptide imaging with 18F-FDG and other tracers likely will be used to diagnose and treat disease. CT scanner development also is rapidly changing. Lower-dose CT scanning should increase patient safety and further decrease scan times. 88. Conclusion Having completed this module, you should now be able to: 1. Discuss the history and evolution of PET-CT. 2. Name the major components of a PET-CT system. 3. Describe the scientific principles associated with PET-CT. 4. Discuss PET-CT patient preparation and imaging indications. 5. List the safety and quality requirements for PET-CT. 6. Discuss the requirements for performing PET-CT scans in cardiology, neurology and oncology. 89. Acknowledgements 90. Bibliography ©2014 ASRT. All rights reserved. CT Basics: Module 6N