Presentation on theme: "105th Annual Meeting of the American Roentgen Ray Society"— Presentation transcript:
1 105th Annual Meeting of the American Roentgen Ray Society Positron Emission Tomography: A Practical Review of Clinical Applications and a Self-examination Neville Irani1 MD, Jorge Vidal2 MD, Natasha Acosta2 MD, Mark Redick2 MD, Akash Sharma1 MD.1Allegheny General Hospital, Pittsburgh, PA2St. Luke’s Hospital of Kansas City/ UMKC, Kansas City, MOSt. Luke’s Hospital of Kansas City
2 Radioactive Decay & Nuclear Imaging Example99mTc 99Tc+18F 18O+++Isomeric transitionAlphaBeta -Beta + [positron]Electron CaptureIn the Nuclide Chart shown in the diagram A below, nuclides are arranged according to the number of protons Z and neutrons N in the nucleus. This arrangement, originally proposed by Segrè, is particularly useful for visualising nuclear decay processes. As a result of nuclear decay, a "parent" nuclide with co-ordinates Z, N decays to one or more "daughter" nuclides with co-ordinates Z', N'; Z'', N''; etc. Nuclides can also be arranged in a plot of A-2Z vs. Z as shown in diagram B. This leads to a more compact form of the decay chain particularly suitable for complex decay chains.As an example, consider a nuclide with co-ordinates Z, N located at the centre (dark grey) of the diagram. Following nuclear decay, this parent nuclide decays (by a, b-, b+/EC, n, or p decay) to one or more daughters. These daughters will, in turn, also decay until eventually stable products are reached.This full set of nuclides, starting from the parent and including all daughters can then be highlighted on the Nuclide Chart to provide a useful way of visualising the decay scheme of the original parent nuclide.A. Nuclide Chart (normal plot of Z vs. N) showing radioactive decay processes. A nuclide with co-ordinates Z, N "decays" to the position shown depending on the process.B. Nuclide Chart (compact plot of A-2Z vs. Z) showing radioactive decay processes. A nuclide with co-ordinates A-2Z, Z "decays" to the position shown depending on the process.Types of Radioactivity:A radioactive nuclide decays by one or several decay processes. Only the main decay mode is shown in the applet when using the Karlsruhe and Strasbourg Colour Schemes. The main decay modes are:· Alpha decay: In alpha decay, the parent nuclide emits a doubly charged ion of helium 4He - with 2 protons and 2 neutrons. With this decay mode, the mass of the resulting nuclide is 4 units less and the atomic number is 2 units less than from the parent nuclide. Example:· Beta-minus (ß-) decay: Beta decay is the name given to the process by which the nucleus emits an electron. Beta decay is also accompanied by the emission of a neutrino following conversion of a neutron to a proton. In this decay mode, the mass doesn't change as the masses of electrons and neutrinos are negligable. The atomic number of the resulting nuclide is 1 more than the atomic number from the starting nuclide. Example:· Beta-plus (ß+) decay: In beta-plus decay, a nuclide emits a positron and a neutrino (formed by the conversion of a proton to a neutron). Again the mass does not change but the atomic number now decreases by one. Example:· Isomeric transitions (IT): An isomeric transition occurs when a nuclide in an relatively long-lived excited or metastable state is converted from the metastable state to the ground state. In contrast to normal gamma emission from a short lived excited state, an isomeric or metastable (denoted by m) state is defined only if the half-life for gamma emission exceeds about 1 ns. Example: half-life = 26 minutes· Spontaneous fission (SF): Nuclides of heavy elements such as U, Pu, Am, Np, Cm, Fm can undergo radioactive decay by spontaneous fission. In this process, the nucleus splits into two nuclides, with a mass and atomic number roughly half that of the parent, together with several neutrons. Example:Half-life:Radioactive nuclides don't decay after a given time; they decay whenever they want. The decay during a given time interval with a special probability. To tell this probability of decay, the half-lives of all nuclides are given.The half-life of a radioactive nuclide is the time for half of the number of atoms to decay. The half-life for different nuclides can range from a few nanosecond (10-9 s) up to millions of years (the longest half-life is more than 1020 years). Stable nuclides, since they do not decay, do not have a half-life. Examples: Half-lives of nuclides mentioned aboveU 238: 4.47*109 years Th 234: 24.1 days He 4: Stable Pa 234: 6.7 hours C 11: 20.3 minutes B 11: stable U 235m: 26 minutes U 235: 7.04*108years Fm 256: 2.62 hours Xe 140: 13.6 seconds Pd 112: 21 hours Po 212: 299 nanoseconds Se 82: 1.3*1020 yRemember: In AX, A = atomic mass (# protons + neutrons)Tc = Technetium [nuclear medicine workhorse] F = Fluorine [Most widely used PET Agent]U = Uranium O = OxygenTh = Thorium Kr = KryptonPa = Protactinium Br = Bromine
3 Positron BasicsA Positron is a positively charged electron emitted during the decay of a proton to a neutron in the atom’s nucleus.During decay, the positron that exits the nucleus encounters an electron, usually within millimeters. The subsequent annihilation results in two annihilation photons which travel in 180° opposite directions.NP+e-Electron capture is not like any other decay - alpha, beta, or position. All other decays shoot something out of the nucleus. In electron capture, something ENTERS the nucleus. These points present a simplified view of what electron capture is:1) An electron from the closest energy level falls into the nucleus, which causes a proton to become a neutron. 2) A neutrino is emitted from the nucleus. 3) Another electron falls into the empty energy level and so on causing a cascade of electrons falling. One free electron, moving about in space, falls into the outermost empty level. (Incidently, this cascade of electrons falling creates a characteristic cascade of lines, mostly (I think) in the X-ray portion of the spectrum. This is the fingerprint of electron capture.) 4) The atomic number goes DOWN by one and mass number remains unchanged.Some points to be made about the equation:1) The nuclide that decays is the one on the left-hand side of the equation. 2) The electron must also be written on the left-hand side. 30 A neutrino is involved , It is ejected from the nucleus where the electron reacts, so it is written on the right-hand side. 3) The way it is written above is the usual way.
4 Positron Radionuclides Most positron emitters have high energy photons but short half-lives:Note: Mean photon energy for 18F is 511 keV.
5 Why 18Fluorine?Most positron emitters are created at a cyclotron facility. Up to 1-2 Curies of 18F are produced per cycle by bombarding 18O with protons. Typical clinical patient dose is mCi.An ideal PET agent should be available to the patient within 1 half life. 18Fluorine has a half-life of about 2 hours allowing adequate time for transportation.For this reason, 18Fluorine tagged biologic compounds are the most practical positron radiopharmaceuticals.
6 Radiopharmaceuticals Radiopharmaceuticals are made by conjugating a radioactive atom with a biologically active compound.Bone scans, for example, are done with 99mTc conjugated with MDP (99mTc - MDP).The most commonly used positron radiopharmaceutical to date is 18F conjugated with glucose to form Fluoro-DeoxyGlucose [FDG].
7 How FDG WorksFollowing injection, during the distribution phase (usually one hour) cells take up and phosphorylate FDG. Non-phosphorylated FDG is excreted by the kidneys.Phosphorylated FDG does not proceed to the next step in glycolysis due to altered configuration (substitution of Fluorine for a hydroxyl group).Malignant cells demonstrate a difference in accumulation due to increased cell membrane transporters and underexpression of glucose 6-phosphatase.This leads to a greater tumor to background uptake, thereby differentiating malignant lesions from benign tissue.Lymphoma, CRC, Melanoma require that the patient not have had a gallium scan within the previous 50 days. Or recent PET if done for restaging (50 days for lymphoma, 12 months for CRC unless rising CEA)For SPN, Lung lesion should be < 4 cm and no PET w/in 90 days.
8 How FDG Works 18Glucose Normal cells Abnormal Cells Hexokinase 18Glucose-6-PGlut TransporterPhosphotaseNormal cellsAbnormal CellsHexokinaseLymphoma, CRC, Melanoma require that the patient not have had a gallium scan within the previous 50 days. Or recent PET if done for restaging (50 days for lymphoma, 12 months for CRC unless rising CEA)For SPN, Lung lesion should be < 4 cm and no PET w/in 90 days.18Glucose18Glucose18Glucose-6-PGlut TransporterPhosphotase
9 Common Indications Medicare Approved: Solitary Pulmonary Nodule LymphomaColorectal CancerLung cancerHead and Neck cancersMelanomaThyroid CancerBreast CancerAlzheimer’s DementiaMyocardial ViabilityLymphoma, CRC, Melanoma require that the patient not have had a gallium scan within the previous 50 days. Or recent PET if done for restaging (50 days for lymphoma, 12 months for CRC unless rising CEA)For SPN, Lung lesion should be < 4 cm and no PET w/in 90 days.Not Yet Approved:Ovarian, GYN tumors*Better than CT for Peritoneal carcinomatosisTesticular cancerPancreatic cancer
10 Common Oncologic Applications Initial staging of biopsy proven cancer (prior to any treatment)Restaging after irradiation, chemotherapy, or surgical resection.*Serves as an indicator of response to therapy -- some treatment protocolsbase regimen changes upon SUV differences.Rarely, diagnosis of malignancy. e.g. indeterminate solitary pulmonary nodule on CT scanLymphoma, CRC, Melanoma require that the patient not have had a gallium scan within the previous 50 days. Or recent PET if done for restaging (50 days for lymphoma, 12 months for CRC unless rising CEA)For SPN, Lung lesion should be < 4 cm and no PET w/in 90 days.
11 FDG-PET has Low Sensitivity for: Prostate Cancer [C-11 Acetate PET shows promise]Renal Cell CarcinomaHepatocellular CarcinomaMucinous carcinomasNeuroendocrine tumors [use MIBG instead]Bronchioalveolar carcinomaTeratoma or ovarian adenocarcinomaCNS neoplasms [due to high background uptake]*Villous adenomasAdrenal Adenomas* PET is helpful in distinguishing scarring and necrosis from recurrent tumor following treatment.Lymphoma, CRC, Melanoma require that the patient not have had a gallium scan within the previous 50 days. Or recent PET if done for restaging (50 days for lymphoma, 12 months for CRC unless rising CEA)For SPN, Lung lesion should be < 4 cm and no PET w/in 90 days.
12 Physiologic Uptake Seen in BrainHeart [non-fasting; during fasting fatty acids are preferentially used]Kidney [Unlike glucose, FDG is not reabsorbed in the proximal tubules]LiverIntestinal Mucosa [especially when loops are clustered together]Skeletal and smooth muscle (neck, larynx, diaphragm)Laryngeal muscle and muscles of mastication [esp. if pt is talking]Periareolar breast [esp. lactating breast]Thymus [in children]Bone Marrow [normally increased post-chemotherapy or following Colony Stimulating Factor administration]Thyroid [in grave’s disease]All have low intracellular glucose-6-phosphate high glucose uptake and utilization.KUB demonstrates calcified retained fetus with overlapping skull fragments, some extremity recognition such as radius and ulna, etc. consistent with lithopedian.Prone films usually have the name stamped in the upper left or lower right, supine films in the lower left or upper right side of the film. The sacrum foramina appear larger (possibly better defined) in the prone films as the sacrum is closer to the source.
13 Normal FDG Uptake Larynx Salivary Glands Patchy Atrial uptake Intestinal MucosaBase of TongueBase of BrainLeft VentricleUreterLiverMarrow UptakeKidneysBladder
14 Quantification of PET Data On CT, each pixel in the field of view represents a Hounsefield unit (HU) of attenuation to x-ray transmission (water = 0 HU; bone 1000 HU).On a PET image, each pixel represents the number of coincident photons (> 480 keV) originating from FDG uptake at that position.SUV is a ratio to compare relative uptake in a Volume of Interest compared to expected background uptake.
15 Standardized Uptake Value (SUV) Initial studies using SUV were done in studying pulmonary nodules led to an SUV of 2.5 as demarcation of benign from malignant pulmonary lesions.Higher SUV in pulmonary lesion is an independent predictor of poorer prognosis.Ahuja V, Coleman RE, Herndon J, Patz EF Jr. Cancer Sep 1;83(5):It’s a good practice to report the maximum SUV in the ROI.Mean SUV is dependent upon the ROI and sensitivity is more important in oncologic imaging.
16 Inter-examination SUV variation (within the same patient) may be due to:Serum glucose levelHyperglycemic state will result in false negative scanFasting vs. Non-fasting [affects cardiac uptake]Change in body fat [fat cells don’t take up FDG]Duration between injection and imaging
17 Non-malignant causes of FDG uptake Inflammatory changesInflammatory bowel disease [CRP is usually also elevated]Reflux esophagitis & GastritisActive granulomatous diseasePneumonitisRadiation-induced inflammationConjunctivitisDegenerative joint diseasePost-Exercise increased muscle uptakeHyperinsulinemia (increased muscle uptake)
19 Gastritis, Inflammatory Hilar Nodes Cardiac Uptake is usually somewhat spotty in the atria compared with the ventricles. This normal variation should not be mistaken for mediastinal lymphadenopathy.Normal Patchy atrial Uptake;This patient was likely not fasting*Usually it is difficult to differentiate physiologic vs inflammatory uptake on PET alone
20 Image AcquisitionThe diagnostic images shown so far are processed by applying attenuation correction.Fewer photons from deeper body structures are detected due to attenuation from surrounding tissue prior to registration on the crystal surface.Transmission images are, therefore, acquired with an emission source such as 137CS (662keV), 68Ge or a CT scanner’s x-ray source.The amount of attenuation in the transmission images at a given position is then used to correct the emission image and produce the attenuation corrected image.
21 Image Construction Emission [NAC] Transmission Attenuation corrected *Non-attenutation corrected[NAC]TransmissionAttenuationcorrected[AC]
22 Clinical Value of emission images Occasionally lesions in liver can be masked by heterogeneity from attenuation correction. Small lung lesions may be missed due to smoothing effect of correction.Improper correction can result from metallic implants and retained bowel contrast causing pseudo-hot spots to appear on attenuation correction images. This occurs mostly when using CT transmission attenuation data for attenuation- correction.
23 Attenuation Correction Corrected[AC]EmissionImageLiver metastasis is more apparent on emission image
24 Acquisition - Transmission Imaging Field Of View
25 Transmission Image Example Photon source2368632Detector arrayImaging in one plane with triangular phantom gives relative attenuation
26 Transmission Image Example 1233SourceDetector4566Imaging in perpendicular plane with same phantom
27 Composite Summation Image 134797431245810854235691196533569119653467101210764578111311875689121412986689121412986Complete ring or circular detector will do this in more than justtwo directions resulting in better resolution and sharper image
28 Emission Coincidence Detection The positron emitted from the Fluorine nucleus only travels a short distance before annihilating with an electron and producing two equal energy (511 keV) photons which travel in exact 180° opposite directions.Conicidence detection distinguishes photons from a true events at a site somewhere along a line between two detectors located directly opposite each other in the ring from scatter photons. Less than 1% of photons included in making the image will be due to scatter if you use this method to ‘screen the photons’.
30 Coincidence Detection in Field of View Represents true eventDetector SignalsRepresents ScatterCoincident photon energies at each detector can be put into a matrix similar to the transmission data to construct an intensity-weighted image*Minimum photon energy allowable for inclusion by detector is about 480 keV
31 Ideal Detection System Dedicated PET scanner(full ring of gamma detectors).Best resolution: 3-7 mmdepends on total number of detectorsScatter photons included in image only 1% of timeEstimated total imaging time for a whole body scan should include both the emission and the transmission scans. Patient throughput and projected number of examinations performed in a typical day are an important consideration in feasibility analysis for any site seeking to procure a new PET scanner.The various vendors reference anywhere from 25 to 75 minutes as the minimum imaging time for a 100-cm FDG whole body scan. These scanning times are, however, subject to such factors as injected dose, uptake time, patient weight, and the desired image quality. Since the actual time is determined by the imaging protocol adopted by the individual sites, it is advisable to ask specific questions when users make on-site visits in order to ensure realistic planning.Patient throughput may be improved at busier sites by having an extra staff person available to help with the injection of the radiopharmaceutical, completing the patient's history questionnaire, and counseling the patient and family members regarding the procedure. The extra person may be a second nuclear medicine technologist, a physician's assistant, or an imaging aide, depending on the duties assigned, which should be in compliance with regulatory requirements.Support. Timely response to inevitable operational issues is of critical importance, particularly since quite often, technical support may be needed after the patient has been prepared and injected with the radiopharmaceutical. In these instances, immediate technical support may be needed to salvage the examination without having to reschedule the patient. As far as possible, preventative maintenance and routine software upgrades should be scheduled on weekends or after hours to minimize scheduling downtime. This needs to be prenegotiated within the service agreementImage courtesy of PET.html
32 Cheaper Alternative for PET Imaging Coincidence SPECT systemIncomplete detection ringCheapest solution but resolution is only mmWastes many photons; longer scan time or higher dose required than dedicated PET
33 Another SPECT Modification Modified SPECTHigh Energy NaI collimator for 511 keVPhotons are imaged without coincidence countingHigh photon attenuation; poor resolution (15-30 mm)Longer acquisition time than dedicated PETMobile services are suitable if there are concerns about low utilization and procedural volumes. This may be applicable in initiating a program in a highly competitive environment where the risks may be reduced initially by committing to only a few days a week through a mobile service, or in a new market where initial acceptance and utilization may be expected to be low.Restricted reimbursement for procedures performed on a SPECT gamma camera, modified for PET (coincidence systems), makes this a less viable option. CMS ruled in 2001 that the approvals for new PET applications will be limited to dedicated PET scanners, although legacy applications will continue to be reimbursed with the coincidence cameras. Superior spatial resolution of a dedicated PET scanner is also an important consideration in making a determination between these two choices.A hybrid combined PET/CT scanner offers the advantage of optimum anatomic/metabolic fusion, but issues such as reimbursement and higher acquisition costs have prevented widespread adoption of this technique to date. Regulatory concerns, such as the need for an additional radiology technologist, in addition to a certified nuclear medicine technologist, also need to be resolved, since this option involves the operation of a CT scanner in addition to the PET camera. The combined PET/CT scanner may be a consideration in sites with low initial anticipated procedure volumes, since the system may be utilized to perform CT scans at times when the PET schedule is light. This rationale may be justified if, in coming years, the price of the combined PET/CT scanner becomes more competitive.
34 Patient Exposure: Effective Biological t1/2 Typical PET examination is done with mCi of FDG.Increasing starting counts to compensate for poor photon detection with modified SPECT systems will increase patient exposure.In general, modified SPECT systems should be avoided.
35 Fusion of 3D Imaging Modalities Self-ExaminationThe following ten cases review most of the concepts we have covered.These cases also demonstrate the variety of display methods possible to display PET images: color vs. grayscale, sequential multi- planar images vs. multi-planar maximum intensity projection [MIP].
36 Case 1 Patient with lymphoma Pre and post-treatment PET scan, Fusion of 3D Imaging ModalitiesCase 1Patient with lymphomaPre and post-treatment PET scan,multi-planar images at same level.PET used to determine whether to change current regimen - 5 months elapsed between pre and post-treatment imaging.
38 Case 2 Solitary pulmonary nodule on CT -- evaluate for malignancy. Fusion of 3D Imaging ModalitiesCase 2Solitary pulmonary nodule on CT-- evaluate for malignancy.
39 Most Likely Benign SPN CT PET MIP No lung uptake; this lesion was a hamartoma. Keep in mind that some malignant lesions can have false negative PET...
40 Case 3 Unresolved ‘pneumonia’ x 6 months Fusion of 3D Imaging ModalitiesCase 3Unresolved ‘pneumonia’ x 6 months
41 Broncho-Alveolar Cell Carcinoma CT PET MIPPET has poor sensitivity for BAC and is often falsely negative! This one just happened to have enough FDG avidity to be detected.Don’t forget the serendipitous findings. This patient has hydronephrosis.
42 Case 4Fusion of 3D Imaging ModalitiesCough and hemoptysis
43 Selected MIP images from PET FDG avid NoduleBrown Fat Physiology
44 Brown Fat and LUL MassLUL mass with SUV 2.1, concerning for malignancy. Infectious process is also possible.Extensive uptake in the paraspinous and supraclavicular regions noted bilaterally consistent with activation of brown fat. Brown fat is activated to generate heat (such as when the patient is shivering). Glucose is required to fuel this process. Increased muscle activity is usually also seen in cold or tense patients and part of the increased paraspinal uptake may also be due to paraspinal muscle activity.
45 Case 5 Patient had CT showing a lung mass. Assess for malignancy Fusion of 3D Imaging ModalitiesPatient had CT showing a lung mass.Assess for malignancy
46 CT ChestFusion of 3D Imaging ModalitiesContinued
47 PET Done 1 Month Later Fusion of 3D Imaging Modalities Malignancy in larynx (note asymmetry on CT), lung (biopsy proven small-cell carcinoma), and mid-retro-peritoneum (not appreciable on prior CT).
48 Case 6Fusion of 3D Imaging ModalitiesPatient post right hemicolectomy for cancer presents with retroperitoneal stranding on CT- hemorrhage or metastatic tumor?Proposed chemotherapy is contraindicated in a patient with active hemorrhage.PET and CT Images were fused to better correlate functional and anatomic findings
49 (Software-based) PET-CT Fusion High uptake – Recurrent tumor much more likely than Hemorrhage
50 Case 7 Patient with lung cancer to undergo radiation treatment. Fusion of 3D Imaging ModalitiesCase 7Patient with lung cancer to undergo radiation treatment.Planning CT shows RLL atelectasis -- can’t exclude tumor in this region.PET recommended to determine whether to include this portion of lung as well within radiation portal.
51 (Software-based) PET-CT Fusion ContinuedAvid uptake at hilar mass superior to atelectasis
52 (Software-based) PET-CT Fusion Non-FDG avid RLL = no significant tumor. Do not irradiate this region
53 Case 8 Initial staging for biopsy proven colon cancer. Simultaneous acquisition PET, CT, and fusion imaging provided.
54 Coronal PET MIP Images Metastatic focus? Continued AC NAC [emission] Courtesy of Barry A Siegel, M.D. -- Mallinckrodt Institute of Radiology, St. Louis, MO.
55 PET Fused PET-CT CT Barium Courtesy of Barry A Siegel, M.D. -- Mallinckrodt Institute of Radiology, St. Louis, MO.
56 CT Attenuation Correction Artifact The apparent metastatic focus is an over-correction artifact due to residual barium in the patient’s colon.This artifact is a product of an error in most algorithms using CT transmission attenuation data to correct PET emission images.The heavier density of barium is not accounted for by the lower density value assignment for bone (usually the highest preset value in Hounsfield range on CT) which results in the over-correction..Maximum attenuation included in correction algorithm for commercially availiable PET/CT scanners is for bone. This is set at 1000 HU. Any object which is denser than bone (such as metal or barium) will be corrected using the 1000 HU cutoff.
57 Case 9 61 yo for colorectal restaging CT shows a large low attenuation lesion in the liver. Evaluate for metastatic disease.Software fusion of CT/PET provided.
60 61 yo for restagingFusion with CT image shows the photopenic area to match the low attenuation lesion.PET shows low FDG uptake in this region; unlikely to be a metastatic deposit -- pattern is compatible with large hepatic cyst.If the border of this lesion on PET showed high activity the differential would be abscess, hematoma, or large centrally necrotic tumor.
61 Fusion of 3D Imaging Modalities Case 10Patient with glioblastoma with abnormal signal on MR close to site of previous tumorIs this post-surgical scar or tumor?Software MR/PET fusion provided
62 PET of Whole Brain Fusion of 3D Imaging Modalities Uptake next to prior resectionNotice diminished uptake in right cortex due to resection / necrosis
63 MR fusion with PETFusion of 3D Imaging ModalitiesRecurrent tumor
64 Fusion vs simultaneous acquisition Simultaneous acquisiton of PET and CT images avoidsInterval change in lesion if enough time passes between acquisitionsGross Software misregistrationTransmission data can be acquired with CT portion of scan = reduced scan timeDecreases artifacts due to differences in patient positioning
65 Future of PET imaging … Other (target-specific) radiopharmaceuticals Ammonia (13NH3) imaging for cardiac lesions.Na18F for bone scans for non-FDG avid metastatic disease.11C acetate for prostate cancer.