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Positron Emission Tomography : A Practical Review of Clinical Applications and a Self-examination Neville Irani 1 MD, Jorge Vidal 2 MD, Natasha Acosta.

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Presentation on theme: "Positron Emission Tomography : A Practical Review of Clinical Applications and a Self-examination Neville Irani 1 MD, Jorge Vidal 2 MD, Natasha Acosta."— Presentation transcript:

1 Positron Emission Tomography : A Practical Review of Clinical Applications and a Self-examination Neville Irani 1 MD, Jorge Vidal 2 MD, Natasha Acosta 2 MD, Mark Redick 2 MD, Akash Sharma 1 MD. St. Luke’s Hospital of Kansas City 105 th Annual Meeting of the American Roentgen Ray Society 1 Allegheny General Hospital, Pittsburgh, PA 2 St. Luke’s Hospital of Kansas City/ UMKC, Kansas City, MO

2 Radioactive Decay & Nuclear Imaging Isomeric transition Alpha Beta - Beta + [positron] Electron CaptureExample 99m Tc  99 Tc+  18 F  18 O+  + + Remember Remember: In A X, A = atomic mass (# protons + neutrons) Tc = Technetium[nuclear medicine workhorse]F = Fluorine[Most widely used PET Agent] U = UraniumO = Oxygen Th = ThoriumKr = Krypton Pa = ProtactiniumBr = Bromine

3 Positron Basics A 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 2-16 millimeters. The subsequent annihilation results in two annihilation photons which travel in 180° opposite directions. N P e-e- ++  

4 Positron Radionuclides Most positron emitters have high energy photons but short half-lives: Note: Mean photon energy for 18 F is 511 keV.

5 Most positron emitters are created at a cyclotron facility. Up to 1-2 Curies of 18 F are produced per cycle by bombarding 18 O with protons. Typical clinical patient dose is 10-20 mCi. An ideal PET agent should be available to the patient within 1 half life. 18 Fluorine has a half-life of about 2 hours allowing adequate time for transportation. For this reason, 18 Fluorine tagged biologic compounds are the most practical positron radiopharmaceuticals. Why 18 Fluorine?

6 The most commonly used positron radiopharmaceutical to date is 18 F conjugated with glucose to form Fluoro-DeoxyGlucose [FDG].  Radiopharmaceuticals Radiopharmaceuticals are made by conjugating a radioactive atom with a biologically active compound. Bone scans, for example, are done with 99m Tc conjugated with MDP ( 99m Tc - MDP).

7 How FDG Works Following 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.

8 How FDG Works CELLMEMBRANECELLMEMBRANE Glut Transporter Hexokinase Phosphotase 18 Glucose Hexokinase Phosphotase 18 Glucose 18 Glucose-6-P Glut Transporter Normal cells Abnormal Cells 18 Glucose 18 Glucose-6- P 18 Glucose

9 Common Indications Medicare Approved: Solitary Pulmonary Nodule Lymphoma Colorectal Cancer Lung cancer Head and Neck cancers Not Yet Approved: Ovarian, GYN tumors *Better than CT for Peritoneal carcinomatosis Testicular cancer Pancreatic cancer Melanoma Thyroid Cancer Breast Cancer Alzheimer’s Dementia Myocardial Viability

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 protocols base regimen changes upon SUV differences. Rarely, diagnosis of malignancy. e.g. indeterminate solitary pulmonary nodule on CT scan

11 FDG-PET has Low Sensitivity for: Prostate Cancer [C-11 Acetate PET shows promise] Renal Cell Carcinoma Hepatocellular Carcinoma Mucinous carcinomas Neuroendocrine tumors [use MIBG instead] Bronchioalveolar carcinoma Teratoma or ovarian adenocarcinoma CNS neoplasms [due to high background uptake]* Villous adenomas Adrenal Adenomas * PET is helpful in distinguishing scarring and necrosis from recurrent tumor following treatment.

12 Physiologic Uptake Seen in –Brain –Heart [non-fasting; during fasting fatty acids are preferentially used] –Kidney [Unlike glucose, FDG is not reabsorbed in the proximal tubules] –Liver –Intestinal 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.

13 Normal FDG Uptake Larynx Intestinal Mucosa Left Ventricle Patchy Atrial uptake Salivary Glands Liver Base of Tongue Base of Brain Ureter Kidneys Bladder Marrow Uptake

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. 1998 Sep 1;83(5):918-24. 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 level –Hyperglycemic state will result in false negative scan Fasting 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 changes –Inflammatory bowel disease [CRP is usually also elevated] –Reflux esophagitis & Gastritis –Active granulomatous disease –Pneumonitis –Radiation-induced inflammation –Conjunctivitis –Degenerative joint disease Post-Exercise increased muscle uptake Hyperinsulinemia (increased muscle uptake)

18 Fasting = Less Cardiac Uptake

19 Gastritis, Inflammatory Hilar Nodes 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 Acquisition The 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 137 CS (662keV), 68 Ge 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 * Non-attenutation corrected [NAC] Transmission Attenuation corrected [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 Attenuation Corrected [AC] Emission Image Liver metastasis is more apparent on emission image

24 Acquisition - Transmission Imaging Field Of View

25 Transmission Image Example Imaging in one plane with triangular phantom gives relative attenuation Detector array Photon source 022368630

26 Transmission Image Example Imaging in perpendicular plane with same phantom 1 3 2 3 4 5 6 6 Source Detector

27 Composite Summation Image 1 3 2 5 3 6 4 6 1 3 2 5 3 6 4 6 3 5 4 7 5 8 6 8 4 6 5 8 6 9 7 9 7 9 8 11 9 12 10 12 9 11 10 13 11 14 12 14 7 9 8 11 9 12 10 12 4 6 5 8 6 9 7 9 3 5 4 7 5 8 6 8 Complete ring or circular detector will do this in more than just two 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’.

29 Photon Coincidence

30 Coincidence Detection in Field of View Detector Signals Coincident 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 Represents true event Represents Scatter

31 Ideal Detection System Dedicated PET scanner –(full ring of gamma detectors). Best resolution: 3-7 mm –depends on total number of detectors Scatter photons included in image only 1% of time Image courtesy of PET.html

32 Cheaper Alternative for PET Imaging Coincidence SPECT system –Incomplete detection ring Cheapest solution but resolution is only 5-10 mm Wastes many photons; longer scan time or higher dose required than dedicated PET

33 Another SPECT Modification Modified SPECT –High Energy NaI collimator for 511 keV Photons are imaged without coincidence counting High photon attenuation; poor resolution (15-30 mm) Longer acquisition time than dedicated PET

34 Patient Exposure: Effective Biological t 1/2 Typical PET examination is done with 10-20 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-Examination The 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 Fusion of 3D Imaging Modalities Case 1 Patient with lymphoma Pre 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.

37 Effective treatment regimen Pre-Rx Post-Rx Resolution of mediastinal & retroperitoneal lymphadenopathy Normal Penile Uptake Normal bowel Uptake

38 Fusion of 3D Imaging Modalities Case 2 Solitary pulmonary nodule on CT -- evaluate for malignancy.

39 Most Likely Benign SPN No lung uptake; this lesion was a hamartoma. Keep in mind that some malignant lesions can have false negative PET... CTPET MIP

40 Fusion of 3D Imaging Modalities Case 3 Unresolved ‘pneumonia’ x 6 months

41 Broncho-Alveolar Cell Carcinoma CTPET MIP PET 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 Fusion of 3D Imaging Modalities Case 4 Cough and hemoptysis

43 Selected MIP images from PET Brown Fat Physiology FDG avid Nodule

44 Brown Fat and LUL Mass LUL 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 Fusion of 3D Imaging Modalities Case 5 Patient had CT showing a lung mass. Assess for malignancy

46 Fusion of 3D Imaging Modalities CT Chest Continued

47 Fusion of 3D Imaging Modalities PET Done 1 Month Later Malignancy in larynx (note asymmetry on CT), lung (biopsy proven small-cell carcinoma), and mid-retro-peritoneum (not appreciable on prior CT).

48 Fusion of 3D Imaging Modalities Case 6 Patient 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 Fusion of 3D Imaging Modalities Case 7 Patient 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 Avid uptake at hilar mass superior to atelectasis Continued

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? ACNAC [emission] Continued Courtesy of Barry A Siegel, M.D. -- Mallinckrodt Institute of Radiology, St. Louis, MO.

55 PETFused 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..

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.

58 61 yo for CRC Restaging Continued

59 Fusion of 3D Imaging Modalities

60 61 yo for restaging Fusion 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 10 Patient with glioblastoma with abnormal signal on MR close to site of previous tumor Is this post-surgical scar or tumor? Software MR/PET fusion provided

62 Fusion of 3D Imaging Modalities PET of Whole Brain Notice diminished uptake in right cortex due to resection / necrosis Uptake next to prior resection

63 Fusion of 3D Imaging Modalities MR fusion with PET Recurrent tumor

64 Fusion vs simultaneous acquisition Simultaneous acquisiton of PET and CT images avoids –Interval change in lesion if enough time passes between acquisitions –Gross Software misregistration Transmission data can be acquired with CT portion of scan = reduced scan time Decreases artifacts due to differences in patient positioning

65 Future of PET imaging … Other (target-specific) radiopharmaceuticals Ammonia ( 13 NH 3 ) imaging for cardiac lesions. Na 18 F for bone scans for non-FDG avid metastatic disease. 11 C acetate for prostate cancer.

66 Ammonia PET -- Dilated Cardiomyopathy

67 Normal NaF bone scan using PET… Gives higher resolution compared to Technetium bone scans.

68 Thank You We hope you enjoyed this basic tutorial on PET imaging. Any comments are welcome at: –nirani @ –vidalja@

69 References Mettler FA Jr., Guiberteau MJ. Essentials of Nuclear Medicine. 4 th ed. W.B. Saunders Company, 1998. Ruhlmann J, Oehr P, Biersack HJ (eds.). PET in Oncology Basics and Clinical Applications. Springer-Verlag, 1999. Delbeke D, Martin WH, Patton JA, Sandler MP (eds.). Practical FDG Imaging: A Teaching File. Springer-Verlag, 2002.

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