Pitfalls in PET-CT studies in the thorax. Non-malignant thoracic findings with pathological correlation.

Transcription

1 Pitfalls in PET-CT studies in the thorax. Non-malignant thoracic findings with pathological correlation. Poster No.: C-0273 Congress: ECR 2016 Type: Educational Exhibit Authors: A. R. Ramírez, M. García García-Esquinas, M. Domínguez Fraga, M. Martínez de Bourio, J. Arrazola; Madrid/ES Keywords: Thorax, Cardiac, Lung, PET-CT, MR, elearning, Education, Inflammation, Infection, Pathology DOI: /ecr2016/C-0273 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 18

2 Learning objectives To identify the physiological uptake of FDG in the thorax and the normal variants that may affect the interpretation of PET-CT studies. To review the most common benign conditions in the thorax that may resemble malignant lesions in PET-CT studies with pathological correlation. To identify therapeutic procedures that can produce false-positive results on PET-CT. Background 18-FDG behaves as an analog of glucose with a distribution that follows that of glucose-metabolizing cells and organs. 18-FDG accumulation results from elevated activity of glucose transporter proteins and of the glucose phosphorylating enzyme hexokinase, as well as metabolic trapping of FDG within the tumor cells. Increased glycolysis is not specific to tumor tissue, and a number of benign processes, particularly inflammation, may result in uptake of 18-FDG that is higher than background tissues. Benign lesions with increased FDG uptake are found in more than 25% of PET-CT studies with FDG avidity of infection and inflammation occasionally greater than that of some malignancies. Knowledge of the normal biodistribution and uptake of FDG in benign conditions affecting the thorax is essential for the accurate interpretation of FDG PET-CT images. Findings and procedure details Physiological uptake of FDG Brown fat Brown fat is a vestigial organ of thermogenesis, sympathetically innervated. Brown fat differs from white adipose tissue by the organization of its lipids and its characteristic color. Brown fat is composed of densely packed brown adipose cells; multilocular Page 2 of 18

3 cytoplasm contains abundant mitochondria and lysosomes which give the tissue its brown color. Figure 1. Uptake in brown fat is more common in winter and in patients with lower BMI, children and females. Common thoracic localizations of brown fat include the axillae, supraclavicular and paravertebral regions. Low attenuation values on CT and symmetrical bilateral uptake are useful to recognize brown fat in PET-CT studies. Metabolic activity in brown fat can obscure malignant lymphadenopathy or may be misinterpreted as tumoral implants. Breast The distribution of radiotracer in the breast correlates with the amount of active glandular tissue and varies mildly with the menstrual cycle being higher in lactating breasts. Bone The physiologic distribution of FDG in bones is variable, with lower uptake in cortical bone than in the marrow. Pediatric patients may have linear uptake in physis. Anemia may increase radiotracer uptake in the marrow. Figure 2. Skeletal muscle Intense physical activity before the examination lead to increased skeletal muscle uptake, attributed to replenishment of glycogen stores. Increased FDG uptake on paraspinal musculature can be seen due to patient anxiety, intercostal and diaphragmatic muscle uptake is frequent in patients with chronic obstructive pulmonary disease. Insulin administration before or directly after FDG infusion or postprandial insulin secretion, results in elevated tracer uptake in the skeletal muscles. Figure 3. Myocardium Myocardial FDG uptake depends on the fasting state, plasma glucose, free fatty acid and insulin. In fasting state the myocardium preferentially uses fatty acids as its energy source and postprandially, glucose is used preferentially. FDG uptake can be seen in the atrium associated with lipomatous hypertrophy of the interatrial septum. Figure 4. Thymus Page 3 of 18

4 Thymic uptake is usually more than that of the blood pool although its variable based on patient age, being higher in younger populations. In general, physiologic uptake disappears with involution of the thymus during adolescence. Figure 5. Gastrointestinal tract Radiotracer uptake within the gastrointestinal tract is highly variable. The esophagus generally does not demonstrate markedly increased uptake in the absence of inflammation or malignancy. Homogeneous increased uptake in the stomach wall and gastroesophageal junction is relatively common. Inflammatory conditions A number of focal benign skeletal pathologies may result in high FDG uptake including bone fractures, Paget's disease and fibrous dysplasia. Figure 6. Sarcoidosis is a systemic disease of unknown etiology which causes noncaseating granulomas. FDG uptake is increased in active inflammation such as lung granulomas. FDG-PET identifies potential diagnostic biopsy sites, and detects disease in unsuspected anatomic locations. Figure 7. Pneumoconiosis includes a group of inhalation and work related restrictive lung diseases. Variable degrees of FDG uptake have been described both in the pulmonary findings and in mediastinal and/or hilar lymph nodes which can become a source of false-positive results. The SUV in parenchymal lesions can reach intensities typically seen in malignant nodules. Figure 8. Inflammatory conditions of the lung parenchyma with high FDG uptake includes atelectasis and idiopathic interstitial pneumonias. Increased FDG uptake can be seen in alveolar hemorrhage. Figure 9. In the gastrointestinal tract, inflammatory conditions are generally FDG avid as seen in gastro-esophageal reflux, typically with focal or linear uptake in conjunction with distal esophageal thickening in Barrett esophagus. Inflammatory reaction in pulmonary embolism can result in focal mild to moderate FDG uptake and if the thrombus is in a lobar branch of the vessel, it can mimic hilar adenopathy on PET. Figure 10. Page 4 of 18

5 Tracer uptake in atherosclerosis occurs due to inflammatory cell migration caused by oxidized low-density lipoproteins, which accumulate in the endothelium causing endothelial dysfunction. Tracer uptake can be seen in in mycotic aneurysms. Infectious diseases In pneumonia and abscess the glycolytic metabolism is elevated in the leukocytic infiltration associated with inflammation. In cases when there is cavitation or necrosis, pneumonia can be indistinguishable from cavitating neoplasms such as squamous carcinoma or large, solid neoplasms with decreased central metabolism or necrosis. Figure 11. The lungs are the most common site of primary infection by tuberculosis and are a major source of spread of the disease and of individual morbidity and mortality. False-positive results are not uncommon in patients with active tuberculosis because the lesions are FDG avid. Preliminary reports have shown the potential value of FDG-PET for the evaluation of infectious endocarditis. Figure 12. The increased tracer accumulation associated with bone infection places FDG-PET at an advantage for its detection and characterization. FDG-PET had the highest diagnostic accuracy in confirming or excluding osteomyelitis, especially in the axial skeleton. Therapeutic and diagnostic procedures Radiation treatment cause tissue inflammation with associated increase in FDG uptake. There is a relationship between radiation dose and the uptake of FDG in radiation pneumonitis. Typically acute radiotherapy changes shows intense FDG uptake. Figure 13. Drugs such as bezafibrate, benzodiazepines and metformin can alter cardiac biodistribution, and nicotine or ephedrine stimulate uptake of brown fat. Growth colony stimulating factor and chemotherapy can diffusely increase marrow tracer uptake. Homogeneous thymic FDG uptake after chemotherapy or corticosteroids therapy, with absence of uptake at pre-therapy FDG-PET, indicate post-therapy thymic hyperplasia. Page 5 of 18

6 Sites of therapeutic and diagnostic procedures such as biopsy, catheter-insertion sites, tracheostomy, mediastinoscopy and sternotomy can be FDG avid. Prosthetics and percutaneously placed devices such as defibrillators and pacemakers can cause increased radiotracer accumulation. Uptake typically decreases with time resolving within 3 to 6 months. FDG avid high-attenuation lymph nodes following talc pleurodesis and reactive lymph nodes following instrumentation should not be mistaken for nodal metastases. Vertebral fractures treated with vertebroplasty can be highly FDG avid and should not be confused with metastatic disease. Artifacts Misregistration artifacts on fused PET-CT images can be caused by patient motion, breathing differences during the PET and CT lung acquisition, and bladder repletion. Attenuation correction artifacts can occur with highly attenuating objects such as: hip prostheses, dental devices, and contrast-enhanced vessels. Figure 14. Recommendations to avoid artifacts Patients should be scanned at exactly the same time after injection of FDG. Patient should be as relaxed as possible at the time of injection and should not take vigorous exercise in the hours previous to the scan. Patient should starve, except for water, for 4 to 6 hours before injection in order to keep insulin levels low. In insulin-dependent diabetic patients with high blood sugar levels, it is better to reschedule the appointment rather than to give insulin. Preparations to reduce brown adipose activation include: keeping the patient warm, pharmacologic interventions, dietary changes, and proper temperature control before and after FDG administration. Misregistration is minimized by performing the CT scan during normal expiration, having patients empty their bladder before the study or catheterize the bladder. Images for this section: Page 6 of 18

7 Fig. 1: Coronal PET image shows multiple sites of increased uptake in brown fat mainly in supraclavicular, paravertebral regions and mediastinum. Biopsy of another patient shows brown fat cells with multilocular cytoplasm with lipid droplet of various sizes Page 7 of 18

8 Fig. 2: Axial PET-CT shows FDG uptake in the trabecular bone of a dorsal vertebrae. Normal cellular marrow have increased cellularity (large arrow) compared to the cellularity seen in cortical bone (short arrow) Fig. 3: Coronal PET-CT and PET images demonstrate extensive muscular uptake related to insulin administration. Page 8 of 18

9 Fig. 4: Axial PET-CT shows FDG uptake in the atrium associated with lipomatous hypertrophy of the interatrial septum (arrow). CT demonstrate the low attenuation values of the fat in the interatrial septum (arrow). Fig. 5: Coronal PET-CT depict thymic uptake (arrow). Photomicrography of thymic hyperplasia show the normal cortex and medulla with Hassall's corpuscles. Page 9 of 18

10 Fig. 6: Areas of focal intense uptake are frequent in fractures. (a) Sagittal PET-CT was performed to characterize an incidentally detected pulmonary nodule, demonstrating increased FDG uptake in a D8-D9 vertebral body fractures. (b) STIR MRI of the patient depicts the vertebral body fractures and bone marrow edema. Page 10 of 18

11 Fig. 7: (a) Axial CT and (b) PET-CT images show subcarinal and left hilar lymph nodes with elevated FDG uptake in a patient with sarcoidosis. (c) Histology show granulomas formed by lymphocytes surrounded by histiocytes. Fig. 8: (a) Axial CT and (b) PET-CT depict a mediastinal lymph node with increased FDG uptake (arrow) in a patient with silico-anthracosis. (c) Histology of the lymph node shows fine anthracotic pigment in cytoplasm of macrophages and histiocytes. Page 11 of 18

12 Fig. 9: (a) Axial lung CT and (b) PET-CT depict an alveolar hemorrhage as a hazy consolidation and ground-glass infiltrates in the lung parenchyma in (a) with increased FDG uptake in (b). Page 12 of 18

13 Fig. 10: (a) Axial CT and (b) PET-CT show a thrombus with FDG uptake in right main pulmonary artery. Page 13 of 18

14 Fig. 11: (a) Axial PET-CT and (b) CT image demonstrate FDG uptake in a left lower lobe consolidation. Page 14 of 18

15 Fig. 12: a) 18 FDG-PET/CT shows elevated levels of FDG uptake in the aortic valve. (b) Hematoxylin and eosin staining (20X photomicrograph) of the valve leaflet of this patient depicts acute neutrophilic inflammation. Fig. 13: (a) Axial CT and (b) PET-CT images show soft tissue radiotherapy changes with increased uptake in a patient with treated breast cancer. Page 15 of 18

16 Fig. 14: (a) PET image shows uptake in the place of a pacemaker (arrow). This artifacts typically disappear on the non-corrected PET images (arrow in b). Page 16 of 18

17 Conclusion It is important to know that thoracic FDG uptake and distribution are not limited to malignant lesions. Familiarity with the normal thoracic biodistribution of FDG and knowledge of the potential benign causes of increased FDG uptake in the thorax are essential to minimize the incidence of incorrect interpretation of FDG-PET images. Information about prior surgeries and surgical complications is essential to interpret properly FDG uptake. Personal information References Shreve PD, Anzai Y, Wahl RL. Pitfalls in oncologic diagnosis with FDG PET imaging: physiologic and benign variants. Radiographics. 1999;19(1): Truong MT, Viswanathan C, Carter BW, Mawlawi O, Marom EM. PET/CT in the thorax: pitfalls. Radiol Clin North Am. 2014;52(1): Metser U, Miller E, Lerman H, Even-Sapir E. Benign nonphysiologic lesions with increased 18F-FDG uptake on PET/CT: characterization and incidence. AJR Am J Roentgenol. 2007;189(5): Cook GJ, Wegner EA, Fogelman I. Pitfalls and artifacts in 18FDG PET and PET/CT oncologic imaging. Semin Nucl Med. 2004;34(2): Wachsmann JW, Gerbaudo VH. Thorax: normal and benign pathologic patterns in FDG-PET/CT imaging. PET Clin. 2014;9(2): Yeung HW, Grewal RK, Gonen M, Schöder H, Larson SM. Patterns of (18)F-FDG uptake in adipose tissue and muscle: a potential source of falsepositives for PET. J Nucl Med Nov;44(11): Blodgett TM, Fukui MB, Snyderman CH, Branstetter BF 4th, McCook BM, Townsend DW, Meltzer CC. Combined PET-CT in the head and neck: part 1. Physiologic, altered physiologic, and artifactual FDG uptake. Radiographics. 2005;25(4): Shammas A, Lim R, Charron M. Pediatric FDG PET/CT: physiologic uptake, normal variants, and benign conditions. Radiographics. 2009;29(5): Page 17 of 18

18 9. James OG, Christensen JD, Wong TZ, Borges-Neto S, Koweek LM. Utility of FDG PET/CT in inflammatory cardiovascular disease. Radiographics ;31(5): Erasmus JJ, Mawlawi O, Howard B, Patz EF Jr. PET-CT: current applications and new developments in the thorax. Semin Respir Crit Care Med. 2014;35(1): Wang Y, Carter BW, Muse V, Digumarthy S, Shepard JA, Sharma A. Potential Pitfall in the Assessment of Lung Cancer with FDG-PET/CT: Talc Pleurodesis Causes Intrathoracic Nodal FDG Avidity. Lung Cancer Int. 2013;2013: Kapoor V, McCook BM, Torok FS. An introduction to PET-CT imaging. Radiographics. 2004;24(2): Page 18 of 18