18 F-FDG PET of Pulmonary Embolism

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1 FDG PET of Pulmonary Embolism Chest Imaging Clinical Observations Conrad Wittram 1 James A. Scott 2 Wittram C, Scott JA Keywords: CT, nuclear medicine, oncology, PET, pulmonary embolism DOI: /AJR Received May 13, 2006; accepted after revision December 29, Division of Thoracic Radiology, Massachusetts General Hospital, Founders 202, 55 Fruit St., Boston, MA Address correspondence to C. Wittram (cwittram@partners.org). 2 Division of Nuclear Medicine, Massachusetts General Hospital, Boston, MA. AJR 2007; 189: X/07/ American Roentgen Ray Society 18 F-FDG PET of Pulmonary Embolism OBJECTIVE. The purpose of this study was to describe the manifestations of pulmonary embolism on 18 F-FDG PET scans in 13 patients. CONCLUSION. The activity of acute pulmonary embolism on FDG PET scans was significantly higher than the activity of vessels not containing thrombi. The shape of the abnormal FDG uptake may be focal or curvilinear. ulmonary embolism (PE) is the P third most common acute cardiovascular disease, after myocardial infarction and stroke, and it leads to thousands of deaths each year because it often goes undetected [1]. Patients with suspected PE are almost exclusively imaged with dedicated CT pulmonary angiography. As recent results [2] show, in comparison with a composite reference standard, CT pulmonary angiography has a sensitivity of 83% and specificity of 96% in the detection of PE, and combined CT pulmonary angiography and CT venography has a sensitivity of 90% and specificity of 95% in the detection of venous thromboembolic disease. The finding of PE on contrast-enhanced CT for indications other than thromboembolic disease ranges from 1.5% to 4% [3, 4] in a mixed population. Among oncology patients, the coincidence rate of PE on contrast-enhanced CT has been cited as being as high as 6% [5]. There is a sustained increase in utilization of 18 F-FDG PET in the evaluation of patients with known or suspected malignancy in the thorax [6]. Integrated PET/CT scanners have the added advantage of high anatomic resolution and the ability to show tissue with increased glucose metabolism. In the literature, a series of three pathologically proven pulmonary infarcts exhibited an increase in FDG uptake [7], and there has been one case report [8] of FDG uptake by pulmonary emboli. The purpose of our study was to evaluate pulmonary emboli on FDG PET scans in a large series of patients. Materials and Methods Patients Our institutional review board approved this retrospective study and waived informed consent. The study was compliant with the requirements of the Health Insurance Portability and Accountability Act. The study period was January 2004 through February All 2,216 consecutive oncology patients who underwent integrated contrast-enhanced PET/CT at our institution were found with our radiology information database search program (Folio). From this group, all cases of coincidental PE were identified. One of the investigators reviewed the charts for corroborative imaging or clinical evidence that confirmed the diagnosis of PE, which was assigned on CT. Other information collected included tumor type and size and change in tumor size. Thirteen patients with coincidental acute PE were identified: two women and 11 men with an age range of years (mean age, 59 years). PET/CT Technique An integrated PET/16-MDCT scanner (Sensation, Siemens Medical Solutions) was used to acquire the images. The patients were given an injection of 15 mci of FDG. Forty-five minutes later, attenuation-correction unenhanced CT scans were acquired from neck to pelvis at 2-mm slice thickness, 83 ± 31 (SD) ma (range, ma) at 120 kvp, and 0.5-second tube rotation time. The imaging field of view was the widest rib-torib distance acquired during quiet breathing. The PET images were acquired at 3.75-mm slice thickness and mean full width at half maximum of 6 ± 0.7 (range, 5 7). For the final CT scan, IV access was through an antecubital vein. An injection of 120 ml of ioxilan 300 mg I/mL was given AJR:189, July

2 through a 20-gauge catheter at 2.5 ml/s. Images were acquired with a collimation and reconstruction width of 2.00 mm, 0.5-second tube rotation time, and 195 ± 43 ma (range, ma) at 140 kvp. Image acquisition was started 48 seconds after commencement of IV administration of contrast medium, and patients were asked to take a small breath in and hold it. CT images were acquired with a standard algorithm. For this study, the chest component was analyzed. Diagnostic Criteria for PE and Pulmonary Infarction One of the investigators identified acute PE as an intraluminal filling defect that had a sharp interface with intravascular contrast enhancement that manifested as follows: Complete arterial occlusion with failure to opacify the entire lumen, sometimes with enlargement of the artery in comparison with pulmonary arteries of the same order of branching [9 11]; a central arterial filling defect surrounded by intravascular contrast enhancement [9]; and a peripheral intraluminal filling defect at an acute angle to the arterial wall [10, 11]. In all three types of manifestation, the anatomic levels of the pulmonary emboli were categorized and recorded as main, right or left, interlobar, lobar, segmental, or subsegmental pulmonary artery. Because FDG can be taken up in both lymphadenopathy and PE, it was important to differentiate these abnormalities on contrast-enhanced CT. Lymph nodes were recognized as being in an extravascular location, and PE was recognized as an intravascular filling defect that fulfilled the three aforementioned diagnostic criteria for PE. The diagnosis of pulmonary infarction was considered on CT when a region of ground-glass opacification or consolidation was identified in lung parenchyma distal to a vessel occluded by thrombus. Evaluation of Systemic Veins in the Abdomen and Pelvis The veins of the abdomen and pelvis were evaluated for adequacy of vascular opacification on contrast-enhanced CT and for the presence of thrombus. If thrombus was identified, the corresponding PET image was evaluated for the presence or absence of increased FDG uptake. Quantitative Evaluation All images were viewed on a Reveal-MVS workstation (Mirada Solutions). The program resampled the contrast-enhanced CT data to accord with PET slice thickness. For each axial level of a study, three images were displayed: the CT image viewed on mediastinal window (width, 350 H; level, 40 H), combined PET/CT image, and PET image. Two radiologists, one with 10 years of experience in thoracic radiology, and a nuclear medicine radiologist with 20 years of experience in nuclear medicine interpretation reviewed the images at one sitting. The largest thrombus in an individual lung was identified, and a region of interest was drawn around the margin of the vessel. After input of the patient s body weight, the maximum standard uptake value (SUV) from the region of interest was recorded. A vessel of similar size, which did not contain thrombus, also was identified. The process was repeated for this vessel, and the data recorded. Region-of-interest measurements of vessels containing and not containing thrombus were obtained from vessels that did not have visually detectable lymphatic tissue or extravascular soft tissue around the vessel. The cases with infarction were identified, an SUV region of interest was drawn around the margin of the opacity, and the maximum SUV was recorded. A normal region of lung on the opposite side with a similarly sized region of interest was used as a control. Qualitative Evaluation All cases were reviewed by consensus to evaluate the shape of the abnormal FDG uptake by pulmonary emboli. Six patients had undergone prior contrast-enhanced CT and PET that did not show PE. In these six cases, the study images and previous PET images were viewed side by side to evaluate for interval change. Statistical Analysis The two-tailed paired Student s t test was used. Statistical significance was considered when p < Results Review of the charts and previous images showed that six patients had lung cancer; two, lymphoma; two, colon cancer; one, melanoma; one, rectal carcinoma; and one, carcinoma of the pancreas. Combined PET/CT was used for initial tumor staging in two cases. In the other 11 cases, PET/CT showed an increase in tumor burden in four patients, a decrease in two, stable disease in two, and no tumor in three cases. All patients had evidence of acute PE on contrast-enhanced CT. No cases of chronic embolism were identified. The site of the largest pulmonary embolus was the right pulmonary artery in two cases, lobar artery in nine cases, and segmental artery in two cases. In two cases, no previous contrast-enhanced CT scans were available. In 11 cases, previous contrast-enhanced CT scans showed evidence of PE in four cases, less thrombus than visualized with PET/CT in three of the four cases, and a larger thrombus in one case. In the other seven cases, previous CT showed no evidence of PE. The mean time between previous CT and PET/CT was 11 ± 9 weeks (range, 2 28 weeks). Followup CT scans were available for eight of the study patients, and all scans showed the thrombus had cleared. The time period between the study CT and follow-up contrastenhanced CT was a mean of 19 ± 12 weeks (range, 7 34 weeks). All but one patient received anticoagulation therapy as a result of the diagnosis of coincidental PE. The other underwent placement of an inferior vena caval filter. The mean SUV of acute PE was 1.65 ± 0.61 (range, ). Vessels without thrombus had a mean SUV of 1.15 ± 0.38 (range, ) (p = 0.009). The average SUV per vessel size was the main pulmonary artery, 1.5 ± 0.27 (range, ); lobar pulmonary artery, 1.75 ± 0.60 (range, ); and segmental pulmonary artery, 1.57 ± 0.75 (range, ). In three cases, CT showed lung opacification peripheral to the acute thrombus: consolidation in two of the cases and ground-glass opacification in one case. These lesions were consistent with infarction and had a mean SUV of 1.84 ± 0.96 (range, ). The normal region of lung had a mean SUV of 0.80 ± 0.29 (range, ) (p =0.129). In all six cases in which previous PET/CT had not shown PE, direct comparison of the study PET scans with the previous images showed evidence of an increase in FDG uptake in the hila. This increased uptake represented a new focal or curvilinear abnormality corresponding to the contrastenhanced CT abnormality that represented PE (Figs. 1 and 2). On review of the images of the abdomen and pelvis, we found that in four cases images had poor opacification of the veins, making them indeterminate for identification of deep venous thrombosis. In five cases there was no evidence of deep venous thrombosis. Deep venous thrombosis was found in four patients: one with thrombus in the right internal iliac vein, one with thrombus in the left common femoral vein, one with thrombus in the left and right common femoral veins (Fig. 3), and one with thrombus in the right common iliac vein. In all of these cases, PET/CT showed an increase in FDG uptake (Fig. 3). 172 AJR:189, July 2007

3 FDG PET of Pulmonary Embolism Discussion Combined PET/CT is likely to become the standard of care for primary staging and evaluation of treatment response in a large proportion of oncology patients. However, a growing number of nonmalignant thoracic abnormalities, including brown fat and benign tumors such as hamartoma, sclerosing hemangioma, and leiomyoma, that take up FDG are being identified on PET scans. Other causes of increased uptake are amyloid deposition, round atelectasis, and inflammatory A C Fig year-old man with history of colon cancer and incidental finding of acute pulmonary embolism. Previous scan had shown no residual tumor. A, Contrast-enhanced CT scan shows acute pulmonary embolism (arrow) in lobar artery of left lower lobe. B, Obtained at same time as A, 18 F-FDG PET scan shows focal increased uptake of FDG at site of acute pulmonary embolism (arrow). C, FDG PET scan obtained 11 weeks before A and B shows normal left hilar FDG PET activity. D, Integrated PET/CT scan shows focal increase in FDG uptake over acute pulmonary embolism (arrow) in A. Normal mediastinal uptake over heart (arrowheads) is evident. and infective lesions, such as organizing pneumonia, actinomycosis, acute and chronic bacterial pneumonia, abscesses, mycobacterial and fungal infections (e.g., coccidioidomycosis), sarcoidosis, parasitic infestations (e.g., Paragonimus westermani), talc pleurodesis, and pneumoconiosis [12, 13]. Pulmonary infarction causing increased uptake of FDG has been described in three cases [7]. This study demonstrates that PE can also cause an increase in FDG uptake on PET scans. The differential diagnosis of vascular uptake of FDG in the thorax includes atheromatous disease, which is common in the systemic arteries [14], and Takayasu arteritis, which can affect both systemic and pulmonary arteries [15]. The pathologic mechanism of acute PE often involves impaction of thrombus within a pulmonary artery by pulsatile flow. Distention of an affected artery can lead to focal vessel wall inflammation and necrosis with aggregation of leukocytes along the endothelial surface. These changes can occur B D AJR:189, July

4 within the first few days of the onset of pulmonary thromboembolic disease. Vascular uptake of FDG in atheroma and Takayasu arteritis is caused by inflammation [14, 15]. It is assumed that a similar process is the cause of acute PE. Although they are not yet clarified, the exact mechanisms of FDG uptake by PE are likely related to the chemical characteristics of the radiopharmaceutical. This glucose analogue has a biodistribution determined in A C Fig year-old man with history of lung cancer and incidental finding of acute pulmonary embolism. Previous scan had shown no residual tumor. A, Contrast-enhanced CT scan shows acute pulmonary embolism (arrow) in lobar artery of right lower lobe. B, Obtained at same level as A, 18 F-FDG PET scan shows curvilinear increase in FDG uptake at site of acute pulmonary embolism (arrow). C, FDG PET scan obtained 26 weeks before B shows normal right hilar FDG PET activity. D, Integrated PET/CT image of A and B shows curvilinear increase in FDG uptake over acute pulmonary embolism (arrow) within lobar artery of right lower lobe. Normal left ventricular uptake (arrowhead) is evident. (Fig. 2 continues on next page) large part by increased numbers of glucose transporter proteins and increased intracellular levels of hexokinase and phosphofructokinase, among other agents, which promote glycolysis. FDG is well known to be taken up by inflammatory cells [16]. The rationale is that activated macrophages and neutrophils in inflammatory tissue use glucose as an energy source for chemotaxis and phagocytosis, whereas fibroblasts use glucose for proliferation [17]. We hypothesize that a local increased influx of inflammatory cells causes a focal increase in uptake of FDG at the embolic site. Further study of the exact mechanism is required. In a population of oncology patients, one concern for this study was how to differentiate thrombotic and tumor emboli as a cause of the intravascular filling defects. As a rule, large tumor emboli that affect vessels of segmental size or larger arise from tumors that invade the inferior vena cava or large feeding B D 174 AJR:189, July 2007

5 FDG PET of Pulmonary Embolism E Fig. 2 (continued) 62-year-old man with history of lung cancer and incidental finding of acute pulmonary embolism. Previous scan had shown no residual tumor. E, Contrast-enhanced CT scan obtained at level more caudal than A shows acute pulmonary embolism (arrow) in posterior basal segment artery of right lower lobe. F, FDG PET scan obtained at same level as E shows focal increase in FDG uptake at site of acute segmental pulmonary embolism (arrow). Fig year-old man with deep venous thrombosis. A, Contrast-enhanced CT scan obtained at level of common femoral veins shows bilateral deep venous thrombosis (arrows). B, Obtained at same level as A, 18 F-FDG PET scan shows bilateral focal increase in FDG uptake at sites of acute thrombosis (arrows). veins. Examples are hepatoma, renal cell carcinoma, and choriocarcinoma [18]. In our group of 13 patients, no patient fit this criterion. In addition, in cases in which follow-up contrast-enhanced CT scans were available, eight patients had complete resolution of PE after anticoagulation therapy. One limitation of our study was the relatively small size of the population. More subjects would have been included if the search had incorporated cases in which FDG PET and contrast-enhanced CT were performed at different times. Use of this criterion, however, would likely have produced less accurate data because of a potential rapid change in size and position of emboli as a result of fragmentation and lysis. We chose fewer subjects and greater accuracy. Another limitation, as in all A PET/CT studies, was that we assumed accurate registration of the CT and PET images. Despite this limitation, our results show the importance of temporal correlation, because an increase in FDG hilar uptake can indicate PE. An additional limitation was that only 13 (0.59%) of 2,216 patients with tumors were identified as having PE. This number is much lower than in other series described [3 5]. The explanation is that our cases were identified with a word-search system, which can miss cases of coincidental PE not reported by radiologists. The objective of this study was not to evaluate the rate of coincidental PE in a group of oncology patients but to describe the manifestations of FDG uptake by PE. In conclusion, many patients undergo integrated PET/CT for tumor detection, staging, and evaluation for response to therapy. The presence of coincidental PE is likely in this population and should be recognized in the contrast-enhanced CT component of PET/CT studies. In patients who do not receive IV contrast material, a focal or curvilinear increase in FDG uptake over a vessel should suggest the possibility of PE, and further imaging with CT angiography should be considered. References 1. Giuntini C, Ricco GD, Marini C, et al. Pulmonary embolism: epidemiology. Chest 1995; 107[suppl]:3S 9S 2. Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary F B AJR:189, July

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