18F-fluorodeoxyglucose positron emission tomography/computed tomography enables the detection of recurrent same-site deep vein thrombosis by illuminating recently formed, neutrophil-rich thrombus

Tetsuya Hara, Jessica Truelove, Ahmed Tawakol, Gregory R Wojtkiewicz, William J Hucker, Megan H MacNabb, Anna-Liisa Brownell, Kimmo Jokivarsi, Chase W Kessinger, Michael R Jaff, Peter K Henke, Ralph Weissleder, Farouc A Jaffer, Tetsuya Hara, Jessica Truelove, Ahmed Tawakol, Gregory R Wojtkiewicz, William J Hucker, Megan H MacNabb, Anna-Liisa Brownell, Kimmo Jokivarsi, Chase W Kessinger, Michael R Jaff, Peter K Henke, Ralph Weissleder, Farouc A Jaffer

Abstract

Background: Accurate detection of recurrent same-site deep vein thrombosis (DVT) is a challenging clinical problem. Because DVT formation and resolution are associated with a preponderance of inflammatory cells, we investigated whether noninvasive (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging could identify inflamed, recently formed thrombi and thereby improve the diagnosis of recurrent DVT.

Methods and results: We established a stasis-induced DVT model in murine jugular veins and also a novel model of recurrent stasis DVT in mice. C57BL/6 mice (n=35) underwent ligation of the jugular vein to induce stasis DVT. FDG-PET/computed tomography (CT) was performed at DVT time points of day 2, 4, 7, 14, or 2+16 (same-site recurrent DVT at day 2 overlying a primary DVT at day 16). Antibody-based neutrophil depletion was performed in a subset of mice before DVT formation and FDG-PET/CT. In a clinical study, 38 patients with lower extremity DVT or controls undergoing FDG-PET were analyzed. Stasis DVT demonstrated that the highest FDG signal occurred at day 2, followed by a time-dependent decrease (P<0.05). Histological analyses demonstrated that thrombus neutrophils (P<0.01), but not macrophages, correlated with thrombus PET signal intensity. Neutrophil depletion decreased FDG signals in day 2 DVT in comparison with controls (P=0.03). Recurrent DVT demonstrated significantly higher FDG uptake than organized day 14 DVT (P=0.03). The FDG DVT signal in patients also exhibited a time-dependent decrease (P<0.01).

Conclusions: Noninvasive FDG-PET/CT identifies neutrophil-dependent thrombus inflammation in murine DVT, and demonstrates a time-dependent signal decrease in both murine and clinical DVT. FDG-PET/CT may offer a molecular imaging strategy to accurately diagnose recurrent DVT.

Keywords: fluorodeoxyglucose F18; inflammation; neutrophils; positron-emission tomography; venous thrombosis.

© 2014 American Heart Association, Inc.

Figures

Figure 1
Figure 1
Induction of stasis-induced DVT model in the murine jugular vein. (A) Surgical ligation of the right jugular vein was performed to induce deep vein thrombosis (DVT). As a sham control, the left jugular vein was surgically exposed and loosely tied without constriction. (B) Contrast-enhanced computed tomography (CT) venography shows a filling defect only in the right jugular vein with DVT (dark signal, yellow arrow). Surgery-induced air artifact was observed in front of ligated jugular vein (asterisk). (C) Resected red-white thrombus in the ligated jugular vein. (D) Hematoxylin-eosin stain. (E) Carstairs’ stain (red = fibrin, yellow = erythrocytes, blue = collagen). Representative DVT images at day 0 (A) and day 4 (B-E). Scale bars, 500 μm.
Figure 2
Figure 2
FDG-PET enhances acute DVT in mice. Representative images of (A) FDG-PET (B) contrast-enhanced CT venography, and (C) fused PET/CT at various timepoints. DVT (yellow arrow) induced filling defects in contrast CT venography not seen in the contralateral sham-operated vein (white arrow). Surgery-induced air artifact (dark signal) is observed anterior to each vein on CT (white asterisk). FDG-PET DVT signal was elevated in acute DVT, and diminished over time. Mild surgery-induced inflammation at wound healing region was observed in the sham surgery left jugular vein region at day 2.
Figure 3
Figure 3
Time-course quantitative changes of FDG signal in DVT. (A) Standard uptake value (SUV), (B) SUVmax , (C) target-to-background ratio (TBR), and (D) %injected dose per gram of tissue (%IDGT) showed a similar trend (p<0.05) in that values were highest at day 2 and significantly decreased over time (4-5 mice per group). (E and F) Subset of mice underwent serial PET imaging at day 2, 7, and 14. FDG accumulation in DVT (yellow arrow, sham control white arrow) demonstrated a time-dependent significant decrease (p=0.03). *p<0.05, **p<0.01, ***p<0.001. (Box-and-Whisker plot) Middle line represents median value, box indicates interquartile range (25th–75th percentiles), and range bars show maximum and minimum.
Figure 4
Figure 4
Recruitment of inflammatory cells into DVT. (A) Representative immunostaining of neutrophil and macrophage from various DVT timepoints. Neutrophils are abundant and predominate in early day 2-4 DVT. Thrombus macrophages were evident from day 7 and resided at the outer DVT edge. (B) The number of neutrophils (black) and macrophages (white) per 5 HPF (high power field) were shown. (*p

Figure 5

FDG signal associations with thrombus…

Figure 5

FDG signal associations with thrombus neutrophils and macrophages. (A) The number of thrombus…

Figure 5
FDG signal associations with thrombus neutrophils and macrophages. (A) The number of thrombus neutrophils correlated with the FDG uptake in DVT (SUV; r=0.41, p=0.004, TBR; r=0.62, p

Figure 6

Experimental neutropenia reduces FDG signal…

Figure 6

Experimental neutropenia reduces FDG signal within DVT. (A) Representative images of contrast-enhanced CT…

Figure 6
Experimental neutropenia reduces FDG signal within DVT. (A) Representative images of contrast-enhanced CT and fused PET/CT from neutropenic mice (left) and uninjected control (right) are shown. DVT (yellow arrow) and sham-operated jugular vein (white arrow) are indicated by arrows. (B) SUV, SUVmax, and TBR of FDG signal of DVT in neutropenic mice are significantly lower than control mice (*p<0.05). N=4 per group. Median SUV and SUVmax value of sham-operated contralateral jugular veins are shown as respective dotted lines.

Figure 7

Establishment of a novel recurrent…

Figure 7

Establishment of a novel recurrent DVT model, and specific detection of recurrent DVT…

Figure 7
Establishment of a novel recurrent DVT model, and specific detection of recurrent DVT by FDG-PET/CT. (A) Two days after the initial ligation, the suture was de-ligated and removed. At day 14, re-ligation was performed at previously ligated site to induce a recurrent DVT. Histological images of resected recurrent DVT (day 2 recurrent DVT (outlined with black dotted line) overlying the day 16 DVT (outlined with blue dotted line)) are shown. (B) Hematoxylin-eosin, (C) Carstairs’ staining, and (D) Masson Trichrome staining shows red blood cell-rich zones in recurrent DVT (red in H&E and yellow in Carstairs’) and collagen-rich zones in older DVT (pink in H&E and blue in Carstairs’ and Masson). (E and F) Immunostaining of neutrophils (E) and macrophages (F) shows the newly formed recurrent DVT is neutrophil-rich, while the older primary DVT shows macrophage predominance. Representative (G) PET, (H) CT, and (I) PET/CT images are shown. FDG enhanced recurrent DVT substantially more than older DVT (G and I). (J-L) FDG signal was significantly higher in recurrent DVT (day 2 overlying the day 16 DVT) than in older day 14 DVT in the contralateral vein. N=6 per group. Scale bar, 500 μm.

Figure 8

18 F-FDG DVT signal is…

Figure 8

18 F-FDG DVT signal is elevated in patients and diminishes over time. Representative…
Figure 8
18F-FDG DVT signal is elevated in patients and diminishes over time. Representative PET/CT images from (A) a patient with DVT and (B) a matched control patient without DVT. Elevated FDG signal was observed in the thrombosed femoral vein (A, yellow arrow). (C) The SUVmax and (D) TBR of the DVT exhibited a time-dependent decrease (p=0.002 for SUVmax, p=0.004 for TBR, n=6-7 per DVT group). FDG uptake in the DVT vein was shown for individuals grouped according to age of the DVT, divided into tertiles. Values from the matched vein from control patients are shown in the No DVT group (n=19 patients).
All figures (8)
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    1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics--2013 update: a report from the american heart association. Circulation. 2013;127:e6–e245. - PMC - PubMed
    1. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123:1788–1830. - PubMed
    1. Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet. 2005;365:1163–1174. - PubMed
    1. Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362:523–526. - PubMed
    1. Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e351S–418S. - PMC - PubMed
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Figure 5
Figure 5
FDG signal associations with thrombus neutrophils and macrophages. (A) The number of thrombus neutrophils correlated with the FDG uptake in DVT (SUV; r=0.41, p=0.004, TBR; r=0.62, p

Figure 6

Experimental neutropenia reduces FDG signal…

Figure 6

Experimental neutropenia reduces FDG signal within DVT. (A) Representative images of contrast-enhanced CT…

Figure 6
Experimental neutropenia reduces FDG signal within DVT. (A) Representative images of contrast-enhanced CT and fused PET/CT from neutropenic mice (left) and uninjected control (right) are shown. DVT (yellow arrow) and sham-operated jugular vein (white arrow) are indicated by arrows. (B) SUV, SUVmax, and TBR of FDG signal of DVT in neutropenic mice are significantly lower than control mice (*p<0.05). N=4 per group. Median SUV and SUVmax value of sham-operated contralateral jugular veins are shown as respective dotted lines.

Figure 7

Establishment of a novel recurrent…

Figure 7

Establishment of a novel recurrent DVT model, and specific detection of recurrent DVT…

Figure 7
Establishment of a novel recurrent DVT model, and specific detection of recurrent DVT by FDG-PET/CT. (A) Two days after the initial ligation, the suture was de-ligated and removed. At day 14, re-ligation was performed at previously ligated site to induce a recurrent DVT. Histological images of resected recurrent DVT (day 2 recurrent DVT (outlined with black dotted line) overlying the day 16 DVT (outlined with blue dotted line)) are shown. (B) Hematoxylin-eosin, (C) Carstairs’ staining, and (D) Masson Trichrome staining shows red blood cell-rich zones in recurrent DVT (red in H&E and yellow in Carstairs’) and collagen-rich zones in older DVT (pink in H&E and blue in Carstairs’ and Masson). (E and F) Immunostaining of neutrophils (E) and macrophages (F) shows the newly formed recurrent DVT is neutrophil-rich, while the older primary DVT shows macrophage predominance. Representative (G) PET, (H) CT, and (I) PET/CT images are shown. FDG enhanced recurrent DVT substantially more than older DVT (G and I). (J-L) FDG signal was significantly higher in recurrent DVT (day 2 overlying the day 16 DVT) than in older day 14 DVT in the contralateral vein. N=6 per group. Scale bar, 500 μm.

Figure 8

18 F-FDG DVT signal is…

Figure 8

18 F-FDG DVT signal is elevated in patients and diminishes over time. Representative…
Figure 8
18F-FDG DVT signal is elevated in patients and diminishes over time. Representative PET/CT images from (A) a patient with DVT and (B) a matched control patient without DVT. Elevated FDG signal was observed in the thrombosed femoral vein (A, yellow arrow). (C) The SUVmax and (D) TBR of the DVT exhibited a time-dependent decrease (p=0.002 for SUVmax, p=0.004 for TBR, n=6-7 per DVT group). FDG uptake in the DVT vein was shown for individuals grouped according to age of the DVT, divided into tertiles. Values from the matched vein from control patients are shown in the No DVT group (n=19 patients).
All figures (8)
Figure 6
Figure 6
Experimental neutropenia reduces FDG signal within DVT. (A) Representative images of contrast-enhanced CT and fused PET/CT from neutropenic mice (left) and uninjected control (right) are shown. DVT (yellow arrow) and sham-operated jugular vein (white arrow) are indicated by arrows. (B) SUV, SUVmax, and TBR of FDG signal of DVT in neutropenic mice are significantly lower than control mice (*p<0.05). N=4 per group. Median SUV and SUVmax value of sham-operated contralateral jugular veins are shown as respective dotted lines.
Figure 7
Figure 7
Establishment of a novel recurrent DVT model, and specific detection of recurrent DVT by FDG-PET/CT. (A) Two days after the initial ligation, the suture was de-ligated and removed. At day 14, re-ligation was performed at previously ligated site to induce a recurrent DVT. Histological images of resected recurrent DVT (day 2 recurrent DVT (outlined with black dotted line) overlying the day 16 DVT (outlined with blue dotted line)) are shown. (B) Hematoxylin-eosin, (C) Carstairs’ staining, and (D) Masson Trichrome staining shows red blood cell-rich zones in recurrent DVT (red in H&E and yellow in Carstairs’) and collagen-rich zones in older DVT (pink in H&E and blue in Carstairs’ and Masson). (E and F) Immunostaining of neutrophils (E) and macrophages (F) shows the newly formed recurrent DVT is neutrophil-rich, while the older primary DVT shows macrophage predominance. Representative (G) PET, (H) CT, and (I) PET/CT images are shown. FDG enhanced recurrent DVT substantially more than older DVT (G and I). (J-L) FDG signal was significantly higher in recurrent DVT (day 2 overlying the day 16 DVT) than in older day 14 DVT in the contralateral vein. N=6 per group. Scale bar, 500 μm.
Figure 8
Figure 8
18F-FDG DVT signal is elevated in patients and diminishes over time. Representative PET/CT images from (A) a patient with DVT and (B) a matched control patient without DVT. Elevated FDG signal was observed in the thrombosed femoral vein (A, yellow arrow). (C) The SUVmax and (D) TBR of the DVT exhibited a time-dependent decrease (p=0.002 for SUVmax, p=0.004 for TBR, n=6-7 per DVT group). FDG uptake in the DVT vein was shown for individuals grouped according to age of the DVT, divided into tertiles. Values from the matched vein from control patients are shown in the No DVT group (n=19 patients).

References

    1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics--2013 update: a report from the american heart association. Circulation. 2013;127:e6–e245.
    1. Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123:1788–1830.
    1. Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet. 2005;365:1163–1174.
    1. Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362:523–526.
    1. Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH. Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e351S–418S.
    1. Schellong SM. Diagnosis of recurrent deep vein thrombosis. Hamostaseologie. 2013;33:195–200.
    1. Saha P, Humphries J, Modarai B, Mattock K, Waltham M, Evans CE, Ahmad A, Patel AS, Premaratne S, Lyons OT, Smith A. Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions. Arterioscler Thromb Vasc Biol. 2011;31:506–512.
    1. Wakefield TW, Myers DD, Henke PK. Mechanisms of venous thrombosis and resolution. Arterioscler Thromb Vasc Biol. 2008;28:387–391.
    1. Zhou Z, Kozlowski J, Goodrich AL, Markman N, Chen DL, Schuster DP. Molecular imaging of lung glucose uptake after endotoxin in mice. Am J Physiol Lung Cell Mol Physiol. 2005;289:L760–768.
    1. Locke LW, Williams MB, Fairchild KD, Zhong M, Kundu BK, Berr SS. FDG-PET Quantification of Lung Inflammation with Image-Derived Blood Input Function in Mice. Int J Mol Imaging. 2011;2011:356730.
    1. de Prost N, Tucci MR, Melo MF. Assessment of lung inflammation with 18F-FDG PET during acute lung injury. AJR Am J Roentgenol. 2010;195:292–300.
    1. Satomi T, Ogawa M, Mori I, Ishino S, Kubo K, Magata Y, Nishimoto T. Comparison of Contrast Agents for Atherosclerosis Imaging Using Cultured Macrophages: FDG Versus Ultrasmall Superparamagnetic Iron Oxide. J Nucl Med. 2013;54:999–1004.
    1. Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, Yates D, LaMuraglia GM, Furie K, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ. In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol. 2006;48:1818–1824.
    1. Diaz JA, Obi AT, Myers DD, Jr., Wrobleski SK, Henke PK, Mackman N, Wakefield TW. Critical review of mouse models of venous thrombosis. Arterioscler Thromb Vasc Biol. 2012;32:556–562.
    1. Varma MR, Varga AJ, Knipp BS, Sukheepod P, Upchurch GR, Kunkel SL, Wakefield TW, Henke PK. Neutropenia impairs venous thrombosis resolution in the rat. J Vasc Surg. 2003;38:1090–1098.
    1. Eliason JL, Hannawa KK, Ailawadi G, Sinha I, Ford JW, Deogracias MP, Roelofs KJ, Woodrum DT, Ennis TL, Henke PK, Stanley JC, Thompson RW, Upchurch GR., Jr Neutrophil depletion inhibits experimental abdominal aortic aneurysm formation. Circulation. 2005;112:232–240.
    1. Henke PK, Pearce CG, Moaveni DM, Moore AJ, Lynch EM, Longo C, Varma M, Dewyer NA, Deatrick KB, Upchurch GR, Jr., Wakefield TW, Hogaboam C, Kunkel SL. Targeted deletion of CCR2 impairs deep vein thombosis resolution in a mouse model. J Immunol. 2006;177:3388–3397.
    1. Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, Williams KC, Lo J, Grinspoon SK. Arterial inflammation in patients with HIV. JAMA. 2012;308:379–386.
    1. Heijink DM, Kleibeuker JH, Nagengast WB, Oosterhuis D, Brouwers AH, Koornstra JJ, de Jong S, de Vries EG. Total abdominal 18F-FDG uptake reflects intestinal adenoma burden in Apc mutant mice. J Nucl Med. 2011;52:431–436.
    1. Nosaka M, Ishida Y, Kimura A, Kondo T. Time-dependent appearance of intrathrombus neutrophils and macrophages in a stasis-induced deep vein thrombosis model and its application to thrombus age determination. Int J Legal Med. 2009;123:235–240.
    1. Deatrick KB, Eliason JL, Lynch EM, Moore AJ, Dewyer NA, Varma MR, Pearce CG, Upchurch GR, Wakefield TW, Henke PK. Vein wall remodeling after deep vein thrombosis involves matrix metalloproteinases and late fibrosis in a mouse model. J Vasc Surg. 2005;42:140–148.
    1. Kahn SR, Shrier I, Julian JA, Ducruet T, Arsenault L, Miron MJ, Roussin A, Desmarais S, Joyal F, Kassis J, Solymoss S, Desjardins L, Lamping DL, Johri M, Ginsberg JS. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med. 2008;149:698–707.
    1. Lecumberri R, Alfonso A, Jimenez D, Fernandez Capitan C, Prandoni P, Wells PS, Vidal G, Barillari G, Monreal M. Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism. Thromb Haemost. 2013;110:834–843.
    1. van Langevelde K, Tan M, Sramek A, Huisman MV, de Roos A. Magnetic resonance imaging and computed tomography developments in imaging of venous thromboembolism. J Magn Reson Imaging. 2010;32:1302–1312.
    1. Kory PD, Pellecchia CM, Shiloh AL, Mayo PH, DiBello C, Koenig S. Accuracy of ultrasonography performed by critical care physicians for the diagnosis of DVT. Chest. 2011;139:538–542.
    1. Geier B, Barbera L, Muth-Werthmann D, Siebers S, Ermert H, Philippou S, Mumme A. Ultrasound elastography for the age determination of venous thrombi. Evaluation in an animal model of venous thrombosis. Thromb Haemost. 2005;93:368–374.
    1. Westerbeek RE, Van Rooden CJ, Tan M, Van Gils AP, Kok S, De Bats MJ, De Roos A, Huisman MV. Magnetic resonance direct thrombus imaging of the evolution of acute deep vein thrombosis of the leg. J Thromb Haemost. 2008;6:1087–1092.
    1. Saha P, Andia ME, Modarai B, Blume U, Humphries J, Patel AS, Phinikaridou A, Evans CE, Mattock K, Grover SP, Ahmad A, Lyons OT, Attia RQ, Renne T, Premaratne S, Wiethoff AJ, Botnar RM, Schaeffter T, Waltham M, Smith A. Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis. Circulation. 2013;128:729–736.
    1. Bates SM, Lister-James J, Julian JA, Taillefer R, Moyer BR, Ginsberg JS. Imaging characteristics of a novel technetium Tc 99m-labeled platelet glycoprotein IIb/IIIa receptor antagonist in patients With acute deep vein thrombosis or a history of deep vein thrombosis. Arch Intern Med. 2003;163:452–456.
    1. Brighton T, Janssen J, Butler SP. Aging of acute deep vein thrombosis measured by radiolabeled 99mTc-rt-PA. J Nucl Med. 2007;48:873–878.
    1. Chang KJ, Zhuang H, Alavi A. Detection of chronic recurrent lower extremity deep venous thrombosis on fluorine-18 fluorodeoxyglucose positron emission tomography. Clin Nucl Med. 2000;25:838–839.
    1. Rondina MT, Lam UT, Pendleton RC, Kraiss LW, Wanner N, Zimmerman GA, Hoffman JM, Hanrahan C, Boucher K, Christian PE, Butterfield RI, Morton KA. (18)F-FDG PET in the evaluation of acuity of deep vein thrombosis. Clin Nucl Med. 2012;37:1139–1145.
    1. Kikuchi M, Yamamoto E, Shiomi Y, Nakamoto Y, Fujiwara K, Watanabe F, Shinohara S. Case report: internal and external jugular vein thrombosis with marked accumulation of FDG. Br J Radiol. 2004;77:888–890.
    1. Enden T, Haig Y, Klow NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbaek G, Sandset PM. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. 2012;379:31–38.
    1. Vedantham S, Goldhaber SZ, Kahn SR, Julian J, Magnuson E, Jaff MR, Murphy TP, Cohen DJ, Comerota AJ, Gornik HL, Razavi MK, Lewis L, Kearon C. Rationale and design of the ATTRACT Study: a multicenter randomized trial to evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis. Am Heart J. 2013;165:523–530. e523.
    1. Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry. Radiology. 1999;211:39–49.
    1. Tawakol A, Migrino RQ, Hoffmann U, Abbara S, Houser S, Gewirtz H, Muller JE, Brady TJ, Fischman AJ. Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol. 2005;12:294–301.
    1. Borregaard N, Herlin T. Energy metabolism of human neutrophils during phagocytosis. J Clin Invest. 1982;70:550–557.
    1. Rodriguez-Prados JC, Traves PG, Cuenca J, Rico D, Aragones J, Martin-Sanz P, Cascante M, Bosca L. Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation. J Immunol. 2010;185:605–614.
    1. Ogawa M, Ishino S, Mukai T, Asano D, Teramoto N, Watabe H, Kudomi N, Shiomi M, Magata Y, Iida H, Saji H. (18)F-FDG accumulation in atherosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med. 2004;45:1245–1250.
    1. Vucic E, Dickson SD, Calcagno C, Rudd JH, Moshier E, Hayashi K, Mounessa JS, Roytman M, Moon MJ, Lin J, Tsimikas S, Fisher EA, Nicolay K, Fuster V, Fayad ZA. Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging. JACC. Cardiovascular imaging. 2011;4:1100–1109.
    1. Hyafil F, Cornily JC, Rudd JH, Machac J, Feldman LJ, Fayad ZA. Quantification of inflammation within rabbit atherosclerotic plaques using the macrophage-specific CT contrast agent N1177: a comparison with 18F-FDG PET/CT and histology. J Nucl Med. 2009;50:959–965.
    1. Hag AM, Pedersen SF, Christoffersen C, Binderup T, Jensen MM, Jorgensen JT, Skovgaard D, Ripa RS, Kjaer A. (18)F-FDG PET imaging of murine atherosclerosis: association with gene expression of key molecular markers. PLoS One. 2012;7:e50908.
    1. Wakefield TW, Linn MJ, Henke PK, Kadell AM, Wilke CA, Wrobleski SK, Sarkar M, Burdick MD, Myers DD, Strieter RM. Neovascularization during venous thrombosis organization: a preliminary study. J Vasc Surg. 1999;30:885–892.
    1. Matsui T, Nakata N, Nagai S, Nakatani A, Takahashi M, Momose T, Ohtomo K, Koyasu S. Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannus formation in rheumatoid arthritis. J Nucl Med. 2009;50:920–926.
    1. Roumen-Klappe EM, Janssen MC, Van Rossum J, Holewijn S, Van Bokhoven MM, Kaasjager K, Wollersheim H, Den Heijer M. Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study. J Thromb Haemost. 2009;7:582–587.
    1. Bouman AC, Smits JJ, Ten Cate H, Ten Cate-Hoek AJ. Markers of coagulation, fibrinolysis and inflammation in relation to post-thrombotic syndrome. J Thromb Haemost. 2012;10:1532–1538.

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