title: 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables the detection of recurrent same-site deep vein thrombosis by illuminating recently formed, neutrophil-rich thrombus.
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.
  
  
  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.
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Tetsuya
authors: T
authors: Hara
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Jessica
authors: J
authors: Truelove
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Ahmed
authors: A
authors: Tawakol
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Gregory R
authors: GR
authors: Wojtkiewicz
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: William J
authors: WJ
authors: Hucker
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Megan H
authors: MH
authors: MacNabb
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Anna-Liisa
authors: AL
authors: Brownell
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Kimmo
authors: K
authors: Jokivarsi
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Chase W
authors: CW
authors: Kessinger
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Michael R
authors: MR
authors: Jaff
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Peter K
authors: PK
authors: Henke
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.).
authors: Ralph
authors: R
authors: Weissleder
authors: From the Cardiovascular Research Center (T.H., C.W.K., F.A.J.), Center for Systems Biology (J.T., G.R.W., R.W.), Cardiology Division (A.T., W.J.H., M.H.M., M.R.J., F.A.J.), and Martinos Biomedical Imaging Center (A.-.L.B., K.J.), Massachusetts General Hospital, Harvard Medical School, Boston, MA; and Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI (P.K.H.). fjaffer@mgh.harvard.edu.
authors: Farouc A
authors: FA
authors: Jaffer
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D015331:Cohort Studies; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D064847:Multimodal Imaging; D009503:Neutropenia / Q000000981:diagnostic imaging; D009504:Neutrophils / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D012008:Recurrence; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013927:Thrombosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D020246:Venous Thrombosis / Q000000981:diagnostic imaging* / Q000378:metabolism
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: fluorodeoxyglucose F18; inflammation; neutrophils; positron-emission tomography; venous thrombosis