title: High Structural Stress and Presence of Intraluminal Thrombus Predict Abdominal Aortic Aneurysm 18F-FDG Uptake: Insights From Biomechanics.
abstract: BACKGROUND
  Abdominal aortic aneurysm (AAA) wall inflammation and mechanical structural stress may influence AAA expansion and lead to rupture. We hypothesized a positive correlation between structural stress and fluorine-18-labeled 2-deoxy-2-fluoro-d-glucose (18F-FDG) positron emission tomography-defined inflammation. We also explored the influence of computed tomography-derived aneurysm morphology and composition, including intraluminal thrombus, on both variables.
  
  
  RESULTS
  Twenty-one patients (19 males) with AAAs below surgical threshold (AAA size was 4.10±0.54 cm) underwent18F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm18F-FDG standardized uptake value within aortic wall and wall structural stress, patient clinical characteristics, aneurysm morphology, and compositions was explored using a hierarchical linear mixed-effects model. On univariate analysis, local aneurysm diameter, thrombus burden, extent of calcification, and structural stress were all associated with18F-FDG uptake (P<0.05). AAA structural stress correlated with18F-FDG maximum standardized uptake value (slope estimate, 0.552; P<0.0001). Multivariate linear mixed-effects analysis revealed an important interaction between structural stress and intraluminal thrombus in relation to maximum standardized uptake value (fixed effect coefficient, 1.68 [SE, 0.10]; P<0.0001). Compared with other factors, structural stress was the best predictor of inflammation (receiver-operating characteristic curve area under the curve =0.59), with higher accuracy seen in regions with high thrombus burden (area under the curve =0.80). Regions with both high thrombus burden and high structural stress had higher18F-FDG maximum standardized uptake value compared with regions with high thrombus burdens but low stress (median [interquartile range], 1.93 [1.60-2.14] versus 1.14 [0.90-1.53]; P<0.0001).
  
  
  CONCLUSIONS
  Increased aortic wall inflammation, demonstrated by18F-FDG positron emission tomography, was observed in AAA regions with thick intraluminal thrombus subjected to high mechanical stress, suggesting a potential mechanistic link underlying aneurysm inflammation.
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.). zt215@cam.ac.uk jhfr2@cam.ac.uk.
authors.forename: Zhongzhao
authors.initials: Z
authors.lastname: Teng
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Maysoon
authors.initials: M
authors.lastname: Elkhawad
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Jason M
authors.initials: JM
authors.lastname: Tarkin
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Nikhil
authors.initials: N
authors.lastname: Joshi
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Boyle
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: John R
authors.initials: JR
authors.lastname: Buscombe
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Fryer
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Yongxue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Ah Yeon
authors.initials: AY
authors.lastname: Park
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Ian B
authors.initials: IB
authors.lastname: Wilkinson
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.).
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Gillard
authors.affiliation: From the Department of Radiology (Y.H., Z.T., Y.Z., J.H.G.), EPSRC Centre for Mathematical and Statistical Analysis of Multimodal Clinical Imaging (Y.H.), Department of Engineering (Z.T.), Division of Cardiovascular Medicine (M.E., J.M.T., I.B.W., J.H.F.R.), Wolfson Brain Imaging Centre (T.D.F.), and Statistical Laboratory (A.Y.P.), University of Cambridge, United Kingdom; British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, United Kingdom (N.J., D.E.N.); Department of Vascular Surgery (J.R. Boyle) and Department of Nuclear Medicine (J.R. Buscombe), Addenbrooke's Hospital, Cambridge, United Kingdom; and Department of Vascular Surgery, Changhai Hospital, Shanghai, China (Y.Z.). zt215@cam.ac.uk jhfr2@cam.ac.uk.
authors.forename: James H F
authors.initials: JH
authors.lastname: Rudd
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging* / Q000503:physiopathology; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D001019:Aortic Rupture / Q000209:etiology / Q000503:physiopathology; D001025:Aortitis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D001027:Aortography / Q000379:methods; D001696:Biomechanical Phenomena; D000072226:Computed Tomography Angiography; D005260:Female; D020342:Finite Element Analysis; D019788:Fluorodeoxyglucose F18 / Q000008:administration & dosage*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000072078:Positron Emission Tomography Computed Tomography; D011237:Predictive Value of Tests; D011379:Prognosis; D011673:Pulsatile Flow; D011857:Radiographic Image Interpretation, Computer-Assisted; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012039:Regional Blood Flow; D012307:Risk Factors; D013314:Stress, Mechanical; D013927:Thrombosis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: abdominal aortic aneurysm; fluorodeoxyglucose F18; inflammation; mechanical stress; positron-emission tomography; thrombosis