title: In vivo imaging of enhanced leukocyte accumulation in atherosclerotic lesions in humans.
abstract: BACKGROUND
  Understanding how leukocytes impact atherogenesis contributes critically to our concept of atherosclerosis development and the identification of potential therapeutic targets.
  
  
  OBJECTIVE
  The study evaluates an in vivo imaging approach to visualize peripheral blood mononuclear cell (PBMC) accumulation in atherosclerotic lesions of cardiovascular (CV) patients using hybrid single-photon emission computed tomography/computed tomography (SPECT/CT).
  
  
  METHODS
  At baseline, CV patients and healthy controls underwent (18)fluorodeoxyglucose positron emission tomography-computed tomography and magnetic resonance imaging to assess arterial wall inflammation and dimensions, respectively. For in vivo trafficking, autologous PBMCs were isolated, labeled with technetium-99m, and visualized 3, 4.5, and 6 h post-infusion with SPECT/CT.
  
  
  RESULTS
  Ten CV patients and 5 healthy controls were included. Patients had an increased arterial wall inflammation (target-to-background ratio [TBR] right carotid 2.00 ± 0.26 in patients vs. 1.51 ± 0.12 in controls; p = 0.022) and atherosclerotic burden (normalized wall index 0.52 ± 0.09 in patients vs. 0.33 ± 0.02 in controls; p = 0.026). Elevated PBMC accumulation in the arterial wall was observed in patients; for the right carotid, the arterial-wall-to-blood ratio (ABR) 4.5 h post-infusion was 2.13 ± 0.35 in patients versus 1.49 ± 0.40 in controls (p = 0.038). In patients, the ABR correlated with the TBR of the corresponding vessel (for the right carotid: r = 0.88; p < 0.001).
  
  
  CONCLUSIONS
  PBMC accumulation is markedly enhanced in patients with advanced atherosclerotic lesions and correlates with disease severity. This study provides a noninvasive imaging tool to validate the development and implementation of interventions targeting leukocytes in atherosclerosis.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Fleur M
authors.initials: FM
authors.lastname: van der Valk
authors.affiliation: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kroon
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Wouter V
authors.initials: WV
authors.lastname: Potters
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Thurlings
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Roelof J
authors.initials: RJ
authors.lastname: Bennink
authors.affiliation: Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Hein J
authors.initials: HJ
authors.lastname: Verberne
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Aart J
authors.initials: AJ
authors.lastname: Nederveen
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Nieuwdorp
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands; Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.affiliation: Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
authors.affiliation: Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jaap D
authors.initials: JD
authors.lastname: van Buul
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: e.s.stroes@amc.nl.
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
mesh_terms: D016022:Case-Control Studies; D002465:Cell Movement / Q000502:physiology; D016001:Confidence Intervals; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D015588:Observer Variation; D049268:Positron-Emission Tomography / Q000379:methods*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods; D014182:Transplantation, Autologous
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: atherosclerosis; imaging; inflammation; peripheral blood mononuclear cells