Fleur M van der Valk1, Jeffrey Kroon2, Wouter V Potters3, Rogier M Thurlings4, Roelof J Bennink5, Hein J Verberne5, Aart J Nederveen3, Max Nieuwdorp1, Willem J M Mulder6, Zahi A Fayad7, Jaap D van Buul2, Erik S G Stroes8. 1. Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. 2. Department of Molecular Cell Biology, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam, the Netherlands. 3. Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands. 4. Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands. 5. Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands. 6. 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. 7. Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 8. Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands. Electronic address: e.s.stroes@amc.nl.
Abstract
BACKGROUND: Understanding how leukocytes impact atherogenesis contributes critically to our concept of atherosclerosis development and the identification of potential therapeutic targets. OBJECTIVES: 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.
BACKGROUND: Understanding how leukocytes impact atherogenesis contributes critically to our concept of atherosclerosis development and the identification of potential therapeutic targets. OBJECTIVES: 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: Fleur M van der Valk; Siroon Bekkering; Jeffrey Kroon; Calvin Yeang; Jan Van den Bossche; Jaap D van Buul; Amir Ravandi; Aart J Nederveen; Hein J Verberne; Corey Scipione; Max Nieuwdorp; Leo A B Joosten; Mihai G Netea; Marlys L Koschinsky; Joseph L Witztum; Sotirios Tsimikas; Niels P Riksen; Erik S G Stroes Journal: Circulation Date: 2016-08-05 Impact factor: 29.690
Authors: Sophie J Bernelot Moens; Simone L Verweij; Fleur M van der Valk; Julian C van Capelleveen; Jeffrey Kroon; Miranda Versloot; Hein J Verberne; Henk A Marquering; Raphaël Duivenvoorden; Liffert Vogt; Erik S G Stroes Journal: J Am Soc Nephrol Date: 2016-10-31 Impact factor: 10.121
Authors: Matthias Nahrendorf; Stefan Frantz; Filip K Swirski; Willem J M Mulder; Gwendalyn Randolph; Georg Ertl; Vasilis Ntziachristos; Jan J Piek; Erik S Stroes; Markus Schwaiger; Douglas L Mann; Zahi A Fayad Journal: J Am Coll Cardiol Date: 2015-04-21 Impact factor: 24.094