Magnetic particle imaging: Development and evaluation of novel methodology for the assessment of the aorta in vivo in a small animal model of aortic aneurysms

• Applicants: Professor Dr. Marcus R. Makowski; Professor Dr. Tobias Schäffter
• Subject Area: Medical Physics, Biomedical Technology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 312920752

• Final Report Year: 2021

Final Report Abstract

The purpose of our research was to develop new magnetic particle imaging (MPI) techniques for characterization of a abdominal aortic aneurysms (AAA) in a murine model and to establish a correlation with magnetic resonance imaging (MRI). In particular, we validated the feasibility of quantitative MPI for detecting nanoparticle (NP) uptake, developed MPI angiography techniques, conducted phantom, in vivo and ex vivo experiments. First, we manufactured silicone tube-models and 3D-printed phantoms filled with the magnetic nanoparticle ferucabotran (Resovist) at varying concentrations. We demonstrated the feasibility of imaging aortic aneurysms using MPI in phantom models of murine abdominal aortic aneurysms. Using these models, a 1-mm-internal diameter vessels can reliably be visualized at comparatively low tracer-concentrations (5 mmol/l). Second, a mouse model of abdominal aortic aneurysm was successfully established by continuous subcutaneous infusion of angiotensin-II in male apolipoprotein E-deficient mice. The model allowed a reliable investigation of the formation and progression of AAAs. There was a strong correlation of NP uptake with pathological changes, marked by inflammatory cell influx in histology. In addition, the areas positive for CD68+ macrophage immunohistology stain and iron specific Perls’ Prussian blue stain were overlaping, confirming the co-localization of macrophages and NPs. There are several factors that influence MP imaging. MPI excitation fields generate systematic background signals, that in turn could limit detection. In addition, the quantification accuracy of MPI is dependent on the employed reconstruction technique and the set of reconstruction parameters. Biological interactions and the NP environment in cell cultures and the body play also play a major role for quantification accuracy. In our study, the vicinity of the AAA to the liver and the resulting shadowing effect hindered us from conducting in vivo MPI imaging. Our proof-of-concept study demonstrates the feasibility of ferucarbotran-enhanced ex vivo MPI for the detection of vascular inflammation in AAA. We are currently working on testing various types of iron-oxide particles for first pass angiography and late contrast enhancement in the above described AAA model as well as in a high fat diet atherosclerosis mouse model for MPI-MRI imaging.

Publications

• Improved sensitivity and limit-of-detection using a receive-only coil in magnetic particle imaging. Phys Med Biol. 2018 Jul 2;63(13):13NT02
  Paysen H, Wells J, Kosch O, Steinhoff U, Franke J, Trahms L, Schaeffter T, Wiekhorst F
  
• Towards quantitative magnetic particle imaging: a comparison with magnetic particle spectroscopy AIP Adv.2018 8 056712
  Paysen H, Wells J, Kosch O, Steinhoff U, Trahms L, Schaeffter T and Wiekhorst F
  
• 2019, 17. Dez: MPI imaging of vascular inflammation in abdominal aortic aneurysm in murine model. CRC 1340 “Matrix in Vision” Colloquium, Berlin
  Makowski, MR
  
• 2020, 31. Aug - 02. Sep: Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model. CRC Days, Berlin
  Mangarova, DM
  
• 2020, 6-8. Sep: Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model. International Workshop on Magnetic Particle Imaging, Würzburg
  Mangarova, DM
  
• Cellular uptake of magnetic nanoparticles imaged and quantified by magnetic particle imaging. Sci Rep. 2020 Feb 5;10(1):1922
  Paysen H, Loewa N, Stach A, Wells J, Kosch O, Twamley S, Makowski MR, Schaeffter T, Ludwig A, Wiekhorst F
  
• Characterization of noise and background signals in a magnetic particle imaging system. Phys Med Biol. 2020 Oct 21
  Paysen H, Kosch O, Wells J, Loewa N, Wiekhorst F
  
• Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model. Sci Rep. 2020;10(1):12410
  Mangarova DM, Brangsch J, Mohtashamdolatshahi A, Kosch O, Paysen H, Wiekhorst F, Klopfleisch R, Buchholz R, Karst U, Taupitz M, Schnorr J, Hamm B, Makowski MR