title: Automated detection and characterization of SPIO-labeled cells and capsules using magnetic field perturbations.
abstract: Understanding how individual cells behave inside living systems will help enable new diagnostic tools and cellular therapies. Superparamagnetic iron oxide particles can be used to label cells and theranostic capsules for noninvasive tracking using MRI. Contrast changes from superparamagnetic iron oxide are often subtle relative to intrinsic sources of contrast, presenting a detection challenge. Here, we describe a versatile postprocessing method, called Phase map cross-correlation Detection and Quantification (PDQ), that automatically identifies localized deposits of superparamagnetic iron oxide, estimating their volume magnetic susceptibility and magnetic moment. To demonstrate applicability, PDQ was used to detect and characterize superparamagnetic iron oxide-labeled magnetocapsules implanted in porcine liver and suspended in agarose gel. PDQ was also applied to mouse brains infiltrated by MPIO-labeled macrophages following traumatic brain injury; longitudinal, in vivo studies tracked individual MPIO clusters over 3 days, and tracked clusters were corroborated in ex vivo brain scans. Additionally, we applied PDQ to rat hearts infiltrated by MPIO-labeled macrophages in a transplant model of organ rejection. PDQ magnetic measurements were signal-to-noise ratio invariant for images with signal-to-noise ratio > 11. PDQ can be used with conventional gradient-echo pulse sequences, requiring no extra scan time. The method is useful for visualizing biodistribution of cells and theranostic magnetocapsules and for measuring their relative iron content.
authors.affiliation: Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
authors.forename: Parker H
authors.initials: PH
authors.lastname: Mills
authors.forename: T Kevin
authors.initials: TK
authors.lastname: Hitchens
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Foley
authors.forename: Thomas
authors.initials: T
authors.lastname: Link
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Weiss
authors.forename: Joe D
authors.initials: JD
authors.lastname: Thompson
authors.forename: Wesley D
authors.initials: WD
authors.lastname: Gilson
authors.forename: Aravind
authors.initials: A
authors.lastname: Arepally
authors.forename: John A
authors.initials: JA
authors.lastname: Melick
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Chien
authors.initials: C
authors.lastname: Ho
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.forename: Eric T
authors.initials: ET
authors.lastname: Ahrens
mesh_terms: D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media; D003911:Dextrans; D008264:Macrophages / Q000166:cytology*; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D010363:Pattern Recognition, Automated; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10