title: Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche.
abstract: The bone marrow (BM) undergoes extensive remodeling following irradiation damage. A crucial part of restoring homeostasis following irradiation is the ability of hematopoietic stem cells (HSCs) to home to and engraft specialized niches within the BM through a remodeling BM vascular system. Here we show that a combination of ultra-high-field strength magnetic resonance imaging (17.6 T, MRI) coupled with fluorescent microscopy (FLM) serves as a powerful tool for the in vivo imaging of cell homing within the BM. Ultra-high-field MRI can achieve high-resolution three-dimensional (3D) images (28 × 28 × 60 μm(3)) of the BM in live mice, sufficient to resolve anatomical changes in BM microstructures attributed to radiation damage. Following intra-arterial infusion with dsRed-expressing BM cells, labeled with superparamagnetic iron oxides, both FLM and MRI could be used to follow initial homing and engraftment of donor HSC to a limited number of preferred sites within a few cell diameters of the calcified bone-the endosteal niche. Subsequent histology confirmed the fidelity and accuracy of MRI to create non-invasive, high-resolution 3D images of donor cell engraftment of the BM in living animals at the level of single-cell detection.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Bengtsson
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: G A
authors.initials: GA
authors.lastname: Walter
authors.forename: E W
authors.initials: EW
authors.lastname: Scott
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002465:Cell Movement; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D055153:Stem Cell Niche / Q000166:cytology*