title: Quantitative assessment of microcirculation and diffusion in the bone marrow of osteoporotic rats using VCT, DCE-MRI, DW-MRI, and histology.
abstract: BACKGROUND
  Etiologic and pathophysiologic role of functional bone marrow processes is not fully understood especially in the case of osteoporosis.
  
  
  OBJECTIVE
  To investigate the role of vascularization and diffusion in rat models of osteoporosis through a cross-correlation between non-invasive in-vivo imaging and invasive ex-vivo imaging of bone, bone marrow, and in particular of microcirculation.
  
  
  METHODS
  Osteoporosis was induced in rats by combining ovariectomy (OVX) with calcium and Vitamin D3 deficiency, or with glucocorticoid (dexamethasone). For comparison, controls underwent a sham surgery. In in-vivo investigations, animals (n = 36) were examined by volumetric CT (VCT) and MRI at 1, 3, or 12 months post surgery. Using VCT, bone morphology was monitored and relative bone density r within pelvis was extracted. With DCE-MRI and DW-MRI, parameters A (amplitude), Kep (exchange rate constant), and ADC (apparent diffusion coefficient) were acquired for regions of lumbar vertebrae, pelvis, and femur. In ex-vivo investigations, selective histological sections of pelvis were either stained with hematoxylin and eosin (HE stain) for quantifying vessel size and density or immunostained for collagen IV and α-smooth muscle actin to assess vessel maturity (SMA/collagen IV ratio).
  
  
  RESULTS
  After 12 months, decrease in DCE-MRI parameter Kep was found in all locations of osteoporotic rats (strongest in femur and lumbar vertebrae) while no significant differences were seen for parameter A and DW-MRI parameter ADC. Furthermore, vessel rarefication and maturation were observed on the histological level in animals with osteoporotic phenotype. In particular in the pelvis, the osteoporotic individuals (irrespective of the osteoporosis inducers applied) exhibited decreased Kep, significantly reduced vessel density, significantly increased vessel maturity, as well as statistically unaltered A, ADC, and vessel diameter.
  
  
  CONCLUSIONS
  Changes in microcirculation but not diffusion in the bone marrow of osteoporotic rats are detected by DCE-MRI and DW-MRI due to vessel rarefication and maturation.
authors: Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.
authors: Yifei
authors: Y
authors: Liu
authors: Liji
authors: L
authors: Cao
authors: Jens
authors: J
authors: Hillengass
authors: Stefan
authors: S
authors: Delorme
authors: Gudrun
authors: G
authors: Schlewitz
authors: Parameswari
authors: P
authors: Govindarajan
authors: Reinhard
authors: R
authors: Schnettler
authors: Christian
authors: C
authors: Heiss
authors: Tobias
authors: T
authors: Bäuerle
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000098:blood supply*; D054893:Cone-Beam Computed Tomography; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006614:Hindlimb; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008833:Microcirculation; D010024:Osteoporosis / Q000378:metabolism / Q000503:physiopathology*; D010384:Pelvic Bones; D051381:Rats; D017207:Rats, Sprague-Dawley