Quantitative assessment of microcirculation and diffusion in the bone marrow of osteoporotic rats using VCT, DCE-MRI, DW-MRI, and histology
Quantitative assessment of microcirculation and diffusion in the bone marrow of osteoporotic rats using VCT, DCE-MRI, DW-MRI, and histology
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DOI：
10.1258/ar.2012.120508
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发表时间：
2013-03-01
期刊：
影响因子：
1.3
通讯作者：
Baeuerle, Tobias
中科院分区：
文献类型：
--
作者：
Liu, Yifei;Cao, Liji;Baeuerle, Tobias
背景资料：功能性骨髓过程的病因学和病理生理学作用尚未完全了解，特别是在骨质疏松症的情况下。目的：通过骨、骨髓和特别是微循环的非侵入性体内成像和侵入性离体成像之间的交叉相关性，研究骨质疏松症大鼠模型中血管化和扩散的作用。材料和方法：通过卵巢切除术（OVX）联合钙和维生素D3缺乏或糖皮质激素（地塞米松）诱导大鼠骨质疏松症。为了比较，对照组进行假手术。在体内研究中，在术后1、3或12个月时通过体积CT（VCT）和MRI检查动物（n = 36）。采用VCT监测骨盆骨形态，提取骨盆内相对骨密度r。使用DCE-MRI和DW-MRI，获取腰椎、骨盆和股骨区域的参数A（振幅）、Kep（汇率常数）和ADC（表观扩散系数）。在离体研究中，选择骨盆的组织切片用苏木精和伊红染色，（HE染色）用于定量血管大小和密度，或对IV型胶原和α-平滑肌肌动蛋白进行免疫染色以评估血管成熟度（SMA/胶原IV比率）。12个月后，DCE-MRI参数Kep在所有位置均降低（在股骨和腰椎中最强），而对于参数A和DW-MRI参数ADC没有观察到显著差异。此外，在组织学水平上观察到血管稀疏和成熟的动物具有血管化表型。特别是在骨盆中，骨质疏松症的个人（不论骨质疏松症诱导剂）表现出降低的Kep，血管密度显着降低，血管成熟度显着增加，以及统计学上不变的A，ADC，和vessel difficulties.Conclusion：微循环的变化，但不扩散的骨质疏松症大鼠骨髓中检测到的DCE-MRI和DW-MRI由于血管稀疏和成熟。
Background: Etiologic and pathophysiologic role of functional bone marrow processes is not fully understood especially in the case of osteoporosis.Purpose: 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.Material and 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 alpha-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.Conclusion: 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.