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  • 1
    Keywords: ANGIOGENESIS ; PERFUSION ; metastases ; CONTRAST-ENHANCED MRI ; MINERAL DENSITY ; LONGITUDINAL IN-VIVO ; FAT-CONTENT
    Abstract: 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.
    Type of Publication: Journal article published
    PubMed ID: 23319721
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  • 2
    Keywords: DISEASE ; metastases ; MUSCLE ; DCE-MRI ; MARROW ; LONGITUDINAL IN-VIVO ; FRACTURES ; VCT
    Abstract: Angiogenesis is pivotal for bone metabolism and bone defect healing. Yet the role of vascularization in osteoporosis and osteoporotic bone repair mechanisms is unclear. Here we investigated effects of osteoporotic phenotype on vascularization during bone defect healing in a rodent osteotomy model using volumetric computed tomography (VCT), dynamic contrast-enhanced VCT (DCE-VCT), dynamic contrast-enhanced MRI (DCE-MRI) and histology. In 16 rats, 8 with physiological bone status (SHAM) and 8 with osteoporotic bone status induced by ovariectomy (OVX) in combination with a vitamin D- and low calcium diet, wedge-shaped defects were created at the left distal femur and stabilized internally by T-shaped miniplate. MRI and VCT were performed in all animals 6 weeks after this procedure. By VCT, relative bone density in the defect was evaluated. Using DCE-VCT and DCE-MRI, parameters associated with regional blood volume were calculated in the bone defect, vicinity of the defect, surrounding muscles and bone marrow: Amplitude A and exchange rate constant Kep (DCE-MRI, respectively) as well as peak enhancement PE and area under the curve AUC (DCE-VCT, respectively). In animals of osteoporotic phenotype, bone density within the osseous defect was significantly reduced as compared to SHAM rats. Vascularization parameters determined by DCE-MRI and DCE-VCT in the defect were significantly elevated compared to the adjacent tissues for both SHAM and OVX groups. However, comparing SHAM and OVX rats, no statistically different values were found by DCE-MRI and DCE-VCT concerning any determined vascularization parameter within the bone defect. Furthermore, parameters of vascularization were increased for OVX as compared to SHAM rats within the bone marrow although significant difference was only found for A. In a rat osteotomy model we showed that at the reparative healing stage, osteoporotic phenotype did influence osteogenic but not angiogenic response within bone defect as imaged by DCE-MRI and DCE-VCT. This study provides insight into the relationship between angiogenesis and osteogenesis during osteoporosis-related compromised bone healing.
    Type of Publication: Journal article published
    PubMed ID: 23522092
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  • 3
    Keywords: radiation ; MRI ; metastases ; COMPUTED-TOMOGRAPHY ; MACHINE ; LONGITUDINAL IN-VIVO ; VCT ; VOLUMETRIC CT
    Abstract: Purpose Cone beam computed tomography (CBCT) has the disadvantage of providing non-quantitative results for bone density determination. The aim of this study is to calibrate CBCT results by using an internal reference (such as muscle) for quantitatively assessing bone density. Methods We developed a new method using the relative attenuation ratio between two nearby materials (such as bone and muscle) for systemic error correction in CBCT that depends on the relative object position in the image volume. Phantom calibration was performed to calculate the acquired attenuation ratio in Hounsfield units (HU), comparable to the results from clinical multislice spiral computed tomography (MSCT). In addition, a small animal study with an osteoporotic rat model was evaluated to show the feasibility of this presented method to quantitatively assess bone density using a CBCT system. Results The phantom study results showed that the calibration process successfully corrected the systemic inaccuracy from CBCT, and the calibrated HU values agreed with the values measured from MSCT. In the small animal study, the quantitative bone densities assessed from the calibrated CBCT results were consistent with the results from MSCT data. Conclusion A practical method to quantitatively estimate attenuation (HU) values for bone tissues from CBCT scans that are comparable to MSCT scans is proposed. The method may improve the quantification ability of CBCT scanning without any additional hardware requirements.
    Type of Publication: Journal article published
    PubMed ID: 23225074
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