Application of ex vivo micro-computed tomography for assessment of in vivo fluorescence and plain radiographic imaging for monitoring bone metastases and osteolytic lesions

PURPOSE The study was undertaken to evaluate the effects of dichloromethylene bisphosphonate (Cl2MDP) on osteolytic and osteoblastic bone lesions from a variety of tumoral primary sites and to investigate the in vivo mechanism underlying the action of this drug. PATIENTS AND METHODS Seventy-six patients participated in the current study: 59 had predominantly osteolytic lesions and 17 osteoblastic metastases. Sixteen patients had hypercalcemia. All of the patients received 300 mg of Cl2MDP intravenously (IV) for 7 days and then 200 mg of Cl2MDP intramuscularly (IM) for 14 days. Biochemical parameters were measured in the patients before the start of treatment and 3, 7, 14, and 21 days after beginning treatment. After the withdrawal of parenteral Cl2MDP, 59 patients with predominantly osteolytic lesions were then randomized to receive chemotherapy alone (group A, 29 cases) or chemotherapy plus Cl2MDP given at an oral dose of 1,200 mg/d (group B, 30 cases). RESULTS Serum calcium (Ca), urinary calcium (UCa) phosphate (UPO4), and hydroxyproline (HOP) excretion levels significantly decreased in all patients, whereas no significant changes occurred in serum alkaline phosphatase (AlkPh) and bone Gla-protein (BGP) levels. In 56 patients with painful bone lesions, a progressive analgesic effect was observed mainly between day 7 and day 14. In patients with predominantly osteoblastic metastases, the Cl2MDP treatment led to a more evident hypocalcemia and an increase in both AlkPh and BGP. However, in the majority of these patients the hypocalcemia was corrected by the concurrent use of effective cytotoxic treatments capable of reducing osteoblast stimulation. During 6 months of follow-up, two pathologic fractures occurred in patients of group A, and none occurred in patients of group B. CONCLUSIONS We conclude that Cl2MDP was effective in patients presenting bone metastases with and without hypercalcemia. Care should be taken particularly in those patients with mixed metastases when the sclerotic component is predominant, as the drug may enhance the possibility of hypocalcemia, which is generally corrected by effective cytotoxic drugs. Therefore, Cl2MDP can be considered a valuable support in the treatment of bone metastases.

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Correlation of Micro-Computed Tomography Assessment of Valvular Mineralisation with Histopathological and Immunohistochemical Features of Calcific Aortic Valve Disease

Journal of Clinical Medicine ◽

10.3390/jcm9010029 ◽

2019 ◽

Vol 9 (1) ◽

pp. 29

Author(s):

Guillermo Solache-Berrocal ◽

Ana María Barral-Varela ◽

Sheila Areces-Rodríguez ◽

Alejandro Junco-Vicente ◽

Aitana Vallina-Álvarez ◽

...

Keyword(s):

Computed Tomography ◽

Aortic Valve ◽

Molecular Mechanisms ◽

Soft Tissues ◽

Ex Vivo ◽

Developed Countries ◽

Macrophage Infiltration ◽

Micro Computed Tomography ◽

Calcific Aortic Valve Disease ◽

Calcium Deposits

Aortic valve stenosis is a serious disease with increasing prevalence in developed countries. Research aimed at uncovering the molecular mechanisms behind its main cause, aortic valve calcification, is thus crucial for the development of future therapies. It is frequently difficult to measure the extent of mineralisation in soft tissues and some methods require the destruction of the sample. Micro-computed tomography (µCT), a non-destructive technique, was used to quantify the density and volume of calcium deposits on cusps from 57 explanted aortic valves. Conventional and immunostaining techniques were used to characterise valve tissue degeneration and the inflammatory and osteogenic stage with several markers. Although most of the analysed cusps came from severe stenosis patients, the µCT parameter bone volume/tissue volume ratio distinguished several degrees of mineralisation that correlated with the degree of structural change in the tissue and the amount of macrophage infiltration as determined by CD68 immunohistochemistry. Interestingly, exosomal markers CD63 and Alix co-localised with macrophage infiltration surrounding calcium deposits, suggesting that those vesicles could be produced at least in part by these immune cells. In conclusion, we have shown that the ex vivo assessment of aortic valve mineralisation with µCT reflects the molecular and cellular changes in pathological valves during progression towards stenosis. Thus, our results give additional validity to quantitative μCT as a convenient laboratory tool for basic research on this type of cardiovascular calcification.

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In vivo micro–computed tomography evaluation of BoneCeramic grafted alveolar defects during orthodontic tooth movement

The Angle Orthodontist ◽

10.2319/112315-797.1 ◽

2016 ◽

Cited By ~ 1

Author(s):

Nan Ru ◽

Sean Shih-Yao Liu ◽

Yuxing Bai ◽

Song Li ◽

Yunfeng Liu ◽

...

Keyword(s):

Computed Tomography ◽

Tooth Movement ◽

Orthodontic Tooth Movement ◽

Micro Computed Tomography

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Demineralized bone matrix-based microcarrier scaffold favors vascularized large bone regeneration in vivo in a rat model

Journal of Biomaterials Applications ◽

10.1177/0885328218784370 ◽

2018 ◽

Vol 33 (2) ◽

pp. 182-195 ◽

Cited By ~ 4

Author(s):

Qiannan Li ◽

Wenjie Zhang ◽

Guangdong Zhou ◽

Yilin Cao ◽

Wei Liu ◽

...

Keyword(s):

Computed Tomography ◽

Stem Cells ◽

Bone Marrow ◽

Bone Regeneration ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Matrix Group ◽

Micro Computed Tomography ◽

Demineralized Bone

Insufficient neo-vascularization of in vivo implanted cell-seeded scaffold remains a major bottleneck for clinical translation of engineered bone formation. Demineralized bone matrix is an ideal bone scaffold for bone engineering due to its structural and biochemical components similar to those of native bone. We hypothesized that the microcarrier form of demineralized bone matrix favors ingrowth of vessels and bone regeneration upon in vivo implantation. In this study, a rat model of femoral vessel pedicle-based bone engineering was employed by filling the demineralized bone matrix scaffolds inside a silicone chamber that surrounded the vessel pedicles, and to compare the efficiency of vascularized bone regeneration between microcarrier demineralized bone matrix and block demineralized bone matrix. The results showed that bone marrow stem cells better adhered to microcarrier demineralized bone matrix and produced more extracellular matrices during in vitro culture. After in vivo implantation, microcarrier demineralized bone matrix seeded with bone marrow stem cells formed relatively more bone tissue than block demineralized bone matrix counterpart at three months upon histological examination. Furthermore, micro-computed tomography three-dimensional reconstruction showed that microcarrier demineralized bone matrix group regenerate significantly better and more bone tissues than block demineralized bone matrix both qualitatively and quantitatively (p < 0.05). Moreover, micro-computed tomography reconstructed angiographic images also demonstrated significantly enhanced tissue vascularization in microcarrier demineralized bone matrix group than in block demineralized bone matrix group both qualitatively and quantitatively (p < 0.05). Anti-CD31 immunohistochemical staining of (micro-) vessels and semi-quantitative analysis also evidenced enhanced vascularization of regenerated bone in microcarrier demineralized bone matrix group than in block demineralized bone matrix group (p < 0.05). In conclusion, the microcarrier form of demineralized bone matrix is an ideal bone regenerative scaffold due to its advantages of osteoinductivity and vascular induction, two essentials for in vivo bone regeneration.

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Determination of the Initial Apical Canal Diameter by the First File to Bind or Cone-beam Computed Tomographic Measurements Using Micro-computed Tomography as the Gold Standard: An Ex Vivo Study in Human Cadavers

Journal of Endodontics ◽

10.1016/j.joen.2019.01.020 ◽

2019 ◽

Vol 45 (5) ◽

pp. 619-622 ◽

Cited By ~ 2

Author(s):

Andrea F. Campello ◽

Marília F. Marceliano-Alves ◽

José F. Siqueira ◽

Fábio V. Marques ◽

Fábio R. Guedes ◽

...

Keyword(s):

Computed Tomography ◽

Gold Standard ◽

Ex Vivo ◽

Cone Beam ◽

Micro Computed Tomography ◽

Computed Tomographic ◽

Canal Diameter ◽

Human Cadavers ◽

Ex Vivo Study

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Intraosteal Behavior of Porous Scaffolds: The mCT Raw-Data Analysis as a Tool for Better Understanding

Symmetry ◽

10.3390/sym11040532 ◽

2019 ◽

Vol 11 (4) ◽

pp. 532 ◽

Cited By ~ 1

Author(s):

Parrilla-Almansa ◽

González-Bermúdez ◽

Sánchez-Sánchez ◽

Meseguer-Olmo ◽

Martínez-Cáceres ◽

...

Keyword(s):

Computed Tomography ◽

Mathematical Analysis ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Hounsfield Unit ◽

In Vivo Studies ◽

Porous Scaffolds ◽

Micro Computed Tomography ◽

Radiological Analysis

The aim of the study is to determine the existing correlation between high-resolution 3D imaging technique obtained through Micro Computed Tomography (mCT) and histological-histomorphometric images to determine in vivo bone osteogenic behavior of bioceramic scaffolds. A Ca-Si-P scaffold ceramic doped and non-doped (control) with a natural demineralized bone matrix (DBM) were implanted in rabbit tibias for 1, 3, and 5 months. A progressive disorganization and disintegration of scaffolds and bone neoformation occurs, from the periphery to the center of the implants, without any differences between histomorphometric and radiological analysis. However, significant differences (p < 0.05) between DMB-doped and non-doped materials where only detected through mathematical analysis of mCT. In this way, average attenuation coefficient for DMB-doped decreased from 0.99 ± 0.23 Hounsfield Unit (HU) (3 months) to 0.86 ± 0.32 HU (5 months). Average values for non-doped decreased from 0.86 ± 0.25 HU (3 months) to 0.66 ± 0.33 HU. Combination of radiological analysis and mathematical mCT seems to provide an adequate in vivo analysis of bone-implanted biomaterials after surgery, obtaining similar results to the one provided by histomorphometric analysis. Mathematical analysis of Computed Tomography (CT) would allow the conducting of long-term duration in vivo studies, without the need for animal sacrifice, and the subsequent reduction in variability.

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