scholarly journals PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charmainne Cruje ◽  
P. Joy Dunmore-Buyze ◽  
Eric Grolman ◽  
David W. Holdsworth ◽  
Elizabeth R. Gillies ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Soft Tissues ◽  
Three Dimensional ◽  
Blood Pool ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Poly Ethylene

AbstractVascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

scholarly journals X-ray-based virtual slicing of TB-infected lungs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana Ortega-Gil ◽  
Juan José Vaquero ◽  
Mario Gonzalez-Arjona ◽  
Joaquín Rullas ◽  
Arrate Muñoz-Barrutia
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
3D Visualization ◽  
Post Mortem ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Preclinical Research ◽  
X Ray ◽  
The Right

AbstractHollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray–based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.

scholarly journals Dual-energy micro-CT of the rodent lung

2012 ◽  
Vol 302 (10) ◽  
pp. L1088-L1097 ◽  
Author(s):  
C. T. Badea ◽  
X. Guo ◽  
D. Clark ◽  
S. M. Johnston ◽  
C. D. Marshall ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Vascular Tissue ◽  
Ex Vivo ◽  
Respiratory Gating ◽  
Three Dimensional ◽  
Dual Energy ◽  
Volume Estimation ◽  
Micro Ct ◽  
Micro Computed Tomography

The purpose of this work is to investigate the use of dual-energy micro-computed tomography (CT) for the estimation of vascular, tissue, and air fractions in rodent lungs using a postreconstruction three material decomposition method. Using simulations, we have estimated the accuracy limits of the decomposition for realistic micro-CT noise levels. Next, we performed experiments involving ex vivo lung imaging in which intact rat lungs were carefully removed from the thorax, injected with an iodine-based contrast agent, and then inflated with different volumes of air ( n = 2). Finally, we performed in vivo imaging studies in C57BL/6 mice ( n = 5) using fast prospective respiratory gating in end inspiration and end expiration for three different levels of positive end expiratory pressure (PEEP). Before imaging, mice were injected with a liposomal blood pool contrast agent. The three-dimensional air, tissue, and blood fraction maps were computed and analyzed. The results indicate that separation and volume estimation of the three material components of the lungs are possible. The mean accuracy values for air, blood, and tissue were 93, 93, and 90%, respectively. The absolute accuracy in determining all fraction materials was 91.6%. The coefficient of variation was small (2.5%) indicating good repeatability. The minimum difference that we could detect in material fractions was 15%. As expected, an increase in PEEP levels for the living mouse resulted in statistically significant increases in air fractions at end expiration but no significant changes at end inspiration. Our method has applicability in preclinical pulmonary studies where changes in lung structure and gas volume as a result of lung injury, environmental exposures, or drug bioactivity would have important physiological implications.

scholarly journals Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
In Vitro Experiments ◽  
Mri Contrast ◽  
In Vivo Experiments ◽  
Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

scholarly journals In Vivo Quantification of Myocardial Infarction in Mice Using Micro-CT and a Novel Blood Pool Agent

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Stefan Sawall ◽  
Danielle Franke ◽  
Anne Kirchherr ◽  
Jan Beckendorf ◽  
Jan Kuntz ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Contrast Agent ◽  
Infarct Size ◽  
Blood Pool ◽  
Signal Enhancement ◽  
Imaging Method ◽  
Micro Ct ◽  
Contrast Agent Injection ◽  
Dependent Signal

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation (R2=0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

scholarly journals The Characteristics of Vascular Growth in VX2 Tumor Measured by MRI and Micro-CT

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
X.-L. Qi ◽  
J. Liu ◽  
P. N. Burns ◽  
G. A. Wright
Keyword(s):  
Volume Fraction ◽  
Tumor Model ◽  
Response To Therapy ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Tumor Vascularity ◽  
Vx2 Tumor ◽  
Relative Blood Volume

Blood supply is crucial for rapid growth of a malignant tumor; medical imaging can play an important role in evaluating the vascular characterstics of tumors. Magnetic resonance imaging (MRI) and micro-computed tomography (CT) are able to detect tumors and measure blood volumes of microcirculation in tissue. In this study, we used MR imaging and micro-CT to assess the microcirculation in a VX2 tumor model in rabbits. MRI characterization was performed using the intravascular contrast agent Clariscan (NC100150-Injection); micro-CT with Microfil was used to directly depict blood vessels with diameters as low as 17 um in tissue. Relative blood volume fraction (rBVF) in the tumor rim and blood vessel density (rBVD) over the whole tumor was calculated using the two imaging methods. Our study indicates that rBVF is negatively related to the volume of the tumor measured by ultrasound (R=0.90). rBVF in the tissue of a VX2 tumor measured by MRIin vivowas qualitatively consistent with the rBVD demonstrated by micro-CTin vitro(R=0.97). The good correlation between the two methods indicates that MRI studies are potentially valuable for assessing characteristics or tumor vascularity and for assessing response to therapy noninvasively.

scholarly journals Investigating PEGDA and GelMA Microgel Models for Sustained 3D Heterotypic Dermal Papilla and Keratinocyte Co-Cultures

2021 ◽  
Vol 22 (4) ◽  
pp. 2143 ◽  
Author(s):  
Justin J.Y. Tan ◽  
Duc-Viet Nguyen ◽  
John E. Common ◽  
Chunyong Wu ◽  
Paul C.L. Ho ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Three Dimensional ◽  
Dermal Papilla ◽  
Glycol Diacrylate ◽  
Prolonged Duration ◽  
Culture Models ◽  
Poly Ethylene

Hair follicle morphogenesis is heavily dependent on reciprocal, sequential, and epithelial-mesenchymal interaction (EMI) between epidermal stem cells and the specialized cells of the underlying mesenchyme, which aggregate to form the dermal condensate (DC) and will later become the dermal papilla (DP). Similar models were developed with a co-culture of keratinocytes and DP cells. Previous studies have demonstrated that co-culture with keratinocytes maintains the in vivo characteristics of the DP. However, it is often challenging to develop three-dimensional (3D) DP and keratinocyte co-culture models for long term in vitro studies, due to the poor intercellular adherence between keratinocytes. Keratinocytes exhibit exfoliative behavior, and the integrity of the DP and keratinocyte co-cultured spheroids cannot be maintained over prolonged culture. Short durations of culture are unable to sufficiently allow the differentiation and re-programming of the keratinocytes into hair follicular fate by the DP. In this study, we explored a microgel array approach fabricated with two different hydrogel systems. Using poly (ethylene glycol) diacrylate (PEGDA) and gelatin methacrylate (GelMA), we compare their effects on maintaining the integrity of the cultures and their expression of important genes responsible for hair follicle morphogenesis, namely Wnt10A, Wnt10B, and Shh, over prolonged duration. We discovered that low attachment surfaces such as PEGDA result in the exfoliation of keratinocytes and were not suitable for long-term culture. GelMA, on the hand, was able to sustain the integrity of co-cultures and showed higher expression of the morphogens overtime.

scholarly journals Deferoxamine Reduces Inflammation and Osteoclastogenesis in Avulsed Teeth

2021 ◽  
Vol 22 (15) ◽  
pp. 8225
Author(s):  
Ko Eun Lee ◽  
Mijeong Jeon ◽  
Seunghan Mo ◽  
Hyo-Seol Lee ◽  
Je Seon Song ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Alveolar Bone ◽  
Root Surface ◽  
Tartrate Resistant Acid Phosphatase ◽  
Micro Ct ◽  
Sprague Dawley ◽  
Micro Computed Tomography ◽  
Model Cell

Replacement and inflammatory resorption are serious complications associated with the delayed replantation of avulsed teeth. In this study, we aimed to assess whether deferoxamine (DFO) can suppress inflammation and osteoclastogenesis in vitro and attenuate inflammation and bone resorption in a replanted rat tooth model. Cell viability and inflammation were evaluated in RAW264.7 cells. Osteoclastogenesis was confirmed by tartrate-resistant acid phosphatase staining, reactive oxygen species (ROS) measurement, and quantitative reverse transcriptase–polymerase chain reaction in teeth exposed to different concentrations of DFO. In vivo, molars of 31 six-week-old male Sprague–Dawley rats were extracted and stored in saline (n = 10) or DFO solution (n = 21) before replantation. Micro-computed tomography (micro-CT) imaging and histological analysis were performed to evaluate inflammation and root and alveolar bone resorption. DFO downregulated the genes related to inflammation and osteoclastogenesis. DFO also reduced ROS production and regulated specific pathways. Furthermore, the results of the micro-CT and histological analyses provided evidence of the decrease in inflammation and hard tissue resorption in the DFO group. Overall, these results suggest that DFO reduces inflammation and osteoclastogenesis in a tooth replantation model, and thus, it has to be further investigated as a root surface treatment option for an avulsed tooth.

scholarly journals 4-D Micro-CT of the Mouse Heart

2005 ◽  
Vol 4 (2) ◽  
pp. 153535002005041 ◽  
Author(s):  
Cristian T. Badea ◽  
Boma Fubara ◽  
Laurence W. Hedlund ◽  
G. Allan Johnson
Keyword(s):  
Cardiac Function ◽  
Contrast Agent ◽  
Blood Pool ◽  
Kidney Cortex ◽  
Mouse Heart ◽  
Micro Ct ◽  
Maximum Enhancement ◽  
Functional Studies ◽  
Iodinated Contrast

Purpose: Demonstrate noninvasive imaging methods for in vivo characterization of cardiac structure and function in mice using a micro-CT system that provides high photon fluence rate and integrated motion control. Materials and Methods: Simultaneous cardiac- and respiratory-gated micro-CT was performed in C57BL/6 mice during constant intravenous infusion of a conventional iodinated contrast agent (Isovue-370), and after a single intravenous injection of a blood pool contrast agent (Fenestra VC). Multiple phases of the cardiac cycle were reconstructed with contrast to noise and spatial resolution sufficient for quantitative assessment of cardiac function. Results: Contrast enhancement with Isovue-370 increased over time with a maximum of ~500 HU (aorta) and 900 HU (kidney cortex). Fenestra VC provided more constant enhancement over 3 hr, with maximum enhancement of ~620 HU (aorta) and ~90 HU (kidney cortex). The maximum enhancement difference between blood and myocardium in the heart was ~250 HU for Isovue-370 and ~500 HU for Fenestra VC. In mice with Fenestra VC, volumetric measurements of the left ventricle were performed and cardiac function was estimated by ejection fraction, stroke volume, and cardiac output. Conclusion: Image quality with Fenestra VC was sufficient for morphological and functional studies required for a standardized method of cardiac phenotyping of the mouse.

scholarly journals Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Justin J. Tse ◽  
P. Joy Dunmore-Buyze ◽  
Maria Drangova ◽  
David W. Holdsworth
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Spectral Band ◽  
Small Animal ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Preclinical Research ◽  
X Ray ◽  
Tissue Specimens ◽  
X Ray Absorption

Micro-computed tomography (micro-CT) facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone). Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV). We have developed a high-atomic number lanthanide (erbium) contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter < 50 nm) suspended in a two-part silicone elastomer produce a perfusable fluid with viscosity of 19.2 mPa-s. Ultrasonic cavitation was used to reduce aggregate sizes to <70 nm. Postmortem intact mice were perfused to investigate the efficacy of contrast agent. The observed vessel contrast was >4000 Hounsfield units, and perfusion of vessels < 10 μm in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium’s K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases.

Molybdenum Dioxide (MoS2)/Gadolinium (Gd) Containing Arginine-Glycine-Aspartic Acid (RGD) Sequences as New Nano-Contrast Agent for Cancer Magnetic Resonance Imaging (MRI)

2021 ◽  
Vol 21 (3) ◽  
pp. 1403-1412
Author(s):  
Xiaoguang Hao ◽  
Weijing Li
Keyword(s):  
Particle Size ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Aspartic Acid ◽  
Nude Mice ◽  
Molybdenum Dioxide ◽  
Signal Value ◽  
Arginine Glycine Aspartic Acid

Molybdenum dioxide-gadolinium-arginine/glycine/aspartic acid (MoS2-Gd-RGD) sequences targeting nano-contrast agents that specifically bind to human hepatocellular carcinoma (HCC) HepG2 cells were synthesized, and their targeting imaging effects on HCC cells and models were evaluated. Zeta potential, particle size and Fourier Transform Infrared Spectrometer (FTIR) were used to characterize the nano-contrast agent, and its cytotoxicity was evaluated. The MoS2-Gd nanoparticles were used as control in vitro to determine the targeting capability of the MoS2-Gd-RGD nanoparticles toward integrin αvβ3. During in vivo animal experiments, 12 nude mice with tumors were randomly divided into three groups to compare the imaging effects of the MoS2-Gd-RGD and MoS2-Gd groups. The hydrodynamic diameter of MoS2-Gd-RGD nanoparticles was approximately 336.43±6.43 nm, and the polydispersity index (PDI) value reached 0.132. Transmission electron microscopy showed the uniform particle size and good dispersion of the nanoparticles. The relaxation rate totaled 1.39 mM−1S−1. The signal value of the T1-weighted image of the HepG2 cells treated with MoS2-Gd-RGD was higher than that of the non-targeted materials (MoS2-Gd) (P < 0.01). The signal value of the tumor increased significantly 15 min after the tail vein injection with MoS2-Gd-RGD, and it peaked at 60 min after injection. A significant difference in tumor signal values was observed between the two groups of nude mice injected with MoS2-Gd-RGD and MoS2- Gd (P < 0.01). At the in vitro and in vivo experiments, the MoS2-Gd-RGD nanoparticles presented the characteristics of integrin αvβ3 targeting. Thus, MoS2-Gd-RGD nanoparticles feature potential as contrast agents for MRI.

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