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

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.

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana Ortega-Gil ◽  
Juan José Vaquero ◽  
Mario Gonzalez-Arjona ◽  
Joaquín Rullas ◽  
Arrate Muñoz-Barrutia

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.


2008 ◽  
Vol 1074 ◽  
Author(s):  
Yoshio Kobayashi ◽  
Kiyoto Misawa ◽  
Motohiro Takeda ◽  
Noriaki Ohuchi ◽  
Atsuo Kasuya ◽  
...  

ABSTRACTIodine compounds have been used as X-ray contrast agents in the field of medicine, because of their low transmittance property for X-ray. The iodine compounds may provoke adverse events as allergic reactions in patients, so that they can not be administered to such people. Core-shell nanoparticles are good candidates for prevention of allergic reactions, because the shell materials can keep the contrast agents from living systems. We have proposed a method for silica-coating of iodine compounds as AgI nanoparticles. In the present work, properties of the silica-coated AgI nanoparticles such as colloidal stability, X-ray absorption and X-ray CT imaging were examined.Silica-coated AgI nanoparticles were prepared with Stöber method, which was performed with 2.3×10-5 M MPS, 11 M water, 0.01 M DMA and 0.01 M tetraethyl orthosilicate in the presence of 5×10-4 M AgI nanoparticles that were prepared from AgClO4 and KI. The particles had an AgI core size of ca. 15 nm and a silica shell thickness of ca. 20 nm.Since high iodine concentration in sample solution is desired for practical use as X-ray contrast agents, the colloid of as-prepared coated particles was concentrated with centrifugation. The particle colloid that was concentrated up to an AgI concentration as high as 0.4 M was colloidally stable in saline, and exhibited properties of X-ray absorption and X-ray contrasting comparable to a commercial X-ray contrast agent. Accordingly, the silica-coated AgI nanoparticles prepared in the present work are expected to be applied to a novel X-ray contrast agent.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charmainne Cruje ◽  
P. Joy Dunmore-Buyze ◽  
Eric Grolman ◽  
David W. Holdsworth ◽  
Elizabeth R. Gillies ◽  
...  

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.


Author(s):  
Mohammadreza Fouladi ◽  
Kamran Gholami ◽  
Hossein Ghadiri

X-ray Computed Tomography (CT), e.g. clinical CT scanners, basically provides Linear Attenuation Coefficients (LACs) of objects under study by the means of algorithmic reconstruction of acquired views of attenuated X-ray passing through the samples in different angles around the imaged sample. Micro Computed Tomography (micro-CT) basically works the same as clinical CT. It provides volumetric information representing the inner structure of objects with a resolution in the micron range. LOTUS-inVivo is a micro-CT scanner dedicated to imaging of small animals and ex-vivo biological samples. In the present study the spatial resolution and Low Contrast Detectability (LCD) of LOTUS-inVivo scanner were evaluated using standard phantoms. We aimed to prove the capability of LOTUS-inVivo for small animal and ex-vivo biological samples imaging using the measured image quality parameters, i.e. spatial resolution and low contrast detectability. By the means of analysis of bar and LCD phantom images, the limiting resolution of LOTUS-inVivo micro-CT scanner was measured about 2.7 µm and has been shown that it’s capable of resolving sizes greater than 12.5 µm. Also, we concluded that LOTUS-inVivo is capable of discriminating tissues with 3% differences in contrast relative to the background, for 1 mm bar size. Thus, the provided technical characteristics in this study have made LOTUS-inVivo as a suitable tool for small animal imaging.


2018 ◽  
Vol 314 (3) ◽  
pp. F493-F499 ◽  
Author(s):  
Ruslan Hlushchuk ◽  
Cédric Zubler ◽  
Sébastien Barré ◽  
Carlos Correa Shokiche ◽  
Laura Schaad ◽  
...  

In the last decades, the contrast-enhanced micro-computed tomography (micro-CT) imaging of a whole animal kidney became increasingly important. The visualization was mainly limited to middle-sized vessels. Since modern desktop micro-CT scanners provide the necessary detail resolution, we developed an approach for rapid visualization and consistent assessment of kidney vasculature and glomeruli number. This method is based on μAngiofil, a new polymerizing contrast agent with homogenous X-ray absorption, which provides continuous filling of the complete vasculature and enables correlative imaging approaches. For rapid and reliable kidney morphometry, the microangio-CT (µaCT) data sets from glial cell line-derived neurotrophic factor (GDNF)+/− mice and their wild-type littermates were used. The results were obtained much faster compared with the current gold standard, histology-based stereology, and without processing artifacts. The histology-based morphometry was done afterward on the same kidneys. Both approaches revealed that the GDNF+/− male mice had about 40% fewer glomeruli. Furthermore, our approach allows for the definition of sites of interest for further histological investigation, i.e., correlative morphology. The polymerized μAngiofil stays in perfused vessels and is autofluorescent, which is what greatly facilitates the matching of histological sections with µaCT data. The presented approach is a time-efficient, reliable, qualitative, and quantitative methodology. Besides glomerular morphometry, the µaCT data can be used for qualitative and quantitative analysis of the kidney vasculature and correlative morphology.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yuhui Chen ◽  
He Cao ◽  
Dawei Sun ◽  
Changxin Lin ◽  
Liang Wang ◽  
...  

Bone fracture is a global healthcare issue for high rates of delayed healing and nonunions. Although n-3 polyunsaturated fatty acid (PUFA) is considered as a beneficial factor for bone metabolism, only few studies till date focused on the effects of n-3 PUFAs on fracture healing. In this study, we investigated the effect of endogenous n-3 PUFAs on fracture healing by measuring femur fracture repair in bothfat-1transgenic mice and WT mice. Proximal femoral fracture model was established infat-1transgenic mice and WT mice, respectively, and then the fracture was analyzed by using X-ray, micro-computed tomography (micro-CT), and histological assessment at 7, 14, 21, 28, and 35 days after fixation. The results showed that compared with WT mice,fat-1mice exhibited acceleration in fracture healing through radiographic and histological analysis (18–21 days versus 21–28 days postfracture). Meanwhile, X-ray and micro-CT analysis that showed better remodeling callus formation were in thefat-1group compared to WT group. Furthermore, histological analysis revealed that endogenous n-3 PUFAs promoted local endochondral ossification and accelerated the remodeling of calcified calluses after fracture. In conclusion, the present study indicated that endogenously produced n-3 PUFAs promote fracture healing process and accelerate bone remodeling in mice, and supplementation of n-3 PUFAs was positively associated with fracture healing.


2019 ◽  
Vol 26 (4) ◽  
pp. 1322-1329 ◽  
Author(s):  
Lorella Pascolo ◽  
Gabriela Sena ◽  
Alessandra Gianoncelli ◽  
Alice Cernogoraz ◽  
Geroge Kourousias ◽  
...  

Laboratory and synchrotron X-ray tomography are powerful tools for non-invasive studies of biological samples at micrometric resolution. In particular, the development of phase contrast imaging is enabling the visualization of sample details with a small range of attenuation coefficients, thus allowing in-depth analyses of anatomical and histological structures. Reproductive medicine is starting to profit from these techniques, mainly applied to animal models. This study reports the first imaging of human ovarian tissue where the samples consisted of surgically obtained millimetre fragments, properly fixed, stained with osmium tetroxide and included in epoxydic resin. Samples were imaged by the use of propagation phase contrast synchrotron radiation micro-computed tomography (microCT), obtained at the SYRMEP beamline of Elettra light source (Trieste, Italy), and X-ray absorption microCT at the Theoretical Biology MicroCT Imaging Laboratory in Vienna, Austria. The reconstructed microCT images were compared with the soft X-ray absorption and phase contrast images acquired at the TwinMic beamline of Elettra in order to help with the identification of structures. The resulting images allow the regions of the cortex and medulla of the ovary to be distinguished, identifying early-stage follicles and visualizing the distribution of blood vessels. The study opens to further application of micro-resolved 3D imaging to improve the understanding of human ovary's structure and support diagnostics as well as advances in reproductive technologies.


2016 ◽  
Vol 27 (9) ◽  
pp. 805-823 ◽  
Author(s):  
Livia Elena Crica ◽  
Jonas Wengenroth ◽  
Hanna Tiainen ◽  
Mariana Ionita ◽  
Håvard Jostein Haugen

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