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Getting better visualization of joint cartilage through cationic CT contrast agents
September 02, 2009(Boston) In its quest to find new strategies to treat osteoarthritis and other diseases, a Boston University-led research team has reported finding a new computer tomography contrast agent for visualizing the special distributions of glycosaminoglycans (GAGs) - the anionic sugars that account for the strength of joint cartilage.
Assessing the local variations in GAGs are of significant interest for the study of cartilage biology and for the diagnosis of cartilage disease like osteoarthritis, which afflicts more than 27 million in people in the United States
In their research paper, "Effect of Contrast Agent Change on Visualization of Articular Cartilage Using Computer Tomography: Exploiting Electrostatic Interactions for Improved Sensitivity," just published on line in the Journal of the American Chemical Society, they describe new contrast agents that selectively bind to the GAGs in articular cartilage.
Articular or joint cartilage is the smooth hydrated tissue in the ends of bones in load-bearing joints, such as knees, hips and shoulders. The loss of GAGs from these joints is the hallmark of osteoarthritis, a degenerative joint disease in which wear or trauma results in damage to the cartilage surface.
To better see the differentiation between healthy and unhealthy cartilage, contrast agents provide the visual tool to assess GAG content. However, the current contrast agents used with computer tomography or magnetic resonance imaging (MRI) rely on limited diffusion of the anionic or negative ion-charged contrast agents into the target tissue, the study noted.
So researchers hypothesized that cationic contrast agents would be electrostatically attracted to anionic GAGs to provide a more sensitive technique for imaging cartilage. And they focused on using the more widely accessible CT equipment because it can image cartilage and bone simultaneously, enable rapid three-dimensional reconstruction of the tissue and achieve higher spatial resolution over shorter acquisition times compared to MRI systems.
The team synthesized three cationic or positive ion-charged iodine-based X-ray contrast agents. Using the femur of a rabbit, they reported gaining better and more specific images for the cartilage tissue than with current negative ion-charged contrast agents.
"Compared to commercially available contrast agents under the same experimental conditions, these new cationic agents are three times more sensitive for imaging cartilage," said Mark W. Grinstaff, Boston University Professor of Chemistry and Biomedical Engineering who led the team with Brian D. Snyder, MD, Ph.D. an orthopedic surgeon at Children's Hospital and Harvard Medical School.
Snyder noted that the ability to acquire information about localized GAG content, morphology and cartilage thickness on tissue samples will, in the future, aid in the diagnosis and treatment of osteoarthritis.
And while the data presented a compelling case for continued development of cationic CT contrast agents, the research team cautioned that the suitability for in vivo applications remains to be determined, adding that toxicity levels and radiation dosage will be the focus of future studies.
"However, the ability to characterize ex vivo cartilage samples is clearly evident," the study concludes. "Currently obtaining data about the spatial distribution of biochemical components in tissue samples is largely accomplished using histology, which is destructive and time consuming, and thus the use of contrast agents in conjunction with CT imaging will result in readily available, nondestructive alternative to histology."
Boston University Medical Center
Articular or joint cartilage is the smooth hydrated tissue in the ends of bones in load-bearing joints, such as knees, hips and shoulders. The loss of GAGs from these joints is the hallmark of osteoarthritis, a degenerative joint disease in which wear or trauma results in damage to the cartilage surface.
To better see the differentiation between healthy and unhealthy cartilage, contrast agents provide the visual tool to assess GAG content. However, the current contrast agents used with computer tomography or magnetic resonance imaging (MRI) rely on limited diffusion of the anionic or negative ion-charged contrast agents into the target tissue, the study noted.
So researchers hypothesized that cationic contrast agents would be electrostatically attracted to anionic GAGs to provide a more sensitive technique for imaging cartilage. And they focused on using the more widely accessible CT equipment because it can image cartilage and bone simultaneously, enable rapid three-dimensional reconstruction of the tissue and achieve higher spatial resolution over shorter acquisition times compared to MRI systems.
The team synthesized three cationic or positive ion-charged iodine-based X-ray contrast agents. Using the femur of a rabbit, they reported gaining better and more specific images for the cartilage tissue than with current negative ion-charged contrast agents.
"Compared to commercially available contrast agents under the same experimental conditions, these new cationic agents are three times more sensitive for imaging cartilage," said Mark W. Grinstaff, Boston University Professor of Chemistry and Biomedical Engineering who led the team with Brian D. Snyder, MD, Ph.D. an orthopedic surgeon at Children's Hospital and Harvard Medical School.
Snyder noted that the ability to acquire information about localized GAG content, morphology and cartilage thickness on tissue samples will, in the future, aid in the diagnosis and treatment of osteoarthritis.
And while the data presented a compelling case for continued development of cationic CT contrast agents, the research team cautioned that the suitability for in vivo applications remains to be determined, adding that toxicity levels and radiation dosage will be the focus of future studies.
"However, the ability to characterize ex vivo cartilage samples is clearly evident," the study concludes. "Currently obtaining data about the spatial distribution of biochemical components in tissue samples is largely accomplished using histology, which is destructive and time consuming, and thus the use of contrast agents in conjunction with CT imaging will result in readily available, nondestructive alternative to histology."
Boston University Medical Center
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An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the body's skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.
Mending meniscals in children, improving diagnosis and recovery
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UF scientists discover new explanation for controversial old patient-care technique
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'Spaghetti' scaffolding could help grow skin in labs
Scientists are developing new scaffolding technology which could be used to grow tissues such as skin, nerves and cartilage using 3D spaghetti-like structures.
Chinese and American paleontologists discover a new Mesozoic mammal
An international team of paleontologists has discovered a new species of mammal that lived 123 million years ago in what is now the Liaoning Province in northeastern China.
Scientists find obesity alone does not cause arthritis in animals
The link between obesity and osteoarthritis may be more than just the wear and tear on the skeleton caused by added weight.
Diabetes weakens your bones
Current research suggests that the inflammatory molecule TNF-α may contribute to delayed bone fracture healing in diabetics.
New study finds way to stop excessive bone growth following trauma or surgery
A recent United States Army study found that excessive bone growth, also known as heterotopic ossificiation (HO), affects up to 70 percent of soldiers who are severely wounded during combat. A much smaller percentage of the civilian population also suffers from HO following trauma or invasive surgery.
New species of ghostshark from California and Baja California
New species are not just discovered in exotic locales-even places as urban as California still yield discoveries of new plants and animals.
Hormone promises to keep joint injuries from causing long-term osteoarthritis
An existing osteoporosis drug is the first ever found to prevent cartilage loss from osteoarthritis following injury to a joint, and may also regenerate some cartilage that has been lost to osteoarthritis.
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