Technology
Although microCT studies can provide images with isotropic spatial resolutions approaching 5 to 10 microns, the interpretation of anatomical features on such thin tomographic slices can be compromised by a lack of soft tissue contrast. In addition, comparatively long acquisition times necessary to overcome motion artifacts can preclude the use of standard water soluble iodinated contrast media.
Because of their comparatively long and stable in vivo residence times, Fenestra imaging agents can overcome these inherent limitations and reveal anatomy and function in a wide range of microCT imaging applications. Fenestra agents are comprised of contrast-enhancing iodinated lipids that are integrated into a novel oil-in-water lipid emulsion that selectively localizes the lipids to various sites within the body. Prolonged contrast enhancement of the entire hepatobiliary system is possible from a single intravenous administration of Fenestra LC, while the intravascular formulation of Fenestra VC provides superior vascular characterization.
Fenestra LC
Fenestra LC provides visualization of the entire hepatobiliary system by exploiting the endogenous lipid metabolism pathways present in the body. Chylomicron remnants (CMR) represent a class of naturally-occurring plasma lipoproteins that selectively shuttle lipids to hepatocytes in the liver. Fenestra LC mimics CMR particles and thereby localizes the contrast-producing lipids it contains to the hepatic parenchyma following intravenous administration. Because the metabolic status of extracellular and intracellular liver lipases determines the uptake and clearance profiles of the lipid molecules, Fenestra LC provides the ability to assess hepatobiliary anatomy and liver function. In normal animals, hepatic contrast enhancement lasts for up to several hours after injection. Moreover, since the contrast-carrying metabolites of Fenestra LC are eliminated into the bile, image enhancement of the gastrointestinal tract is possible as well.
Fenestra LC can be used to:
- Detect, stage, and monitor primary and metastatic focal lesions in the hepatobiliary system.
- Detect, characterize, and monitor parenchymal liver diseases such as hepatitis, fibrosis, steatosis, and cirrhosis, as well as therapeutic efficacy against these diseases.
- Assess the efficacy of pharmacological, surgical, radiological, and ablative therapies against lesions in the hepatobiliary system.
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| Before injecting Fenestra LC (left image), the abdominal organs of a mouse are indistinguishable. After Fenestra LC injection (center and right images), the boundaries of the contrast-enhanced liver tissue are revealed. The transversal view of a female CD1 mouse, image on the right, courtesy of Dr. André Constantinesco and Dr. Philippe Choquet, Service de Biophysique et Médecine Nucléaire, Hôpitaux Universitaires de Strasbourg, CHU Hautpierre. |
Fenestra VC
Fenestra VC is a refined version of Fenestra LC in which the surface of the lipid emulsion particles is modified to alter recognition of the particle by the receptors on the hepatocytes that are responsible for uptake into the liver. This delayed uptake produces contrast enhancement of the entire vascular system that can last for several hours. Fenestra VC remains intravascular as long as the endothelial integrity of the vessel is maintained. Like its liver-selective counterpart, Fenestra VC is eventually metabolized and eliminated through the hepatobiliary system.
Fenestra VC can be used to:
- Visualize the blood vasculature for extended periods of time at sub-millimeter resolution.
- Visualize and quantify the therapeutic efficacy of drugs modulating anti-angiogenesis, stroke, atherosclerosis or other conditions with a vascular component to their etiology.
- Confirm manipulations of organs or tissues, including cell implantations, ablative procedures, and local drug delivery.
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| Coronal, sagittal, and longitudinal views of a CD-1 Nude mouse 20 minutes after tail vein injection of 400 ul of Fenestra VC. Images obtained on a SkyScan 1076 microCT scanner. Note that contrast enhancement provided by Fenestra helps distinguish heart chambers and major blood vessels. |
Hepatic Imaging with Fenestra VC
Since all Fenestra imaging agents are metabolized and eliminated through the hepatobiliary system, both Fenestra LC and VC can be used as hepatic contrast enhancement agents. Compared to Fenestra LC, which accumulates rapidly in the liver after administration, Fenestra VC will only accumulate in the hepatic parenchyma several hours after injection.
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| Axial scans of a female rat obtained at 10 minutes, 6 hours, and 24 hours after intravascular administration of Fenestra VC at 15 ml/kg. At 10 minutes, the aorta and inferior vena cava, as well as major vessels traversing diagonally through the liver, are contrast enhanced. At 6 hours, the axial image shows the aorta and inferior vena cava, as well as small vessels. Increased enhancement is observed in the liver due to the elimination of the contrast agent. At 24 hours, the liver is significantly enhanced due to the accumulation of metabolites as the contrast agent undergoes hepatobiliary elimination. The aorta and inferior vena cava, as well as hepatic vasculature, become visible due to the negative contrast effect. |