Radiopague Indicators Of Physiological Spaces And Processes

Essentially all current X-ray micro-CT scanners, like clinical CT scanners, use the attenuation of the X-ray by tissues as the signal for generating the X-ray images. In micro-CT scanners, this means that for a given X-ray photon energy the contrast signal is most closely related to the atomic number (Z) and the concentration of that element (45). At the X-ray exposures tolerated by living tissues, this means that the signal-to-noise in the CT image is adequate primarily for differentiating air, fatty tissue (e.g., brain white matter), non fatty tissue [e.g., muscle, brain gray matter (46)], and bone [in which

Diagram Pulmonary Artery Wedge

Figure 2 Illustration of function deducible from micro-CT imaged anatomic micro-schematic. The upper two panels are of the pulmonary arterial tree of a rat left control and right with monocrotaline-induced pulmonary hypertension. The greatly narrowed lumen diameters (right panel ) translate to changes in arterial resistance that can be computed from the arterial tree branching geometry. The lower panels relate to measurement of myocardial fiber direction as a function of transmural location in the LV heart wall. The left shows a short axis CT image of a rat heart and the labeled panels around it are images of transmural and tangential sections through heart wall computed from the 3D image of the heart. The right-most shows the fiber direction as a function of transmural location. This information allows analysis of regional wall stresses and strains. Source: From Ref. 37.

several layers, at different stages of mineralization, can be distinguished (10)]. In some tissues there are normally fairly high concentrations of heavy elements (e.g., iodine in the thyroid, iron in hemoglobin and in the hemochromatotic liver) at concentrations which just reach a level at which a pathological increase, or decrease, can be detected by change in CT image contrast (47,48).

The most commonly used clinical contrast agents are based on the highly attenuating element iodine. Iodine is attractive because it is readily attached to biologically relevant molecules, such as

Figure 3 Computer-generated display of 3D CT images of the opacified colonic vasculature in mice. In the left panel the normal colonic lumen, which is clear. In the right panel there are several adenomas within the colonic lumen. Note that with adenomas the native vessels increase in diameter as well as showing the new vessels within the adenomas. Source: Courtesy of Chinery RK.

Figure 3 Computer-generated display of 3D CT images of the opacified colonic vasculature in mice. In the left panel the normal colonic lumen, which is clear. In the right panel there are several adenomas within the colonic lumen. Note that with adenomas the native vessels increase in diameter as well as showing the new vessels within the adenomas. Source: Courtesy of Chinery RK.

sugars, which are tolerated at relatively high concentrations in blood (49). The relatively low sensitivity (relative to radionuclide imaging) of X-ray attenuation imaging of these agents requires that relatively high concentrations are needed for quantitation of local concentrations of the contrast agent in small regions-of-interest. The discrimination of physiological spaces, other than the intravascular, can be achieved by selectively opacifying those spaces with administered contrast agents. For instance, as a fraction of soluble intravascular contrast agent passes through the vascular endothelium, especially if it is impaired by reduced oxygen levels, inflammation or because it is newly formed, as is often the case in malignancies. As the contrast media remains in the extravascular space for up to several minutes endo-thelial permeability can also be estimated from the images. Moreover, as these contrast agents are generally preferentially excreted through the kidney, the opacification of the nephrons (which occurs over many minutes) could be used to quantitate several aspects of renal function as well. An intra-peritoneal injection of iodinated contrast agents has two effects. One is the immediate ability to better delineate the gut and liver within the abdominal cavity and, because of fairly rapid transfer of the contrast medium to the blood stream, the cardiac chambers and large vessels as well as the filtration by the kidneys are subsequently opacified (2). Iodinated contrast agents encapsulated in micrometer-diameter liposomes, can be used as markers of the intravascular space or to be conveyed into the lymphatic space or biliary ducts (50-52). Chylomicron-like sub-micrometer diameter particles can also be iodinated and serve as obligatory intravascular contrast agents which do not enter the extravascular space (or the renal tubules) but are excreted selectively through the biliary system and hence are a liver-enhancing contrast agent (52).

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