Imaging

Recent advances in noninvasive imaging have greatly enhanced the ability to phenotypically characterize genetically engineered mice. Through the use of MRI, PET, and ultrasound, to name a few, the internal biochemical processes manipulated through transgene expression can be studied and visualized in minute detail. This capability has lead to many discoveries and developments in the world of genetic mutations. This section gives a general overview of a few of the advanced technologies now available for imaging transgenic mice.

In use by clinical practitioners for quite some time, ultrasonic imaging is becoming more widely used as a tool for the study of transgenic mice. Ultrasound can image the internal organs by detecting the echoes of ultrasound waves passed from a transducer through animals' bodies. Depending on the tissue, the image received will appear as a structure ranging in visualization on the gray scale from black to white with mineralized structure such as bone viewed as white and liquid structures such as urine and blood shown as black. Echocardiography is based on the same principles, applied to cardiac structure and function.

An emerging technology in advanced imaging is PET, or positron emission tomography.14 Because disease is often expressed physiologically first, before it is anatomically observable, PET imaging provides a way to identify and characterize the nature of early onset, before it is clinically expressed. PET is an analytical nuclear medicine imaging technology that uses positron-labeled molecules in very low mass amounts to image and measure the function of biological processes, such as tumorigenesis, with minimal tissue and cellular disruption. Measuring, but not disturbing, the biological process is a fundamental and biologically important aspect of the tracer technique of PET. The assay depends on synthesizing a positron-labeled molecule that mimics a few steps of tumorigenesis so that kinetic analysis can estimate the concentration of reactants and products and the rates of reactions, using PET scanning. The PET scanner measures the changing regional tissue concentration of the labeled molecule and its labeled product over time.

Another category of noninvasive imaging useful in the study of transgenic mice, especially for cardiac and brain anatomy and function, is MRI, magnetic resonance imaging. Most MRI machines image hydrogen protons within the tissues. MRI is based on the property of the protons to have weak magnetic fields that will create an electrical current when exposed to a magnet. The "magnetic resonance" produced by the spinning, electrified nuclei registers as an electrical signal, determining the degree of brightness produced and creating an image of individual organs based on their specific amounts of hydrogen present. The differing degrees of brightness between separate organs provides contrast and leads to the ability to distinguish different areas of tissue. Adding a contrast agent, such as a gadolinium chelate, enhances the visualization of the tissues.15

Optical imaging can also be used to visualize the structure and function of tissues in genetically engineered mice. There are several methods in which the use of light is the basis of the imaging technique. Near-infrared spectroscopy is the transmission of light through tissue; absorption of one or more of the light wavelengths allows characterization of the region through which the light has passed. Infrared spectroscopy measures the reflection of light that has been differentially absorbed. Fluorescence optical imaging visualizes tissues that have taken up fluorescent dyes or natural chromaphores. Optical coherence tomography is analogous to B-mode ultrasonagrophy, but the acoustical waves used in ultrasound are replaced with infrared light.15

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