Thermoacoustic Computed Tomography (TCT)
Thermoacoustic Computed Tomography (TCT) relies on the absorption of electromagnetic energy and the subsequent emission of an acoustic wave (sound). The thermoacoustic process, illustrated by the graphic above, has been around since first reported by Alexander Graham Bell at the end of the 19th century. However, it is only in the past few years that OptoSonics has devised sophisticated instrumentation and software allowing us to make precise images based on the energy-absorption patterns within living organisms. In addition, many frequencies of light can be used, including infrared, microwaves or radio waves, all of which make good excitation sources for the formation and detection of thermoacoustic signals. Light scattering, which can blur image detail and limit how deeply we can see into tissue, is not an issue because the "signal" we detect is carried by the thermoacoustic waves with virtually no scatter.
TCT combines three significant benefits not found in other competing technologies:
- Produces three-dimensional images
- Offers high image detail
- Promotes high sensitivity to molecular probes
Three-Dimensional Capability is Key
Using Thermoacoustic CT, the images we produce are fully three dimensional in nature (based on transducer arrays that have varying geometries — see the following figures), and offer significant improvements in spatial resolution and sensitivity compared to competing technologies. Our platform technology can be applied in a variety of in vivo applications from small animals (e.g., mice) to humans. Especially exciting is the potential of using TCT to localize labeled molecular probes which target specific diseases, such as cancer, in vivo.
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Alternative Form of Optical Imaging
The most common alternative form of optical imaging in small animals is fluorescence imaging. The basic approach to fluorescence imaging is straightforward. The idea is to attach a fluorophore (fluorescing dye) to a "smart" probe that is attached to some specific receptor that is present (expressed) in a targeted tissue, e.g., breast cancer. To detect if the fluorophore has been deposited at some target site, the animal is irradiated with light of a particular wavelength. The wavelength is chosen so that fluorescence is stimulated at a second, longer wavelength, which is then emitted from the animal (this is the key property of a fluorescing dye). Using appropriate optical filters, the fluorescing light is separated from the stimulating light. The greater the fluorescing signal, the greater is the accumulation of the molecular probe at the target site.
The Limits of Fluorescence Imaging
While this approach is potentially very powerful, in vivo fluorescence imaging has several significant limitations. The most severe of these limitations is the inability of the fluorescing light to penetrate through more than a millimeter or two of soft tissue without excessive scattering. The scattering of this light both decreases its intensity and smears out the image recorded by the TV camera. The greater the depth, the greater the scattering and smearing. Consequently, this approach is only useful for studying tissues that lie close to the surface of the animal.
Why TCT is Superior to Fluorescence Imaging
TCT can be used to detect dye-labeled molecular probes by employing a dual-wavelength imaging approach to isolate the optical dye. We can effectively discriminate between dye absorption (which changes rapidly with wavelength) and that of other tissues (which change little) by choosing one wavelength near peak dye absorption and a second at a slightly greater wavelength. The dyes may be the exact same dyes used in fluorescence imaging. The key difference is that thermoacoustic emission, which does not suffer from excessive scatter, is detected rather than fluorescent emission, which does. Therefore, excellent 3-D spatial resolution can be achieved throughout several centimeters of tissue, not just near the skin surface.
