Ultrasound-modulated optical tomography (UOT), also known as Acousto-Optic Tomography (AOT), is a hybrid imaging modality that combines light and sound; it is a form of tomography involving ultrasound. It is used in imaging of biological soft tissues and has potential applications for early cancer detection. As a hybrid modality which uses both light and sound, UOT provides some of the best features of both: the use of light provides strong contrast and sensitivity (both molecular and functional); these two features are derived from the optical component of UOT. The use of ultrasound allows for high resolution, as well as a high imaging depth. However, the difficulty of tackling the two fundamental problems with UOT (low SNR in deep tissue and short speckle decorrelation time) have caused UOT to evolve relatively slowly; most work in the field is limited to theoretical simulations or phantom / sample studies.
Basic Description of Acousto-Optic Tomography In UOT, ultrasound transducers are used to apply ultrasounds wave into a medium, usually some biological tissue. Applying these ultrasound waves, or an ultrasound field, to a region of tissue will change the optical properties of the tissue in time and space. This region of ultrasound-modulated tissue is the region of interest (ROI) which will be analyzed. Photons are then sent into the tissue from some source, such as a laser. Eventually, despite the strength of optical scattering in tissue, some of these photons will pass through the ROI. The photons that pass through the ROI will change according to the modulation of the tissue; this causes the photons to be "tagged". Typically, this tagging will cause the frequency of the light to shift by the frequency of the US field. Sufficiently coherent light traveling through a medium creates a speckle pattern (Fig 1 of next citation). Modulating the ultrasound field applied to the ROI will cause the speckle patterns to change, due to the 3 modulation mechanisms which are explained below. The changes of these speckle patterns are used to derive various properties of the tissue during reconstruction and analysis. Optical properties that can be derived include the optical absorption coefficient, the optical scattering coefficient, and the fluence in the region of interest; UOT can also be used to derive mechanical properties as well.
Use of Light and Sound in Conjunction Optical imaging modalities typically rely on ballistic photons to collect and convey information. However, as a result of strong optical scattering in tissue, conventional imaging modalities struggle to image deeper into tissue, past the optical diffusion limit (typically about 1 mm into tissue). Various imaging modalities have been developed to peer deeper into tissue, such as diffuse optical tomography (DOT) and optical coherence tomography (OCT). While OCT has fantastic spatial resolution (3.5 and 7 micrometer resolutions, axially and lateral respectively), its imaging depth is limited to the millimeter range (e.g. 2.5 mm). DOT has fantastic penetration, on the scale of centimeters, but suffers from inferior resolution (~1cm). To address the difficulty of deep optical imaging, hybrid ultrasound and optical imaging modalities have been developed, namely UOT and photoacoustic imaging (PAI). Both imaging modalities use diffuse photons, which typically cannot be used to transmit information from deep within the tissue. This is because strong optical scattering means that it is incredibly difficult to determine where the photons have traveled and how many scattering events they might have gone through. UOT and PAI have different ways to effectively transfer information from the diffuse photons within the tissue back to the system, which allows for centimeter imaging depths (deeper than DOT) while retaining high spatial resolutions (millimeters to 100s of micrometers). Photoacoustic imaging sends a pulse of light into tissue; as photons are absorbed by the tissue, the resulting heating rise results in thermoelastic expansion. This leads to a pressure wave propagation, which is collected by ultrasound transducers. Thus, PAI uses photons to acquire information deep inside tissue and uses ultrasound to transmit that information to the system. In contrast, UOT relies on photons for information transmission and uses ultrasound to acquire information. Ultrasound is used in UOT to "tag" or identify photons which have passed through the region of interest; these photons can be trusted to carry information back to the system regarding the region of interest. The modulation of the ultrasound will accordingly change the optical properties of the tissue, which can be used to derive both optical and mechanical properties. The difference in the use of ultrasound between PAI and UOT means that different types of information can be derived from the two different modalities. PAI is proficient in delivering information regarding optical absorption; UOT can provide information regarding both optical absorption and optical scattering. Thus, UOT has a strong advantage over PAI in that UOT can provide information about tissue/organ structure as well as tissue metabolism.
Advantages UOT utilizes all photons within deep tissue; as long as they have not been absorbed and they pass through the ROI, those photons can still be used to convey information in UOT. Thus, UOT can achieve imaging depths (exploiting diffuse photons) deeper than 9 cm into the body while retaining high spatial resolutions (from the dimensions of the ultrasound focus), ~mm scale, as of 2017. UOT can be used to derive mechanical and optical properties of the tissue; compared to PAI, which can only derive optical absorption, UOT can derive absorption and scattering properties of the tissue.
Disadvantages There are two fundamental problems with UOT:
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