DYnamic Near-Infrared Optical Tomography, DYNOT, is a new noninvasive functional imaging method that employs low-energetic laser radiation to probe highly scattering media, such as tissue. The method is called dynamic because multiple optical tomographic data sets are acquired in a continuous fashion at high repetition rates (about several images per second) thus allowing the study of physiologic changes inside the target. The concept is illustrated in the figure below.
Each large horizontal arrow represents the process of acquiring one tomographic dataset, i.e., the optical measurements that result in one tomographic image. The small arrows positioned around the medium, pointing toward the target and pointing away from it, represent the source and detector positions, respectively, that are involved in the measurement. Only one source position is illuminated at any one time, and the illumination spot needs to be moved about the target in order to provide a full tomographic view of the medium. The resulting reconstructed image for the measurement process represented by each row is indicated by the symbolic images to the right.
To complete the measurement for one image takes much less than a second (typically on the order of 0.3 s). After this, the process is repeated to acquire the data set for the next image, and so on. In this fashion, an entire time series of reconstructed images can be generated, allowing the study of dynamic changes inside the target.
The DYNOT system produces 2D and 3D reconstructed images of the hemodynamics in real-time thus presenting the researcher with a new tool in functional imaging of the vascular bed.
An understanding of some basic principles of vascular physiology is key to appreciating the expected application range of the DYNOT system. The vascular system has many functions. It is the principle mechanism responsible for the delivery of essential nutrients to tissue and removal of wastes. It also plays a critical role in temperature regulation, control of blood pressure and is the conduit for action of the immune system, and other physiological effectors (e.g., hormones).
There are three features of the vascular system that render it particular well suited for study using time-series optical methods. One of these is the fact that hemoglobin, the principle molecular species responsible for oxygen delivery to tissue, is also a principle factor responsible for light absorption in tissue in the near infrared region. By performing optical measurements with more than one wavelength of light simultaneously, it is possible to differentiate among the different forms of hemoglobin, namely its oxygenated and deoxygenated forms. Measures of these, including their rate of change, can be used to determine imbalances in tissue oxygen supply/demand.
A second feature related to time-series optical studies of tissue is the fact that whereas there are other compounds in tissue that can absorb near infrared light (e.g., water, fat), it is essentially only hemoglobin that also experiences rhythmic fluctuations in its absorption. This occurs because hemoglobin is ordinarily restricted to the vascular space and because blood vessels vary their diameter in response to a range of natural vascular rhythms. Thus, temporal fluctuations in light intensity levels measured from living tissue can be taken as a reliable indicator of modulation in vessel diameter and hence is a specific marker for vascular reactivity.
A third factor important in the utility of DYNOT measures is the fact that the principle elements of the vascular tree have different natural beat frequencies. Thus, it is only the arteries that have a cardiac beat frequency (~1 Hz). Similarly, the veins are known to predominately have a respiratory beat frequency (~0.3 Hz), whereas the microvessels undergo variations in their diameter over a lower frequency range still (< 0.15 Hz). By performing a time-series measure, it is possible to differentiate among activities occurring in the difference branches of the vascular tree. Notably, these measures can be obtained without the need of exogenous contrast agents. Contrast is provided by the naturally occurring time variations in the hemoglobin signal.
Armed with this knowledge, we can now consider the multitude of applications we believe are achievable using the DYNOT system.
While presently not intended for use as a clinically approved diagnostic tool, the nature of the measures achievable using the DYNOT system are well positioned to allow researchers to investigate a range of issues related to disease processes. One area of interest are imaging studies of breast cancer. The optical properties of the female breast allow for light energy to penetrate deeply into breast tissue. Transmission measurements through as much as 12 cm of tissue are readily achievable. In addition to baseline measures of the vascular rhythms for subjects at rest, the introduction of specific provocations that serve to challenge the vascular/hemoglobin response are likely to yield useful results. By use of the appropriately designed measuring head, similar studies can be conducted on nearly any body structure. Other areas of interest include functional studies of the vascular response in the brain, detection characterization of peripheral vascular disease, and characterization of autonomic dysfunction. Still another aspect of DYNOT measures is the ability to characterize the vascular response to pharmacoactive agents. Agents that activate or suppress angiogenesis, modulate autonomic control, or cause focal destruction to tissue would appear well suited for study using the DYNOT system.