Measurements of the intensity of light transmitted between two points on the surface of tissue are not only relatively straightforward and inexpensive to obtain, but also contain a remarkable amount of useful information, as demonstrated by the clinical successes of NIRS (Obrig and Villringer 2003). So-called continuous wave (CW) systems require a source that either emits at a constant intensity, or is modulated at a low (a few kHz) frequency in order to exploit the significant improvements in sensitivity available from phase-locked detection techniques. CW sources have been used to investigate the head, testes and breast by viewing light which has been transmitted through the body since at least as far back as the early nineteenth century (Bright 1831, Curling 1843, Cutler 1929). CW transillumination of the breast (or diaphanography) received a brief revival of interest during the 1970s and 1980s with the introduction of NIR sources and detectors, but no significant clinical utility was demonstrated (Hebden and Delpy 1997)
Probably the most highly developed application of CW imaging technology is the study of haemodynamic and oxygenation changes in superficial tissues, and of the outer (cortical) regions of the brain in particular using optical topography. This typically involves acquiring multiple measurements of diffuse reflectance at small source-detector separations over a large area of tissue simultaneously or in rapid succession (see section 4.1). By keeping the separation small, measured signals are relatively high and therefore may be acquired quickly, enabling haemodynamic changes with characteristic responses as fast as a few tens of milliseconds to be studied. Thus, optical topography of the cortex represents a mapping technique analogous to electro-encephalography (EEG), which is sensitive to electrical activity in the cortex.
Recent technological advances have led to the development of arrays of individual sources and detectors which can be coupled to the head using flexible pads held in direct contact with the scalp. The availability of low cost, high power (several mW) and narrow bandwidth (< few nm) laser diodes over a broad range of NIR wavelengths have made them the popular choice of source for most optical imaging applications. The detector selected for a given application will depend on issues such as the desired sensitivity, stability, and dynamic range, as well as more practical concerns such as size and cost. A variety of semiconductor photodiodes are available, usually offering very good dynamic range at low cost. Avalanche photodiodes (APDs) are generally the most sensitive of the semiconductor detectors. However, for optimum sensitivity, photomultipliers (PMTs) are required, which can provide single-photon counting performance, although with a more limited dynamic range and at significantly greater cost. A thorough review of detection methods is given by Knoll (1999).
The number of distinct sources or detectors required can be reduced by switching components sequentially to different optical fibres within the array (known as multiplexing), at the expense of reduced temporal resolution. Most current systems use multiple detectors to record signals continuously in parallel, while sources are either activated sequentially, or are intensity-modulated at different frequencies simultaneously. In the latter case, detected signals from specific sources are isolated either by using lock-in amplifiers (Yamashita et al. 1999) or by Fourier transformation and appropriate filtration (Franceschini et al. 2003, Everdell et al. 2004). The former technique is used by the first commercial optical topography system, the Hitachi ETG-100 system. It consists of eight laser diodes at 780 nm and eight laser diodes at 830 nm, each modulated at a different frequency between 1 and 8.7 kHz (Yamashita et al. 1999). The sources are coupled in pairs to eight distinct positions on the subject, while light is detected at eight further positions using APDs. An array of 48 lock-in amplifiers is used to sample 24 distinct source-detector combinations at two wavelengths, and thus Hitachi refer to this device as a 24-channel system. The system has been widely evaluated for brain imaging (see section 4.1) where the sources and detectors are distributed over one or two lobes of the brain (Yamashita et al. 1999). A new model, the ETG-7000, is a 120�channel device which can image the entire adult cortex with 40 pairs of laser diodes and 40 APD detectors.
CW measurements have also been used for the considerably more challenging approach to imaging known as optical tomography, which involves generating a transverse slice or three-dimensional (3D) image (see section 3). Adequate sensitivity to deep tissues requires measurements at large source-detector separations, and consequently transmitted light must be integrated over periods of several seconds per source in order to obtain adequate signal. While this largely prohibits the analysis of short, isolated haemodynamic events, Schmitz et al. (2002) have demonstrated a CW tomography system which uses gating and averaging of the detected signals to reveal cyclic haemodynamic changes (Barbour et al. 2004). Their DYNOT (DYnamic Near Infrared Optical Tomography) system is currently marketed commercially by NIRx Medical Technologies (USA).
During the late 1990s, Philips Research Laboratories (Netherlands) began evaluating a breast tomography system based on CW measurements and a simple back-projection algorithm (Colak et al. 1999). The patient lay on a bed with her breast suspended within a conical chamber filled with a tissue-like scattering liquid. This approach had the very attractive benefit of eliminating the variability in surface coupling. The clinical performance of the Philips system was lower than desired, partly because of the inability of CW imaging to distinguish between internal absorbing and scattering properties (Arridge and Lionheart 1998). Similar commercial systems based on CW measurements have been developed by Imaging Diagnostic Systems Inc. (Grable et al. 2004), see Figure 1, and Advanced Research Technologies Inc. (Hawrysz and Sevick-Muraca 2000).
There are a number of disadvantages associated with CW imaging using absolute measurements of intensity:
- Intensity measurements are far more sensitive to the optical properties of tissues at or immediately below the surface than to the properties of localised regions deeper within the tissue. This is due to the characteristic banana shape of the volume of tissue over which the measurement is sensitive (known as the photon measurement density function or PMDF), which is narrow near the source and detector and very broad in the middle (Arridge 1995, Arridge and Schweiger 1995).
- The detected intensity is highly dependent on surface coupling. For example, an optical fibre moved slightly or pressed more or less firmly against the skin can result in a very large change in the measurement. The presence of hair or local variation in skin colour can also have a major influence on intensity measurements. Although means of calibrating for variable surface coupling have been implemented (see section 3.4.6), NIRS and imaging using CW sources have largely focussed on recording differences in intensity, acquired over a period short enough so that the unknown coupling can be assumed to have remained constant.
- Measurements of intensity alone at a single wavelength are unable to distinguish between the effects of absorption and scatter (Arridge and Lionheart 1998), nor between changes in blood volume and oxygenation.
Alternative types of measurement have been explored in order to circumvent some of these problems inherent in CW data. The techniques which have demonstrated the most promise for imaging through larger thicknesses of tissue are those based on the temporal measurement of transmitted radiation, or an equivalent measurement in the frequency domain. These are now reviewed separately in the following two sections.
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