Tissue visualization with light is probably the most common imaging practice in medicine and medical research. Historically, visual inspection of a patient or observation of tissues using optical microscopes has been widely used to assess structure and function. Those two examples use the human retina as the recording medium. Generally, medical optical imaging encompasses a large set of imaging technologies that use light from the ultraviolet to the infrared region to image tissue optical characteristics. Light offers wavelength-dependent interactions with tissue that yield unique contrast mechanisms for imaging; scattering, absorption, and fluorescence of intrinsic and extrinsic tissue elements reveal information on structure, physiology, biochemistry, and molecular function.
Because of the important information that light reveals, optical imaging has found many applications for in vivo
tissue measurements. Optical imaging has been used to probe surface structures, such as the functional activation of the exposed brain regions [1
], skin cancers [2
], and those revealed by endoscopic procedures [3
], but it has also been used to investigate noninvasively the internal function of large organs such as the breast [5
] and the unexposed brain [8
]. There are, however, fundamental differences between optical imaging of surface structures and of large organs. Optical imaging, a high-resolution technique for surface imaging, becomes an imaging method with millimeter-scale resolution when probing large organs. This is because tissue scatters light significantly. Hence, photons that propagate inside tissue do not follow straight paths as do X-ray photons, but rather they diffuse and follow random paths [10**
]. This process impairs resolution. Tissue absorption may also be a complication in imaging large tissues, depending on the wavelength used and the target organ. For this reason the near infrared (NIR) part of the spectrum is typically selected for imaging large organs because tissue exhibits low absorption in the NIR and allows light of safe power to penetrate to depths of several centimeters.
Optical imaging may have a major role in breast cancer research and detection, despite its low resolution, by assessing functional and molecular cancer characteristics. Intrinsically, the main light absorbers of the breast in the NIR window are oxyhemoglobin and deoxyhemoglobin. Hence, the optical technique is a unique noninvasive technology for imaging and quantifying vascularization, and especially oxygen saturation of breast tumors. These features are associated with angiogenesis and hypoxia, which are two correlates of breast malignancy. Furthermore, there is an intensified effort to produce extrinsic absorbing and fluorescent probes, especially for the NIR region, that target physiologic and genetic responses [11
]. These probes could increase cancer contrast and target specific gene expression that could eventually improve early detection limits and specificity, but also help in the design of optimum treatments and in assessing treatment efficacy.
The unique features of the optical method, along with its high sensitivity for detecting photons and use of nonionizing radiation, renders optical imaging a technology that could complement existing breast imaging techniques for cancer detection and characterization. The compatibility of the technology with most other radiologic imaging techniques allows the creation of combined modalities for simultaneous breast examinations that yield a superior feature set. Furthermore, optical methods are economic and can acquire data continuously; hence, they may be used for real-time monitoring.
In the following commentary, a brief historical perspective on breast cancer optical imaging is presented and current advances in this field are discussed. Specific focus is given to the infant clinical steps of DOT, a method that uses light and that can image and quantify tissue optical properties (and thus function) in three dimensions. The combination of the technique with novel vascular and molecular contrast agents is also discussed, and the possibility of coupling the optical method with other medical modalities for improving the information content of the composite examination is outlined.