Developments Toward Diagnostic Breast Cancer Imaging Using Near-Infrared Optical Measurements and Fluorescent Contrast Agents1

Abstract

The use of near-infrared (NIR) light to interrogate deep tissues has enormous potential for molecular-based imaging when coupled with NIR excitable dyes. More than a decade has now passed since the initial proposals for NIR optical tomography for breast cancer screening using time-dependent measurements of light propagation in the breast. Much accomplishment in the development of optical mammography has been demonstrated, most recently in the application of time-domain, frequency-domain, and continuous-wave measurements that depend on endogenous contrast owing to angiogenesis and increased hemoglobin absorbance for contrast. Although exciting and promising, the necessity of angiogenesis-mediated absorption contrast for diagnostic optical mammography minimizes the potential for using NIR techniques to assess sentinel lymph node staging, metastatic spread, and multifocality of breast disease, among other applications. In this review, we summarize the progress made in the development of optical mammography, and focus on the emerging work underway in the use of diagnostic contrast agents for the molecular-based, diagnostic imaging of breast.

A systematic approach to the development of fluorescent contrast agents for optical imaging of mouse cancer models

“…Absorption and scattering of light are largely a function of the wavelength of the excitation source [3]. Light is absorbed by endogenous chromophores found in living tissue, including hemoglobin, melanin, and lipid [3], [4], [5], [6], and [7]. In general, light absorption and scattering decrease with increasing wavelength.…”

“…Above 900 nm, water absorption can interfere with signal-to-background ratio. Because the absorption coeffi cient of tissue is considerably lower in the near infrared (NIR) region (700-900 nm), light can penetrate more deeply, to depths of several centimeters [3], [4], [5] and [6]. Fluorochromes with emissions in the NIR are not hindered by interfering autofl uorescence, so they tend to yield the highest signal-to-background.…”

“…Important criteria for effective optical imaging fl uorochromes include excitation and emission maxima in the NIR between 700 and 900 nm, high quantum yield [3], [4], [5], [6] and [7], chemical and optical stability, and suitable pharmacological properties including aqueous solubility, low nonspecifi c binding, rapid clearance of the free dye, and low toxicity. The dyes most commonly used for fl uorescent optical imaging are listed in Table 1.…”

Diffuse Optical Imaging

“…Also the optical contrast between a lesion and normal tissue can be enhanced using an absorbing contrast agent (Ntziachristos et al, 2000). Hybrid techniques employing fluorescent contrast agents (Hawrysz and Sevick-Muraca 2000;Ebert et al, 2001) and ultrasonic enhancement (Holboke et al, 2000) have been used to improve the sensitivity of optical mammography.…”

Effects of the approximations of light propagation on quantitative photoacoustic tomography using two-dimensional photon diffusion equation and linearization

“…The absorption coefficient of the photon absorber can reflect the conditions of biological tissues. Angiogenesis in cancer tissues increases the concentration of hemoglobin, which increases the absorption coefficient [9][10][11][12][13][14][15]. Some contrast agent molecules and nanoparticles increasing the light absorption coefficient are useful for finding diseased tissues [16,17] and mapping the sentinel lymph nodes [18,19].…”