Near‐Infrared Fluorescence Optical Imaging and Tomography

Abstract

The advent of recent advances in near-infrared laser diodes and fast electro-optic detection has spawned a new research field of diagnostic spectroscopy and imaging based on targeting and reporting exogenous fluorescent agents. This review seeks to concisely address the physics, instrumentation, advancements in tomography, and near-infrared fluorescent contrast agent development that promises selective and specific molecular targeting of diseased tissues. As an example of one area of the field, recent work focusing on pharmacokinetic analysis of fluorophores targeting the epidermal growth factor receptor (EGFR) is presented in a human breast cancer xenograft mouse model to demonstrate specificity of molecularly targeted contrast agents. Finally, a critical evaluation of the limitations and the opportunities for future translation of fluorescence-enhanced optical imaging of deep tissues is presented.

Hyaluronidase Expression Induces Prostate Tumor Metastasis in an Orthotopic Mouse Model

“…However, considerable caution must be exercised in these interpretations because the planar imaging method used is less reliable at increasing tissue depths. 14,16 For relatively small, superficial tumors, detected fluorescence signal increases are approximately linear with depth, as we have assumed in our calculations and validated with empirical measurement. As the size of the tumor increases, fluorescence intensity from deeper regions of the tumor is diminished in a nonlinear manner by tissue-dependent scattering of emitted photons.…”

“…(Several excellent recent reviews describe existing noninvasive imaging modalities including magnetic resonance imaging, ultrasound, and optical techniques. [13][14][15][16][17][18][19] ) Optical imaging has the potential to monitor growth and regression of tumors in a continuous and noninvasive manner if sites of malignancy are optically distinguishable from normal tissue. Because the absorbance spectra of bodily fluids and tissues exhibit local minima in the near-infrared (NIR) region, 20 imaging in the NIR offers the advantages of relatively deep tissue penetration and low autofluorescence.…”

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.…”