Abstract In vivo fluorescence imaging in second near-infrared biological window
(NIR-II) is an emerging imaging technique in both fundamental research and clinical
application. NIR-II fluorescence affords high-resolution images with increasing
penetration depths due to the reduced scattering, minimal absorption, and negligible
autofluorescence. In this chapter, we review the recent 10-year progress made on
NIR-II fluorescence imaging in 1,000–1,700 nm NIR-II windows by summarizing
an increasingly advanced NIR-II fluorophores including organic dyes and inorganic
nanoparticles, with tunable emission wavelengths. The NIR-II fluorescence emission
mechanism and the strategy for synthesis of high quantum yield with more biocompatible and higher photostability NIR-II fluorophores will be highlighted. In addition, we provide our perspective on the current development and bright future
direction of NIR-II fluorophores development in frontier fields.
Keywords Quantum dots, Rare-earth-doped nanoparticles, Second near-infrared
window, Single-walled carbon nanotubes, Small-molecule dye
1 Introduction
Noninvasive imaging is being used for many preclinical or clinical purposes from
disease diagnosis to the visualization drug targeting [1–3]. Fluorescence imaging is a
fast-growing noninvasive imaging technique that has been well-established for
identification and diagnosis of lesion in real time at a relatively higher signal-tonoise ratio and relatively higher spatial and temporal resolution [4, 5]. In vivo
fluorescence imaging requires an excitation light source, an emission light detector
to generate a visual representation of the imaged object on the basis of the spatiotemporal distribution of fluorescent probes. It is well-known that scattering,
autofluorescence, and penetration depth are the major factors that cause attenuation
of fluorescence signal proportional to the depth of biological tissue. Briefly, with the
increasing propagation distance, photons will be attenuated by the effects of scattering and absorption, resulting in a reduction in image quality. Absorption of light
in tissue media can occur by biomolecules, such as collagen and elastin, lipids,
hemoglobin, or water in tissue media, while scattering can be caused by cells or
intracellular matrix. Water greatly affects image quality and penetration depth due to
strong absorption peaks from vibrational modes at $900 nm, $1,200 nm, and
$1,400 nm. In the visible window (400–700 nm) and the first near-infrared (NIR)
window (NIR-I, 700–900 nm), image quality is reduced due to strong absorption
peaks from lipids and from hemoglobin and deoxyhemoglobin and is blurred due to
the molecular process of Rayleigh–Mie scattering (Fig. 1a). Compared with visible
imaging and the NIR-I imaging, the second NIR biological window (NIR-II,
1,000–1,700 nm) provides considerable advantages due to the reduced photon
scattering, lower absorption, and minimal autofluorescence (Fig. 1b–d) [6]. Generally, the sub-windows such as the NIR-IIa (1,300–1,400 nm) and the NIR-IIb
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S. He and Z. Cheng
(NIR-II) is an emerging imaging technique in both fundamental research and clinical
application. NIR-II fluorescence affords high-resolution images with increasing
penetration depths due to the reduced scattering, minimal absorption, and negligible
autofluorescence. In this chapter, we review the recent 10-year progress made on
NIR-II fluorescence imaging in 1,000–1,700 nm NIR-II windows by summarizing
an increasingly advanced NIR-II fluorophores including organic dyes and inorganic
nanoparticles, with tunable emission wavelengths. The NIR-II fluorescence emission
mechanism and the strategy for synthesis of high quantum yield with more biocompatible and higher photostability NIR-II fluorophores will be highlighted. In addition, we provide our perspective on the current development and bright future
direction of NIR-II fluorophores development in frontier fields.
Keywords Quantum dots, Rare-earth-doped nanoparticles, Second near-infrared
window, Single-walled carbon nanotubes, Small-molecule dye
1 Introduction
Noninvasive imaging is being used for many preclinical or clinical purposes from
disease diagnosis to the visualization drug targeting [1–3]. Fluorescence imaging is a
fast-growing noninvasive imaging technique that has been well-established for
identification and diagnosis of lesion in real time at a relatively higher signal-tonoise ratio and relatively higher spatial and temporal resolution [4, 5]. In vivo
fluorescence imaging requires an excitation light source, an emission light detector
to generate a visual representation of the imaged object on the basis of the spatiotemporal distribution of fluorescent probes. It is well-known that scattering,
autofluorescence, and penetration depth are the major factors that cause attenuation
of fluorescence signal proportional to the depth of biological tissue. Briefly, with the
increasing propagation distance, photons will be attenuated by the effects of scattering and absorption, resulting in a reduction in image quality. Absorption of light
in tissue media can occur by biomolecules, such as collagen and elastin, lipids,
hemoglobin, or water in tissue media, while scattering can be caused by cells or
intracellular matrix. Water greatly affects image quality and penetration depth due to
strong absorption peaks from vibrational modes at $900 nm, $1,200 nm, and
$1,400 nm. In the visible window (400–700 nm) and the first near-infrared (NIR)
window (NIR-I, 700–900 nm), image quality is reduced due to strong absorption
peaks from lipids and from hemoglobin and deoxyhemoglobin and is blurred due to
the molecular process of Rayleigh–Mie scattering (Fig. 1a). Compared with visible
imaging and the NIR-I imaging, the second NIR biological window (NIR-II,
1,000–1,700 nm) provides considerable advantages due to the reduced photon
scattering, lower absorption, and minimal autofluorescence (Fig. 1b–d) [6]. Generally, the sub-windows such as the NIR-IIa (1,300–1,400 nm) and the NIR-IIb
82
S. He and Z. Cheng