Next-generation in vivo optical imaging with short-wave infrared quantum dots.

For in vivo imaging, the short-wavelength infrared region (SWIR; 1000-2000 nm) provides several advantages over the visible and near-infrared regions: general lack of autofluorescence, low light absorption by blood and tissue, and reduced scattering. However, the lack of versatile and functional SWIR emitters has prevented the general adoption of SWIR imaging by the biomedical research community. Here, we introduce a class of high-quality SWIR-emissive indium-arsenide-based quantum dots (QDs) that are readily modifiable for various functional imaging applications, and that exhibit narrow and size-tunable emission and a dramatically higher emission quantum yield than previously described SWIR probes. To demonstrate the unprecedented combination of deep penetration, high spatial resolution, multicolor imaging and fast-acquisition-speed afforded by the SWIR QDs, we quantified, in mice, the metabolic turnover rates of lipoproteins in several organs simultaneously and in real time as well as heartbeat and breathing rates in awake and unrestrained animals, and generated detailed three-dimensional quantitative flow maps of the mouse brain vasculature.

Review of short-wave infrared spectroscopy and imaging methods for biological tissue characterization.

We present a review of short-wave infrared (SWIR, defined here as ∼1000 to 2000 nm) spectroscopy and imaging techniques for biological tissue optical property characterization. Studies indicate notable SWIR absorption features of tissue constituents including water (near 1150, 1450, and 1900 nm), lipids (near 1040, 1200, 1400, and 1700 nm), and collagen (near 1200 and 1500 nm) that are much more prominent than corresponding features observed in the visible and near-infrared (VIS-NIR, defined here as ∼400 to 1000 nm). Furthermore, the wavelength dependence of the scattering coefficient has been observed to follow a power-law decay from the VIS-NIR to the SWIR region. Thus, the magnitude of tissue scattering is lower at SWIR wavelengths than that observed at VIS or NIR wavelengths, potentially enabling increased penetration depth of incident light at SWIR wavelengths that are not highly absorbed by the aforementioned chromophores. These aspects of SWIR suggest that the tissue spectroscopy and imaging in this range of wavelengths have the potential to provide enhanced sensitivity (relative to VIS-NIR measurements) to chromophores such as water and lipids, thereby helping to characterize changes in the concentrations of these chromophores due to conditions such as atherosclerotic plaque, breast cancer, and burns.

Quantitative short-wave infrared multispectral imaging of in vivo tissue optical properties.

Extending the wavelength range of spatial frequency domain imaging (SFDI) into the short-wave infrared (SWIR) has the potential to provide enhanced sensitivity to chromophores such as water and lipids that have prominent absorption features in the SWIR region. Here, we present, for the first time, a method combining SFDI with unstructured (zero spatial frequency) illumination to extract tissue absorption and scattering properties over a wavelength range (850 to 1800 nm) largely unexplored by previous tissue optics techniques. To obtain images over this wavelength range, we employ a SWIR camera in conjunction with an SFDI system. We use SFDI to obtain in vivo tissue reduced scattering coefficients at the wavelengths from 850 to 1050 nm, and then use unstructured wide-field illumination and an extrapolated power-law fit to this scattering spectrum to extract the absorption spectrum from 850 to 1800 nm. Our proof-of-principle experiment in a rat burn model illustrates that the combination of multispectral SWIR imaging, SFDI, and unstructured illumination can characterize in vivo changes in skin optical properties over a greatly expanded wavelength range. In the rat burn experiment, these changes (relative to normal, unburned skin) included increased absorption and increased scattering amplitude and slope, consistent with changes that we previously reported in the near-infrared using SFDI.

Efficient luminescent down-shifting detectors based on colloidal quantum dots for dual-band detection applications.

A colloidal quantum dot (QD) luminescent down-shifting (LDS) layer is used to sensitize an InGaAs short wavelength infrared photodetector to the near UV spectral band. An average improvement in the external quantum efficiency (EQE) from 1.8% to 21% across the near UV is realized using an LDS layer consisting of PbS/CdS core/shell QDs embedded in PMMA. A simple model is used to fit the experimental EQE data. A UV sensitive InGaAs imaging array is demonstrated and the effect of the LDS layer on the optical resolution is calculated. The bandwidth of the LDS detector under UV illumination is characterized and shown to be determined by the photoluminescence lifetime of the QDs.