Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents.

He Wei et al. Proc. Natl. Acad. Sci. USA 2021, 118 (42), e2102340118.

Magnetic nanoparticles are robust contrast agents for MRI and often produce particularly strong signal changes per particle. Leveraging these effects to probe cellular- and molecular-level phenomena in tissue can, however, be hindered by the large sizes of typical nanoparticle contrast agents. To address this limitation, we introduce single-nanometer iron oxide (SNIO) particles that exhibit superparamagnetic properties in conjunction with hydrodynamic diameters comparable to small, highly diffusible imaging agents. These particles efficiently brighten the signal in T 1-weighted MRI, producing per-molecule longitudinal relaxation enhancements over 10 times greater than conventional gadolinium-based contrast agents.

Absorption by water increases fluorescence image contrast of biological tissue in the shortwave infrared.

Jessica A. Carr et al. Proc. Natl. Acad. Sci. USA 2018, 30 (11), 3734-372.

Shortwave infrared (SWIR) fluorescence imaging is a tool for visualizing biological processes deep within tissue or living animals. Our study shows that the contrast in a SWIR fluorescence image is primarily mediated by the absorptivity of the tissue, and can therefore be tuned through deliberate selection of imaging wavelength. We show, for example, that, in 3D tissue phantoms and in brain vasculature in vivo in mice, imaging at SWIR wavelengths of the highest water absorptivity results in the greatest fluorescence contrast. We further demonstrate, in microscopy of ex vivo mouse liver tissue, that imaging at wavelengths of high tissue absorptivity can also increase imaging penetration depth, and use a theoretical contrast model to explain this effect.

Shortwave Infrared in Vivo Imaging with Gold Nanoclusters. 

Yue Chen et al. Nano Letters. 2017, 17 (10), 6330-6334.

The use of visible/NIR-emitting gold nanoclusters (Au NCs), previously proposed for in vivo imaging, has been limited to some extent by low quantum yields (QYs) and the limited penetration of visible light in tissue. Here we report short wavelength infrared (SWIR, λ = 1–2 μm) emitting Au NCs with a good photoluminescence QY for this wavelength range (0.6% to 3.8% for λem = 1000 to 900 nm) and excellent stability under physiological conditions. We show that surface ligand chemistry is critical to achieving these properties. We demonstrate the potential of these SWIR-emitting Au NCs for in vivo imaging in mice. The Au NCs have a hydrodynamic diameter that is small (∼5 nm) enough that they exhibit a rapid renal clearance, and images taken in the SWIR region show better resolution of the blood vessels than in the NIR region.

Non-invasive monitoring of chronic liver disease via near-infrared and shortwave-infrared imaging of endogenous lipofuscin. 

Mari Saif et al. Nat. Biomed. Eng. 2020, 1-13.

Monitoring the progression of non-alcoholic fatty liver disease is hindered by a lack of suitable non-invasive imaging methods. Here, we show that the endogenous pigment lipofuscin displays strong near-infrared and shortwave-infrared fluorescence when excited at 808 nm, enabling label-free imaging of liver injury in mice and the discrimination of pathological processes from normal liver processes with high specificity and sensitivity. We also show that the near-infrared and shortwave-infrared fluorescence of lipofuscin can be used to monitor the progression and regression of liver necroinflammation and fibrosis in mouse models of non-alcoholic fatty liver disease and advanced fibrosis, as well as to detect non-alcoholic steatohepatitis and cirrhosis in biopsied samples of human liver tissue.

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents. 

Wei He et al. Proc. Natl. Acad. Sci. USA 2017, 114, 2325-2330.

Gadolinium (Gd)-based contrast agents (GBCAs) are currently the mainstream clinical MRI contrast agents. Some GBCAs have shown a long-term toxicity—nephrogenic systemic fibrosis (NSF)—and Gd depositions in the brain. The NSF has triggered a Food and Drug Administration (FDA) black-box warning and a contraindication of some GBCAs. The finding of Gd depositions led to an ongoing FDA investigation to monitor their possible long-term adverse effects. Here, we present T1-weighted contrast-enhanced MR imaging and angiography using zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) in mice and rats. Renal clearance and biodistribution results further demonstrate that ZES-SPIONs are qualitatively different from previously reported SPIONs.

 Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green.

Jessica A. Carr et al. Proc. Natl. Acad. Sci. USA 2018, 115, 9080.

Imaging in the shortwave IR (SWIR) spectral window allows the observation of processes deep within living animals. Recent studies have shown that SWIR imaging enables unprecedented imaging opportunities, including contact-free monitoring of vital signs, generation of microvasculature blood flow maps, real-time metabolic imaging, and molecularly targeted imaging. Yet, whereas bright SWIR fluorophores have been developed for preclinical research settings, applications in the clinic have been held back by the conventional belief that no clinically approved fluorophore is available. Here, we show that indocyanine green, a clinically approved near-IR dye, exhibits a remarkable amount of SWIR emission, which enables state-of-the-art SWIR imaging with direct translation potential into clinical settings, and even outperforms other commercially available SWIR emitters.

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

Oliver T. Bruns et al. Nat. Biomed. Eng. 2017, 1, 0056.

For in vivo imaging, the short-wavelength infrared region (SWIR; 1,000–2,000 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 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.