In vivo fluorescence imaging in the visible and traditional near-infrared (NIR-I) windows with wavelengths of 400~900 nm has been limited with sub-optimal resolution at >500 µm depths, due to strong scattering and absorption of photons by the turbid biological tissue, as well as high autofluorescence interference from the tissue in these windows. By exploiting the unique second near-infrared (NIR-II, 1.0~1.7 µm) fluorescence of single-walled carbon nanotubes (SWNTs), in vivo fluorescence imaging can be significantly improved with crisper resolution at deeper tissue penetration. This talk will cover our recent research progress on NIR-II fluorescence imaging, from in vivo mouse hindlimb vascular imaging (Nature Medicine, 2012; Circ. Cardiovasc. Imag. 2014) to brain vascular imaging (Nature Photonics, 2014; Angew. Chem. 2015) using SWNTs as the NIR-II fluorophore. In the first work, we have demonstrated microvascular angiography with improved spatial resolution over X-ray based computed tomography (CT), and hemodynamic measurement with larger dynamic range than ultrasonography. Owing to the high resolution, deep tissue penetration and the ability to record fast dynamics, NIR-II fluorescence imaging has allowed us to detect ischemic blood hypoperfusion in an animal model of lower limb ischemia with high sensitivity. In the second work, we have achieved sub-10 µm resolution mouse cerebrovascular imaging at millimeter depth inside the mouse brain through intact scalp and skull, using chemically purified SWNTs with enriched fluorescence emission in two optimized NIR-II sub-regions, the NIR-IIa window (1.3~1.4 µm) and the NIR-IIb window (1.5~1.7 µm). The non-invasive NIR-II brain imaging has allowed us to visualize and quantify the severity of middle cerebral arterial occlusion in a mouse model of stroke. Finally I will discuss potential future directions of NIR-II fluorescence imaging, such as the development of novel NIR-II fluorophores with more favorable emission wavelength and higher quantum efficiency, and the use of NIR-II fluorescence imaging for understanding the brain functions with new technological advances of NIR-II imaging.

References:

1. “Multifunctional in vivo vascular imaging using near-infrared II fluorescence” Nature Medicine 2012, 18, 1841-1846

2. “Near-infrared II fluorescence for imaging hindlimb vessel regeneration with dynamic tissue perfusion measurement” Circulation: Cardiovascular Imaging 2014, 7, 517-525

3. “Through Skull Fluorescence Imaging of the Brain in a New Near-Infrared Window” Nature Photonics, 2014, 8, 723-730

4. “Fluorescence Imaging In Vivo at Wavelengths beyond 1500 nm” Angew. Chem. Int. Ed. 2015, 127, 14971-14975

5. “Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy” Chemical Reviews 2015, 115, 10816-10906