Deep-tissue optical imaging of near cellular-sized features

• Published in: Scientific reports Vol. 9; no. 1; p. 3873
• Main Authors: Dang, Xiangnan, Bardhan, Neelkanth M., Qi, Jifa, Gu, Li, Eze, Ngozi A., Lin, Ching-Wei, Kataria, Swati, Hammond, Paula T., Belcher, Angela M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.03.2019; Nature Publishing Group
• Subjects: 14; 14/69; 140/125; 59; 59/5; 631/1647/245/2226; 639/624/1107/510; 9/10; Algorithms; Animals; Aquatic mammals; Data processing; Fluorophores; Gastrointestinal tract; Humanities and Social Sciences; I.R. radiation; Magnetic resonance imaging; Microscopy; multidisciplinary; Probes; Quantum dots; Radiation; Science; Science (multidisciplinary); Sensors; Tissues; Tumors; Ultrasonic imaging
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-39502-w

Detection of biological features at the cellular level with sufficient sensitivity in complex tissue remains a major challenge. To appreciate this challenge, this would require finding tens to hundreds of cells (a 0.1 mm tumor has ~125 cells), out of ~37 trillion cells in the human body. Near-infrared optical imaging holds promise for high-resolution, deep-tissue imaging, but is limited by autofluorescence and scattering. To date, the maximum reported depth using second-window near-infrared (NIR-II: 1000–1700 nm) fluorophores is 3.2 cm through tissue. Here, we design an NIR-II imaging system, “Detection of Optically Luminescent Probes using Hyperspectral and diffuse Imaging in Near-infrared” (DOLPHIN), that resolves these challenges. DOLPHIN achieves the following: (i) resolution of probes through up to 8 cm of tissue phantom; (ii) identification of spectral and scattering signatures of tissues without a priori knowledge of background or autofluorescence; and (iii) 3D reconstruction of live whole animals. Notably, we demonstrate noninvasive real-time tracking of a 0.1 mm-sized fluorophore through the gastrointestinal tract of a living mouse, which is beyond the detection limit of current imaging modalities.