Video-Rate Molecular Imaging in Vivo with Stimulated Raman Scattering

• Published in: Science (American Association for the Advancement of Science) Vol. 330; no. 6009; pp. 1368 - 1370
• Main Authors: Saar, Brian G, Freudiger, Christian W, Reichman, Jay, Stanley, C. Michael, Holtom, Gary R, Xie, X. Sunney
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 03.12.2010
• Subjects: Administration, Cutaneous; Animals; Backscattering; Biocompatibility; Biological and medical sciences; Biomedical materials; Capillaries; Dimethyl Sulfoxide - administration & dosage; Dimethyl Sulfoxide - pharmacokinetics; Epidermis; Epidermis - chemistry; Epidermis - metabolism; Erythrocytes - physiology; Hair; Human; Humans; Imaging; Imaging, Three-Dimensional; In vivo testing; In vivo tests; Investigative techniques, diagnostic techniques (general aspects); Laser beams; Light; Lipids; Magnetic resonance imaging; Male; Medical sciences; Mice; Mice, Nude; Microscopy; Miscellaneous. Technology; Molecular Imaging - methods; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pumps; Raman scattering; Skin; Skin - blood supply; Skin - chemistry; Skin - metabolism; Spectrum Analysis, Raman - methods; Surgical implants; Time Factors; Vitamin A - administration & dosage; Vitamin A - pharmacokinetics; Water; Molecular imaging; Prostaglandin-endoperoxide synthase; Enzyme; Rodentia; Vitamin; Enzyme inhibitor; Epidermis; Optical imaging; Retinol; In vivo; Vertebrata; Mammalia; Stimulated Raman scattering; Microscopy; Mouse; Animal; Dimethyl sulfoxide; Medical imagery; Skin; Oxidoreductases; Technique; Pharmacokinetics; Topical administration; Functional imaging
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1197236

Optical imaging in vivo with molecular specificity is important in biomedicine because of its high spatial resolution and sensitivity compared with magnetic resonance imaging. Stimulated Raman scattering (SRS) microscopy allows highly sensitive optical imaging based on vibrational spectroscopy without adding toxic or perturbative labels. However, SRS imaging in living animals and humans has not been feasible because light cannot be collected through thick tissues, and motion-blur arises from slow imaging based on backscattered light. In this work, we enable in vivo SRS imaging by substantially enhancing the collection of the backscattered signal and increasing the imaging speed by three orders of magnitude to video rate. This approach allows label-free in vivo imaging of water, lipid, and protein in skin and mapping of penetration pathways of topically applied drugs in mice and humans.