Technical Report abstract
Nature Medicine 15, 1219 - 1223 (2009)
Published online: 13 September 2009 | doi:10.1038/nm.1971
Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging
Benjamin J Vakoc1,2,3,6, Ryan M Lanning3,4,6, James A Tyrrell4, Timothy P Padera4, Lisa A Bartlett1, Triantafyllos Stylianopoulos4, Lance L Munn4, Guillermo J Tearney1,3,5, Dai Fukumura4, Rakesh K Jain4 & Brett E Bouma1,2,3
Abstract
Intravital multiphoton microscopy has provided powerful mechanistic insights into health and disease and has become a common instrument in the modern biological laboratory. The requisite high numerical aperture and exogenous contrast agents that enable multiphoton microscopy, however, limit the ability to investigate substantial tissue volumes or to probe dynamic changes repeatedly over prolonged periods. Here we introduce optical frequency domain imaging (OFDI) as an intravital microscopy that circumvents the technical limitations of multiphoton microscopy and, as a result, provides unprecedented access to previously unexplored, crucial aspects of tissue biology. Using unique OFDI-based approaches and entirely intrinsic mechanisms of contrast, we present rapid and repeated measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy, thereby demonstrating the potential of OFDI to facilitate the exploration of physiological and pathological processes and the evaluation of treatment strategies.
- Wellman Center for Photomedicine, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA.
- Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA.
- Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
- Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
- Department of Pathology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA.
- These authors contributed equally to this work.
Correspondence to: Rakesh K Jain4 e-mail: jain@steele.mgh.harvard.edu
Correspondence to: Brett E Bouma1,2,3 e-mail: bouma@helix.mgh.harvard.edu
