Vakoc Benjamin J, Lanning Ryan M, Tyrrell James A, Padera Timothy P, Bartlett Lisa A, Stylianopoulos Triantafyllos, Munn Lance L, Tearney Guillermo J, Fukumura Dai, Jain Rakesh K, Bouma Brett E
Wellman Center for Photomedicine, Department of Dermatology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, USA.
Nat Med. 2009 Oct;15(10):1219-23. doi: 10.1038/nm.1971. Epub 2009 Sep 13.
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.
活体多光子显微镜已为健康和疾病研究提供了强大的机制性见解，并成为现代生物实验室中的常用仪器。然而，实现多光子显微镜所需的高数值孔径和外源性造影剂限制了对大量组织体积进行研究或长时间反复探测动态变化的能力。在此，我们引入光学频域成像（OFDI）作为一种活体显微镜技术，它克服了多光子显微镜的技术局限性，从而以前所未有的方式揭示了组织生物学中以前未被探索的关键方面。利用基于OFDI的独特方法和完全内在的造影机制，我们展示了对肿瘤血管生成、淋巴管生成、组织活力以及血管和细胞对治疗的反应进行快速且重复的测量，从而证明了OFDI在促进生理和病理过程探索以及治疗策略评估方面的潜力。
