Biophotonic Imaging: From Nano- to Macro

Daniel L. Farkas, PhD

Vice Chairman, Department of Surgery
and Director, Minimally Invasive Surgical Technologies Institute
Cedars-Sinai Medical Center
Los Angeles CA, (310) 423-7746
Email: farkasd@cshs.org

Abstract

This talk will attempt to (1) summarize new technology advances in optical imaging, (2) review some of their more exciting applications and (3) discuss our best hopes for biophotonics’ future.

(1) Optical methods yield the most versatile, highest resolution non-invasive bioimaging. Microscopy - an icon of the sciences and long the dominant technique - has enjoyed a veritable renaissance recently. Dynamic, three-dimensional study of molecules in action, within the basic units of life, living cells [1-2], was aided by some of our contributions in automated/robotic live microscopy of subcellular events [3]. Quantitation and temporal resolution can further be enhanced spectrally and temporally by acousto-optic tunable filters with no moving parts that we perfected to yield diffraction limited, sub-millisecond optical imaging with 2 nm resolution [4-8].

(2) Applying these advances in the pre-clinical and clinical domain necessitates further development, to be discussed with emphasis on enabling technologies such as hyperspectral and lifetime imaging. Performance enhancements and their engineering underpinnings will be highlighted, all moving us closer to the ultimate in bioimaging: molecular (nanoscale) detection, resolution and quantitation at the tissue, organ and whole body level [9-11], preferably of function, in vivo (in animals and humans).

(3) The potential of such mesoscopic imaging for addressing important biotechnology goals (such as high throughput screening and multiplexed intracellular proteomics) and medical challenges, including neurobiology, surgery, blood oxygenation imaging, cancer detection and regenerative medicine will be illustrated with a few relevant results [12-19]. A discussion of academia-industry-medical interactions [20], of ongoing projects Cedars-Sinai Medial Center, and of strategies for the future will conclude the talk.

References:

  1. Farkas, DL, et al. (eds.) (1997-2004) Progr. Biomed. Optics, vols. 2983, 3260, 3604, 3921, 4260, 4622, 4962, 5322.
  2. Farkas, D.L. & Hell, S. (editors) (2001) Frontiers in Microscopy, Special edition, J. Biomed. Optics, vol. 6 (3).
  3. Taylor, D.L., et al. (1997) Ann. New York Acad. Sci., 820, 208-228.
  4. Wachman, E.S., Niu, W., Farkas, D.L. (1996) Applied Optics, 35, 5220-5226.
  5. Wachman, E.S. et al. (1997) Biophysical Journal, 73, 1215-1222.
  6. Wachman E.S., Farkas D.L., Niu, W. (1998) U.S. Patents 5,796,512 and 5,841,577 (and corresp. international ones).
  7. Farkas, D. L., et al. (1998) Springer Lecture Notes in Computer Science, 1311, 663-671.
  8. Farkas, D.L. (2001) in Methods in Cellular Imaging, Oxford University Press, pp. 345-361.
  9. Shonat, R. D., et al. (1997) Biophysical Journal, 73, 1223-1231.
  10. Farkas, D. L., et al. (1998) Computerized Medical Imaging and Graphics, 22, 89-102.
  11. Ballou, B. et al. (1997) Biotechnology Progress, 13, 649-658.
  12. Ballou et al. (1998) Cancer Detection and Prevention, 22, 251-257.
  13. Pan, Y. and Farkas, D.L. (1998) J. Biomed. Optics, 3, 446-455; (2001) Medical Physics, 28: 2432-2440.
  14. Kirkwood, J.M., Farkas D.L. et al. (1999) Molecular Medicine, 5, 11-20
  15. Yang, P. et al. (1999) Molecular Medicine, 5, 785-794; Yin, X.-Y. et al. (2001) Oncogene, 20, 4650-4664.
  16. Farkas D.L. and Becker, D. (2001) Pigment Cell Research 14, 2-8.
  17. Valesky, M. et al. (2002) Molecular Medicine, 8: 103-112; Pfaff-Smith, A. et al. (2003) Molecular Imaging, 2: 65-73.
  18. Wachman, E.W. et al. (2004) J. Neurosci., in press
  19. Askenasy, N., Farkas, D.L. et al. (2002) Stem Cells, 20: 80-85; 301-310; 501-513; (2003) 21: 200-207; Exper. Hematol. 12: 1292-1300; Br. J. Hematol. 120: 1-11; 505-515; Biol. Bone Marrow Transpl. 9: 496-504.
  20. Farkas, D.L. (2003) Nature Biotechnology, 21: 1269-1271.