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Xingde Li, PhD (1994-1998 PhD at JF)

Immuno ICG Nanocapsules and Scanning Nonlinear Optical Endomicroscopy for Translational Biophotonics Imaging. Xingde Li, PhD (1994-1998 PhD at JF). Department of Biomedical Engineering Johns Hopkins University. BC Legacy Workshop, June 4, 2011. Thank you!. phase shift and demodulation.

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Xingde Li, PhD (1994-1998 PhD at JF)

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  1. Immuno ICG Nanocapsules and Scanning Nonlinear Optical Endomicroscopyfor Translational Biophotonics Imaging Xingde Li, PhD (1994-1998 PhD at JF) Department of Biomedical Engineering Johns Hopkins University BC Legacy Workshop, June 4, 2011

  2. Thank you!

  3. phase shift and demodulation due to fluorophore concentration and lifetime h ( r ) w L (r, ) = w t 1 - i ( r ) f f em ex Point Fluorophore Source Detector r r r s d Joining the Lab: June 1994 Fluorescence Imaging in Turbid Media? Source Intensity

  4. Near-infrared Fluorescence Contrast Agents

  5. Ratio of Max Fluorescence Typical Fluorescence Signal and Tumor Size Theory Tumor 3.5 Ratio (T/N) 2 10 3 Ratio (Tumor / Control) Tumor Size (cm Fluorescence (Arb. Units) 8 1.5 2.5 6 3 Tumor size ) Normal 2 1 4 1.5 2 0.5 Time (min) Days After Injection of Tumor Cells 1 0 0 2 4 6 8 0.5 0 0 5 10 15 20 25 30 35 40 In vivo Fluorescence SignalsTumor versus Control Ratio of max fluorescence signal: tumor / normal ~2.5 fold Ratio of initial clearance velocity: tumor / normal ~4 fold. Theoretical contrast: Nobj/Nbg ~7-fold S-D separation: 8 mm Tumor depth: 2 mm (subcutaneous) Summer 1994

  6. Patient (M84) Dosage: 0.4 mg / Kg BW ( limit ~2.0 mg / Kg BW) Tumor 2.5 2.0 1.5 Fluorescence (Arb. Units) Normal 1.0 0.5 0.0 0 2 4 6 8 10 12 Time (min) Preliminary Clinical Study Patient with breast tumor palpable, ~2cm deep, 0.8 cm in diameter Ratio of max fluorescence signal: tumor / normal ~1.5 fold Ratio of initial clearance velocity: tumor / normal ~2.0 fold Summer 1994

  7. Fluorescent Polymeric Micelles (pluronic micelles) Encapsulate ICG into its hydrophobic core. Enhancing fluorescence emission and stability Potentially bioconjugatible, enhanced permeation and retention (EPR) FAD approval? V. Rodriguez, S. Henry, A. Hoffman, P. Stayton, X. D. Li, and S. H. Pun, Journal of Biomedical Optics (2008)

  8. ICG Encapsulation by Pluronic Micelle ICG in Chloroform OH OH Stirring 3h Evaporation (Emulsification and Evaporation) OH OH Polymer (Aqueous Solution) ATM Image of ICG Nanocapsules ~30 nm in diameter Size is small, suitable for in vivo tumor delivery.

  9. ICG Fluorescence Stability of in Micelles Excellent ICG fluorescence stability micellar nanocapsules. T. H. Kim et al., Pharmaceutical Research 27 (9), 1900-1913 (2010).

  10. XENOGEN IVIS System Tomography System nM Tumor Tumor Tumor Tumor Tumor Tumor Micelle/ICG mAb-micelle/ICG (3 days post injection of ICG micelles with an ICG dose of 0.5 mg/Kg ) Strong ICG fluorescence from targeted tumor with immunomicelles. In vivo Tumor Imaging with ICG-Immunomicelles

  11. In-tumor ICG Concentration vs Time (Initial Pharmacokinetics Study)

  12. About Graduation Chatting with BC about what to do next: Metabolic/Functional Imaging, in vivo • Scanning Nonlinear Endomicroscopy: • Enabling in vivo Two-photon Fluorescence (TPF) • & Second Harmonic Generation (SHG) Imaging

  13. Two-photon Fluorescence Imaging Single-photon Flr Two-photon Flr Mucosal mast cells: Green: plasma membrane Blue: nuclei Red: mitochondria www.biorad.com Nature Biotechnology  21, 1369 - 1377 (2003)

  14. TPF Endomicroscope (distal end) Distal End Accessory Port (2.8 mm) Motivation: Nonlinear Optical Microscope  Endomicroscope

  15. Standard Endoscope Endomicroscope Distal End Photo of Scanning TFP Endomicroscope 2.4 mm Diameter Report in Biophotonics International, June 2006. M. T. Myaing, D. J. MacDonald, and X. D. Li, Optics Letters 31(8):1076-1078 (2006).

  16. Cancer Visualization of Histopathology in situ Barrett’s Concept R. Kiesslich and M. I. Canto, GI Endoscopy Clinics N Am 19(2):261-272(2009).

  17. 20um (Active) Neuron / Brain Function Imaging (ultimately on freely walking animals) Vessel Endomicroscope Astrocyte? Freely-walking animal Astrocyte (star-shaped glial cells): provision of nutrients, maintenance of extracellular ion balance, long-distance propagation of Ca+2 wave, etc.

  18. Resonant PZT Scanner (1mm, kHz) Miniature Compound Lens Double-clad Fiber: Delivery and Collection Photonic Crystal Fiber (Dispersion Management) (b) Compound lens DCF with MMF PZT Outer Cladding Miniature Scanning Head 5 mm Core Inner Cladding Basic Building Blocks

  19. Rapid SpiralScanning Pattern X. M. Liu, M. J. Cobb, M. B. Kimmey, and X. D. Li, Optics Letters (2004) Y. C. Wu, Y. Leng, J. F. Xi, and X. D. Li, Optics Express (2009). L. Huo, J. F. Xi, Y. C. Wu, and X. D. Li, Optics Express (2010).

  20. Photo of TPF/SHG Endomicroscope fs Fiber Laser 18” Microendoscope 12” 7” The whole system is very compact!

  21. Pancreas Liver Salivary Gland 20um 20um 20um Kidney Brain Spleen 20um 20um 20um TPF Images of GFP Mouse Tissues (ex = 870nm) Collaboration with Dr. R. Weigert at NIH

  22. Intrinsic TPF Endomicroscopy of Fresh Tissues 20µm 20µm 20µm 20µm 20µm 20µm Fresh Rat Lip Fresh Rat Oral Cavity Fresh Mouse Dorsal Skin 50mW 50mW 60mW Fresh Mouse Xenograft Tumor Fresh Pig Esophagus Fresh Mouse Colon 60mW 60mW 60mW

  23. 10 μm 10 μm 10 μm 10 μm 10 μm 10 μm 10 μm 10 μm Further Comparison of Endomicroscopy with Microscopy for SHG Imaging of Breast Tissues Normal Endo Microscopy Endo Microscopy Tumor

  24. Thank you!

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