Fake "Frank" Lu
Assistant Professor
Biomedical Engineering
Background
The Biophotonics and Translational Optical Imaging Lab is dedicated to developing novel optical technologies for imaging of living systems to improve understanding, diagnosis, and intervention of human diseases, focusing on cancer and neuro-oncology diseases. Ongoing projects include:
Stimulated Raman Imaging for Label-Free Pathology and Image-Guided Neurosurgery
Stimulated Raman scattering (SRS) microscopy is a hybrid technology between multiphoton microscopy and Raman spectroscopy. SRS microscopy can do rapid, high-resolution Raman imaging of the chemical bonds in the native biomolecules. The stain-free biomolecular contrasts of SRS imaging enables numerous biomedical applications. In particular, two-color SRS imaging of lipids and proteins has been used to render stain-free digital neuropathology for rapid diagnosis using fresh tissue. This methodology can potentially replace the intraoperative histopathological consultation, which requires long turn-back time and intense labor for sample preparation in the pathology division.
The essential diagnostic feature in oncologic pathology is the cancer cell nuclei. In stain-free SRS pathology images, the contrast of cell nuclei is lower than in H&E-stained images. To achieve rapid segmentation and quantification of cell nuclei from the heterogeneous tissue background, collaborating with computer and data science experts, we are using deep neural networks (DNN) to analyze SRS images of cancer cells. We developed a two-photon fluorescence imaging-based automated labeling approach to provide large-scale labeled data as the ground truth for the training of U-NET and MASK RCNN networks. The trained machine learning models are able to rapidly identify cell nuclei from two-color SRS images with high accuracy. The AI-powered SRS rapid fresh tissue digital pathology will be eventually used for image-guided brain tumor surgery in the operating room.
Live-Cell Imaging with SRS and Multiphoton Microscopy for Cancer Lipid Metabolism Studies
We are developing live-cell imaging technologies for long-term, time-lapse tracking of lipid droplets (LDs) in cancer cells using SRS and multiphoton microscopy. Abnormal lipid metabolism is a newly identified hallmark of cancer, such as gliomas (GBM) or ovarian cancer. Stain-free imaging of the native LDs in live cells with SRS has a few unique advantages over fluorescence-stained imaging. Unlike fluorescence, SRS imaging has no photobleaching issue. In addition, SRS can image all newly synthesized LDs, which may not carry any fluorescence staining. More importantly, hyperspectral SRS imaging can decode the biochemical composition of the LDs, which cannot be achieved with two-photon fluorescence imaging. Imaging the quantification and dynamics of LDs in cancer cells may help discover new anti-cancer therapeutics.
Imaging Drug Delivery Using SRS Microscopy with Raman Tags
Collaborating with pharmaceutical experts, we are developing novel Raman tags for SRS imaging of drug delivery with improved sensitivity. As a proof-of-principle study, we synthesize non-fluorescent lysosome trackers with bright Raman tags. Overlay imaging of stain-free lipid droplets (LDs) and lysosomes with the Raman Lysotracker reveals active interaction between the two cellular organelles. Current work focuses on imaging the transmembrane trafficking and the dynamics of Raman-tagged drug molecules in live cancer cells.
Selected Publications
Yuan Y, Shah N, Almohaisin MI, Saha S, Lu F. Assessing fatty acid-induced lipotoxicity and its therapeutic potential in glioblastoma using stimulated Raman microscopy. Scientific Reports. 2021 Apr 1;11(1):1-4.
Sun M, Yuan Y, Lu F., and Di Pasqua, AJ. Physicochemical Factors That Influence the Biocompatibility of Cationic Liposomes and Their Ability to Deliver DNA to the Nuclei of Ovarian Cancer SK-OV-3 Cells. Materials (Basel, Switzerland). 2021 Jan 16;14(2):416.
Wang F, Yuan Y, Sun Q, Dai M, Ai L, Lu F. Design and implementation of the galvanometer scanning system for reflectance confocal and stimulated Raman scattering microscopy. Chinese Optics Letters. 2020 Dec 10;18(12):121703.
Randall EC, Emdal KB, Laramy JK, Kim M, Roos A, Calligaris D, Regan MS, Gupta SK, Mladek AC, Carlson BL, Johnson AJ, Lu F.K., Xie XS, et. al. Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma. Nature communications. 2018 Nov 21;9(1):1-3.
Yang W., Li A., Suo Y., Lu F.K., Xie X.S. Simultaneous two-color stimulated Raman scattering microscopy by adding a fiber amplifier to a two-picosecond OPO-based SRS microscope. Opt. Lett. 42:523-526 (2017).
Lu F.K., Calligaris D., Olubiyi O.I., Norton I., Yang W., Santagata S., Xie X.S., Golby A.J., Agar N.Y.R. Label-Free Neurosurgical Pathology with Stimulated Raman Imaging. Cancer Res. 76(12):3451-62 (2016).
Valdes P.A., Roberts D.W., Lu F.K., Golby AJ. Optical technologies for intraoperative neurosurgical guidance. Neurosurg. Focus; 40(3):E8 (Invited Review; Cover Page; 2016).
Lu F.K., Basu S., Igras V., Hoang M.P., Ji M., Fu D., Holtom G.R., Neel V.A., Freudiger C.W., Fisher D.E., Xie X.S. Label-free DNA imaging in vivo with stimulated Raman scattering microscopy. PNAS 112(37):11624-9 (2015).
Lu F.K., Ji M., Fu D., Ni X., Freudiger C.W., Holtom G., Xie X.S. Multicolor stimulated Raman scattering (SRS) microscopy. Mol. Phys. 110(15-16):1927-32 (Invited paper; 2012).
Fu D., Lu F.K., Zhang X., Freudiger C., Pernik D.R., Holtom G., Xie X.S. Quantitative chemical imaging with multiplex stimulated Raman scattering microscopy. J. Am. Chem. Soc. (8): 3623-6 (2012).
Lu F., Zheng W., Huang Z. Coherent anti-Stokes Raman scattering microscopy using tightly focused radially polarized light. Opt. Lett. 34(12):1870-2 (2009).
Lu F., Zheng W., Sheppard C., Huang Z. Interferometric polarization coherent anti-Stokes Raman scattering (IP-CARS) microscopy. Opt. Lett. 33(6):602-4 (2008).
Education
- BS, Zhejiang University
- MS, Zhejiang University
- PhD, National University of Singapore
Research Interests
- Stimulated Raman scattering (SRS) microscopy
- Multiphoton microscopy and ptychography
- AI-based SRS label-free digital neuropathology
- Live-cell imaging for lipid metabolism studies in cancer
- Imaging drug delivery using SRS/Raman-tags
Awards
- The first place of Art of Science Competition at BU 2021 (Visualizing the Unseen Category)
- SSD Recognition Honoree 2020
- Best Poster Award on SPIE Photonics West BiOS Conference, 2020
- K99/R00 NIH Pathway to Independence Award, 2015-20
