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Biomedical Engineering Department

Our Faculty

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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 interventions of human diseases, focusing on neuro-oncologic and neurodegenerative diseases. Ongoing projects include:

- Translational: label-free neurosurgical pathology for image-guided brain tumor surgery.

Precision operation in neurosurgery is highly desired because complete removal of tumor with no injury to the critical brain/spinal functional structures yields improved outcomes in patients. Neuronavigation system with MRI data is being used for image-guided surgery (IGS). However, accuracy of the guidance decreases as surgery progresses due to the “brain shift”. While standard histopathology provides information that could assist tumor delineation, it cannot be performed iteratively during surgery since the procedure of cryosectioning and H&E staining is time-consuming and labor-intensive. Stimulated Raman scattering (SRS) microscopy is a powerful label-free chemical imaging technology that enables rapid mapping of biomolecules, such as lipid, protein and nucleic acids within a fresh specimen. This information can be rendered into pathology-like images for histopathology evaluation. Our previous work has established the methodology of label-free neurosurgical pathology. Collaborating with the neurosurgery programs at Upstate Medical University – SUNY and Brigham and Women's Hospital, the long-term goal of this project is to develop a medical device based on video-rate SRS imaging to provide instant label-free surgical pathology to help decision-making of the neurosurgeons.

- Fundamental: imaging dynamics in living systems.

Tumor microenvironment (TME) is the cellular environment in which cancer cells, immune cells, fibroblastic cells, blood vessels and extracellular matrix are closely interacting. The role of TME is now realized to be of critical importance for drug delivery, therapeutic response, immune-escape, and distant metastasis. Intravital microscopy (IVM) with integrated multimodality of SRS, two-photon fluorescence (TPF) and second harmonic generation (SHG) will provide multiple chemical contrasts for imaging of lipids, proteins, nucleic acids, blood vessels, collagen, or small-molecule drugs, either label-free or with click-chemistry. Aims of this project are to develop an integrative nonlinear optical microscopy platform with various modalities for intravital imaging of live cells and small animals, and using this platform to monitor the dynamics of cellular and molecular profiles of the TME as tumor progresses and upon drug treatment.

- Pioneering: quantitative imaging and correlation of label-free biomolecules in Alzheimer's Disease. Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is the most common cause of dementia. Molecular pathogenesis of AD is poorly understood. AD can be characterized by degeneration of myelin sheath of axons, loss of neurons and synapses, deposition of amyloid plaques, aggregation of neurofibrillary tangles. Although these biomolecular changes can be detected using staining methods, systematic high-resolution imaging and quantification of the essential tissue markers in AD remains to be difficult. Aim of this pioneering study is to use multicolor SRS microscopy for label-free biomolecular imaging characterization to uncover co-distribution and quantitative correlation among the AD-related biomolecules along the disease progression.

Relevant Publications

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).

Tian F., Yang W., Mordes D.A., Wang J.Y., Salameh J.S., Mok J., Chew J., Sharma A., Leno-Duran E., Suzuki-Uematsu S., Suzuki N., Han S.S., Lu F.K., Ji M., Zhang R., Liu Y., Strominger J., Shneider N.A., Petrucelli L., Xie X.S., Eggan K. Monitoring peripheral nerve degeneration in ALS cases and mouse models by label-free stimulated Raman scattering imaging. Nat. Commun. 7:13283 (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; 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).

Lin J., Lu F., Zheng W., Xu S., Tai D., Yu H., Huang Z. Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique. J. Biomed. Opt. 16(11):116024 (2011).

Lu F., Zheng W., Lin J., Huang Z. Integrated coherent anti-Stokes Raman scattering and multiphoton microscopy for biomolecular imaging using spectral filtering of a femtosecond laser. Appl. Phys. Lett. 96(13) (2010).

Lin J., Lu F., Zheng W., Huang Z. Annular aperture-detected coherent anti-Stokes Raman scattering microscopy for high contrast vibrational imaging. Appl. Phys. Lett. 97(8):083701 (2010).

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).

Liu C., Huang Z., Lu F., Zheng W., Hutmacher D.W., Sheppard C. Near-field effects on coherent anti-Stokes Raman scattering microscopy imaging. Opt. Express 15(7):4118-31 (2007).

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).

Lu F., Zheng W., Huang Z. Heterodyne polarization coherent anti-Stokes Raman scattering microscopy. Appl. Phys. Lett. 92(12):123901 (2008).

Lu F., Zheng W., Huang Z. Phase-controlled polarization coherent anti-Stokes Raman scattering microscopy for high-sensitivity and high-contrast molecular imaging. J. Opt. Soc. Am. B 25(11):1907-13 (2008).

Lu F., Zheng W., Huang Z. Elliptically polarized coherent anti-Stokes Raman scattering microscopy. Opt. Lett. 33(23):2842-4 (2008).

Book Chapter: Olubiyi O.I., Lu F.K., Calligaris D., Jolesz F.A., Agar N.Y.R. “Advanced Molecular Imaging for Surgery” in the book “Image-Guided Neurosurgery”, edited by Golby A.J. (2015).

Education

  • BS, Zhejiang University
  • MS, Zhejiang University
  • PhD, National University of Singapore

Research Interests

  • multiphoton microscopy
  • label-free digital histopathology
  • Stimulated Raman scattering (SRS) microscopy
  • live-cell imaging
  • dynamic imaging into the tumor microenvironment
  • optical bioimaging for neurosurgical guidance and neuro-oncologic studies
  • computer-visi

Awards

    • K99/R00 NIH Pathway to Independence Award
    • 2015 – 2020
    • Chinese Government Award for Outstanding Self-Financed Students Abroad
    • 2009
    • President's Graduate Fellowship
    • Singapore
    • 2009
    • Lee Foundation
    • Singapore
    • 2009

Last Updated: 4/12/17