AREA OF FOCUS

In vivo optical microscopy imaging aims to non-invasively observe the (sub)cellular structures of living tissues or model organisms and track their functional dynamics. It has broad applications in both life sciences and clinical diagnosis and treatment. Compared to thin samples such as tissue sections or adherent cultured cells, imaging of living tissues presents two major challenges, which are also technical hurdles: 
(1) it requires three-dimensional resolution (also known as depth sectioning) to directly probe thick samples.
(2) it must possess sufficient four-dimensional spatiotemporal resolution (three-dimensional space x one-dimensional time) to capture the dynamic functional information of the living organism. 

With the development of new calcium ion-sensitive fluorescent proteins and voltage-sensitive molecular fluorescent probes capable of resolving single action potentials, the neuroscience field urgently needs new three-dimensional in vivo microscopy techniques with higher spatiotemporal resolution. One of the strategic directions of our research group is to innovate imaging principles and acquisition strategies to continually improve key performance metrics such as spatiotemporal resolution, field of view, and imaging depth in in vivo three-dimensional microscopy. 

On the other hand, in clinical scenarios such as non-invasive (early) diagnosis, biopsy assistance, micro-surgical navigation, and treatment follow-up, the miniaturization and micro-miniaturization of imaging devices is crucial. Another strategic direction of our group is to develop handheld or endoscopic small (micro) microscopy probes capable of real-time, non-invasive, in situ acquisition of three-dimensional micro-pathological structure and functional information of subepidermal tissues, achieving an imaging effect that provides 'as if sectioning, but without the need for sectioning' through breakthroughs in architecture design and core components.

PUBLICATIONS

1. Liang W†, Liu Y, Guan H, Sakulsaengprapha V, Luby-Phelps K, Mahendroo M, and Li X. Cervical Collagen Network Porosity Assessed by SHG Endomicroscopy Distinguishes Preterm and Normal Pregnancy — a Pilot Study. 
   IEEE Transactions on Biomedical Engineering, 72(2), 777-785 (2025) †Correspondence    DOI: 10.1109/TBME.2024.3472015
   

2. Hall G*, Liang W*†, Bhujwalla ZM, and Li X†. SHG fiberscopy assessment of collagen morphology and its potential for breast cancer optical histology. 
   IEEE Transactions on Biomedical Engineering 71(8), 2414-2420 (2024). *Equal contribution, †Correspondence     DOI: 10.1109/TBME.2024.3372629
   

3. Liang W, Chen D, Guan H, Park HC, Li K, Li A, Li MJ and Li X. Label-Free metabolic imaging in vivo by two-photon fluorescence lifetime endomicroscopy. 
   ACS Photonics, 9(12), 4017-4029 (2022)         https://doi.org/10.1021/acsphotonics.2c01493

4. Patel KB, Liang W, Casper MJ, Voleti V, Zhao HT, Perez-Campos C, Liu JM, Coley SM, and Hillman EMC. High-speed light-sheet microscopy for the in-situ acquisition of volumetric histological images of living tissue. 
   Nature Biomedical Engineering 6, 569-583 (2022)         https://doi.org/10.1038/s41551-022-00849-7

5. Liang W, Park HC, Li K, Li A, Chen D, Guan H, Yue Y, Gau YT, Bergles DE, Li MJ, Lu H, and Li X. Throughput-speed product augmentation for scanning fiber-optic two-photon endomicroscopy. 
   IEEE Transactions on Medical Imaging 39(12), 3779-3787 (2020)         https://doi.org/10.1109/TMI.2020.3005067

6. Li K*, Liang W*, Yang Z, Liang Y, and Wan S. Robust, accurate depth-resolved attenuation characterization in optical coherence tomography. 
   Biomedical Optics Express 11(2), 672-687 (2020) *Equal contribution         https://doi.org/10.1364/BOE.382493

7. Voleti V, Patel KB, Li W, Campos CP, Bharadwaj S, Yu H, Ford C, Casper MJ, Yan RW, Liang W, Wen C, Kimura KD, Targoff KL, and Hillman EMC. Real-time volumetric microscopy of in vivo dynamics and large-scale samples with SCAPE 2.0. 
   Nature Methods 16(10), 1054–1062 (2019)         https://doi.org/10.1038/s41592-019-0579-4

8. Li K, Liang W, Mavadia-Shukla J, Park HC, Li D, Yuan W, Wan S, and Li X. Super-achromatic optical coherence tomography capsule for ultrahigh‐resolution imaging of esophagus. 
   Journal of Biophotonics 12(3), e201800205 (2019)         https://doi.org/10.1002/jbio.201800205

9. Liang W*, Hall G*, and Li X. Spectro-temporal dispersion management of femtosecond pulses for fiber-optic two-photon endomicroscopy. 
   Optics Express 26(18), 22877-22893 (2018) *Equal contribution         https://doi.org/10.1364/OE.26.022877

10. Liang W, Hall G, Messerschmidt B, Li MJ, and Li X. Nonlinear optical endomicroscopy for label-free functional histology in vivo. 
    Light: Science and Applications 6, e17082 (2017)         https://doi.org/10.1038/lsa.2017.82