Interventional Fluorescence Lifetime Imaging (iFLIM)
Led by Dr. Laura Marcu, TRD1 will technologically advance and integrate Interventional Fluorescence Lifetime Imaging (iFLIM) technology in clinical settings for real-time in-situ tissue diagnosis and guidance of surgical procedures.
Intraoperative assessment of site-specific tissue properties relevant to intraoperative surgical decisions is limited. iFLIM can potentially address this unmet need and improve surgical outcomes. While basic principles of Fluorescence Lifetime Imaging (FLIM) technology are well-established and FLIM-based techniques are in use, FLIM has been employed in few clinical research studies and its clinical utility remains largely unexplored.
TRD1 has four specific aims, illustrated in the image below. Aim 1 and Aim 2 advance iFLIM technology advancement and scalability (prototyping, standardization). Aim 3 seeks synergistic integration of iFLIM with other optical imaging modalities for clinical use, and Aim 4 targets intra-procedural workflow and database cluster creation.
The iFLIM research in this TRD seeks to accomplish the following deliverables:
- iFLIM detectors with significantly enhanced sensitivity (10-fold) and speed (5-to-10-fold) compared to current technology
- Innovative packaging strategies that will help in building a miniaturized (<1mm x 1mm) planar FLIM imaging platform (spectrometer-on-a-chip)
- Double-clad fiber-based intraoperative probe/endomicroscope capable of multimodal imaging (iFLIM and OCT, iFLIM and iDOS)
- Standardization and integration of iFLIM devices into clinical workflow: FLIM-based biochemical/metabolic data complementary to other data streams (PET, CT, MRI) in informing clinical decisions
- Aggregated data for development of the analytical methods of TRD3 and distribution to the national scientific community
- Alba Alfonso-Garcia, Ph.D.
- Mohamed Hassan, Ph.D.
- Dinesh Jackson Samuel Ravindran Charles, Ph.D.
- Brent Weyers, Ph.D.
- Xiangnan Zhou, Ph.D.
- Kelsey T Hadfield
- Silvia Noble Anbunesan
- Ankit Singh
- Cesar Bartolo-Perez
- Cheng-Yu Lee, UC Davis – JHU
- Ahasan Ahamed
- Kacie Sorfleet
- Alex Condon
- Optical Imaging to Improve Surgery & Targeted Therapy in Brain Tumors
- Full Field OCT for cellular level structural and functional retinal imaging
- Perioperative diffuse optical imaging of tissue blood flow and oxygenation for optimization of mastectomy skin flap viability
- In utero Repair of Fetal Myelomeningocele
- Bimodal Intraoral imaging device for detection of oral epithelial neoplasia
- Imaging Goggles for Fluorescence-Guided Surgery
- iFLIM-based In vivo Evaluation of Thermal Injury by Cautery during Robotic Surgery Procedures
- Navigated Neurosurgical Procedures via 3D Augmented iFLIM
- Marcu Biophotonics Laboratory and clinical manufacturing facility at UC Davis
- Li Laboratory at Johns Hopkins School of Medicine, including multiple vibration isolation optical tables, laser sources and imaging systems.
- Miller Research Building and Small Animal Research Program (SAIRP)
- Islam Laboratory, including a cold-wall CVD reactor and equipped for the characterization of semiconductor devices and optical systems.
- UC Davis Center for Nano- and Microb-Manufacturing (CNM2)
- UC Davis Biomedical Engineering Machine Shop: "TEAM Lab"
- UCD Comprehensive Cancer Center Shared Resources, including capabilities for genomics, flow cytometry, molecular pharmacology, biorepository and biostatics support.
- UC Davis Genome Center - DNA Technologies and Expression Core
Wang N, Lee CY, Park HC, Nauen DW, Chaichana KL, Quinones-Hinojosa A, Bettegowda C, Li X. Deep learning-based optical coherence tomography image analysis of human brain cancer. Biomedical Optics Express. 2023 Jan 1;14(1):81-8. doi: 10.1364/BOE.477311
Noble Anbunesan S, Alfonso‐Garcia A, Zhou X, Bec J, Lee HS, Jin LW, Bloch O, Marcu L. Intraoperative detection of IDH‐mutant glioma using fluorescence lifetime imaging. Journal of Biophotonics. e202200291. PMID: 36510639. doi: 10.1002/jbio.202200291
Li C, Bec J, Zhou X, Marcu L. Dual-modality fluorescence lifetime imaging-optical coherence tomography intravascular catheter system with freeform catheter optics. Journal of biomedical optics. 2022 Jul;27(7):076005. PMID: 35864574. doi: 10.1117/1.JBO.27.7.076005
Bartolo-Perez C, Ahamed A, Mayet AS, Rawat A, McPhillips L, Ghandiparsi S, Bec J, Ariño-Estrada G, Cherry S, Wang SY, Marcu L, Islam S. Engineering the gain and bandwidth in avalanche photodetectors. Optics Express. 2022 May 9;30(10):16873-82. doi: 10.1364/OE.446507
Weyers BW, Birkeland AC, Marsden MA, Tam A, Bec J, Frusciante RP, Gui D, Bewley AF, Abouyared M, Marcu L, Farwell DG. Intraoperative delineation of p16+ oropharyngeal carcinoma of unknown primary origin with fluorescence lifetime imaging: Preliminary report. Head & Neck. 2022 May 5. PMID: 35511208. doi: 10.1002/hed.27078
Alfonso-Garcia A, Cevallos SA, Lee JY, Li C, Bec J, Bäumler AJ, Marcu L. Assessment of Murine Colon Inflammation Using Intraluminal Fluorescence Lifetime Imaging. Molecules. 2022 Feb 15;27(4):1317. PMID: 35209104. doi: 10.3390/molecules27041317
Alfonso-García A, Zhou X, Bec J, Anbunesan SN, Fereidouni F, Jin LW, Lee HS, Bloch O, Marcu L. First in patient assessment of brain tumor infiltrative margins using simultaneous time-resolved measurements of 5-ALA-induced PpIX fluorescence and tissue autofluorescence. Journal of biomedical optics. 2022 Feb;27(2):020501. PMID: 35112514. doi: 10.1117/1.JBO.27.2.020501
A. Li, H. Guan, H. C. Park, Y. Yue, D. Chen, W. Liang, M.-J. Li, H. Lu, and X. D. Li. "Twist-free ultralight two-photon fiberscope enabling neuroimaging on freely rotating/walking mice," Optica 8(6), 870-879, (2021).
D. Chen, D. W. Nauen, H. C. Park, D. Li, W. Yuan, A. Li, H. Guan, C. Kut, K. L. Chaichana, C. Bettegowda, A. Quiñones-Hinojosa, and X. D. Li. "Label-free imaging of human brain tissue at subcellular resolution for potential rapid intra-operative assessment of glioma surgery," Theranostics 11(15), 7222-7234, (2021).
W. Yuan, D. Chen, R. Sarabia-Estrada, H. Guerrero-Cázares, D. W. Li, A. Quiñones-Hinojosa, and X. D. Li. "Theranostic OCT microneedle for fast ultrahigh-resolution deep-brain imaging and efficient laser ablation in vivo," Science Advances 6(15), eaaz9664, (2020).
Bartolo-Perez, C., Chandiparsi, S., Mayet, A.S., Cansizoglu, H., Gao, Y., Qarony, W., AhAmed, A., Wang, S.Y., Cherry, S.R., Islam, M.S. and Ariño-Estrada, G., 2021. "Avalanche photodetectors with photon trapping structures for biomedical imaging applications," Optics Express, 29(12), pp.19024-19033.
Bartolo-Perez, C., Qarony, W., Ghandiparsi, S., Mayet, A.S., Ahamed, A., Cansizoglu, H., Gao, Y., Ponizovskaya Devine, E., Yamada, T., Elrefaie, A.F. and Wang, S.Y., Islam, M.S., 2021. "Maximizing Absorption in Photon‐Trapping Ultrafast Silicon Photodetectors," Advanced Photonics Research, p.2000190.
Devine, E.P., Qarony, W., Ahamed, A., Mayet, A.S., Ghandiparsi, S., Bartolo-Perez, C., Elrefaie, A.F., Yamada, T., Wang, S.Y. and Islam, M.S., 2021. "Single Microhole per Pixel in CMOS Image Sensors with Enhanced Optical Sensitivity in Near-Infrared," IEEE Sensors Journal, 21(9), pp.10556-10562.
Label–Free Fluorescence Lifetime Imaging: Applications in Surgical Oncology, Precision Surgery, Intraoperative Molecular Imaging UPenn Abramson Cancer Center, November 11, 2022 (Laura Marcu - Invited Talk)
Fluorescence Lifetime Imaging in Surgical Oncology, Miami Global Brain Tumor Symposium, November 2, 2022 (Laura Marcu - Invited Seminar)
FLIM in Surgical Oncology, Virtual BioPhotonics Conference, October 26, 2022 (Laura Marcu - Keynote Talk)
Bringing Malignancy to Light in the Operating Theater, Gordon Research Conference on Optics and Photonics in Medicine and Biology: Biophotonics Spanning the Biology-Medicine Continuum, Bates College, Lewiston, ME, July 2022 (Laura Marcu - Invited Talk)
FLIM-Guided Robotic Surgery, The Hamlyn Symposium in Medical Robotics, London/UK June 2022 (Laura Marcu - Keynote Talk)