FLIm for Cardiovascular Imaging

The clinical management of Coronary Artery Disease (CAD) and the prevention of Acute Coronary Syndromes (ACS) require knowledge of the underlying atherosclerotic plaque pathobiology. Current intravascular standalone imaging techniques are limited in their ability to evaluate processes that lead to plaque progression and sudden changes in plaque structure (e.g. rupture or erosion) conducive to ACS in humans. Hybrid intravascular imaging systems hold premises for more comprehensive evaluation of plaque pathobiology in patients and are urgently needed. 

The goal of the Marcu Lab is to address this need through the development of an intravascular imaging approach capable of simultaneous assessment of changes in plaque biochemical composition and morphology associated with critical pathobiological processes in patients. Time-resolved measurements of endogenous fluorophores present key advantages compared to intensity-based measurements, such as independence of contrast from the probe to wall distance or residual blood absorption, and do not require the lengthy approval required for exogenous contrast agents thus facilitating future translational work. 

Over the years, we have studied how the autofluorescence signature of atherosclerotic lesions relates to their composition and how FLIm could be used to yield greater insight into the interplay of biochemical-morphological features that have a key role in plaque progression, destabilization, and/or remodeling.

fluorescence lifetime images of artery
Sources of FLIm contrast

 

To achieve this goal, we have developed unique instrumentation, see FLIm-OCT, FLIm-Ultrasound, Intravascular imaging.

 

Collaborators

Dr. Jeffrey A. Southard, M.D. (UC Health)

Deborah Vela, M.D. (Texas Heart Institute)

L. Maximilian Buja, M.D. (Texas Heart Institute)

Kenneth B. Margulies, M.D. (Cardiovascular Institute, UPenn)

 

Funding

NIH (National Institutes of Health): R01HL67377

 

IP

US20190374195A1: Single catheter system that provides both intravascular ultrasound and fluorescence lifetime imaging

US20200275828A1: Broadband, freeform focusing micro optics for side-viewing imaging catheters

 

Publications
C. Li, J. Bec, X. Zhou, and L. Marcu, "Dual-modality fluorescence lifetime imaging-optical coherence tomography intravascular catheter system with freeform catheter optics," J Biomed Opt, 27(7), 076005 (2022)
J. Bec, D. Vela, J. E. Phipps, M. Agung, J. Unger, K. B. Margulies, J. A. Southard, L. M. Buja, and L. Marcu, "Label-Free Visualization and Quantification of Biochemical Markers of Atherosclerotic Plaque Progression Using Intravascular Fluorescence Lifetime," JACC: Cardiovascular Imaging (2020).
J. Bec, T. A. Shaik, C. Krafft, T. W. Bocklitz, A. Alfonso-Garcia, K. B. Margulies, J. Popp, and L. Marcu, "Investigating Origins of FLIm Contrast in Atherosclerotic Lesions Using Combined FLIm-Raman Spectroscopy," Front Cardiovasc Med 7, 122 (2020).
C. V. Bourantas, F. A. Jaffer, F. J. Gijsen, G. van Soest, S. P. Madden, B. K. Courtney, A. M. Fard, E. Tenekecioglu, Y. Zeng, A. F. W. van der Steen, S. Emelianov, J. Muller, P. H. Stone, L. Marcu, G. J. Tearney, and P. W. Serruys, "Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology," Eur Heart J 38, 400-412 (2017). 
J. Bec, J. E. Phipps, D. Gorpas, D. Ma, H. Fatakdawala, K. B. Margulies, J. A. Southard, and L. Marcu, "In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system," Sci Rep 7, 8960 (2017).
S. Dochow, H. Fatakdawala, J. E. Phipps, D. L. Ma, T. Bocklitz, M. Schmitt, J. W. Bishop, K. B. Margulies, L. Marcu, and J. Popp, "Comparing Raman and fluorescence lifetime spectroscopy from human atherosclerotic lesions using a bimodal probe," Journal of Biophotonics 9, 958-966 (2016).
H. Fatakdawala, D. Gorpas, J. W. Bishop, J. Bec, D. Ma, J. A. Southard, K. B. Margulies, and L. Marcu, "Fluorescence Lifetime Imaging Combined with Conventional Intravascular Ultrasound for Enhanced Assessment of Atherosclerotic Plaques: an Ex Vivo Study in Human Coronary Arteries," J Cardiovasc Transl Res 8, 253-263 (2015).
D. Gorpas, H. Fatakdawala, J. Bec, D. Ma, D.R. Yankelevich, J. Qi, L. Marcu, “Fluorescence Lifetime Imaging and Intravascular Ultrasound: Co-registration Study using ex vivo Human Coronaries”, Medical Imaging, IEEE Transactions on , vol.34, no.1, pp.156,166, (2015) 
D. Ma, J. Bec, D. R. Yankelevich, D. Gorpas, H. Fatakdawala, and L. Marcu, "Rotational multispectral fluorescence lifetime imaging and intravascular ultrasound: bimodal system for intravascular applications," J Biomed Opt 19, 066004 (2014).
N. Ghata, R. C. Aldredge, J. Bec, and L. Marcu, "Computational analysis of the effectiveness of blood flushing with saline injection from an intravascular diagnostic catheter," Int J Numer Method Biomed Eng 30, 1278-1293 (2014).
J. Bec, D. Ma, D. Yankelevich, J. Liu, W. Ferrier, J. Southard, L. Marcu. “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries.” Journal of Biophotonics, 1864-0648, DOI: 10.1002/jbio.201200220, (2013).