Abstract

Detection of atherosclerotic plaque vulnerability has critical clinical implications for avoiding sudden death in patients with high risk of plaque rupture. We report on multimodality imaging of ex-vivo human carotid plaque samples using a system that integrates fluorescence lifetime imaging (FLIM), ultrasonic backscatter microscopy (UBM), and photoacoustic imaging (PAI). Biochemical composition is differentiated with a high temporal resolution and sensitivity at the surface of the plaque by the FLIM subsystem. 3D microanatomy of the whole plaque is reconstructed by the UBM. Functional imaging associated with optical absorption contrast is evaluated from the PAI component. Simultaneous recordings of the optical, ultrasonic, and photoacoustic data present a wealth of complementary information concerning the plaque composition, structure, and function that are related to plaque vulnerability. This approach is expected to improve our ability to study atherosclerotic plaques. The multimodal system presented here can be translated into a catheter based intraluminal system for future clinical studies.

© 2011 OSA

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2011 (1)

2010 (2)

2009 (6)

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

J. Phipps, Y. H. Sun, R. Saroufeem, N. Hatami, and L. Marcu, “Fluorescence lifetime imaging microscopy for the characterization of atherosclerotic plaques,” Proc. Soc. Photo Opt. Instrum. Eng. 7161, 71612G (2009).
[PubMed]

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

Y. H. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Opt. Lett. 34(13), 2081–2083 (2009).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

S. Sathyanarayana, S. Carlier, W. Li, and L. Thomas, “Characterisation of atherosclerotic plaque by spectral similarity of radiofrequency intravascular ultrasound signals,” EuroIntervention 5(1), 133–139 (2009).
[CrossRef] [PubMed]

2008 (2)

2007 (2)

D. S. Elson, J. A. Jo, and L. Marcu, “Miniaturized side-viewing imaging probe for fluorescence lifetime imaging (FLIM): validation with fluorescence dyes, tissue structural proteins and tissue specimens,” N. J. Phys. 9(127), 1–13 (2007).

S. Sethuraman, J. H. Amirian, S. H. Litovsky, R. W. Smalling, and S. Y. Emelianov, “Ex vivo characterization of atherosclerosis using intravascular photoacoustic imaging,” Opt. Express 15(25), 16657–16666 (2007).
[CrossRef] [PubMed]

2006 (2)

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the vulnerable plaque,” J. Am. Coll. Cardiol. 47(8Suppl), C13–C18 (2006).
[CrossRef] [PubMed]

2005 (2)

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

2003 (1)

J. M. Cannata, T. A. Ritter, W. H. Chen, R. H. Silverman, and K. K. Shung, “Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 50(11), 1548–1557 (2003).
[CrossRef] [PubMed]

2002 (2)

P. Libby, “Inflammation in atherosclerosis,” Nature 420(6917), 868–874 (2002).
[CrossRef] [PubMed]

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

2000 (1)

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

1999 (1)

C. Studholme, D. L. G. Hill, and D. J. Hawkes, “An overlap invariant entropy measure of 3D medical image alignment,” Pattern Recognit. 32(1), 71–86 (1999).
[CrossRef]

1996 (1)

R. Richards-Kortum and E. M. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Annu. Rev. Phys. Chem. 47(1), 555–606 (1996).
[CrossRef] [PubMed]

Amirian, J.

Amirian, J. H.

Aretz, H. T.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Baker, J. D.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Berry, G. J.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Bouma, B. E.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Brisken, A. F.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Burke, A. P.

R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the vulnerable plaque,” J. Am. Coll. Cardiol. 47(8Suppl), C13–C18 (2006).
[CrossRef] [PubMed]

Cannata, J. M.

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

J. M. Cannata, T. A. Ritter, W. H. Chen, R. H. Silverman, and K. K. Shung, “Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 50(11), 1548–1557 (2003).
[CrossRef] [PubMed]

Carlier, S.

S. Sathyanarayana, S. Carlier, W. Li, and L. Thomas, “Characterisation of atherosclerotic plaque by spectral similarity of radiofrequency intravascular ultrasound signals,” EuroIntervention 5(1), 133–139 (2009).
[CrossRef] [PubMed]

Chen, W. H.

J. M. Cannata, T. A. Ritter, W. H. Chen, R. H. Silverman, and K. K. Shung, “Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 50(11), 1548–1557 (2003).
[CrossRef] [PubMed]

Choi, K. B.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Chuang, F. S.

Dorafshar, A.

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Dorafshar, A. H.

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

Elson, D. S.

Emelianov, S.

Emelianov, S. Y.

A. B. Karpiouk, B. Wang, and S. Y. Emelianov, “Development of a catheter for combined intravascular ultrasound and photoacoustic imaging,” Rev. Sci. Instrum. 81(1), 014901 (2010).
[CrossRef] [PubMed]

S. Sethuraman, J. H. Amirian, S. H. Litovsky, R. W. Smalling, and S. Y. Emelianov, “Ex vivo characterization of atherosclerosis using intravascular photoacoustic imaging,” Opt. Express 15(25), 16657–16666 (2007).
[CrossRef] [PubMed]

Fang, Q.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Farb, A.

R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the vulnerable plaque,” J. Am. Coll. Cardiol. 47(8Suppl), C13–C18 (2006).
[CrossRef] [PubMed]

Farwell, D. G.

Fishbein, M. C.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Fitzgerald, P. J.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Freischlag, J. A.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Hatami, N.

J. Phipps, Y. H. Sun, R. Saroufeem, N. Hatami, and L. Marcu, “Fluorescence lifetime imaging microscopy for the characterization of atherosclerotic plaques,” Proc. Soc. Photo Opt. Instrum. Eng. 7161, 71612G (2009).
[PubMed]

Hawkes, D. J.

C. Studholme, D. L. G. Hill, and D. J. Hawkes, “An overlap invariant entropy measure of 3D medical image alignment,” Pattern Recognit. 32(1), 71–86 (1999).
[CrossRef]

Hill, D. L. G.

C. Studholme, D. L. G. Hill, and D. J. Hawkes, “An overlap invariant entropy measure of 3D medical image alignment,” Pattern Recognit. 32(1), 71–86 (1999).
[CrossRef]

Hollars, C. W.

Houser, S. L.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Jang, I. K.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Jo, J. A.

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Y. H. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time- and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Opt. Lett. 33(6), 630–632 (2008).
[CrossRef] [PubMed]

D. S. Elson, J. A. Jo, and L. Marcu, “Miniaturized side-viewing imaging probe for fluorescence lifetime imaging (FLIM): validation with fluorescence dyes, tissue structural proteins and tissue specimens,” N. J. Phys. 9(127), 1–13 (2007).

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Kang, D. H.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Karpiouk, A. B.

A. B. Karpiouk, B. Wang, and S. Y. Emelianov, “Development of a catheter for combined intravascular ultrasound and photoacoustic imaging,” Rev. Sci. Instrum. 81(1), 014901 (2010).
[CrossRef] [PubMed]

Kolodgie, F. D.

R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the vulnerable plaque,” J. Am. Coll. Cardiol. 47(8Suppl), C13–C18 (2006).
[CrossRef] [PubMed]

Kolz, M. L.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Komiyama, N.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Li, W.

S. Sathyanarayana, S. Carlier, W. Li, and L. Thomas, “Characterisation of atherosclerotic plaque by spectral similarity of radiofrequency intravascular ultrasound signals,” EuroIntervention 5(1), 133–139 (2009).
[CrossRef] [PubMed]

Libby, P.

P. Libby, “Inflammation in atherosclerosis,” Nature 420(6917), 868–874 (2002).
[CrossRef] [PubMed]

Litovsky, S. H.

Liu, R.

Marcu, L.

Y. H. Sun, Y. Sun, D. Stephens, H. Xie, J. Phipps, R. Saroufeem, J. Southard, D. S. Elson, and L. Marcu, “Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis,” Opt. Express 19(5), 3890–3901 (2011).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Y. H. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Opt. Lett. 34(13), 2081–2083 (2009).
[CrossRef] [PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

J. Phipps, Y. H. Sun, R. Saroufeem, N. Hatami, and L. Marcu, “Fluorescence lifetime imaging microscopy for the characterization of atherosclerotic plaques,” Proc. Soc. Photo Opt. Instrum. Eng. 7161, 71612G (2009).
[PubMed]

Y. H. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time- and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Opt. Lett. 33(6), 630–632 (2008).
[CrossRef] [PubMed]

D. S. Elson, J. A. Jo, and L. Marcu, “Miniaturized side-viewing imaging probe for fluorescence lifetime imaging (FLIM): validation with fluorescence dyes, tissue structural proteins and tissue specimens,” N. J. Phys. 9(127), 1–13 (2007).

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Meier, J.

Metz, J. A.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Moore, M. P.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Oshima, A.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Papaioannou, T.

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Papaloannou, T.

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

Park, J.

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

Y. H. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time- and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Opt. Lett. 33(6), 630–632 (2008).
[CrossRef] [PubMed]

Park, S. J.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Park, S. W.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Phipps, J.

Poirier, B.

Pomerantsev, E.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Preuss, P.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Qiao, J. H.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaloannou, J. H. Qiao, M. C. Fishbein, J. D. Baker, and J. A. Freischlag, “Detection of high-risk atherosclerotic plaques by time-resolved laser induced fluorescence spectroscopy,” Circulation 112, U678 (2005).

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Reil, T.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

J. A. Jo, Q. Fang, T. Papaioannou, J. D. Baker, A. H. Dorafshar, T. Reil, J. H. Qiao, M. C. Fishbein, J. A. Freischlag, and L. Marcu, “Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions,” J. Biomed. Opt. 11(2), 021004 (2006).
[CrossRef] [PubMed]

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

Richards-Kortum, R.

R. Richards-Kortum and E. M. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Annu. Rev. Phys. Chem. 47(1), 555–606 (1996).
[CrossRef] [PubMed]

Ritter, T. A.

J. M. Cannata, T. A. Ritter, W. H. Chen, R. H. Silverman, and K. K. Shung, “Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 50(11), 1548–1557 (2003).
[CrossRef] [PubMed]

Saroufeem, R.

Y. H. Sun, Y. Sun, D. Stephens, H. Xie, J. Phipps, R. Saroufeem, J. Southard, D. S. Elson, and L. Marcu, “Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis,” Opt. Express 19(5), 3890–3901 (2011).
[CrossRef] [PubMed]

J. Phipps, Y. H. Sun, R. Saroufeem, N. Hatami, and L. Marcu, “Fluorescence lifetime imaging microscopy for the characterization of atherosclerotic plaques,” Proc. Soc. Photo Opt. Instrum. Eng. 7161, 71612G (2009).
[PubMed]

Saroufeem, R. M.

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

Sathyanarayana, S.

S. Sathyanarayana, S. Carlier, W. Li, and L. Thomas, “Characterisation of atherosclerotic plaque by spectral similarity of radiofrequency intravascular ultrasound signals,” EuroIntervention 5(1), 133–139 (2009).
[CrossRef] [PubMed]

Schlendorf, K.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Sethuraman, S.

Seung, K. B.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Sevick-Muraca, E. M.

R. Richards-Kortum and E. M. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Annu. Rev. Phys. Chem. 47(1), 555–606 (1996).
[CrossRef] [PubMed]

Shishkov, M.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Shung, K. K.

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

J. M. Cannata, T. A. Ritter, W. H. Chen, R. H. Silverman, and K. K. Shung, “Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 50(11), 1548–1557 (2003).
[CrossRef] [PubMed]

Silverman, R. H.

J. M. Cannata, T. A. Ritter, W. H. Chen, R. H. Silverman, and K. K. Shung, “Design of efficient, broadband single-element (20-80 MHz) ultrasonic transducers for medical imaging applications,” IEEE Trans. Ultrason. Ferroelectr. Freq. Control 50(11), 1548–1557 (2003).
[CrossRef] [PubMed]

Smalling, R.

Smalling, R. W.

Southard, J.

Stephens, D.

Stephens, D. N.

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

Stoy, H.

Studholme, C.

C. Studholme, D. L. G. Hill, and D. J. Hawkes, “An overlap invariant entropy measure of 3D medical image alignment,” Pattern Recognit. 32(1), 71–86 (1999).
[CrossRef]

Su, J. L.

Sun, L.

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

Sun, Y.

Y. H. Sun, Y. Sun, D. Stephens, H. Xie, J. Phipps, R. Saroufeem, J. Southard, D. S. Elson, and L. Marcu, “Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis,” Opt. Express 19(5), 3890–3901 (2011).
[CrossRef] [PubMed]

Y. Sun, J. Park, D. N. Stephens, J. A. Jo, L. Sun, J. M. Cannata, R. M. Saroufeem, K. K. Shung, and L. Marcu, “Development of a dual-modal tissue diagnostic system combining time-resolved fluorescence spectroscopy and ultrasonic backscatter microscopy,” Rev. Sci. Instrum. 80(6), 065104 (2009).
[CrossRef] [PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

Y. H. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time- and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Opt. Lett. 33(6), 630–632 (2008).
[CrossRef] [PubMed]

Sun, Y. H.

Tearney, G. J.

I. K. Jang, B. E. Bouma, D. H. Kang, S. J. Park, S. W. Park, K. B. Seung, K. B. Choi, M. Shishkov, K. Schlendorf, E. Pomerantsev, S. L. Houser, H. T. Aretz, and G. J. Tearney, “Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound,” J. Am. Coll. Cardiol. 39(4), 604–609 (2002).
[CrossRef] [PubMed]

Thomas, L.

S. Sathyanarayana, S. Carlier, W. Li, and L. Thomas, “Characterisation of atherosclerotic plaque by spectral similarity of radiofrequency intravascular ultrasound signals,” EuroIntervention 5(1), 133–139 (2009).
[CrossRef] [PubMed]

Tinling, S.

Virmani, R.

R. Virmani, A. P. Burke, A. Farb, and F. D. Kolodgie, “Pathology of the vulnerable plaque,” J. Am. Coll. Cardiol. 47(8Suppl), C13–C18 (2006).
[CrossRef] [PubMed]

Wang, B.

Wang, L. V.

L. V. Wang, “Tutorial on photoacoustic microscopy and computed tomography,” IEEE J. Sel. Top. Quantum Electron. 14(1), 171–179 (2008).
[CrossRef]

Xie, H.

Yock, P. G.

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Am. Heart J. (1)

N. Komiyama, G. J. Berry, M. L. Kolz, A. Oshima, J. A. Metz, P. Preuss, A. F. Brisken, M. P. Moore, P. G. Yock, and P. J. Fitzgerald, “Tissue characterization of atherosclerotic plaques by intravascular ultrasound radiofrequency signal analysis: an in vitro study of human coronary arteries,” Am. Heart J. 140(4), 565–574 (2000).
[CrossRef] [PubMed]

Annu. Rev. Phys. Chem. (1)

R. Richards-Kortum and E. M. Sevick-Muraca, “Quantitative optical spectroscopy for tissue diagnosis,” Annu. Rev. Phys. Chem. 47(1), 555–606 (1996).
[CrossRef] [PubMed]

Atherosclerosis (2)

L. Marcu, Q. Fang, J. A. Jo, T. Papaioannou, A. Dorafshar, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 181(2), 295–303 (2005).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Circulation (1)

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Figures (3)

Fig. 1
Fig. 1

Representative co-registered FLIM and UBM measurements of a human carotid plaque sample. (a) Photo of the carotid plaque sample with the imaging area outlined by the red dashed line (12.2 mm x 4 mm). (b) The combined probe integrating an ultrasonic transducer and an optical fiber. (c)-(e) FLIM images overlaid on top of the plaque photo at three different wavelengths, where the color represented average lifetime values from 0 ns to 4 ns for each pixel. Three regions were labeled in (c) and analyzed (f) Histogram of the average lifetime values at 390 nm from the three regions in (c) corresponding to three tissue types (IT: intimal thickening, FL: fibro-lipidic plaque, and FP: fibrotic plaque). (g)-(h) 3D UBM volume data from the investigated region (12.2 x 4 x 2 mm3). Surface renderings of the UBM volume with orthogonal planes are shown with 45 dB displaying dynamics range and jet color map. (i) FLIM map at 390 nm coregistered with and overlaid onto a 3D UBM volume rendering. The minor differences in color scale between (c) and (i) are a by-product of 3D rendering. The PAI data can be displayed similarly but is not shown here to simplify the figure.

Fig. 2
Fig. 2

Multimodal measurements and correlation analysis with histology from the scanning position indicated by the black dashed line in Fig. 1(c). (a) Plots of the average lifetime as a function of scanning position. Four ROIs were analyzed to show the changes in lumen-surface composition. (b) Transverse UBM images from the same position as (a) showed the reconstruction of the plaque structure, where an acoustic shadowing area indicated calcific deposits. (c) The PAI image provided optical absorption contrast and structural information. HS: hot spot. (d) Co-registered UBM and PAI images were fused as one combined image. (e) The corresponding trichrome stained tissue section. (f)-(k) Zoomed-in histological images of the regions labeled with HS1 to HS4 in (c): (f) HS1, trichrome staining showing fibro-lipidic plaque and calcification. Macrocalcification, and microcalcification deposits (tens of microns) were observed (dark blue circles), (g) HS1, H&E staining confirming the microcalcification, (h) HS2, trichrome staining demonstrating the fibrotic collagen-rich region (blue lines) and lipid-rich area underneath (white clefts), (i) HS2, H&E, (j) HS3, dense fibrotic knot and intimal thickening with elastin fibers (black lines) and smooth muscle cells (red), and (k) HS4, knot of collagen fibers.

Fig. 3
Fig. 3

Example of the multimodal measurements from a different scanning location of the carotid plaque sample and data correlation. (a) Plots of the average lifetime as a function of scanning position. Three ROIs were analyzed to show the changes in surface composition. (b) Transverse UBM images from the same position as (a) showed the reconstruction of the plaque structure, where an acoustic shadowing area indicated calcific deposits. (c) The PAI image provided optical absorption contrast. (d) Co-registered UBM and PAI images were fused as one combined image. (e) The corresponding trichrome stained tissue section. (f)-(k) Zoomed-in histological images of the regions labeled with arrows in (e): (f) and (i) inflammation\macrophages, (g) fibrotic-calcific region using the trichrome stain, (j) H&E staining confirming the presence of calcification, (h) and (k) fibrotic plaque, respectively

Tables (1)

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Table 1 Quantification of the Multimodal (FLIM-UBM-PAI) Data for Plaque Characterization (4 Locations)

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