Abstract

Cardiac arrhythmias are often triggered by ectopic membrane depolarization originating deep inside the myocardial wall. Here we propose a new method utilizing a novel near-infrared voltage-sensitive fluorescent dye DI-4-ANBDQBS to determine the three-dimensional (3D) coordinates of the sources of such depolarization. We tested the method in live preparations of pig left and right ventricular myocardium (thickness 8-18 mm) and phantoms imitating the optical properties of myocardial tissue. The method utilizes an alternating transillumination approach that involves comparing pairs of simultaneously recorded broad-field epifluorescence and transillumination images produced at two alternating directions of illumination. Recordings were taken simultaneously by two CCD cameras facing the endocardial and epicardial surfaces of the heart at a frame rate up to 3 KHz. In live preparations, we were able to localize the origin of the depolarization wave with a precision of ±1.3mm in the transmural direction and 3 mm in the image plane. The accuracy of detection was independent of the depth of the source inside ventricular wall.

© 2011 OSA

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]

2010 (1)

P. W. Venable, T. G. Taylor, J. Shibayama, M. Warren, and A. V. Zaitsev, “Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart,” Am. J. Physiol. Heart Circ. Physiol. 299(5), H1405–H1418 (2010).
[CrossRef] [PubMed]

2009 (2)

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

B. G. Mitrea, M. Wellner, and A. M. Pertsov, “Monitoring intramyocardial reentry using alternating transillumination,” Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 4194–4197 (2009).
[PubMed]

2008 (1)

L. Li, Q. Jin, J. Huang, K.-A. Cheng, and R. E. Ideker, “Intramural foci during long duration fibrillation in the pig ventricle,” Circ. Res. 102(10), 1256–1264 (2008).
[CrossRef] [PubMed]

2007 (3)

E. M. C. Hillman, O. Bernus, E. Pease, M. B. Bouchard, and A. Pertsov, “Depth-resolved optical imaging of transmural electrical propagation in perfused heart,” Opt. Express 15(26), 17827–17841 (2007).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

2006 (2)

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

V. D. Khait, O. Bernus, S. F. Mironov, and A. M. Pertsov, “Method for the three-dimensional localization of intramyocardial excitation centers using optical imaging,” J. Biomed. Opt. 11(3), 034007 (2006).
[CrossRef] [PubMed]

2005 (2)

O. Bernus, M. Wellner, S. F. Mironov, and A. M. Pertsov, “Simulation of voltage-sensitive optical signals in three-dimensional slabs of cardiac tissue: application to transillumination and coaxial imaging methods,” Phys. Med. Biol. 50(2), 215–229 (2005).
[CrossRef] [PubMed]

B. J. Caldwell, I. J. Legrice, D. A. Hooks, D. C.-S. Tai, A. J. Pullan, and B. H. Smaill, “Intramural measurement of transmembrane potential in the isolated pig heart: validation of a novel technique,” J. Cardiovasc. Electrophysiol. 16(9), 1001–1010 (2005).
[CrossRef] [PubMed]

2004 (1)

D. L. Beaudoin and B. J. Roth, “Effect of plunge electrodes in active cardiac tissue with curving fibers,” Heart Rhythm 1(4), 476–481 (2004).
[CrossRef] [PubMed]

2003 (1)

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

2002 (1)

J. M. Rogers, S. B. Melnick, and J. Huang, “Fiberglass needle electrodes for transmural cardiac mapping,” IEEE Trans. Biomed. Eng. 49(12), 1639–1641 (2002).
[CrossRef] [PubMed]

2001 (3)

L. Ding, R. Splinter, and S. B. Knisley, “Quantifying spatial localization of optical mapping using Monte Carlo simulations,” IEEE Trans. Biomed. Eng. 48(10), 1098–1107 (2001).
[CrossRef] [PubMed]

W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80(1), 516–530 (2001).
[CrossRef] [PubMed]

A. K. Popp, A. M. Pertsov, and D. A. Weitz, “Internal point spread imaging of cardiac tissue to provide depth resolution for bulk tissue imaging experiments,” Proc. SPIE 4431, 141–152 (2001).
[CrossRef]

1997 (2)

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

S. R. Arridge and J. C. Hebden, “Optical imaging in medicine: II. Modelling and reconstruction,” Phys. Med. Biol. 42(5), 841–853 (1997).
[CrossRef] [PubMed]

1996 (1)

S. D. Girouard, K. R. Laurita, and D. S. Rosenbaum, “Unique properties of cardiac action potentials recorded with voltage-sensitive dyes,” J. Cardiovasc. Electrophysiol. 7(11), 1024–1038 (1996).
[CrossRef] [PubMed]

1985 (1)

E. Fluhler, V. G. Burnham, and L. M. Loew, “Spectra, membrane binding, and potentiometric responses of new charge shift probes,” Biochemistry 24(21), 5749–5755 (1985).
[CrossRef] [PubMed]

1981 (1)

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

1979 (1)

L. M. Loew, S. Scully, L. Simpson, and A. S. Waggoner, “Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential,” Nature 281(5731), 497–499 (1979).
[CrossRef] [PubMed]

1976 (2)

L. N. Horowitz, J. F. Spear, and E. N. Moore, “Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction,” Circulation 53(1), 56–63 (1976).
[PubMed]

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40(4), 575–583 (1976).
[PubMed]

Arridge, S. R.

S. R. Arridge and J. C. Hebden, “Optical imaging in medicine: II. Modelling and reconstruction,” Phys. Med. Biol. 42(5), 841–853 (1997).
[CrossRef] [PubMed]

Baxter, W. T.

W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80(1), 516–530 (2001).
[CrossRef] [PubMed]

Beaudoin, D. L.

D. L. Beaudoin and B. J. Roth, “Effect of plunge electrodes in active cardiac tissue with curving fibers,” Heart Rhythm 1(4), 476–481 (2004).
[CrossRef] [PubMed]

Berenfeld, O.

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

Bernus, O.

E. M. C. Hillman, O. Bernus, E. Pease, M. B. Bouchard, and A. Pertsov, “Depth-resolved optical imaging of transmural electrical propagation in perfused heart,” Opt. Express 15(26), 17827–17841 (2007).
[CrossRef] [PubMed]

V. D. Khait, O. Bernus, S. F. Mironov, and A. M. Pertsov, “Method for the three-dimensional localization of intramyocardial excitation centers using optical imaging,” J. Biomed. Opt. 11(3), 034007 (2006).
[CrossRef] [PubMed]

O. Bernus, M. Wellner, S. F. Mironov, and A. M. Pertsov, “Simulation of voltage-sensitive optical signals in three-dimensional slabs of cardiac tissue: application to transillumination and coaxial imaging methods,” Phys. Med. Biol. 50(2), 215–229 (2005).
[CrossRef] [PubMed]

Bouchard, M. B.

Braimbridge, M. V.

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

Burnham, V. G.

E. Fluhler, V. G. Burnham, and L. M. Loew, “Spectra, membrane binding, and potentiometric responses of new charge shift probes,” Biochemistry 24(21), 5749–5755 (1985).
[CrossRef] [PubMed]

Caldwell, B. J.

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

B. J. Caldwell, I. J. Legrice, D. A. Hooks, D. C.-S. Tai, A. J. Pullan, and B. H. Smaill, “Intramural measurement of transmembrane potential in the isolated pig heart: validation of a novel technique,” J. Cardiovasc. Electrophysiol. 16(9), 1001–1010 (2005).
[CrossRef] [PubMed]

Cankovic-Darracott, S.

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

Cheng, K.-A.

L. Li, Q. Jin, J. Huang, K.-A. Cheng, and R. E. Ideker, “Intramural foci during long duration fibrillation in the pig ventricle,” Circ. Res. 102(10), 1256–1264 (2008).
[CrossRef] [PubMed]

Cubeddu, R.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

Ding, L.

L. Ding, R. Splinter, and S. B. Knisley, “Quantifying spatial localization of optical mapping using Monte Carlo simulations,” IEEE Trans. Biomed. Eng. 48(10), 1098–1107 (2001).
[CrossRef] [PubMed]

Fakhari, N.

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

Fast, V. G.

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

Feuvray, D.

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

Fluhler, E.

E. Fluhler, V. G. Burnham, and L. M. Loew, “Spectra, membrane binding, and potentiometric responses of new charge shift probes,” Biochemistry 24(21), 5749–5755 (1985).
[CrossRef] [PubMed]

Girouard, S. D.

S. D. Girouard, K. R. Laurita, and D. S. Rosenbaum, “Unique properties of cardiac action potentials recorded with voltage-sensitive dyes,” J. Cardiovasc. Electrophysiol. 7(11), 1024–1038 (1996).
[CrossRef] [PubMed]

Hearse, D. J.

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

Hebden, J. C.

S. R. Arridge and J. C. Hebden, “Optical imaging in medicine: II. Modelling and reconstruction,” Phys. Med. Biol. 42(5), 841–853 (1997).
[CrossRef] [PubMed]

Hillman, E. M. C.

Hooks, D. A.

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

B. J. Caldwell, I. J. Legrice, D. A. Hooks, D. C.-S. Tai, A. J. Pullan, and B. H. Smaill, “Intramural measurement of transmembrane potential in the isolated pig heart: validation of a novel technique,” J. Cardiovasc. Electrophysiol. 16(9), 1001–1010 (2005).
[CrossRef] [PubMed]

Horowitz, L. N.

L. N. Horowitz, J. F. Spear, and E. N. Moore, “Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction,” Circulation 53(1), 56–63 (1976).
[PubMed]

Huang, J.

L. Li, Q. Jin, J. Huang, K.-A. Cheng, and R. E. Ideker, “Intramural foci during long duration fibrillation in the pig ventricle,” Circ. Res. 102(10), 1256–1264 (2008).
[CrossRef] [PubMed]

J. M. Rogers, S. B. Melnick, and J. Huang, “Fiberglass needle electrodes for transmural cardiac mapping,” IEEE Trans. Biomed. Eng. 49(12), 1639–1641 (2002).
[CrossRef] [PubMed]

Hyatt, C. J.

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

Ideker, R. E.

L. Li, Q. Jin, J. Huang, K.-A. Cheng, and R. E. Ideker, “Intramural foci during long duration fibrillation in the pig ventricle,” Circ. Res. 102(10), 1256–1264 (2008).
[CrossRef] [PubMed]

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

Jalife, J.

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80(1), 516–530 (2001).
[CrossRef] [PubMed]

Jin, Q.

L. Li, Q. Jin, J. Huang, K.-A. Cheng, and R. E. Ideker, “Intramural foci during long duration fibrillation in the pig ventricle,” Circ. Res. 102(10), 1256–1264 (2008).
[CrossRef] [PubMed]

Jynge, P.

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

Khait, V. D.

V. D. Khait, O. Bernus, S. F. Mironov, and A. M. Pertsov, “Method for the three-dimensional localization of intramyocardial excitation centers using optical imaging,” J. Biomed. Opt. 11(3), 034007 (2006).
[CrossRef] [PubMed]

Knisley, S. B.

L. Ding, R. Splinter, and S. B. Knisley, “Quantifying spatial localization of optical mapping using Monte Carlo simulations,” IEEE Trans. Biomed. Eng. 48(10), 1098–1107 (2001).
[CrossRef] [PubMed]

Kong, W.

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

Kwant, G.

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40(4), 575–583 (1976).
[PubMed]

Landsman, M. L.

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40(4), 575–583 (1976).
[PubMed]

Laurita, K. R.

S. D. Girouard, K. R. Laurita, and D. S. Rosenbaum, “Unique properties of cardiac action potentials recorded with voltage-sensitive dyes,” J. Cardiovasc. Electrophysiol. 7(11), 1024–1038 (1996).
[CrossRef] [PubMed]

LeGrice, I. J.

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

B. J. Caldwell, I. J. Legrice, D. A. Hooks, D. C.-S. Tai, A. J. Pullan, and B. H. Smaill, “Intramural measurement of transmembrane potential in the isolated pig heart: validation of a novel technique,” J. Cardiovasc. Electrophysiol. 16(9), 1001–1010 (2005).
[CrossRef] [PubMed]

Li, L.

L. Li, Q. Jin, J. Huang, K.-A. Cheng, and R. E. Ideker, “Intramural foci during long duration fibrillation in the pig ventricle,” Circ. Res. 102(10), 1256–1264 (2008).
[CrossRef] [PubMed]

Loew, L. M.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

E. Fluhler, V. G. Burnham, and L. M. Loew, “Spectra, membrane binding, and potentiometric responses of new charge shift probes,” Biochemistry 24(21), 5749–5755 (1985).
[CrossRef] [PubMed]

L. M. Loew, S. Scully, L. Simpson, and A. S. Waggoner, “Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential,” Nature 281(5731), 497–499 (1979).
[CrossRef] [PubMed]

Mahalu, W.

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

Matiukas, A.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

Melnick, S. B.

J. M. Rogers, S. B. Melnick, and J. Huang, “Fiberglass needle electrodes for transmural cardiac mapping,” IEEE Trans. Biomed. Eng. 49(12), 1639–1641 (2002).
[CrossRef] [PubMed]

Millard, A. C.

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

Mironov, S. F.

V. D. Khait, O. Bernus, S. F. Mironov, and A. M. Pertsov, “Method for the three-dimensional localization of intramyocardial excitation centers using optical imaging,” J. Biomed. Opt. 11(3), 034007 (2006).
[CrossRef] [PubMed]

O. Bernus, M. Wellner, S. F. Mironov, and A. M. Pertsov, “Simulation of voltage-sensitive optical signals in three-dimensional slabs of cardiac tissue: application to transillumination and coaxial imaging methods,” Phys. Med. Biol. 50(2), 215–229 (2005).
[CrossRef] [PubMed]

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80(1), 516–530 (2001).
[CrossRef] [PubMed]

Mitrea, B. G.

B. G. Mitrea, M. Wellner, and A. M. Pertsov, “Monitoring intramyocardial reentry using alternating transillumination,” Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 4194–4197 (2009).
[PubMed]

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

Mook, G. A.

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40(4), 575–583 (1976).
[PubMed]

Moore, E. N.

L. N. Horowitz, J. F. Spear, and E. N. Moore, “Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction,” Circulation 53(1), 56–63 (1976).
[PubMed]

O’Brien, K.

P. Jynge, D. J. Hearse, D. Feuvray, W. Mahalu, S. Canković-Darracott, K. O’Brien, and M. V. Braimbridge, “The St. Thomas’ hospital cardioplegic solution: a characterization in two species,” Scand. J. Thorac. Cardiovasc. Surg. Suppl. 30, 1–28 (1981).
[PubMed]

Pease, E.

Pertsov, A.

Pertsov, A. M.

B. G. Mitrea, M. Wellner, and A. M. Pertsov, “Monitoring intramyocardial reentry using alternating transillumination,” Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 4194–4197 (2009).
[PubMed]

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

V. D. Khait, O. Bernus, S. F. Mironov, and A. M. Pertsov, “Method for the three-dimensional localization of intramyocardial excitation centers using optical imaging,” J. Biomed. Opt. 11(3), 034007 (2006).
[CrossRef] [PubMed]

O. Bernus, M. Wellner, S. F. Mironov, and A. M. Pertsov, “Simulation of voltage-sensitive optical signals in three-dimensional slabs of cardiac tissue: application to transillumination and coaxial imaging methods,” Phys. Med. Biol. 50(2), 215–229 (2005).
[CrossRef] [PubMed]

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

A. K. Popp, A. M. Pertsov, and D. A. Weitz, “Internal point spread imaging of cardiac tissue to provide depth resolution for bulk tissue imaging experiments,” Proc. SPIE 4431, 141–152 (2001).
[CrossRef]

W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80(1), 516–530 (2001).
[CrossRef] [PubMed]

Pifferi, A.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

Popp, A. K.

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

A. K. Popp, A. M. Pertsov, and D. A. Weitz, “Internal point spread imaging of cardiac tissue to provide depth resolution for bulk tissue imaging experiments,” Proc. SPIE 4431, 141–152 (2001).
[CrossRef]

Pullan, A. J.

B. J. Caldwell, I. J. Legrice, D. A. Hooks, D. C.-S. Tai, A. J. Pullan, and B. H. Smaill, “Intramural measurement of transmembrane potential in the isolated pig heart: validation of a novel technique,” J. Cardiovasc. Electrophysiol. 16(9), 1001–1010 (2005).
[CrossRef] [PubMed]

Qin, M.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

Rogers, J. M.

J. M. Rogers, S. B. Melnick, and J. Huang, “Fiberglass needle electrodes for transmural cardiac mapping,” IEEE Trans. Biomed. Eng. 49(12), 1639–1641 (2002).
[CrossRef] [PubMed]

Rosenbaum, D. S.

S. D. Girouard, K. R. Laurita, and D. S. Rosenbaum, “Unique properties of cardiac action potentials recorded with voltage-sensitive dyes,” J. Cardiovasc. Electrophysiol. 7(11), 1024–1038 (1996).
[CrossRef] [PubMed]

Roth, B. J.

D. L. Beaudoin and B. J. Roth, “Effect of plunge electrodes in active cardiac tissue with curving fibers,” Heart Rhythm 1(4), 476–481 (2004).
[CrossRef] [PubMed]

Sands, G. B.

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

Scully, S.

L. M. Loew, S. Scully, L. Simpson, and A. S. Waggoner, “Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential,” Nature 281(5731), 497–499 (1979).
[CrossRef] [PubMed]

Sharifov, O. F.

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

Shibayama, J.

P. W. Venable, T. G. Taylor, J. Shibayama, M. Warren, and A. V. Zaitsev, “Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart,” Am. J. Physiol. Heart Circ. Physiol. 299(5), H1405–H1418 (2010).
[CrossRef] [PubMed]

Shvedko, A. G.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

Simpson, L.

L. M. Loew, S. Scully, L. Simpson, and A. S. Waggoner, “Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential,” Nature 281(5731), 497–499 (1979).
[CrossRef] [PubMed]

Smaill, B. H.

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

B. J. Caldwell, I. J. Legrice, D. A. Hooks, D. C.-S. Tai, A. J. Pullan, and B. H. Smaill, “Intramural measurement of transmembrane potential in the isolated pig heart: validation of a novel technique,” J. Cardiovasc. Electrophysiol. 16(9), 1001–1010 (2005).
[CrossRef] [PubMed]

Smith, W. M.

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

Spear, J. F.

L. N. Horowitz, J. F. Spear, and E. N. Moore, “Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction,” Circulation 53(1), 56–63 (1976).
[PubMed]

Splinter, R.

L. Ding, R. Splinter, and S. B. Knisley, “Quantifying spatial localization of optical mapping using Monte Carlo simulations,” IEEE Trans. Biomed. Eng. 48(10), 1098–1107 (2001).
[CrossRef] [PubMed]

Tai, D. C.-S.

B. J. Caldwell, I. J. Legrice, D. A. Hooks, D. C.-S. Tai, A. J. Pullan, and B. H. Smaill, “Intramural measurement of transmembrane potential in the isolated pig heart: validation of a novel technique,” J. Cardiovasc. Electrophysiol. 16(9), 1001–1010 (2005).
[CrossRef] [PubMed]

Taroni, P.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

Taylor, T. G.

P. W. Venable, T. G. Taylor, J. Shibayama, M. Warren, and A. V. Zaitsev, “Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart,” Am. J. Physiol. Heart Circ. Physiol. 299(5), H1405–H1418 (2010).
[CrossRef] [PubMed]

Torricelli, A.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

Trew, M. L.

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

Valentini, G.

R. Cubeddu, A. Pifferi, P. Taroni, A. Torricelli, and G. Valentini, “A solid tissue phantom for photon migration studies,” Phys. Med. Biol. 42(10), 1971–1979 (1997).
[CrossRef] [PubMed]

Venable, P. W.

P. W. Venable, T. G. Taylor, J. Shibayama, M. Warren, and A. V. Zaitsev, “Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart,” Am. J. Physiol. Heart Circ. Physiol. 299(5), H1405–H1418 (2010).
[CrossRef] [PubMed]

Waggoner, A. S.

L. M. Loew, S. Scully, L. Simpson, and A. S. Waggoner, “Evidence for a charge-shift electrochromic mechanism in a probe of membrane potential,” Nature 281(5731), 497–499 (1979).
[CrossRef] [PubMed]

Warren, M.

P. W. Venable, T. G. Taylor, J. Shibayama, M. Warren, and A. V. Zaitsev, “Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart,” Am. J. Physiol. Heart Circ. Physiol. 299(5), H1405–H1418 (2010).
[CrossRef] [PubMed]

Warren, M. D.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

Watras, J.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

Wei, M. D.

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

Wei, M.-d.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

Weitz, D. A.

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

A. K. Popp, A. M. Pertsov, and D. A. Weitz, “Internal point spread imaging of cardiac tissue to provide depth resolution for bulk tissue imaging experiments,” Proc. SPIE 4431, 141–152 (2001).
[CrossRef]

Wellner, M.

B. G. Mitrea, M. Wellner, and A. M. Pertsov, “Monitoring intramyocardial reentry using alternating transillumination,” Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 4194–4197 (2009).
[PubMed]

O. Bernus, M. Wellner, S. F. Mironov, and A. M. Pertsov, “Simulation of voltage-sensitive optical signals in three-dimensional slabs of cardiac tissue: application to transillumination and coaxial imaging methods,” Phys. Med. Biol. 50(2), 215–229 (2005).
[CrossRef] [PubMed]

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

Wuskell, J. P.

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

Zaitsev, A. V.

P. W. Venable, T. G. Taylor, J. Shibayama, M. Warren, and A. V. Zaitsev, “Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart,” Am. J. Physiol. Heart Circ. Physiol. 299(5), H1405–H1418 (2010).
[CrossRef] [PubMed]

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80(1), 516–530 (2001).
[CrossRef] [PubMed]

Zijlstra, W. G.

M. L. Landsman, G. Kwant, G. A. Mook, and W. G. Zijlstra, “Light-absorbing properties, stability, and spectral stabilization of indocyanine green,” J. Appl. Physiol. 40(4), 575–583 (1976).
[PubMed]

Am. J. Physiol. Heart Circ. Physiol. (2)

A. Matiukas, B. G. Mitrea, A. M. Pertsov, J. P. Wuskell, M. D. Wei, J. Watras, A. C. Millard, and L. M. Loew, “New near-infrared optical probes of cardiac electrical activity,” Am. J. Physiol. Heart Circ. Physiol. 290(6), H2633–H2643 (2006).
[CrossRef] [PubMed]

P. W. Venable, T. G. Taylor, J. Shibayama, M. Warren, and A. V. Zaitsev, “Complex structure of electrophysiological gradients emerging during long-duration ventricular fibrillation in the canine heart,” Am. J. Physiol. Heart Circ. Physiol. 299(5), H1405–H1418 (2010).
[CrossRef] [PubMed]

Biochemistry (1)

E. Fluhler, V. G. Burnham, and L. M. Loew, “Spectra, membrane binding, and potentiometric responses of new charge shift probes,” Biochemistry 24(21), 5749–5755 (1985).
[CrossRef] [PubMed]

Biophys. J. (2)

C. J. Hyatt, S. F. Mironov, M. Wellner, O. Berenfeld, A. K. Popp, D. A. Weitz, J. Jalife, and A. M. Pertsov, “Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns,” Biophys. J. 85(4), 2673–2683 (2003).
[CrossRef] [PubMed]

W. T. Baxter, S. F. Mironov, A. V. Zaitsev, J. Jalife, and A. M. Pertsov, “Visualizing excitation waves inside cardiac muscle using transillumination,” Biophys. J. 80(1), 516–530 (2001).
[CrossRef] [PubMed]

Circ Arrhythm Electrophysiol (1)

B. J. Caldwell, M. L. Trew, G. B. Sands, D. A. Hooks, I. J. LeGrice, and B. H. Smaill, “Three distinct directions of intramural activation reveal nonuniform side-to-side electrical coupling of ventricular myocytes,” Circ Arrhythm Electrophysiol 2(4), 433–440 (2009).
[CrossRef] [PubMed]

Circ. Res. (1)

L. Li, Q. Jin, J. Huang, K.-A. Cheng, and R. E. Ideker, “Intramural foci during long duration fibrillation in the pig ventricle,” Circ. Res. 102(10), 1256–1264 (2008).
[CrossRef] [PubMed]

Circulation (1)

L. N. Horowitz, J. F. Spear, and E. N. Moore, “Subendocardial origin of ventricular arrhythmias in 24-hour-old experimental myocardial infarction,” Circulation 53(1), 56–63 (1976).
[PubMed]

Conf. Proc. IEEE Eng. Med. Biol. Soc. (1)

B. G. Mitrea, M. Wellner, and A. M. Pertsov, “Monitoring intramyocardial reentry using alternating transillumination,” Conf. Proc. IEEE Eng. Med. Biol. Soc. 2009, 4194–4197 (2009).
[PubMed]

Heart Rhythm (3)

A. Matiukas, B. G. Mitrea, M. Qin, A. M. Pertsov, A. G. Shvedko, M. D. Warren, A. V. Zaitsev, J. P. Wuskell, M.-d. Wei, J. Watras, and L. M. Loew, “Near-infrared voltage-sensitive fluorescent dyes optimized for optical mapping in blood-perfused myocardium,” Heart Rhythm 4(11), 1441–1451 (2007).
[CrossRef] [PubMed]

D. L. Beaudoin and B. J. Roth, “Effect of plunge electrodes in active cardiac tissue with curving fibers,” Heart Rhythm 1(4), 476–481 (2004).
[CrossRef] [PubMed]

W. Kong, N. Fakhari, O. F. Sharifov, R. E. Ideker, W. M. Smith, and V. G. Fast, “Optical measurements of intramural action potentials in isolated porcine hearts using optrodes,” Heart Rhythm 4(11), 1430–1436 (2007).
[CrossRef] [PubMed]

IEEE Trans. Biomed. Eng. (2)

L. Ding, R. Splinter, and S. B. Knisley, “Quantifying spatial localization of optical mapping using Monte Carlo simulations,” IEEE Trans. Biomed. Eng. 48(10), 1098–1107 (2001).
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Figures (8)

Fig. 1
Fig. 1

(a) Schematic of the experimental setup. The coronary perfused pig ventricular wall preparation is placed in a glass chamber between two CCD cameras facing the epicardium (P) and endocardium (N). The fluorescence is excited by two 671 nm CW lasers, P and N, illuminating the respective surfaces in rapid succession by alternating the light using a mechanical chopper synchronized with the digital recordings. Boxes 1, 2, and 3 show the holographic diffuser, dichroic mirror, and long pass fluorescence filter, respectively. (b) Views of the right ventricular wall preparation from P and N. The gray squares show the fields of view of respective CCD cameras. The white arrow indicates the perfusion cannula. The black arrow shows the multi-lead plunge needle electrode used for initiation and electrical recordings of intramural electrical waves. The projection of the impaled portion of the electrode is shown by the dashed line. (c) Single pixel recordings from P (top) and N (bottom) cameras. The black points indicate the discarded transitional frames and the red points the retained frames. Double letter notations indicate the position of the light and the camera, respectively. (d) Transmural cross section of the ventricular wall with the inserted plunge needle electrode. Green circles indicate the position of each of the eight unipolar leads.

Fig. 4
Fig. 4

Validation of the wave source detection method in live tissue. Initiation and recording of intramural electrical waves at different depths using a multi-lead plunge needle electrode. Numbers near the extracellular signals indicate the lead from which the unipolar recording was taken. (a) Stimulation applied through lead 1, located near the N surface. A gradual increase of the activation time from lead 2 to 6 can be seen, consistent with excitation of the endocardial surface. (b) Stimulation through lead 4, located 6 mm under the P surface. The earliest activation is detected near leads 3 and 5. The activation time increases as the distance from the recording and stimulation site is increased, consistent with intramural expansion of the excitation front. (c) and (d) show activation time vs distance from the stimulation site for left ventricle (n = 3) and right ventricle (n = 6), respectively.

Fig. 2
Fig. 2

PP, PN, NP and NN snapshots of the wave expansion following stimulation 3 mm below the P surface. The first and second letter in the image notation indicate the position of the light and the camera, respectively. Colors indicate the intensity of the fluorescent signal. The white dotted line indicates the projection of the plunge needle electrode. The yellow square is the stimulating lead. The time of the snapshot is referenced to the onset of the stimulating pulse.

Fig. 3
Fig. 3

Validation of the source detection technique in phantom experiments. (a) Reflection (PP, NN) and transillumination (PN, NP) images of a fluorescent capillary placed 3 mm below the P surface. The white bar on the bottom right of the NN image corresponds to 10 mm. (b) Horizontal intensity profiles for the four images in Panel a. Scan lines are shown as dashed lines in Panel a. The profiles in PP and NP images are narrower and have larger amplitudes than those in NN and PN, which reflects the proximity of the capillary to the P surface. (c) The actual depth of the capillary vs the reconstructed depth in two different experiments (white and black circles). The red line is the identity line.

Fig. 5
Fig. 5

(a) Changes in integral intensities of the PP, PN, NP and NN images produced by expanding intramural excitation wave (ensemble average). The stimulus is applied from the lead located 10 mm below P surface. The black arrow at the bottom of the plot indicates the moment of the stimulation. (b) and (c) show signal dynamics during early stages of front expansion corresponding to the grey box in (a) and (b), respectively. The horizontal lines in (c) indicate the integral intensities threshold at two standard deviations above mean background intensity. The depth of the source is detected at the moment indicated by the vertical line.

Fig. 6
Fig. 6

PP, PN, NP and NN snapshots of the excitation wave at the moment of detection. The stimulus is applied from the electrode located 10 mm below P surface. The colors show the normalized voltage sensitive fluorescence. The NN image is the brightest, consistent with the wave being initiated in the mid-myocardium, closer to the N surface. The dashed line is the projection of the plunge needle electrode with the stimulating electrode indicated by the square. ΔR is the radial displacement between the stimulation site coordinates and the reconstructed source coordinates. The white bar on the bottom right corresponds to 10 mm.

Fig. 7
Fig. 7

(a) Changes in integral intensities of the PP, PN, NP and NN images produced by a single intramural excitation wave for the same preparation as in Fig. 5. The black arrow at the bottom of the plot indicates the moment of the stimulation. (b) and (c) show signal dynamics during early stages of front expansion corresponding to the grey box in (a) and (b) respectively. The red vertical line in (c) indicates the moment of detection for the periodic wave. The black vertical line indicates the time of detection for a single wave.

Fig. 8
Fig. 8

Accuracy of the reconstruction of the wave origin from the dynamic integral intensities. (a) The 3D image illustrates the reconstructed origin of the excitation wave (red sphere), the actual stimulation site (green) and the position of plunge needle electrode inside a right ventricle preparation. The size of the preparation is 24 × 24 × 10 mm (b) The depth of stimulation site versus the reconstructed depth for periodic sources. (c) The depth of stimulation site versus reconstructed depth for single wave sources. Different colors indicate different experiments. Open and closed circles indicate right and left ventricle experiments respectively.

Tables (1)

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Table 1 Comparison between detection accuracy for periodic and single waves

Equations (3)

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I i , j = ( 1 Δ F i , j F i , j ) F ^
J P P J P N = sinh [ ( L Z + d ) / δ ] sinh [ ( Z + d ) / δ ]
J N N J N P = sinh [ ( Z + d ) / δ ] sinh [ ( L Z + d ) / δ ]

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