Abstract

Organs such as the heart and brain possess intricate fiber structures that are best characterized with three-dimensional imaging. For instance, diffusion-based, magnetic resonance tractography (MRT) enables studies of connectivity and remodeling during development and disease macroscopically on the millimeter scale. Here we present complementary, high-resolution microscopic optical coherence imaging and analysis methods that, when used in conjunction with clearing techniques, can characterize fiber architecture in intact organs at tissue depths exceeding 1 mm. We anticipate that these techniques can be used to study fiber architecture in situ at microscopic scales not currently accessible to diffusion magentic resonance (MR), and thus, to validate and complement macroscopic structural imaging techniques. Moreover, as these techniques use intrinsic signals and do not require tissue slicing and staining, they can be used for high-throughput, nondestructive evaluation of fiber architecture across large tissue volumes.

© 2012 Optical Society of America

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References

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  1. D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
    [CrossRef]
  2. T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
    [CrossRef]
  3. V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
    [CrossRef]
  4. M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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2012 (1)

2011 (3)

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

2010 (1)

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

2009 (1)

2008 (2)

C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, A. M. Rollins, J. Biomed. Opt. 13, 030505 (2008).
[CrossRef]

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

1995 (1)

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

1969 (1)

D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
[CrossRef]

Abosch, A.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Akkin, T.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Al-Qaisi, M. K.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Ando, R.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Arous, J. B.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Barry, S.

Benner, T.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Binding, J.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Black, A. J.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Boccara, A. C.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Bourdieu, L.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Cable, A. E.

Casado, M.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

D’Arceuil, H.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Dai, G.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

de Crespigny, A. J.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Dinsmore, R. E.

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

Efimov, I. R.

C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, A. M. Rollins, J. Biomed. Opt. 13, 030505 (2008).
[CrossRef]

Figueiredo, J.-L.

Fleming, C. P.

C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, A. M. Rollins, J. Biomed. Opt. 13, 030505 (2008).
[CrossRef]

Fukami, K.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Ghosh, N.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Gigan, S.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Hagmann, P.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Hama, H.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Jiang, J. Y.

Kawano, H.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Kurokawa, H.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Leger, J.-F.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Li, R.-K.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Li, S.-H.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Miyawaki, A.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Nahrendorf, M.

Netoff, T. I.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Noda, H.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Ntziachristos, V.

Pandya, D. N.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Patel, D. P.

D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
[CrossRef]

Radhakrishnan, H.

Razansky, D.

Reese, T. G.

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

Ripplinger, C. M.

C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, A. M. Rollins, J. Biomed. Opt. 13, 030505 (2008).
[CrossRef]

Rollins, A. M.

C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, A. M. Rollins, J. Biomed. Opt. 13, 030505 (2008).
[CrossRef]

Rosen, B. R.

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

Ross, J.

D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
[CrossRef]

Sakaue-Sawano, A.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Schmahmann, J. D.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Shimogori, T.

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

Smith, R. N.

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

Sonnenblick, E. H.

D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
[CrossRef]

Spotnitz, H. M.

D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
[CrossRef]

Srinivasan, V. J.

Stigen, T. W.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Streeter, D. D.

D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
[CrossRef]

Topilko, P.

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Tseng, W. Y.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Vinegoni, C.

Vitkin, I. A.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Wallenburg, M. A.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Wang, H.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Wang, R. P.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Webb, B.

C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, A. M. Rollins, J. Biomed. Opt. 13, 030505 (2008).
[CrossRef]

Wedeen, V. J.

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

Weisel, R. D.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Weisskoff, R. M.

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

Weissleder, R.

Wilson, B. C.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Wood, M. F. G.

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

Zhu, J.

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

Circ. Res. (1)

D. D. Streeter, H. M. Spotnitz, D. P. Patel, J. Ross, E. H. Sonnenblick, Circ. Res. 24, 339 (1969).
[CrossRef]

J. Biomed. Opt. (3)

M. F. G. Wood, N. Ghosh, M. A. Wallenburg, S.-H. Li, R. D. Weisel, B. C. Wilson, R.-K. Li, I. A. Vitkin, J. Biomed. Opt. 15, 047009 (2010).
[CrossRef]

C. P. Fleming, C. M. Ripplinger, B. Webb, I. R. Efimov, A. M. Rollins, J. Biomed. Opt. 13, 030505 (2008).
[CrossRef]

J. B. Arous, J. Binding, J.-F. Leger, M. Casado, P. Topilko, S. Gigan, A. C. Boccara, L. Bourdieu, J. Biomed. Opt. 16, 116012 (2011).
[CrossRef]

Magn. Reson. Med. (1)

T. G. Reese, R. M. Weisskoff, R. N. Smith, B. R. Rosen, R. E. Dinsmore, V. J. Wedeen, Magn. Reson. Med. 34, 786 (1995).
[CrossRef]

Nat. Neurosci. (1)

H. Hama, H. Kurokawa, H. Kawano, R. Ando, T. Shimogori, H. Noda, K. Fukami, A. Sakaue-Sawano, A. Miyawaki, Nat. Neurosci. 14, 1481 (2011).
[CrossRef]

NeuroImage (2)

H. Wang, A. J. Black, J. Zhu, T. W. Stigen, M. K. Al-Qaisi, T. I. Netoff, A. Abosch, T. Akkin, NeuroImage 58, 984 (2011).
[CrossRef]

V. J. Wedeen, R. P. Wang, J. D. Schmahmann, T. Benner, W. Y. Tseng, G. Dai, D. N. Pandya, P. Hagmann, H. D’Arceuil, A. J. de Crespigny, NeuroImage 41, 1267 (2008).
[CrossRef]

Opt. Express (1)

Opt. Lett. (1)

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Figures (3)

Fig. 1.
Fig. 1.

Myofiber direction can be quantified from OCT images. (a) Representative OCT image of the left ventricle of a mouse is shown. (b) Image of the same specimen from a two-photon microscope, showing myocytes (red) and collagen (green). (c) Example orientation distribution function (ODF) from the OCT image shows a maximum at 42.4 ° (red line). Orientations of (d) ODF peaks and (e) streamlines, show myofiber orientation over the region of interest. (f) Representative tract histogram shows consistent fiber direction. From the ODF peak distribution (blue), the mean direction was 48.0 ° with a circular variance of 0.13. With tractography (red), the mean direction was 37.1 ° and had a lower circular variance (0.02). Scale bars are 0.1 mm.

Fig. 2.
Fig. 2.

Myofiber orientation changes with depth. (a) Representative H&E stained histology; (b) OCT images with tracts overlaid showing myofiber direction of the lateral left ventricular wall exhibiting a clear transition in orientation with depth. Directions are shown for a single heart as histograms at selected depths. (c) Directions are shown for a single heart as a continuous function of depth. (d) Fiber orientations from six hearts show an approximately linear transition with respect to depth from 60 ° in the epicardial layer to + 60 ° in the endocardial layer. (e) Images are shown in the same orientation as Fig. 1. Scale bars are 0.1 mm.

Fig. 3.
Fig. 3.

Representative imaging and tractography of two intact mouse brains. (a) Sagittal section of cortical myelination (maximum intensity projection over 25 μm), showing the corpus callosum (CC). (b) Imaging of the corpus callosum at roughly 1.5 mm depth; (c) both tracts (circular variance of 0.02) and ODF maxima (circular variance of 0.22) show a predominantly horizontal (mediolateral) orientation of ± 90 ° . (d) Example of crossing fibers in the optic chiasm. (e) ODF showing two local peaks (dotted and solid red lines) corresponding to the crossing fibers. (f) Histogram of tract orientations shows two predominant orientation populations, representing contralaterally projecting fibers. Scale bars are 0.1 mm.

Equations (3)

Equations on this page are rendered with MathJax. Learn more.

ODF ( θ ) = | F w ( f x , f y ) | 2 H ( f x , f y ) d f ,
θ ¯ = 1 2 Arg ( 1 N n = 1 N e i 2 θ n ) and
Var = 1 [ 1 N n = 1 N cos ( 2 θ n ) ] 2 + [ 1 N n = 1 N sin ( 2 θ n ) ] 2 .

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