Abstract

The in vitro investigation of many optically opaque biological microstructures requires 3D analysis at high resolution over a large field of view. We demonstrate a new nondestructive volumetric imaging technique that eliminates the structural and computational limitations of conventional 2D optical microscopy by combining x-ray phase-contrast tomography with critical point drying sample preparation. We experimentally demonstrate the enhancement of small features afforded by phase-contrast imaging and show the contrast improvement afforded by the drying of a hydrated specimen. We further demonstrate the biological application of this technique by imaging the microstructure of the accommodative apparatus in a primate eye using a benchtop phase-contrast tomography system.

© 2012 OSA

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2010 (2)

E. Lütjen-Drecoll, P. L. Kaufman, R. Wasielewski, L. Ting-Li, and M. A. Croft, “Morphology and accommodative function of the vitreous zonule in human and monkey eyes,” Invest. Ophthalmol. Vis. Sci. 51(3), 1554–1564 (2010).
[CrossRef] [PubMed]

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

2008 (1)

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

2007 (2)

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

T. Latychevskaia and H.-W. Fink, “Solution to the twin image problem in holography,” Phys. Rev. Lett. 98(23), 233901 (2007).
[CrossRef] [PubMed]

2005 (1)

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

2004 (1)

M. A. Anastasio, D. Shi, F. De Carlo, and X. Pan, “Analytic image reconstruction in local phase-contrast tomography,” Phys. Med. Biol. 49(1), 121–144 (2004).
[CrossRef] [PubMed]

2003 (1)

D. Gardella, W. J. Hatton, H. B. Rind, G. D. Rosen, and C. S. von Bartheld, “Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections,” J. Neurosci. Methods 124(1), 45–59 (2003).
[CrossRef] [PubMed]

2001 (1)

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A. 98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

1997 (2)

A. Pogany, D. Gao, and S. W. Wilkins, “Contrast and resolution in imaging with a microfocus x-ray source,” Rev. Sci. Instrum. 68(7), 2774–2782 (1997).
[CrossRef]

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

1996 (3)

K. A. Nugent, T. E. Gureyev, D. J. Cookson, D. Paganin, and Z. Barnea, “Quantitative phase imaging using hard x-rays,” Phys. Rev. Lett. 77(14), 2961–2964 (1996).
[CrossRef] [PubMed]

J. R. Kuszak, K. L. Peterson, and H. G. Brown, “Electron microscopic observations of the crystalline lens,” Microsc. Res. Tech. 33(6), 441–479 (1996).
[CrossRef] [PubMed]

S. W. Wilkins, T. E. Gureyev, D. Gao, A. Pogany, and A. W. Stevenson, “Phase-contrast imaging using polychromatic hard x-rays,” Nature 384(6607), 335–338 (1996).
[CrossRef]

1995 (1)

A. Snigirev, I. Snigireva, V. Kohn, S. Kuznetsov, and I. Schelokov, “On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation,” Rev. Sci. Instrum. 66(12), 5486–5492 (1995).
[CrossRef]

1994 (1)

A. S. Jones, B. K. Milthorpe, and C. R. Howlett, “Measurement of microtomy-induced section distortion and its correction for 3-dimensional histological reconstructions,” Cytometry 15(2), 95–105 (1994).
[CrossRef] [PubMed]

1988 (1)

E. Lütjen-Drecoll, E. Tamm, and P. L. Kaufman, “Age changes in rhesus monkey ciliary muscle: light and electron microscopy,” Exp. Eye Res. 47(6), 885–899 (1988).
[CrossRef] [PubMed]

1984 (1)

1969 (1)

G. A. Horridge and S. L. Tamm, “Critical point drying for scanning electron microscopic study of ciliary motion,” Science 163(3869), 817–818 (1969).
[CrossRef] [PubMed]

1948 (1)

D. Gabor, “A new microscopic principle,” Nature 161(4098), 777–778 (1948).
[CrossRef] [PubMed]

Anastasio, M. A.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

M. A. Anastasio, D. Shi, F. De Carlo, and X. Pan, “Analytic image reconstruction in local phase-contrast tomography,” Phys. Med. Biol. 49(1), 121–144 (2004).
[CrossRef] [PubMed]

Ayache, N.

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

Barnea, Z.

K. A. Nugent, T. E. Gureyev, D. J. Cookson, D. Paganin, and Z. Barnea, “Quantitative phase imaging using hard x-rays,” Phys. Rev. Lett. 77(14), 2961–2964 (1996).
[CrossRef] [PubMed]

Baruchel, J.

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

Brown, H. G.

J. R. Kuszak, K. L. Peterson, and H. G. Brown, “Electron microscopic observations of the crystalline lens,” Microsc. Res. Tech. 33(6), 441–479 (1996).
[CrossRef] [PubMed]

Buffière, J. Y.

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

Cloetens, P.

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

Condé, F.

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

Cookson, D. J.

K. A. Nugent, T. E. Gureyev, D. J. Cookson, D. Paganin, and Z. Barnea, “Quantitative phase imaging using hard x-rays,” Phys. Rev. Lett. 77(14), 2961–2964 (1996).
[CrossRef] [PubMed]

Croft, M. A.

E. Lütjen-Drecoll, P. L. Kaufman, R. Wasielewski, L. Ting-Li, and M. A. Croft, “Morphology and accommodative function of the vitreous zonule in human and monkey eyes,” Invest. Ophthalmol. Vis. Sci. 51(3), 1554–1564 (2010).
[CrossRef] [PubMed]

Dauguet, J.

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

Davis, L. C.

De Carlo, F.

M. A. Anastasio, D. Shi, F. De Carlo, and X. Pan, “Analytic image reconstruction in local phase-contrast tomography,” Phys. Med. Biol. 49(1), 121–144 (2004).
[CrossRef] [PubMed]

Delzescaux, T.

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

Derdak, Z.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Diebold, G.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Feldkamp, L. A.

Fink, H.-W.

T. Latychevskaia and H.-W. Fink, “Solution to the twin image problem in holography,” Phys. Rev. Lett. 98(23), 233901 (2007).
[CrossRef] [PubMed]

Frouin, V.

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

Furukawa, A.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Gabor, D.

D. Gabor, “A new microscopic principle,” Nature 161(4098), 777–778 (1948).
[CrossRef] [PubMed]

Gao, D.

A. Pogany, D. Gao, and S. W. Wilkins, “Contrast and resolution in imaging with a microfocus x-ray source,” Rev. Sci. Instrum. 68(7), 2774–2782 (1997).
[CrossRef]

S. W. Wilkins, T. E. Gureyev, D. Gao, A. Pogany, and A. W. Stevenson, “Phase-contrast imaging using polychromatic hard x-rays,” Nature 384(6607), 335–338 (1996).
[CrossRef]

Gardella, D.

D. Gardella, W. J. Hatton, H. B. Rind, G. D. Rosen, and C. S. von Bartheld, “Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections,” J. Neurosci. Methods 124(1), 45–59 (2003).
[CrossRef] [PubMed]

Gureyev, T. E.

S. W. Wilkins, T. E. Gureyev, D. Gao, A. Pogany, and A. W. Stevenson, “Phase-contrast imaging using polychromatic hard x-rays,” Nature 384(6607), 335–338 (1996).
[CrossRef]

K. A. Nugent, T. E. Gureyev, D. J. Cookson, D. Paganin, and Z. Barnea, “Quantitative phase imaging using hard x-rays,” Phys. Rev. Lett. 77(14), 2961–2964 (1996).
[CrossRef] [PubMed]

Hamilton, T. J.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Hantraye, P.

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

Hatton, W. J.

D. Gardella, W. J. Hatton, H. B. Rind, G. D. Rosen, and C. S. von Bartheld, “Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections,” J. Neurosci. Methods 124(1), 45–59 (2003).
[CrossRef] [PubMed]

Honda, C.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Horridge, G. A.

G. A. Horridge and S. L. Tamm, “Critical point drying for scanning electron microscopic study of ciliary motion,” Science 163(3869), 817–818 (1969).
[CrossRef] [PubMed]

Howlett, C. R.

A. S. Jones, B. K. Milthorpe, and C. R. Howlett, “Measurement of microtomy-induced section distortion and its correction for 3-dimensional histological reconstructions,” Cytometry 15(2), 95–105 (1994).
[CrossRef] [PubMed]

Jansen, J. A.

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

Jericho, M. H.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A. 98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Jones, A. S.

A. S. Jones, B. K. Milthorpe, and C. R. Howlett, “Measurement of microtomy-induced section distortion and its correction for 3-dimensional histological reconstructions,” Cytometry 15(2), 95–105 (1994).
[CrossRef] [PubMed]

Kasper, F. K.

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

Kaufman, P. L.

E. Lütjen-Drecoll, P. L. Kaufman, R. Wasielewski, L. Ting-Li, and M. A. Croft, “Morphology and accommodative function of the vitreous zonule in human and monkey eyes,” Invest. Ophthalmol. Vis. Sci. 51(3), 1554–1564 (2010).
[CrossRef] [PubMed]

E. Lütjen-Drecoll, E. Tamm, and P. L. Kaufman, “Age changes in rhesus monkey ciliary muscle: light and electron microscopy,” Exp. Eye Res. 47(6), 885–899 (1988).
[CrossRef] [PubMed]

Kohn, V.

A. Snigirev, I. Snigireva, V. Kohn, S. Kuznetsov, and I. Schelokov, “On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation,” Rev. Sci. Instrum. 66(12), 5486–5492 (1995).
[CrossRef]

Kress, J. W.

Kretlow, J. D.

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

Kreuzer, H. J.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A. 98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Kuszak, J. R.

J. R. Kuszak, K. L. Peterson, and H. G. Brown, “Electron microscopic observations of the crystalline lens,” Microsc. Res. Tech. 33(6), 441–479 (1996).
[CrossRef] [PubMed]

Kuznetsov, S.

A. Snigirev, I. Snigireva, V. Kohn, S. Kuznetsov, and I. Schelokov, “On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation,” Rev. Sci. Instrum. 66(12), 5486–5492 (1995).
[CrossRef]

Laperle, C. M.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Latychevskaia, T.

T. Latychevskaia and H.-W. Fink, “Solution to the twin image problem in holography,” Phys. Rev. Lett. 98(23), 233901 (2007).
[CrossRef] [PubMed]

Lütjen-Drecoll, E.

E. Lütjen-Drecoll, P. L. Kaufman, R. Wasielewski, L. Ting-Li, and M. A. Croft, “Morphology and accommodative function of the vitreous zonule in human and monkey eyes,” Invest. Ophthalmol. Vis. Sci. 51(3), 1554–1564 (2010).
[CrossRef] [PubMed]

E. Lütjen-Drecoll, E. Tamm, and P. L. Kaufman, “Age changes in rhesus monkey ciliary muscle: light and electron microscopy,” Exp. Eye Res. 47(6), 885–899 (1988).
[CrossRef] [PubMed]

Mangin, J.-F.

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

Matsuo, S.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Meinertzhagen, I. A.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A. 98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Mikos, A. G.

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

Milthorpe, B. K.

A. S. Jones, B. K. Milthorpe, and C. R. Howlett, “Measurement of microtomy-induced section distortion and its correction for 3-dimensional histological reconstructions,” Cytometry 15(2), 95–105 (1994).
[CrossRef] [PubMed]

Murata, K.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Nitta, N.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Noma, K.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Nugent, K. A.

K. A. Nugent, T. E. Gureyev, D. J. Cookson, D. Paganin, and Z. Barnea, “Quantitative phase imaging using hard x-rays,” Phys. Rev. Lett. 77(14), 2961–2964 (1996).
[CrossRef] [PubMed]

Oohara, H.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Ota, S.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Paganin, D.

K. A. Nugent, T. E. Gureyev, D. J. Cookson, D. Paganin, and Z. Barnea, “Quantitative phase imaging using hard x-rays,” Phys. Rev. Lett. 77(14), 2961–2964 (1996).
[CrossRef] [PubMed]

Pan, X.

M. A. Anastasio, D. Shi, F. De Carlo, and X. Pan, “Analytic image reconstruction in local phase-contrast tomography,” Phys. Med. Biol. 49(1), 121–144 (2004).
[CrossRef] [PubMed]

Pateyron-Salomé, M.

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

Peix, G.

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

Peterson, K. L.

J. R. Kuszak, K. L. Peterson, and H. G. Brown, “Electron microscopic observations of the crystalline lens,” Microsc. Res. Tech. 33(6), 441–479 (1996).
[CrossRef] [PubMed]

Peyrin, F.

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

Pogany, A.

A. Pogany, D. Gao, and S. W. Wilkins, “Contrast and resolution in imaging with a microfocus x-ray source,” Rev. Sci. Instrum. 68(7), 2774–2782 (1997).
[CrossRef]

S. W. Wilkins, T. E. Gureyev, D. Gao, A. Pogany, and A. W. Stevenson, “Phase-contrast imaging using polychromatic hard x-rays,” Nature 384(6607), 335–338 (1996).
[CrossRef]

Rind, H. B.

D. Gardella, W. J. Hatton, H. B. Rind, G. D. Rosen, and C. S. von Bartheld, “Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections,” J. Neurosci. Methods 124(1), 45–59 (2003).
[CrossRef] [PubMed]

Rosen, G. D.

D. Gardella, W. J. Hatton, H. B. Rind, G. D. Rosen, and C. S. von Bartheld, “Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections,” J. Neurosci. Methods 124(1), 45–59 (2003).
[CrossRef] [PubMed]

Rose-Petruck, C.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Sakashita, Y.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Schelokov, I.

A. Snigirev, I. Snigireva, V. Kohn, S. Kuznetsov, and I. Schelokov, “On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation,” Rev. Sci. Instrum. 66(12), 5486–5492 (1995).
[CrossRef]

Schlenker, M.

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

Shi, D.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

M. A. Anastasio, D. Shi, F. De Carlo, and X. Pan, “Analytic image reconstruction in local phase-contrast tomography,” Phys. Med. Biol. 49(1), 121–144 (2004).
[CrossRef] [PubMed]

Snigirev, A.

A. Snigirev, I. Snigireva, V. Kohn, S. Kuznetsov, and I. Schelokov, “On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation,” Rev. Sci. Instrum. 66(12), 5486–5492 (1995).
[CrossRef]

Snigireva, I.

A. Snigirev, I. Snigireva, V. Kohn, S. Kuznetsov, and I. Schelokov, “On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation,” Rev. Sci. Instrum. 66(12), 5486–5492 (1995).
[CrossRef]

Spicer, P. P.

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

Stevenson, A. W.

S. W. Wilkins, T. E. Gureyev, D. Gao, A. Pogany, and A. W. Stevenson, “Phase-contrast imaging using polychromatic hard x-rays,” Nature 384(6607), 335–338 (1996).
[CrossRef]

Takahashi, M.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Tamm, E.

E. Lütjen-Drecoll, E. Tamm, and P. L. Kaufman, “Age changes in rhesus monkey ciliary muscle: light and electron microscopy,” Exp. Eye Res. 47(6), 885–899 (1988).
[CrossRef] [PubMed]

Tamm, S. L.

G. A. Horridge and S. L. Tamm, “Critical point drying for scanning electron microscopic study of ciliary motion,” Science 163(3869), 817–818 (1969).
[CrossRef] [PubMed]

Tanaka, T.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Ting-Li, L.

E. Lütjen-Drecoll, P. L. Kaufman, R. Wasielewski, L. Ting-Li, and M. A. Croft, “Morphology and accommodative function of the vitreous zonule in human and monkey eyes,” Invest. Ophthalmol. Vis. Sci. 51(3), 1554–1564 (2010).
[CrossRef] [PubMed]

Tsuchiya, K.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Vacanti, C. A.

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

von Bartheld, C. S.

D. Gardella, W. J. Hatton, H. B. Rind, G. D. Rosen, and C. S. von Bartheld, “Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections,” J. Neurosci. Methods 124(1), 45–59 (2003).
[CrossRef] [PubMed]

Walker, E. J.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Wands, J. R.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Wasielewski, R.

E. Lütjen-Drecoll, P. L. Kaufman, R. Wasielewski, L. Ting-Li, and M. A. Croft, “Morphology and accommodative function of the vitreous zonule in human and monkey eyes,” Invest. Ophthalmol. Vis. Sci. 51(3), 1554–1564 (2010).
[CrossRef] [PubMed]

Wilkins, S. W.

A. Pogany, D. Gao, and S. W. Wilkins, “Contrast and resolution in imaging with a microfocus x-ray source,” Rev. Sci. Instrum. 68(7), 2774–2782 (1997).
[CrossRef]

S. W. Wilkins, T. E. Gureyev, D. Gao, A. Pogany, and A. W. Stevenson, “Phase-contrast imaging using polychromatic hard x-rays,” Nature 384(6607), 335–338 (1996).
[CrossRef]

Wintermeyer, P.

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

Xu, W.

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A. 98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Yamada, A.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Yamasaki, M.

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

Cytometry (1)

A. S. Jones, B. K. Milthorpe, and C. R. Howlett, “Measurement of microtomy-induced section distortion and its correction for 3-dimensional histological reconstructions,” Cytometry 15(2), 95–105 (1994).
[CrossRef] [PubMed]

Exp. Eye Res. (1)

E. Lütjen-Drecoll, E. Tamm, and P. L. Kaufman, “Age changes in rhesus monkey ciliary muscle: light and electron microscopy,” Exp. Eye Res. 47(6), 885–899 (1988).
[CrossRef] [PubMed]

Invest. Ophthalmol. Vis. Sci. (1)

E. Lütjen-Drecoll, P. L. Kaufman, R. Wasielewski, L. Ting-Li, and M. A. Croft, “Morphology and accommodative function of the vitreous zonule in human and monkey eyes,” Invest. Ophthalmol. Vis. Sci. 51(3), 1554–1564 (2010).
[CrossRef] [PubMed]

Invest. Radiol. (1)

T. Tanaka, C. Honda, S. Matsuo, K. Noma, H. Oohara, N. Nitta, S. Ota, K. Tsuchiya, Y. Sakashita, A. Yamada, M. Yamasaki, A. Furukawa, M. Takahashi, and K. Murata, “The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube,” Invest. Radiol. 40(7), 385–396 (2005).
[CrossRef] [PubMed]

J. Appl. Phys. (1)

P. Cloetens, M. Pateyron-Salomé, J. Y. Buffière, G. Peix, J. Baruchel, F. Peyrin, and M. Schlenker, “Observation of microstructure and damage in materials by phase sensitive radiography and tomography,” J. Appl. Phys. 81(9), 5878–5886 (1997).
[CrossRef]

J. Neurosci. Methods (2)

D. Gardella, W. J. Hatton, H. B. Rind, G. D. Rosen, and C. S. von Bartheld, “Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections,” J. Neurosci. Methods 124(1), 45–59 (2003).
[CrossRef] [PubMed]

J. Dauguet, T. Delzescaux, F. Condé, J.-F. Mangin, N. Ayache, P. Hantraye, and V. Frouin, “Three-dimensional reconstruction of stained histological slices and 3D non-linear registration with in-vivo MRI for whole baboon brain,” J. Neurosci. Methods 164(1), 191–204 (2007).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (1)

Microsc. Res. Tech. (1)

J. R. Kuszak, K. L. Peterson, and H. G. Brown, “Electron microscopic observations of the crystalline lens,” Microsc. Res. Tech. 33(6), 441–479 (1996).
[CrossRef] [PubMed]

Nature (2)

D. Gabor, “A new microscopic principle,” Nature 161(4098), 777–778 (1948).
[CrossRef] [PubMed]

S. W. Wilkins, T. E. Gureyev, D. Gao, A. Pogany, and A. W. Stevenson, “Phase-contrast imaging using polychromatic hard x-rays,” Nature 384(6607), 335–338 (1996).
[CrossRef]

Phys. Med. Biol. (2)

C. M. Laperle, T. J. Hamilton, P. Wintermeyer, E. J. Walker, D. Shi, M. A. Anastasio, Z. Derdak, J. R. Wands, G. Diebold, and C. Rose-Petruck, “Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue,” Phys. Med. Biol. 53(23), 6911–6923 (2008).
[CrossRef] [PubMed]

M. A. Anastasio, D. Shi, F. De Carlo, and X. Pan, “Analytic image reconstruction in local phase-contrast tomography,” Phys. Med. Biol. 49(1), 121–144 (2004).
[CrossRef] [PubMed]

Phys. Rev. Lett. (2)

T. Latychevskaia and H.-W. Fink, “Solution to the twin image problem in holography,” Phys. Rev. Lett. 98(23), 233901 (2007).
[CrossRef] [PubMed]

K. A. Nugent, T. E. Gureyev, D. J. Cookson, D. Paganin, and Z. Barnea, “Quantitative phase imaging using hard x-rays,” Phys. Rev. Lett. 77(14), 2961–2964 (1996).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

W. Xu, M. H. Jericho, I. A. Meinertzhagen, and H. J. Kreuzer, “Digital in-line holography for biological applications,” Proc. Natl. Acad. Sci. U.S.A. 98(20), 11301–11305 (2001).
[CrossRef] [PubMed]

Rev. Sci. Instrum. (2)

A. Snigirev, I. Snigireva, V. Kohn, S. Kuznetsov, and I. Schelokov, “On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation,” Rev. Sci. Instrum. 66(12), 5486–5492 (1995).
[CrossRef]

A. Pogany, D. Gao, and S. W. Wilkins, “Contrast and resolution in imaging with a microfocus x-ray source,” Rev. Sci. Instrum. 68(7), 2774–2782 (1997).
[CrossRef]

Science (1)

G. A. Horridge and S. L. Tamm, “Critical point drying for scanning electron microscopic study of ciliary motion,” Science 163(3869), 817–818 (1969).
[CrossRef] [PubMed]

Tissue Eng. Part A (1)

J. D. Kretlow, P. P. Spicer, J. A. Jansen, C. A. Vacanti, F. K. Kasper, and A. G. Mikos, “Uncultured marrow mononuclear cells delivered within fibrin glue hydrogels to porous scaffolds enhance bone regeneration within critical-sized rat cranial defects,” Tissue Eng. Part A 16(12), 3555–3568 (2010).
[CrossRef] [PubMed]

Other (8)

P. Echlin, Handbook of Sample Preparation for Scanning Electron Microscopy and X-Ray Microanalysis (Springer, New York, 2009).

A. Limaye, “Drishti—volume exploration and presentation tool,” presented at IEEE Visualization (Vis 2006), Baltimore, Oct. 29–Nov. 3, 2006.

R. C. Gonzalez and R. E. Woods, Digital Image Processing, 3rd ed. (Prentice Hall, Upper Saddle River, New Jersey, 2008).

P. L. Kaufman, Adler’s Physiology of the Eye, 10th ed. (Mosby, St. Louis, Missouri, 2003).

J. R. Kuszak and M. J. Costello, “Embryology and anatomy of human lenses,” in Duane's Foundations of Clinical Ophthalmology, W. Tasman and E. A. Jaeger, eds. (Lippincott Williams & Wilkins, Philadelphia, 1992).

M. Salzmann, The Anatomy and Histology of the Human Eyeball in the Normal State (University of Chicago Press, 1912).

B. J. Anson, Morris’ Human Anatomy, 12th ed. (McGraw-Hill, New York, 1966).

British Standards, “Method for measurement of the effective focal spot size of mini-focus and micro-focus x-ray tubes used for industrial radiography,” BS 6932:1988 (BSI, 1988).

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Figures (5)

Fig. 1
Fig. 1

In-line phase-contrast tomography system. The planar x-ray intensity is shown as it propagates from the microfocus source to the sample (distance R1) and from the sample to the detector (distance R2). Intensity fringes develop with propagation and are measured by a digital detector. An example simulated phase-contrast image of a sphere is shown on the right.

Fig. 2
Fig. 2

The contrast improvement induced by drying is shown here in projection images and plots of image histogram statistics. The cranial defect specimen, which was dried over a period of 58 minutes, shows fibrous polymer layer structures when dried (far right) that are relatively difficult to discern in the un-dried specimen (far left). Quantitative improvements in contrast are shown in the graphs of the time-dependent behavior of intensity histogram variance and uniformity. Note that the specimen occupies the entire frame in these images. The grayscale window is the same for all images.

Fig. 3
Fig. 3

The effect of propagation distance on phase contrast in projection images of a critical point dried baboon eye. In the low-propagation case (left), the fine structure of the crystalline lens and focusing structures are relatively indistinct. In the high-propagation case (right), in which phase-contrast is enhanced, these features are more easily visualized. Quantitative assessment of image statistics in two regions (boxes in the images) shows the effect of phase-enhancement on intensity histogram variance and uniformity. The grayscale window is the same for both images.

Fig. 4
Fig. 4

Transverse slices of the reconstructed tomography data of a critical point dried baboon eye. The proximal plane slice in (a) clearly shows the iris (i), ciliary structures (ci), and choroid (ch). The distal plane slice in (b) additionally shows the crystalline lens (cl). Note that although there is little absorption contrast visible in the interior of many structures, boundaries display significant edge contrast (e.g., the iris). A threshold was applied to the data for display purposes. The grayscale window is the same for both images.

Fig. 5
Fig. 5

A 3D volumetric rendering of the focusing apparatus of a critical point dried baboon eye. Anterior (a), lateral (b), and posterior (c) images show the large field of view that can be captured relative to microscopy. The transverse slice data exposed in the anterior view (d) demonstrate the simultaneous visualization of interior and exterior sample structures. Finally, the zoomed-in posterior view (e) shows the highly detailed visualization of ciliary structures emanating from the crystalline lens. A threshold was applied to the volumetric data for display purposes. Scale bars are 1 mm in length.

Equations (4)

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

r= R 1 R 1 + R 2 ( R 2 R 1 s ) 2 + d 2 ,
I(x,y)= I o M 2 ( exp[ 2k dzβ(r) ] R 2 M x,y 2 { exp[ 2k dzβ(r) ] dzδ(r) } ),
σ 2 = n=0 255 ( I ¯ n E) 2 p( I ¯ n ),
U= n=0 255 p 2 ( I ¯ n )

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