- Email: [email protected]
Diffraction-enhanced imaging of a porcine eye
Diffraction-enhanced imaging of a porcine eye Michael E. Kelly, MD;* Dustin J. Coupal, MD;† R. Cole Beavis, MD;‡ Elisabeth Schultke, MD, PhD;§ Kenneth Romanchuk, MD;|| Bernhard H.J. Juurlink, PhD;§ Zhong Zhong, PhD;¶ L. Dean Chapman, PhD§ ABSTRACT • RÉSUMÉ
Background: Diffraction-enhanced imaging (DEI) is a synchrotron-based x-ray imaging technique that has dramatically improved contrast over standard x-ray imaging techniques. It is possible to acquire images that analyze the x-ray refraction and the apparent absorption (elimination of small-angle scattering) of the object. Methods: Three formalin-fixed porcine eyes were studied at the National Synchrotron Light Source using DEI. Conventional absorption-type radiography was conducted for comparison. Results: Conventional absorption radiography did not yield significant detail of the eye anatomy. DEI showed excellent characterization of many ocular structures. The cornea, iris, lens, retina, optic nerve, as well as choroidal vasculature and the ampullae of the vortex veins could all be visualized. Interpretation: DEI represents a novel, high-resolution imaging technique that has excellent characterization of ocular anatomy. Further application of this imaging modality will be undertaken to study cataract and choroidal tumors and to examine ocular surface structures, such as the extraocular muscle insertions, more closely. Contexte : L’imagerie améliorée par diffraction (IAD) repose sur une technique ordinaire de radiographie par radiation de synchrotron qui améliore de façon spectaculaire le contraste du rayon X standard. On peut ainsi obtenir des images qui analysent la réfraction de la radiographie et l’apparente absorption de l’objet (par l’élimination de la dispersion micro-angulaire). Méthodes : Étude de trois yeux de porc conservés dans le formol à la National Synchrotron Light Source effectuée par IAD. La radiographie conventionnelle par absorption a servi d’élément de comparaison. Résultats : La radiographie conventionnelle par absorption n’a pas donné de détails significatifs sur l’anatomie des yeux. L’IAD a fait voir d’excellentes caractéristiques de plusieurs structures oculaires. La cornée, l’iris, la lentille, la rétine, le nerf optique de même que la vascularisation choroïdienne et les ampoules des veines vortiqueuses peuvent tous être visualisés. Interprétation : L’imagerie améliorée par diffraction présente une nouvelle technique d’imagerie à haute résolution montrant de façon excellente les caractéristiques de l’anatomie oculaire. D’autres applications de ce mode d’imagerie permettront d’étudier les cataractes et les tumeurs de la choroïde, et d’examiner de plus près les structures de la surface oculaire, telles les insertions musculaires extraoculaires.
he synchrotron was first produced in 1947 by General Electric, and since that time there have been many synchrotrons built around the world, including one that recently opened in Canada. Collectively, these synchrotrons have allowed for significant discoveries in the fields of physics, medicine, and engineering. Synchrotron-supported imaging techniques are currently under development for medical imaging. A novel technique called diffraction-enhanced imaging (DEI) was introduced by Chapman et al.1 in 1997. DEI is an x-ray–based imaging technique using monochromatic x-rays from a synchrotron
T
light source that produces images of thick absorbing objects that are almost completely free of scatter. Images obtained by DEI show dramatically improved contrast over standard imaging applied to the same object. When x-rays interact with a biological substance, they are either absorbed, scattered, or refracted. DEI is able to use x-ray refraction and rejection of scatter to obtain more information about the object than conventional absorption x-ray imaging. This was previously demonstrated in DEI studies of soft tissues, such as articular cartilage, cadaveric foot, and spine and breast specimens at the National Synchrotron Light
From *the Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio; †the Department of Ophthalmology, Pasqua Hospital, University of Saskatchewan, Regina, Sask.; ‡the Division of Orthopaedic Surgery, Royal University Hospital, University of Saskatchewan, Saskatoon, Sask.; §the Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Sask.; ||the Department of Ophthalmology, University of Calgary, Calgary, Alta.; and ¶the National Synchrotron Light Source, Brookhaven National Laboratory, Upton, N.Y.
Correspondence to: Michael E. Kelly, MD, Section of Cerebrovascular and Endovascular Neurosurgery, Department of Neurosurgery, Cleveland Clinic, 9500 Euclid Ave., S80, Cleveland, OH 44195; [email protected] This article has been peer-reviewed. Cet article a été évalué par les pairs. Can J Ophthalmol 2007;42:731–3 doi: 10.3129/can j ophthalmol.i07-132
Originally received Jan. 8, 2006. Revised Mar. 12, 2007 Accepted for publication Apr. 30, 2007 Published online Sep. 6, 2007
Diffraction-enhanced imaging—Kelly et al.
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Diffraction-enhanced imaging—Kelly et al. Source.2–9 We describe the first known attempt to use DEI to study a porcine model of the eye. METHODS
Three formalin-fixed porcine eyes were studied at beamline X15A at the National Synchrotron Light Source in Brookhaven National Laboratory, Upton, N.Y. DEIs and standard x-ray radiographs were performed using a standard technique and dedicated imaging system.1,10 An energy of 40 kiloelectron volts (keV) was used, and images were captured with a charged coupled device x-ray detector. The eyes were mounted on wooden holders using epoxy glue and submerged in distilled water. The container was then agitated to remove air bubbles that had formed on the specimen and container. The eyes were placed in 3 separate orientations. The set-up is shown in Fig. 1. Image analysis was performed using Interactive Data Language software (Research Systems Inc., Boulder, Colo.). The procedure of DEI is briefly described below but can be found in more detail in other publications.1,9,10 The analyzer crystal used in DEI is composed of silicon, usually in a 3,3,3 lattice configuration. The silicon crystal is able to select for either refraction of light or apparent absorption of light. This selection is done by moving the analyzer crystal. Apparent absorption results because the analyzer crystal is sensitive to scatter and removes it from the image. The rejected scatter is considered to be small-angle scattering that arises from the scattering of very small, fine structures. This scattering normally appears on conventional radiography but is missing in DEI. Improved image contrast is possible because of this scatter rejection.9 Apparent absorption is the result of the absorption of x-rays by the object with scatter rejection or extinction. The crystal detects refraction of the x-rays as they pass through the sample. Refraction is a change in direction of the x-ray beam when it passes between the boundaries of 2 materials in which the velocity of propagation is differ-
ent. Refraction images can also be obtained, and they show superior image contrast.9 By using DEI, significantly more information can be obtained about the specimen characteristics than with conventional radiography. Conventional absorption radiography was performed using standard x-ray image plates (Fuji Medical Systems) and synchrotron radiation source using the same x-ray energy and dose as DEI. These images were used for comparison. RESULTS Absorption radiography
The conventional absorption radiograph, shown in Fig. 2, was acquired with 40 keV x-rays. Because of the low x-ray absorption of the eyes, this technique provided only an indistinct image of the porcine eyes, as is typical of conventional x-ray imaging techniques performed on soft-tissues. DEI
DEI was performed on the specimen. Image resolution was estimated to be 100 μm. Image analysis with Interactive Data Language software revealed that the refraction images of the eyes allowed for the most image detail (Fig. 3). Analysis of the images revealed excellent characterization of many ocular structures that were not identifiable on the comparative absorption radiograph image (Fig. 2). Most apparent on the refraction images are the cornea, ciliary body, ciliary processes, lens, choroid, vortex veins, sclera, and optic nerve. We also used the Interactive Data Language software to analyze the scatter rejection of the image (Fig. 4). This image demonstrated impressive detail of the choroidal vasculature and corresponding ampullae of the vortex veins. However, this scatter rejection image provided less detail of the intraocular structures than seen in the refraction image. DISCUSSION
We present the first ocular images obtained from DEI using synchrotron radiation. The full utility of synchrotron biomedical beamlines has yet to be completely defined. DEI is one such advanced imaging technique that demonstrates detailed anatomic ocular images, not possible with other x-ray imaging techniques. The images produced from DEI are 2-dimensional
Fig. 1—Set up for diffraction-enhanced imaging of porcine eyes.
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Fig. 2—Conventional absorption radiography of porcine eyes. (Scale bar = 1 cm.)
Diffraction-enhanced imaging—Kelly et al. planar images. The 3-dimensional appearance is secondary to the significantly improved contrast. The modality uses not only x-ray absorption but also small-angle scattering to improve image contrast. The detector also has an excellent resolution, but it must be noted that the conventional x-ray absorption radiography used the same detector. Ocular imaging is most commonly performed using computerized tomography, magnetic resonance imaging, or low-frequency ultrasound imaging with the resultant images often being of low contrast and detail. As newer techniques are developed, such as ocular coherence tomography and high-resolution ultrasound biomicroscopy, new levels of detail that were previously unachievable are being obtained. DEI represents another novel, ocular imaging technique that provides high-resolution ocular images. In this initial study, we imaged the eye without the surrounding orbit and skull. To assess the eventual clinical and research potential of this technique, further study of the eye in the orbit must be performed. Synchrotron-based DEI imaging is a safe way of imaging. Radiation exposure from DEI can be limited with various safety features. The most widely applied synchrotron imaging modality in human subjects is coronary angiography. It has been safely performed in over 500 patients worldwide.11 The dose of approximately 1 milligray (mGy) used in the present study is far less than that used for angiography (more than 10 mGy). Thus, we believe that it is also possible to perform DEI in a safe manner on a live animal model or human without adverse effects. One significant disadvantage of DEI in the practice of clinical ophthalmology is that the procedure is dependent on a synchrotron radiation source. The Canadian Light Source in Saskatoon, Sask., is the only synchrotron in Canada. Currently, there
Fig. 3—Diffraction-enhanced imaging (refraction image) of porcine eyes illustrating cornea, lens, iris, retina, and optic nerve. Scattered air bubbles are noted as surface artifacts.
Fig. 4—Diffraction-enhanced imaging (apparent absorption highlighting scatter rejection) of porcine eyes illustrating cornea, lens, iris, retina, and optic nerve, as well as choroidal vasculature and the ampulae of the vortex veins.
are limited clinical applications for DEI, and it remains only a research tool. Work is under way at several institutions, including the Canadian Light Source, to create a more “portable” DEI imaging device. Further experiments are required prior to undertaking limited human imaging. In summary, DEI represents a novel imaging technique that can be applied to ocular imaging. Exquisite delineation of the ocular anatomy was obtained in this first ever report of DEI imaging of an eye. To further evaluate the utility of DEI in ophthalmology we intend to analyze ocular conditions such as cataract and choroidal tumors and also to examine ocular surface structures more closely, including the extraocular muscle insertions. The authors acknowledge the support of the Saskatchewan Synchrotron Institute, Departments of Surgery and Ophthalmology, University of Saskatchewan. Dr. Kelly is supported in part by the American Association of Neurological Surgeons, Neurosurgery Research and Education Foundation Fellowship. Dr. Chapman is supported in part by a Canadian Institutes of Health Research Establishment Grant. Utilization of the X15A beamline was supported by the U.S. Department of Energy contract DE-AC02-76CH00016. Institutional review board approval was not needed and therefore not obtained for this experiment.
REFERENCES 1. Chapman D, Thomlinson W, Johnston RE, et al. Diffraction enhanced x-ray imaging. Phys Med Biol 1997;42(11):2015–25. 2. Dilmanian FA, Zhong Z, Ren B, et al. Computed tomography of x-ray index of refraction using the diffraction enhanced imaging method. Phys Med Biol 2000;45(4):933–46. 3. Hasnah MO, Zhong Z, Oltulu O, et al. Diffraction enhanced imaging contrast mechanisms in breast cancer specimens. Med Phys 2002;29(10):2216–21. 4. Johnston RE, Washburn D, Pisano E, et al. Mammographic phantom studies with synchrotron radiation. Radiology 1996;200(3):659–63. 5. Lewis RA, Hall CJ, Hufton AP, et al. X-ray refraction effects: application to the imaging of biological tissues. Br J Radiol 2003;76(905):301–8. 6. Mollenhauer J, Aurich ME, Zhong Z, et al. Diffractionenhanced x-ray imaging of articular cartilage. Osteoarthritis Cartilage 2002;10(3):163–71. 7. Muehleman C, Chapman LD, Kuettner KE, et al. Radiography of rabbit articular cartilage with diffraction-enhanced imaging. Anat Rec A Discov Mol Cell Evol Biol 2003;272A(1):392–7. 8. Pisano ED, Johnston RE, Chapman D, et al. Human breast cancer specimens: diffraction-enhanced imaging with histologic correlation—improved conspicuity of lesion detail compared with digital radiography. Radiology 2000;214(3):895–901. 9. Kelly ME, Beavis RC, Fourney DR, et al. Diffraction-enhanced imaging of the rat spine. Can Assoc Radiol J 2006;57(4):204–10. 10. Zhong Z, Thomlinson W, Chapman D, Sayers D. Implementation of diffraction enhanced imaging experiments: at the NSLS and APS. Nucl Instrum Meth Phys Res A 2000;450:556–67. 11. Suortti P, Thomlinson W. Medical applications of synchrotron radiation. Phys Med Biol 2003;48(13):R1–35. Key words: diffraction enhanced imaging, eye, synchrotron CAN J OPHTHALMOL—VOL. 42, NO. 5 2007
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Background: Diffraction-enhanced imaging (DEI) is a synchrotron-based x-ray imaging technique that has dramatically improved contrast over standard x-ray imaging techniques. It is possible to acquire images that analyze the x-ray refraction and the apparent absorption (elimination of small-angle scattering) of the object. Methods: Three formalin-fixed porcine eyes were studied at the National Synchrotron Light Source using DEI. Conventional absorption-type radiography was conducted for comparison. Results: Conventional absorption radiography did not yield significant detail of the eye anatomy. DEI showed excellent characterization of many ocular structures. The cornea, iris, lens, retina, optic nerve, as well as choroidal vasculature and the ampullae of the vortex veins could all be visualized. Interpretation: DEI represents a novel, high-resolution imaging technique that has excellent characterization of ocular anatomy. Further application of this imaging modality will be undertaken to study cataract and choroidal tumors and to examine ocular surface structures, such as the extraocular muscle insertions, more closely. Contexte : L’imagerie améliorée par diffraction (IAD) repose sur une technique ordinaire de radiographie par radiation de synchrotron qui améliore de façon spectaculaire le contraste du rayon X standard. On peut ainsi obtenir des images qui analysent la réfraction de la radiographie et l’apparente absorption de l’objet (par l’élimination de la dispersion micro-angulaire). Méthodes : Étude de trois yeux de porc conservés dans le formol à la National Synchrotron Light Source effectuée par IAD. La radiographie conventionnelle par absorption a servi d’élément de comparaison. Résultats : La radiographie conventionnelle par absorption n’a pas donné de détails significatifs sur l’anatomie des yeux. L’IAD a fait voir d’excellentes caractéristiques de plusieurs structures oculaires. La cornée, l’iris, la lentille, la rétine, le nerf optique de même que la vascularisation choroïdienne et les ampoules des veines vortiqueuses peuvent tous être visualisés. Interprétation : L’imagerie améliorée par diffraction présente une nouvelle technique d’imagerie à haute résolution montrant de façon excellente les caractéristiques de l’anatomie oculaire. D’autres applications de ce mode d’imagerie permettront d’étudier les cataractes et les tumeurs de la choroïde, et d’examiner de plus près les structures de la surface oculaire, telles les insertions musculaires extraoculaires.
he synchrotron was first produced in 1947 by General Electric, and since that time there have been many synchrotrons built around the world, including one that recently opened in Canada. Collectively, these synchrotrons have allowed for significant discoveries in the fields of physics, medicine, and engineering. Synchrotron-supported imaging techniques are currently under development for medical imaging. A novel technique called diffraction-enhanced imaging (DEI) was introduced by Chapman et al.1 in 1997. DEI is an x-ray–based imaging technique using monochromatic x-rays from a synchrotron
T
light source that produces images of thick absorbing objects that are almost completely free of scatter. Images obtained by DEI show dramatically improved contrast over standard imaging applied to the same object. When x-rays interact with a biological substance, they are either absorbed, scattered, or refracted. DEI is able to use x-ray refraction and rejection of scatter to obtain more information about the object than conventional absorption x-ray imaging. This was previously demonstrated in DEI studies of soft tissues, such as articular cartilage, cadaveric foot, and spine and breast specimens at the National Synchrotron Light
From *the Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio; †the Department of Ophthalmology, Pasqua Hospital, University of Saskatchewan, Regina, Sask.; ‡the Division of Orthopaedic Surgery, Royal University Hospital, University of Saskatchewan, Saskatoon, Sask.; §the Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Sask.; ||the Department of Ophthalmology, University of Calgary, Calgary, Alta.; and ¶the National Synchrotron Light Source, Brookhaven National Laboratory, Upton, N.Y.
Correspondence to: Michael E. Kelly, MD, Section of Cerebrovascular and Endovascular Neurosurgery, Department of Neurosurgery, Cleveland Clinic, 9500 Euclid Ave., S80, Cleveland, OH 44195; [email protected] This article has been peer-reviewed. Cet article a été évalué par les pairs. Can J Ophthalmol 2007;42:731–3 doi: 10.3129/can j ophthalmol.i07-132
Originally received Jan. 8, 2006. Revised Mar. 12, 2007 Accepted for publication Apr. 30, 2007 Published online Sep. 6, 2007
Diffraction-enhanced imaging—Kelly et al.
731
Diffraction-enhanced imaging—Kelly et al. Source.2–9 We describe the first known attempt to use DEI to study a porcine model of the eye. METHODS
Three formalin-fixed porcine eyes were studied at beamline X15A at the National Synchrotron Light Source in Brookhaven National Laboratory, Upton, N.Y. DEIs and standard x-ray radiographs were performed using a standard technique and dedicated imaging system.1,10 An energy of 40 kiloelectron volts (keV) was used, and images were captured with a charged coupled device x-ray detector. The eyes were mounted on wooden holders using epoxy glue and submerged in distilled water. The container was then agitated to remove air bubbles that had formed on the specimen and container. The eyes were placed in 3 separate orientations. The set-up is shown in Fig. 1. Image analysis was performed using Interactive Data Language software (Research Systems Inc., Boulder, Colo.). The procedure of DEI is briefly described below but can be found in more detail in other publications.1,9,10 The analyzer crystal used in DEI is composed of silicon, usually in a 3,3,3 lattice configuration. The silicon crystal is able to select for either refraction of light or apparent absorption of light. This selection is done by moving the analyzer crystal. Apparent absorption results because the analyzer crystal is sensitive to scatter and removes it from the image. The rejected scatter is considered to be small-angle scattering that arises from the scattering of very small, fine structures. This scattering normally appears on conventional radiography but is missing in DEI. Improved image contrast is possible because of this scatter rejection.9 Apparent absorption is the result of the absorption of x-rays by the object with scatter rejection or extinction. The crystal detects refraction of the x-rays as they pass through the sample. Refraction is a change in direction of the x-ray beam when it passes between the boundaries of 2 materials in which the velocity of propagation is differ-
ent. Refraction images can also be obtained, and they show superior image contrast.9 By using DEI, significantly more information can be obtained about the specimen characteristics than with conventional radiography. Conventional absorption radiography was performed using standard x-ray image plates (Fuji Medical Systems) and synchrotron radiation source using the same x-ray energy and dose as DEI. These images were used for comparison. RESULTS Absorption radiography
The conventional absorption radiograph, shown in Fig. 2, was acquired with 40 keV x-rays. Because of the low x-ray absorption of the eyes, this technique provided only an indistinct image of the porcine eyes, as is typical of conventional x-ray imaging techniques performed on soft-tissues. DEI
DEI was performed on the specimen. Image resolution was estimated to be 100 μm. Image analysis with Interactive Data Language software revealed that the refraction images of the eyes allowed for the most image detail (Fig. 3). Analysis of the images revealed excellent characterization of many ocular structures that were not identifiable on the comparative absorption radiograph image (Fig. 2). Most apparent on the refraction images are the cornea, ciliary body, ciliary processes, lens, choroid, vortex veins, sclera, and optic nerve. We also used the Interactive Data Language software to analyze the scatter rejection of the image (Fig. 4). This image demonstrated impressive detail of the choroidal vasculature and corresponding ampullae of the vortex veins. However, this scatter rejection image provided less detail of the intraocular structures than seen in the refraction image. DISCUSSION
We present the first ocular images obtained from DEI using synchrotron radiation. The full utility of synchrotron biomedical beamlines has yet to be completely defined. DEI is one such advanced imaging technique that demonstrates detailed anatomic ocular images, not possible with other x-ray imaging techniques. The images produced from DEI are 2-dimensional
Fig. 1—Set up for diffraction-enhanced imaging of porcine eyes.
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CAN J OPHTHALMOL—VOL. 42, NO. 5, 2007
Fig. 2—Conventional absorption radiography of porcine eyes. (Scale bar = 1 cm.)
Diffraction-enhanced imaging—Kelly et al. planar images. The 3-dimensional appearance is secondary to the significantly improved contrast. The modality uses not only x-ray absorption but also small-angle scattering to improve image contrast. The detector also has an excellent resolution, but it must be noted that the conventional x-ray absorption radiography used the same detector. Ocular imaging is most commonly performed using computerized tomography, magnetic resonance imaging, or low-frequency ultrasound imaging with the resultant images often being of low contrast and detail. As newer techniques are developed, such as ocular coherence tomography and high-resolution ultrasound biomicroscopy, new levels of detail that were previously unachievable are being obtained. DEI represents another novel, ocular imaging technique that provides high-resolution ocular images. In this initial study, we imaged the eye without the surrounding orbit and skull. To assess the eventual clinical and research potential of this technique, further study of the eye in the orbit must be performed. Synchrotron-based DEI imaging is a safe way of imaging. Radiation exposure from DEI can be limited with various safety features. The most widely applied synchrotron imaging modality in human subjects is coronary angiography. It has been safely performed in over 500 patients worldwide.11 The dose of approximately 1 milligray (mGy) used in the present study is far less than that used for angiography (more than 10 mGy). Thus, we believe that it is also possible to perform DEI in a safe manner on a live animal model or human without adverse effects. One significant disadvantage of DEI in the practice of clinical ophthalmology is that the procedure is dependent on a synchrotron radiation source. The Canadian Light Source in Saskatoon, Sask., is the only synchrotron in Canada. Currently, there
Fig. 3—Diffraction-enhanced imaging (refraction image) of porcine eyes illustrating cornea, lens, iris, retina, and optic nerve. Scattered air bubbles are noted as surface artifacts.
Fig. 4—Diffraction-enhanced imaging (apparent absorption highlighting scatter rejection) of porcine eyes illustrating cornea, lens, iris, retina, and optic nerve, as well as choroidal vasculature and the ampulae of the vortex veins.
are limited clinical applications for DEI, and it remains only a research tool. Work is under way at several institutions, including the Canadian Light Source, to create a more “portable” DEI imaging device. Further experiments are required prior to undertaking limited human imaging. In summary, DEI represents a novel imaging technique that can be applied to ocular imaging. Exquisite delineation of the ocular anatomy was obtained in this first ever report of DEI imaging of an eye. To further evaluate the utility of DEI in ophthalmology we intend to analyze ocular conditions such as cataract and choroidal tumors and also to examine ocular surface structures more closely, including the extraocular muscle insertions. The authors acknowledge the support of the Saskatchewan Synchrotron Institute, Departments of Surgery and Ophthalmology, University of Saskatchewan. Dr. Kelly is supported in part by the American Association of Neurological Surgeons, Neurosurgery Research and Education Foundation Fellowship. Dr. Chapman is supported in part by a Canadian Institutes of Health Research Establishment Grant. Utilization of the X15A beamline was supported by the U.S. Department of Energy contract DE-AC02-76CH00016. Institutional review board approval was not needed and therefore not obtained for this experiment.
REFERENCES 1. Chapman D, Thomlinson W, Johnston RE, et al. Diffraction enhanced x-ray imaging. Phys Med Biol 1997;42(11):2015–25. 2. Dilmanian FA, Zhong Z, Ren B, et al. Computed tomography of x-ray index of refraction using the diffraction enhanced imaging method. Phys Med Biol 2000;45(4):933–46. 3. Hasnah MO, Zhong Z, Oltulu O, et al. Diffraction enhanced imaging contrast mechanisms in breast cancer specimens. Med Phys 2002;29(10):2216–21. 4. Johnston RE, Washburn D, Pisano E, et al. Mammographic phantom studies with synchrotron radiation. Radiology 1996;200(3):659–63. 5. Lewis RA, Hall CJ, Hufton AP, et al. X-ray refraction effects: application to the imaging of biological tissues. Br J Radiol 2003;76(905):301–8. 6. Mollenhauer J, Aurich ME, Zhong Z, et al. Diffractionenhanced x-ray imaging of articular cartilage. Osteoarthritis Cartilage 2002;10(3):163–71. 7. Muehleman C, Chapman LD, Kuettner KE, et al. Radiography of rabbit articular cartilage with diffraction-enhanced imaging. Anat Rec A Discov Mol Cell Evol Biol 2003;272A(1):392–7. 8. Pisano ED, Johnston RE, Chapman D, et al. Human breast cancer specimens: diffraction-enhanced imaging with histologic correlation—improved conspicuity of lesion detail compared with digital radiography. Radiology 2000;214(3):895–901. 9. Kelly ME, Beavis RC, Fourney DR, et al. Diffraction-enhanced imaging of the rat spine. Can Assoc Radiol J 2006;57(4):204–10. 10. Zhong Z, Thomlinson W, Chapman D, Sayers D. Implementation of diffraction enhanced imaging experiments: at the NSLS and APS. Nucl Instrum Meth Phys Res A 2000;450:556–67. 11. Suortti P, Thomlinson W. Medical applications of synchrotron radiation. Phys Med Biol 2003;48(13):R1–35. Key words: diffraction enhanced imaging, eye, synchrotron CAN J OPHTHALMOL—VOL. 42, NO. 5 2007
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