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Optics Express

Optics Express

  • Editor: Michael Duncan
  • Vol. 14, Iss. 4 — Feb. 20, 2006
  • pp: 1547–1556
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In vivo detection of exercise-induced ultrastructural changes in genetically-altered murine skeletal muscle using polarization-sensitive optical coherence tomography

James J. Pasquesi, Simon C. Schlachter, Marni D. Boppart, Eric Chaney, Stephen J. Kaufman, and Stephen A. Boppart  »View Author Affiliations


Optics Express, Vol. 14, Issue 4, pp. 1547-1556 (2006)
http://dx.doi.org/10.1364/OE.14.001547


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Abstract

Skeletal muscle fibers are a known source of form birefringence in biological tissue. The birefringence present in skeletal muscle is associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Certain structural proteins that prevent damage and maintain the structural and functional health of the muscle fiber preserve the organization of the A-bands in skeletal muscle. Therefore, the level of birefringence detected can estimate the health of the muscle as well as the damage incurred during exercise. Murine skeletal muscle from both genetically-altered (mdx) and normal (wild-type) specimens were imaged in vivo with a fiber-based PS-OCT imaging system to quantitatively determine the level of birefringence present in the tissue before and after exercise. The mdx muscle lacks dystrophin, a structural protein that is mutated in Duchenne muscular dystrophy in humans. Muscle from these mdx mice exhibited a marked decrease in birefringence after exercise, whereas the wild-type muscle was highly birefringent before and after exercise. The quantitative results from this tissue optics study suggest for the first time that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.

© 2006 Optical Society of America

1. Introduction

Duchenne muscular dystrophy (DMD) is associated with the progressive degeneration of skeletal and cardiac muscle fibers and ultimately leads to death from respiratory or cardiac failure. Acute bouts of intense exercise can induce an inflammatory response as well as ultrastructural changes [1

1. K. P. O’Reilly, M. J. Warhol, R. A. Fielding, W. R. Frontera, C. N. Meredith, and W. J. Evans, “Eccentric exercise-induced muscle damage impairs muscle glycogen repletion,” J. Appl. Physiol. 63, 252 (1987). [PubMed]

]. DMD is the most frequent form of muscular dystrophy, occurring in approximately 1 out of 3000 males. A recessive gene located on the X chromosome has been identified as the gene responsible for DMD. The gene codes for a protein known as dystrophin, which is a cytoskeletal protein involved in maintaining the structural integrity of muscle cell membranes, and the association of muscle fibers with the surrounding extracellular matrix [2

2. J. F. Watchko, T. L. O’Day, and E. P. Hoffman, “Functional characteristics of dystrophic skeletal muscle: insights from animal models,” J. Appl. Physiol. 93, 407 (2002). [PubMed]

,3

3. J. Sherman, A. Vander, and D. Luciano, Human Physiology: The Mechanisms of Body Function, 8th ed. New York, NY: the McGraw-Hill Companies, Inc. (2001).

]. Due to mutations in this gene, the protein dystrophin is either absent or present in a non-functional form, leaving muscle fibers susceptible to structural damage. Such damage may disrupt A-band organization and alignment, as well as affect the normal association of the muscle fiber with the surrounding basal lamina. Genetically-altered mice, known as mdx mice (X-linked muscular dystrophy), have been shown to possess traits similar to DMD (i.e., lacking dystrophin) [4

4. S. De la Porte, S. Morin, and J. Koenig, “Characteristics of skeletal muscle in mdx mutant mice,” Int. Rev. Cytol 191, 99 (1999). [CrossRef] [PubMed]

].

The elongated, asymmetrical shape of muscle fibers in general suggests the presence of a fast optical axis. However, the actual source of birefringence in skeletal muscle is highly dependent on biological, physiological, and environmental conditions. A series of light and dark “bands” perpendicular to the long axis of the muscle fiber appear when imaging both skeletal and cardiac muscle fibers through a light microscope. The presence of these bands or striations is due to the arrangement of thick (myosin) and thin (actin) filaments in the myofibrils of the muscle cell. The light and dark bands are referred to as A-bands (anisotropic) and I-bands (isotropic), respectively. The thick (myosin) filaments in the A-bands are considered to be the anisotropic source of form birefringence present in muscle tissue [5

5. A. V. Smolensky, J. Ragozzino, S. H. Gilbert, C. Y. Seow, and L. E. Ford, “Length-dependent filament formation assessed from birefringence increases during activation of porcine tracheal muscle,” J. Physiol. 563, 517 (2005). [CrossRef]

]. Therefore, as the presence and organization of thick filaments in muscle type varies, so does the overall birefringence of the tissue.

Polarization-sensitive optical coherence tomography (PS-OCT) is an optical imaging technology that maps depth-resolved changes in the polarization state of light induced by anisotropic tissue properties [6

6. M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging”, J. Opt. Soc. Am. B 9, 903“908 (1992). [CrossRef]

]. By exploiting the interaction between the polarization state of light and biological tissue, additional structural and possibly functional (physiological) information can be extracted [7

7. T. E. Milner and J. F. de Boer, “Review of polarization sensitive optical coherence tomography and Stokes vector determination,” J. Biomed. Opt. 7, 359 (2002). [CrossRef] [PubMed]

]. Form birefringence is the main optical property present in biological tissues responsible for altering the polarization state of light. Common sources of form birefringence in biological tissue are muscle, tendons, nerve, bone, cartilage, and teeth. Many of these sources of birefringence have been investigated for potential medical applications [8–15

8. Y. Chen, L. Otis, D. Piao, and Q. Zhu, “Characterization of dentin, enamel, and carious lesions by a polarization-sensitive optical coherence tomography system,” Appl. Opt. 44, 2041 (2005). [CrossRef] [PubMed]

]. However, few PS-OCT investigations have been performed in skeletal muscle, and none of these have investigated the contributions that ultrastructural changes in skeletal muscle have on the tissue optical properties measured by PS-OCT [12

12. S. Guo, J. Zhang, L. Wang, J. S. Nelson, and Z. Chen, “Depth-resolved birefringence and differential optical axis orientation measurements with fiber-based polarization-sensitive optical coherence tomography,” Opt. Lett. 29, 2025 (2004). [CrossRef] [PubMed]

, 16

16. J. F. de Boer, T. E. Milner, and J. S. Nelson, “Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography,” Opt. Lett. 24, 300“302 (1999). [CrossRef]

].

2. Materials and methods

2.1 Animal studies

Trials were performed in vivo on mdx (Jackson Labs, Bar Harbor, ME) and wild-type (C57BL6) murine skeletal muscle (gastrocnemius) in compliance with an experimental protocol approved by the Institutional Animal Care and Use Committee at the University of Illinois at Urbana-Champaign. Five-week-old male mdx and wild-type mice (n=2/group) were exercised and compared to non-exercised mice from each group (n=2/group). The mice were individually housed, fed daily, and kept on a 12 hour light-dark cycle prior to exercising and imaging. Before in vivo PS-OCT was performed, the mice were anaesthetized with xylazine (10mg/kg), ketamine (100mg/kg), and atropine (1mg/kg), and the skin overlaying the gastrocnemius muscle was incised and reflected back, exposing the muscle tissue. A normal (0.9%) saline solution was used prior to imaging to prevent dehydration of the exposed tissue. Controlled exercise of the muscle was used to induce potential ultrastructural changes in myofibers 24 hours prior to imaging. Wild-type and mdx mice were run on a rodent treadmill (Exer-6M, Columbus Instruments, Columbus, OH) modified to accommodate a downhill running decline of 20°. Ninety minutes prior to downhill running, wild-type and mdx mice were injected with Evans blue fluorescent dye (50 μL/10 g body wt) for later validation studies of muscle injury and damage. The injection of Evans blue fluorescent dye is an established method for visualizing and quantifying muscle injury. In excised specimens, muscle fibers with intact membranes exhibit Evans blue fluorescence localized to regions surrounding the fibers, while the damaged fibers contain Evans blue fluorescence within individual fibers. Wild-type and mdx mice were subjected to an exercise protocol that included an initial 2 min warm-up run at a velocity of 10 m/min, followed by a 30 min run at a maximal velocity of 17 m/min. Wild-type mice were able to run for this duration and at this maximal velocity. However, mdx mice were only able to complete a run for 25 min at a maximal speed of 15 m/min due to the physical limitations imposed by their genetically-altered muscle.

2.2 Polarization-sensitive OCT system

A schematic of the PS-OCT system used in the experiment is illustrated in Fig. 1. The PS-OCT system was a fiber-based, time-domain system, constructed using a 1300 nm center-wavelength (75 nm bandwidth) SLD source (MenloSystems, Martinsried, Germany). Conventional single-mode optical fiber (SMF-28, Corning, Inc.) was used throughout the system. System parameters included a measured axial resolution of ∼10 μm (in free-space), a transverse resolution of ∼18 μm, and 5 mW of incident optical power on the specimens. A rapid-scanning optical delay (RSOD) was implemented to perform fast axial scanning at 400 Hz. A polarization controller (P2) was used to align the RSOD polarization state with the state of maximum diffraction efficiency.

A wavelength-independent lithium niobate polarization modulator (EOSpace, Inc.) consisting of a waveguide with single-mode fiber input and output connectors, and a modulator controller, was used to toggle the incident polarization state on the sample between two orthogonal linear states of polarization. The lithium niobate polarization controller was designed to alter (rotate) any input state of polarization to any output polarization state on the Poincaré sphere. The polarization transformation was electro-optically adjusted by varying voltages applied to electrodes surrounding the waveguide. The electric field lines induced between the electrodes alter the optical properties of the waveguide such as birefringence (retardation factor) and fast optical axis orientation. Optical circulators were used to avoid a double-pass through the modulator and promote dual-balance detection.

Fig. 1. Schematic of the PS-OCT system. Abbreviations: SLD, super luminescent diode; Pol., linear polarizer; Pol. Mod., polarization modulator; 90/10, 50/50, fiber couplers; RSOD, rapid scanning optical delay; OC, optical circulator; P#, polarization paddles; PBS, polarization beam splitter; P.D., photodetector.

Polarization diversity detection was implemented in order to perform depth-resolved birefringence mapping. The detection scheme also incorporated dual-balance detection in order to improve the system signal-to-noise ratio (SNR). This involved two balanced photodetectors receiving orthogonal polarization states of light from the output fibers of a polarization beam splitter (PBS). The polarization-controlling paddles (P3 and P4) were implemented to balance the reference arm power equally between the two detectors. Additional control signals were used to perform the following tasks: (1) synchronize the toggling of the modulator electrodes with each axial scan of the delay line, (2) control the channel selection of a 2-channel analog multiplexer designed to switch between orthogonal photodetectors for every two axial scans, and (3) generate step functions for the x-galvanometer for every fourth axial scan. The control signal and timing diagram is illustrated in Fig. 2.

Fig. 2. Synchronized signals used to control the RSOD delay galvanometer (blue), the polarization modulator (red), the analog two-channel multiplexer (orange), and the x-galvanometer (green). Fringe data was collected during the rising slope of the pseudo-sawtooth delay waveform (blue).

2.3 Data acquisition

Before data acquisition, the polarization modulator was tuned to produce two orthogonal linear polarization states incident on the sample. The modulator was calibrated by placing a bulk linear polarizer in the sample arm beam delivery system. A retro-reflecting mirror was used in place of a biological sample to assist in the procedure. The power returning from the mirror was measured before placing the linear polarizer into the setup. The voltages applied to the electrodes of the polarization modulator were tuned until the power returning from the sample arm retro-reflector was approximately equivalent to the initial power measurement taken without the linear polarizer present, which signified optimal alignment of the incident polarization with the linear polarizer. A polarization controller (P1) was also used to assist in this process in order to minimize the voltage sweep needed to find the first polarization state. The polarizer was then rotated 90° and the procedure was repeated to produce a linear polarization state orthogonal to the original incident state (without changing P1). The electrode voltages for the polarization modulator were recorded for each setting and were used to toggle the modulator between the two orthogonal linear polarizations states on every axial scan of the delay line.

After calibrating the polarization states of the incident sample arm beam, various muscle specimens were placed into the sample arm for imaging (data acquisition). Each muscle specimen was placed in the sample arm with the direction of the muscle fibers aligned at approximately 45° with respect to the orientation of the two orthogonal, linearly polarized, incident beams. It is well-established that anisotropic thick filaments present in skeletal muscle create a fast and slow optical axis, parallel and perpendicular to the orientation of the muscle fibers. Therefore, probing with two linearly orthogonal beams at ± 45° off axis with respect to the orientation of the muscle fibers would produce the most evident phase retardation due to sample birefringence. If either incident state were aligned with the fast or slow axis, then no birefringence would be observed. To ensure that optimal birefringence occurred with orthogonal states aligned at ± 45° with respect to the orientation of the muscle fibers, each sample was rotated ± 30° at each image location and re-imaged.

2.4 Image processing and data quantification

Structural images were generated using 10log|Av+Ah|. PS-OCT birefringence images were plotted using the sgn(Av-Ah)10log|Av-Ah| of the data. The regions of the B-scan used to calculate zero-crossing distances and subsequently the birefringence of the muscle tissue were outlined by a black box overlaid on the birefringence images (see, for example, Fig. 3(B)). These regions typically consisted of 100 A-scans, and averages were obtained from 10 A-scans in each of 10 non-overlapping segments. This analysis was performed on four separate B-scans (not shown) per mouse for both incident polarization states. For the special case of the exercised mdx muscle, the measured birefringence was very low (δ ≈ 1.44 x 10-3), making it difficult to resolve zero-crossing points; for this reason 10 A-scans from between 3 and 9 non-overlapping segments of the B-scan were averaged.. Only 3 B-scans had any measurable birefringence in this case, so it is likely that the actual birefringence of the exercised mdx muscle was even lower than the value reported in this study. For each specimen, black points plotted on the images mark the zero-crossings identified by our algorithm, and the mean and standard deviation was calculated for comparisons between groups. Since the tissue was probed with two orthogonal polarization states, the measured birefringence should be the same regardless of incident polarization state provided that the incident state is not perfectly aligned with the fast or slow axis. This possibility was accounted for by rotating the sample until the highest polarimetric SNR was observed [19

19. N. Kemp, H. Zaatari, J. Park, H. Rylander III, and T. Milner, “Form-biattenuance in fibrous tissues measured with polarization-sensitive optical coherence tomography (PS-OCT),” Opt. Express 13, 4611–4628 (2005), http://www.opticsinfobase.org/abstract.cfm?URI=oe-13-12-4611 [CrossRef] [PubMed]

].

2.5 Tissue processing and validation

After imaging, the muscle was dissected and flash-frozen in liquid nitrogen-cooled isopentane (Sigma) and stored at -80°C until sectioned. The corresponding gastrocnemius muscle from the contralateral leg was dissected and drop-fixed for transmission electron microscopy (TEM). The gastrocnemius muscles samples for TEM were fixed in 2% glutaraldehyde and 2.5% paraformaldehyde in 0.2 M Sorenson’s phosphate buffer, embedded in Epon 812 (Ted Pella, Inc.), sectioned at 0.1 μm using an ultramicrotome (Reichert Ultracut E), stained with uranyl acetate and lead citrate, and viewed with a transmission electron microscope (Philips CM200) at 5000x magnification. The TEM results were used to validate the arrangement and order of individual sarcomeres for the wild-type and mdx muscle specimens both before and after exercise. In addition, serial sections (10 μm thick) from each muscle were collected and viewed for Evans blue uptake and hematoxylin and eosin (H&E) staining in order to assess myofiber damage. Frozen sections were obtained from the distal gastrocnemius (10 sections/specimen) and observed using fluorescence and brightfield microscopy for the Evans blue and H&E sections, respectively. Muscle fiber injury was assessed by microscopic observation, by positive-fiber counting with intact membranes exhibiting Evans blue fluorescence localized to regions surrounding the fibers, and by positive-fiber counting of damaged fibers containing Evans blue fluorescence within individual fibers.

3. Results and discussion

Fig. 3. Non-exercised wild-type murine skeletal muscle. A) Structural OCT image. B) False-color birefringence image. The black box outlines the region over which the mean zero-crossing distance was calculated and the black points represent the zero-crossing points identified by the algorithm. Histological images are shown using (C) Evans blue fluorescence at 20x, (D) H&E at 20x, and (E) TEM at 5000x magnifications. Scale bar represents 500 μm.

A similar imaging experiment was conducted on wild-type and mdx muscle in animals that were subjected to treadmill exercise prior to imaging. The PS-OCT results of skeletal muscle following exercise revealed that the wild-type muscle (Fig. 5(B)) remained highly birefringent at δ = (1.94 ± 0.17)×10-3, similar to the images and the quantified birefringence from the non-exercised wild-type muscle (Fig. 3(B)). The validation histology (Figs. 5(C),(D),(E)) confirmed minimal changes in these wild-type muscles, with only 4 Evans blue-positive fibers in the exercised wild-type muscle (compared to 0 for non-exercised wild-type), and no significant changes on H&E sections or TEM.

The exercised mdx muscle (Fig. 6), however, exhibited very little birefringence at δ = (1.44 ± 0.12)×10-3. This lack of phase retardation signified a drastic reduction in birefringence compared to the non-exercised mdx muscle (Fig. 4). The histological observations validate these findings. The Evans blue fluorescence (Fig. 6(C)) was strongly indicative of muscle injury. In a total of 50 fields each, there were 391 positive fibers, compared to 157 positive fibers in the non-exercised mdx muscle. The H&E-stained sections (Fig. 6(D)) did not reveal significant structural changes. The TEM observations supported these findings of ultrastructural damage, and a representative TEM image (Fig. 6(E)) shows damaged sarcomeres. These results suggests that the muscle fiber structure in the mdx mouse was considerably more damaged during exercise, resulting in a deterioration of A-band structure and an overall loss of birefringence as detected by PS-OCT. These mdx mice were physically unable to complete the full duration and intensity of the exercise protocol, which the wild-type mice did complete. The PS-OCT and histological findings validate that severe ultrastructural damage was present following the portion of the exercise protocol that was completed, and that additional exercise would only induce further injury and further reduce the detected level of birefringence.

Fig. 4. Non-exercised mdx murine skeletal muscle. A) Structural OCT image. B) False-color birefringence image. The black box outlines the region over which the mean zero-crossing distance was calculated and the black points represent the zero-crossing points identified by the algorithm. Histological images are shown using (C) Evans blue fluorescence at 10x, (D) H&E at 10x, and (E) TEM at 5000x magnifications. Scale bar represents 500 μm.

A direct comparison of the quantified average birefringence for each of the two incident polarization states on the skeletal muscle specimens from these four groups is shown in Fig. 7. The numerical data in Fig. 7 for all the muscle types confirm the image-based qualitative observations and quantifies the amount of birefringence associated with the ultrastructure within the muscle. Similarly, Fig. 8 shows the relationship between the PS-OCT measured birefringence and the number of Evans blue-positive muscle fibers (which correlate with muscle injury). There are distinct differences between the wild-type muscle (both non-exercised and exercised) and the mdx muscle. The exercised mdx muscle clearly shows significant differences in both the measured birefringence and the number of Evans blue-positive muscle fibers, validating the findings of PS-OCT.

4. Conclusion

Polarization-sensitive OCT provides a sensitive, non- or minimally-invasive means for assessing in vivo changes in the birefringent properties of tissue. In this tissue optics study, the effect of varying skeletal muscle ultrastructure on the detected PS-OCT signal, and the quantified birefringence, was investigated. We found that non-exercised mdx murine skeletal muscle exhibited similar birefringence as non-exercised wild-type muscle. Exercising the dystrophic mdx muscle, however, drastically reduced the birefringence, compared to exercised wild-type muscle. The results from PS-OCT and birefringence calculations were validated with H&E histology, Evans blue fluorescence, and TEM images, confirming the exercise-induced damage to the arrangement of individual sarcomeres present in the dystrophic mdx muscle.

Fig. 5. Exercised wild-type murine skeletal muscle. A) Structural OCT image. B) False-color birefringence image. The black box outlines the region over which the mean zero-crossing distance was calculated and the black points represent the zero-crossing points identified by the algorithm. Histological images are shown using (C) Evans blue fluorescence at 20x, (D) H&E at 20x, and (E) TEM at 5000x magnifications. Scale bar represents 500 μm.
Fig. 6. Exercised mdx murine skeletal muscle. A) Structural OCT image. B) False-color birefringence image. The black box outlines the region over which the mean zero-crossing distance was calculated and the black points represent the zero-crossing points identified by the algorithm. Histological images are shown using (C) Evans blue fluorescence at 10x, (D) H&E at 10x, and (E) TEM at 5000x magnifications. Scale bar represents 500 μm.
Fig. 7. Quantitative comparison of birefringence values from skeletal muscle types. Error bars represent the standard deviation of the birefringence.
Fig. 8. Plot showing calculated birefringence values vs. measured Evans blue positive fiber count for the four muscle types. Error bars represent standard deviation of the birefringence.

These results suggest that PS-OCT can detect birefringence changes due to the ultrastructural alterations occurring in the sarcomeres of skeletal muscle due to genetic alterations and due to damage during exercise. This damage can be attributed to the lack of dystrophin in the mdx muscle, and hence, the lack of preservation of structural integrity following exercise. The preservation of phase retardation after exercise in the wild-type muscle further supports that ultrastructural order (A-band organization) was maintained due to the abundance of these structural proteins.

Future studies will include the implementation of quantitative phase-based PS-OCT measurements following hardware upgrades to enable more phase-stable imaging methods. Larger numbers of specimens will be imaged to determine levels of statistical differences of birefringence measurements within single specimens, between specimens within a group, and between different groups. Based on the qualitative and quantitative findings presented in this paper, we demonstrate that a direct relationship exists between the ultrastructure of skeletal muscle fibers and the PS-OCT-detected birefringence.

Acknowledgments

We wish to thank Dr. Daniel Marks of the Beckman Institute for Advanced Science and Technology for his technical contributions to the image acquisition software and for his intellectual contributions to the design of this imaging system. This research was supported in part by the National Institutes of Health (S.A.B., S.J.K.), the Beckman Institute for Advance Science and Technology (S.A.B.), the Muscular Dystrophy Association (S.J.K.) and the UIUC-UIC Intercampus Research Initiative in Biotechnology (S.A.B.). Additional information can be found at http://biophotonics.uiuc.edu.

References and links

1.

K. P. O’Reilly, M. J. Warhol, R. A. Fielding, W. R. Frontera, C. N. Meredith, and W. J. Evans, “Eccentric exercise-induced muscle damage impairs muscle glycogen repletion,” J. Appl. Physiol. 63, 252 (1987). [PubMed]

2.

J. F. Watchko, T. L. O’Day, and E. P. Hoffman, “Functional characteristics of dystrophic skeletal muscle: insights from animal models,” J. Appl. Physiol. 93, 407 (2002). [PubMed]

3.

J. Sherman, A. Vander, and D. Luciano, Human Physiology: The Mechanisms of Body Function, 8th ed. New York, NY: the McGraw-Hill Companies, Inc. (2001).

4.

S. De la Porte, S. Morin, and J. Koenig, “Characteristics of skeletal muscle in mdx mutant mice,” Int. Rev. Cytol 191, 99 (1999). [CrossRef] [PubMed]

5.

A. V. Smolensky, J. Ragozzino, S. H. Gilbert, C. Y. Seow, and L. E. Ford, “Length-dependent filament formation assessed from birefringence increases during activation of porcine tracheal muscle,” J. Physiol. 563, 517 (2005). [CrossRef]

6.

M. R. Hee, D. Huang, E. A. Swanson, and J. G. Fujimoto, “Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging”, J. Opt. Soc. Am. B 9, 903“908 (1992). [CrossRef]

7.

T. E. Milner and J. F. de Boer, “Review of polarization sensitive optical coherence tomography and Stokes vector determination,” J. Biomed. Opt. 7, 359 (2002). [CrossRef] [PubMed]

8.

Y. Chen, L. Otis, D. Piao, and Q. Zhu, “Characterization of dentin, enamel, and carious lesions by a polarization-sensitive optical coherence tomography system,” Appl. Opt. 44, 2041 (2005). [CrossRef] [PubMed]

9.

M. C. Pierce, J. Strasswimmer, B. H. Park, B. Cense, and J. F. de Boer, “Birefringence measurements in human skin using polarization-sensitive optical coherence tomography,” J. Biomed. Opt. 9, 287 (2004). [CrossRef] [PubMed]

10.

W. Drexler, D. Stamper, C. Jesser, X. Li, C. Pitris, K. Saunders, S. Martin, M. B. Lodge, J. G. Fujimoto, and M. E. Brezinski, “Correlation of collagen organization with polarization sensitive imaging of in vitro cartilage: implications for osteoarthritis,” J. Rheumatol. 28, 1311 (2001). [PubMed]

11.

B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 45, 2606 (2004). [CrossRef] [PubMed]

12.

S. Guo, J. Zhang, L. Wang, J. S. Nelson, and Z. Chen, “Depth-resolved birefringence and differential optical axis orientation measurements with fiber-based polarization-sensitive optical coherence tomography,” Opt. Lett. 29, 2025 (2004). [CrossRef] [PubMed]

13.

B. H. Park, M. C. Pierce, B. Cense, and J. F. de Boer, “Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components,” Opt. Lett. 29, 2512 (2004). [CrossRef] [PubMed]

14.

N. A. Patel, J. Zoeller, D. L. Stamper, J. G. Fujimoto, and M. E. Brezinski, “Monitoring osteoarthritis in the rat model using optical coherence tomography,” IEEE Trans. Med. Imaging 24, 155 (2005). [CrossRef] [PubMed]

15.

S. Jiao, M. Todorovic, G. Stoica, and L. V. Wang, “Fiber-based polarization-sensitive Mueller matrix optical coherence tomography with continuous source polarization modulation,” Appl. Opt. 44, 5463 (2005). [CrossRef] [PubMed]

16.

J. F. de Boer, T. E. Milner, and J. S. Nelson, “Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography,” Opt. Lett. 24, 300“302 (1999). [CrossRef]

17.

C. Hitzenberger, E. Goetzinger, M. Sticker, M. Pircher, and A. F. Fercher, “Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography,” Opt. Express 9, 780–790 (2001), http://www.opticsinfobase.org/abstract.cfm?URI=oe-9-13-780 [CrossRef] [PubMed]

18.

J. de Boer, T. Milner, M. van Gemert, and J. Nelson, “Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography,” Opt. Lett. 22, 934–936 (1997). [CrossRef] [PubMed]

19.

N. Kemp, H. Zaatari, J. Park, H. Rylander III, and T. Milner, “Form-biattenuance in fibrous tissues measured with polarization-sensitive optical coherence tomography (PS-OCT),” Opt. Express 13, 4611–4628 (2005), http://www.opticsinfobase.org/abstract.cfm?URI=oe-13-12-4611 [CrossRef] [PubMed]

OCIS Codes
(170.1530) Medical optics and biotechnology : Cell analysis
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(170.5380) Medical optics and biotechnology : Physiology
(230.5440) Optical devices : Polarization-selective devices
(260.1440) Physical optics : Birefringence

ToC Category:
Medical Optics and Biotechnology

History
Original Manuscript: December 22, 2005
Revised Manuscript: January 31, 2006
Manuscript Accepted: February 2, 2006
Published: February 20, 2006

Virtual Issues
Vol. 1, Iss. 3 Virtual Journal for Biomedical Optics

Citation
James J. Pasquesi, Simon C. Schlachter, Marni D. Boppart, Eric Chaney, Stephen J. Kaufman, and Stephen A. Boppart, "In vivo detection of exercised-induced ultrastructural changes in genetically-altered murine skeletal muscle using polarization-sensitive optical coherence tomography," Opt. Express 14, 1547-1556 (2006)
http://www.opticsinfobase.org/oe/abstract.cfm?URI=oe-14-4-1547


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References

  1. K. P. O'Reilly, M. J. Warhol, R. A. Fielding, W. R. Frontera, C. N. Meredith, and W. J. Evans, "Eccentric exercise-induced muscle damage impairs muscle glycogen repletion," J. Appl. Physiol. 63, 252 (1987). [PubMed]
  2. J. F. Watchko, T. L. O’Day, and E. P. Hoffman, "Functional characteristics of dystrophic skeletal muscle: insights from animal models," J. Appl. Physiol. 93, 407 (2002). [PubMed]
  3. J. Sherman, A. Vander, and D. Luciano, Human Physiology: The Mechanisms of Body Function, 8th ed. (McGraw-Hill Companies Inc., New York, NY 2001).
  4. S. De la Porte, S. Morin, and J. Koenig, "Characteristics of skeletal muscle in mdx mutant mice," Int. Rev. Cytol 191, 99 (1999). [CrossRef] [PubMed]
  5. A. V. Smolensky, J. Ragozzino, S. H. Gilbert, C. Y. Seow, and L. E. Ford, "Length-dependent filament formation assessed from birefringence increases during activation of porcine tracheal muscle," J. Physiol. 563, 517 (2005). [CrossRef]
  6. T. E. Milner and J. F. de Boer, "Review of polarization sensitive optical coherence tomography and Stokes vector determination," J. Biomed. Opt. 7, 359 (2002). [CrossRef]
  7. Y. Chen, L. Otis, D. Piao, and Q. Zhu, "Characterization of dentin, enamel, and carious lesions by a polarization-sensitive optical coherence tomography system," Appl. Opt. 44, 2041 (2005). [CrossRef] [PubMed]
  8. M. C. Pierce, J. Strasswimmer, B. H. Park, B. Cense, and J. F. de Boer, "Birefringence measurements in human skin using polarization-sensitive optical coherence tomography," J. Biomed. Opt. 9, 287 (2004). [CrossRef] [PubMed]
  9. W. Drexler, D. Stamper, C. Jesser, X. Li, C. Pitris, K. Saunders, S. Martin, M. B. Lodge, J. G. Fujimoto, and M. E. Brezinski, "Correlation of collagen organization with polarization sensitive imaging of in vitro cartilage: implications for osteoarthritis," J. Rheumatol. 28, 1311 (2001). [CrossRef] [PubMed]
  10. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, "Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography," Invest. Ophthalmol. Vis. Sci. 45, 2606 (2004). [PubMed]
  11. S. Guo, J. Zhang, L. Wang, J. S. Nelson, and Z. Chen, "Depth-resolved birefringence and differential optical axis orientation measurements with fiber-based polarization-sensitive optical coherence tomography," Opt. Lett. 29, 2025 (2004). [CrossRef] [PubMed]
  12. B. H. Park, M. C. Pierce, B. Cense, and J. F. de Boer, "Jones matrix analysis for a polarization-sensitive optical coherence tomography system using fiber-optic components," Opt. Lett. 29, 2512 (2004). [CrossRef] [PubMed]
  13. N. A. Patel, J. Zoeller, D. L. Stamper, J. G. Fujimoto, and M. E. Brezinski, "Monitoring osteoarthritis in the rat model using optical coherence tomography," IEEE Trans. Med. Imaging 24, 155 (2005). [CrossRef] [PubMed]
  14. S. Jiao, M. Todorovic, G. Stoica, and L. V. Wang, "Fiber-based polarization-sensitive Mueller matrix optical coherence tomography with continuous source polarization modulation," Appl. Opt. 44, 5463 (2005). [CrossRef] [PubMed]
  15. J. F. de Boer, T. E. Milner, and J. S. Nelson, "Determination of the depth-resolved Stokes parameters of light backscattered from turbid media by use of polarization-sensitive optical coherence tomography," Opt. Lett. 24, 300-302 (1999). [CrossRef] [PubMed]
  16. C. Hitzenberger, E. Goetzinger, M. Sticker, M. Pircher, and A. F. Fercher, "Measurement and imaging of birefringence and optic axis orientation by phase resolved polarization sensitive optical coherence tomography," Opt. Express 9, 780-790 (2001). [CrossRef]
  17. J. de Boer, T. Milner, M. van Gemert, and J. Nelson, "Two-dimensional birefringence imaging in biological tissue by polarization-sensitive optical coherence tomography," Opt. Lett. 22, 934-936 (1997). [CrossRef] [PubMed]
  18. M. R. Hee, D. Huang, E. A. Swanson, J. G. Fujimoto, "Polarization-sensitive low-coherence reflectometer for birefringence characterization and ranging", J. Opt. Soc. Am. B 9, 903-908 (1992). [CrossRef] [PubMed]
  19. N. Kemp, H. Zaatari, J. Park, H. RylanderIII, and T. Milner, "Form-biattenuance in fibrous tissues measured with polarization-sensitive optical coherence tomography (PS-OCT)," Opt. Express 13, 4611-4628 (2005). [CrossRef] [PubMed]

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